Els J. M. Nieveen van Dijkum

Pooling of prognostic studies in cancer of the pancreatic head and periampullary region: the Triple‐P study

OBJECTIVEnDevelopment of a prognostic tool for patients with unresectable pancreatic cancer to distinguish between with low or high probabilities of survival 3 to 9 months after diagnosis.nnnDESIGNnData about individual patients from five studies were pooled. A multivariate proportional hazards model with time-dependent covariates was developed, including age, sex, and metastases. An extended model was developed on a subset of patients, including weight loss, pain, and jaundice at diagnosis.nnnSETTINGnMulticentre study, The Netherlands, Norway, USA, UK, and Canada.nnnSUBJECTSn1020 patients with unresectable pancreatic cancer.nnnMAIN OUTCOME MEASURESnPrediction of prognosis.nnnRESULTSnPatients with metastases, pain, or weight loss at diagnosis had a significantly poorer prognosis than the others. Older men had a worse prognosis than younger men, while older women had a better prognosis than younger ones. Patients with jaundice had a relatively good prognosis. Differences in survival among the studies were incorporated in a prognostic score chart.nnnCONCLUSIONnThe prognostic score chart can be used to select patients with relatively low expectation of survival for endoscopic palliation, and patients with relatively high expectation for surgical palliation.

A nationwide comparison of laparoscopic and open distal pancreatectomy for benign and malignant disease

BACKGROUNDnCohort studies from expert centers suggest that laparoscopic distal pancreatectomy (LDP) is superior to open distal pancreatectomy (ODP) regarding postoperative morbidity and length of hospital stay. But the generalizability of these findings is unknown because nationwide data on LDP are lacking.nnnSTUDY DESIGNnAdults who had undergone distal pancreatectomy in 17 centers between 2005 and 2013 were analyzed retrospectively. First, all LDPs were compared with all ODPs. Second, groups were matched using a propensity score. Third, the attitudes of pancreatic surgeons toward LDP were surveyed. The primary outcome was major complications (Clavien-Dindo grade ≥III).nnnRESULTSnAmong 633 included patients, 64 patients (10%) had undergone LDP and 569 patients (90%) had undergone ODP. Baseline characteristics were comparable, except for previous abdominal surgery and mean tumor size. In the full cohort, LDP was associated with fewer major complications (16% vs 29%; pxa0= 0.02) and a shorter median [interquartile range, IQR] hospital stay (8 days [7-12 days] vs 10 days [8-14 days]; pxa0= 0.03). Of all LDPs, 33% were converted to ODP. Matching succeeded for 63 LDP patients. After matching, the differences in major complications (9 patients [14%] vs 19 patients [30%]; pxa0= 0.06) and median [IQR] length of hospital stay (8 days [7-12 days] vs 10 days [8-14 days]; pxa0= 0.48) were not statistically significant. The survey demonstrated that 85% of surgeons welcomed LDP training.nnnCONCLUSIONSnDespite nationwide underuse and an impact of selection bias, outcomes of LDP seemed to be at least noninferior to ODP. Specific training is welcomed and could improve both the use and outcomes of LDP.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

BackgroundEither 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.MethodsRetrospective 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.ResultsTumor enucleation was performed in 60/205 patients (29xa0%), pancreatoduodenectomy in 65/205 (31xa0%), distal pancreatectomy in 72/205 (35xa0%) and central pancreatectomy in 8/205 (4xa0%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69xa0%) versus 52/65 (80xa0%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58xa0%). 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 ≤2xa0cm, 55xa0% had lymph node metastasis. Tumor in the head and BMI ≥25xa0kg/m2 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 19xa0%) compared to the tumor enucleation and distal pancreatectomy(resp. 5 and 7xa0% vs.8 and 13xa0%). After tumor enucleation 19xa0% developed recurrent disease.ConclusionSince 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.

Postoperative Complications, In-Hospital Mortality and 5-Year Survival after Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review

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 75xa0%. 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 45xa0%; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14–14–58xa0%. Delayed gastric emptying rates were, respectively, 5–5–18–16xa0%. Postoperative hemorrhage rates were, respectively, 6–1–7–4xa0%. In-hospital mortality rates were, respectively, 3–4–6–4xa0%. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85–93xa0%. 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 80xa0%. 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.

Pancreatic fistulae after pancreatic resections for neuroendocrine tumours compared with resections for other lesions

BACKGROUNDnResection 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.nnnMETHODSnPatients 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.nnnRESULTSnEighty-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 <3u2009mm and central pancreatectomy remained independent risk factors [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.22-3.07 and OR 3.04, 95% CI 1.05-8.82, respectively].nnnCONCLUSIONSnHigh rates of POPF were found in patients operated for PNET. However, this was mainly owing to the fact that atypical resections, known to be associated with a higher fistula rate, were performed more frequently in these patients.

Surgical treatment of gastrinomas: a single-centre experience

BACKGROUNDnGastrinomas are rare neuroendocrine tumours, and responsible for Zollinger-Ellison syndrome (ZES). Surgery is the only treatment that can cure gastrinomas. The success of surgical treatment of gastrinomas in a single centre was evaluated.nnnMETHODSnA retrospective review of all patients who underwent resection for a gastrinoma between 1992 and 2011 at a single institution was performed. Presentation, diagnostics, operative management and outcome were analysed.nnnRESULTSnEleven patients with a median age of 46 years were included. All patients had fasting hypergastrinaemia and a primary tumour was localized using imaging studies in all patients. A pylorus-preserving pancreaticoduodenectomy was performed in three patients: two patients underwent duodenectomy and one patient central pancreatectomy. The remaining five patients underwent enucleation. A primary tumour was removed in nine patients: five tumours were situated in the pancreas, three in the duodenum and one patient was considered to have a primary lymph node gastrinoma. The median follow-up was 3 years (range 1-15) after which 7 patients were disease-free and 3 patients had (suspected) metastatic disease. One patient died 13 years after initial surgery.nnnCONCLUSIONnThe success of surgical treatment of a gastrinoma in this series was 7/11 with a median follow-up of 3 years; comparable to recent published studies.

Expression of HIF-1α in medullary thyroid cancer identifies a subgroup with poor prognosis

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.

Emergency Management in Patients with Late Hemorrhage after Pancreatoduodenectomy for a Periampullary Tumor

BackgroundThe mortality rate due to late hemorrhage after surgery for periampullary tumors is high, especially in patients with anastomotic leakage. Patients usually require emergency intervention for late hemorrhage. In this study patients with late hemorrhage and their outcomes were analyzed. Furthermore, independent predictors for late hemorrhage, the need for emergency intervention, and type of intervention are reported.MethodsFrom a prospective database that includes 1,035 patients who underwent pancreatoduodenectomy for periampullary tumors between 1992 and 2012, patients with late hemorrhage (>24xa0h after index operation) were identified. Patient, disease-specific, and operation characteristics, type of intervention, and outcomes were analyzed. Emergency intervention was defined as surgical or radiological intervention in hemodynamically unstable patients.ResultsOf the 47 patients (4.5xa0%) with late hemorrhage, pancreatic fistula was an independent predictor for developing late hemorrhage (OR 10.2). The mortality rate in patients with late hemorrhage was 13xa0% compared with 1.5xa0% in all patients without late hemorrhage. Twenty patients required emergency intervention; 80xa0% underwent primary radiological intervention and 20xa0% primary surgical intervention. Extraluminal location of the bleeding (OR 5.6) and occurrence of a sentinel bleed (OR 6.6) are indications for emergency intervention.ConclusionThe type of emergency intervention needed for late hemorrhage is unpredictable. Radiological intervention is preferred, but if it fails, immediate change to surgical treatment is mandatory. This can be difficult to manage but possible when both radiological and surgical interventions are in close proximity such as in a hybrid operating room and should be considered in the emergency management of patients with late hemorrhage.

Standard pre- and postoperative determination of chromogranin a in resectable non-functioning pancreatic neuroendocrine tumors--diagnostic accuracy: NF-pNET and low tumor burden.

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.

Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age.