Whole-exome sequencing of calcitonin-producing pancreatic neuroendocrine neoplasms indicates a unique molecular signature.

Introduction: Calcitonin-producing pancreatic neuroendocrine neoplasms (CT-pNENs) are an extremely rare clinical entity, with approximately 60 cases reported worldwide. While CT-pNENs can mimic the clinical and diagnostic features of medullary thyroid carcinoma, their molecular profile is poorly understood. Methods: Whole-exome sequencing (WES) was performed on tumor and corresponding serum samples of five patients with increased calcitonin serum levels and histologically validated calcitonin-positive CT-pNENs. cBioPortal analysis and DAVID gene enrichment analysis were performed to identify dysregulated candidate genes compared to control databases. Immunohistochemistry was used to detect the protein expression of MUC4 and MUC16 in CT-pNEN specimens. Results: Mutated genes known in the literature in pNENs like MEN1 (35% of cases), ATRX (18-20% of cases) and PIK3CA (1.4% of cases) were identified in cases of CT-pNENs. New somatic SNVs in ATP4A, HES4, and CAV3 have not been described in CT- pNENs, yet. Pathogenic germline mutations in FGFR4 and DPYD were found in three of five cases. Mutations of CALCA (calcitonin) and the corresponding receptor CALCAR were found in all five tumor samples, but none of them resulted in protein sequelae or clinical relevance. All five tumor cases showed single nucleotide variations (SNVs) in MUC4, and four cases showed SNVs in MUC16, both of which were membrane-bound mucins. Immunohistochemistry showed protein expression of MUC4 in two cases and MUC16 in one case, and the liver metastasis of a third case was double positive for MUC4 and MUC16. The homologous recombination deficiency (HRD) score of all tumors was low. Discussion: CT-pNENs have a unique molecular signature compared to other pNEN subtypes, specifically involving the FGFR4, DPYD, MUC4, MUC16 and the KRT family genes. However, a major limitation of our study was the relative small number of only five cases. Therefore, our WES data should be interpreted with caution and the mutation landscape in CT-pNENs needs to be verified by a larger number of patients. Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation and whole genome sequencing could be informative.

The Expression of Autophagy-Associated Genes Represents a Valid Footprint for Aggressive Pancreatic Neuroendocrine Neoplasms.

Pancreatic neuroendocrine neoplasms (pNEN) are rare and heterogeneous tumors. Previous investigations have shown that autophagy can be a target for cancer therapy. This study aimed to determine the association between the expression of autophagy-associated gene transcripts and clinical parameters in pNEN. In total, 54 pNEN specimens were obtained from our human biobank. The patient characteristics were retrieved from the medical record. RT-qPCR was performed to assess the expression of the autophagic transcripts BECN1, MAP1LC3B, SQSTM1, UVRAG, TFEB, PRKAA1, and PRKAA2 in the pNEN specimens. A Mann-Whitney U test was used to detect differences in the expression of autophagic gene transcripts between different tumor characteristics. This study showed that G1 sporadic pNEN have a higher expression of autophagic genes compared to G2. Lymphatic and distant metastasis occurred significantly more often in pNEN with a decreased expression of the autophagic genes. Within sporadic pNEN, the insulinomas express higher levels of autophagic transcripts than gastrinomas and non-functional pNEN. MEN1-associated pNEN show a higher expression of autophagic genes than sporadic pNEN. In summary, a decreased expression of autophagic transcripts distinguishes metastatic from non-metastatic sporadic pNEN. The significance of autophagy as a molecular marker for prognosis and therapy decisions needs to be further investigated.

Pancreaticoduodenectomy Is the Best Surgical Procedure for Zollinger-Ellison Syndrome Associated with Multiple Endocrine Neoplasia Type 1.

AIM: The aim of this research was to evaluate the long-term outcome of pancreaticoduodenectomy (PD) versus other duodenopancreatic resections (non-PD) for the surgical treatment of the Zollinger-Ellison syndrome (ZES) in patients with multiple endocrine neoplasia type 1 (MEN1). METHODS: Prospectively recorded patients with biochemically confirmed MEN1-ZES who underwent duodenopancreatic surgery were retrospectively analyzed in terms of clinical characteristics, complications, cure rate, and long-term morbidity, including quality of life assessment (EORTC QLQ-C30). RESULTS: 35 patients (16 female, 19 male) with MEN1-ZES due to duodenopancreatic gastrinomas with a median age of 42 (range 30-74) years were included. At the time of diagnosis, 28 (80%) gastrinomas were malignant, but distant metastases were only present in one (3%) patient. Eleven patients (31.4%) underwent pancreatoduodenectomy (PD) as the initial procedure, whereas 24 patients underwent non-PD resections involving duodenotomy with gastrinoma excision, enucleation of the pNEN from the head of the pancreas, and peripancreatic lymphadenectomy, either with or without distal pancreatectomy (i.e., either Thompson procedure, n = 12, or DUODX, n = 12). There was no significant difference in perioperative morbidity and mortality between the two groups (p ≥ 0.05). One (9%) patient of the PD group required reoperation for recurrent or metastatic ZES compared to eight (22.8%) patients of the non-PD resection groups. After a median follow-up time of 134 months (range 6-480) nine of 11 (82%) patients in the PD group, two of 12 (16%) patients in the Thompson procedure group, and three of 12 (25%) patients in the DUODX group had normal serum gastrin levels. In addition, the global health QoLScore was better in the PD group (76.9) compared to the Thompson procedure (57.4) and DUODX (59.5) groups. CONCLUSIONS: Initial PD seems to be the superior surgical procedure for MEN1-ZES, resulting in a long-term cure rate of about 80%, fewer duodenopancreatic reoperations, and an acceptable quality of life.

ENETS standardized (synoptic) reporting for endoscopy in neuroendocrine tumors.

Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.

Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms.

There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.

Postoperative morbidity following pancreatic cancer surgery is significantly associated with worse overall patient survival; systematic review and meta-analysis.

BACKROUND: The influence of postoperative morbidity on survival after potentially curative resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: Medline, Web of Science and Cochrane Library were searched for studies reporting survival in patients with and without complications, defined according to the Clavien-Dindo classification, after primary, potentially curative resection for pancreatic cancer followed by adjuvant treatment. Meta-analysis was performed using a random-effects model. RESULTS: Fourteen retrospective cohort studies comprising a total of 7.604 patients with an overall complication rate of 40.8% (n = 3.103 patients) were included. Median overall survival for the entire patient cohort ranged from 15.5 to 24 months. Overall survival in patients with severe postoperative complications ranged from 7.1 to 37.1 months and was significantly worse compared to the overall survival in patients without severe complications ranging from 16.5 to 38.2 months. Postoperative complication rates ranged from 24.3% to 64%, severe (Clavien-Dindo ≥ III) complication rates from 4.2% to 31%. Results sufficient for meta-analysis were reported by ten studies, representing 6.028 patients. Meta-analysis showed reduced overall survival following any complication (summary adjusted HR 1.47; 95% CI 1.23-1.76, p < 0.0001). Hazard of death was 1.5 times higher in patients experiencing severe postoperative complications than in patients without severe complications (summary adjusted HR 1.45; 95% CI 1.13-1.85, p = 0.003). CONCLUSIONS: Postoperative complications after potentially curative resection of PDAC are significantly associated with worse overall patient survival.

The German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa)­Knowledge Gained in 20 Years.

BACKGROUND: Familial pancreatic carcinoma (FPC) is a rare hereditary tumor syndrome with a heterogeneous clinical phenotype. The study of FPC also contributes to a better understanding of the more common sporadic pancreatic ductal adenocarcinoma (PDAC). We report on the past 20 years' experience of the German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa) of the German Cancer Aid (Deutsche Krebshilfe). METHODS: From 1999 onward, families in which at least two first-degree relatives had PDAC, and which did not meet the criteria for any other tumor syndrome, have been entered into the FaPaCa registry and analyzed both clinically and with molecular genetic techniques. Persons at risk are offered the opportunity to participate in an early detection program. RESULTS: From June 1999 to June 2019, 227 families (a total of 2579 persons) met the criteria for entry into the FaPaCa registry. PDAC was the sole tumor entity present in 37% of the families (95% confidence interval [31.1; 44.1]); in the remaining 63% [55.9; 68.9], other tumor types were present as well, particularly breast cancer (70 families, 31% [24.9; 37.3]), colon carcinoma (25 families, 11% [7.3; 15.8]) , and melanoma (22 families, 9.7% [6.2; 14.3]). The mode of inheritance of PDAC was autosomal dominant in 72% [65.5; 77.6] of the families. Predisposing germ-line mutations were found in 25 of the 150 (16.7%) families studied, in the following genes: BRCA2 (9 families), CDKN2A (5 families), PALB2 (4 families), BRCA1 (3 families), ATM (2 families), and CHEK2 (2 families). The early detection program revealed high-grade cancer precursor lesions or a PDAC in 5 of the participating 110 persons at risk (4.5%, [1.5; 10.3] during a period of observation of at least five years. CONCLUSION: The care of families with FPC is complex and should be provided in centers with the necessary expertise. Prospective, controlled longitudinal studies are needed to determine whether the screening of persons at risk for PDAC truly lessens mortality and is cost-effective.

Adult Proinsulinomatosis Associated With a MAFA Germline Mutation as a Rare Cause of Recurrent Hypoglycemia.

ABSTRACT: Sporadic adult insulinomatosis is an extremely rare clinical condition. Adult proinsulinomatosis has not yet been described. We report the case of a 48-year-old female patient with recurrent hypoglycemia caused by benign proinsulin-secreting pancreatic neuroendocrine neoplasias (pNENs) with no history of multiple endocrine neoplasia type 1. Initial workup revealed elevated serum proinsulin levels and a positive fasting test. Magnetic resonance imaging and endosonography visualized 2 pNENs in the pancreatic body and tail that were treated by robotic-assisted enucleation. After initial biochemical cure, the patient's hypoglycemia recurred 3 months after surgery. Imaging showed a new lesion in the pancreatic body, so that now a spleen-preserving subtotal distal pancreatectomy was performed. The pathological examination revealed 17 neuroendocrine microadenomas and 1 well-differentiated pNEN (Ki-67% 1%-2%) of 22-mm size as well as more than 200 (pro)insulin-producing ß-cell precursor lesions, confirming the diagnosis of adult proinsulinomatosis. Mutation analysis of the germline DNA identified the in-frame deletion mutation (p.His207del) in the MAFA gene on chromosome 8. The patient was biochemically cured 16 months after the last surgical resection. Similarly to adult insulinomatosis, the presence of proinsulin-secreting tumors causes recurrent hypoglycemia and might be associated with germline mutations in the MAFA gene.

C-reactive protein and drain amylase accurately predict clinically relevant pancreatic fistula after partial pancreaticoduodenectomy.

BACKROUND: C-reactive protein (CRP) and procalcitonin (PCT) have shown to be reliable predictors of inflammatory complications and anastomotic leak after colorectal surgery. Their predictive value after partial pancreaticoduodenectomy (PD) remains unclear. MATERIALS AND METHODS: All consecutive pancreaticoduodenectomies (2009-2018) at our hospital were included. Drain amylase was evaluated on postoperative day (POD) 1, serum CRP and PCT were evaluated on POD 1-3. Receiver-operating characteristics curves were performed and significant cut-off values were tested using logistic regression. RESULTS: Among 188 patients who underwent partial PD, clinically relevant pancreatic fistulas (POPF) occurred in 30 (16%) patients, including 20 (10.6%) with Grade B and 10 (5.3%) patients with Grade C. Postoperative complications (Clavien-Dindo ≥ III) were reported in 46 (24.5%) patients, including Grade IIIa in 16 (8.5%), IIIb in 18 (9.6%), IVa in 3 (1.6%), IVb in 2 (1.1%) and V in 7 (3.7%) patients. Drain amylase on POD 1 showed the largest area under the curve (0.872, p < 0.001), followed by CRP (0.803, p < 0.001) and PCT on POD 3 (0.651, p < 0.011). Drain amylase on POD 1 > 303 U/l (OR 0.045, 95% CI 0.010-0.195, p < 0.001), CRP > 203 mg/l (OR 0.098, 95% CI 0.041-0.235, p < 0.001) and PCT > 0.85 µg/l (OR 0.393, 95%CI 0.178-0.869, p = 0.02) were significant predictors of relevant POPF in the univariate analysis. CRP > 203 mg/l (OR 0.098, 95% CI 0.024-0.403, p = 0.001) and drain amylase > 303 U/l (OR 0.064, 95% CI 0.007-0.554, p = 0.01) remained independent predictors in the multivariable analysis. The combination of drain amylase on POD 1 and CRP on POD 3 had a sensitivity and specificity of 87.4% and 90.9% to predict relevant POPF. CONCLUSION: Drain amylase on POD 1 and CRP on POD 3 can accurately predict clinically relevant POPF after partial pancreaticoduodenectomy. The accuracy of PCT on POD 3 is limited.

Palliative surgical bypass is superior to palliative endoscopic stenting in patients with malignant gastric outlet obstruction: systematic review and meta-analysis.

BACKGROUND: Gastrojejunostomy (GJ) and self-expanding metal stents (SEMS) are the two most common palliative treatment options for patients with malignant gastric outlet obstruction (GOO). Randomised trials and retrospective studies have shown discrepant results, so that there is still a controversy regarding the optimal treatment of GOO. METHODS: Medline, Web of Science and Cochrane Library were systematically searched for studies comparing GJ to SEMS in patients with malignant GOO. Primary outcomes were survival and postoperative mortality. Secondary outcomes were frequency of re-interventions, major complications, time to oral intake and length of hospital stay. RESULTS: Twenty-seven studies, with a total of 2.354 patients, 1.306 (55.5%) patients in the SEMS and 1.048 (44.5%) patients in the GJ group, were considered suitable for inclusion. GJ was associated with significantly longer survival than SEMS (mean difference 43 days, CI 12.00, 73.70, p = 0.006). Postoperative mortality (OR 0.55, CI 0.27, 1.16, p = 0.12) and major complications (OR 0.73, CI 0.5, 1.06, p = 0.10) were similar in both groups. The frequency of re-interventions, however, was almost three times higher in the SEMS group (OR 2.95, CI: 1.70, 5.14, p < 0.001), whereas the mean time to oral intake and length of hospital stay were shorter in the SEMS group (mean differences - 5 days, CI - 6.75, - 3.05 days, p < 0.001 and - 10 days, CI - 11.6, - 7.9 days, p < 0.001, respectively). CONCLUSIONS: Patients with malignant GOO and acceptable performance status should be primarily considered for a palliative GJ rather than SEMS.

Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry.

PURPOSE: Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. METHODS: Patients who underwent surgery for pNENs (April 2013-June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. RESULTS: A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016-0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. CONCLUSION: In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.

Implementation of Current ENETS Guidelines for Surgery of Small (≤2 cm) Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis of the Prospective DGAV StuDoQ|Pancreas Registry.

BACKGROUND: ENETS guidelines recommend parenchyma-sparing procedures without formal lymphadenectomy, ideally with a minimally invasive laparoscopic approach for sporadic small pNENs (≤2 cm). Non-functioning (NF) small pNENs can also be observed. The aim of the study was to evaluate how these recommendations are implemented in the German surgical community. METHODS: Data from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery were analyzed regarding patient's demographics, tumor characteristics, surgical procedures, histology and perioperative outcomes. RESULTS: Eighty-four (29.2%) of 287 patients had sporadic pNENs ≤2 cm. Forty-three (51.2%) patients were male, and the mean age at diagnosis was 58.8 ± 15.6 years. Twenty-five (29.8%) pNENs were located in the pancreatic head. The diagnosis pNEN was preoperatively established in 53 (65%) of 84 patients. Sixty-two (73.8%) patients had formal pancreatic resections, including partial pancreaticoduodenectomy or total pancreatectomy (21.4%). Only 22 (26.2%) patients underwent parenchyma-sparing resections and 23 (27.4%) patients had minimally invasive procedures. A lymphadenectomy was performed in 63 (75.4%) patients, and lymph node metastases were diagnosed in 6 (7.2%) patients. Eighty-two (97.7%) patients had an R0 resection. Sixty (72%) tumors were classified G1, 24 (28%) tumors G2. Twenty-seven (32.2%) of 84 patients had postoperative relevant Clavien-Dindo grade ≥3 complications. Thirty- and 90-day mortalities were 2.4% and 3.6%. CONCLUSIONS: ENETS guidelines for surgery of small pNENs are yet not well accepted in the German surgical community, since the rate of formal resections with standard lymphadenectomy is high and the minimally invasive approach is underused. The attitude to operate small NF tumors seems to be rather aggressive.

Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with pancreatic cancer: Systematic review and meta-analysis.

BACKROUND: The role of sarcopenia and sarcopenic obesity in patients with pancreatic ductal adenocarcinoma(PDAC) remains controversial. MATERIAL AND METHODS: Medline and Web of Science were searched for studies reporting survival in sarcopenic and/or sarcopenic obese patients with pancreatic cancer. Primary outcome was mortality in patients with sarcopenia and/or sarcopenic obesity versus non-sarcopenic and/or non-sarcopenic obese patients. Secondary outcome was the incidence of major postoperative complications. RESULTS: Eleven studies comprising 2.297 patients were considered suitable for inclusion. Overall 959 of 2.111(45.4%) patients were defined as sarcopenic and 163 of 1.254(13%) as sarcopenic obese. Patients' age was above 60 years(range 63-69) with a male proportion ranging from 50.8% to 68.0%. Of 2.297 patients, 958(41.7%) underwent palliative treatment, 1.339(58.3%) curative resections. Follow-up ranged from 11 to 57.7 months. Median overall survival ranged from 4.3 to 12 months in palliative patients and 17.4 to 25.8 months after curative resection. Overall proportions of sarcopenic patients varied from 21.3% to 65.3%. Sarcopenia was significantly associated with poorer overall survival(HR 1.49; 95%CI 1.27-1.74,p<0.001). Sarcopenic obesity was reported in 0.6% to 25.0% of patients, and was also significantly associated with poorer overall survival(HR 2.01; 95%CI 1.55-2.61,p<0.001). The incidence of major complications ranged from 8.6% to 33.9%. Rates of clinically relevant(grade B/C) postoperative pancreatic fistulas varied from 8.3% to 17.8%. Sarcopenic obesity was an independent predictor of major postoperative complications in one study, in another study sarcopenia was significantly associated with clinically relevant pancreatic fistulas. CONCLUSIONS: Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with PDAC.

High risk of fistula formation in vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis-a retrospective analysis.

PURPOSE: The aim of this study was to evaluate the efficacy of vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis and to identify possible risk factors of fistula formation. METHODS: The hospital OPS-database (time period 2005-2014) was searched to identify patients treated with an open abdomen due to secondary peritonitis, who underwent vacuum-assisted closure therapy. Medical records were retrospectively analyzed for patients' characteristics, cause of peritonitis, duration of vacuum therapy, number of relaparotomies, fascial closure rates, and risk factors of fistula formation. RESULTS: Forty-three patients (19 male, 24 female) with a median age of 65 years (range 24-90 years) were identified. The major cause of secondary peritonitis was anastomotic leakage after intestinal anastomosis or bowel perforation, the median APACHE II score was 11. Median duration of VAC treatment was 12 days (range 3-88 days). Twenty of 43 (47 %) patients died from septic complications. Delayed fascial closure was obtained by suturing in 20 of 43 patients (47 %). Overall 16 of 43 (37 %) patients developed enteroatmospheric fistulas. Re-explorations after starting VAC treatment and duration of VAC therapy were significantly associated with the occurrence of enteroatmospheric fistulas (p < 0.001). ROC curve analysis determined the optimal duration of VAC therapy to reduce the risk of fistula formation at 13 days. CONCLUSIONS: Long-term VAC treatment of patients with an open abdomen due to secondary peritonitis results in a relatively low fascial closure rate and a high risk of fistula formation.

Pancreatic polypeptide-rich islets in the posterior portion of the pancreatic head--a tumor mimic in somatostatin receptor scintigraphy.

A 74-year-old man with recurrent duodenal ulcers underwent somatostatin receptor scintigraphy (SRS) in suspicion of gastrinoma. A 2-cm area of focal uptake was visualized within the pancreatic head. Serum chromogranin A levels were elevated, but serum gastrin levels and the secretin test were normal. Computed tomography and endoscopic ultrasonography were not conclusive. After partial duodenopancreatectomy, pathological examination failed to reveal any neuroendocrine tumor. Instead, the dorsal portion of the pancreatic head was found to be densely populated by pancreatic polypeptide cell-rich islets. This area correlated with the site of tracer uptake seen on SRS. Thus, pancreatic polypeptide cell-rich islets in elderly patients should be kept in mind when interpreting SRS results to avoid unnecessary major pancreatic resections.

Intracutaneous suture versus transcutaneous skin stapling for closure of midline or horizontal skin incision in elective abdominal surgery and their outcome on superficial surgical site infections--INTRANS: study protocol for a randomized controlled trial.

BACKGROUND: Surgical site infections are the third most frequent type of nosocomial infections. Evidence-based recommendations have been given regarding preoperative hospitalization, hygiene and air-conditioning, patient conditions, and wound dressing. However, no general recommendations concerning wound closure exist. Systematic reviews and meta-analyses suppose a benefit of intracutaneous suture compared to skin staples in orthopedic and obstetric surgery. Literature data for skin closure in elective abdominal surgery are still deficient. METHODS/DESIGN: Patients scheduled for any elective abdominal surgery requiring midline or horizontal laparotomy are potentially eligible for the trial. Trial-specific exclusion criteria are date of admission exceeding four days prior to surgery, antibiotic treatment within the past 14 days, any previous midline or horizontal laparotomy in case the procedure requires the same skin incision as before, neurophysiological deficits or severe psychiatric or neurologic diseases that do not allow an informed consent or compliance, and participation in any other interventional trial with interference of intervention and outcome. The trial is created for process innovation within standardized surgical procedures. It is designed as a prospective randomized controlled single center trial in a parallel design including an active comparator and an intervention group. The intervention addresses the closure of skin after the main surgical procedure: intracutaneous suture in the intervention group and transcutaneous skin stapling in the control group. The rate of superficial surgical site infections is defined as the primary endpoint. Secondary endpoints are time for skin closure, satisfaction with the cosmetic outcome 30 days after surgery, prolongation of hospital stay, and duration of sick-leave due to surgical site infections. The primary efficacy analysis follows the intention-to-treat principle. A χ2 test will be applied. DISCUSSION: The trial is expected to balance the shortcomings of the current evidence. It will help to define the gold standard for wound closure in elective abdominal surgery. Patients' safety and quality of life are assumed to be enhanced. Therapy costs are likely to be reduced and health care optimized. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00004542.

Reduced complication rate after modified binding purse-string-mattress sutures pancreatogastrostomy versus duct-to-mucosa pancreaticojejunostomy.

BACKGROUND AND PURPOSE: A 2011 metaanalysis demonstrated no difference in postoperative complications between pancreatogastrostomy and pancreaticojejunostomy after pancreaticoduodenectomy with the limitation of heterogeneity among the analysed studies. The present study compares postoperative complications after duct-to-mucosa pancreaticojejunostomy with a modified binding purse-string-mattress sutures pancreatogastrostomy in a teaching hospital. METHODS: One-hundred consecutive pancreaticoduodenectomies were reconstructed either by pancreaticojejunostomy (n = 50, 2004-2008) or modified pancreatogastrostomy (n = 50, 2008-2011). Prospective patients' data was retrospectively analysed for postoperative complications. MAIN FINDINGS: Complications occurred significantly less after modified pancreatogastrostomy compared to pancreaticojejunostomy (p = 0.016). This was mainly due to a significantly lower rate of pancreatic fistula (p = 0.029), especially a lower rate of clinically relevant B and C fistulas (p = 0.011). In particular, the fistula rate was reduced in patients with a soft, non-fibrotic pancreas (p = 0.0231). Postoperative mortality was also lower after modified pancreatogastrostomy (p = 0.042). Uni- and multivariate analyses revealed a soft, non-fibrotic pancreatic texture (odds ratio 5.4, p = 0.028), a non-dilatated pancreatic duct (p = 0.047) and pancreaticojejunostomy (odds ratio 10.7, p = 0.026) as independent, negative factors for pancreatic fistula. CONCLUSION: In a teaching hospital, modified pancreatogastrostomy seems to be superior to pancreaticojejunostomy regarding pancreatic fistula, especially in patients with a soft, non-fibrotic pancreas and/or a small duct. An ongoing prospective randomised multicentre trial (RECOPANC) might confirm these results.

Total versus near-total thyroidectomy in Graves' disease and their outcome on postoperative transient hypoparathyroidism: study protocol for a randomized controlled trial?

BACKGROUND: Graves' disease is an independent risk factor for transient postoperative hypoparathyroidism. Besides the disease itself, preparation techniques are influential. Transient postoperative hypoparathyroidism has severe consequences for patients' physical and psychological state. It can be life threatening during the acute phase and may impair patients' health, psyche and quality of life thereafter. For the surgical therapy of Graves' disease, total thyroidectomy is recommended according to the national S2-guideline. The evidence- based on a metaanalysis- is criticized by the Cochrane diagnostic review commentary for substantial methodological deficits. Two randomized controlled trials lead to the hypothesis that a near-total resection with bilateral remnants of ≤ 1g on each side compared to total thyroidectomy will significantly reduce the occurrence of transient postoperative hypoparathyroidism with equal therapeutic safety. METHODS/DESIGN: Patients with Graves' disease indicated for definite surgery are eligible for the trial. Trial-specific exclusion criteria are: conservative treatment, malignancy, previous thyroid surgery and coincident hypoparathyroidism. The trial is created for therapeutic purpose through process innovation. It is designed as a prospective randomized controlled patient and observer blinded multicentered trial in a parallel design including an active comparator and an intervention group. The intervention addresses the surgical procedure: near-total thyroidectomy leaving bilateral remnants of ≤ 1g on each side in the intervention group and total thyroidectomy in the control group. The occurrence of transient postoperative hypoparathyroidism is defined as primary endpoint. Secondary endpoints are: reoperations due to bleeding, recurrent laryngeal nerve palsy, permanent hypoparathyroidism, recurrent disease, changes of endocrine orbitopathy and quality of life within a one-year follow-up period. The primary efficacy analysis follows the intention-to-treat principle. A binary logistic regression model will be applied. Complications and serious adverse events will be descriptively analyzed. DISCUSSION: The trail is expected to balance out the shortcomings of the current evidence. It will define the surgical gold standard for the surgical therapy of Graves' disease. Patients' safety and quality of life are assumed to be enhanced. Therapy costs are likely to be reduced and health care optimized. The conduction of the trial is feasible through the engagement and commitment of the German association of endocrine surgeons and the National Network for Surgical Trials. TRIAL REGISTRATION: German clinical trials register (DRKS) DRKS00004161.

Does contrast-enhanced cervical ultrasonography improve preoperative localization results in patients with sporadic primary hyperparathyroidism?

OBJECTIVE: Pre-operative localization studies are inevitable in patients with primary hyperparathyroidism (pHPT), who are eligible for focused or minimally invasive parathyroidectomy (MIP). High-resolution ultrasonography (US) in combination with planar (99m)Tc-Sestamibi-scintigraphy (MIBI) and additional single-photon emission computed tomography (SPECT) are the standard procedures to localize enlarged parathyroid glands. Our aim was to evaluate the practicability and significance of contrast-enhanced ultrasonography (CEUS) in patients with pHPT. MATERIALS AND METHODS: All investigations were performed at the University Hospital Marburg. Totally, 25 patients with biochemical proven pHPT underwent preoperative US, MIBI/SPECT, and CEUS. For CEUS, a suspension of phospholipid-stabilized sulfur-hexafluoride (SF6) microbubbles in combination with a special 12 MHz linear US probe was used. All patients were investigated by two sonographers, who did not get to view the findings noted by the other. Finally, surgery was performed and histopathological results were obtained from 24 patients. RESULTS: In 17 (68%) patients, US and MIBI/SPECT already raised suspicion of parathyroid lesions and all suspected lesions were reassessed by CEUS. However, no additional information was obtained using CEUS. Especially in eight patients with negative or inconsistent US and MIBI/SPECT results, CEUS did not provide additional information regarding the site of the suspected parathyroid adenoma. Overall, no side effects were observed using CEUS. Surgical cure was achieved in all patients. CONCLUSION: In this limited cohort of patients, no additional information could be obtained using the costly CEUS compared to results of US and MIBI/SPECT.