Search

Background and Study Aims: No previous studies have evaluated the ability of endoscopic ultrasonography to describe the anatomic location of lymph nodes on the basis of a node-to-node comparison. The aim of this study was to assess the feasibility and safety of a new endoscopic ultrasound (EUS)-guided fine-needle technique for marking lymph nodes. Patients and Methods: Twenty-five patients with suspected or confirmed malignancies of the upper gastrointestinal tract were prospectively included. EUS-guided fine-needle marking (EUS-FNM) was performed with a silver pin with a diameter that allowed it to fit into a 19-gauge needle. The position of the pin was verified by EUS. End points were the ability to identify and isolate the marked lymph node during surgery and a comparison between the location of the pin as suggested by EUS and the actual location found in the resected specimen. Results: Twenty-three lymph nodes were marked. Nineteen intended surgical isolations were performed. The lymph nodes were isolated in the resection specimens in 18 patients (95 %). In 2 out of 20 cases the pin was not localized by laparoscopic ultrasonography. In 89 % of the cases the marked lymph node was in the same location as described by EUS. One pin (5 %) was not retrieved. In three cases, a small hematoma was observed. There was no sign of long-term complications. Conclusion: EUS-FNM with a silver pin in lymph nodes is feasible and safe. EUS-FNM seems to be a suitable tool for evaluating lymph nodes on the basis of a node-to-node comparison. [ABSTRACT FROM AUTHOR]

Background/objectives: Median survival of pancreatic ductal adenocarcinoma (PDAC) is around eight months and new prognostic tools are needed. Circular RNAs (circRNAs) have gained interest in different types of cancer. However, only a few studies have evaluated their potential in PDAC. We aimed to identify the most differentially expressed circRNAs in PDAC compared to controls and to explore their potential as prognostic markers., Methods: Using frozen specimens with PDAC and controls, we performed RNA sequencing and identified 20,440 unique circRNAs. A custom code set of capture- and reporter probes for NanoString nCounter analysis was designed to target 152 circRNAs, based on abundancy, differential expression and a literature study. Expression of these 152 circRNAs was examined in 108 formalin-fixed and paraffin-embedded surgical PDAC specimens and controls. The spatial expression of one of the most promising candidates, ciRS-7 (hsa_circ_0001946), was evaluated by chromogenic in situ hybridization (CISH) using multi-punch tissue microarrays (TMAs) and digital imaging analysis., Results: Based on circRNA expression profiles, we identified different PDAC subclusters. The 30 most differentially expressed circRNAs showed log2 fold changes from -3.43 to 0.94, where circNRIP1 (hsa_circ_0004771), circMBOAT2 (hsa_circ_0007334) and circRUNX1 (hsa_circ_0002360) held significant prognostic value in multivariate analysis. CiRS-7 was absent in PDAC cells but highly expressed in the tumor microenvironment., Conclusions: We identified several new circRNAs with biomarker potential in surgically treated PDAC, three of which showed an independent prognostic value. We also found that ciRS-7 is absent in cancer cells but abundant in tumor microenvironment and may hold potential as marker of activated stroma., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias., Methods: We used population-based Danish health-care registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient were duplicated; one copy was assigned to the surgery protocol, and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting., Results: We included 1744 patients with a median age of 68 years: 73.6% underwent surgery, and 18.6% had chemotherapy without surgery; 7.8% received no treatment. The 3-year survival was 39.7% (95% confidence interval [CI] = 36.7% to 42.6%) after surgery and 22.7% (95% CI = 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI = 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI = 17.0% to 29.0%)., Conclusion: Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: There are few data on Pressurized IntraPeritoneal Aerosol Chemotherapy with cisplatin and doxorubicin (PIPAC C/D) in women with primary unresectable or recurrent platinum-resistant peritoneal metastasis (PM) from ovarian cancer (OC). We evaluated survival, histological and cytological response, Quality of Life (QoL) and toxicity after PIPAC C/D in these patients., Methods: Retrospective analysis of patients from the prospective PIPAC-OPC1 and -OPC2 studies. The histological response was evaluated by the Peritoneal Regression Grading Score (PRGS). QoL questionnaires were collected at baseline and after third PIPAC or 60 days. Adverse events were collected until 30 days after the last PIPAC. Demographic and survival data were analysed based on intention to treat. Response, QoL and toxicity were analysed per protocol (≥1 PIPAC)., Results: Twenty-nine patients were included. Five patients (17 %) were non-accessible at PIPAC 1. One patient was excluded due to liver metastases at PIPAC 1. Thus, 23 patients had 76 PIPACs (median 2, range 1-12). Median overall survival was 8.2 months (95 % CI 4.4-10.3) from PIPAC 1. Biopsy data were available for 22 patients, and seven (32 %) patients had a major/complete histological response (PRGS≤2) at PIPAC 3. No cytological conversions were registered. Symptoms and function scores worsened, while emotional scores improved. Three patients had severe adverse reactions (two ileus, one pulmonary embolism); no life-threatening reactions or treatment-related mortality was observed., Conclusions: PIPAC C/D was feasible and induced histological regression in a substantial proportion of patients with platinum-resistant PM from OC. Larger studies are needed to evaluate impact on survival., Competing Interests: Competing interests: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: In this Danish nationwide population-based study, we evaluated the prognostically relevant minimum tumour-free margin width following pancreaticoduodenectomy (PD) for ampullary adenocarcinoma (AAC) and evaluated whether certain margins hold independent prognostic information., Methods: We included 128 patients who underwent PD for AAC from 2015 to 2019. Clinical and pathological data including well-known prognostic factors were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. All PD specimens were examined using a standardised pathological protocol including multicolour inking, axial slicing and exact reporting of margin widths. The cohort was dichotomised into involved and uninvolved groups, using different margin clearance definitions (0.5-≥3.0 mm)., Results: Following PD for AAC, margin clearance of ≥1 mm was independently associated with improved chance of survival compared with <1 mm (HR: 0.30, 95 % CI: 0.14-0.64 (p = 0.002)). Posterior and anterior margin widths were narrower compared with superior mesenteric artery and vein margins. Posterior margin and anterior surface had isolated prognostic significance in multivariable analysis., Conclusion: Following PD for AAC, margin clearance of at least 1 mm is independently associated with improved survival. Our data further indicate that anterior surface and posterior margin hold particular prognostic value., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The prognostic role of resection margin status following total (TP) and distal (DP) pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) is insufficiently evaluated. In Denmark, pancreatic surgery, including the postoperative pathological examination of the resection specimens, is confined to four centres, all reporting to the Danish Pancreatic Cancer Database (DPCD). In this Danish population-based nationwide study on TP and DP for PDAC from 2015-2019, based on data from DPCD, we evaluated whether there is a prognostically relevant minimum margin clearance definition and whether certain margins hold independent prognostic information., Methods: Clinical and pathological data were retrieved from DPCD and supplemented by review of pathology reports and re-microscopy, if needed. One of the study pathologists performed all re-microscopy. The prognostic significance of margin status was evaluated by dichotomisation of the TP cohort (n = 101) and the DP cohort (n = 90) into involved and uninvolved groups, using different clearance definitions (0.5 - ≥3.0 mm)., Results: Following TP, direct involvement of the superior mesenteric artery (SMA) margin had independent prognostic value. When using a clearance definition of ≥ 0.5 or ≥ 1.5 mm for SMA, median survival for R0 versus R1 was 19 (95% CI 14-26) versus 10 (95% CI 5-20) months (p = 0.010), and 21 (95% CI 15-30) versus 10 (95% CI 8-19) months (p = 0.011), respectively. Overall margin status was not of significant prognostic importance following neither DP nor TP., Conclusion: In this Danish population-based nationwide study, SMA margin involvement was a significant isolated prognostic factor following TP, whereas combined assessment of all circumferential margins did not hold statistically significant prognostic information. Following DP, resection margin status did not affect survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objectives: A definition of long-term survival (LTS) in patients with peritoneal metastasis (PM) from gastric cancer (GC), pancreatic cancer (PC) or colorectal cancer (CRC) treated with systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC) is lacking. We aimed to define LTS and investigate characteristics and treatment response in patients who reached LTS in data from two prospective trials., Methods: Retrospective study of patients with GC-, PC-, or CRC-PM from the prospective PIPAC-OPC1 and PIPAC-OPC2 studies. The definition of LTS was based on published systematic reviews and randomized controlled trials. LTS was defined at the time point where 25 % of the patients were alive in these studies. Histology based response was evaluated by the mean Peritoneal Regression Grading Score (PRGS) using biopsies obtained prior to PIPAC 3, and defined by a mean PRGS of ≤2.0 or a decrease of mean PRGS of ≥1, compared to baseline., Results: LTS was defined at 21 (GC), 15 (PC), and 24 (CRC) months. Fifty-one (47.2 %) patients (nine GC, 17 PC, 25 CRC) reached LTS calculated from the date of PM diagnosis. All but one received palliative chemotherapy before PIPAC, and 37 % received bidirectional treatment. More than 90 % of the LTS patients had response according to PRGS. The mOS from PIPAC 1 was 23.3, 12.4, and 28.5 months for GC, PC, and CRC LTS patients., Conclusions: Patients with PM from GC, PC, and CRC treated with systemic chemotherapy and PIPAC can reach LTS and most show histological response. Causality must be further investigated., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: To monitor the results of PIPAC directed therapy based on data from the International Society for the Study of the Pleura and Peritoneum (ISSPP) PIPAC database., Methods: Analysis of data from patients entered between June 15th, 2020, and February 28th, 2023., Results: Twelve centers reported 2,456 PIPAC procedures in 809 patients (median 2, range 1-18) with peritoneal metastasis (PM) from different primary tumors. Approximately 90 % had systemic chemotherapy prior to PIPAC. Twenty-eight percent were treated in prospective protocols. Overall non-access rate was 3.5 %. Concomitant surgical procedures were performed during PIPAC in 1.6 % of the patients. Median length of stay was 2 days. A total of 95 surgical complications were recorded, but only 22 % of these were graded ≥3b. Seventeen-hundred-and-three adverse events were noted, and 8 % were classified ≥3. The rate of complete or major histological response (peritoneal regression grade score, PRGS≤2) increased between the first and the third PIPAC in the group of patients who were evaluated by PRGS, and a PRGS ≤2 or a reduction of the mean PRGS of at least 1 between first and third PIPAC were observed in 80 %. Disease progression (50 %) or technical issues (19 %) were the most important reasons for stopping PIPAC treatment. Median overall survival from first PIPAC directed treatment varied from 10.7 months (CI 8.7-12.5) in gastric cancer to 27.1 months (16.4-50.5) in mesothelioma., Conclusions: The ISSPP PIPAC database provides substantial real-world data supporting the use of PIPAC directed therapy in patients with PM from different primary tumors., Competing Interests: Competing interests: Olivier Glehen is consultant for GAMIDA. Marc Pocard is consultant for Thermasolutions. M. Pocard receives Research funding by Capnomed GmbH, IDImed, Thermasolutions as INSERM laboratory unit U 1275 responsible for peritoneal metastasis research. All other authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC)., Methods: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m 2 ) and doxorubicin (2.1 mg/m 2 ) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy., Results: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy., Conclusions: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe., (© 2023. Society of Surgical Oncology.)

Background: In this nationwide population-based cohort study, we investigated the overall minimum margin width that is independently associated with improved survival following pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) and evaluated whether certain margins or surfaces hold independent prognostic significance., Methods: Data from 367 patients who underwent PD for PDAC in the period 2015-2019 were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. Surgical specimens were evaluated using a standardised pathological protocol involving multicolour inking, axial slicing and exact reporting of circumferential margin clearances in 0.5 mm increments., Results: When categorised according to margin widths of <0.5, <1.0, <1.5, <2.0, <2.5 and <3.0 mm, R1 resections were detected in 34%, 57%, 75%, 78%, 86% and 87% of cases, respectively. In multivariable analyses, an overall margin clearance of ≥1.5 mm was associated with improved survival compared with a clearance of <1.5 mm (HR 0.70 95% CI 0.51-0.97 (p = 0.031)). When evaluating the margins separately, no margin had independent prognostic significance., Conclusion: Margin clearance of at least 1.5 mm was independently associated with improved survival following PD for PDAC., Competing Interests: Conflict of Interest None to declare., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC) is a local treatment for peritoneal metastasis (PM). Prospective data are scarce and evaluation of treatment response remains difficult. This study evaluated the use of the Peritoneal Regression Grading score (PRGS) and its prognostic value., Patients and Methods: This was a prospective, controlled phase II trial in patients with PM from gastrointestinal, gynaecological, hepatopancreatobiliary, primary peritoneal, or unknown primary cancer. Patients in performance status 0-1, with a non-obstructed gastrointestinal tract, and a maximum of one extraperitoneal metastasis were eligible. Colorectal or appendiceal PM had PIPAC with oxaliplatin, other primaries had PIPAC with cisplatin and doxorubicin. Biopsies were taken at each PIPAC and evaluated using the PRGS. Quality-of-life questionnaires were reported at baseline and after three PIPACs., Results: One hundred ten patients were treated with 336 PIPACs (median 3, range 1-12). One hundred patients had prior palliative chemotherapy and 45 patients received bidirectional treatment. Complete or major histological response to treatment (PRGS 1-2) was observed in 38 patients (61%) who had three PIPACs, which was the only independent prognostic factor in a multivariate analysis. The median overall survival (mOS) from PIPAC 1 was 10 months, while patients with PM from gastric, colorectal, and pancreatic cancer had a mOS of 7.4, 16.7, and 8.2 months, respectively. Global health scores were significantly reduced, but patients were less fatigued, nauseated, constipated, and had better appetite after three PIPACs., Conclusions: PIPAC with oxaliplatin or cisplatin and doxorubicin was able to induce a major or complete histological response during three PIPACs, which may provide significant prognostic information, both at baseline and after treatment., (© 2023. Society of Surgical Oncology.)

To investigate whether pancreatic resections (PR) for pancreatic ductal adenocarcinoma (PDAC) is associated with worse survival when resection of the superior mesenteric vein/portal vein (SMV/PV) is required., Background: PR for PDAC with resection of the superior mesenteric vein/portal vein (SMV/PV, PR+V resection) may be associated with inferior overall survival (OS) compared with PR without the need for SMV/PV resection (PR-V). We hypothesized that PR+V results in lower OS compared with PR-V., Method: Retrospective study using data from the nationwide Danish Pancreatic Cancer Database from 2011 to 2020. Data on patients who underwent PR for PDAC were extracted. A group of PR patients found nonresectable on exploratory laparotomy (EXP) was also included. OS was assessed using Kaplan-Meier and Cox proportional hazards models adjusting for confounders (age, sex, R-resection level, chemotherapy, comorbidities, histology T and N classification, procedure subtype as well as tumor distance to the SMV/PV)., Results: Overall, 2403 patients were identified. Six hundred two underwent exploration only (EXP group), whereas 412 underwent pancreatic resection with (PR+V group) and 1389 (PR-V) without SMV/PV resection. Five-year OS for the PR+V group was lower (20% vs 30%) compared with PR-V, although multivariate Cox proportional hazards modeling could not associate PR+V status with OS (Hazard ratio 1.11, P = 0.408)., Conclusion: When correcting for confounders, PR+V was not associated with lower OS compared with PR-V., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest or financial disclosures., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To describe the use of healthcare prior to a diagnosis of pancreatic cancer in Denmark., Design: A population-based cohort study using prospectively recorded data from Danish National Health Registries., Setting: Danish general practice and hospitals., Subjects: A total of 5926 patients diagnosed with pancreatic cancer in 2012-2018 and 59,260 matched references without pancreatic cancer from the Danish general population., Main Outcome Measures: The monthly frequency of healthcare use (contacts and tests in general practice and contacts and diagnostic investigations in hospitals) during the 12 months preceding the pancreatic cancer diagnosis and a corresponding index date assigned to the references., Results: Compared to the references, the patients had increased contacts and diagnostic tests, especially blood glucose testing, in general practice from 7 to 12 months before diagnosis. Hospital contacts and diagnostic imaging increased from 5 months before the diagnosis., Conclusions: The pattern of increasing healthcare contacts before a diagnosis of pancreatic cancer may represent a window of opportunity to diagnose pancreatic cancer earlier. The increased use of blood glucose test in general practice may represent an important sign of an underlying disease. Key pointsPancreatic cancer is a rapidly progressing and highly lethal disease. Focus on early diagnosis is essential to improve the prognosis.Patients with pancreatic cancer had increased number of healthcare contacts from 7 months before the diagnosis.Patients with pancreatic cancer had increased number of blood glucose tests taken throughout almost the entire year before the diagnosis.The results may indicate that a window of opportunity exists to diagnose pancreatic cancer earlier.

Objectives: The four-tiered peritoneal regression grading score (PRGS) is used for histological response evaluation in patients with peritoneal metastasis (PM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Four quadrant biopsies (QBs) from the parietal peritoneum should be assessed by PRGS, but consensus on biopsy site strategy for follow-up biopsies during repeated PIPACs is lacking. We aimed to evaluate whether there is a difference between PRGS in QBs from clips marked PM (QB-CM) compared to biopsies from PM with the visually most malignant features (worst biopsy, WB)., Methods: Prospective, descriptive study. During the first PIPAC, index QBs sites were marked with metal clips. During the second PIPAC, an independent surgical oncologist selected biopsy site for WB and biopsies were taken from QB-CM and WB. One blinded pathologist evaluated all biopsies according to PRGS. From each biopsy, three step sections were stained H&E, followed by an immunostained section, and another three step sections stained H&E., Results: Thirty-four patients were included from March 2020 to May 2021. Median age 64 years. Maximum mean PRGS in QB-CM at PIPAC 1 was 3.3 (SD 1.2). Maximum mean PRGS in QB-CM at PIPAC 2 was 2.6 (SD 1.2), whereas mean PRGS in WB at PIPAC 2 was 2.4 (SD 1.3). At PIPAC 2, there was agreement between maximum PRGS from QB-CM and PRGS from WB in 21 patients. Maximum PRGS from QB-CM was higher in nine and lower in four patients, compared to PRGS from WB., Conclusions: Biopsies from QB-CM did not overestimate treatment response compared to biopsies from WB., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Mojib Fallah et al., published by De Gruyter, Berlin/Boston.)

Aim: Academic and high volume hospitals have better outcome for pancreatic cancer (PC) surgery, but there are no reports on oncological treatment. We aimed to determine the influence of facility types on overall survival (OS) after treatment with chemotherapy for inoperable PC., Material and Methods: 2,657 patients were treated in Denmark from 2012 to 2018 and registered in the Danish Pancreatic Cancer Database. Facilities were classified as either secondary oncological units or comprehensive, tertiary referral cancer centers., Results: The average yearly number of patients seen at the four tertiary facilities was 71, and 31 at the four secondary facilities. Patients at secondary facilities were older, more frequently had severe comorbidity and lived in non-urban municipalities. As compared to combination chemotherapy, monotherapy with gemcitabine was used more often (59%) in secondary facilities than in tertiary (34%). The unadjusted median OS was 7.7 months at tertiary and 6.1 months at secondary facilities. The adjusted hazard ratio (HR) of 1.16 (confidence interval 1.07-1.27) demonstrated an excess risk of death for patients treated at secondary facilities, which disappeared when taking type of chemotherapy used into account. Hence, more use of combination chemotherapy was associated with the observed improved OS of patients treated at tertiary facilities. Declining HR's per year of first treatment indicated improved outcomes with time, however the difference among facility types remained significant., Discussion: Equal access to modern combination chemotherapy at all facilities on a national level is essential to ensure equality in treatment results.

Background: Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver., Methods: The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines., Discussion: The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness., Trial Registration: ClinicalTrials.gov NCT03326791 . Registered on 31 October 2017., (© 2021. The Author(s).)

Objectives: The aim of this study was to identify patterns of palliative chemotherapy (CTh) and the associated overall survival (OS) in patients with pancreatic cancer, with specific focus on age., Methods: Between May 1, 2011, and April 30, 2016, 4260 patients were registered in the Danish Pancreatic Cancer Database. The 1715 patients receiving palliative CTh were retrieved. Age was grouped into less than 70, 70 to less than 75, and 75 years or more., Results: Of the 1715 patients receiving first-line CTh, 586 (34%) underwent second-line CTh and 151 (9%) third-line CTh. First-line gemcitabine resulted in a significant worse survival compared with combination CTh, hazard ratio 1.51. For combination CTh, OS differed between the age groups, P < 0.01. The median OS in the less than 70 years (n = 547), 70 to less than 75 years (n = 163), and 75 years or more (n = 67) groups were 9.3, 9.6, and 7.2 months, respectively. No differences in survival were observed among patients receiving first-line gemcitabine (P = 0.35)., Conclusions: Our findings are useful in treatment-related decision making in patients with pancreatic cancer. A significant survival benefit was observed for all patients after first-line combination CTh. The effect of combination CTh was most prominent among patients aged less than 75 years. By age, no differences in survival were observed in those receiving gemcitabine., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Several trials have documented the favorable safety profile, and promising clinical results of pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed treatment in different types of peritoneal malignancies. However, until the results of randomized trials are available, the quality of documentation and acceptance by the users may be improved through a worldwide registry. The International Society for the Study of Pleura and Peritoneum (www.ISSPP.org) facilitated this process by creating a dedicated focus group and providing the funding needed for the creation and implementation of an international database. This article describes the design and the journey of establishing this international database and the first, preliminary results from the ISSPP PIPAC online database., Methods: In 2019 the ISSPP PIPAC Registry Group started to create a database with a minimal dataset relevant to many diseases and applicable in different framework conditions. The task was divided into three phases including design, testing, implementation, protocol, handbook, legal requirements, as well as registry rules and bylaws for the registry group., Results: The ISSPP PIPAC online database has six key elements (patient, consent, treatment, complications, response evaluation and follow-up). Following design, testing and implementation the database was successfully launched in June 2020. Ten institutions reported on 459 PIPAC procedures in 181 patients during the first 6 months, and the recorded data were comparable to the present literature., Conclusions: A new international multicenter PIPAC database has been developed, tested and implemented under the auspices of ISSPP. The database is accessible through the ISSPP website (www.ISSPP.org), and PIPAC institutions worldwide are highly encouraged to participate., Competing Interests: Competing interests: Olivier Glehen is consultant for GAMIDA. All other authors state no conflict of interest., (© 2021 Michael Bau Mortensen et al., published by De Gruyter, Berlin/Boston.)

Background: Most patients undergo follow-up after surgery for cancers of the gastro-oesophageal junction, stomach or pancreas, but data to support which modalities to use and the frequency of investigation are limited., Methods: Patients in the EUFURO study were randomized to either visits to the outpatient clinic at 3, 6, 9, 12, 18, and 24 months after surgery (standard), or to the addition of [18F]fluorodeoxyglucose (FDG) PET-CT and endoscopic ultrasonography (EUS) with guided fine-needle aspiration biopsy to clinical assessments (intervention). Data from the intervention arm were used to analyse the diagnostic performance of endosonography or [18F]FDG PET-CT in detecting recurrences., Results: During the scheduled follow-up, 42 of 89 patients developed recurrence; PET-CT and EUS in combination detected 38 of these recurrences. EUS detected 23 of the 42 patients with recurrent disease during follow-up and correctly diagnosed 17 of 19 locoregional recurrences. EUS was able to detect isolated locoregional recurrence in 11 of 13 patients. In five patients, EUS was false-positive for isolated locoregional recurrence owing to missed distant metastases. PET-CT detected locoregional recurrence in only 12 of 19 patients, and isolated locoregional recurrence in only 7 of 13. False-positive PET-CT results in 23 patients led to a total of 44 futile procedures., Conclusion: Accuracy in detecting recurrences by concomitant use of PET-CT and EUS was high (90 per cent). PET-CT had moderate to high sensitivity for overall recurrence detection, but low specificity. EUS was superior to PET-CT in the detection of locoregional and isolated locoregional recurrences., (© The Author(s) 2020. Published by Oxford University Press on behalf of BJS Society Ltd.)

Self-expandable metallic stent (SEMS) is a preferred option to relieve dysphagia and to palliate patients with incurable esophageal or gastro-esophageal junction (GEJ) cancer. Health Related Quality of Life (QoL) represents a clinically relevant outcome measure in research focused on palliation of patients with advanced GI cancer. In this context, home visits by a nurse carry the potential to offer important advantages. Eighty patients with incurable esophageal or GEJ cancer were randomized to either standard follow up or to an intervention containing regular home visits by a nurse. The primary outcome variable QoL was assessed by EORTC QLQ-C30 and OES-18 before insertion of SEMS, and at 2, 7 and 12 weeks thereafter. Secondary outcomes were; need for re-interventions, number of patients receiving palliative oncological therapy and overall survival. Sixty-six males and 13 females, with a median age of 71, were included. Self-reported overall QoL was significantly higher in the intervention group (P = 0.03). The organ specific module OES-18 revealed a significant reduction in dysphagia by the intervention (P = 0.03) as well as fewer eating disabilities (P = 0.04). No differences were observed in secondary outcomes except for overall survival, where the median survival was increased from 114 to 183 days by the active intervention (P = 0.02). Home visits by a nurse seem to play an important palliative role after placement of SEMS in patients with incurable esophageal or GEJ cancer by improving QoL and may carry the potential to increase overall survival., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) represents a novel approach to intraperitoneal chemotherapy. Hereby results, obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from colorectal cancer (CRC), are presented., Methods: Data from CRC patients ( n  = 24) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 trials are reported. Oxaliplatin 92 mg/m 2 was administered at 4-6-week intervals. A CE certified nebulizer was used to aerosolize the chemotherapeutics. Outcome criteria were objective tumor response, survival and adverse events., Results: Retrospective analysis of 74 PIPAC procedures carried out in 24 consecutive patients with PM from CRC included from October 2015 to February 2019. Five patients had still the primary tumor in situ, and 22 patients had received palliative systemic chemotherapy. Nineteen patients completed more than two PIPAC procedures, and objective tumor response according to the histological Peritoneal Regression Grading Score (PRGS) was observed in 67% of the patients, while 21% had stable disease. Four patients (21%) had complete response (mean PRGS = 1 and negative cytology). We recorded a median survival of 37.6 (range 7.3-48.9) months from the time of PM diagnosis, whereas it was 20.5 (range 0.13-34.7) months following the first PIPAC session. Minor postoperative complications were noted, and few were considered causally related to the PIPAC treatment. However, two cases of severe postoperative complications were recorded (urosepsis and iatrogenic bowel perforation)., Conclusions: PIPAC with low-dose oxaliplatin can induce objective tumor regression in selected patients with advanced PM from colorectal cancer., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Ellebæk et al., published by De Gruyter.)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel approach to deliver intraperitoneal chemotherapy. We report our experience with PIPAC in patients with peritoneal metastasis (PM) from gastric cancer (GC). Data from GC patients (n = 20) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 studies are reported. All patients had received prior systemic chemotherapy. The mean peritoneal cancer index (PCI) was 10.5 (range 0-39) and nine patients had diffuse GC. PIPAC with cisplatin 7.5 mg/m 2 and doxorubicin 1.5 mg/m 2 were administered at 4-6-week intervals. Outcome criteria were objective tumour response, survival and adverse events. Twenty patients had 52 PIPAC procedures with a median follow-up of 10.4 months (3.3-26.5). Median survival from the time of PM diagnosis and after the first PIPAC procedure was 11.5 months and 4.7 months, respectively. Fourteen patients had repeated PIPAC (> 2), and the objective tumour response according to the histological peritoneal regression grading score (PRGS) was observed in 36%, whereas 36% had stable disease. Ten patients completed the three prescheduled sessions (per protocol group) and 40% of those displayed an objective tumour response, while 20% had stable disease. Only minor postoperative complications were noted, and none were considered causally related to the PIPAC treatment. PIPAC with low-dose cisplatin and doxorubicin can induce a quantifiable objective tumour response in selected patients with PM from GC. Survival data are encouraging and warrant further clinical studies.

Background: Nationwide register data on the effect of primary treatment on survival in an unselected population of patients with pancreatic cancer (PC) have not been reported before. The study aim was to investigate the overall survival (OS) related to initial treatment with resection, chemotherapy, or best supportive care (BSC) in all patients diagnosed with PC in Denmark from 2011 to 2016., Methods: From 1 May 2011 to 30 April 2016, 4260 patients with PC were identified in the Danish Pancreatic Cancer Database. Ninety-seven patients (2%) were excluded, 56 because of treatment with preoperative chemotherapy, 39 because of incorrect registration of diagnosis or treatment, and 2 because of loss to follow-up; thus, 4163 patients were included., Results: The 718 patients (17%) receiving resection had a median overall survival (mOS) of 21.9 months (range 20.0-24.2). In the chemotherapy group of 1746 patients (42%), those treated with FOLFIRINOX had the longest mOS of 10.0 months (9.2-11.0), whereas those treated with gemcitabine had the shortest mOS of 5.1 months (4.8-5.6). The 1697 patients (41%) receiving BSC had a mOS of only 1.6 months (1.5-1.7)., Conclusions: The resected PC cohort had an OS comparable with that reported in randomised controlled trials (RCTs). The mOS of the chemotherapy-treated patients was slightly shorter compared with the results from RCTs and reflects the unselected population in this study. During the last decade, a larger fraction of patients received anticancer treatment, but the BSC group was still large and showed extremely poor OS., Competing Interests: Conflict of interest statement The authors report no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Pancreatic cancer is among the most lethal malignancies with a five-year survival of about 5%, and the only curative treatment is surgical resection. Denmark consists of five governmental regions and has four surgical centres. Our aim was to explore the regional and socio-economic differences in overall survival following a pancreatic cancer diagnosis in Denmark., Methods: We included a total of 5,244 pancreatic cancer patients (WHO International Classification of Diseases, tenth version C25) registered in the Danish Pancreatic Cancer Database during 2012-2017. The data sources used were the Danish Civil Registration System, the Danish National Patient Registry and the Danish national registers on education and income at Statistics Denmark. Cox regression analysis was used to examine all-cause mortality of pancreatic cancer patients by region of residence and socio-economic status., Results: Compared to The Capital Region, there was an excess mortality in the Central Denmark Region and the North Denmark Region in both men and women, whereas no increased mortality was observed in the Region of Southern Denmark or in Region Zealand. Estimates were adjusted for age, year of diagnosis and comorbidity. Adjustment for surgical resection greatly attenuated the variation in survival between the regions., Conclusions: We found significant differences in overall survival across the five Danish regions following a diagnosis of pancreatic cancer. The regional variation in survival was largely attributable to differences in the propensity to use surgical resection., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Upper gastrointestinal malignancies have a poor prognosis. There is no consensus on how patients should be followed after surgery. The authors hypothesized that a structured follow-up programme including endoscopic ultrasonography (EUS) and [ 18 F]fluorodeoxyglucose (FDG) PET/CT would detect cancer recurrences, leading to more patients being eligible for therapy., Methods: After surgery with curative intent for adenocarcinomas in the gastro-oesophageal junction, stomach or pancreas, patients were randomized 1 : 1 to standard clinical assessment in the outpatient clinic at 3, 6, 9, 12, 18 and 24 months after operation, or clinical assessment plus imaging including [ 18 F]FDG PET/CT and EUS. The primary endpoint was number of patients receiving oncological treatment for recurrence. Secondary endpoints were overall and progression-free survival, survival after recurrence detection of isolated locoregional recurrences and risk factors affecting survival., Results: In total, 183 patients were enrolled, including 93 who underwent standard follow-up and 90 who had follow-up plus imaging. A recurrence was detected in 84 patients within 2 years after surgery (42 in each group), including 33 of 42 patients in the imaging group who were asymptomatic. Some 25 of 42 patients in the imaging group and 14 of 42 in the standard group received chemotherapy (P = 0·028). Although survival after detection of recurrence in asymptomatic patients was significantly longer than that for symptomatic patients (P < 0·001), overall survival from date of surgery in the two treatment groups was comparable., Conclusion: Follow-up after surgery for upper gastrointestinal cancer with EUS and PET/CT leads to detection of more asymptomatic cancer recurrences and patients referred for treatment without prolonging overall survival. Registration number: NCT02209415 ( http://www.clinicaltrials.gov)., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: Minimally invasive oesophagectomy (MIO) has gained increasing popularity. This study reports the results of the first patients operated using this technique at our department., Methods: All procedures were prospectively registered in a database. Patients were followed until death, two years after surgery or 1 January 2019., Results: A total of 150 procedures were performed (from 23 November 2015 to 27 February 2018). The median proced-ure time decreased from 350 minutes for the initial 75 pa-tients to 320 minutes for the final 75 patients (p < 0.05). Blood loss decreased from 200 ml to 100 ml (p < 0.05), respectively. The conversion rate for the abdominal procedure was 7% for the initial 75 patients and 8% for the final 75 patients (not significant (NS)). For the thoracic procedure, the corresponding figures were 11% and 7% (NS), respectively. Anastomotic leakage was seen in 17% (initial patients) and 11% (final patients) (NS); however, less than 20% of the leakages needed surgical treatment. The median length of post-operative stay was nine days for both groups. For all 150 patients, pulmonary complications were observed in 18% and cardiac complications in 11%. The 30-day mortality rate was 2% and the one-year survival rate was 86% (124 registered patients)., Conclusions: MIO was introduced at our department with acceptable morbidity and mortality rates and the short-term oncological result was not compromised., Funding: none., Trial Registration: The study was approved as a quality project by the Region of Southern Denmark (18/37355)., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Aims: The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS., Methods and Results: Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect., Conclusions: Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS., (© 2019 John Wiley & Sons Ltd.)

Objective: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation., Design: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models., Results: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application., Conclusion: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Surgical treatment for pancreatic cancer carries a high risk of both morbidity and mortality. Even so, it remains the best curative treatment option. In Denmark, pancreatic surgery has been extensively centralised since the millennium, but the effect of this centralisation on patient outcome has not been evaluated. This study describes regional variation within pancreatic surgery on a malignant indication, focusing on production volume, length of stay, readmission rates and mortality., Methods: This is a retrospective cohort study of all patients with pancreatic cancer who underwent surgical treatment in Denmark from 2011 to 2015. We obtained data from the Danish National Patient Registry and the National Pathology Data Bank on length of stay, transfers, mortality (both short and long term), age, co-morbidity, and disease stage., Results: Four hospital units performed a total of 691 surgical procedures (476 pancreaticoduodenectomies) in the study period. Production volume varied considerably across units with two units accounting for nearly 80% of surgery performed. Data revealed variation on rates of transfers and readmissions as well as disease stage and mortality (both short and long term)., Conclusions: Data suggest that mortality is linked to production volume as well as disease stage, but the small data quantity impedes rigorous statistical analysis. Further studies on the observed associations are required., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

It is unknown whether urban versus rural residency affects pancreatic cancer survival in a universal tax-financed healthcare system. We conducted a nationwide, population-based cohort study of all patients diagnosed with pancreatic cancer in Denmark from 2004-2015. We used nationwide registries to collect information on characteristics, comorbidity, cancer-directed treatment, and vital status. We followed the patients from pancreatic cancer diagnosis until death, emigration, or 1 October 2017, whichever occurred first. We truncated at five years of follow up. We stratified patients into calendar periods according to year of diagnosis (2004-2007, 2008-2011, and 2012-2015). We used Cox proportional hazards model to compute hazard ratios (HRs) with associated 95% confidence intervals (CIs) of death, comparing patients in urban and rural areas. HRs were adjusted for age, sex, comorbidity, tumor stage, and localization. In a sub-analysis, we also adjusted for cancer-directed treatment. We included 10,594 patients diagnosed with pancreatic cancer. Median age was 71 years (inter-quartile range: 63-78 years), and half were men. The majority (61.7%) lived in an urban area at the time of diagnosis. When adjusting for potential confounders, we observed a better survival rate among pancreatic cancer patients residing in urban areas compared with rural areas (adjusted HR: 0.92; 95% CI: 0.87-0.98). When taking treatment into account, the association was unclear (adjusted HR: 0.96; 95% CI: 0.88-1.04). Pancreatic cancer patients residing in urban areas had a slightly better survival rate compared with patients in rural areas., Competing Interests: The authors have declared that no competing interests exist.

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopy-guided administration of aerosolized chemotherapy. PIPAC seems to improve objective tumor response, survival and quality of life in patients with peritoneal metastasis. We assessed feasibility and efficacy of PIPAC in patients with peritoneal metastasis (PM)., Methods: Patients were included in a prospective PIPAC protocol. Patients with colorectal PM were treated with oxaliplatin, patients with other primary tumors were treated with cisplatin and doxorubicin. Any chemotherapy exposure for healthcare workers was monitored by environmental and biological sampling. Feasibility was quantified by completion and complication rates. Response evaluation was documented by the peritoneal regression grading score (PRGS) and by peritoneal lavage cytology. Biopsy sites were marked by clips. Quality of life questionnaires were collected at baseline and after 60, 120 and 180 days., Results: A total of 35 patients with PM were treated with a median of three PIPAC procedures (range 1-9). Intraperitoneal access and completion of PIPAC was achieved in all patients. Few complications and adverse events were noted. There was no risk of chemotherapy exposure for healthcare workers. The mean PRGS was reduced significantly and a reduction of the PRGS was seen in 67% of the patients. Conversion from positive to negative cytology was achieved in 23% of the patients. Quality of life was stabilized from baseline to day 60., Conclusions: PIPAC is feasible and well tolerated, may stabilize the quality of life in patients with end-stage PM and may induce histological and cytological regression.This study is registered at www.clinicaltrials.gov [ClinicalTrials.gov identifier: NCT02320448]., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Aim: The aim of this study was to assess the potential clinical value of contrast enhanced laparoscopic ultrasonography (CE-LUS) as a screening modality for liver metastases during robotic assisted surgery for primary colorectal cancer (CRC)., Method: A prospective, descriptive (feasibility) study including 50 consecutive patients scheduled for robotic assisted surgery for primary CRC. CE-LUS was performed by 2 experienced specialists. Only patients without metastatic disease were included. Follow-up was obtained with contrast-enhanced CT imaging at 3 and 12 months postoperatively., Results: Fifty patients were included; 45 patients were available for final analysis. The patients were equally distributed between stage I, II, and III according to the TNM classification system. No liver metastasis was detected during LUS and CE-LUS. CE-LUS was easy to perform and there was no complication. Follow-up revealed no liver metastasis in any of the patients., Conclusion: CE-LUS did not increase the detection rate of occult liver metastasis during robotic assisted primary CRC surgery. The use of CE-LUS as a screening modality for detection of liver metastasis cannot be recommended based on this study, but larger controlled studies on high-risk patients seem relevant., (© 2017 Wiley Periodicals, Inc.)

Background and Study Aim: Due to the scarcity of specific data on endoscopic ultrasound (EUS)-guided fine-needle biopsies (SharkCore) FNB in the evaluation of pancreatic lesions, we performed a prospective study of the diagnostic performance of EUS SharkCore FNB in patients with pancreatic lesions. The aim of this study was to evaluate the diagnostic accuracy., Patients and Methods: Single-center prospective study of 41 consecutive patients referred for EUS-FNB from October 2015 to April 2016 at our center. EUS-FNB was obtained in a predefined setting regarding the procedure and pathological evaluation. Data regarding demographics, lesion, technical parameters, and diagnostic accuracy were obtained., Results: The study included 41 consecutive patients (22 males (54 %); median age 68 years). The average size of the lesions was 28 mm (median: 30 mm). A diagnostic specimen was identified in 40 (98 %) cases during microscopy with an average of 2.4 passes. The route was trans-duodenal in 20 cases (49 %). The histological diagnosis of the specimens was malignant in 29 cases (71 %), benign in 8 (20 %), suspicious in 2 (5 %), atypical in 1 (2 %) and in 1 (2 %) no material for microscopic evaluation was obtained. This led to a diagnostic accuracy of 93 %, sensitivity of 91 % and a specificity of 100 %. 2 cases (5 %) of self-limiting bleeding were observed. The diagnosis at follow up was malignant in 32 (78 %) of the patients., Conclusions: EUS-FNB of pancreatic mass lesions with the SharkCore needle produced specimens with a diagnostic accuracy of 93 %. The procedure was safe and easy to perform, and these data support the use of EUS-FNB in a routine setting.

Background: Intraoperative ultrasonography during open surgery for colorectal cancer may be useful for the detection of unrecognized liver metastases. Laparoscopic ultrasonography (LUS) for the detection of unrecognized liver metastasis has not been studied in a randomized trial. This RCT tested the hypothesis that LUS would change the TNM stage and treatment strategy., Methods: Patients with colorectal cancer and no known metastases were randomized (1 : 1) to laparoscopic examination (control or laparoscopy plus LUS) in three Danish centres. Neither participants nor staff were blinded to the group assignment., Results: Three hundred patients were randomized, 150 in each group. After randomization, 43 patients were excluded, leaving 128 in the control group and 129 in the LUS group. Intraoperative T and N categories were not altered by LUS, but laparoscopy alone identified previously undetected M1 disease in one patient (0·8 per cent) in the control group and three (2·3 per cent) in the LUS group. In the latter group, LUS suggested that an additional six patients (4·7 per cent) had M1 disease with liver (4) or para-aortal lymph node (2) metastases. The change in treatment strategy was greater in the LUS than in the control group (7·8 (95 per cent c.i. 3·8 to 13·8) and 0·8 (0 to 4·2) per cent respectively; P = 0·010), but the suspected M1 disease was benign in half of the patients., Conclusion: Routine LUS during resection of colorectal cancer is not recommended. Registration number: NCT02079389 (http://www.clinicaltrials.gov)., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Colorectal cancer (CRC) is one of the most common cancer diseases worldwide. One in 4 patients with CRC will have a disseminated disease at the time of diagnosis and often in the form of synchronous liver metastases. Studies suggest that up to 30% of patients have non-recognized hepatic metastases during primary surgery for CRC. Intraoperative ultrasonography examination (IOUS) of the liver to detect liver metastases was considered the gold standard during open CRC surgery. Today laparoscopic surgery is the standard procedure, but laparoscopic ultrasound examination (LUS) is not performed routinely. Aim To perform a systematic review of the test performance of IOUS and LUS regarding the detection of synchronous liver metastases in patients undergoing surgery for primary CRC. Method The literature was systematically reviewed using the search engines: PubMed, Cochrane, Embase and Google. 21 studies were included in the review and the key words: intraoperative ultrasound, laparoscopic ultrasound, staging colon and rectum cancer. Results Intraoperative ultrasound showed a higher sensitivity, specificity, positive predictive value and overall accuracy for the detection liver metastases during surgery for primary CRC, compared to preoperative imaging modalities (ultrasound, computed tomography (CT) and contrast-enhanced computed tomography (CE-CT)). LUS showed a higher detection rate for liver metastases compared to CT, CE-CT and magnetic resonance imaging (MRI). Conclusion This systematic review found that both IOUS and LUS had a higher detection rate regarding liver metastases during primary CRC surgery, especially liver metastases<10 mm in diameter, when compared to US, CT, CE-CT and MRI.

Up to 20% of the patients with colorectal cancer (CRC) will have liver metastases at the time of the diagnosis, and some of these metastases may be missed during preoperative evaluation. While intraoperative ultrasound is considered the gold standard for liver evaluation during primary open CRC surgery, laparoscopic ultrasound (LUS) is not performed routinely during laparoscopic CRC surgery. Based on the available literature LUS had a higher detection rate for especially small liver metastases compared to preoperative imaging modalities, but better prospective trials are needed.

Thickened stomach wall is sometimes found incidentally in abdominal CT scans. A review of the literature supports our general perception that normal findings or benign diseases are found in the majority of the cases. Gastroscopy seems to be sufficient for making the diagnosis in most patients; and endoscopic ultrasonograhy is only indicated for those patients in whom malignant diseases or benign submucosal lesions with need for therapy are still suspected after standard upper endoscopy has been performed.

Diaphragmatic hernia is a rare complication in pregnancy which due to misdiagnosis or management delays may be life-threatening. We report a case of a woman in the third trimester of pregnancy who presented with sudden onset of severe epigastric and thoracic pain radiating to the back. Earlier in the index pregnancy, she had undergone laparoscopic antireflux surgery (ARS) for a hiatus hernia because of severe gastro-oesophageal reflux. Owing to increasing epigastric pain a CT scan was carried out which diagnosed wrap disruption with gastric herniation into the thoracic cavity and threatened incarceration. This is, to our knowledge, the first report of severe adverse outcome after ARS during pregnancy, with acute intrathoracic gastric herniation. We recommend the avoidance of ARS in pregnancy, and the need to advise women undergoing ARS of the postoperative risks if pregnancy occurs within a few years of ARS.

Purpose: There is a lack of studies on the intra- and interobserver variability of endoscopic ultrasonography (EUS) and especially endoscopic sonoelastography (ES). The aim of this study was to evaluate the intra- and interobserver agreement of EUS and ES during the evaluation of a specific lymph node in patients with upper gastrointestinal malignancies (UGIM). The ES strain ratio was used to differentiate between benign and malignant lymph nodes and the interobserver agreement was evaluated., Materials and Methods: This study prospectively enrolled 62 patients with UGIM. EUS and ES were performed by two observers in randomized order of a specific lymph node using a linear Pentax echoendoscope and the Hitachi EUB-8500 US unit. The lymph node was classified as malignant or benign on the basis of EUS, ES, an ES scoring system, and 5 repeated strain ratio measurements. The intraobserver variation was evaluated by each observer performing 20 strain ratio measurements of the same lymph node. Finally, EUS fine needle aspiration was performed. The kappa statistic was used to test for interobserver variability., Results: One patient was excluded due to inadequate ES imaging. Thus, 61 patients were included in the analysis of the interobserver agreement. Using EUS, ES, and an ES scoring system, the kappa values were 0.80, 0.58, and 0.35, respectively. An ES strain ratio of 3.81 was defined as the cut-off value between benign and malignant lymph nodes using cytology as the gold standard (n = 55). Using this modality, a kappa value of 0.59 was obtained. A t-test comparison of the measured strain ratios for the two observers found no significant differences., Conclusion: ES and ES strain ratio evaluation of lymph nodes were feasible and may be reproduced with good interobserver agreement in a blinded clinical setup. The predefined ES scoring system provided only poor interobserver agreement. Image selection should be part of the intra- and interobserver evaluation. ES strain ratio seemed promising but larger studies are needed to evaluate this new feature., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Cancer of the papilla of Vater is a relatively rare disease. It is difficult to separate from other periampullary tumours at the time of diagnosis. Recent studies have shown that patients with cancer of the papilla tend survive longer than patients with pancreatic cancer and cancers of biliary and duodenal origin. The aim of this study was to compare our results with those reported in the international literature., Material and Methods: The study included all patients who were referred with cancer of the papilla to the Department of Surgical Gastroenterology, Odense University Hospital, between 1995 and 2005. The data were collected retrospectively from hospital and departmental databases., Results: Among the 35 patients, 30 underwent operation. A total of 27 had a Whipple resection performed, 26 of whom were radical resections. Three patients had a palliative gastroenteroanastomosis performed. Postoperative mortality was 7%, and the 1, 3 and 5-year survival was 74%, 59% and 43%, respectively. Resected patients without lymph node involvement had an estimated 5-year survival of 58%., Conclusion: The estimated 5-year survival of over 40% in resected patients was comparable with that reported in international studies. We found a significantly higher 5-year survival in patients without lymph node involvement, and the general prognosis for patients with cancer of the papilla was better than the prognosis reported for other periampullary tumours.

Objective: The value of repeating endoscopic ultrasound (EUS) is seldom described. This study evaluates a patient population in which EUS was repeated., Material and Methods: This was a retrospective study of patients who between January 2002 and December 2006 had an EUS scan performed; this EUS scan (re-EUS) was the second or more EUS scan performed., Results: Over the study period, the department performed 3024 EUS procedures, of which 561 investigations were defined as re-EUS. According to defined exclusion criteria, 244 procedures were not analyzed further. The study group thus consisted of 317 procedures (242 patients). In 163 cases (126 patients), re-EUS was planned by the endosonographer for control of an undetermined lesion. The first re-EUS scan performed changed the further management in 91 of 126 patients (72%). Sensitivity and specificity of re-EUS regarding pancreatic cancer were 0.65 and 1.00, respectively. Re-EUS was performed in 82 cases (77 patients) where no re-investigation had been planned at the initial EUS scan but worsening of symptoms or new findings of other imaging procedures had led to an additional EUS scan. Thirteen of these patients (17%) proved to have pancreatic cancer. In 62 cases (57 patients) re-EUS and EUS-guided fine-needle aspiration (FNA) had been planed in order to confirm the suspicion of malignant disease. Following re-EUS and EUS-FNA, 40 of these patients could be referred for either oncology or surgery. In the remaining 10 cases, re-EUS was performed for miscellaneous indications., Conclusion: Re-EUS has a substantial clinical impact on the further management of the patient.

Treatment of patients with locally advanced pancreatic cancer remains a challenge, and the exact role of surgery with vascular resection remains unclear. Several studies on selected patient populations have addressed the problem, but with varying results. Although venous resection may be performed without increased morbidity and mortality, the majority of studies found no improved long-term survival when compared to oncological treatment.

Introduction: Cancer in the upper gastrointestinal tract has a poor prognosis and the best results are obtained by the few resectable patients. Earlier studies indicated that Danish survival might be inferior to that of other Scandinavian countries. The aim of this study was to evaluate the long-term survival after curative resections for these patients., Material and Methods: All patients referred for treatment of cancer of the oesophagus, stomach or pancreas were prospectively included. Data were registered with regard to pre-therapeutic examination and operative results. Deceased patients were found by comparison with the Danish Central Personal Register in January 2007., Results: A total of 398 patients were included, of whom 164 were found to be possibly resectable. In total 118 (30%) patients underwent complete surgical resection. The median survival period for patients with oesophageal cancer, stomach cancer and pancreatic cancer was: 22.7 months (18.7-39.4), above 36 months and 31.4 months (19.2-) respectively. The observed 3-year survival was 40% (26-53), 56% (38-71) and 47% (31-62). The estimated 5-year survival was 35% (22-48), 56% (39-72), 43% (27-59)., Conclusion: The observed long-term survival was comparable to international results. However, only one third of the patients were eligible for complete surgical resection. It is therefore important to establish a close cooperation between surgeons and oncologist to improve the overall survival for this group of patients.

Background: Endoscopic ultrasonography (EUS) is a valuable diagnostic tool for evaluating pathologies in or in relation to the upper gastrointestinal tract. The aim of this study was to evaluate the diagnostic yield of EUS in patients suspected of neuroendocrine tumours (NETs)., Materials and Methods: Retrospective analysis of data from the department's local EUS database and from hospital records., Results: From November 2001 to December 2006, 21 patients were referred for EUS due to suspected neuroendocrine tumour. 17 patients were females and 4 were males. The median age was 48 years (range 14-93 years). 13 patients had symptoms (hypoglycaemia) suggesting that an insulinoma could be present. The remaining 8 patients had different kinds of symptoms including patients whose tumour was found by chance by another imaging modality. In 8 patients, EUS did not show any pathology. At follow-up, 6 of these were without any symptoms. One patient had died and one patient had subsequent surgery for intestinal obstruction due to a neuroendocrine carcinoma in the ileum and liver metastases. EUS revealed a mass lesion in 13 patients. 7 of these have had a CT scan which showed normal findings in 4. External ultrasound had been performed in 8 of the 13 patients, and showed normal findings in 4 out of the 8. All 13 patients with mass lesions had subsequent surgery showing different kinds of NETs in 11 patients, adenocarcinoma of the pancreas in one patient, and normal findings in one case., Conclusion: EUS may detect NETs which have not being visualised by other imaging modalities. EUS should be performed early in the diagnostic work up if a NET is suspected.

Introduction: Only 10-20% of patients with pancreatic cancer are offered operation with curative intent. If this is not possible, treatment with pre-operative radiotherapy in combination with chemotherapy offers the opportunity to reduce tumor size in patients with locally advanced disease, and possibly resection with curative intent afterwards. This treatment has been offered for the last three years at the Department of Oncology, Odense University Hospital. In the following we present our results., Materials and Methods: A total of 26 patients with locally advanced unresectable pancreatic cancer were offered a combination of radiotherapy and chemotherapy. 4-6 weeks after treatment the patients were evaluated for resection., Results: Of the 26 patients 24 completed planned treatment. Eight patients were subsequently assessed resectable. One patient refused surgery; the other 7 patients had a R0-resection. Median survival for the whole group is 12 months. Six of the patients who went through surgery are without signs of recurrent disease after median 16 months, one patient died with recurrent disease after 37 months., Conclusion: These results are similar to results from other countries. Therefore patients with locally advanced unresectable pancreatic cancer should be offered radiotherapy in combination with chemotherapy. Evaluation for surgery should be carried out 4-6 weeks after end of treatment. This strategy offers the opportunity for R0-recection and consequently cure.

Introduction: Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor identified by a positive immunostaining (KIT tyrosine kinase). Surgical resection is the primary treatment, but non-resectable and recurrent disease may be treated by specific tyrosine kinase inhibitors. This study evaluates the clinical and pathological presentation of a Danish GIST population., Materials and Methods: Retrospective evaluation of patients diagnosed, treated and/or followed under the GIST diagnosis at the Department of Surgery, Odense University Hospital, during the period from January 1995 to September 2006., Results: 41 patients with GIST were identified (25 males, 16 females, median age 62 years). The predominant symptoms leading to the diagnosis were upper gastrointestinal bleeding and abdominal pain. The majority of tumors were located in the stomach (63%) or in the small intestine (22%). 95% of the patients had a complete surgical resection, whereas resection was impossible in 2 patients. Approximately (2)/3 of the patients had a low or medium risk of developing metastases according to tumor size and number of mitoses. 1 in 4 patients was treated with a tyrosine kinase inhibitor during the course of the disease., Conclusion: GIST is a rare mesenchymal tumor but due to immunostaining methods the detection rate is increasing. The clinical and pathological presentation of this Danish GIST population is comparable to international data.

Background: This study evaluated the ability of combined endoscopic and laparoscopic ultrasonography to predict R0 resection and avoid unnecessary surgery in patients with upper gastrointestinal tract cancer (UGIC)., Methods: A total of 411 consecutive patients with UGIC (182 pancreatic cancers, 134 gastric cancers and 95 oesophageal cancers) treated between January 2002 and May 2004 were analysed prospectively. The allocation of patients into resectability groups by endoscopic ultrasonography (EUS) and laparoscopic ultrasonography (LUS) was compared with the treatment actually undertaken., Results: The combination of EUS and LUS correctly predicted R0 resection in 90.6 per cent, R1-R2 in 91 per cent and irresectability in 91.4 per cent of patients. Ten patients (2.4 per cent) had explorative laparotomy only. There were no complications associated with the EUS and LUS procedures., Conclusion: The routine use of EUS and LUS before surgery predicted R0 resection in nine of ten patients and reduced the number of unnecessary laparotomies to less than 3 per cent., (Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)