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BACKGROUND Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING Swiss Cancer Research foundation.

Backgrounds: COVID-19 related reduction of surgical procedures jeopardizes learning on the job of surgical residents. Many educators resorted to digital resources in the search for alternatives. However, these resources are often limited to the extent they offer resident-surgeon interaction like a joint surgical performance does. Here we present a roadmap of livestreaming surgical procedures, and evaluate how surgical livestreams on human cadavers address the unmet educational needs of surgical residents in our Dutch nationwide initiative. Methods: Technical and organizational feasibility, and definition of outcome deliverables for the livestream series and per livestream were essential in livestream development. Faculty selected interventions, lecture contents, and participant preparations. Appropriate location, technical setup, and support were imperative for a stable, high-quality stream with integrated interaction, while maintaining digital privacy. A survey was sent to livestream participants to evaluate each livestream, and allow for constant improvement during the broadcasting of the series. Only surveys which were completed by surgical residents were included in the analysis of this study. Results: Each livestream attracted 139–347 unique viewers and a total of 307 surveys were completed by participants (response rate of 23–38% per livestream). Sixty percent of surveys (n = 185) were completed by surgical residents. Livestreams were highly valued (appreciation 7.7 ± 1.1 and recommendation 8.6 ± 1.1), especially the live procedures combined with interaction and theoretical backgrounds. Criticized were technical difficulties and timing of the livestreams between 5 and 7 pm, which interfered with clinical duties. Conclusion: Livestreaming surgical procedures on human cadavers is a valid and valued solution to augment resident education. Digital privacy and a stable, high-quality interactive stream are essential, as are appropriate moderation and relevant lectures. While livestreaming cannot replace hands-on training in the operating room, it enables surgeon-resident interaction which is key in education—and missed in pre-recorded surgical procedures which are currently available online.

Recurrence after resection in patients with non-functional pancreatic neuroendocrine tumors (NF-pNET) has a considerable impact on overall survival. Accurate risk stratification will tailor optimal follow-up strategies. This systematic review assessed available prediction models, including their quality. This systematic review followed PRISMA and CHARMS guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2022 for studies that developed, updated, or validated prediction models for recurrence in resectable grade 1 or 2 NF-pNET. Studies were critically appraised. After screening 1883 studies, 14 studies with 3583 patients were included: 13 original prediction models and 1 prediction model validation. Four models were developed for preoperative and nine for postoperative use. Six models were presented as scoring systems, five as nomograms, and two as staging systems. The c statistic ranged from 0.67 to 0.94. The most frequently included predictors were tumor grade, tumor size, and lymph node positivity. Critical appraisal deemed all development studies as having a high risk of bias and the validation study as having a low risk of bias. This systematic review identified 13 prediction models for recurrence in resectable NF-pNET with external validations for 3 of them. External validation of prediction models improves their reliability and stimulates use in daily practice.

Background Thyroid storm is a feared complication in patients with hyperthyroidism undergoing surgery. We assessed the risk of thyroid storm for different preoperative treatment options for patients with primary hyperthyroidism undergoing surgery. Methods Pubmed, EMBASE, and The Cochrane Library were searched systematically for all studies reporting on adult hyperthyroid patients undergoing elective surgery under general anaesthesia. Selected studies were categorised based on preoperative treatment: no treatment, antithyroid medication (thionamides), iodine, β-blocking medication, or a combination thereof. Treatment effect, that is restoring euthyroidism, was extracted from the publications if available. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) or the Cochrane Risk of Bias tool for randomised studies. Results The search yielded 7009 articles, of which 26 studies published between 1975 and 2020 were selected for critical appraisal. All studies had moderate to critical risk of bias, mainly attributable to risk of confounding, classification of intervention status, and definition of the outcome. All studies reported on thyroidectomy patients. We found no randomised studies comparing the risk of thyroid storm between treated and untreated patients. Cases of thyroid storm were reported in all treatment groups with incidences described ranging from 0% to 14%. Conclusion Evidence assessing the risk of perioperative thyroid storm is of insufficient quality. Given the seriousness of this complication and the impossibility of identifying patients at increased risk, preoperative treatment of these patients remains warranted.

Aim To investigate the impact of family visit restrictions during the COVID-19 pandemic on deliriums, falls, pneumonia, pressure ulcers and readmissions among surgical inpatients with gastrointestinal (oncologic) diseases. Design Cohort study. Methods This study was conducted among adult inpatients undergoing gastrointestinal surgery in two academic hospitals. During the COVID-19 outbreak in 2020, over a 10-week period, one cohort was subjected to family visit restrictions. Per patient, one person per day was allowed to visit for a maximum of 30 min. This cohort was compared with another cohort in which patients were not subjected to such restrictions during a 10-week period in 2019. Logistic regression analyses were used to investigate the impact of the restrictions on deliriums, falls, pneumonia, pressure ulcers and readmissions. Results In total, 287 patients were included in the 2020 cohort and 243 in the 2019 cohort. No differences were observed in the cohorts with respect to baseline characteristics. Logistic regression analyses showed no significant differences in deliriums, falls, pneumonia, pressure ulcers and readmissions between the cohorts. Conclusion We cautiously conclude that the family visit restrictions during the COVID-19 pandemic did not contribute to deliriums, falls, pneumonia, pressure ulcers or readmissions in surgical patients with gastrointestinal (oncologic) diseases. Impact COVID-19 influenced family-centred care due to family visit restrictions. Nurses need to continue monitoring outcomes known to be sensitive to family-centred care to gain insight into the effects of visit restrictions and share the results in order to include nurses' perspectives in COVID-19-decision-making. Re-implementing of family visit restrictions should be carefully considered in policy-making.

Aim Open resection of small bowel neuroendocrine neoplasms (SB-NEN) is still considered standard-of-care, mainly because of frequently encountered multifocality and central mesenteric masses. The aim of this study was to evaluate surgical approach for SB-NEN at a national level and determine predictors for overall survival. Methods Patients with SB-NEN who underwent resection between 2005 and 2015 were included from the Netherlands Cancer Registry. Patient and tumor characteristics were compared between laparoscopic and open approach. Overall survival was assessed by Kaplan–Meier and compared with the Log-rank test. Independent predictors were determined by Cox proportional hazards model. Results In total, 482 patients were included, of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection. The open resection group had significantly more multifocal tumors resected (24% vs. 14%), pN2 lymph nodes (18% vs. 7%) and stage IV disease (36% vs. 22%). Overall survival after open resection was significantly shorter compared to laparoscopic resection (3-year: 81% vs. 89%, 5-year: 71% vs. 84%, p = 0.004). In multivariable analysis, age above 60-years (60–75, HR 3.38 (95% CI 1.84–6.23); > 75 years, HR 7.63 (95% CI 3.86–15.07)), stage IV disease (HR 1.86 (95% CI 1.18–2.94)) and a laparoscopic approach (HR 0.51 (95% CI 0.28–0.94)) were independently associated with overall survival, whereas multifocal primary tumor, grade and resection margin status were not. Conclusion Laparoscopic resection was the approach in 29% of SB-NEN at a national level with selection of the more favorable patients. Laparoscopic resection remained independently associated with better overall survival besides age and stage, but residual confounding cannot be excluded.

Surgical errors often occur because of human factor-related issues. A medical data recorder (MDR) may be used to analyze human factors in the operating room. The aims of this study were to assess intraoperative safety threats and resilience support events by using an MDR and to identify frequently discussed safety and quality improvement issues during structured postoperative multidisciplinary debriefings using the MDR outcome report.In a cross-sectional study, 35 standard laparoscopic procedures were performed and recorded using the MDR. Outcome data were analyzed using the automated Systems Engineering Initiative for Patient Safety model. The video-assisted MDR outcome report reflects on safety threat and resilience support events (categories: person, tasks, tools and technology, psychical and external environment, and organization). Surgeries were debriefed by the entire team using this report. Qualitative data analysis was used to evaluate the debriefings.A mean (SD) of 52.5 (15.0) relevant events were identified per surgery. Both resilience support and safety threat events were most often related to the interaction between persons (272 of 360 versus 279 of 400). During the debriefings, communication failures (also category person) were the main topic of discussion.Patient safety threats identified by the MDR and discussed by the operating room team were most frequently related to communication, teamwork, and situational awareness. To create an even safer operating culture, educational and quality improvement initiatives should aim at training the entire operating team, as it contributes to a shared mental model of relevant safety issues.

Purpose Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE induces objective response in up to 57% of pancreatic neuroendocrine neoplasms (panNENs). Therefore, PRRT may comprise a downstaging option for panNEN patients who are not eligible for upfront curative surgery or are at high risk for recurrence. The aim of this study was to assess the potency of induction PRRT for locally advanced panNENs and to evaluate the effect of surgery after PRRT on overall survival (OS). Methods Retrospective cohort study of panNEN patients treated with induction 177Lu-DOTATATE. Results After PRRT, 26 out of 49 patients underwent pancreatic surgery with curative intent (PRRT + surgery). Partial objective response was obtained in 62% of the PRRT + surgery group versus 26% of the patients not undergoing panNEN surgery (PRRT-only group, p = 0.02). Downstaging in tumour-vessel interface was observed in 38% of all patients with at least one involved vessel. Median OS was 14.7 years (95% CI 5.9–23.6) for the PRRT + surgery group compared to 5.5 years (95% CI 4.5–6.5) for the PRRT-only group (p = 0.003). In the Cox proportional hazards analysis, surgery was not significantly associated with OS after propensity score adjustment with cumulative activity, performance status, tumour size after PRRT, and tumour grade. Median progression-free survival was 5.3 years (95% CI 2.4–8.1) for the PRRT + surgery group and 3.0 years (95% CI 1.6–4.4) for the PRRT-only group (p = 0.02). Conclusion Early administration of PRRT followed by surgery is associated with favourable long-term outcomes in patients with locally advanced or oligometastatic panNEN and can be considered for selected patients with vascular involvement and/or increased risk of recurrence.

BACKGROUND Literature on laparoscopic resection of small-bowel neuroendocrine neoplasms consists of single case descriptions or small selected case-series only, likely because of challenging mesenteric lymphadenectomy. OBJECTIVE We evaluated an institutional change in approach from open to laparoscopic resection of small-bowel neuroendocrine neoplasm independent from lymph node involvement. DESIGN This is a retrospective comparative cohort study. SETTING This study was conducted at a tertiary referral center. PATIENTS Patients with small-bowel neuroendocrine neoplasms were included. INTERVENTIONS Laparoscopic or open segmental bowel resection with central mesenteric lymphadenectomy was the studied intervention. MAIN OUTCOME MEASURES Complexity of lymphadenectomy was assessed by determining the distance between suspect lymph nodes and main mesenteric branches on preoperative CT. Number of (tumor-positive) lymph nodes, conversion to open surgery, and postoperative complications according to Clavien-Dindo classification and length of stay were measured. RESULTS A total of 34 patients were identified, of whom 11 (32%) underwent open and 23 (68%) laparoscopic surgery. Distances between lymph nodes and main mesenteric branches and number of examined and tumor-positive lymph nodes did not differ significantly. Laparoscopy was converted in 7 patients (30%). Major postoperative complications (grades 3-5) occurred in 1 patient (9%) in the open surgery group (grade 5) and 2 patients (9%) in the laparoscopic surgery group (grade 3b). The length of stay was 8 days (range, 6-18 d) in the open surgery group and 4 days (4-8 d) in the laparoscopic group (p = 0.036). LIMITATIONS Long-term outcomes could not reliably be assessed because of the relatively short follow-up time of the laparoscopy group. CONCLUSIONS Laparoscopic bowel resection with central mesenteric lymphadenectomy for small-bowel neuroendocrine neoplasm appears safe and associated with similar pathologic outcome and shorter length of stay in the setting of a tertiary referral center. See Video Abstract at http://links.lww.com/DCR/B512. VALOR DE LA LAPAROSCOPIA PARA LA RESECCIN DE NEOPLASIAS NEUROENDOCRINAS DEL INTESTINO DELGADO, INCLUIDA LA LINFADENECTOMA MESENTRICA CENTRAL ANTECEDENTES:La literatura sobre la reseccion laparoscopica de neoplasias neuroendocrinas del intestino delgado consiste en descripciones de casos unicos o en series de pequenos casos seleccionados, probablemente debido a la dificultad de la linfadenectomia mesenterica.OBJETIVO:Evaluamos un cambio institucional en el enfoque de la reseccion abierta a laparoscopica de SB-NEN independientemente de la afectacion de los ganglios linfaticos.DISENO:Este es un estudio de cohorte comparativo retrospectivo.AJUSTE:Este estudio se realizo en un centro de referencia terciario.PACIENTES:Pacientes con neoplasias neuroendocrinas de intestino delgado.INTERVENCIONES:Reseccion intestinal segmentaria laparoscopica o abierta con linfadenectomia mesenterica central.PRINCIPALES MEDIDAS DE RESULTADO:La complejidad de la linfadenectomia se evaluo determinando la distancia entre los ganglios linfaticos sospechosos y las principales ramas mesentericas en la TC preoperatoria. Numero de ganglios linfaticos (tumor positivos), conversion a cirugia abierta, complicaciones postoperatorias segun Clavien-Dindo y duracion de la estancia.RESULTADOS:Se identificaron 34 pacientes, de los cuales 11 (32%) fueron sometidos a cirugia abierta y 23 (68%) laparoscopica. Las distancias entre los ganglios linfaticos y las principales ramas mesentericas y el numero de ganglios linfaticos examinados y con tumores positivos no difirieron significativamente. La laparoscopia se convirtio en 7 pacientes (30%). Se produjeron complicaciones posoperatorias importantes (grados 3-5) en un paciente (9%) en el grupo de cirugia abierta (grado 5) y en 2 (9%) pacientes en el grupo de cirugia laparoscopica (grado 3b). La estancia intrahospitalaria fue de 8 dias (rango 6-18) en el grupo de cirugia abierta y 4 dias (4-8) en el grupo laparoscopico (p = 0.036).LIMITACIONES:Los resultados a largo plazo no se pudieron evaluar de manera confiable debido al seguimiento relativamente corto del grupo de laparoscopia.CONCLUSIONES:La reseccion intestinal laparoscopica con linfadenectomia mesenterica central para SB-NEN parece segura y se asocia con un resultado patologico similar y una estadia mas corta en el contexto de un centro de referencia terciario. Consulte Video Resumen en http://links.lww.com/DCR/B512.

Background Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American Association of Clinical Endocrinologists and Endocrine Surgeons, and the Endocrine Society are ambiguous about the appropriate duration of follow-up. The aim of this systematic review and meta-analysis is to evaluate the recurrence rate of sporadic pheochromocytomas after curative adrenalectomy. Materials and Methods A literature search in PubMed, Embase, and the Cochrane Library was performed. A study was eligible if it included a clear report on the number of sporadic patients, recurrence rate, and follow-up duration. Studies with an inclusion period before 1990, Results A total of 13 studies, including 430 patients, were included in the synthesis. The meta-analysis results describe a pooled recurrence rate after curative surgery of 3% (95% confidence interval: 2–6%, I2 = 0%), with a weighted mean time to recurrence of 49.4 months (SD = 30.7) and a weighted mean follow-up period of 77.3 months (SD = 32.2). Conclusions This meta-analysis shows a very low recurrence rate of 3%. Prospective studies, including economical and health effects of limited follow-up strategies for patients with truly sporadic pheochromocytomas should be considered.

Objective To perform a nationwide population based study in ATC on incidence, treatment and survival. Design Retrospective cohort study. Methods All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan–Meier method and univariable statistically significant factors were included in a multivariable regression model. Results In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11–0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4–2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases. Conclusions ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.

Insulin-producing pancreatic neuroendocrine tumors (PanNETs)/insulinomas are generally considered to be indolent tumors with an excellent prognosis after complete resection. However, some insulinomas have a poor prognosis due to relapses and metastatic disease. Recently, studies in non-functional PanNETs indicated that behavior can be stratified according to alpha- and beta-cell differentiation, as defined by expression of the transcription factors ARX and PDX1, respectively. It is unknown whether similar mechanisms play a role in insulinomas. Therefore, we determined ARX and PDX1 expression in a cohort of 35 sporadic primary insulinomas and two liver metastases of inoperable primary insulinomas. In addition, WHO grade and loss of ATRX or DAXX were determined by immunohistochemistry, and alternative lengthening of telomeres (ALT) and CDKN2A status by fluorescence in situ hybridization. These findings were correlated with tumor characteristics and clinical follow-up data. In total, five out of 37 insulinoma patients developed metastatic disease. Metastatic insulinomas were all larger than 3 cm, whereas the indolent insulinomas were smaller (p value CDKN2A as opposed to absence of ARX expression, ALT, or CDKN2A deletions in the 32 non-metastatic cases. The two liver metastases also showed ARX expression and ALT (2/2). The presence of ARX expression, which is usually absent in beta-cells, and genetic alterations not seen in indolent insulinomas strongly suggest a distinct tumorigenic mechanism in malignant insulinomas, with similarities to non-functional PanNETs. These observations may inform future follow-up strategies after insulinoma surgery.

Simple Summary: Patients with the rare cancer adrenocortical carcinoma are exposed to many symptoms and treatment side-effects. Research on how this can affect their health-related quality of life (HRQoL) is limited, however. This article includes the first assessment of HRQoL in a population-based cohort of patients with adrenocortical carcinoma with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire and the newly developed disease-specific additional questionnaire ACC-QOL. The ACC-QOL has good psychometric properties in terms of validity, reliability, and responsiveness. Patients diagnosed more than 5 years ago reported a relatively good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients after additional surgery reported a slightly lower HRQoL due to physical limitations. Patients who had recently received mitotane or chemotherapy reported a worse HRQoL and problems in many domains. This knowledge and the new disease-specific questionnaire can aid future research, side-effect monitoring, treatment guidance, and shared decision making. We aimed to develop a disease-specific adrenocortical carcinoma (ACC) health-related quality of life (HRQoL) questionnaire (ACC-QOL) and assess HRQoL in a population-based cohort of patients with ACC. Development was in line with European Organization for Research and Treatment of Cancer (EORTC) guidelines, though not an EORTC product. In phase I and II, we identified 90 potential HRQoL issues using literature and focus groups, which were reduced to 39 by healthcare professionals. Pilot testing resulted in 28 questions, to be used alongside the EORTC QLQ-C30. In Phase III, 100 patients with ACC were asked to complete the questionnaires twice in the PROFILES registry (3-month interval, respondents: first 67, second 51). Confirmatory factor analysis demonstrated the structural validity of 26 questions with their scale structure (mitotane side-effects, hypercortisolism/hydrocortisone effects, emotional effects). Internal consistency and reliability were good (Cronbach's alpha 0.897, Interclass correlation coefficient 0.860). Responsiveness analysis showed good discriminative ability (AUC 0.788). Patients diagnosed more than 5 years ago reported a good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients who underwent recent treatment reported a lower HRQoL and problems in several domains. In conclusion, we developed an ACC-specific HRQoL questionnaire with good psychometric properties.

Peptide receptor radionuclide therapy (PRRT) withRetrospective cohort study of panNEN patients treated with inductionAfter PRRT, 26 out of 49 patients underwent pancreatic surgery with curative intent (PRRT + surgery). Partial objective response was obtained in 62% of the PRRT + surgery group versus 26% of the patients not undergoing panNEN surgery (PRRT-only group, p = 0.02). Downstaging in tumour-vessel interface was observed in 38% of all patients with at least one involved vessel. Median OS was 14.7 years (95% CI 5.9-23.6) for the PRRT + surgery group compared to 5.5 years (95% CI 4.5-6.5) for the PRRT-only group (p = 0.003). In the Cox proportional hazards analysis, surgery was not significantly associated with OS after propensity score adjustment with cumulative activity, performance status, tumour size after PRRT, and tumour grade. Median progression-free survival was 5.3 years (95% CI 2.4-8.1) for the PRRT + surgery group and 3.0 years (95% CI 1.6-4.4) for the PRRT-only group (p = 0.02).Early administration of PRRT followed by surgery is associated with favourable long-term outcomes in patients with locally advanced or oligometastatic panNEN and can be considered for selected patients with vascular involvement and/or increased risk of recurrence.

BackgroundSmall bowel neuroendocrine neoplasms (SB-NEN) are rare cancers, population-based studies are needed to study this rare indolent disease. The aim of this study was to explore trends in epidemiology, treatment and survival outcomes of patients with SB-NEN based on Dutch nationwide data.Patients and methodsPatients with grade 1 or 2 SB-NEN diagnosed between 2005 and 2015 were retrieved from the Netherlands Cancer Registry and linked to The Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands. Age-adjusted incidence rates were calculated based using the direct standardization method. Survival analyses were performed with the Kaplan–Meier method.ResultsA total of 1132 patients were included for epidemiological analyses. The age-adjusted incidence rate of SB-NEN increased from 0.52 to 0.81 per 100.000 person-years between 2005 and 2015. Incidence was higher for males than females (0.93 vs. 0.69 in 2015). Most patients had grade 1 tumours (83%). Surgery was performed in 86% of patients, with resection of the primary tumour in 99%. During the study period, administration of somatostatin analogues (SSAs) increased from 5 to 22% for stage III and from 27 to 63% for stage IV disease. Mean follow-up was 61 (standard deviation 38) months. Survival data were complete for 975/1132 patients and five-year overall survival was 75% for stage I-II, 75% for stage III and 57% for stage IV.ConclusionsThis study shows an increase in the incidence of SB-NEN in the Netherlands. A predominant role of surgery was found in all disease stages. Use of SSAs has increased over time.

Although small bowel resection is generally considered a low risk gastrointestinal procedure, this might not be true for small bowel neuroendocrine neoplasms (SB‐NEN) as a result of potential central mesenteric involvement. We aimed to determine the reported morbidity and mortality after resection of SB‐NEN in the literature and assess the effect of hospital volume on postoperative morbidity and mortality. A systematic review was performed by searching MEDLINE and Embase in March 2021. All studies reporting morbidity and/or mortality after SB‐NEN resection were included. Pooled proportions of overall morbidity (Clavien‐Dindo I‐IV), severe morbidity (Clavien‐Dindo III‐IV), 30‐day mortality, 90‐day mortality and in‐hospital mortality were calculated, as well as the association with hospital volume (high volume defined as the fourth quartile). Thirteen studies were included, with a total of 1087 patients. Pooled proportions revealed an overall morbidity of 13% (95% confidence interval [CI] = 7%‐24%, I 2 = 90%), severe morbidity of 7% (95% CI = 4%‐14%, I 2 = 70%), 30‐day mortality of 2% (95% CI = 1%‐3%, I 2 = 0%), 90‐day mortality of2% (95% CI = 2%‐4%, I 2 = 35%) and in‐hospital mortality of 1% (95% CI = 0%‐2%, I 2 = 0%). An annual hospital volume of nine or more resections was associated with lower overall and severe morbidity compared to lower volume: 10% vs 15% and 4% vs 9%, respectively. Thirty‐day mortality was similar (2% vs 1%) and 90‐day mortality was higher in high‐volume hospitals: 4% vs 1%. This systematic review with meta‐analyses showed severe morbidity of 7% and low mortality rates after resection of SB‐NEN. The currently available literature suggests a certain impact of hospital volume on postoperative outcomes, although heterogeneity among the included studies constrains interpretation., Resection of small bowel neuroendocrine neoplasms in high‐volume centres is associated with less postoperative complications.

Background: In a first step toward standardization, the Primary Aldosteronism Surgical Outcomes investigators introduced consensus criteria defining the clinical outcomes after adrenalectomy for primary aldosteronism. Within this retrospective cohort study, we evaluated the use of these consensus criteria in daily clinical practice in 16 centers in Europe, Canada, Australia, and the United States.Methods: Patients who underwent unilateral adrenalectomy for primary aldosteronism between 2010 and 2016 were included. Patients with missing data regarding preoperative or postoperative blood pressure or their defined daily dose were excluded. According to the Primary Aldosteronism Surgical Outcomes criteria, patients were classified as complete, partial, or absent clinical success.Results: A total of 380 patients were eligible for analysis. Complete, partial, and absent clinical success was achieved in 30%, 48%, and 22%, respectively. Evaluation of the Primary Aldosteronism Surgical Outcomes criteria showed that in 11% and 47% of patients with partial and absent clinical success, this classification was incorrect or debatable (16% of the total cohort). This concept of a "debatable classification of success" was due mainly to the cutoff of >= 20 mmHg used to indicate a clinically relevant change in systolic blood pressure and the use of percentages instead of absolute values to indicate a change in defined daily dose.Conclusion: Although introduction of the Primary Aldosteronism Surgical Outcomes consensus criteria induced substantial advancement in the standardization of postoperative outcomes, our study suggests that there is room for improvement in the concept for success given the observed limitations when the criteria were tested within our international cohort. In line, determining clinical success remains challenging, especially in patients with opposing change in blood pressure and defined daily dose. (C) 2019 Elsevier Inc. All rights reserved.

Background Cure of hypertension after adrenalectomy for primary aldosteronism is no certainty and therefore preoperative patient counseling is essential. The Primary Aldosteronism Surgical Outcome (PASO) Score is a useful prediction model with an area under the curve (AUC) of 0.839. The PASO Score includes ‘Target Organ Damage’ (TOD) (i.e., left ventricular hypertrophy and/or microalbuminuria), which is often unavailable during preoperative counseling and might therefore limit its use in clinical practice. We hypothesized that the PASO score would still be useful if TOD is unknown at time of counseling. Therefore, we aimed to examine the predictive performance of the simplified PASO Score, without taking TOD into account. Materials and methods In this retrospective cohort study, patients who underwent unilateral adrenalectomy between 2010 and 2016 in 16 medical centers from North America, Europe and Australia were included. TOD was unknown in our database and therefore assigned as absent. Patients were classified as complete, partial or absent clinical success using the PASO consensus criteria. Results A total of 380 (73.9%) patients were eligible for analysis. Complete, partial and absent clinical success were observed in 29.5%, 55.8% and 14.7% of patients, respectively. The simplified PASO Score had an AUC of 0.730 (95% confidence interval 0.674–0.785) in our total cohort. Conclusion Without taking TOD into account, the simplified PASO Score had a lower predictive value as compared to the original derivation cohort. Ideally, the complete PASO Score should be used, but when data on TOD are not readily available, the simplified PASO Score is a useful and reasonable alternative., Highlights • We aimed to examine the predictive performance of the PASO Score, without taking ‘target organ damage’ (TOD) into account. • This simplified PASO Score had a lower predictive value as compared to the PASO Score in the original derivation cohort. • The simplified PASO Score increases the applicability of the model and is reasonable for clinicians to use in daily practice. • Ideally, the complete PASO Score should be used, but the simplified PASO Score is a useful and reasonable alternative.

ObjectiveRecent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.DesignAn international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS).ResultsATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (pConclusionsATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Objective: To examine among surgical nurses whether work–role conflict, work–role ambiguity, respect, distress and trust in collaboration due to interactions with family caregivers in the nursing ward are associated with the quality of contact with patients and their families. Methods: A multicentre cross-sectional study was conducted between January and March 2020. Surgical nurses completed a questionnaire recording work–role conflict, work–role ambiguity, sense of respect, distress, trust in collaboration and quality of contact with patients and their families. Data were analysed using correlation analysis, multiple linear regression analysis and mediation regression analysis. Results: A total of 135 nurses completed the questionnaire. The correlation analysis showed significant correlations between nurses’ impaired quality of contact with patients and their families and nurses’ work–role conflicts, work–role ambiguity, trust in collaboration and distress (p

Change of respiratory rate (RespR) is the most powerful predictor of clinical deterioration. Brady- (RespR ≤ 8) and tachypnea (RespR ≥ 31) are associated with serious adverse events. Simultaneously, RespR is the least accurately measured vital parameter. We investigated the feasibility of continuously measuring RespR on the ward using wireless monitoring equipment, without impeding mobilization. Continuous monitoring of vital parameters using a wireless SensiumVitals® patch was installed and RespR was measured every 2 mins. We defined feasibility of adequate RespR monitoring if the system reports valid RespR measurements in at least 50% of time-points in more than 80% of patients during day- and night-time, respectively. Data from 119 patients were analysed. The patch detected in 171,151 of 227,587 measurements valid data for RespR (75.2%). During postoperative day and night four, the system still registered 68% and 78% valid measurements, respectively. 88% of the patients had more than 67% of valid RespR measurements. The RespR’s most frequently measured were 13–15; median RespR was 15 (mean 16, 25th- and 75th percentile 13 and 19). No serious complications or side effects were observed. We successfully measured electronically RespR on a surgical ward in postoperative patients continuously for up to 4 days post-operatively using a wireless monitoring system. While previous studies mentioned a digit preference of 18–22 for RespR, the most frequently measured RespR were 13–16. However, in the present study we did not validate the measurements against a reference method. Rather, we attempted to demonstrate the feasibility of achieving continuous wireless measurement in patients on surgical postoperative wards. As the technology used is based on impedance pneumography, obstructive apnoea might have been missed, namely in those patients receiving opioids post-operatively.

© 2021 European Society of Endocrinology, Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Calcimimetics are currently indicated for severe secondary hyperparathyroidism (SHPT). However, the role of parathyroidectomy (PTX) for these patients is still under debate, and its impact on subsequent kidney transplantation (KTX) is unclear. In this study, we compare the outcomes of kidney transplantation after PTX or medical treatment.Patients who underwent KTX and had SHPT were analyzed retrospectively. Two groups were selected (patients who had either PTX or calcimimetics prior to KTX) using a propensity score for sex, age, donor type, and parathyroid hormone levels (PTH) during dialysis. The primary outcome was graft failure, and secondary outcomes were surgical KTX complications, survival, serum PTH, serum calcium, and serum phosphate levels post-KTX.Matching succeeded for 92 patients. After PTX, PTH was significantly lower on the day of KTX as well as at 1 and 3 years post-KTX (14.00 pmol/L (3.80-34.00) vs. 71.30 pmol/L (30.70-108.30), p 0.01, 10.10 pmol/L (2.00-21.00) vs. 32.35 pmol/L (21.58-51.76), p 0.01 and 13.00 pmol/L (6.00-16.60) vs. 19.25 pmol/L (13.03-31.88), p = 0.027, respectively). No significant differences in post-KTX calcium and phosphate levels were noted between groups. Severe KTX complications were more common in the calcimimetics group (56.5% vs. 30.4%, p = 0.047). There were no differences in 10-year graft failure and overall survival.PTX resulted in lower PTH after KTX in comparison to patients who received calcimimetics. Severe complications were more common after calcimimetics, but graft failure and overall survival were similar.

Background: Recurrence of pancreatic neuroendocrine tumors (pNET) after surgery is common. Strategies to detect recurrence have limitations. We investigated the role of clinical criteria and the multigene polymerase chain reaction–based NETest during post-operative follow-up of pNET. Methods: We studied 3 groups of resections: R0 with no recurrence (n = 11), R0 with recurrence (n = 12), and R1 with no recurrence (n = 12). NETest levels (>40%) were compared with chromogranin A (CgA) and clinicopathological criteria (CC; grade, lymph node metastases, size). Nonparametric, receiver operating characteristics, logistic regression, and predictive feature importance analyses were performed. Results: NETest was higher in R0 with recurrence (56 ± 8%) compared with R1 with no recurrence (39 ± 6%) and R0 with no recurrence (28 ± 6%, P

Small bowel neuroendocrine neoplasms (SB-NEN) present with mesenteric lymph node metastases and multifocal primary tumours [1]. Although laparoscopic surgery is gaining acceptance as a standard approach for gastrointestinal malignancies, it is still thought to compromise oncological safety in SB-NEN. This case illustrates a laparoscopic D3 lymphadenectomy for central mesenteric lymph node metastases for SB-NEN.

IMPORTANCE In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects.OBJECTIVE To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism.DESIGN, SETTING, AND PARTICIPANTS A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded.MAIN OUTCOMES AND MEASURES Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery.RESULTS On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P CONCLUSIONS AND RELEVANCE In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

Background Active involvement of relatives has the potential to improve postoperative patient outcomes by prevention of complications sensitive to basic care and unplanned readmissions. The aim of this study was to assess the feasibility of a program in which relatives participated in postoperative care. Methods A pragmatic feasibility trial conducted at the surgical ward of a University hospital in the Netherlands. Patients undergoing esophageal or pancreatic resection with a relative who was willing and able to participate formed the intervention group ( n = 20). A control group ( n = 20) received usual postoperative care. The program consisted of the following: (1) information; (2) shared goal setting; (3) task-oriented training; (4) participation in basic care, focusing on mobilization, breathing exercises, cognitive activities and oral hygiene; (5) presence of relatives during ward rounds; and (6) rooming-in. Feasibility criteria were adherence to basic care, caregiver burden, and satisfaction of patients, family, and healthcare professionals. Results All participants completed the program. Patients in the intervention group mobilized more (estimated difference for walking 170 meters per day, P = . 037, and for sitting 109 minutes per day, P 001), and showed more adherence to breathing exercises (estimated difference per day 1.4, P = . 003), oral hygiene (estimated difference 1.52, P = . 001), and cognitive activities (estimated difference 2.6, P 001). Relatives’Care-Related Quality of Life instrument score did not deteriorate over time ( P = . 64); 96% of relatives would recommend the program and 92% felt better prepared for discharge. Patients in the intervention group were more satisfied with hospital admission. Healthcare professionals valued the program positively. Conclusion This program is feasible and is positively appreciated by patients, family, and healthcare professionals. Patients following the program showed more adherence to basic care activities.

The original version of this article unfortunately contained a mistake on the fifth and eleventh author names, from Schelto Kruijf to Schelto Kruijff and from Tessa van Ginhoven to Tessa M. van Ginhoven. The corrected author names are shown below. Schelto Kruijff and Tessa M. van Ginhoven.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. Objective: To describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. Methods: Robot-assisted pancreatectomies of the DutchMEN1 study group and the Universite de Lorraine, Nancy, France were compared to a historical cohort of laparoscopic treated MEN1 patients. Perioperative outcomes were compared. Results: A total of 21 MEN1 patients underwent minimally invasive pancreatic surgery for pancreatic neuroendocrine tumors, seven patients were subjected to robot-assisted surgery, and 14 patients underwent laparoscopic surgery. Demographics and clinical characteristics did not differ between the cohorts and no significant differences in operative outcomes were found. A high number of ISGPS grade B/C pancreatic fistulas were observed in both cohorts (38%), and no conversions were seen in the robot-assisted cohort (respectively 0% vs. 43%, P = 0.06). In one laparoscopic and one robot-assisted case the primary tumor was not resected. Conclusions: Minimally invasive spleen-preserving surgery in MEN1 patients is safe and feasible. Patients who underwent robot-assisted surgery did not require conversion to open surgery.

Background Physical and mental complaints are common in patients with primary hyperparathyroidism (PHPT) and negatively impact quality of life (QOL). Subjective symptoms in current guidelines are not considered an indication for surgery. The purpose of this study was to assess the effect of parathyroidectomy on QOL in patients with PHPT. Methods This multicenter case-control study investigated preoperative and postoperative QOL scores in patients operated for PHPT, measured with the Short Form Health Survey-36 (SF-36) questionnaire. Results were compared with patients undergoing a hemithyroidectomy, the control group. Results Fifty-two patients and 49 controls were included. Patients with PHPT had significantly lower QOL scores preoperatively and improved significantly after successful surgical treatment. Postoperatively, no differences were observed between the 2 groups. Conclusion QOL was significantly lower in patients with untreated PHPT. Surgical treatment was associated with a significant increase in QOL. Decreased QOL should also be considered as an indicator for surgical treatment in patients with PHPT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000-2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75 %. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45 %; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14-14-58 %. Delayed gastric emptying rates were, respectively, 5-5-18-16 %. Postoperative hemorrhage rates were, respectively, 6-1-7-4 %. In-hospital mortality rates were, respectively, 3-4-6-4 %. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85-93 %. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80 %. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.

Background Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. Methods Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. Results Tumor enucleation was performed in 60/205 patients (29 %), pancreatoduodenectomy in 65/205 (31 %), distal pancreatectomy in 72/205 (35 %) and central pancreatectomy in 8/205 (4 %) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69 %) versus 52/65 (80 %). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs. 58 %). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size = 25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19 %) compared to the tumor enucleation and distal pancreatectomy(resp. 5 and 7 % vs. 8 and 13 %). After tumor enucleation 19 % developed recurrent disease. Conclusion Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and functional status of the pNET.

Purpose As recovery time after oncological surgery can be long, family caregivers often play an important role in the delivery of care after patients’ discharge. To prepare carers for this role, we developed a family involvement program (FIP) to enhance their active involvement in post-surgical oncology care during hospitalization. The purpose of this qualitative study was to explore family caregivers experience of participating in a FIP. Methods We conducted semi-structured interviews with 12 family caregivers who participated in the family involvement program. The program is comprised of two main components (1) training and coaching of physicians and nurses; (2) active involvement of family caregivers in fundamental care activities. This active involvement included six activities. Data were analyzed using interpretative phenomenological analysis. Results Family caregivers positively valued the program. Active participation in post-surgical care was experienced as an acceptable burden. The program gave participants the ability to simply be present (‘being there’) which was considered as essential and improved their understanding of care, although family caregivers sometimes experienced emotional moments. Active involvement strengthened existent relationship between the family caregiver and the patient. Participants thought clinical supervision. by nurses is important. Conclusions Physical proximity appeared as an essential part of the family involvement program. It helped carers to feel they made a meaningful contribution to their loved ones’ wellbeing. Asking families to participate in fundamental care activities in post-surgical oncology care was acceptable, and not over-demanding for caregivers.

PURPOSE: Medullary thyroid carcinoma (MTC) derives from the parafollicular C-cells of the thyroid gland. Somatostatin receptors (SSTRs) are expressed in various neuroendocrine tumours including MTC. The aim of this study was to evaluate SSTR2A as a prognostic factor for MTC, to study distribution of SSTR2A expression within tumours and to compare expression of SSTR2A between primary tumours and corresponding lymph node metastases.METHODS: Patients who underwent surgery between 1988 and 2014 for MTC from five tertiary referral centres in The Netherlands were included. In total, primary tumours of 114 patients and lymph node metastases of 34 patients were analysed for expression of SSTR2A using a tissue microarray, and correlated with clinicopathological variables and survival.RESULTS: The mean age of patients was 45.5 years (SD 16.2), 55 patients were male (49.5%). Primary tumours of 58 patients (50.9%) showed SSTR2A expression. In multivariate Cox-regression analysis, SSTR2A positivity correlated independently with better overall survival (OS) (HR 0.3; 95% CI 0.1-1.0). In stage IV MTC patients, 10-year survival rates for SSTR2A-negative and positive patients were 43% and 96%, respectively. In 53.9% of patients with lymph node metastases, expression in primary tumour and lymph node metastases differed.CONCLUSION: SSTR2A expression is correlated with longer OS in MTC, especially for stage IV patients, suggesting that SSTR2A expression might be a useful prognostic factor in MTC. The SSTR2A status of the primary MTC does not predict expression in lymph node metastases.

Summary Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and originates from the parafollicular C-cells. Prostate-specific membrane antigen (PSMA) is known for its expression in the epithelium of prostate cancer and has been demonstrated to be useful both for therapeutic and diagnostic purposes as a so-called theranostic target. As PSMA is also expressed in the neovasculature of other solid tumor types, our aim was to assess PSMA expression and its prognostic role in MTC. Tissues from patients that underwent surgery for MTC between 1988 and 2014 in five tertiary referral centers in The Netherlands were included in a tissue microarray. Using immunohistochemistry, total numbers of PSMA and CD31-positive microvessels were evaluated. Results showed that 92% of MTC expressed PSMA in the neovasculature, whereas the tumor cells were consistently negative. The average number of PSMA-positive microvessels did not differ significantly between the primary tumor and initial lymph node metastases (P = .09), nor between initial and recurrent lymph node metastases (P = 1.00). The PSMA score was found to be correlated with progression-free survival and overall survival. In multivariate analysis, a higher number of PSMA-positive microvessels was associated with favorable prognosis (odds ratio 3.6; 95% confidence interval 1.0–12.8; P = .05). In conclusion, over 90% of MTC appears to express PSMA in the neovasculature. A higher number of PSMA-positive microvessels is prognostically favorable. Since it is highly expressed in MTC, PSMA is an interesting novel target for imaging and potentially also as a target for peptide radioligand therapy in MTC.

Background: Resection for pancreatic neuroendocrine tumours (PNET) is suggested to be associated with an increased risk of a post-operative pancreatic fistula (POPF). The aim of this study was to describe morbidity after resections for PNET, focusing on POPF. Outcomes were compared with resections for other lesions. Methods: Patients undergoing an elective pancreatic resection during a 12-year period were retrospectively analysed. Morbidity was defined according to the International Study Group of Pancreatic Surgery (ISGPS) definitions. Results: Eighty-eight out of 832 patients (10.6%) underwent a resection for PNET. Atypical pancreatic resections (enucleation and central pancreatectomy) and distal pancreatectomies were more frequently performed for PNET. The POPF rate was 22.7% in patients operated for PNET compared with 17.2% in other patients (P = 0.200). In univariate analysis, body mass index (BMI), pancreatic duct diameter, somatostatin analogue administration, type of resection and type of pathology were associated with a POPF. In multivariate analysis, BMI, a pancreatic duct diameter

// Lutske Lodewijk 1 , Paul van Diest 2 , Petra van der Groep 2 , Natalie ter Hoeve 2 , Abbey Schepers 4 , Johannes Morreau 5 , Johannes Bonenkamp 6 , Adriana van Engen - van Grunsven 7 , Schelto Kruijff 8 , Bettien van Hemel 9 , Thera Links 10 , Els Nieveen van Dijkum 11 , Susanne van Eeden 12 , Gerlof Valk 3 , Inne Borel Rinkes 1 , Menno Vriens 1 1 University Medical Center Utrecht, Department of Surgery, 3584CX Utrecht, The Netherlands 2 University Medical Center Utrecht, Department of Pathology, 3584CX Utrecht, The Netherlands 3 University Medical Center Utrecht, Department of Endocrine Oncology, 3584CX Utrecht, The Netherlands 4 Leiden University Medical Center, Department of Surgery, 2333ZA Leiden, The Netherlands 5 Leiden University Medical Center, Department of Pathology, 2333ZA Leiden, The Netherlands 6 Radboud University Medical Center, Department of Surgery, Nijmegen 6525GA, The Netherlands 7 Radboud University Medical Center, Department of Pathology, Nijmegen 6525GA, The Netherlands 8 University Medical Center Groningen, Department of Surgery, 9700 RB, Groningen, The Netherlands 9 University Medical Center Groningen, Department of Pathology, 9700 RB, Groningen, The Netherlands 10 University Medical Center Groningen, Department of Internal Medicine, 9700 RB, Groningen, The Netherlands 11 Academic Medical Center Amsterdam, Department of Surgery, 1105 AZ, Amsterdam, The Netherlands 12 Academic Medical Center Amsterdam, Department of Pathology, 1105 AZ, Amsterdam, The Netherlands Correspondence to: Menno Vriens, email: mvriens@umcutrecht.nl Keywords: medullary thyroid cancer, hypoxia inducible factor 1 alpha, immunohistochemistry, tissue microarray, oncology Received: October 12, 2016 Accepted: January 24, 2017 Published: February 22, 2017 ABSTRACT Background: Medullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC. Methods: All patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were included. A tissue microarray was constructed in which 111 primary tumors could be analyzed for expression of HIF-1α, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic variables and survival. Results: The mean age of patients was 46.3 years (SD 15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF-1α negative and 62 (55.9%) were HIF-1α positive. Positive HIF-1α expression was an independent negative indicator for progression free survival (PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 – 7.3). Five-years survival decreased from 94.0% to 65.9% for the HIF-1α positive group (p=0.007). Even within the group of patients with TNM-stage IV disease, HIF-1α positivity was associated with a worse prognosis, shown by a decrease in 5-years survival of 88.0% to 49.3% (p=0.020). Conclusion: Expression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.

Background: Chromogranin A (CgA) is often used in metastatic patients with nonfunctioning pancreatic neuroendocrine tumors (NF-pNET). The aim of this study is to assess the diagnostic accuracy of CgA in patients with low tumor burden. Methods: Resectable patients with NF-pNET without metastases at time of diagnosis were included between 2002 and 2013 in the Academic Medical Center of Amsterdam. CgA was determined at time of diagnosis and during follow-up according to a standardized method. The upper reference range was 94 µg/l. Results: Overall, 47 patients were included in this study. CgA was elevated preoperatively in only 10 patients (27%). In the detection of metastases during follow-up, the positive predictive value for CgA was 50% and negative predictive value was 81%. In 50% of the patients with an elevated CgA during follow-up, this test result was false-positive. Conclusions: The diagnostic accuracy of CgA was low preoperatively in patients with resectable NF-pNET and low tumor burden. In the detection of recurrent disease after curative resection of NF-pNET, the diagnostic accuracy of CgA was moderate (50%). We conclude that the routine measurement of CgA at time of diagnosis or during follow-up after curative resection had limited value in patients with resectable NF-pNET.

Contains fulltext : 172109.pdf (Publisher’s version ) (Open Access) PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hurthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were

Physical and mental complaints are common in patients with primary hyperparathyroidism (PHPT) and negatively impact quality of life (QOL). Subjective symptoms in current guidelines are not considered an indication for surgery. The purpose of this study was to assess the effect of parathyroidectomy on QOL in patients with PHPT.This multicenter case-control study investigated preoperative and postoperative QOL scores in patients operated for PHPT, measured with the Short Form Health Survey-36 (SF-36) questionnaire. Results were compared with patients undergoing a hemithyroidectomy, the control group.Fifty-two patients and 49 controls were included. Patients with PHPT had significantly lower QOL scores preoperatively and improved significantly after successful surgical treatment. Postoperatively, no differences were observed between the 2 groups.QOL was significantly lower in patients with untreated PHPT. Surgical treatment was associated with a significant increase in QOL. Decreased QOL should also be considered as an indicator for surgical treatment in patients with PHPT. © 2016 Wiley Periodicals, Inc. Head Neck 38:1213-1220, 2016.