Surgical therapy for hepatopancreaticobiliary disease has a rich history with meteoric advances occurring over the last century. Perhaps surprisingly, it was not until 1848, and the description of pancreatic lipase by French physiologist Claude Bernard, that the exocrine function of the pancreas was recognized.1 In 1899, William Stewart Halsted first successfully resected the head of the pancreas along with the duodenum for ampullary cancer. This evolved into the one-stage pancreaticoduodenectomy described by Allen Oldfather Whipple in 1940.2 Puestow and Gillesby introduced the lateral pancreaticojejunostomy for the management of chronic pancreatitis in 1958, and Frey and Child introduced the 95% distal pancreatectomy in 1965. Carl Langenbuch performed the first successful cholecystectomy in 1882, and the first elective hepatic resection for tumor in 1888.3 The modern era of hepatic resection was brought about in 1952 when Lortat-Jacob and Robert performed the first true anatomic liver resection with primary vascular control.4
Advances in technology over the next few decades were crucial in the evolution of hepatopancreaticobiliary surgery. The first laparoscopic cholecystectomy was performed by Mouret in 1987 and more widely described by Dubois in 1988.5 Andrew Warshaw described the utility of laparoscopy in the diagnosis and staging of pancreatic cancer. The first endoscopic papillotomy for calculi removal was performed by Safrany in 1980, and this evolved into endoscopic retrograde cholangiopancreatography (ERCP), a crucial adjunct for management of biliary disease.6 The development of new surgical instruments such as the harmonic scalpel and LigaSure vessel-sealing system made liver resections more expeditious and decreased transfusion requirements.
With improved surgical technique, the indications for pancreaticobiliary surgery have also expanded. Surgical resection of pancreatic cancer can now include portomesenteric venous resection if arterial inflow can be preserved.7 Techniques for resection have also been refined and optimized. Pylorus-preserving pancreatoduodenectomy, for example, is equally effective from an oncologic perspective when compared to the standard Whipple procedure, with similar recovery and complication profiles.8 The DISPACT trial examined stapled and hand-sewn closure for distal pancreatectomy and showed no difference in subsequent pancreatic fistula formation.9 This chapter will also discuss nonoperative advancements in the field, including the utility of prophylactic octreotide to reduce pancreatic fistulas,10,11 and new chemotherapeutic regimens for metastatic pancreatic cancer.12 In addition to cancer, this chapter will also discuss the management of benign pancreatic disease, including pancreatic cysts13 and severe pancreatitis.14,15,16
Despite advancements in management, pancreatic cancer remains a leading cause in cancer-related death, and pancreatic resection is still associated with significant complications.1 The development of risk assessment tools and consensus statements has helped guide decision making and improve outcomes.17 International study groups have also reached consensus on the definition of several of the more common postoperative complications. This consensus is essential for future research, as it enables accurate comparisons between trials. Pancreatic fistula is now defined as a drain output of any measurable volume of fluid over postoperative day 3, with amylase content greater than 3 times the serum amylase activity.18 Delayed gastric emptying is defined as the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation.19
Advances continue in the realm of liver surgery as well. Hepatocellular carcinoma (HCC) is effectively treated with major hepatectomy.20 For the treatment of centrally located tumors, postresection adjuvant radiation therapy is feasible and safe, but has no survival benefit versus surgery alone.21 For patients with advanced HCC and no feasible surgical treatment option, sorafenib prolongs survival and time to progression.22 We will also discuss the surgical management of colorectal cancer liver metastases, and the potential benefit of neoadjuvant chemotherapy.23 Finally, we will review the new technique of associating liver partition and portal vein ligation for staged hepatectomy, which, although feasible in initial trials, still lacks outcome and safety data.24
The low number of randomized controlled trials limits further advancements in the treatment of hepatopancreatobiliary disease. Many prior efforts at trial development have been thwarted by poor accrual, due in part to the relative rarity of the diseases. Some progress has been made in this area with the more recent multi-institution and international collaborative efforts. In addition, the recent advent of the HPB-NSQIP and Pancreatectomy Project allows for more widespread and standardized data acquisition.25
Since its inception, hepatopancreaticobiliary surgery has become more widely practiced, although no less challenging. In 1978 Sir Andrew Watt Kay famously wrote “For me, the tiger country is removal of the pancreas. The anatomy is very complex and one encounters abnormalities.”26 Surgeons play a key role in the management of both benign and malignant hepatopancreaticobiliary diseases, and a thorough understanding of the anatomy, physiology, and ever-evolving treatment options is crucial.
Does prophylactic octreotide decrease the rate of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial.
Yeo CJ, Cameron JL, Lillemoe KD, Sauter PK, Coleman J, Sohn TA, Campbell KA, Choti MA
Ann Surg. 2000;232(3):419–429.Takeaway Point: Prophylactic octreotide does not decrease rates of pancreatic fistula, postoperative complications, or mortality in patients undergoing pancreaticoduodenectomy (PD).
Commentary: This was a well-designed prospective, randomized, double-blinded trial that sought to clarify conflicting data from previous studies regarding the role of prophylactic octreotide therapy for preventing complications, specifically pancreatic fistula, in patients undergoing PD. Whereas other studies demonstrating a benefit to prophylactic octreotide included patients undergoing other types of pancreatic resection as well, this study solely included patients undergoing PD and clearly demonstrated that octreotide does not reduce overall complications, fistula formation, death, or hospital stay. Interestingly, those patients on octreotide therapy who did develop a fistula had longer hospital stays than those who developed a fistula with placebo therapy. The implication of this finding in a small patient group is not clear, and the trial was not powered for subgroup analyses. The study also specifically looked at patients considered at high risk of fistula formation secondary to a soft pancreas texture and did not show a benefit in those patients, either. The additional cost of octreotide in the prophylactic setting cannot be justified and should be eliminated from practice in patients undergoing PD. This study confirmed the findings of the study published 3 years earlier by Lowy et al, which also showed that routine use of perioperative octreotide in patients undergoing PD was not effective in decreasing the incidence of pancreatic fistula or any other complication.11
Introduction: Four previous randomized trials demonstrated the utility of prophylactic octreotide in reducing pancreatic fistula and overall complications rates in patients undergoing pancreatic resection. However, a fifth trial examining only patients undergoing PD showed no benefit.
Objectives: To evaluate the role of prophylactic octreotide in reducing pancreatic fistula, overall complications, and death in patients undergoing PD.
Trial Design: Double-blinded, randomized controlled trial.
Inclusion Criteria: All patients with anticipated elective PD.
Exclusion Criteria: After randomization patients who did not undergo PD or did not receive at least a 5-day course of the study drug were excluded from the outcome analysis.
Intervention: Patients received either 250 μg octreotide or saline placebo preoperatively and then every 8 hours after surgery for 7 days, for a total of 22 doses. Postoperative drains were left in place until at least postoperative day 4. Amylase levels were checked on days 3 and 7 and if no fistula was demonstrated, drains were removed.
Primary Endpoint: Pancreatic fistula, overall postoperative complications, and death.
Secondary Endpoint: Cost analysis.
Sample Size: 383 patients were enrolled between February 1998 and February 2000 at a single institution. 383 were randomized and 211 were analyzed for outcome analyses, with 107 in the control group and 104 in the octreotide group.
Statistical Analysis: Student t-test and χ2 statistics for univariate comparisons, with multivariate stepwise regression of the variables found to be significant on univariate analysis. Sample size calculations predicted 129 patients per arm were needed to demonstrate 10% decrease in fistula rate.
Baseline Data: There was no difference between the two groups in terms of gender, race, preoperative factors, intraoperative factors, or pathologic findings.
Outcomes: The most common complications in both groups were pancreatic fistula, wound infection, and early delayed gastric emptying. The complications rates were not significantly different between the two groups, nor were the lengths of hospital stay or mortality. Complications including fistula formation were stratified by surgeon-described pancreatic texture. Complications were more frequent with a soft texture, but octreotide had no effect on the rate in any group. The total cost of octreotide was $61 per dose and $1408 per patient for the course administered in this study.
Conclusion: Prophylactic octreotide does not decrease the rate of postoperative pancreatic fistula, hospital length of stay, or death overall for all patients or for those considered high risk due to soft pancreatic texture. Eliminating the use of prophylactic octreotide would result in a cost savings of $1408 per patient.
Limitations: A higher dose of octreotide was used in this study (250 μg) than was reported in any of the previous studies (100 or 150 μg). Patients undergoing pancreatic resections other than PD were not examined in this study as they were in previous European trials. The trial was terminated early because of lack of demonstrated benefit, and was not powered for the subgroup analyses they report.
Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: A prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors.
Tran KT, Smeenk HG, van Eijck CH, Kazemier G, Hop WC, Greve JW, Terpstra OT, Zijlstra JA, Klinkert P, Jeekel H
Ann Surg. 2004;240(5):738–745.Takeaway Point: The standard Whipple procedure (SW) and pylorus-preserving pancreaticoduodenectomy (PPPD) are equally effective for the treatment of pancreatic and periampullary carcinoma.
Commentary: This study compares PPPD with SW for clinical and oncologic outcomes. The authors hypothesized that PPPD would be associated with reduced operative times, lower blood loss, shorter hospital stays, and more physiologic food passage. On analysis, the two procedures were not statistically different by any measure, including perioperative data, postoperative complications, resection margins, or overall and disease-free survival. The trial demonstrated the acceptability of either approach for the treatment of periampullary and pancreatic cancer. It is worthwhile to note that the debate between PPPD or SW remains contentious, with different studies having conflicting results. Furthermore, many studies on this question use delayed gastric emptying as the primary outcome measure rather than estimated blood loss (EBL), operative time, and length of stay, perhaps explaining the conflicting conclusions. Additionally, adjuvant therapy protocols for pancreatic cancer in the Netherlands (where this trial was performed) typically consist of chemotherapy only, rather than the chemoradiation that would be used in the United States, and the patients in this trial received no adjuvant therapy. This may limit generalizability of the results. Finally, the average blood loss in this single-center trial was much greater than that observed in prior studies, raising the possibility that center-specific techniques might impact the primary outcomes of EBL and operative time. These and other limitations emphasize the still unsettled nature of the controversy regarding PPPD versus SW.
Introduction: The PPPD, a modification to the classic Whipple operation, was initially described in 1944 and reintroduced in the 1970s. Some potential benefits include improvement in postoperative gastrointestinal function, shorter operative times, and less intraoperative blood loss; however, some studies have also reported a higher incidence of complications and concern about resection margins.
Objectives: “To evaluate whether PPPD has an advantage over the standard Whipple (SW) procedure.”
Trial Design: Prospective randomized controlled trial.
Inclusion Criteria: Suspected pancreatic or periampullary cancer determined to be resectable based on preoperative imaging (CT and/or MRI).
Exclusion Criteria: Previous gastric resection, distant metastasis, positive peripyloric lymph nodes, or local unresectability were excluded from the analysis for efficacy. Patients with lesions other than pancreatic or periampullary adenocarcinoma were excluded from the survival analysis.
Intervention: Patients were randomized to undergo either PPPD or SW. Follow-up evaluations were conducted every 3 months.
Primary Endpoints: Operative time, blood loss, duration of hospital stay.
Secondary Endpoints: Delayed gastric emptying, disease-free and overall survival rates.
Sample Size: 170 patients from seven Dutch hospitals enrolled between 1992 and 2000; 87 patients were randomized to PPPD and 83 to SW.
Statistical Analysis: Survival was calculated from the date of surgery using the Kaplan–Meier method and compared with the log-rank test. Percentages were compared between groups using the Fisher exact test or the χ2 test, and other data were compared using the Mann–Whitney U-test. Sample size calculations estimated 65 patients per arm to demonstrate a 30% reduction in blood loss and 20% reduction in operative time.
Baseline Data: Treatment groups were similar in terms of patient characteristics and pathologic diagnoses.
Outcomes: Follow-up was up to 115 months, median 18.5 months, range 1–115 months. There was no statistically significant difference in procedure-related outcomes or postoperative complications including blood loss, hospital stay, incidence of delayed gastric emptying (DGE), margin positivity, or mortality. Differences in the median disease-free survival (49 months in SW group and 23 months in PPPD group, p 0.60) and overall survival rates (17 months in SW group and 29 months in PPPD group, p 0.50) were not statistically significant.
Conclusion: The two operations are comparable with respect to short-term recovery and complications, as well as long-term and disease-free survival.
Limitations: Both small- and large-volume centers were included. No adjuvant chemotherapy or radiotherapy was provided to the patients.
Sorafenib in advanced hepatocellular carcinoma.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, de Oliveira AC, Santoro A, Raoul J-L, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz J-F, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, for the SHARP Investigators Study Group
NEJM. 2008;359(4):378–390.Takeaway Point: Sorefenib prolongs survival and time to progression by nearly 3 months in patients with advanced HCC.
Commentary: This important study was the first to demonstrate a survival benefit from treatment with a systemic therapy for locally advanced HCC. Sorafenib was well tolerated and improved survival and time to progression by nearly 3 months, and is now considered first line treatment in patients with HCC who are not candidates for surgical resection. This is a promising treatment, and its utility in the adjuvant setting should be explored as well.
Introduction: HCC remains a major world health problem, and when surgical resection is not an option, prognosis is dismal. No systemic therapy to date has demonstrated improved survival in patients with advanced HCC. An uncontrolled phase 2 study of sorafenib, a small-molecule inhibitor that inhibits tumor cell proliferation, showed a beneficial effect in extending survival and time to progression.
Objectives: To assess the efficacy and safety of sorafenib in patients with advanced HCC.
Trial Design: A multicenter, phase 3, double-blind, placebo-controlled trial.
Inclusion Criteria: Patients with pathology-proven advanced-stage HCC who had not received previous systemic therapy; Eastern Cooperative Oncology Group (ECOG) score of ≤2; Child–Pugh class A; life expectancy of ≥12 weeks; adequate hematologic, renal, and liver function; and at least one untreated target lesion.
Exclusion Criteria: Patients who had previously received molecular target therapies or other systemic treatment.
Intervention: Randomization to either sorafenib (400 mg twice daily) or placebo. Randomization was stratified by region, ECOG status, and presence of macrovascular invasion. Treatment was continued until radiologic progression, unacceptable adverse events, or death.
Primary Endpoint: Overall survival and time to symptomatic progression.
Secondary Endpoints: Time to radiologic progression, disease control rate, and safety.
Sample Size: 121 centers in 21 countries; 602 patients randomized from March 2005 to April 2006, with 299 to sorafenib and 303 to placebo.
Statistical Analysis: A Cox proportional-hazards model for overall survival. A stratified log-rank test was used for analysis of radiologic progression, disease control rates using the Cochran–Mantel–Haenszel test. Adverse events were compared with Fisher’s exact test.
Baseline Data: There were no relevant differences between the two groups in terms of demographics, cause of liver disease, previous therapy, prognostic indicators, or tumor stage.
Outcomes: Overall median survival was significantly longer in the sorafenib group (10.7 vs. 7.9 months, hazard ratio 0.69, 95% CI 0.55–0.87, p <0.001), and at one year there was a 31% relative reduction in the risk of death. After adjustment for other prognostic indicators, the effect of sorafenib on overall survival remained significant (hazard ratio 0.73, 95% CI, 0.58–0.92, p 0.004). The median time to progression was significantly longer in the sorafenib group than in the placebo group (5.5 vs. 2.8 months, hazard ratio 0.58, 95% CI, 0.45–0.74, p <0.001). The overall incidence of treatment-related adverse events was 80% and in the sorafenib group consisted mainly of grade 1 or 2 gastrointestinal, constitutional, and dermatologic side effects. The study was stopped at the second planned interim analysis because of the significant reduction in risk of death in the sorafenib group.
Conclusion: In patients with advanced HCC, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
Limitations: Quality of life was not well assessed. Symptomatic progression was evaluated using a self-reported functional health status questionnaire, which may have been influenced by the adverse effects of the drug, tumor-related symptoms, and symptoms attributable to liver failure, which persisted regardless of whether the tumor responded to therapy.
Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: A prospective multicenter study.
van Santvoort HC, Besselink MG, de Vries AC, Boermeester MA, Fischer K, Bollen TL, Cirkel GA, Schaapherder AF, Nieuwenhuijs VB, van Goor H, Dejong CH, van Eijck CH, Witteman BJ, Weusten BL, van Laarhoven CJ, Wahab PJ, Tan AC, Schwartz MP, van der Harst E, Cuesta MA, Siersema PD, Gooszen HG, van Erpecum KJ, Dutch Acute Pancreatitis Study Group
Ann Surg. 2009;250(1):68–75.Takeaway Point: Early endoscopic retrograde cholangiopancreatography (ERCP) reduces complications in patients with acute biliary pancreatitis (ABP) and concurrent cholestasis [defined as total bilirubin > 2.3 and/or dilated common bile duct (CBD), without fever].
Commentary: This study examined a subset of patients that were enrolled in the Probiotics in Pancreatitis Trial (PROPATRIA) from the Dutch Acute Pancreatitis Study Group. That trial enrolled adult patients presenting with their first episode of predicted severe acute pancreatitis of all causes. This study looked specifically at patients with ABP, excluding those with concurrent cholangitis, to determine whether early ERCP is also beneficial for patients without cholangitis. When compared to conservative management, early ERCP in patients with ABP with cholestasis reduces complications overall and reduces serious complications such as substantial pancreatic necrosis, and should be recommended in this subset. The same benefit was not seen in patients with ABP in the absence of cholestasis, for whom conservative management and early ERCP yielded similar clinical outcomes.
Introduction: Gallstones are the most common etiology of acute pancreatitis in the western world. Severe complications occur in 20% of patients with ABP, with a subsequent 30% mortality. Previous studies have concluded that early ERCP is indicated for patients with ABP and cholangitis; however, the role of early ERCP for patients with predicted severe ABP without cholangitis remains unclear.
Objectives: To determine whether early ERCP, as compared to conservative treatment, reduces the risk of complications and mortality for patients with predicted severe ABP without cholangitis.
Trial Design: A prospective, observational, multicenter study of a subset of patients from a larger cohort enrolled in the Probiotics in Pancreatitis Trial (PROPATRIA).
Inclusion Criteria: Adult patients with primary episode of severe acute pancreatitis who developed ABP [defined as gallstones and/or sludge, or dilated CBD, or two of the following laboratory abnormalities: serum bilirubin >1.3 mg/dL; alanine transaminase (ALT) >100 U/L and greater than aspartate aminotransferase (AST); or alkaline phosphatase >195 U/L with γ-glutamyltransferase (GGT) >45 U/L].
Exclusion Criteria: Chronic pancreatitis and potential cholangitis.
Intervention: Patients were stratified as having potential cholangitis (bilirubin >1.2 mg/dL and/or dilated CBD and fever), cholestasis (bilirubin >2.3 mg/dL and/or dilated CBD and afebrile), or neither cholestasis nor potential cholangitis. The decision to perform ERCP was left to the treating physician. Patients who underwent ERCP within 72 hours were considered in the early ERCP group and those that did not constituted the conservative treatment group. Patients with potential cholangitis were excluded from the analysis.
Primary Endpoint: Mortality and overall complications during admission and during 90-day follow-up.
Secondary Endpoints: CT severity index, the need for percutaneous drainage or operative intervention for infected necrosis, hospital stay, and ICU stay.
Sample Size: Of the 296 patients from 15 Dutch hospitals enrolled on the PROPATRIA trial between March 2004 and March 2007, this trial included 153 patients, 81 who underwent early ERCP and 72 who were treated conservatively.
Statistical Analysis: Continuous data by Student’s t-test or Mann–Whitney U-test. Proportions were compared by the Fisher exact test. Multivariate logistic regression to adjust for cofounders.
Baseline Data: For patients with cholestasis, the APACHE II score on admission was slightly higher in the conservative treatment group (p 0.064). For patients without cholestasis, the ASA class was significantly higher in the conservative treatment group (p 0.016).
Outcomes: For patients with cholestasis, 67% underwent early ERCP and had significantly fewer overall complications (25% vs. 54%, p 0.02) and fewer substantial complications, including >30% pancreatic necrosis (8% vs. 31%, p 0.01). On multivariate analysis early ERCP remained associated with a lower risk of overall complications (OR 0.35; 95% CI; 0.13–0.99, p 0.049). Mortality was not significantly different. For patients without cholestasis, 39% underwent early ERCP and no benefit was demonstrated when compared to conservative treatment. Differences in secondary endpoints were not demonstrated in either group.
Conclusion: Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.
Limitations: This study was not randomized, and there was variation in indication for ERCP amongst the different centers.
A step-up approach or open necrosectomy for necrotizing pancreatitis.
van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG, Dutch Pancreatitis Study Group
NEJM. 2010;362(16):1491–1502.Takeaway Point: For patients with necrotizing pancreatitis and secondary infection, a step-up approach reduces both short- and long-term complications as well as overall healthcare costs when compared to upfront open necrosectomy.
Commentary: The trial compared two treatment approaches for necrotizing pancreatitis: primary open necrosectomy, and a step-up approach of initial percutaneous or endoscopic drainage with subsequent additional drainage or necrosectomy if needed. The aims of these approaches differed; the goal of open necrosectomy is complete debridement of necrotic tissue, whereas the step-up approach aims to control the source of infection. Although some patients in the step-up approach ultimately required necrosectomy, 40% avoided an open operation and were sufficiently treated with less invasive procedures. Major short- and long-term complications and healthcare costs were reduced in the step-up approach group. This trial supports the step-up approach as the standard of care for necrotizing pancreatitis; however, several subsequent letters to the editor and an editorial by Dr. Andrew Warshaw expressed concern over the high mortality rates that did not differ between groups, as well as the limited applicability of the step-up approach as it mandates a retroperitoneal access route, and cautioned against using this approach as a default therapy for all necrotizing pancreatitis patients.27,28,29
Introduction: Necrotizing pancreatitis has traditionally been treated with open necrosectomy to remove infected necrotic tissue, an operation with high morbidity and mortality. Less invasive approaches, including percutaneous and endoscopic drainage and minimally invasive necrosectomy, have been explored, and can be performed in a so-called step-up approach with subsequent open necrosectomy if needed.
Objectives: To compare open necrosectomy to a minimally invasive step-up approach for the treatment of necrotizing pancreatitis.
Trial Design: A multicenter, randomized controlled trial.
Inclusion Criteria: Adults with acute pancreatitis and signs of pancreatic or peripancreatic necrosis.
Exclusion Criteria: Patients with chronic pancreatitis, previous exploratory laparotomy during the current episode of pancreatitis, previous surgery for pancreatic necrosis, or pancreatitis secondary to abdominal surgery or an acute intraabdominal event.
Intervention: Patients were randomly assigned to either primary open necrosectomy or the minimally invasive step-up approach. Randomization occurred once a decision to perform a surgical intervention had been made, and if percutaneous or endoscopic drainage of the fluid collection was deemed possible.
Primary Endpoint: Composite of major complication or death during admission or within 3 months of discharge.
Secondary Endpoints: Individual components of the primary endpoint, other complications, healthcare resource utilization, and total medical costs.
Sample Size: 88 patients were randomized from 19 Dutch hospitals between November 2005 and October 2008; 45 to open necrosectomy and 43 to step-up approach.
Statistical Analysis: Occurrences of endpoints were compared between treatment groups, and results are presented as risk ratios with 95% confidence intervals. Differences in other outcomes were assessed with the use of the Mann–Whitney U-test. Power analysis estimated 88 patients needed to detect a 64% relative reduction in the composite primary endpoint. Intention-to-treat analysis.
Baseline Data: Baseline characteristics of the treatment groups were similar.
Outcomes: In the primary necrosectomy group, patients underwent a median of one necrosectomy with 42% requiring at least one additional operation and 33% requiring additional percutaneous drainage after laparotomy. In the step-up group, 44% of patients required a second drainage procedure and 60% ultimately underwent necrosectomy, with 33% requiring one or more additional operations and 27% undergoing subsequent percutaneous drainage after laparotomy. The composite primary endpoint of major complications or death occurred in 69% of the necrosectomy group and 40% of the step-up approach group (RR 0.57, 95% CI 0.38–0.87, p 0.006). Mortality was not significantly different between the two groups. After 6 months, patients in the necrosectomy group had significantly more incisional hernias (7% vs. 24%, p 0.03), new-onset diabetes (16% vs. 38%, p 0.02), and pancreatic enzyme requirement (16% vs. 38%, p 0.02). Utilization of healthcare resources was lower for the step-up group (p 0.004) and at 6-month follow-up the step-up approach had reduced costs by 12%.
Conclusion: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end points of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue.
Limitations: The study was not designed or powered to demonstrate a difference in death rate alone. Initial power analysis assumed a very large relative reduction in primary endpoint.
International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.
Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K, International Association of Pancreatology
Pancreatology. 2012;12(3):183–197.Takeaway Point: In the absence of randomized controlled trials and high-grade evidence, these consensus guidelines offer the best recommendations for the management of intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) of the pancreas.
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