Interactions between the Exocrine and the Endocrine Pancreas.

The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.

Endoscopic workup in pancreatic cancer.

Pancreatic cancer is a highly lethal disease with a rising incidence. It is projected to become the second leading cause of cancer-related mortality by 2030. The staging of pancreatic cancer can be broadly categorized into three groups: resectable cancers, locally advanced or borderline resectable cancers, and metastatic cancers. Endoscopy plays a crucial role in the management of pancreatic cancer for the establishment of the diagnosis, for palliation of symptoms due to biliary and/or gastric outlet obstructions, and more recently, for palliative ablation of cancer. The objective of this review is to provide an overview of the endoscopic evaluation and management of patients with pancreatic cancer. It will specifically cover the diagnostic approach utilizing endoscopic ultrasound (EUS), palliative interventions such as endoscopic retrograde cholangiopancreatography (ERCP), and the emerging field of tumor debulking through radiofrequency ablation (RFA).

Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia: A pilot study.

OBJECTIVES: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs. METHODS: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis. RESULTS: In total, 46 patients, 48% females, mean age (range) 67 years (45-82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas. CONCLUSION: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.

Lumen apposing metal stents vs double pigtail plastic stents for the drainage of pancreatic walled-off necrosis.

BACKGROUND: Few studies compared lumen-apposing metal stents (LAMS) and standard double pigtail plastic stents (PS) for the endoscopic drainage of pancreatic walled-off necrosis (WON). Albeit sometimes large, previously described cohorts display considerable heterogeneity and often pooled together data from several centers, involving multiple operators and techniques. Moreover, they often lack a control group for the comparison of outcomes. AIM: to compare clinical efficacy and safety of PS versus LAMS for the endoscopic drainage of infected WON. METHODS: Single-centre, 1:1 case-control study. We compared patients undergoing endoscopic drainages of infected WON through LAMS (cases) or PS (controls). The primary endpoint was the clinical efficacy (resolution of the WON/sepsis), the secondary endpoint was safety (procedure-related complications). RESULTS: Thirty patients were enrolled between 2011 and 2017. Cases and controls were homogeneous in terms of etiology and clinical characteristics. 93% of cases and 86.7% of controls were clinically successfully treated, with no significant differences in rates of post-operative infections, bleedings and stent migrations (respectively 13.3% vs 21.4%; p=0.65; 13.3% vs 0%; p=0.48; 13.3% vs 7.1%; p=1.00). No difference was shown regarding the need for additional percutaneous or surgical treatments (33.3% vs 13.3%; p=0.39). Cases, however, displayed a significantly prolonged mean hospital stay (90.2 days vs 18.5 days; p<0.01) and a higher mean number of endoscopic procedures per patient (4.8 vs 1.5; p<0.01). CONCLUSIONS: PS might be not inferior to LAMS for the treatment WONs. Further prospective RCT is needed to compare clinical efficacy and safety in the two groups.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors. An international multicenter comparative study.

BACKGROUND: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. METHODS: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. RESULTS: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). CONCLUSION: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

Benchmarks in Pancreatic Surgery: A Novel Tool for Unbiased Outcome Comparisons.

OBJECTIVE: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches. RESULTS: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Pancreatectomy with arterial resection is superior to palliation in patients with borderline resectable or locally advanced pancreatic cancer.

BACKGROUND: Few studies have investigated the outcome of pancreatectomy associated with artery resection (PAR). METHODS: Retrospective analysis of a cohort of operated borderline or locally advanced pancreatic cancer patients with surgically confirmed arterial involvement. Short and long-term outcome were analyzed and compared in patients who underwent PAR (Group 1) and palliative surgery (Group 2). RESULTS: Of 73 patients who underwent surgical exploration with intent of resection, 34 underwent PAR (±venous resection) (Group 1) and 39 underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined artery-vein resection (AVR). Operation time was longer and blood loss higher in group 1 compared to group 2. There were no differences in post-operative mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003). CONCLUSION: PAR seems to be safe and feasible in well selected patients and associated with an advantage of survival compared to palliation, in patients affected by locally advanced pancreatic cancer.

Surgical outcomes of oesophagectomy or gastrectomy due to cancer for patients ≥75 years of age: a single-centre cohort study.

BACKGROUND: The increasing age of the population and prolonged life expectancy result in a widening of age limit criteria for a variety of surgical procedures. Oesophagectomy and total gastrectomy are complex operations associated with significant risks of post-operative complications. METHODS: This is a single-centre cohort study of patients operated with curative intent due to oesophageal or gastric cancer. RESULTS: From 2007 to 2017, 548 patients underwent surgery with curative intent, with 122 patients (22.3%) classified as elderly (≥75 years). There was no difference in total complication rates between the groups. The adjusted odds ratio for 90-day mortality after oesophageal resection in the elderly group was 3.65 (95% confidence interval (CI): 1.33-10.03) and after gastrectomy was 1.62 (95% CI: 0.55-4.79). The adjusted hazard ratio for 1-year mortality after oesophagectomy was 2.29 (95% CI: 1.25-4.19), and after gastrectomy the adjusted hazard ratio was 1.48 (95% CI: 0.75-2.92). In the event of a complication with Clavien-Dindo score IIIb or higher, there was a statistically significant increase of 90-day mortality to over 50% among elderly patients both after oesophagectomy and gastrectomy (50.0% versus 19.8%; P = 0.005 and 57.1% versus 17.4%; P = 0.012, respectively). CONCLUSION: There is a statistically significant increase in 90-day mortality after oesophageal and gastric cancer surgery in elderly compared with younger patients. Post-operative complications with high Clavien-Dindo score in patients undergoing oesophagectomy or gastrectomy, with age ≥75 years, are a dramatic risk factor for post-operative death.

Pancreatectomies for pancreatic neoplasms in pediatric and adolescent age: A single institution experience.

BACKGROUND: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth. METHODS: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017. RESULTS: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection. CONCLUSIONS: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant.

Long-term functional outcomes after replacement of the esophagus in pediatric patients: A systematic literature review.

BACKGROUND: The indications of esophageal replacement (ER) in pediatric patients include long gap esophageal atresia (LGEA), intractable post-corrosive esophageal strictures (PCES), and some rare esophageal diseases. Various conduits and procedures are currently used worldwide with a lack of consensus regarding the ideal substitute to replace the esophagus replacement. The short-term outcomes of these advanced procedures are well known; there are few data available describing long-term functional outcomes of these patients with long life expectancy. OBJECTIVES: The objective of this study is to investigate the long-term functional outcomes of the most widely used techniques for ER in pediatric patients based on a comprehensive literature search covering the last 10years. METHODS: Eligible were all clinical studies reporting outcomes after esophagectomy in pediatric patients, which contained information on at least 3years of follow-up after the operation. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic web-based search using MEDLINE, the Cochrane Library and EMBASE databases was performed, reviewing all medical literature published between January 2006 and December 2015. RESULTS: The scientific quality of the data was generally poor, converging toward only 14 full-text articles for the final analysis. The stomach was the preferred organ for esophageal replacement, where the tubulization of the stomach resulted in significant gastroesophageal reflux. Dysphagia symptoms were more seldom reported, but several authors presented growing figures with the length of follow-up. Dumping syndrome and delayed gastric emptying were only scarcely reported upon. Following colonic graft, chronic gastrocolic reflux affects these patients, in the range of 35-70.8%, while 4 studies reported any dysphagia from 2.7% to 50% of the children. Only one study reported the outcome of the use of a long jejunal segment, where presence of symptoms of functional obstruction was mentioned in 46% of cases. Very few if any data were available on a structured assessment of postprandial dumping and disturbed bowel functions. CONCLUSIONS: Available data in pediatric patients, on the long-term functional outcomes after esophageal replacement with a gastric tube, colonic graft or a long jejunal segment, are of poor scientific quality. Although symptoms are frequently reported currently no conclusions can be drawn regarding potential advantages of one graft over another. TYPE OF STUDY: Treatment study, systematic review. LEVEL OF EVIDENCE: IV.

Cattell-Braasch Maneuver Combined with Artery-First Approach for Superior Mesenteric-Portal Vein Resection During Pancreatectomy.

Pancreatectomy associated with superior mesenteric-portal vein (SMPV) resection is currently considered the standard of care for patients with pancreatic tumors involving the major peripancreatic veins. However, a standard approach for resection and reconstruction is not defined yet. The aim of this study is to analyze the feasibility and short-term results of an original Cattell-Braasch artery-first approach (CBAF) for the resection of SMPV during pancreatectomy. Of 144 pancreatectomies with vascular resection undertaken from 2008 to 2013 at Karolinska University Hospital, 45 (31.2 %) were performed combining a Cattell-Braasch maneuver with an artery-first approach (from 2011 to 2013). The mean patient age was 65.2 years. Thirty-seven (82.2 %) patients underwent pancreatoduodenectomy and 8 (17.8 %) total pancreatectomy. Histology showed pancreatic ductal adenocarcinoma in 42 patients (93.3 %). The median length of the resected SMPV segment was 4.6 cm (range 3-7). In all patients, a direct end-to-end anastomosis was performed without graft interposition. In nine cases (20 %), an arterial resection was also performed. There was no mortality in this series, and the morbidity rate was 35.5 %. Combined CBAF for the resection of SMPV during pancreatectomy seems to be safe and effective. The reconstruction of the resected vessels is possible in many cases without graft interposition, even if the resected vein segment is of considerable length.

Pseudoachalasia: A peculiar case report and review of the literature.

Pseudoachalasia is a rare secondary achalasia, which accounts for only a small subgroup of patients. We describe a 77-year-old woman with recent onset of dysphagia and typical esophageal manometric findings of achalasia. Moreover, esophageal manometric findings of vascular compression at 36 cm from the nose were associated with dysphagia. An upper endoscopy showed the absence of lesions both in the esophagus and gastro-esophageal junction, whilst a 15-mm ulcer on the gastric angulus was detected. The gastric ulcer resulted in being a diffuse signet ring cell carcinoma at histology, suggesting pseudoachalasia. An abdominal computed tomography scan showed an irregular concentric thickening of the gastro-esophageal junction wall extending for 7 cm and a dilated ascending thoracic aorta with no presence of the inferior vena cava, with an enlarged azygos as the source of vascular compression of esophagus. Moreover, cardia involvement from diffuse signet ring cell carcinoma of the gastric angulus was also recognized as the cause of dysphagia. The cancer was not suitable for a surgical approach in an old patient with cardiovascular comorbidities and support therapy was started. In our ambulatory series, pseudoachalasia was eventually diagnosed in 4.7% of 234 consecutive patients with esophageal manometric finding suggestive of achalasia. We also reviewed cases in the literature and aimed to evaluate the reported causes of pseudoachalasia.