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1. Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine

Author

David G. Alleva, Eline A. Feitsma, Yester F. Janssen, Hendrikus H. Boersma, Thomas M. Lancaster, Thillainaygam Sathiyaseelan, Sylaja Murikipudi, Andrea R. Delpero, Melanie M. Scully, Ramya Ragupathy, Sravya Kotha, Jeffrey R. Haworth, Nishit J. Shah, Vidhya Rao, Shashikant Nagre, Shannon E. Ronca, Freedom M. Green, Stephen A. Shaw, Ari Aminetzah, Schelto Kruijff, Maarten Brom, Gooitzen M. van Dam, and Todd C. Zion

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60–68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

Published
2024
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2. Pre-Transplant Hyperparathyroidism and Graft or Patient Outcomes After Kidney Transplantation

Author

Fernanda Guedes Rodrigues, Willemijn Y. Van Der Plas, Camilo German Sotomayor, Amarens Van Der Vaart, Daan Kremer, Robert A. Pol, Schelto Kruijff, Ita Pfeferman Heilberg, Stephan J. L. Bakker, TransplantLines Investigators, and Martin H. De Borst

Subjects
kidney transplantation, graft survival, delayed graft function, hyperparathyroidism, mineral metabolism, Specialties of internal medicine, RC581-951
Abstract

The impact of pre-transplant parathyroid hormone (PTH) levels on early or long-term kidney function after kidney transplantation is subject of debate. We assessed whether severe hyperparathyroidism is associated with delayed graft function (DGF), death-censored graft failure (DCGF), or all-cause mortality. In this single-center cohort study, we studied the relationship between PTH and other parameters related to bone and mineral metabolism, including serum alkaline phosphatase (ALP) at time of transplantation with the subsequent risk of DGF, DCGF and all-cause mortality using multivariable logistic and Cox regression analyses. In 1,576 kidney transplant recipients (51.6 ± 14.0 years, 57.3% male), severe hyperparathyroidism characterized by pre-transplant PTH ≥771 pg/mL (>9 times the upper limit) was present in 121 patients. During 5.2 [0.2–30.0] years follow-up, 278 (15.7%) patients developed DGF, 150 (9.9%) DCGF and 432 (28.6%) died. A higher pre-transplant PTH was not associated with DGF (HR 1.06 [0.90–1.25]), DCGF (HR 0.98 [0.87–1.13]), or all-cause mortality (HR 1.02 [0.93–1.11]). Results were consistent in sensitivity analyses. The same applied to other parameters related to bone and mineral metabolism, including ALP. Severe pre-transplant hyperparathyroidism was not associated with an increased risk of DGF, DCGF or all-cause mortality, not supporting the need of correction before kidney transplantation to improve graft or patient survival.

Published
2024
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3. Unraveling the role of computed tomography derived body composition metrics on anastomotic leakages rates in rectal cancer surgery: A protocol for a systematic review and meta-analysis.

Author

Mark Broekman, Charlotte M S Genders, Ritchie T J Geitenbeek, Klaas Havenga, Schelto Kruijff, Joost M Klaase, Alain R Viddeleer, and Esther C J Consten

Subjects
Medicine, Science
Abstract

IntroductionAnastomotic leakage is a major concern following total mesorectal excision for rectal cancer, affecting oncological outcomes, morbidity an treatment costs. Body composition has been suggested to influence anastomotic leakage rates. However, literature on how body composition impact anastomotic leakage rates is conflicting. This systematic review aims to evaluate the role of computed tomography derived body composition metrics on anastomotic leakage rates in rectal cancer patients.MethodsDatabases PubMed/MEDLINE, Cochrane Library, web of science, and EMBASE, will be systematically searched for papers from January 2010 onwards. Study selection, data collection and quality assessment will be independently performed by three research fellows. Outcomes described in three or more studies will be included in the meta-analysis. The Q-test and I2 statistic will be used to assess statistical heterogeneity between studies. Publication bias will be examined by visual inspection of funnel plots and quantified by Egger's test. Sensitivity analyses will be conducted to examine the robustness of the meta-analysis. Reporting of the findings will be in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.ConclusionsThis systematic review will synthesize the current evidence and will identify knowledge gaps. Results of the systematic review will aid health care professional in pre-operative decision making and will be distributed through a peer-reviewed publication and presentation of results at international meetings.Trial registrationPROSPERO protocol number: CRD42023471537.

Published
2024
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4. Impact of parathyroidectomy on quality of life in multiple endocrine neoplasia type 1

Author

Marília D’Elboux Guimarães Brescia, Karine Candido Rodrigues, André Fernandes d’Alessandro, Wellington Alves Filho, Willemijn Y van der Plas, Schelto Kruijff, Sergio Samir Arap, Sergio Pereira de Almeida Toledo, Fábio Luiz de Menezes Montenegro, and Delmar Muniz Lourenço Jr

Subjects
quality of life, multiple endocrine neoplasia type 1, parathyroidectomy, hyperparathyroidism, hypoparathyroidism, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background: Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown. Method: Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume. Results: Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = −0.60, P = 0.0004) and MCS (r = −0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities. Conclusion: A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.

Published
2022
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6. Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules

Author

Marcus C. M. Stroet, Bianca M. Dijkstra, Sebastiaan E. Dulfer, Schelto Kruijff, Wilfred F. A. den Dunnen, Frank A. E. Kruyt, Rob J. M. Groen, Yann Seimbille, Kranthi M. Panth, Laura Mezzanotte, Clemens W. G. M. Lowik, and Marion de Jong

Subjects
800CW-TATE, Molecular fluorescence-guided surgery, Somatostatin receptor subtype 2, Fluorescent molecular probes, Necrosis-avidity, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Background There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Results Binding of 800CW-TATE could be blocked with DOTA0-Tyr3-octreotate (DOTA-TATE) on cultured SSTR2-positive U2OS cells and was absent in SSTR2 negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR2 negative cells. No SSTR2-mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. Conclusion This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents.

Published
2021
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7. Double venipuncture is not required for adequate S-100B determination in melanoma patients

Author

Samantha Damude, Anneke C Muller Kobold, Esther Bastiaannet, Schelto Kruijff, Harald J Hoekstra, and Kevin P Wevers

Subjects
adipocytes, biological tumor markers, clinical laboratory techniques, melanoma, S100B protein, Biology (General), QH301-705.5
Abstract

S-100B is used in melanoma follow-up. This serum biomarker is also present in adipocytes; therefore, subcutaneous adipocytes trapped in the needle before performing a venipuncture could contaminate the serum. The aim was to study the influence of adipocyte contamination on blood samples used for S-100B analysis, possibly resulting in falsely elevated S-100B values. A total of 294 serum samples were collected from 147 American Joint Committee on Cancer staging stage III melanoma patients. The mean difference between the first (dummy) and second tubes was 0.003 μg/l (p = 0.077), with a decrease in the second tube. Compared with the second tube, the S-100B level was higher in the first tube in 33.3% of the samples, equal in 36.8% of the samples and lower in 29.9% of the samples. No significant difference between the two consecutively drawn tubes was found. There seems to be no necessity of implementing a dummy tube system for accurate S-100B determination in melanoma patients.

Published
2020
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8. Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial): study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial

Author

Wouter B Nagengast, J Marc C van Dijk, André P van Beek, Rob A Vergeer, Mark R Postma, Iris Schmidt, Astrid GW Korsten-Meijer, Robert A Feijen, Schelto Kruijff, Wilfred F A den Dunnen, Jos M A Kuijlen, and Gerrit van den Berg

Subjects
Medicine
Published
2021
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9. The Value of Pre-Ablative I-131 Scan for Clinical Management in Patients With Differentiated Thyroid Carcinoma

Author

Trynke van der Boom, Wouter T. Zandee, Claire C. J. Dekkers, Anouk N. A. van der Horst-Schrivers, Liesbeth Jansen, Schelto Kruijff, Adrienne H. Brouwers, and Thera P. Links

Subjects
postoperative I-131 diagnostic scan, differentiated thyroid carcinoma, uptake, clinical management, thyroid cancer, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundA diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management.MethodsPatients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression.ResultsIn 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 – 63.8), TSH

Published
2021
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10. Optimization of parathyroid 11C-choline PET protocol for localization of parathyroid adenomas in patients with primary hyperparathyroidism

Author

Milou E. Noltes, Schelto Kruijff, Walter Noordzij, Eef D. Telenga, David Vállez García, Malgorzata Trofimiuk-Müldner, Marta Opalińska, Alicja Hubalewska-Dydejczyk, Gert Luurtsema, Rudi A. J. O. Dierckx, Mostafa El Moumni, Ronald Boellaard, and Adrienne H. Brouwers

Subjects
Primary hyperparathyroidism, 11C-Choline PET, Inter-observer agreement, Scan protocol, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Purpose To evaluate the optimal tracer uptake time, the minimal amount of radioactivity and the inter-observer agreement for 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with primary hyperparathyroidism (pHPT). Methods Twenty-one patients with biochemically proven pHPT were retrospectively studied after injection of 6.3 ± 1.2 MBq/kg 11C-choline. PET data of the first nine patients, scanned for up to 60 min, were reconstructed in 10-min frames from 10- to 60-min postinjection (p.i.), mimicking varying 11C-choline uptake times. Parathyroid adenoma to background contrast ratios were calculated and compared, using standardized uptake values (SUVs). Data was reconstructed with varying scan durations (1, 2.5, 5, and 10 min) at 20–30-min p.i. (established optimal uptake time), mimicking less administered radioactivity. To establish the minimal required radioactivity, the SUVs in the shorter scan durations (1, 2.5, and 5 min) were compared to the 10-min scan duration to determine whether increased variability and/or statistical differences were observed. Four observers analyzed the 11C-choline PET/CT in four randomized rounds for all patients. Results SUVpeak of the adenoma decreased from 30 to 40 p.i. onwards. All adenoma/background contrast ratios did not differ from 20- to 30-min p.i. onwards. The SUVs of adenoma in the scan duration of 1, 2.5, and 5 min all differed significantly from the same SUV in the 10-min scan duration (all p = 0.012). However, the difference in absolute SUV adenoma values was well below 10% and therefore not considered clinically significant. The inter-observer analysis showed that the Fleiss’ kappa of the 1-min scan were classified as “moderate,” while these values were classified as “good” in the 2.5-, 5-, and 10-min scan duration. Observers scored lower certainty scores in the 1- and 2.5-min scans compared to the 5- and 10-min scan durations. Conclusion The optimal time to start PET/CT scanning in patients with pHPT is 20 min after mean injection of 6.3 MBq/kg 11C-choline, with a recommended scan duration of at least 5 min. Alternatively, the radioactivity dose can be lowered by 50% while keeping a 10-min scan duration without losing the accuracy of 11C-choline PET/CT interpretation.

Published
2019
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11. Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

Author

Koen P. Rovers, Checca Bakkers, Geert A. A. M. Simkens, Jacobus W. A. Burger, Simon W. Nienhuijs, Geert-Jan M. Creemers, Anna M. J. Thijs, Alexandra R. M. Brandt-Kerkhof, Eva V. E. Madsen, Ninos Ayez, Nadine L. de Boer, Esther van Meerten, Jurriaan B. Tuynman, Miranda Kusters, Nina R. Sluiter, Henk M. W. Verheul, Hans J. van der Vliet, Marinus J. Wiezer, Djamila Boerma, Emma C. E. Wassenaar, Maartje Los, Cornelis B. Hunting, Arend G. J. Aalbers, Niels F. M. Kok, Koert F. D. Kuhlmann, Henk Boot, Myriam Chalabi, Schelto Kruijff, Lukas B. Been, Robert J. van Ginkel, Derk Jan A. de Groot, Rudolf S. N. Fehrmann, Johannes H. W. de Wilt, Andreas J. A. Bremers, Philip R. de Reuver, Sandra A. Radema, Karin H. Herbschleb, Wilhelmina M. U. van Grevenstein, Arjen J. Witkamp, Miriam Koopman, Nadia Haj Mohammad, Eino B. van Duyn, Walter J. B. Mastboom, Leonie J. M. Mekenkamp, Joost Nederend, Max J. Lahaye, Petur Snaebjornsson, Cornelis Verhoef, Hanneke W. M. van Laarhoven, Aeilko H. Zwinderman, Jeanette M. Bouma, Onno Kranenburg, Iris van ‘t Erve, Remond J. A. Fijneman, Marcel G. W. Dijkgraaf, Patrick H. J. Hemmer, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. J. T. de Hingh, Dutch Peritoneal Oncology Group (DPOG), and Dutch Colorectal Cancer Group (DCCG)

Subjects
Colorectal neoplasms, Peritoneal neoplasms, Cytoreduction surgical procedures, Hyperthermia, induced, Neoadjuvant therapy, Adjuvant chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. Methods This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0–10 or 11–20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician’s discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. Discussion This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. Trial registration Clinicaltrials.gov/NCT02758951, NTR/NTR6301, ISRCTN/ISRCTN15977568, EudraCT/2016–001865-99.

Published
2019
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13. Heterogeneity in Utilization of Optical Imaging Guided Surgery for Identifying or Preserving the Parathyroid Glands—A Meta-Narrative Review

Author

Eline A. Feitsma, Hugo M. Schouw, Milou E. Noltes, Wido Heeman, Wendy Kelder, Gooitzen M. van Dam, and Schelto Kruijff

Subjects
optical imaging, fluorescence, thyroidectomy, parathyroid glands, hypoparathyroidism, near-infrared imaging, Science
Abstract

Background: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy. Over the past years, optical imaging techniques, such as parathyroid autofluorescence, indocyanine green (ICG) angiography, and laser speckle contrast imaging (LSCI) have been employed to save parathyroid glands during thyroid surgery. This study provides an overview of the utilized methods of the optical imaging techniques during total thyroidectomy for parathyroid gland identification and preservation. Methods: PUBMED, EMBASE and Web of Science were searched for studies written in the English language utilizing parathyroid autofluorescence, ICG-angiography, or LSCI during total thyroidectomy to support parathyroid gland identification or preservation. Case reports, reviews, meta-analyses, animal studies, and post-mortem studies were excluded after the title and abstract screening. The data of the studies were analyzed qualitatively, with a focus on the methodologies employed. Results: In total, 59 articles were included with a total of 6190 patients. Overall, 38 studies reported using parathyroid autofluorescence, 24 using ICG-angiography, and 2 using LSCI. The heterogeneity between the utilized methodology in the studies was large, and in particular, regarding study protocols, imaging techniques, and the standardization of the imaging protocol. Conclusion: The diverse application of optical imaging techniques and a lack of standardization and quantification leads to heterogeneous conclusions regarding their clinical value. Worldwide consensus on imaging protocols is needed to establish the clinical utility of these techniques for parathyroid gland identification and preservation.

Published
2022
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14. Increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvement

Author

Eric A Deckers, Marieke WJ Louwman, Schelto Kruijff, and Harald J Hoekstra

Subjects
elderly, head and neck, melanoma, sentinel lymph node, socioeconomic status, staging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aim: To investigate implementation of the seventh American Joint Committee on Cancer melanoma staging with sentinel lymph node biopsy (SLNB) and associations with socioeconomic status (SES). Patients & methods: Data from The Netherlands Cancer Registry on patient and tumor characteristics were analyzed for all stage IB–II melanoma cases diagnosed 2010–2016, along with SES data from The Netherlands Institute for Social Research. Results: The proportion of SLNB-staged patients increased from 40% to 65% (p

Published
2020
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15. Application of CO2 laser evaporation in locally advanced melanoma

Author

Otis M Vrielink, Schelto Kruijff, Barbara L van Leeuwen, and Jan LN Roodenburg

Subjects
CO2 laser, in-transit, melanoma, metastases, satellite, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aim: This study aims to investigate the role of CO2 laser evaporation in the treatment of melanoma patients with satellite or in-transit metastases. Materials & methods: Patients who underwent CO2 laser evaporation were retrospectively included between November 2002 and August 2018. The Sharplan 40C CO2 laser was used with a high pulse wave mode. Data concerning patient and tumor characteristics, CO2 laser evaporation and subsequent therapies were collected. Results: A total of 26 patients were included. Median duration of local control was 5.5 months. The median number of lesions evaporated per treatment was three (1–16); patients received a median of three (1–19) treatments. Conclusion: In a selected group of melanoma patients with satellite or in-transit metastases, CO2 laser evaporation should be considered as treatment for local control.

Published
2019
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16. Salvage surgery for a giant melanoma on the back

Author

Joost Klaase, Schelto Kruijff, and Robert Vink

Subjects
giant melanoma, salvage surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

We report a case of a giant melanoma on the back with a very extreme Breslow thickness. On physical examination a large odorous and ulcerating tumour was seen adjacent to two large crusted lesions, probably in transit metastases. In the right and left axilla enlarged lymph nodes were palpated. The patient underwent salvage surgery consisting of a complete wide excision of the tumors on the back as well as axillary lymph node dissection on both sides. Histopathology showed a malignant melanoma with a Breslow thickness of 48 mm. Four of fifteen nodes in the right axilla and one of nine nodes in the left axilla, were positive for metastatic disease. Also various in transit and subcutaneous metastases were found in the wide excision specimen. The interest of our observation relies in the rarity of a melanoma with such an extreme Breslow thickness and the difficulty in performing adequate palliative therapy that offers quality of life by means of tumor control.

Published
2011
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17. Towards in vivo characterization of thyroid nodules suspicious for malignancy using multispectral optoacoustic tomography

Author

Milou E. Noltes, Maximilian Bader, Madelon J. H. Metman, Jasper Vonk, Pieter J. Steinkamp, Jan Kukačka, Henriette E. Westerlaan, Rudi A. J. O. Dierckx, Bettien M. van Hemel, Adrienne H. Brouwers, Gooitzen M. van Dam, Dominik Jüstel, Vasilis Ntziachristos, and Schelto Kruijff

Subjects
Multispectral optoacoustic tomography, Photoacoustic, Radiology, Nuclear Medicine and imaging, Optoacoustic, General Medicine, Thyroid cancer, Thyroid nodule
Abstract

Purpose Patient-tailored management of thyroid nodules requires improved risk of malignancy stratification by accurate preoperative nodule assessment, aiming to personalize decisions concerning diagnostics and treatment. Here, we perform an exploratory pilot study to identify possible patterns on multispectral optoacoustic tomography (MSOT) for thyroid malignancy stratification. For the first time, we directly correlate MSOT images with histopathology data on a detailed level. Methods We use recently enhanced data processing and image reconstruction methods for MSOT to provide next-level image quality by means of improved spatial resolution and spectral contrast. We examine optoacoustic features in thyroid nodules associated with vascular patterns and correlate these directly with reference histopathology. Results Our methods show the ability to resolve blood vessels with diameters of 250 μm at depths of up to 2 cm. The vessel diameters derived on MSOT showed an excellent correlation (R2-score of 0.9426) with the vessel diameters on histopathology. Subsequently, we identify features of malignancy observable in MSOT, such as intranodular microvascularity and extrathyroidal extension verified by histopathology. Despite these promising features in selected patients, we could not determine statistically relevant differences between benign and malignant thyroid nodules based on mean oxygen saturation in thyroid nodules. Thus, we illustrate general imaging artifacts of the whole field of optoacoustic imaging that reduce image fidelity and distort spectral contrast, which impedes quantification of chromophore presence based on mean concentrations. Conclusion We recommend examining optoacoustic features in addition to chromophore quantification to rank malignancy risk. We present optoacoustic images of thyroid nodules with the highest spatial resolution and spectral contrast to date, directly correlated to histopathology, pushing the clinical translation of MSOT.

Published
2023

18. International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers

Author

Kristy K, Broman, Tasha M, Hughes, Brooke C, Bredbeck, James, Sun, Dennis, Kirichenko, Michael J, Carr, Avinash, Sharma, Edmund K, Bartlett, Amanda A G, Nijhuis, John F, Thompson, Tina J, Hieken, Lisa, Kottschade, Jennifer, Downs, David E, Gyorki, Emma, Stahlie, Alexander, van Akkooi, David W, Ollila, Kristin, O'shea, Yun, Song, Giorgos, Karakousis, Marc, Moncrieff, Jenny, Nobes, John, Vetto, Dale, Han, Meghan, Hotz, Jeffrey M, Farma, Jeremiah L, Deneve, Martin D, Fleming, Matthew, Perez, Kirsten, Baecher, Michael, Lowe, Roger Olofsson, Bagge, Jan, Mattsson, Ann Y, Lee, Russell S, Berman, Harvey, Chai, Hidde M, Kroon, Juri, Teras, Roland M, Teras, Norma E, Farrow, Georgia M, Beasley, Jane Yuet Ching, Hui, Lukas, Been, Schelto, Kruijff, Brandy, Sinco, Amod A, Sarnaik, Vernon K, Sondak, Jonathan S, Zager, and Lesly A, Dossett

Subjects
implementation science, sentinel lymph node, active surveillance, melanoma, de-implementation, Surgery, adjuvant therapy, completion lymph node dissection
Abstract

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Published
2023

19. Patient-derived parathyroid organoids as a tracer and drug-screening application model

Author

Milou E. Noltes, Luc H.J. Sondorp, Laura Kracht, Inês F. Antunes, René Wardenaar, Wendy Kelder, Annelies Kemper, Wiktor Szymanski, Wouter T. Zandee, Liesbeth Jansen, Adrienne H. Brouwers, Robert P. Coppes, Schelto Kruijff, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
Technetium Tc 99m Sestamibi, Cell Biology, endocrine diseases, Hyperparathyroidism, Primary, SPECT/PET tracer, Biochemistry, Organoids, hyperparathyroidism, stem cells, patient-derived organoid model, Genetics, Humans, parathyroid glands, Calcium, drug screening, Developmental Biology
Abstract

Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish a patient-derived parathyroid organoid model representing human parathyroid tissue. Hyperplastic parathyroid tissue was dispersed, and parathyroid organoids (PTOs) were cultured and characterized. PTO-derived cells exhibited self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA sequencing confirmed that PTOs phenocopy hyperplastic parathyroid tissue. Exposure of PTOs to increasing calcium concentrations and PTH-lowering drugs resulted in significantly reduced PTH excretion. PTOs showed specific binding of the imaging tracers 11C-methionine and 99mTc-sestamibi. These data show the functionality of PTOs resembling the parathyroid. This PTO model recapitulates the originating tissue on gene and protein expression and functionality, paving the way for future physiology studies and therapeutic target and tracer discovery.

Published
2022

20. Feasibility of bevacizumab-IRDye800CW as a tracer for fluorescence-guided meningioma surgery

Author

Bianca M, Dijkstra, Julie, Nonnekens, Wouter, Nagengast, Schelto, Kruijff, Gert Jan, Meersma, Wilfred F A, den Dunnen, Frank A E, Kruyt, Rob J M, Groen, Radiology & Nuclear Medicine, and Molecular Genetics

Subjects
SDG 3 - Good Health and Well-being, General Medicine
Abstract

OBJECTIVE Meningiomas are frequently occurring, often benign intracranial tumors. Molecular fluorescence can be used to intraoperatively identify residual meningioma tissue and optimize safe resection; however, currently no clinically approved agent is available for this specific tumor type. In meningiomas, vascular endothelial growth factor α (VEGFα) is upregulated, and this biomarker could be targeted with bevacizumab-IRDye800CW, a fluorescent agent that is already clinically applied for the resection of other tumors and neoplasms. Here, the authors investigated the feasibility of using bevacizumab-IRDye800CW to target VEGFα in a CH-157MN xenografted mouse model. METHODS Five mice with CH-157MN xenografts with volumes of 500 mm3 were administered intravenous bevacizumab-IRDye800CW. Mice were imaged in vivo at 24 hours, 48 hours, and 72 hours after injection with the FMT2500 fluorescence imaging system. Biodistribution was determined ex vivo using the Pearl fluorescent imager at 72 hours after injection. To mimic a clinical scenario, 2 animals underwent postmortem xenograft resection using both white-light and fluorescence guidance. Lastly, fresh and frozen human meningioma specimens were incubated ex vivo with bevacizumab-IRDye800CW, stained with anti-VEGFα, and microscopically examined. RESULTS In vivo, tumors fluoresced at all time points after tracer administration and background fluorescence decreased with time. Ex vivo analyses of tracer biodistribution showed the highest fluorescence in resected tumor tissue. Brain, skull, and muscle tissue showed very low fluorescence. Microscopically, fluorescence was observed in the cytoplasm and was correlated with VEGFα expression patterns. During postmortem surgery, both the tumor bulk and a small tumor remnant were detected. Bevacizumab-IRDye800CW bound specifically to all tested human meningioma samples, as indicated by a high fluorescent signal in the tumor bulk compared with the surrounding healthy dura mater. CONCLUSIONS Bevacizumab-IRDye800CW showed meningioma specificity, as illustrated by high VEGFα-mediated uptake in the meningioma xenograft mouse model. Small tumor lesions were detected using fluorescence guidance. Thus, the next step will be to assess the feasibility of using already available clinical grade bevacizumab-IRDye800CW to optimize meningioma resection in a human trial.

Published
2023

21. Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism

Author

Milou E. Noltes, Justin Cottrell, Amin Madani, Lorne Rotstein, Karen Gomez-Hernandez, Karen Devon, Miranda K. Boggild, David P. Goldstein, Evelyn M. Wong, Adrienne H. Brouwers, Schelto Kruijff, Antoine Eskander, Eric Monteiro, Jesse D. Pasternak, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Canada, Otorhinolaryngology, OF-CARE, MORTALITY, CLINICAL INDICATORS, Humans, Reproducibility of Results, Surgery, Hyperparathyroidism, Primary, GUIDELINES, Quality Improvement, Original Investigation, Quality Indicators, Health Care
Abstract

IMPORTANCE Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways.OBJECTIVE To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease.DESIGN, SETTING, AND PARTICIPANTS This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021.MAIN OUTCOMES AND MEASURES Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care.RESULTS Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings.CONCLUSIONS AND RELEVANCE This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT.

Published
2022

22. State of the art and future directions in the systemic treatment of medullary thyroid cancer

Author

Eline C Jager, K Esther Broekman, Thera P. Links, and Schelto Kruijff

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Endothelium, Cabozantinib, Angiogenesis, Multiple Endocrine Neoplasia Type 2a, Vandetanib, Multikinase inhibitor, chemistry.chemical_compound, Internal medicine, medicine, Humans, Thyroid Neoplasms, Adverse effect, Kinase, business.industry, Proto-Oncogene Proteins c-ret, Medullary thyroid cancer, medicine.disease, Carcinoma, Neuroendocrine, medicine.anatomical_structure, chemistry, Carcinoma, Medullary, business, medicine.drug
Abstract

Purpose of review Systemic treatment is the only therapeutic option for patients with progressive, metastatic medullary thyroid cancer (MTC). Since the discovery of the rearranged during transfection (RET) proto-oncogene (100% hereditary, 60-90% sporadic MTC), research has focused on finding effective systemic therapies to target this mutation. This review surveys recent findings. Recent findings Multikinase inhibitors are systemic agents targeting angiogenesis, inhibiting growth of tumor cells and cells in the tumor environment and healthy endothelium. In the phase III EXAM and ZETA trials, cabozantinib and vandetanib showed progression-free survival benefit, without evidence of prolonged overall survival. Selpercatinib and pralsetinib are kinase inhibitors with high specificity for RET; phase I and II studies showed overall response rates of 73% and 71% in first line, and 69% and 60% in second line treatment, respectively. Although resistance mechanisms to mutation-driven therapy will be a challenge in the future, phase III studies are ongoing and neo-adjuvant therapy with selpercatinib is being studied. Summary The development of selective RET-inhibitors has expanded the therapeutic arsenal to control tumor growth in progressive MTC, with fewer adverse effects than multikinase inhibitors. Future studies should confirm their effectiveness, study neo-adjuvant strategies, and tackle resistance to these inhibitors, ultimately to improve patient outcomes.

Published
2022

23. Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

Author

Argandykov, Dias, Dorken-Gallastegi, Ander, El Moheb, Mohamad, Gebran, Anthony, Proaño-Zamudio, Jefferson A, Bokenkamp, Mary, Renne, Angela M, Nepogodiev, Dmitri, Bhangu, Aneel, Kaafarani, Haytham M A, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Aneel, Bhangu, Dmitri, Nepogodiev, Irida, Dajti, Arben, Gjata, Luis, Boccalatte, Mariamarta, Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Kamral, Hossain, Gabrielle, Vanramshorst, Ismail, Lawani, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maria Marta Modolo, Maricarmen, Olivos, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Jaroslav, Klat, René, Novysedlak, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Dhruv, Ghosh, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, Gaetano, Francesco, Pata, Gianluca, Pellino, Sohei, Satoi, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Mohammad, Jamal, Muhammed, Elhadi, Aiste, Gulla, April, Roslani, Laura, Martinez, Antonio Ramos De La Medina, Oumaima, Outani, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Dejan, Radenkovic, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Ana, Minaya-Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Arda, Isik, Sezai, Leventoğlu, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Sattar, Alshryda, Osaid, Alser, Kerry, Breen, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Hassan, Mashbari, Hamza Al Naggar, Dennis, Mazingi, J J, Wong, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, S M, Roser, K A, Olson, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, A B, Haynes, Mcelhinney, K, Roward, S, M D, Trust, C E, Hill, P G, Teixeira, Etchill, E, Stevens, K, M R, Ladd, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, L R, Maurer, El Moheb, M, Gaitanidis, A, Naar, L, M A, Christensen, Kapoen, C, Langeveld, K, El Hechi, M, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, Martin, Rcg, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, Brathwaite, Cem, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, M El Moheb, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, Monson, Jrt, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, Dauer, E, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, and N Martins, P

Subjects
COVID-19, COVIDSurg, mortality, postoperative complications, Surgery, Critical Care and Intensive Care Medicine
Published
2023

24. A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Toward Clinical Implementation

Author

Tessa M van Ginhoven, Schelto Kruijff, Gooitzen M. van Dam, Adrienne H. Brouwers, Christiaan E Boerma, Anton F. Engelsman, Jesse D. Pasternak, Milou E Noltes, Menno R. Vriens, Lorne Rotstein, Wido Heeman, Madelon J H Metman, Surgery, Health & Food, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Microbes in Health and Disease (MHD)

Subjects
Indocyanine Green, Male, medicine.medical_specialty, genetic structures, Standardization, medicine.medical_treatment, Population, Proof of Concept Study, Workflow, Parathyroid Glands, chemistry.chemical_compound, Postoperative Complications, medicine, Humans, Prospective Studies, education, education.field_of_study, business.industry, Organ dysfunction, Angiography, Thyroidectomy, Reproducibility of Results, medicine.disease, eye diseases, medicine.anatomical_structure, chemistry, Hypoparathyroidism, Feasibility Studies, Female, Surgery, Parathyroid gland, Radiology, medicine.symptom, business, Indocyanine green, Perfusion
Abstract

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user.SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of have been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion.METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland are an ideal model as parathyroid function post-surgery is only affected by perfusion.RESULTS: We show that visual -subjective- interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases.CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population.

Published
2021

25. Let’s embrace optical imaging

Author

Riemer H. J. A. Slart, Gooitzen M. van Dam, Schelto Kruijff, Wouter B. Nagengast, Rudi Dierckx, Milou E Noltes, Pieter J van der Zaag, Wiktor Szymanski, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Microbes in Health and Disease (MHD), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Molecular Biophysics, Cardiovascular Centre (CVC), Translational Immunology Groningen (TRIGR), Synthetic Organic Chemistry, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
THERANOSTICS, medicine.medical_specialty, business.industry, General Medicine, Molecular Imaging, Tree (data structure), Optical imaging, PET, ATHEROSCLEROSIS, TOMOGRAPHY, SPECT, HISTORY, medicine, 1ST-IN-HUMAN, Humans, VISUALIZATION, Radiology, Nuclear Medicine and imaging, Tomography, Radiology, Molecular imaging, business, 11 CANCERS, IN-VIVO
Published
2021

26. Bispecific antibody CD73xEpCAM selectively inhibits the adenosine-mediated immunosuppressive activity of carcinoma-derived extracellular vesicles

Author

Isabel Britsch, Emily M. Ploeg, Xiurong Ke, Wijnand Helfrich, Hao Zhang, Douwe F. Samplonius, Schelto Kruijff, Mark A. J. M. Hendriks, and Femke A Van der Zant

Subjects
Cancer Research, medicine.medical_treatment, Cell, Cancer immunotherapy, Proinflammatory cytokine, Immune system, Ecto-5 '-nucleotidase, medicine, Extracellular, Bifunctional antibody, EXOSOMES, biology, Tumor exosomes, Chemistry, Microvesicles, Immune checkpoint, medicine.anatomical_structure, TARGET, Oncology, biology.protein, Cancer research, T-CELLS, CD73, Antibody
Abstract

Tumor-derived extracellular vesicles (EVs) carry potent immunosuppressive factors that affect the antitumor activities of immune cells. A significant part of the immunoinhibitory activity of EVs is attributable to CD73, a GPI-anchored ecto-5′-nucleotidase involved in the conversion of tumor-derived proinflammatory extracellular ATP (eATP) to immunosuppressive adenosine (ADO). The CD73-antagonist antibody oleclumab inhibits cell surface-exposed CD73 and is currently undergoing clinical testing for cancer immunotherapy. However, a strategy to selectively inhibit CD73 exposed on EVs is not available. Here, we present a novel bispecific antibody (bsAb) CD73xEpCAM designed to bind with high affinity the common EV surface marker EpCAM and concurrently inhibit CD73. Unlike oleclumab, bsAb CD73xEpCAM potently inhibited the immunosuppressive activity of EVs from CD73pos/EpCAMpos carcinoma cell lines and patient-derived colorectal cancer cells. Taken together, selective blockade of EV-exposed CD73 by bsAb CD73xEpCAM may be useful as an alternate or complementary targeted approach in cancer immunotherapy.

Published
2021

27. Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA

Author

Osaid, Alser, Ander Dorken Gallastegi, Anthony, Gebran, Kerry, Breen, Mohamad El Moheb, Apostolos, Gaitanidis, Leon, Naar, Brittany, Bankhead-Kendall, Hassan, Mashbari, Robert, D Sinyard, Lydia, R Maurer, Charu, Paranjape, George, C Velmahos, Dmitri, Nepogodiev, Aneel, Bhangu, Haytham M, A Kaafarani, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Irida, Dajti, Arben, Gjata, Oussama, Kacimi, Luis, Boccalatte, Maria Marta Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Ahmed, Elgun, Amer, Alderazi, Kamral, Hossain, Greg, Padmore, Gabrielle, Vanramshorst, Ismail, Lawani, Duane, Wedderburn, Sonam, Dargay, Israël, Feraudy, Cerovac, Anis, Samir, Delibegovic, Alemayehu Ginbo Bedada, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Jean Marie Vianney Butoyi, Chukwuemeka, Nwegbu, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maricarmen, Olivos, Dong-Lin, Ren, Wenhui, Lou, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Pablo, Avilés, Nikolaos, Gouvas, Jaroslav, Klat, René, Novysedlak, Nicolas, Amisi, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Danilo Alfonso Arévalo Sandoval, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Roumanatou Bankole Sapin, Kebba, Marenah, Zaza, Demetrashvili, Andreas, A Schnitzbauer, Magdalena, Gruendl, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Bernard Ofori Appiah, Daniel, Acquah, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Atul, Suroy, Dhruv, Ghosh, Pranay, Pawar, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, G, Pata, Francesco, Gianluca, Pellino, Naoto, Kuroda, Sohei, Satoi, Yuki, Fujimoto, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Intisar, Hisham, Jin-Young, Jang, Enver, Fekaj, Mohammad, Jamal, Anvar, Beisembaev, Muhammed, Elhadi, Aiste, Gulla, Luc, Samison, Jupsi, Neny, Palesa, Chisala, April, Roslani, Iran Irani Duran Sanchez, Laura Martinez Perez Maldonado, Antonio Ramos De La Medina, Jade, Nunez, Oumaima, Outani, Abd'Rashid, Nashidengo, Ashish Lal Shrestha, Rakesh, Shah, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Chris, Varghese, Deborah, Wright, Jorge, Neira, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Kjetil, Soreide, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Chris, Munguas, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Abdourahmane, Ndong, Dejan, Radenkovic, Ibrahim, Sesay, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Arpad, Panyko, Jurij, Kosir, Uros, Bele, Hassan, Ali, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Eleftherios, Gialamas, Karoline, Horisberger, Michel, Adamina, Muhammad, Alshaar, Abel, Huang, Ben, Mbwele, Varut, Lohsiriwat, Shane, Charles, Haithem, Jlassi, Arda, Isik, Sezai, Leventoğlu, Lekuya, Herve, Lekuya, Monka, Herman, Lule, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Slava, Kopetskiy, Sattar, Alshryda, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Fernando, Bonilla, Hamza Al Naggar, Mayaba, Maimbo, Dennis, Mazingi, J Wong, J, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, M Roser, S, A Olson, K, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, B Haynes, A, Mcelhinney, K, Roward, S, D Trust, M, E Hill, C, G Teixeira, P, Etchill, E, Stevens, K, R Ladd, M, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, R Maurer, L, M El Moheb, Gaitanidis, A, Naar, L, A Christensen, M, Kapoen, C, Langeveld, K, M El Hechi, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, R C, G Martin, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, C E, M Brathwaite, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, J R, T Monson, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, D Dauer, M, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, N Martins, P, Xiao, Liu, and Alistair, Denniston

Subjects
Male, medicine.medical_specialty, Revised Cardiac Risk Index, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pulmonary complications, Malignancy, Time-to-Treatment, Postoperative Complications, Sex Factors, Risk Factors, medicine, COVID-19, COVIDSurg, elective surgery, emergency surgery, mortality, pulmonary complications, Humans, In patient, Prospective Studies, emergency surgery, Elective surgery, Aged, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, Pulmonary Complication, Age Factors, COVID-19, Pneumonia, Perioperative, Middle Aged, COVIDSurg, elective surgery, mortality, medicine.disease, United States, Surgery, Multicenter study, Elective Surgical Procedures, Female, business
Abstract

Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

Published
2021

28. Thickness of Biceps and Quadriceps Femoris Muscle Measured Using Point-of-Care Ultrasound as a Representation of Total Skeletal Muscle Mass

Author

Rianne N. M. Hogenbirk, Alain R. Viddeleer, Judith E. K. R. Hentzen, Willemijn Y. van der Plas, Cees P. van der Schans, Geertruida H. de Bock, Schelto Kruijff, Joost M. Klaase, Surgery, Health Psychology Research (HPR), Extremities Pain and Disability (EXPAND), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Organ Transplantation (GIOT), and Value, Affordability and Sustainability (VALUE)

Subjects
sarcopenia, POCUS, muscle force, muscle status, skeletal muscle index, General Medicine
Abstract

Generalized loss of muscle mass is associated with increased morbidity and mortality in patients with cancer. The gold standard to measure muscle mass is by using computed tomography (CT). However, the aim of this prospective observational cohort study was to determine whether point-of-care ultrasound (POCUS) could be an easy-to-use, bedside measurement alternative to evaluate muscle status. Patients scheduled for major abdominal cancer surgery with a recent preoperative CT scan available were included. POCUS was used to measure the muscle thickness of mm. biceps brachii, mm. recti femoris, and mm. vasti intermedius 1 day prior to surgery. The total skeletal muscle index (SMI) was derived from patients’ abdominal CT scan at the third lumbar level. Muscle force of the upper and lower extremities was measured using a handheld dynamometer. A total of 165 patients were included (55% male; 65 ± 12 years). All POCUS measurements of muscle thickness had a statistically significant correlation with CT-derived SMI (r ≥ 0.48; p < 0.001). The strongest correlation between POCUS muscle measurements and SMI was observed when all POCUS muscle groups were added together (r = 0.73; p < 0.001). Muscle strength had a stronger correlation with POCUS-measured muscle thickness than with CT-derived SMI. To conclude, this study indicated a strong correlation between combined muscle thickness measurements performed by POCUS- and CT-derived SMI and measurements of muscle strength. These results suggest that handheld ultrasound is a valid tool for the assessment of skeletal muscle status.

Published
2022

29. Targeted optical fluorescence imaging: a meta-narrative review and future perspectives

Author

L. A. Huisman, G. M. van Dam, J.M. van Dijl, Schelto Kruijff, Rudi Dierckx, H. M. Schouw, Ronald Borra, Adrienne H. Brouwers, Antoon T. M. Willemsen, Wiktor Szymanski, Riemer H. J. A. Slart, Y. F. Janssen, and Hendrikus H. Boersma

Subjects
medicine.medical_specialty, INDOCYANINE GREEN, Cardiology, Optical fluorescence imaging, Review Article, Medical Oncology, Fluorescence, Optical imaging, RENAL-CELL CARCINOMA, GUIDED SURGERY, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, HEAD, Head and neck, Reimbursement, COLORECTAL ORIGIN, Inflammation, Developmental stage, Infectious disease, Infectious Disease Medicine, business.industry, Gynaecological oncology, Optical Imaging, General Medicine, OPEN-LABEL, Cardiovascular disease, CANCER, Optical fluorescence, PERITONEAL CARCINOMATOSIS, Oncology, Infectious disease (medical specialty), Narrative review, business, SENTINEL LYMPH-NODE, SINGLE-CENTER, Forecasting
Abstract

Purpose The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice.

Published
2021

30. Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases A Phase 2 Randomized Clinical Trial

Author

Arjen J. Witkamp, Joost Nederend, Andreas J A Bremers, Philip R. de Reuver, Wilhelmina M U van Grevenstein, Henk M.W. Verheul, Koen P. Rovers, Max J. Lahaye, Niels F. M. Kok, Jurriaan B. Tuynman, Checca Bakkers, Maartje Los, Ignace H. J. T. de Hingh, Anna M.J. Thijs, Patrick H. J. Hemmer, Alexandra R. M. Brandt-Kerkhof, Miriam Koopman, Onno Kranenburg, Petur Snaebjornsson, Marcel G. W. Dijkgraaf, Simon W. Nienhuijs, Arend G. J. Aalbers, Schelto Kruijff, Jacobus W. A. Burger, Tineke E. Buffart, Derk Jan A. de Groot, Esther van Meerten, Iris van 't Erve, Geert-Jan Creemers, Miranda Kusters, Pieter J. Tanis, Eva V. E. Madsen, Remond J.A. Fijneman, Kathelijn S. Versteeg, Djamila Boerma, Cornelis J A Punt, Marinus J. Wiezer, Surgery, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, Internal medicine, VU University medical center, Epidemiology and Data Science, APH - Methodology, Oncology, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Epidemiologie, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy

Subjects
Male, PROGNOSIS, medicine.medical_treatment, CARCINOMATOSIS, MULTICENTER, Hyperthermic Intraperitoneal Chemotherapy, 030230 surgery, Peritoneal Neoplasms/secondary, law.invention, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, FOLFOX, Randomized controlled trial, law, Adenocarcinoma/secondary, Adjuvant/adverse effects, Neoadjuvant therapy, Original Investigation, Bevacizumab/administration & dosage, Cytoreduction Surgical Procedures, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Middle Aged, OPEN-LABEL, CANCER, Neoadjuvant Therapy, Fluorouracil/administration & dosage, Capecitabine/administration & dosage, 030220 oncology & carcinogenesis, FOLFIRI, Leucovorin/administration & dosage, Hyperthermic intraperitoneal chemotherapy, Female, medicine.drug, medicine.medical_specialty, Camptothecin/administration & dosage, Capecitabine, 03 medical and health sciences, Chemotherapy, Adjuvant/adverse effects, Oxaliplatin/administration & dosage, REGRESSION, medicine, MANAGEMENT, Chemotherapy, Humans, Organoplatinum Compounds/administration & dosage, Perioperative Period, Response Evaluation Criteria in Solid Tumors, Aged, Colorectal Neoplasms/pathology, HIPEC, business.industry, Perioperative, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Irinotecan, Mitomycin/administration & dosage, Feasibility Studies, business, CONSENSUS
Abstract

Contains fulltext : 238268.pdf (Publisher’s version ) (Closed access) IMPORTANCE: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). OBJECTIVE: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. INTERVENTIONS: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. MAIN OUTCOMES AND MEASURES: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). RESULTS: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. CONCLUSIONS AND RELEVANCE: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02758951.

Published
2021

32. Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection

Author

Pascal K. C. Jonker, Madelon J. H. Metman, Luc H. J. Sondorp, Mark S. Sywak, Anthony J. Gill, Liesbeth Jansen, Thera P. Links, Paul J. van Diest, Tessa M. van Ginhoven, Clemens W. G. M. Löwik, Anh H. Nguyen, Robert P. Coppes, Dominic J. Robinson, Gooitzen M. van Dam, Bettien M. van Hemel, Rudolf S. N. Fehrmann, Schelto Kruijff, Surgery, Radiology & Nuclear Medicine, Pathology, Otorhinolaryngology and Head and Neck Surgery, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Microbes in Health and Disease (MHD), and Targeted Gynaecologic Oncology (TARGON)

Subjects
SDG 3 - Good Health and Well-being, Thyroid Cancer, Papillary, Spectrum Analysis, Carcinoma, Thyroidectomy, Humans, Radiology, Nuclear Medicine and imaging, Lymph Nodes, Thyroid Neoplasms, General Medicine, Neoplasm Recurrence, Local, Carcinoma, Papillary
Abstract

Purpose Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively. Methods We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET. Results MET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p p Conclusion MET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%. Clinical trial registration. NCT03470259.

Published
2022

33. Association of time-updated plasma calcium and phosphate with graft and patient outcomes after kidney transplantation

Author

Stefan P Berger, Schelto Kruijff, Martin H. de Borst, Willemijn Y. van der Plas, Antonio W. Gomes Neto, Robert A. Pol, Stephan J. L. Bakker, Groningen Institute for Organ Transplantation (GIOT), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
Adult, Graft Rejection, Male, hyperparathyrodism, medicine.medical_specialty, Renal function, kidney transplantation/nephrology, kidney (allograft) function/dysfunction, 030230 surgery, clinical research/practice, Gastroenterology, Phosphates, 03 medical and health sciences, Hyperphosphatemia, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Prospective Studies, Prospective cohort study, Kidney transplantation, Transplantation, business.industry, Proportional hazards model, Graft Survival, Confounding, Middle Aged, Clinical Science, health services and outcomes research, medicine.disease, Kidney Transplantation, Kidney Failure, Chronic, Calcium, Female, Original Article, ORIGINAL ARTICLES, business, Homeostasis, Hypophosphatemia
Abstract

Disturbances in calcium‐phosphate homeostasis are common after kidney transplantation. We aimed to assess the relationship between deregulations in plasma calcium and phosphate over time and mortality and death‐censored graft failure (DCGF). In this prospective cohort study, we included kidney transplant recipients with ≥2 plasma calcium and phosphate measurements. Data were analyzed using time‐updated Cox regression analyses adjusted for potential confounders including time‐updated kidney function. We included 2769 patients (mean age 47 ± 14 years, 42.3% female) with 138 496 plasma calcium and phosphate levels (median [IQR] 43 [31–61] measurements per patient). During follow‐up of 16.3 [8.7–25.2] years, 17.2% developed DCGF and 7.9% died. Posttransplant hypercalcemia was associated with an increased risk of mortality (1.63 [1.31–2.00], p, This prospective cohort study shows that, in patients with preserved kidney function, hypercalcemia is associated with increased mortality risk.

Published
2021

34. Necrosis binding of Ac-Lys(0)(IRDye800CW)-Tyr(3)-octreotate

Author

Marion de Jong, Yann Seimbille, Schelto Kruijff, Rob J. M. Groen, Clemens W G M Löwik, Bianca M. Dijkstra, Wilfred F. A. den Dunnen, Laura Mezzanotte, Frank A.E. Kruyt, Sebastiaan E. Dulfer, Marcus C. M. Stroet, Kranthi M. Panth, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Molecular Neuroscience and Ageing Research (MOLAR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Radiology & Nuclear Medicine, Molecular Genetics, and Clinical sciences

Subjects
Necrosis, R895-920, Inflammation, Somatostatin receptor subtype 2, 030218 nuclear medicine & medical imaging, Medical physics. Medical radiology. Nuclear medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Necrosis-avidity, 800CW-TATE, Fluorescent molecular probes, Molecular fluorescence-guided surgery, medicine, Radiology, Nuclear Medicine and imaging, FORMULATION, Octreotate, biology, business.industry, Small molecule, Fluorescence, CANCER, Staining, FLUORESCENT, chemistry, 030220 oncology & carcinogenesis, Biophysics, biology.protein, TUMOR NECROSIS, Tumor necrosis factor alpha, RECEPTOR RADIONUCLIDE THERAPY, medicine.symptom, Antibody, business
Abstract

Background There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Results Binding of 800CW-TATE could be blocked with DOTA0-Tyr3-octreotate (DOTA-TATE) on cultured SSTR2-positive U2OS cells and was absent in SSTR2 negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR2 negative cells. No SSTR2-mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. Conclusion This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents.

Published
2021

35. Postoperative muscle loss, protein intake, physical activity and outcome associations

Author

Rianne N M Hogenbirk, Willemijn Y van der Plas, Judith E K R Hentzen, Laura van Wijk, Allard G Wijma, Carlijn I Buis, Alain R Viddeleer, Geertruida H de Bock, Cees P van der Schans, Gooitzen M van Dam, Schelto Kruijff, Joost M Klaase, Surgery, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Health Psychology Research (HPR), Extremities Pain and Disability (EXPAND), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Microbes in Health and Disease (MHD), Value, Affordability and Sustainability (VALUE), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
Surgery
Abstract

Background Skeletal muscle loss is often observed in intensive care patients. However, little is known about postoperative muscle loss, its associated risk factors, and its long-term consequences. The aim of this prospective observational study is to identify the incidence of and risk factors for surgery-related muscle loss (SRML) after major abdominal surgery, and to study the impact of SRML on fatigue and survival. Methods Patients undergoing major abdominal cancer surgery were included in the MUSCLE POWER STUDY. Muscle thickness was measured by ultrasound in three muscles bilaterally (biceps brachii, rectus femoris, and vastus intermedius). SRML was defined as a decline of 10 per cent or more in diameter in at least one arm and leg muscle within 1 week postoperatively. Postoperative physical activity and nutritional intake were assessed using motility devices and nutritional diaries. Fatigue was measured with questionnaires and 1-year survival was assessed with Cox regression analysis. Results A total of 173 patients (55 per cent male; mean (s.d.) age 64.3 (11.9) years) were included, 68 of whom patients (39 per cent) showed SRML. Preoperative weight loss and postoperative nutritional intake were statistically significantly associated with SRML in multivariable logistic regression analysis (P < 0.050). The combination of insufficient postoperative physical activity and nutritional intake had an odds ratio of 4.00 (95 per cent c.i. 1.03 to 15.47) of developing SRML (P = 0.045). No association with fatigue was observed. SRML was associated with decreased 1-year survival (hazard ratio 4.54, 95 per cent c.i. 1.42 to 14.58; P = 0.011). Conclusion SRML occurred in 39 per cent of patients after major abdominal cancer surgery, and was associated with a decreased 1-year survival.

Published
2022

36. Correction to: Lebbink et al. Opposite Incidence Trends for Differentiated and Medullary Thyroid Cancer in Young Dutch Patients over a 30-Year Time Span. (Cancers 2021, 13, 5104)

Author

Chantal A. Lebbink, Medard F. M. van den Broek, Annemiek B. G. Kwast, Joep P. M. Derikx, Miranda P. Dierselhuis, Schelto Kruijff, Thera P. Links, A. S. Paul van Trotsenburg, Gerlof D. Valk, Menno R. Vriens, Annemarie A. Verrijn Stuart, Hanneke M. van Santen, Henrike E. Karim-Kos, Paediatric Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Paediatric Endocrinology, Pediatric surgery, and Pediatrics

Subjects
Cancer Research, Oncology
Abstract

Error in Figure In the original article [1], there was a mistake in Figure 1 as published. In this figure, two years are missing (2000 and 2001). The AAPC values as previously published are correct. The corrected Figure 1 appears below. In addition, in the original article, there was a mistake in Figure 2A–C as published. In these figures, two years are missing (2000 and 2001). The AAPC values were correct and do not require adjustment. The corrected Figure 2A–C appears below. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. (figure presented).

Published
2022

37. Impact of cumulative complications on 1-year treatment-related healthcare costs in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Author

Femke A van der Zant, Bob J L Kooijman, Judith E K R Hentzen, Wijnand Helfrich, Emily M Ploeg, Robert J van Ginkel, Barbara L van Leeuwen, Lukas B Been, Joost M Klaase, Patrick H J Hemmer, Christian S van der Hilst, Schelto Kruijff, Translational Immunology Groningen (TRIGR), Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Value, Affordability and Sustainability (VALUE), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
Humans, General Medicine, Cytoreduction Surgical Procedures, Health Care Costs, Hyperthermia, Induced, Hyperthermic Intraperitoneal Chemotherapy, Colorectal Neoplasms, Peritoneal Neoplasms, Retrospective Studies
Abstract

Background The aim of this study was to evaluate the impact of all minor and major complications on treatment-related healthcare costs in patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal metastases (PMs). Method Patients with histologically proven colorectal PMs who underwent CRS + HIPEC from March 2006 to October 2019 in a tertiary referral centre were retrospectively identified from a prospectively maintained database. Patients were divided into six subgroups according to the severity of the complications, which were scored using the comprehensive complication index (CCI) (CCI 0–9.9, CCI 10–19.9, CCI 20–29.9, CCI 30–39.9, CCI 40–49.9, and CCI 50 or higher). Treatment-related healthcare costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the chi-squared test and Kruskal–Wallis H test. Results A total of 142 patients were included (CCI 0–9.9, 53 patients; CCI 10–19.9, 0 patients; CCI 20–29.9, 45 patients; CCI 30–39.9, 14 patients; CCI 40–49, 9 patients; and CCI 50 or higher, 21 patients). Median (interquartile range) treatment-related healthcare costs increased significantly and exponentially for the CCI 30–39, CCI 40–49, and CCI 50 or higher groups (€48 993 (€44 262–€84 805); €57 167 (€43 047–€67 591); and €82 219 (€55 487–€145 314) respectively) compared with those for the CCI 0–9.9 and CCI 20–29.9 groups (€33 856 (€24 433–€40 779) and €40 621 (€31 501–€58 761) respectively, P Conclusion Treatment-related healthcare costs increase exponentially as more complications develop among patients who undergo CRS + HIPEC for the treatment of colorectal PMs. Anastomotic leakages after CRS + HIPEC lead to an increase of 295 per cent of treatment-related healthcare costs.

Published
2022

38. Intraoperative imaging in pathology-assisted surgery

Author

F. J. Voskuil, Vasilis Ntziachristos, Max J. H. Witjes, Gooitzen M. van Dam, Pieter Jan Van Der Zaag, Jasper Vonk, Schelto Kruijff, Bert van der Vegt, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Zernike Institute for Advanced Materials, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Microbes in Health and Disease (MHD)

Subjects
0303 health sciences, medicine.medical_specialty, business.industry, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, 3. Good health, Computer Science Applications, Resection, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, Biomarker (medicine), Tumor type, business, Intraoperative imaging, Radiological imaging, 030304 developmental biology, Biotechnology
Abstract

The pathological assessment of surgical specimens during surgery can reduce the incidence of positive resection margins, which otherwise can result in additional surgeries or aggressive therapeutic regimens. To improve patient outcomes, intraoperative spectroscopic, fluorescence-based, structural, optoacoustic and radiological imaging techniques are being tested on freshly excised tissue. The specific clinical setting and tumour type largely determine whether endogenous or exogenous contrast is to be detected and whether the tumour specificity of the detected biomarker, image resolution, image-acquisition times or penetration depth are to be prioritized. In this Perspective, we describe current clinical standards for intraoperative tissue analysis and discuss how intraoperative imaging is being implemented. We also discuss potential implementations of intraoperative pathology-assisted surgery for clinical decision-making.

Published
2022

39. Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

Author

Marieke Everts, Wilfred F. A. den Dunnen, Julie Nonnekens, Rob J. M. Groen, Frank A.E. Kruyt, Fritz Andreae, Marcus C. M. Stroet, Bianca M. Dijkstra, Schelto Kruijff, Marion de Jong, Sebastiaan E. Dulfer, Radiology & Nuclear Medicine, Molecular Genetics, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Molecular Neuroscience and Ageing Research (MOLAR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Clinical sciences

Subjects
Cancer Research, Biodistribution, medicine.medical_specialty, Somatostatin receptor subtype 2, Fluorescence, Meningioma, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, In vivo, Meningeal Neoplasms, medicine, Animals, Somatostatin receptor 2, Tissue Distribution, 800CW-TATE, Octreotate, Intra-operative guidance, Somatostatin receptor, Chemistry, Molecular fluorescence guided surgery, Correction, medicine.disease, Surgery, Neurology, Oncology, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Laboratory Investigation, Immunohistochemistry, Neurology (clinical), 030217 neurology & neurosurgery, Ex vivo
Abstract

Purpose Meningioma recurrence rates can be reduced by optimizing surgical resection with the use of intraoperative molecular fluorescence guided surgery (MFGS). We evaluated the potential of the fluorescent tracer 800CW-TATE for MFGS using in vitro and in vivo models. It targets somatostatin receptor subtype 2 (SSTR2), which is overexpressed in all meningiomas. Methods Binding affinity of 800CW-TATE was evaluated using [177Lu] Lu-DOTA-Tyr3-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR2-positive) NCI-H69 or (SSTR2-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR2-specific binding was measured by comparing tumor uptake in NCI-H69 and CH-157MN xenografts, blocking experiments and non-targeted IRDye800CW-carboxylate binding. Tracer distribution was analyzed ex vivo, and the tumor-to-background ratio (TBR) was calculated. SSTR2 expression was determined by immunohistochemistry (IHC). Lastly, 800CW-TATE was incubated on frozen and fresh meningioma specimens and analyzed by microscopy. Results 800CW-TATE binding affinity assays showed an IC50 value of 72 nM. NCI-H69 xenografted mice showed a TBR of 21.1. 800CW-TATE detection was reduced after co-administration of non-fluorescent DOTA-Tyr3-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR2 expression, thereby serving as a negative control. The tracer bound specifically to SSTR2-positive meningioma tissues representing all WHO grades. Conclusion 800CW-TATE demonstrated sufficient binding affinity, specific SSTR2-mediated tumor uptake, a favorable biodistribution, and high TBR. These features make this tracer very promising for use in MFGS and could potentially aid in safer and a more complete meningioma resection, especially in high-grade meningiomas or those at complex anatomical localizations.

Published
2021

40. Fluorescence-Guided Visualization of Soft-Tissue Sarcomas by Targeting Vascular Endothelial Growth Factor A

Author

Bobby K Pranger, Schelto Kruijff, F. J. Voskuil, Lukas B. Been, Robert J. van Ginkel, Wouter B. Nagengast, Meifang Li, Barbara L. van Leeuwen, Albert J. H. Suurmeijer, Matthijs D. Linssen, Gooitzen M. van Dam, Pieter J. Steinkamp, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Microbes in Health and Disease (MHD)

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, MARGIN, SURGERY, Phases of clinical research, LOCAL RECURRENCE, Radiation Dosage, Single Center, 1ST, 03 medical and health sciences, 0302 clinical medicine, In vivo, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Aged, Aged, 80 and over, business.industry, tumor targeting, Soft tissue sarcoma, Optical Imaging, Soft tissue, Sarcoma, Middle Aged, soft-tissue sarcoma, medicine.disease, molecular imaging, vascular endothelial growth factor A, SERIES, Bevacizumab, Vascular endothelial growth factor A, 030104 developmental biology, Surgery, Computer-Assisted, 030220 oncology & carcinogenesis, near-infrared fluorescence, SAFETY, NAVIGATION, Female, Histopathology, business, Nuclear medicine, Ex vivo, fluorescence-guided surgery
Abstract

Rationale: Resection of soft tissue sarcomas (STS) is accompanied by a high rate of tumor-positive surgical margins (14-34%), which potentially leads to decreased disease-free survival. Vascular Endothelial Growth Factor-A (VEGF-A) is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety and optimal dose of bevacizumab-800CW for fluorescence-guided surgery (FGS) in STS for in- and ex vivo tumor detection. Methods: Patients with a histopathologically diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 days prior to surgery (10, 25 and 50 mg, n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab-800CW at the optimal dose. Fluorescence images in- and ex vivo were obtained during all stages of standard of care. The optimal dose was determined by calculating in- and ex vivo Tumor-to-Background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in- and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg with a median in vivo TBR of 2.0 (±0.58) and an ex vivo TBR of 2.67 (±1.6). All seven tumor-positive margins could be observed real-time after surgical resection. Conclusion: FGS using 10 mg bevacizumab-800CW is feasible and safe for intra-operative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase II study is needed to confirm the diagnostic accuracy.

Published
2021

41. Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease

Author

Willemijn Y. van der Plas, Leigh Delbridge, Anton F. Engelsman, Mark Sywak, Schelto Kruijff, Stan B. Sidhu, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Parathyroidectomy, medicine.medical_specialty, Cinacalcet, medicine.medical_treatment, 030230 surgery, Tertiary hyperparathyroidism, CALCIUM, Subtotal Parathyroidectomy, End stage renal disease, 03 medical and health sciences, 0302 clinical medicine, medicine, Hyperparathyroidism, TERTIARY HYPERPARATHYROIDISM, business.industry, TRANSPLANTATION, medicine.disease, Surgery, Transplantation, PHOSPHORUS, CINACALCET, 030220 oncology & carcinogenesis, PATTERNS, Secondary hyperparathyroidism, business, medicine.drug, PTH
Abstract

Background: The landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease-related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy.Methods: We performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited (Results: In total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210-868), 1,087 (627-1,795), and 1,070 (475-1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively).Conclusion: Subtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach. (C) 2020 Elsevier Inc. All rights reserved.

Published
2021

42. Perioperative SARS-CoV-2 infections increase mortality, pulmonary complications, and thromboembolic events

Author

Pascal K.C. Jonker, Willemijn Y. van der Plas, Pieter J. Steinkamp, Ralph Poelstra, Marloes Emous, Wout van der Meij, Floris Thunnissen, Wouter F.W. Bierman, Michel M.R.F. Struys, Philip R. de Reuver, Jean-Paul P.M. de Vries, Schelto Kruijff, Djamilla Boerma, Sarah L. Gerritsen, André S. van Petersen, Charles T. Stevens, Marc van Sambeek, Marleen Hölscher, Apollo Pronk, Wouter J. Bakker, Patrick Whe Vriens, Thymen Houwen, Johannes A. Wegdam, Tammo S. de Vries Reilingh, Ellis Schipper, Pascal HE. Teeuwen, Tessa M. van Ginhoven, Charlotte Viëtor, Mark JW. van der Oest, Sarah Gans, Peter van Duijvendijk, Tanneke Herklots, Tom de Hoop, Michelle de Graaff, Didi Sloothaak, Marieke Bolster - van Eenennaam, Jedidja Baaij, Maarten Vermaas, Kelly R. Voigt, Gijs A. Patijn, Amarins TA. Bransma, Wouter KG. Leclercq, Julie ML. Sijmons, Martine Uittenbogaart, Paul M. Verheijen, Thijs A. Burghgraef, Manon Teunissen, Herman Frima, Said Bachiri, Lennaert CB. Groen, Floris M. Thunissen, Britt AM. Vermeulen, Anna Groen, Ramon RJP. van Eekeren, Ernst J. Spillenaar Bilgen, Niels J. Harlaar, Fredrik HW. Jonker, Sjirk W. van der Burg, Lisanne AE. Posma-Bouman, Steven J. Oosterling, Josephine Franken, David R. Nellensteijn, Elena Argia Bianca Bensi, Wim van den Broek, Eduard R. Hendriks, Anna AW. van Geloven, Pascal KC. Jonker, Wouter FW. Bierman, Michel MRF. Struys, Yester F. Janssen, Gooitzen M. van Dam, Frank FA. IJpma, Claire van der Riet, Eline Feitsma, Kirsten Ma, Simone Kleiss, Milan C. Richir, Menno R. Vriens, Mando D. Filipe, Frank C. den Boer, Nicole AM. Dekker, Tim Verhagen, Floor ter Brugge, Emmanuel AGL. Lagae, Evert-Jan G. Boerma, Donald Schweitzer, Mark HF. Keulen, Shirley Ketting, Anesthesiology, Cardiothoracic Surgery, Orthopedics and Sports Medicine, Erasmus MC other, Internal Medicine, Plastic and Reconstructive Surgery and Hand Surgery, Obstetrics & Gynecology, Surgery, Dermatology, AII - Inflammatory diseases, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), ​Robotics and image-guided minimally-invasive surgery (ROBOTICS), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
Male, medicine.medical_specialty, SURGERY, Matched-Pair Analysis, Hemorrhage, 030230 surgery, Article, Cohort Studies, 03 medical and health sciences, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Postoperative Complications, Interquartile range, Internal medicine, Thromboembolism, Diabetes Mellitus, Medicine and Health Sciences, Medicine, Humans, Elective surgery, Aged, Netherlands, Peripheral Vascular Diseases, business.industry, Mortality rate, COVID-19, Odds ratio, Perioperative, Middle Aged, Confidence interval, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, Propensity score matching, Cohort, Hypertension, Female, business
Abstract

Background: A direct comparison of severe acute respiratory syndrome coronavirus 2 positive patients with a severe acute respiratory syndrome coronavirus 2 negative control group undergoing an operative intervention during the current pandemic is lacking, and a reliable estimate of the assumed difference in morbidity and mortality between both patient categories remains unknown.Methods: We included all consecutive patients with a confirmed pre- or postoperative severe acute respiratory syndrome coronavirus 2 positive status (operated in 27 hospitals) and negative control patients (operated in 4 hospitals) undergoing emergency or elective operations. A propensity score-matched comparison of clinical outcomes was performed between severe acute respiratory syndrome coronavirus 2 positive and negative tested patients (control group). Primary outcome was overall 30-day mortality rate between both groups. Main secondary outcomes were overall, pulmonary, and thromboembolic complications.Results: In total, 161 severe acute respiratory syndrome coronavirus 2 positive and 342 control severe acute respiratory syndrome coronavirus 2 negative patients were included in this study. The 30-day overall postoperative mortality rate was greater in the severe acute respiratory syndrome coronavirus 2 positive cohort compared with the negative control group (16% vs 4% respectively; P = .007). After propensity score matching, the severe acute respiratory syndrome coronavirus 2 positive group consisted of 123 patients (median 70 years of age [interquartile range 59-77] and 55% male) were compared with 196 patients in the matched control group (median 69 years (interquartile range 58-75] and 53% male). The 30-day mortality rate and risk were greater in the severe acute respiratory syndrome coronavirus 2 positive group compared with the matched control group (12% vs 4%; P = .009 and odds ratio 3.4 [95% confidence interval 1.5-8.5]; P = .005, respectively). Overall, pulmonary and thromboembolic complications occurred more often in severe acute respiratory syndrome coronavirus 2 positive patients (P Conclusion: Patients diagnosed with perioperative severe acute respiratory syndrome coronavirus 2 have an increased risk of 30-day mortality, pulmonary complications, and thromboembolic events. These findings serve as an evidence-based argument to postpone elective surgery and selected emergency cases. (C) 2020 The Author(s). Published by Elsevier Inc.

Published
2021

43. Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

Author

Dmitri Nepogodiev, Joana Ff Simoes, Elizabeth Li, Maria Picciochi, James C Glasbey, Glauco Baiocchi, Ruth Blanco-Colino, Daoud Chaudhry, Ehab AlAmeer, Kariem El-Boghdadly, Funmilola Wuraola, Dhruva Ghosh, Rohan R Gujjuri, Ewen M Harrison, Herman Lule, Haytham Kaafarani, Mohammad Khosravi, Irmgard Kronberger, Sezai Leventoğlu, Harvinder Mann, Kenneth A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin Ntirenganya, Lisa Norman, Oumaima Outani, Riinu Pius, Peter Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei Satoi, Catherine Shaw, Aneel Bhangu, Omar M Omar, Waheed-Ul-Rahman Ahmed, Leah Argus, Alasdair Ball, Edward P Bywater, Amanpreet Brar, Brett E Dawson, Irani Duran, Muhammed Elhadi, Conor S Jones, Sivesh K Kamarajah, James M Keatley, Samuel Lawday, Ella J Marson, Riinu Ots, Irène Santos, Elliott H Taylor, Isobel M Trout, Chris Varghese, Mary L Venn, William Xu, Irida Dajti, Arben Gjata, Salah Eddine Oussama Kacimi, Luis Boccalatte, Daniel Cox, Philip Townend, Felix Aigner, Irmgard Elisabeth Kronberger, Elgun Samadov, Amer Alderazi, Kamral Hossain, Greg Padmore, Gabrielle van Ramshorst, Ismaïl Lawani, Anis Cerovac, Samir Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad Gohar, Mihail Slavchev, Chukwuemeka Nwegbu, Arnav Agarwal, Janet Martin, Joshua Ng-Kamstra, Maricarmen Olivos, Wenhui Lou, Dong-Lin Ren, Jose Andres Calvache, Carlos J Perez Rivera, Ana Danic Hadzibegovic, Tomislav Kopjar, Jakov Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos Gouvas, Jaroslav Klat, René Novysedlák, Nicolas Amisi, Peter Christensen, Alaa El-Hussuna, Sylvia Batista, Eddy Lincango-Naranjo, Sameh Emile, Danilo Alfonso Arévalo Sandoval, Hailu Dhufera, Samuel Hailu, Mengistu G Mengesha, Joonas H Kauppila, Alexis P Arnaud, Zaza Demetrashvili, Markus Albertsmeier, Hans Lederhuber, Markus W Löffler, Daniel Kwesi Acquah, Bernard Ofori, Stephen Tabiri, Symeon Metallidis, Georgios Tsoulfas, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Tamás Mersich, Dániel Wettstein, Gabriele Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud Mozafari, Ahmed Hilmi, Helen Mohan, Oded Zmora, Gaetano Gallo, Francesco Pata, Gianluca Pellino, Yuki Fujimoto, Naoto Kuroda, Mohamad K Abou Chaar, Faris Ayasra, Ildar Fakhradiyev, Intisar Hisham Said Hamdun, Jang Jin-Young, Mohammad Jamal, Lina Karout, Aiste Gulla, Fanjandrainy Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura Martinez, María José Martínez, Alejandra Nayen, Antonio Ramos-De la Medina, Jade Nunez, Pueya Rashid Nashidengo, Rakesh Shah, Ashish Lal Shrestha, Pascal Jonker, Schelto Kruijff, Milou Noltes, Pieter Steinkamp, Deborah Wright, Lukman Abdur-Rahman, Adesoji Ademuyiwa, Adewale Adisa, Babatunde Osinaike, Justina Seyi-Olajide, Omolara Williams, Emmanuel Williams, Sofija Pejkova, Zainab Al Balushi, Raza Sayyed, Mustafa Abo Mohsen, Sadi A Abukhalaf, Moises Cukier, Hugo Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr Major, José Azevedo, Miguel F Cunha, Ahmad Zarour, Eduard-Alexandru Bonci, Ionut Negoi, Sergey Efetov, Viktor Kochetkov, Andrey Litvin, Jc Allen Ingabire, Georges Bucyibaruta, Ntirenganya Faustin, Sosthene Habumuremyi, Alphonsine Imanishimwe, Haragirimana Jean de Dieu, Emmanuel Munyaneza, Isaie Ncogoza, Ehab Alameer, Abdourahmane Ndong, Dejan Radenkovic, Min Hoe Chew, Frederick Koh, James Ngu, Arpád Panyko, Uros Bele, Jurij Aleš Košir, Hassan Daoud, Ana Maria Minaya Bravo, Umesh Jayarajah, Dakshitha Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin Rutegård, Malin Sund, Michel Adamina, Eleftherios Gialamas, Karoline Horisberger, Muhammad Alshaar, Abel Huang, Varut Lohsiriwat, Shane Charles, Haithem Jlassi, Arda Isik, Hervé Monka Lekuya, Slava Kopetskyi, Hayder Alsaadi, Sattar Alshryda, Osaid Alser, Brittany Bankhead-Kendall, Kerry Breen, Hassan Mashbari, Fernando Bonilla Cal, Hamza Al-Naggar, Mayaba Maimbo, Dennis Mazingi, Tom 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Montenegro, Julia Rodriguez-Abreu, Dolores Mejía, Galal Abouelnagah, Sameh Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy A Hassan, Mahmoud M Saad, Mohamed Reda Loaloa, Badr Mostafa, Mohamed Qassem, Mohamed Fahmy, Hesham Abozied, Ahmed Y Azzam, Sherief Ghozy, Asser Sallam, Ahmed Shehta, Mohamed Abdelkhalek, Rehab Samaka, Amr Morsy, Ahmed Elshawadfy Sherif, Abraham Negussie, Tigist Fisseha, Kibruyisfaw Shumbash, Metasebia Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe Megersa, Teshome Tefera, Melatework Assefa, Bahru Atnafu, Bereket Tsegaye, Yoseph Solomon Bezabih, Silamlak Sisay, Kebebe Bekele, Moa Jira, Habtamu Derilo, Eyueal Degefa, Anteneh Tadesse, Melkamu Nidaw, Elise Sarjanoja, Sylvie Testelin, Sophie Boucher, Lionel Jouffret, Zaher Lakkis, Alban Zarzavadjian Le Bian, Luke Harper, Marc Danguy des Déserts, Benoît André, Karem Slim, Romain Verhaeghe, Andrea Police, Edouard Girard, Alexandre Chebaro, Armande Subayi Nkembi, Laurent Arnalsteen, Quentin Ballouhey, Diane 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Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, 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Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, Muhammad Fahadullah, Éanna Ryan, Tara Connelly, Oded Zmora, Daisuke Hashimoto, Majdi Ali Alqudah, Amer Alajalen, Rand Y Omari, Faris Ayasra, Abdulrahman Qasem, Yazan Alawneh, Amer Ahmad, Omar Aladawi, Bourhan Alrayes, Hanan Haidar, Shatha Husain, Faisal Qassem, Adnan Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid Alsunna, Hazim Ra'ed, Faten Reyad Bani Hamad, Amro Abuleil, Mohamad K Abou Chaar, Elmi Ahmed Mohamed Jimaale, Marah Abu-Mehsen, Noor Olaywah, Omar Wafi, Hazim Ababneh, Luai Abu-Ismail, Almu'atasim Khamees, Ahmad Alkhatib, Raikhan Bolatbekova, Mukhtar Kulimbet, Talgat Nurgozhin, Timur Saliev, Baurzhan Zhussupov, Ydyrys Almabayev, Ildar Fakhradiyev, Timur Saliev, Dilyara Kaidarova, Khalil Tamoos, Ahmed Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah Alkadeeki, Milad Gahwagi, Wafa Aldressi, Mohamed Amnaina, Arowa Hassan Abdulrahman Alansari, Akram Alkaseek, Ghozlan Yagoub, Anass Ben Amer, Marwa Salem, Ayman Almugaddami, Dania Burgan, Mohammed Abdelkabir, Khayriyah Alshareef, Rayet Al Islam Ben Jouira, Ayman Meelad, Ahmad Bouhuwaish, Sumayya Essayah Dwaga, Houda Khalifa, Bushray Almiqlash, Taha Suliaman, Mohammed Alawami, Fras Elhajdawe, Hajir Aboazamazem, Ibrahim Ellojli, Ahmed Msherghi, Ismail Ali Saleh, Mohammed Alayan, April Camilla Roslani, Marcel Didier Ndayishyigikiye, Akutu Munyika, Philipp Plarre, David W Borowski, Pueya Rashid Nashidengo, Milou Noltes, Pieter Steinkamp, Cameron Wells, Rebecca Teague, Brodie Elliott, David Kieser, Omar Mohyieldin, Chris Varghese, Nick McIntosh, Cheyaanthan Haran, Sarah Rennie, Jasmin King, Jeong Ha, Matthew James McGuinness, Opeoluwa Adesanya, Julius Olaogun, Akinola Akinmade, Kefas Bwala, Peter Agbonrofo, Akinwale Afolabi, Usang Usang, Sebastian Ekenze, Samson Olori, Taiwo Akeem Lawal, Justina Seyi-Olajide, Abiodun Okunlola, Omolara Williams, Adewale Adisa, Lukman Abdur-Rahman, Stephen 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Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Marie Dione Sacdalan, Piotr Major, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, José Azevedo, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, Miguel F Cunha, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Ahmad Zarour, Ahmad Zarour, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Ionut Negoi, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Eduard-Alexandru Bonci, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Andrey Litvin, Vadim Pykhteev, Marianna Raevskaya, Sergey Efetov, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Azah Althumairi, Mohammad Alyami, Abdulrahman Al Amri, Azah Althumairi, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Abdourahmane Ndong, Jacques Tendeng, Nan Zun Teo, Frederick Koh, Jurij Aleš Košir, Uros Bele, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Jorge Nuñez, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Ana Maria Minaya Bravo, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Umesh Jayarajah, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Dakshitha Wickramasinghe, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Eleftherios Gialamas, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Arda Isik, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Hervé Monka Lekuya, Ronald Kiweewa, Herman Lule, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Sattar Alshryda, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Mohamed Mashhour, Mohamed Mashhour, Antony Louis Rex Michael, Hayder Alsaadi, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Sivesh K Kamarajah, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Grant D Stewart, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Kariem El-Boghdadly, Cyrus Kerawala, Chetan Parmar, Tom Abbott, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, John Edwards, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Joseph Incorvia, Sameer Hirji, Matthew Naunheim, Frederick Drake, Haytham Kaafarani, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Henry E Rice, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Brittany Bankhead-Kendall, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Hamza Al-Naggar, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Ervis Agastra, Enton Bollano, Kostandin Gjyli, Dariel Thereska, Irida Dajti, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Veronica Laudani, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Luis Boccalatte, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, Ricardo Esteban Mentz, Pedro Mercado, Pablo Moyano, Florencia Noll, Diego Odetto, Agustina Rene Oliva, Rafael Perez Vidal, Catalina Poggi, Eduardo Jorge Premoli, María Lourdes Ramos, Patricio Rosas, Luciano Rossi, Gustavo Rossi, Jose Saadi, Jordán Scherñuk, Pablo Slullitel, María Verona Stang, María Victoria Taboada, Sebastian Tirapegui, Constanza Uffelmann, Carlos Vaccaro, Roberto Vagni, Ana Clara Valerio, Celeste Soledad Zarratea, Carina Chwat, Silvina Montal, Brian Morris, Pedro Valdez, Fernando Diaz-Couselo,Ricci C, Casadei R, Fruscio, R, Ornaghi, S, Felice Pecoraro, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Vito Chiantera, Mariano Catello Di Donna, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Simoes, J, Rosati, R, on behalf of COVIDSurg Collaborative, GlobalSurg Collaborative, Aldrighetti, L, Mortini, P, Olmi, S, Medical Oncology, Assoc Surg Training ASiT, European Soc Coloproctology ESCP, EuroSurg, G4 Alliance, GlobalPaedSurg, GICS, ItSURG, ISRC, Italian Soc Colorectal Surg SICCR, PTSurg, S-ECCO, South African Soc, and SpainSurg

Subjects
Lung Diseases, Male, Internationality, SARS-Cov-2, COVID-19, surgery, pathways, pre-operative isolation, Settore MED/18 - CHIRURGIA GENERALE, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Lung Disease, ESTUDOS PROSPECTIVOS, Cohort Studies, Patient Isolation, Postoperative Complications, 80 and over, Prospective Studies, Prospective cohort study, 610 Medicine & health, Aged, 80 and over, Incidence (epidemiology), Treatment Outcome, Elective Surgical Procedures, Female, Elective Surgical Procedure, Cohort study, Human, medicine.medical_specialty, Isolation (health care), Preoperative care, NO, Anesthesiology, Preoperative Care, medicine, Humans, Elective surgery, LS7_4, Aged, business.industry, pathway, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Prospective Studie, Anesthesiology and Pain Medicine, Human medicine, Postoperative Complication, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

Published
2021

45. Double venipuncture is not required for adequate S-100B determination in melanoma patients

Author

Esther Bastiaannet, Kevin Wevers, Schelto Kruijff, Harald J. Hoekstra, Samantha Damude, Anneke C. Muller Kobold, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Urology, Comorbidity, S100 Calcium Binding Protein beta Subunit, General Biochemistry, Genetics and Molecular Biology, Mean difference, 03 medical and health sciences, 0302 clinical medicine, Phlebotomy, Serum biomarkers, Adipocytes, Humans, Medicine, Stage III melanoma, Melanoma, Aged, Cancer staging, Aged, 80 and over, Venipuncture, business.industry, Significant difference, Middle Aged, Serum samples, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Multivariate Analysis, Regression Analysis, Female, business, Biotechnology
Abstract

S-100B is used in melanoma follow-up. This serum biomarker is also present in adipocytes; therefore, subcutaneous adipocytes trapped in the needle before performing a venipuncture could contaminate the serum. The aim was to study the influence of adipocyte contamination on blood samples used for S-100B analysis, possibly resulting in falsely elevated S-100B values. A total of 294 serum samples were collected from 147 American Joint Committee on Cancer staging stage III melanoma patients. The mean difference between the first (dummy) and second tubes was 0.003 μg/l (p = 0.077), with a decrease in the second tube. Compared with the second tube, the S-100B level was higher in the first tube in 33.3% of the samples, equal in 36.8% of the samples and lower in 29.9% of the samples. No significant difference between the two consecutively drawn tubes was found. There seems to be no necessity of implementing a dummy tube system for accurate S-100B determination in melanoma patients.

Published
2020

46. The association between active tumor volume, total lesion glycolysis and levels of S-100B and LDH in stage IV melanoma patients

Author

Kevin Wevers, John F. Thompson, K van der Steen, Schelto Kruijff, Eric A. Deckers, Harald J. Hoekstra, D. Vallez Garcia, Adrienne H. Brouwers, Pediatrics, Surgery, Radiology and nuclear medicine, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
Male, Staging, Skin Neoplasms, PROTEIN, GUIDELINES, Gastroenterology, 030218 nuclear medicine & medical imaging, MALIGNANT-MELANOMA, chemistry.chemical_compound, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Medicine, Melanoma, LACTATE-DEHYDROGENASE, General Medicine, Middle Aged, Tumor Burden, Total lesion glycolysis, Oncology, 030220 oncology & carcinogenesis, Stage iv melanoma, SURVIVAL, Female, Glycolysis, medicine.drug, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, LDH, Standardized uptake value, Ipilimumab, S100 Calcium Binding Protein beta Subunit, DIAGNOSIS, Disease-Free Survival, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal medicine, Lactate dehydrogenase, Humans, In patient, ASSAYS, Aged, Neoplasm Staging, L-Lactate Dehydrogenase, business.industry, IPILIMUMAB, Disease progression, medicine.disease, FDG-PET/CT, PET, chemistry, Surgery, Radiopharmaceuticals, business, Biomarkers, S-100B, SERUM S-100B
Abstract

Introduction: The Standardized Uptake Value (SUV) in single lesions on F-18-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUVmean/max, metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for follow-up.Methods: In 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed.Results: S-100B was elevated (>0.15 mu g/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R-2 = 0.19). S-100B was correlated to both MATV (R-2 = 0.375) and TLG (R-2 = 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p 250 U/l) (p Conclusion: In newly diagnosed stage IV melanoma patients S-100B correlates with F-18-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis. (C) 2020 The Authors. Published by Elsevier Ltd.

Published
2020

47. Patient-derived parathyroid organoids as tracer and drug-screening application model

Author

Milou E. Noltes, Luc H.J. Sondorp, Laura Kracht, Inês F. Antunes, René Wardenaar, Wendy Kelder, Annelies Kemper, Wiktor Szymanski, Wouter T. Zandee, Liesbeth Jansen, Adrienne H. Brouwers, Robert P. Coppes, and Schelto Kruijff

Abstract

Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The understanding of parathyroid hyperplastic growth and the development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish stem cell-derived, three-dimensional organoids representing human parathyroid tissue in vitro. Patient-derived hyperplastic parathyroid tissue was dispersed and parathyroid organoids (PTO) were cultured and characterized. PTO-derived cells were shown to exhibit in vitro self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA-sequencing confirm that PTO phenocopy hyperplastic parathyroid tissue. Exposure of PTO to increasing calcium concentrations and to PTH-lowering drugs resulted in a significantly reduced PTH excretion. Next to this, the PTO showed specific binding of 11C-methionine to the targeted receptor. Additionally, when organoids were incubated with 99mTc-sestamibi, we observed a higher uptake in PTOs from patients with a 99mTc-sestamibi positive scan compared to patients with a negative scan. These data show functionality of PTOs resembling the parathyroid. In conclusion, we present a patient-derived PTO culture, that recapitulates the originating tissue on gene and protein expression and functionality. This PTO model paves the way for future physiology studies and therapeutic target and tracer discovery.

Published
2022

48. Parathyroid Function Saving Total Thyroidectomy Using Autofluorescence and Quantified Indocyanine Green Angiography

Author

Emma W M Peeperkorn, Anton F. Engelsman, Milou E Noltes, Schelto Kruijff, Madelon J H Metman, and Liesbeth Jansen

Subjects
Total thyroidectomy, medicine.medical_specialty, business.industry, Indocyanine green angiography, hypoparathyroidism, macromolecular substances, autofluorescence, medicine.disease, Article, total thyroidectomy, ICG angiography, Autofluorescence, Hypoparathyroidism, Postoperative hypoparathyroidism, medicine, parathyroid, Radiology, business
Abstract

Introduction: Postoperative hypoparathyroidism is one of the most common complications after total thyroidectomy. In recent years, several techniques have been employed, trying to save parathyroid glands during thyroid surgery, such as autofluorescence and indocyanine green (ICG) angiography. In this study, we present a systematic approach to a parathyroid function saving total thyroidectomy using autofluorescence and quantified ICG angiography. Materials and Methods: Step-by-step video demonstration of a total thyroidectomy for thyroid cancer utilizing parathyroid autofluorescence and ICG angiography. Results: A systematic step-wise approach to a total thyroidectomy using autofluorescence and quantified ICG angiography is demonstrated. The set moments of deployment, settings of the camera, and a standardized workflow model for parathyroid autofluorescence and ICG angiography are noted. Conclusion: A systematic approach to parathyroid autofluorescence and quantified ICG angiography during total thyroidectomy may eventually guide the surgeon in early identification of the parathyroid glands and the need for parathyroid autotransplantation, thereby predicting and preventing postoperative hypoparathyroidism. The authors have no related personal conflicts of interest to declare that could be perceived as prejudicing the impartiality of the research reported. For this study, the Quest Spectrum was used. The authors have no conflicts with this or any other commercial entity. This research did not receive any specific grant from any funding agency in the public or commercial sector. Runtime of video: 9 mins 59 secs This video was presented at the Third Symposium on Parathyroid Fluorescence 2021.

Published
2022

49. Surgical treatment for non-parasitic liver cysts improves quality of life

Author

Gijs A. Patijn, Joost M. Klaase, Esther Bastiaannet, Schelto Kruijff, Marieke T. de Boer, Vincent E de Meijer, Martijn P D Haring, Yester F. Janssen, Groningen Institute for Organ Transplantation (GIOT), Value, Affordability and Sustainability (VALUE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Health Status, Population, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Internal medicine, Hepatectomy, Humans, Medicine, education, Surgical treatment, Liver cysts, Aged, Netherlands, Retrospective Studies, education.field_of_study, Cysts, business.industry, Liver Diseases, Retrospective cohort study, Length of Stay, Middle Aged, humanities, Treatment Outcome, 030220 oncology & carcinogenesis, Quality of Life, Treatment strategy, Female, 030211 gastroenterology & hepatology, Surgery, business
Abstract

BACKGROUND&PURPOSE: Liver cysts occur frequently. Most are harmless, however some carry a significant patient burden. Optimizing treatment strategy is complicated as needs differ between patients. The current study assesses the effect of surgery on quality of life (QoL) of patients with non-parasitic liver cysts.METHODS: A retrospective cohort study of all patients who underwent surgery for non-parasitic liver cysts in three major Dutch medical centers from 1993 to 2017. Patient characteristics and surgery related variables were collected from the electronic patient file. QoL was measured before and after surgery using the EORTC QLQ-C30. Summary scores (SumSc) were calculated and compared to reference values of the general population. Multivariate analysis using logistic regression was performed for identifying outcome related factors. Increase of ≥ 10% in SumSc was defined as clinically relevant.MAIN FINDINGS: Eighty-eight of 132 eligible patients (67%) completed two QoL assessments. Respondents demonstrated significant improvement in the global health status, on all 5 functional scales (all p ≤ 0.005), on all 9 symptom scales after surgery (all p < 0.05), and on SumSc (p < 0.001) to levels similar or better than the general population. Patients with complications demonstrated a significant QoL gain (p < 0.05), and reported a similar postoperative status compared to patients without complications (p = 0.74). QoL gain for patients who underwent open and laparoscopic cyst fenestration were similar (p = 0.08). Multivariate analysis of SumSc found mechanical complaints as significant factor for ≥ 10% SumSc increase (OR 0.11, 95% CI (0.02-0.55).CONCLUSIONS: Surgery is a safe and effective strategy to significantly improve QoL in patients with symptomatic liver cysts.

Published
2020

50. Impact of extent of disease on 1‐year healthcare costs in patients who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: retrospective observational cohort study

Author

R. J. van Ginkel, C. S. van der Hilst, Joost M. Klaase, B. J. L. Kooijman, Lukas B. Been, Judith E. K. R. Hentzen, Schelto Kruijff, Patrick H. J. Hemmer, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Value, Affordability and Sustainability (VALUE), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
Male, SURFACE MALIGNANCIES, CARCINOMATOSIS, Hyperthermic Intraperitoneal Chemotherapy, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, Health care, Peritoneal Neoplasms, Netherlands, COMPLICATIONS, OUTCOMES, ORIGIN, Health Care Costs, General Medicine, Middle Aged, Combined Modality Therapy, CANCER, Tumor Burden, surgical procedures, operative, 030220 oncology & carcinogenesis, Lower GI, Original Article, Female, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, Colorectal Neoplasms, Cohort study, medicine.medical_specialty, lcsh:Surgery, 03 medical and health sciences, MORBIDITY, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, Retrospective Studies, business.industry, MORTALITY, Cancer, Retrospective cohort study, Original Articles, Hyperthermia, Induced, lcsh:RD1-811, medicine.disease, Chemotherapy, Cancer, Regional Perfusion, Conventional PCI, Peritoneal Cancer Index, business
Abstract

Background The goal of this retrospective observational study was to determine the impact of the extent of peritoneal disease on 1‐year healthcare costs in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). The extent of peritoneal disease, expressed by the Peritoneal Cancer Index (PCI), directly affects the complexity of CRS + HIPEC and ultimately survival outcomes. The impact of the PCI on treatment‐related healthcare costs remains unknown. Methods Data from patients with colorectal PM who underwent CRS + HIPEC between January 2012 and November 2017 were extracted retrospectively from an institutional database. Patients were divided into four subgroups with PCI scores ranging from 0 to 20. Treatment‐related costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the χ 2 test and Kruskal−Wallis H test. Results Seventy‐three patients were included (PCI 0–5, 22 patients; PCI 6–10, 19 patients; PCI 11–15, 17 patients; PCI 16–20, 15 patients). Median (i.q.r.) costs were significantly increased for the PCI 11–15 and PCI 16–20 groups (€51 029 (42 500–58 575) and €46 548 (35 194–60 533) respectively) compared with those for the PCI 0–5 and PCI 6–10 groups (€33 856 (25 293–42 235) and €39 013 (30 519–51 334) respectively) (P = 0·009). Conclusion Treatment‐related healthcare costs are significantly increased among patients with extensive tumour burden (PCI score 10 or above) who undergo CRS + HIPEC for the treatment of colorectal PM., Well selected patients with colorectal peritoneal metastases can be treated with curative intent by cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Treatment‐related healthcare costs are significantly increased among patients with extensive peritoneal disease, although the associated survival gain is limited. These results might help to balance economic healthcare costs with a possible survival benefit. Higher costs with extensive disease.

Published
2020

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