The relationship between cholecystokinin secretion and pancreatic [11C]methionine uptake in patients after partial pancreaticoduodenectomy.

OBJECTIVE: The pancreatic uptake of [11C]methionine ([11C]MET) is associated with beta-cell function and insulin secretion, but [11C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [11C]MET in the residual pancreas following pancreaticoduodenectomy. METHODS: Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56-67 years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8-26 years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180 min after ingestion. Simultaneously, 800 MBq of [11C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60 min after injection. RESULTS: Integrated CCK (AUC30) correlated with SUVmax (AUC60, R2 = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC60) and CCK concentrations and young age as significant independent predictors of [11C] methionine uptake. CONCLUSION: The association between CCK concentrations and pancreatic [11C]MET uptake might indicate a causal relationship. Further research should assess whether [11C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity.

Gastric Emptying and Distal Gastrectomy Independently Enhance Postprandial Glucagon-Like Peptide-1 Release After a Mixed Meal and Improve Glycemic Control in Subjects Having Undergone Pancreaticoduodenectomy.

OBJECTIVES: New-onset diabetes frequently resolves after pancreaticoduodenectomy (PD). Glucagon-like peptide-1 (GLP-1) conceivably is involved as its release is enhanced by rapid gastric emptying and distal bowel exposure to nutrients. We aimed at studying factors associated with GLP-1 release after PD. METHODS: Fifteen PD subjects with distal gastrectomy (Whipple) and 15 with pylorus preservation were evaluated. A test meal containing 1 g paracetamol to measure gastric emptying was ingested. Blood for the measurement of paracetamol, glucose, insulin, and GLP-1 was drawn at baseline and 10, 20, 30, 60, 90, 120, 150, and 180 minutes thereafter. The Matsuda index of insulin sensitivity was calculated. RESULTS: In univariate analysis, gastric emptying correlated with GLP-1. Glucagon-like peptide-1 responses to the modes of operation did not differ. Multiple regression analysis confirmed gastric emptying and Whipple versus pylorus-preserving pancreaticoduodenectomy as independent predictors of GLP-1 release. The Matsuda index of insulin sensitivity correlated with GLP-1 concentrations and inversely with body mass index. Patients after Whipple procedure revealed lower glycated hemoglobin as compared with pylorus-preserving pancreaticoduodenectomy. CONCLUSIONS: Following PD, the postprandial GLP-1 release seems to be enhanced by rapid gastric emptying and to improve insulin sensitivity. Partial gastrectomy versus pylorus preservation enhanced the release of GLP-1, conceivably because of greater distal bowel exposure to undigested nutrients.

Tension-Free Inlay Repair of Large Hiatal Hernias Using Dual-Sided Composite PTFE/ePTFE Meshes in Laparoscopic Surgery for Gastroesophageal Reflux Disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) also frequently suffer from concomitant hiatal hernia. It has been described that a preoperative hiatal hernia of ≥3 cm is associated with a more than threefold relative risk for reflux symptom recurrence after fundoplication without mesh reinforcement. In this report, we describe our experience with the implantation of dual-sided composite PTFE/ePTFE meshes in a tension-free fashion during laparoscopic antireflux surgery (LARS). METHODS: A prospective database containing data of all patients undergoing LARS and hiatal hernia repair with mesh implantation from January 2009 until December 2014 was interrogated. Ten patients with preoperative esophageal high resolution manometry and 24-hour pH impedance monitoring because of symptoms suggestive of GERD who received hiatal repair using dual-sided meshes in inlay technique were identified and included in this analysis. RESULTS: There were no conversions to open surgery in the study group. Median operative time was 138 minutes (interquartile range Q1-Q3: 119-151 minutes) and average length of postoperative stay was 3.5 days (interquartile range Q1-Q3: 2.3-4.0 days). During a median follow-up period of 43.3 months (interquartile range Q1-Q3: 18.9-47.1 months), no redo operations had to be performed. Noteworthy, 2 patients complained about dysphagia (20%) during follow-up, but symptoms resolved after endoscopic interventions. CONCLUSIONS: Tension-free inlay repair of large hiatal hernias using dual-sided composite PTFE/ePTFE meshes during LARS provides promising results. It provides satisfactory symptom relief and prolonged control of GERD. Further studies to validate its efficiency in a larger collective are needed.

**-Postprandial pancreatic [11C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release.

PURPOSE: [S-methyl-11C]-L-methionine ([11C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [11C]MET uptake. METHODS: Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [11C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. RESULTS: The uptake of [11C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC30 correlated with the SUVmax increment between 15 and 30 minutes (R2 = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [11C]MET. Total integrated SUVmax correlated with insulin AUC60 (R2 = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of 11C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R2 = 0.78, p < 0.0001). CONCLUSION: Postprandial [11C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.

Impact of the reconstruction method on delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy: a prospective randomized study.

BACKGROUND: Delayed gastric emptying (DGE) is of considerable concern in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prolonged hospital stay, increased cost, and decreased quality of life add on to interventions needed to treat DGE. This study was conducted to determine if performing duodenojejunostomy via the antecolic rather than the retrocolic route improved incidence of DGE. METHODS: Patients undergoing PPPD between April 2007 and November 2009 were randomized for either antecolic or retrocolic reconstruction of the duodenojejunostomy. DGE was then assessed by clinical criteria on postoperative day (POD) 10. A paracetamol absorption test was also administered with a liquid meal, and serial plasma levels of intestinal peptides were measured. RESULTS: Overall, 64 patients were amenable for analysis: 36 in the antecolic group and 28 in the retrocolic group. The incidences of DGE on POD 10 were 17.6 and 23.1 % (antecolic vs. retrocolic, respectively) (p = 0.628). The two groups did not differ in regard to their median (interquartile range) postoperative hospital length of stay [13.0 (10.0­17.5) vs. 12.5 (11.0­17.0) days; p = 0.446], time to regular diet [5 (5­7) vs. 5 (4­6) days; p = 0.353], or morbidity (52.9 vs. 50.0 %; p = 0.777). The median length of nasogastric tube decompression was similar in the two groups [4 (3­7) vs. 3 (3­5) days; p = 0.600]. Levels of paracetamol and glucagon-like peptide-1 were markedly decreased in patients with DGE. CONCLUSIONS: Antecolic reconstruction after PPPD does not improve the occurrence/the incidence of DGE and is similar to retrocolic reconstruction with regard to secondary outcome parameters.

Distal gastrectomy in pancreaticoduodenectomy is associated with accelerated gastric emptying, enhanced postprandial release of GLP-1, and improved insulin sensitivity.

OBJECTIVE: This study aims to investigate the relationship between gastric emptying, postprandial GLP-1 and insulin sensitivity after pancreaticoduodenectomy (PD). BACKGROUND: Abnormal glucose regulation is highly prevalent in patients with pancreatic neoplasm and resolves in some after PD, the cause of which is unclear. The procedure is carried out with pylorus preservation (PPPD) or with distal gastrectomy (Whipple procedure). Accelerated gastric emptying and ensuing enhanced release of glucagon-like peptide-1 (GLP-1) conceivably play a role in glucose metabolism after PD. It was the purpose of this study to shed light on the relationship between gastric emptying, GLP-1 and glycemic control after PPPD and the Whipple procedure. METHODS: A 75-g oral glucose tolerance test was carried out in 13 patients having undergone PPPD and in 13 after the Whipple procedure, median age 61 (range, 32-70) years, following an interval of 23 (range, 5-199) months. Gastric emptying was measured by the paracetamol absorption method. Plasma concentrations of glucose, insulin, GLP-1 and paracetamol were measured at baseline, 10, 20, 30 60, 90, 120, 150 and 180 min. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) and oral glucose insulin sensitivity were calculated from glucose and insulin concentrations. RESULTS: Patients with Whipple procedure as compared to PPPD had accelerated gastric emptying (p = 0.01) which correlated with early (0-30 min) integrated GLP-1 (AUC30; r (2) = 0.61; p = 0.02) and insulin sensitivity (r (2) = 0.41; p = 0.026) and inversely with HOMA-IR (r (2) = 0.17; p = 0.033). Two of 13 Whipple patients (15 %) as compared to seven of 13 after PPPD (54 %) had postload glucose concentrations (i.e. 120 min postmeal) ≥200 mg/dl (p < 0.05). None of 13 (0 %) after Whipple procedure but four of 13 patients (31 %) after PPPD had fasting glucose concentrations ≥126 mg/dl (p < 0.05) CONCLUSIONS: Gastric emptying was accelerated after Whipple procedure as compared to patients who have undergone PPPD, resulting in higher postprandial GLP-1 concentrations and insulin sensitivity and improved glycemic control.

Hiatal hernia, Barrett's esophagus, and long-term symptom control after laparoscopic fundoplication for gastroesophageal reflux.

BACKGROUND: The aim of this study was to determine the long-term symptom control after laparoscopic fundoplication for gastroesophageal reflux disease (GERD), and possible prognostic factors. METHODS: A cohort of 271 patients, operated on at a university hospital from 1996 through 2002, was eligible for evaluation after a median interval of 102 months (range = 12-158). The time between surgery and recurrence of reflux symptoms (i.e., time to treatment failure) served as the end point for statistical analysis. Putative risk factors for symptom recurrence were analyzed by univariate analysis and by using Cox's multiple-hazards regression. RESULTS: According to Kaplan-Meier estimates, the rate of reflux symptom recurrence was 15 % after 108 months, 11 % in cases without intestinal metaplasia, but 43 % in patients with long-segment (≥ 3 cm) Barrett's esophagus (BE; p < 0.0001). Reflux symptoms recurred in 22 % of cases with a hiatal hernia (HH) ≥ 3 cm before operation, but only in 7 % with smaller or absent HH (p = 0.005). Multivariate analysis revealed a relative risk of 6.6 (CI = 3.0-13.0) for long-segment BE and 3.0 (CI = 1.7-10.1) for HH ≥ 3 cm. A strong statistical interaction was found between HH ≥ 3 cm and long-segment BE: the small group (n = 18) of cases exhibiting both risk factors had an exaggerated recurrence rate of 72 % at 108 months. CONCLUSIONS: Laparoscopic fundoplication for symptomatic GERD provided a long-lasting abolition of reflux symptoms in 231 of 271 (85 %) patients. HH ≥ 3 cm and long-segment BE were shown as independent prognostic factors favoring recurrence.

Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate.

OBJECTIVE: Food intake inhibits bone resorption by a mechanism thought to involve gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose of the study was to investigate patients with short-bowel syndrome (SBS) or total gastrectomy in order to elucidate whether the signal for the meal-induced reduction of bone resorption is initiated from the stomach or the intestine. MATERIAL AND METHODS: Bone resorption was assessed from the serum concentration of collagen type I C-telopeptide cross-links (s-CTX) and compared with the plasma concentrations of GLP-2. Bone formation was assessed from serum osteocalcin concentrations. Seven SBS patients with a preserved colon and 7 with SBS and colectomy and 7 healthy controls were given a breakfast test meal (936 kcal). Eight patients who had undergone total gastrectomy had an oral glucose load (75 g in 150 ml). RESULTS: The SBS patients without a colon showed no reduction in bone resorption (s-CTX) to a meal, whereas SBS patients with a colon had an intermediate response with a 27% (p<0.05) reduction of s-CTX from baseline after 120 min as compared with 66% (p<0.001) for normal controls. A significant reduction of 53% (p<0.001) was seen in gastrectomized patients after receiving oral glucose, which is comparable with the published data for the oral glucose tolerance test (OGGT) in healthy subjects (50% reduction over 120 min). Bone formation was unchanged for both SBS and gastrectomy patients. GLP-2 concentrations increased significantly in all groups with the exception of the SBS plus colectomy group. CONCLUSIONS: An intestinal factor is responsible for the postprandial reduction in bone resorption, and our findings are compatible with such a function for GLP-2.

Management of postoperative esophageal leaks with the Polyflex self-expanding covered plastic stent.

BACKGROUND: Esophageal anastomotic leaks can lead to prolonged hospitalization. In this article we present our experience with the placement of the Polyflex self-expanding plastic stent (Willy Ruesch GMBH, Kernen, Germany) for leak occlusion. METHODS: Between April 2000 and November 2003, 24 patients were included into this prospective study and underwent Polyflex stent placement for postoperative esophageal anastomotic leaks. The primary operation was esophagectomy in 13 patients, gastrectomy in 7, cardia resection in 2, and other procedures in 2 patients. The median interval between operation and stent placement was 19 days (range, 4 to 65). The effectiveness of leak occlusion was evaluated by water-soluble contrast swallow and the clinical course. RESULTS: In 2 patients stent misplacement produced an enlarged anastomotic dehiscence that necessitated reoperation. Radiologic evaluation was impossible in 4 patients because of their generally restricted condition. Among 18 evaluable patients, leak occlusion was successful with a single stent in 16 patients (89%) based on radiologic evaluation. Immediate oral feeding was well tolerated by these patients. After a median follow-up of 220 days (range, 7 to 1221), 9 cases of late stent dislocation were observed. Stent removal in patients after esophagectomy with gastric pull-up led to dysphagia from anastomotic strictures in 2 patients. Symptomatic strictures did not develop in the 5 evaluable postgastrectomy patients after stent removal. CONCLUSIONS: The placement of self-expanding plastic stents is a highly effective treatment for esophageal anastomotic leaks. Because clinically-relevant anastomotic strictures can be expected, we do not recommend stent removal after esophagectomy with gastric pull-up reconstruction.