Background Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic ...injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). Methods This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Results Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0–10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients ( P < .004). Conclusion Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government–sponsored, multicenter, randomized controlled PREBOT trial.
Background Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present ...systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas. Methods A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals. Results A total of 4,148 citations were retrieved initially; available data of 29 observational studies (3,701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited. Conclusion Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more nonrandomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined end points, and cost-effectiveness.
Background Delayed gastric emptying (DGE) is one of the most common complications after pancreatic resection. In the literature, the reported incidence of DGE after pancreatic surgery varies ...considerably between different surgical centers, primarily because an internationally accepted consensus definition of DGE is not available. Several surgical centers use a different definition of DGE. Hence, a valid comparison of different study reports and operative techniques is not possible. Methods After a literature review on DGE after pancreatic resection, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition with grades of DGE based primarily on severity and clinical impact. Results DGE represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management. Conclusion The proposed definition, which includes a clinical grading of DGE, should allow objective and accurate comparison of the results of future clinical trials and will facilitate the objective evaluation of novel interventions and surgical modalities in the field of pancreatic surgery.
Background Postoperative hemorrhage is one of the most severe complications after pancreatic surgery. Due to the lack of an internationally accepted, universal definition of postpancreatectomy ...hemorrhage (PPH), the incidences reported in the literature vary considerably, even in reports from randomized controlled trials. Because of these variations in the definition of what constitutes a PPH, the incidences of its occurrence are not comparable. Methods The International Study Group of Pancreatic Surgery (ISGPS) developed an objective, generally applicable definition of PPH based on a literature review and consensus clinical experience. Results Postpancreatectomy hemorrhage is defined by 3 parameters: onset, location, and severity. The onset is either early (≤24 hours after the end of the index operation) or late (>24 hours). The location is either intraluminal or extraluminal. The severity of bleeding may be either mild or severe. Three different grades of PPH (grades A, B, and C) are defined according to the time of onset, site of bleeding, severity, and clinical impact. Conclusions An objective, universally accepted definition and clinical grading of PPH is important for the appropriate management and use of interventions in PPH. Such a definition also would allow comparisons of results from future clinical trials. Such standardized definitions are necessary to compare, in a nonpartisan manner, the outcomes of studies and the evaluation of novel operative treatment modalities in pancreatic surgery.
Background Postoperative pancreatic fistula (POPF) is the most important complication after pancreatic surgery. In 2005, the International Study Group of Pancreatic Surgery (ISGPS) introduced a ...standardized POPF definition with severity grading from A to C. In recent years, interventional drainage (ID) has become the standard of care for symptomatic postoperative fluid collections or undrained POPF. From the original definition, it is unclear whether ID is categorized as POPF grade B or C. Therefore, international authors shift ID between grades B and C. The aim of the study was to analyze patients with ID (proposed new grade B) versus patients who underwent reoperation (grade C) for POPF. Methods Between 2005 and 2013, all patients undergoing pancreatic resection were analyzed regarding POPF grade A-C. Demographic data, type of operation, postoperative complications, therapies and outcome were examined with focus on ID versus reoperation. Results Of the 2,955 patients included, 403 developed POPF (13.6%). Among all POPF, 11% were grade A, 17% grade B (clinically symptomatic without ID), and 72% grade C. These patients underwent either ID ( n = 165) or reoperation ( n = 123). Patients with ID had an average hospital stay of 33 days and POPF-associated mortality of 0%. This was strikingly different from patients undergoing reoperation with a hospital stay of 47 days and POPF-associated mortality of 37% ( P < .0001). Conclusion After 10 years of the ISGPS classification, there is a clear-cut outcome difference between patients undergoing POPF-associated ID or reoperation. We propose assigning all patients undergoing ID as POPF grade B. Patients undergoing reoperation should definitely remain within category C.
Background Because of the lack of standardized definitions of complications in gastrointestinal operations, consensus definitions have been developed in recent years. The aim of the current study was ...to systematically review the available consensus definitions and to report their use, acceptance, and results. Methods A systematic search of the literature was conducted of the Medline, Cochrane, and ISI Web of Science databases. All articles published until August 2011 and that applied the identified consensus definitions were considered. Inclusion criteria for quantitative analysis were studies with correct usage of the definition and 100 or more patients who were treated after the year 2000. Results Seven consensus definitions were identified: postoperative pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, posthepatectomy liver failure, bile leakage after hepatobiliary and pancreatic surgery, posthepatectomy hemorrhage, and anastomotic leakage after anterior resection of the rectum. Of 1,637 articles retrieved from the literature search, 59 articles that correctly applied the definitions met the inclusion criteria. Subanalyses were feasible for definitions after pancreatic surgery. According to the consensus definitions, the median complication rates of retrospective studies were 21.9% (postoperative pancreatic fistula, n = 11,244 patients), 5.9% (postpancreatectomy hemorrhage, n = 3,311 patients), and 22.8% (delayed gastric emptying, n = 4,553 patients) after pancreatic resections. The incidences were not substantially different in prospective trials. Validation was performed for all three definitions, demonstrating that the severity grades significantly correlated with the clinical course of the patients. Conclusion The available consensus definitions were increasingly cited and facilitate scientific comparability and transparency if appropriately applied. The present data update the incidences of major pancreatic complications.
Background The International Study Group of Rectal Cancer (ISREC) has proposed a generally applicable definition and severity grading of (AL) after sphincter-preserving resection of the rectum. This ...work has been carried out to test for validity. Methods A total of 746 patients who were identified from a prospective rectal cancer database underwent sphincter-preserving anterior resection of the rectum between October 2001 and January 2011. The incidence and severity of AL was determined using the criteria established by the ISREC. Patients with AL were categorized according to the ISREC scheme. The clinical outcomes were analyzed and compared between the groups. Results The overall AL rate was 7.5% (56/746). The 56 patients with AL were distributed among the different groups as follows: Grade A, 16%; grade B, 23%; and grade C, 61%. Compared with the grade A patients, grades B and C patients had significantly elevated serum C-reactive protein levels ( P < .01). None of the grade A patients were transferred to the intensive care unit (ICU). Their further hospital stay was uneventful. The length of stay in the ICU was significantly longer for grade C patients compared with grade B patients ( P < .001). The median hospital stay of grade C patients was significantly longer than that of grades A and B patients ( P < .001). Conclusion The definition and severity grading of AL after anterior resection of the rectum proposed by the ISREC provides a simple, easily applicable, and valid classification. Using this classification system may facilitate comparison of results from different studies on AL after sphincter-preserving rectal surgery.
Background For pancreatic cancer, complete macroscopic resection in combination with chemotherapy is the only potentially curative treatment. Many patients present with locally advanced cancers ...deemed unresectable. We sought to assess the results of exploration after neoadjuvant therapy for locally advanced possibly unresectable pancreatic cancer. Methods From a prospective database, all consecutive patients undergoing operation from October 2001 to December 2009 after neoadjuvant therapy for locally advanced pancreatic cancer were identified. Main criteria for “unresectability” were infiltration of the celiac axis or superior mesenteric artery. Resection rates, perioperative results, and survival were analyzed. Results Of 257 patients, 199 (77.4%) had received neoadjuvant chemoradiation, and 58 (22.6%) chemotherapy only. Of 257 patients, 120 (46.7%) underwent successful resection, whereas 137 patients underwent exploration only; 47 (39.2%) multivisceral and 45 (37.5%) vascular resections (12 arterial reconstructions) were performed. There were 6 (5%) ypT0 neoplasms, 36 (30.0%) R0, 61 (50.8%) R1, and 16 (13.3%) R2 resections. The median follow-up of surviving patients ( n = 22) was 22 months. Median postoperative survival was greater after resection (12.7 months) than after exploration alone (8.8 months; P < .0001). Median postoperative survival was 24.6 months after R0, 11.9 months after R1, and 8.9 months after R2 resection. The 3-year survival rate after R0 resection was 24%. To determine survival after start of neoadjuvant therapy, 3.7 months (median) have to be added. Conclusion In locally advanced, unresectable pancreatic cancer, R0/R1 resections can be achieved in up to 40% of patients who undergo operation after neoadjuvant therapy. In these cases, survival rates are similar to those observed for initially resectable pancreatic cancer.
Background Small, asymptomatic, branch-duct intraductal papillary mucinous neoplasms of the pancreas are often kept under surveillance despite their malignant potential. The management of branch-duct ...intraductal papillary mucinous neoplasm is controversial with regard to indications and extent of any operative intervention. The present study aimed to evaluate enucleation as an alternative operative approach for branch-duct intraductal papillary mucinous neoplasms to exclude and prevent malignancy. Methods For branch-duct intraductal papillary mucinous neoplasms of <30 mm in diameter and an acceptable distance from the main pancreatic duct, enucleation was considered as the operative approach of choice. All patients scheduled for enucleation of branch-duct intraductal papillary mucinous neoplasm on the basis of these features between January 2004 and September 2014 were analyzed. Among these, patients with successful enucleation were compared with those who were scheduled for enucleation but converted intraoperatively to pancreatic resection (intention-to-treat analysis). End points were hospital morbidity and mortality as well as histopathology and functional outcome at a mean follow-up of 32 months. Results In the study, 115 patients with presumed branch-duct intraductal papillary mucinous neoplasm and the intention to perform pancreatic enucleation were included; 87 enucleations were performed in 74 patients. In 41 patients, enucleation was converted to a pancreatic resection (procedure-specific success rate 64%); indications for conversion included location or size (46%), presence of multicystic lesions (39%), or involvement of the main pancreatic duct (15%). Of the 74 patients with enucleation, 64 branch-duct intraductal papillary mucinous neoplasms revealed low- (85%), 11% moderate dysplasia-, and 4% high-grade dysplasia on histology. Among converted resections, 6 intraductal papillary mucinous neoplasms revealed high-grade dysplasia or invasive carcinoma (15%). Intention-to-treat analysis with patients converted to pancreatic resection showed that enucleations resulted in less blood loss (100 vs 400 mL) and a shorter operation time (146 vs 255 minutes; P < .001 each). Postoperative morbidity including postoperative pancreatic fistula was similar in both groups. No mortality occurred after enucleation; after formal resection, 1 patient died due to multiorgan failure. Both hospital stay (10 vs 14 days) and rates of postoperative endocrine and exocrine dysfunction rates were less after enucleation ( P < .02 each). Intraductal papillary mucinous neoplasm-specific recurrence rates (3% vs 6%) were similar in both groups. Conclusion Enucleation is a safe procedure that can be performed successfully in a high proportion of branch-duct intraductal papillary mucinous neoplasms and should be considered instead of standard resections as an important function-preserving alternative. Limitations may occur due to malignancy, size, localization, multilocularity, or main-duct involvement requiring conversion to a formal, anatomic resection. Beside the advantages in the short-term course, functional outcome seems to be superior after enucleation, and intraductal papillary mucinous neoplasm-specific recurrence rates are not increased compared with standard resections, at least at a mean follow-up of 32 months.
Objective A prospective, randomized study was performed to evaluate two variations of the duodenum-preserving pancreatic head resection (DPPHR), either with (Beger procedure) or without (Berne ...modification) the division of the pancreas anterior to the portal vein, in patients with chronic pancreatitis. Methods Randomized, controlled, patient-blinded trial of patients with inflammatory pancreatic head tumors. The primary endpoint was the duration of surgery. Other a priori-ordered endpoints were length of ICU stay, postoperative complication, length of hospital stay, and quality of life after 24 months. Results Sixty-five patients were randomized to the Berne or Beger procedures. The Berne modification could be performed faster (46 minutes difference, P < .05). The median length of stay on the ICU was one day in both groups ( P = .97) but the median hospital stay was shorter in the Berne group (11 (8–39) versus 15 (8–47); P = .015). The quality of life two years after surgery did not differ significantly between the two groups (EORTC-QLQ-C30, Beger 65.6% vs. Berne 71.3%, P = .371). Three patients who had received the Berne procedure were reoperated on during the follow-up period due to ongoing pancreatitis and bile duct obstruction ( P = .22). Conclusion The Berne technique is technically simpler compared with the original Beger procedure, reflected in its significantly shorter operation times and hospital stays. The quality of life is similar after both procedures. The Berne modification of DPPHR adds to our panel of surgical procedures that can be applied with effective early and late outcomes.
