Resection of Non-Functional Pancreatic Neuroendocrine Neoplasms—A Single-Center Retrospective Outcome Analysis

Surgery remains the only curative treatment of pancreatic neuroendocrine neoplasms (pNEN). Here, we report the outcome after surgery for non-functional pNEN at a European Neuroendocrine Tumor Society (ENETS) center in Germany between 2000 and 2019; cases were analyzed for surgical (Clavien–Dindo classification; CDc) and oncological outcomes. Forty-nine patients (tumor grading G1 n = 25, G2 n = 22, G3 n = 2), with a median age of 56 years, were included. Severe complications (CDc ≥ grade 3b) occurred in 11 patients (22.4%) and type B/C pancreatic fistulas (POPFs) occurred in 5 patients (10.2%); in-hospital mortality was 2% (n = 1). Six of seven patients with tumor recurrence (14.3%) had G2 tumors in the pancreatic body/tail. The median survival was 5.7 years (68 months; [1–228 months]). Neither the occurrence (p = 0.683) nor the severity of complications had an influence on the relapse behavior (p = 0.086). This also applied for a POPF (≥B, p = 0.609). G2 pNEN patients (n = 22) with and without tumor recurrence had similar median tumor sizes (4 cm and 3.9 cm, respectively). Five of the six relapsed G2 patients (83.3%) had tumor-positive lymph nodes (N+); all G2 pNEN patients with recurrence had initially been treated with distal pancreatic resection. Pancreatic resections for pNEN are safe but associated with relevant postoperative morbidity. Future studies are needed to evaluate suitable resection strategies for G2 pNEN.

Distal Pancreatic Resection with Splenectomy in the Rat: A Pancreatic Fistula Model to Investigate Postsurgical Damage?

<b><i>Background:</i></b> Postoperative pancreatic fistula (POPF) is a major complication in pancreatic surgery and can cause considerable postoperative morbidity. Advanced surgical-technical approaches to prevent POPF did not yield a substantial improvement. To investigate innovative treatments, experimental animal models of distal pancreatic resection and pancreaticoduodenectomy are of fundamental importance. After a failed attempt to replicate a previously described rat model for pancreatic fistula induction, we proceeded to distal pancreatic resection with splenectomy to provoke pancreatic leakage and generate a suitable animal model. <b><i>Methods:</i></b> Distal pancreatic resection with splenectomy was performed in 40 rats. The rats were sacrificed on postoperative day (POD) 1, 2, 4, 6, 8, or 10, and the abdominal cavity was explored. Ascites probes were collected pre- and postoperatively for the detection of pancreas amylase and lipase. Tissue samples from the naïve pancreas (POD 0) and the postoperatively harvested remnant were evaluated histologically. The extent of necrosis was determined, and samples were examined for neutrophil infiltration. TUNEL staining served for the verification of necrosis in distinct cases. Immunohistochemistry of Ki67, von Willebrand factor, and CD68 was performed to evaluate proliferation, blood-vessel sprouting, and macrophage invasion. <b><i>Results:</i></b> The rats showed no clinical symptoms or severe complications in the postoperative course up to 10 days. Abdominal exploration revealed adhesions in the upper abdomen, but no intra-abdominal fluid accumulations were found. Signs of inflammation and tissue damage were evident at the pancreatic resection margin on histological examination whereas the naïve pancreatic tissue was widely unaffected. Statistically significant differences were seen between the preoperative and postoperative extent of necrosis, the presence of neutrophil infiltrate, and levels of ascitic amylase and lipase. Immunohistochemical staining on Ki67, von Willebrand factor, and CD68 did not reveal any workable results on nonstatistical examination, and it was therefore not considered for further analyses. <b><i>Conclusion:</i></b> Creating a functional animal model of pancreatic fistula that reflects the clinical and pathophysiological impact of pancreatic leakage in humans has not been achieved. Our approach of left pancreatic resection recapitulated inflammation and tissue damage, early events in the development of fistulas, and it could be suitable for the experimental testing of novel targeting methods.

Pancreatic fistula risk assessment after distal pancreatectomy: a retrospective controlled study

Background. Despite declining mortality, postoperative pancreatic fistula (PPF) remains a common complication of distal pancreatic resection surgery challenging to clinical prediction.Objectives. Prognostic analysis of the postoperative pancreatic fistula risk factors in patients with previous distal pancreatectomy.Methods. A retrospective controlled assay enrolled 107 patients, including 63 (58.9%) male and 44 (41.1%) female patients. All patients underwent distal pancreatectomy followed by a morphological examination of resected material. All patients had a general and biochemical blood panel profiling. Pancreatic tissue density at a putative resection zone was assessed with computed tomography. The patients were allocated to two cohorts: (1) not developing PPF (77 patients) and (2) having postoperative PPF complications (30 patients.Results. No statistically significant differences by age, gender, ASA and BMI scores were observed in study cohorts. Multivariate analysis revealed a statistically significant correlation of the PPF rate with the following factors: main pancreatic duct diameter <3 mm (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01–1.05, p = 0.01), pancreatic density at putative resection zone <30 HU in CT (OR 3.18, 95% CI 1.38–7.74, p < 0.01) and differential albumin of postoperative day 1 vs. pre-surgery >14 g/L (OR 3.13, 95% CI 1.19–8.24, p < 0.01).Conclusion. A main pancreatic duct diameter <3 mm, pancreatic density at putative resection zone <30 HU in CT and differential albumin of postoperative day 1 vs. pre-surgery >14 g/L are independent risk factors of postoperative fistulae.

Protocol for a randomised controlled trial to compare postoperative complications between minimally invasive and open DIStal PAnCreaTectomy (DISPACT-2 trial)

IntroductionIn recent years, minimally invasive distal pancreatectomy (MIDP) has been used with increasing frequency to accelerate patient recovery. Distal pancreatectomy has an overall morbidity rate of 30%–40%. The known advantages of minimally invasive techniques must be rigorously compared with those of open surgery before they can be completely implemented into clinical practice.Methods and analysisDISPACT-2 is a multicentre randomised controlled trial comparing minimally invasive (conventional laparoscopic or robotic assisted) with open distal pancreatic resection in patients undergoing elective surgery for benign as well as malign diseases of the pancreatic body and tail. After screening for eligibility and obtaining informed consent, a total of 294 adult patients will be preoperatively randomised in a 1:1 ratio. The primary hypothesis is that MIDP is non-inferior to open distal pancreatectomy in terms of postoperative mortality and morbidity expressed as the Comprehensive Complication Index (CCI) within 3 months after index operation, with a non-inferiority margin of 7.5 CCI points. Secondary endpoints include pancreas-specific complications, oncological safety and patient reported outcomes. Follow-up for each individual patient will be 2 years.Ethics and disseminationThe DISPACT-2 trial has been approved by the Ethics Committee of the medical faculty of Heidelberg University (S-693/2017). Results of the primary endpoint will be available in 2024 and will be published at national and international meetings. Full results will be made available in an open access, peer-reviewed journal. The website www.dispact.de contains up-to-date information regarding the trial.Trial registration numberDRKS00014011

Pancreatogenic Splenic Pseudocysts: Pathogenesis, Diagnosis and Treatment

Background: Pancreatogenic splenic pseudocysts are a relatively rare condition. Intra-splenic localization is of the splenic pseudocysts is dangerous because of the possibility of massive haemorrhage and organ rupture. Aim: To analyse our experience in the diagnosis and treatment of pancreatogenic pseudocysts of the spleen. Materials and Methods: The analysis of the short and long-term results of treatment of the 34 patients with pancreatogenic splenic pseudocysts (extrapancreatic localization) (1985-2019) was performed. In the study, the majority of male patients - 88.2%, the age of patients was 45 ± 7 years. Results: Percutaneous drainage under US-control was performed in 11 (32.4%) patients, distal pancreatic resection with splenectomy was performed in 23 (67.6%) in the cases of pancreatic tail calcific pancreatitis. In all cases of percutaneous treatment, a high level of amylase was found in the fluid from pseudocysts. Bacteriological confirmation of the growth of any bacteria in the content was not obligatory. Suppuration of the fluid of the pseudocyst was observed in 85.3% of the cases. Conclusion: Pancreatogenic pseudocysts of the spleen are one of the complications of destructive pancreatitis. They can remain undiagnosed for a long time, become infected and aggravate the course of the disease. They are often the cause of the development of sepsis and peritonitis due to the rupture of the organ capsule and bleeding into the abdominal cavity. The use of percutaneous minimally invasive methods of treatment for intra-organ pancreatogenic pseudocysts makes it possible to improve the results of treatment in this group of patients, and also, in the optimal case, be the final method of treatment.

Disturbances of carbohydrate metabolism and postoperative complications after distal pancreatic resection

Objective. To study the state of carbohydrate metabolism in patients after distal pancreatic resection and its effect on the development of postoperative complications. Materials and methods. Over 10 years, 47 patients have been operated on with various tumors of the body/tail of the pancreas and complications of chronic pancreatitis. In 16 of them, concomitant diabetes mellitus was diagnosed before surgery, and in 31 patients, carbohydrate metabolism was normal. Results. After surgery, from a group of patients with unchanged carbohydrate metabolism, 8 (25.8 %) developed diabetes mellitus. The following postoperative complications pancreatic fistula, inflammatory infiltrates and "fluid leakages in the abdominal cavity occurred in 68 % of cases. Out of 24 patients with diabetes mellitus, complications were registered in 21 (87.5 %) and of 23 diabetes-free patients in 11 (47.8 %). Conclusions. The total risk for the development of the postoperative abdominal complications after the distal resection in patients with diabetes mellitus, diagnosed before and after the intervention, is 7.6 times higher than in patients without diabetes.

Prevention of complications of pancreatoduodenal resection in pancreatic cancer

Introduction. Over the past few decades, the incidence of pancreatic cancer has dramatically increased worldwide. Despite the high prevalence of this oncological pathology, there is currently no consensus on the expediency of performing radical reconstructive-plastic surgeries in case of malignant pancreatic tumors. Aim: to study the influence of reconstructive-plastic techniques of surgical treatment of pancreatic cancer on the life expectancy of patients and its quality. Materials and methods. Analysis of the short and long-term outcomes of surgical treatment of pancreatic cancer was conducted. In total, radical operative interventions were carried out in 32 patients, including 14 men (56.25%) and 18 women (43,75%), aged 37 to 72 (61,5±10,0) years. Pyloro-preserving pancreatoduodenal resection was performed in 20 (62.5%) patients, gastropancreatoduodenal resection — in 6 (18.8%) patients, proximal resection — in 5 (15.6%) patients, distal pancreatic resection — in 1 case (3,1%). Areflux pancreatojejunal anastomosis was formed in patients by the clinic technique. Results. Hospital mortality was 6.25%. More than three years after surgery, 15.6% of patients are alive; the median survival rate is 19.5±2.4 months. An assessment of the quality of life and the function of the formed pancreatojejunostomy conducted in the immediate and remote periods showed that the presence of areflux valve reliably prevents the development of pancreatic stump, providing a high level of quality of life for patients. Conclusions. The use of organ-preserving and organ-modulating techniques in the treatment of operable pancreatic cancer does not affect survival, but provides an acceptable level of quality of life for patients in the short and long-term perspective after surgery.

Overall Postoperative Morbidity and Pancreatic Fistula Are Relatively Higher after Central Pancreatectomy than Distal Pancreatic Resection: A Systematic Review and Meta-Analysis

Objective. To compare the intraoperative and postoperative outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP). Methods. A systematic literature search was performed on electronic databases from MEDLINE, Embase, and PubMed from 1998 to 2018. Statistical analysis and meta-analysis were performed using statistics/data analysis (Stata®) software, version 12.0 (StataCorp LP, College Station, Texas 77845, USA). Dichotomous variables were analyzed by estimation of relative risk (RR) with a 95 percent (%) confidence interval (CI) and continuous variables were analyzed by standardized mean differences (SMD) with 95% CI. Results. Twenty-four studies with 593 CP and 1226 DP were included in the meta-analysis. CP had significantly longer operation time (SMD: 1.03; 95% CI 0.62 to 1.44; P<0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P<0.01). Estimated blood loss was significantly lower in CP (SMD: −0.34; 95% CI −0.58 to −0.09; P=0.007). Overall postoperative morbidity (RR: 1.30; 95% CI: 1.13 to 1.50; P<0.001), overall pancreatic fistula (RR: 1.41; 95% CI: 1.20 to 1.66; P<0.001), clinically relevant fistula (RR: 1.64; 95% CI: 1.25 to 2.16; P<0.001), and postoperative hemorrhage (RR: 1.90; 95% CI: 1.18 to 3.06; P<0.05) were all significantly higher after CP. On long-term follow-up, DP patients were more likely to have postoperative exocrine (RR: 0.56; 95% CI: 0.37 to 0.84; P<0.05) and endocrine (RR: 0.27; 95% CI: 0.18 to 0.40; P<0.001) insufficiency. There was no statistically significant difference in transfusion requirement, postoperative mortality, reoperation, and tumor recurrence. Conclusion. CP is associated with significantly higher morbidity and clinically relevant pancreatic fistula. CP should only be reserved for selected patients who require postoperative pancreatic function preservation.