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Background and Aims: Recent advances have introduced molecular subtyping of pancreatic cystic lesions (PCLs) as a possible amendment to the diagnostic algorithm. The study evaluated the feasibility and diagnostic accuracy of molecular analysis and subtyping of PCLs using the recently introduced EUS-guided through-the-needle-biopsy (TTNB) sampling., Methods: We prospectively included 101 patients in the study who presented with PCLs >15 mm in the largest cross-section. EUS-guided TTNB samples were obtained by a micro-biopsy forceps introduced through a 19-gauge needle. The TTNB samples were analyzed by next-generation sequencing (NGS) for point mutations in tumor suppressors and oncogenes using a 51-gene customized hotspot panel. Sensitivity and specificity were calculated with the histologic diagnosis as reference., Results: After initial microscopic evaluation of the samples, 91 patients had residual TTNB samples available for NGS. Of these, 49 harbored mutations, most frequently in KRAS and GNAS, reflecting an excess frequency of intraductal papillary mucinous neoplasms (IPMNs) in the study population. A sensitivity and specificity of 83.7% (95% confidence interval [CI], 70.3-92.7) and 81.8% (95% CI, 48.2-97.7), respectively, were demonstrated for the diagnosis of a mucinous cyst and 87.2% (95% CI, 74.2-95.2) and 84.6% (95% CI, 54.5-98.1) for the diagnosis of an IPMN., Conclusions: Thus, molecular analysis of TTNB samples by NGS has high sensitivity and specificity for diagnosing mucinous cysts and IPMNs. Although the procedure comes with a risk of adverse events of 9.9%, TTNB samples are a robust alternative to cyst fluid for a combined histologic and molecular diagnosis of PCLs. (Clinical trial registration number: NCT03578445.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Insulinomas are rare neoplasms which may cause significant symptoms and substantially reduce quality of life. In operable patients, the current treatment is primarily surgery with either enucleation or resection of all or parts of the gland. This treatment is associated with high morbidity and long convalescence. Endoscopic ultrasound-guided radiofrequency ablation is a new and minimally invasive treatment for patients with insulinomas. The purpose of this review is to draw attention to the method and to communicate our preliminary experience with this procedure in Denmark.

Introduction: Obstructive jaundice is a common problem in pancreatic and periampullary tumors, but preoperative biliary drainage in patients with hyperbilirubinemia is still controversial. This study aimed to assess the risk of complications after preoperative drainage of biliary obstruction in patients who underwent pancreaticoduodenectomy., Method: A retrospective cohort study of all patients who underwent pancreaticoduodenectomy from January 1st, 2015 to September 30th, 2021. Patients who had preoperative bile duct drainage were compared to patients without intervention. Type of interventions, complications, and outcomes after surgery were compared using univariate and multivariate analysis., Results: Of 722 patients who underwent pancreatoduodenectomy, 389 patients had preoperative drainage of the bile ducts by ERC or PTC. There was an incidence of 27% drainage-related complications, all categorized as minor (Clavien-Dindo <3) and mainly related to PTC-aided drainage. After pancreaticoduodenectomy, 23% of patients who had a preoperative biliary drain, had minor complications. Patients without biliary drainage had a higher risk of a complicated postoperative course (p = 0.001) and had a higher 30-day (p = 0.002) and 90-day mortality (p = 0.025)., Conclusion: Our study found preoperative bile duct drainage to be a safe procedure without severe complications. Patients undergoing preoperative bile duct drainage had fewer post-pancreatoduodenectomy complications and lower mortality., (© 2022 The Authors.)

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.)

Background: Several variables have been described as prognostic factors for resected distal cholangiocarcinoma (dCC), including lymph node metastases (N status) and lymph node ratio (LNR). The present study aimed to evaluate the prognostic value of LNR on survival and to establish a novel prognostic nomogram to predict the cancer-specific recurrence-free survival (RFS) of dCC., Study Design: Between December 2006 and September 2020, 415 consecutive patients who underwent pancreaticoduodenectomy (PD) for dCC in 10 centers were identified. Multivariate Cox analysis was used to identify all independent risk factors among several prognostic factors. A nomogram was then developed and assessed by integrating the independent prognostic factors into the model, and the concordance index (C-index) was used to evaluate its performance., Results: According to Cox regression multivariate analysis, a nomogram based on independent prognostic factor for RFS was performed including LNR 15 (hazard ratio [HR] 2.442, 95% CI 1.348-4.425, p = 0.003), perineural invasion (HR 3.100, 95% CI 1.183-8.122, p = 0.025), differentiation grade (HR 2.100, 95% CI 1.172-4.143, p = 0.021), and radicality of PD (HR 2.276, 95% CI 1.223-4.234, p = 0.009). The C-index of the nomogram, tailored based on the previous significant factors, was 0.8., Conclusions: LNR15 yields a high prognostic efficiency for RFS. The nomogram based on LNR can provide an accurate prognosis assessment for patients with resected dCC., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Opinion Statement: In the 2019 WHO guidelines, the classification of gastro-entero-pancreatic neuroendocrine neoplasms (GEP NEN) has changed from one being based on Ki-67 proliferation index alone to one that also includes tumor differentiation. Consequently, GEP NENs are now classified as well-differentiated neuroendocrine tumor (NET), NET G1 (Ki-67 <3%), NET G2 (Ki-67 3-20%) and NET G3 (Ki-67 >20%), and poorly differentiated neuroendocrine carcinoma (NEC) (Ki-67 >20%). It has been suggested that NET G3 should be treated as NET G2 with respect to surgery, while surgical management of NEC should be expanded from local disease to also include patients with advanced disease where curative surgery is possible. High grade mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have a neuroendocrine and a non-neuroendocrine component mostly with a poor prognosis. All studies evaluating the effect of surgery in NEC and MiNEN are observational and hold a risk of selection bias, which may overestimate the beneficial effect of surgery. Further, only a few studies on the effect of surgery in MiNEN exist. This review aims to summarize the data on the outcome of surgery in patients with GEP NET G3, GEP NEC and high grade MiNEN. The current evidence suggests that patients with NEN G3 and localized disease and NEN G3 patients with metastatic disease where curative surgery can be achieved may benefit from surgery. In patients with MiNEN, it is currently not possible to evaluate on the potential beneficial effect of surgery due to the low number of studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: During the COVID pandemic there has been limited access to elective surgery including oncologic surgery in several countries world-wide. The aim of this study was to investigate if there was any lockdown effect on pancreatic surgery with special focus on malignant pancreatic and periampullary tumours., Methods: Patients who underwent pancreatic surgery during the two Danish lockdown periods from 11. March 2020 and the following 12 months were compared with patients who were operated the preceding 3 years. Data on patients' characteristics, waiting time, operations, and clinical outcomes were evaluated., Results: During lockdown and the previous three years the annual number of resections were 242, 232, 253, and 254, respectively (p = 0.851). Although the numbers were not significantly different, there were fluctuations in operations and waiting time during the lockdown. During the second outbreak of COVID October 2020 to March 2021 the overall median waiting time increased to 33 days (quartiles 26;39) compared to 23 (17;33) days during the first outbreak from March to May 2020 (p = 0.019). The same difference was seen for patients with malignant tumours, 30 (23;36) vs. 22 (18;30) months (p = 0.001). However, the fluctuations and waiting time during lockdown was like the preceding three years. Neither 30- nor 90-days mortality, length of stay, number of extended operations, and complications and tumour stage were significantly different from previous years., Conclusions: There were significant fluctuations in waiting time for operations during the lockdown, but these variations were not different from the preceding three years, wherefore other explanations than an impact from COVID are conceivable., (© 2022. The Author(s).)

Purpose: Pancreatic cancer (PC) has high morbidity and mortality and is stressful for patients and their partners. We investigated the psychological symptom burden in partners of PC patients., Methods: We followed 5774 partners of PC patients diagnosed from 2000 to 2016 up for first redeemed prescriptions of antidepressants or hospital admission, anxiolytics, and hypnotics as proxies for clinical depression, anxiety, and insomnia and compared them with 59,099 partners of cancer-free spouses. Data were analysed using Cox regression and multistate Markov models., Results: The cumulative incidence proportion of first depression was higher in partners of PC patients compared to comparisons. The highest adjusted HR of first depression was seen the first year after diagnosis (HR 3.2 (95% CI: 2.9; 3.7)). Educational level, chronic morbidity, and bereavement status were associated with an increased risk of first depression. There was a significantly higher first acute use (1 prescription only) of both anxiolytics and hypnotics and chronic use (3+ prescriptions) of hypnotics in partners of PC patients than in comparisons., Conclusion: Being a partner to a PC patient carries a substantial psychological symptom burden and increases the risk for first depression and anxiolytic use and long-term use of hypnotics. Attention should be given to the psychological symptom burden of partners of PC patients, as this may pose a barrier for the optimal informal care and support of the PC patient, as well as a risk for non-optimal management of symptoms in the partner., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Neuroendocrine neoplasms (NEN) of the appendix are often incidentally discovered after appendectomy. Appropriate management is debated. The purpose was to characterize a cohort of 335 appendix NEN and evaluate the risk of recurrence., Methods: Retrospective collection of data from 335 patients referred to the Neuroendocrine Tumor Center at Rigshospitalet 2000-2019. Appendix goblet cell carcinoids and mixed neuroendocrine non-neuroendocrine neoplasms were excluded. Patients were followed until December 31st, 2019. No patients were lost to follow-up., Results: Sixty-three percent of the patients were female. The median (range) age at diagnosis was 34 (9-92) years. Median follow-up was 66 (1-250) months. Median tumor size was 7 (1-45) mm with 10 (3%) tumors >20 mm. In 18 specimens (5%) resection margins were positive. Mesoappendiceal invasion was found in 113 (35%). Sixty-three (19%) patients underwent right-sided completion hemicolectomy (RHC) after appendectomy according to ENETS guidelines. Among these, 11 (17%) had lymph node metastases in the resected tissue. Further, one patient who underwent initial RHC due to colonic adenocarcinoma had lymph node metastases. All lymph node metastases were detected in patients with serotonin positive tumors. No patients with glucagon positive tumors (n = 85) had lymph node metastases. Mesoappendiceal invasion >3 mm and positive resection margins were associated with presence of lymph node metastases. No recurrences were recorded., Conclusion: Following ENETS guidelines may lead to overtreatment of patients with respect to completion RHC. The risk of over- and undertreatment needs to be further evaluated., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients' response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58-15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.

Acinar cystic transformation (ACT) is a rare cystic lesion of the pancreas lately reclassified as a non-neoplastic entity. This is a presentation of a case of ACT and a review of the literature. A systematic PubMed search was conducted, yielding a result of 24 publications. Including our case report, 75 cases of ACT have been reported in the literature. The patients are mainly females with initial symptoms of abdominal pain. The cysts are primarily located in the head of the pancreas and are often multilocular on cross section and have a mean size of 53.2 mm. Microscopically, the cysts are lined by an acinar epithelium with abortive acinar formations. The cells are immunohistochemically positive in stains for trypsin, chymotrypsin and CK7. The Ki67-index is low; 1-2 %. No genetic alterations indicative of a neoplastic pathogenesis have been found. The mean follow up time is 37.4 months and no malignant transformation has been observed. A preoperative diagnosis is difficult to establish, but microbiopsies seem a promising tool. The indication for surgical intervention should be founded on the symptoms of the patients since no malignant transformation has ever been reported., Competing Interests: Declaration of Competing Interest Charlotte Vestrup Rift received a grant from the Research foundation of Copenhagen University Hospital Rigshospitalet and The Novo Nordisk Foundation. No conflicts of interests were declared for the remaining authors. The funding sources had no role in conducting the review or preparing the manuscript., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Centralization has improved the outcome of complex operations including cancer surgery. Moreover, the implementation of multidisciplinary team conferences (MDT) has ameliorated the decision making, but the impact on patient outcome is controversial. The aim of the study was to investigate the outcome of pancreatic surgery in the setting of centralization and upfront multidisciplinary decision making., Method: The decisions of MDT from 2010 to 2016 and the outcome of operations were compared with operations from 2003 to 2009 before centralization of pancreatic surgery and implementation of MDT. Data were drawn from the department's database and from hospital's electronic patient files., Results: From 2010 to 2016, 7.015 patients were evaluated at the MDT. In 72.6% of patients a treatment plan followed the first evaluation, the referral diagnosis was changed in 12.4% of cases. Of 3.362 solid neoplasms, 1.680 (50.0%) were evaluated as resectable and 1.080 (32.1%) patients were operated. The annual resection rate of operated patients was78.3%-88.5% (median 80.0%) compared to 21.4% to 80.% (median 68.6%, p = 0.0001) from 2003 to 2009 with 279 operated patients. The post-operative 30 - and 90-days mortality from 2003 to 2009 and 2010 to 2016 was 3.4% vs. 1.8% (NS) and 5.0% vs 3.6% (NS). In the same periods explorative laparotomies and palliative resections decreased from 18.3% to 3.6% (p = 0.0001) and 18.6%-10.2% (p = 0.0002). The median survival of radically resected pancreatic adenocarcinoma (PAC) from 2003 to 2009 and from 2010 to 2016 was 20.2 and 21.9 months, respectively (p = 0.687)., Conclusion: The MDT increased patient flow, improved quality of decision-making and offered more patients surgical treatment without increasing morbidity or mortality. But an impact on the long-term survival of patients with PAC was not found., Competing Interests: Declaration of competing interest None., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background/objective: To investigate the psychological symptom burden in patients with pancreatic cancer., Methods: We used Danish population-based registries to identify 10,793 pancreatic cancer patients and 109,238 age and gender matched cancer-free comparison persons between the years 2000-2016. The cohorts were followed up to five years for first prescription for antidepressants, anxiolytics or hypnotics as proxies for the psychological symptom burden of depression, anxiety or insomnia. Cumulated incidence proportions were analysed using the pseudo-value approach and hazards were estimated with Cox regression models adjusted for potential confounders., Results: The highest HR for first antidepressant use was seen in the first six months after diagnosis (HR 8.73 (95% CI: 7.57; 10.06)). Within the first two years the overall estimated cumulated probability of 12.9% (95% CI: 12%; 13.8%) in pancreatic cancer patients, and 4.6% (95% CI: 4.5%; 4.8%) in comparisons, and 20.4% and 31.4% patients received first prescription of anxiolytics or hypnotics, respectively. We found no difference in HRs of first antidepressant by gender, year of diagnosis, cohabitation, education or comorbidity in the patient cohort, however younger age (<59 years) was associated with depression., Conclusions: Pancreatic cancer patients are at risk for first antidepressant, anxiolytic and hypnotic use up to five years after diagnosis. Patients younger than 59 years, newly diagnosed with advanced pancreatic cancer, and not treated with surgery were more likely to have first antidepressant use. The study calls for interventions to reduce the psychological burden in advanced pancreatic cancer patients which may improve quality of life and survival., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim was to determine whether serum levels of carbohydrate antigen (CA) 19-9, interleukin 6 (IL-6), and YKL-40 could identify advanced disease and poor prognosis in pancreatic cancer (PC) patients intraoperatively diagnosed with locally advanced or metastatic disease., Methods: Two hundred ninety patients were included with preoperative blood samples. Plasma IL-6 and YKL-40 were determined by enzyme-linked immunosorbent assays., Results: Interleukin 6 was elevated in patients with unresectable PC compared with resectable PC (P = 0.03). Carbohydrate antigen 19-9 and YKL-40 were similar. Patients with resectable tumors and greater than median preoperative CA 19-9, IL-6, and YKL-40 had shorter overall survival than patients with low levels (CA 19-9: hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.13-2.83; P = 0.01; IL-6: HR, 1.83; 95% CI, 1.20-2.78; P = 0.01; YKL-40: HR, 1.60; 95% CI, 1.02-2.49; P = 0.04). Patients with resectable tumors and 2 or 3 high biomarker levels had significantly reduced overall survival compared with patients with low levels (2 high: HR, 2.97; 95% CI, 1.44-6.10; P = 0.00; 3 high: HR, 3.10; 95% CI, 1.45-6.65; P = 0.00)., Conclusions: Preoperative levels of CA 19-9, IL-6, and YKL-40 may be useful to identify a subgroup of PC patients with poor prognosis.

Introduction: The effect of waiting time to surgery on survival in pancreatic cancer patients is unclear. We examined this association in a nationwide population-based cohort study., Materials and Methods: A nationwide population-based cohort study of all patients undergoing surgery for pancreatic cancer (resection or a palliative procedure) registered in the Danish Pancreatic Cancer Database from May 2011 to May 2016. We defined waiting time to surgery in two ways: 1) from the date of entry into the National Cancer Pathway to the date of surgery and 2) from the date of the last preoperative computed tomography (CT) or positron emission tomography (PET-CT) scan to the date of surgery. Waiting time was grouped into three groups: <28 days (<4 weeks), 28-55 days (4-8 weeks), and ≥56 days (≥8 weeks). We calculated median survival with associated 95% confidence intervals (CIs) for patients undergoing resection and for patients undergoing a palliative procedure., Results: We included 873 patients. Mean age was 67 years (range: 35-86 years). Resection was performed in 701 patients (80%); the remaining 172 patients (20%) underwent an explorative laparotomy or palliative surgery. 652 patients (75%) had a registration in the National Cancer Pathway (median waiting time: 31 days, and 818 patients (94%) had registration of a preoperative CT or PET-CT scan (median waiting time: 32 days). We saw similar resection rates (∼80%) and median survival (∼22 months) in all thee groups., Conclusion: In this study, waiting time to surgery did not affect survival in patients undergoing surgery for pancreatic cancer., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Pancreatic cancer has a low five-year survival rate, which in part is due to late recognition of the disease making surgical intervention impossible. Some pancreatic cancers stem from cystic lesions. The expanded use of advanced diagnostic imaging like CT and MRI has led to an increase in incidental and potentially malignant pancreatic cysts. This review presents the newest international guidelines and gives a Danish perspective in order to increase knowledge on how to deal with incidental pancreatic cysts as regards further diagnostic investigation, treatment and follow-up.

Background and Objectives: Cystic lesions of the pancreas represent a diagnostic dilemma. Recently, a through-the-needle microbiopsy forceps has become available, enabling procurement of EUS-guided histological specimens from the pancreatic cyst wall. The aim of this study was to evaluate the use of this novel instrument in a multicenter clinical setting., Patients and Methods: Patients referred for EUS evaluation of pancreatic cysts and attempted EUS-guided microbiopsy was included retrospectively from six international tertiary centers. Patient's demographics, EUS findings, technical and clinical success, and histopathological results were recorded., Results: : A total of 28 patients were identified. We report a technical success rate of 85.7% (n = 24). Biopsies were generally of good quality and contributed to the diagnosis in 20 patients (clinical success of 71.4%). Three adverse events were recorded (10.7%)., Conclusions: The use of the microbiopsy forceps is feasible with acceptable rates of technical and clinical success. Prospective studies are warranted to determine the diagnostic potential compared to the other modalities. However, the results from this preliminary study are promising., Competing Interests: There are no conflicts of interest

Introduction: Pancreatogenic diabetes develops in patients undergoing total pancreatectomy and complicates post-surgical management. The aim of this study was to compare parenteral nutrition (PN) with protocolled insulin treatment to intravenous glucose treatment after total pancreatectomy., Methods: This was a retrospective study of 97 patients undergoing total pancreatectomy between 2009 and 2014. Patients were divided into a PN cohort (n = 57) and a glucose cohort (n = 40). The PN cohort was given PN with one international unit (IU) rapid-acting insulin per 10 g of carbohydrate. The glucose cohort was given a continuous 5% glucose infusion with 2 IU rapid-acting insulin per 10 g of carbohydrate. Both cohorts were given insulin detemir 0.2 IU/kg/day., Results: Within the first 13 post-operative days, plasma glucose values were within the target range (4.0-10.0 mmol/l) in the PN cohort more frequently than in the glucose cohort (46% versus 42%, p = 0.01) without any increase in hypoglycaemia. Non-infectious complications occurred less frequently in the parenteral cohort than in the glucose cohort (23% versus 43%, p = 0.04). Infectious complications occurred in 19% versus 33% of patients, respectively (p = 0.14). The mean length of hospitalisation was 19.8 ± 12.7 versus 25.0 ± 21.5 days, p = 0.14., Conclusions: After total pancreatectomy, PN with insulin treatment per protocol improves glycaemic control compared with glucose infusion and reduces the number of non-infectious post-operative complications without increasing hypoglycaemia., 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.)

Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later., (© 2015 S. Karger AG, Basel.)

Introduction: Pancreatic cancer is one of the most serious gastrointestinal cancers, and in the US and Europe it is a leading cause of cancer-related mortality. Radical surgery is the only option available for long-term survival. The aim of this study was to describe the surgical technique and the results of portal vein/superior mesenteric vein resection in patients with pancreatic cancer., Material and Methods: Between 1 April 2009 and 1 April 2013, 354 patients underwent resection for pancreatic malignancy. A total of 47 portal vein/superior mesenteric vein resections were performed in 22 men and 25 women., Results: A total of 44 patients (93.7%) had ductal adenocarcinomas. In all, 39 patients (83%) had T3 tumours, and 38 patients (80.9%) had involvement of lymph nodes. Furthermore, 29 patients (62%) had a pancreaticoduodenectomy, 15 patients (32%) a total pancreatectomy and three patients (6%) had a distal pancreatectomy. Six patients (17%) were reconstructed with interposition grafts, and vessels (83%) were reconstructed with an end-to-end anastomosis in the remaining 39 patients. Surgical morbidity was 29.8%, and 19.1% had non-surgical complications. The perioperative mortality (30 days) was 0%. The median survival was 25.2 months (confidence interval: 19-31.4)., Conclusion: Resection of the portal vein/superior mesenteric vein is a safe procedure. It is not associated with an increased perioperative morbidity and mortality. This latter finding is in accordance with the findings in other high-volume centres. The median survival was far better than expected, especially since our material included a considerable number of patients with lymph node metastases., Funding: not relevant., Trial Registration: not relevant.

Aim: Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this treatment option still needs clinical evaluation., Methods: In this study, we evaluated the PRRT treatment response of 69 Danish patients with NET mainly originating from the gastroenteropancreatic system. Fifty-six patients (81%) were referred for PRRT to the Department of Nuclear Medicine, University Hospital Basel, Switzerland, between 2004 and 2008 due to progression assessed by the referring physicians. However, when retrospectively evaluated, only 42 of the 69 patients (61%) had progression according to RECIST (Response Evaluation Criteria in Solid Tumors). Most patients were treated with ⁹⁰Y-DOTATOC., Results: Based on RECIST, a complete response was observed in 5 patients (7.4%), a partial response in 11 patients (16.2%) and stable disease in 42 patients (61.8%). Progressive disease after completed therapy was observed in 10 patients (14.7%). The median progression-free survival was 29 months (95% CI: 22-36 months). Pancreatic NET seemed to respond better to PRRT than small intestinal carcinoid tumors (p = 0.03). The overall frequency of serious adverse events was low., Conclusion: Implementation of PRRT in clinical routine has provided a valuable new therapeutic option for the treatment of advanced NET. We suggest that PRRT may advance from second- or third-line to first- or second-line therapy in inoperable/unresectable NET patients., (Copyright © 2011 S. Karger AG, Basel.)

Localization diagnostics of neuroendocrine tumours is relevant in relation to staging and planning of therapy, including surgery. Imaging modalities are also relevant in relation to biopsy guidance. Currently, the most frequently used methods are somatostatin receptor scintigraphy, computed tomography with contrast and endoscopic ultrasound. The strengths of the different modalities are discussed and it is concluded that frequently a combination of imaging modalities is necessary in the work-up of patients with neuroendocrine tumours.

Peptide receptor radionuclide therapy using somatostatin analogues labelled with beta-emitting isotopes can be given to patients with metastasized or inoperable neuroendocrine tumours provided these have increased uptake on octreotide scintigraphy. This is a brief review of the treatment principle, indications and contraindications and practices with (177)Lu-DOTATATE treatment used at Rigshospitalet. Side effects are generally mild and reversible. Severe long-term side effects are rare. The majority of patients will experience increased quality of life and partial tumour reduction or stabilization for a period of time. However, up to 20% will experience no treatment effect.

The prognosis of neuroendocrine tumours of the gastrointestinal tract and pancreas is difficult to estimate due to their heterogeneous nature. Survival without dissemination may reach 90%, while metastases reduce the 5-year survival to less than 50%. Radical surgery offers the only possibility of cure. Palliative therapy includes surgery and intra-arterial embolization of hepatic metastases, chemotherapy, biotherapy with interferon-alpha and radionuclear treatment. Tumour-targeted therapy with tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors or monoclonal antibodies are under investigation in phase-III studies.

Gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) are unusual. Their incidence, the different tumour types and growth patterns are described. The tumours should be classified according to the WHO 2000 classification and the Tumour Node Metastasis classification according to guidelines from the European Neuroendocrine Tumour Society. Important parameters are localization, size, hormonal secretion, mitotic index, and proliferation index (Ki-67) of the primary tumour. Patients with GEP NET should be referred to as few centres as possible in order to obtain the highest experience and the greatest understanding of these tumours thereby achieving the capacity to offer patients the best possible treatment and to create optimal conditions for research.

Appendiceial carcinoid tumors (CAT) and goblet cell carcinoids (GCCAT) are rare. Most are asymptomatic and found after appendectomy. Metastases to regional nodes are seen in 10% of CATs larger than two cm. Ovarian or peritoneal metastases are seen in 20% of all GCCATs. Further surgical treatments are shown in Tables. Non-resectable CAT are treated with interferon-alpha, somatostatin analogs or radionuclides. Non-resectable GCCATs are treated like colo-rectal cancer. Patients with CAT larger than two cm, involvement of mesoappendix or metastases and all GCCAT should be followed life-long.

Surgery remains the only hope for cure in pancreatic cancer. The most common procedures are reviewed. Postoperative morbidity and mortality below 30% and 5%, respectively, are the standard. The benefit of extended lymph node dissection and portal-mesenteric vein resection is dubious. Selected patients with locally advanced cancer may be down-staged with chemo-radiotherapy and eventually resected. Endoscopic stent placement is the preferred method to relieve biliary and/or gastrointestinal obstruction. The outcome is better for patients treated at high-volume centres than at smaller hospitals.

Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth is less convincing although a stabilization of disease is recorded in almost 50% of patients. Interferon treatment should mainly be considered for tumours with a low proliferation index.

Introduction: Reading a wireless capsule endoscopy (WCE) may be time-consuming. In order to reduce the time needed by a physician to view a WCE, we investigated if other medical professions could preview the video and detect bowel pathology in advance., Materials and Methods: A specialist in gastroenterology and two laboratory technicians independently viewed 34 consecutive WCEs and noted all findings. Thereafter, two specialists reviewed the findings made by the technicians independently in order to make a diagnosis. The results were compared with the diagnosis made by the first specialist, who viewed the entire WCE himself., Results: The reviewing specialists were able to make a correct diagnosis based on the technicians' findings in 97% and 85% of the patients, respectively., Conclusion: The study indicates that it is safe and timesaving to use other medical professions than physicians to preview WCEs.

The elimination of progastrin-derived peptides was a first-order process, also at supraphysiological concentrations in plasma. The site of extraction was dependent on the molecular size of the peptides and not on their bioactivity. Apart from the kidneys and brain, where the extraction was nonselective, elimination was found in the gastrointestinal tract and limb (Gastrin-17, Gastrin-17 Gly and Gastrin-6). The porcine liver eliminated postprandial gastrin, while human gastrin except gastrin-6 passed unhindered. Metabolism of circulating gastrin was neither recorded in the lungs nor in the heart. In the kidneys peptides were mainly metabolized rather than excreted, since the recovery of intact peptide in urine was minimal. However, urinary clearance varied with the molecular form of the peptides under influence of glomerular filtration and handling in the renal tubules. Thus, N-terminal fragments had a higher urinary clearance than C-terminal peptides. Gastrin degrading enzymes were present in human and porcine plasma, but their contribution to whole-body metabolism was small. It is concluded that there is a differential metabolism of progastrin products in the vascular beds of which the integrated metabolism in nonorgan tissue such as limbs and trunk accounts for the major part of whole-body clearance.