Biliary Stenosis and Gastric Outlet Obstruction: Late Complications After Acute Pancreatitis With Pancreatic Duct Disruption.

OBJECTIVES: Pancreatic duct disruption (PDD) after acute pancreatitis can cause pancreatic collections in the early phase and biliary stenosis (BS) or gastric outlet obstruction (GOO) in the late phase. We aimed to document those late complications after moderate or severe acute pancreatitis. METHODS: Between September 2010 and August 2014, 141 patients showed pancreatic collections on computed tomography. Percutaneous drainage was primarily performed for patients with signs or symptoms of uncontrolled pancreatic juice leakage. Pancreatic duct disruption was defined as persistent amylase-rich drain fluid or a pancreatic duct cut-off on imaging. Clinical course of the patients who developed BS or GOO was investigated. RESULTS: Among the 141 patients with collections, 33 patients showed PDD in the pancreatic head/neck area. Among them, 9 patients (27%) developed BS 65 days after onset and required stenting for 150 days, and 5 patients (15%) developed GOO 92 days after onset and required gastric decompression and jejunal tube feeding for 147 days (days shown in median). All 33 patients recovered successfully without requiring surgical intervention. CONCLUSIONS: Anatomic proximity of the bile duct or duodenum to the site of PDD and severe inflammation seemed to contribute to the late onset of BS or GOO. Conservative management successfully reversed these complications.

Five-Year Actual Overall Survival in Resected Pancreatic Cancer: A Contemporary Single-Institution Experience from a Multidisciplinary Perspective.

BACKGROUND: Successful surgical resection combined with effective perioperative therapy is essential for maximizing long-term survival for pancreatic adenocarcinoma. PATIENTS AND METHODS: All patients with pancreatic adenocarcinoma who underwent curative resection at our institution from January 2003 to May 2010 were reviewed. Demographic and clinical details were retrospectively collected from medical records and cancer registry data. RESULTS: Overall, 176 patients were included in the analysis (148 with de novo resectable disease and 28 with borderline resectable disease at presentation). Among 106 patients who received all perioperative therapy at our institution, 94% received neoadjuvant and/or adjuvant treatment in addition to resection. Actual all-cause 5-year overall survival (OS) for all 176 patients was 30.7%, with a median OS of 33.9 months [95% confidence interval (CI) 28.1-39.6 months]. For patients who received all perioperative therapy at our institution, actual all-cause 5-year disease-free survival (DFS) was 32.1%, with a median DFS of 28.8 months (95% CI 20.1-43.6 months). Of these patients, 67/106 (63%) recurred: 8 (8%) locoregional only; 52 (49%) systemic only; and 7 (7%) combined recurrence. No difference in survival rates or recurrence patterns was seen between resectable and borderline resectable patients. In multivariate analysis, tumor differentiation (poor vs. non-poor) and lymph node ratio >20% produced a useful clinical model. CONCLUSION: The actual OS rates for resected pancreatic cancer shown in this study are reflective of those currently achievable at a tertiary medical center dedicated to this patient population. In considering these results, both frequency and type of adjuvant/neoadjuvant therapy administered in the context of the clinical experience/management techniques of providers administering these treatments will be discussed.

Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the Course of Necrotizing Pancreatitis.

PURPOSE: To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard. MATERIALS AND METHODS: Between September 2010 and August 2014, CT-guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial. RESULTS: The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P < .05 for all). CONCLUSIONS: Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective.

Interferon-based Adjuvant Chemoradiation for Resected Pancreatic Head Cancer: Long-term Follow-up of the Virginia Mason Protocol.

OBJECTIVE: To report the long-term impact of adjuvant interferon-based chemoradiation therapy (IFN-CRT) after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). BACKGROUND: In 2003, we reported an actuarial 5-year overall survival (OS) of 55% (22 months median follow-up) using adjuvant IFN-CRT after PD. As the original cohort is now 10 years distant from PD, we sought to examine their actual survival, describe patterns of recurrence, and determine prognostic factors. METHODS: From 1995 to 2002, 43 patients underwent PD for PDAC and received adjuvant IFN-CRT consisting of external-beam irradiation, continuous 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α. Survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using a log-rank test and a Cox proportional hazards model. RESULTS: With all patients at least 10 years from PD, the 5-year actual survival was 42% and 10-year actual survival was 28% with median OS of 42 months (95% confidence interval: 22-110 months). Nine patients survived beyond 10 years with 7 currently alive without evidence of disease. Initial recurrence included 4 local, 17 distant, and 4 combined sites at a median of 25 months. IFN-CRT was interrupted in 70% of patients because of grade 3 or 4 toxicity, whereas 42% of patients required hospitalization. Adverse prognostic factors included lymph node ratio of 50% or more, Eastern Cooperative Oncology Group performance status of 1 or higher, and IFN-CRT treatment interruption. CONCLUSIONS: Adjuvant IFN-CRT after PD can provide long-term survival in resected PDAC. Further studies should focus on patient and tumor factors to maximize benefit and minimize toxicity.

Epidural anesthesia dysfunction is associated with postoperative complications after pancreatectomy.

BACKGROUND: Epidural anesthesia is an accepted measure of pain control after major abdominal surgery. However, if the epidural anesthesia is unsuccessful, a variety of adverse effects can occur - excessive stress response, poor patient mobilization, increased opioid use, and hypotension due to vasodilation. The aim of this study was to evaluate the influence of epidural dysfunction on outcomes after pan-createctomy. METHODS: Between August 2010 and October 2014, 72 patients underwent open pancreatectomy with epidural anesthesia. Epidural dysfunction was defined as either hypo-function due to inadequate pain control (requirement of epidural replacement, conversion to intravenous continuous opioid infusion, or intravenous bolus opioid use) or hyper-function (hypotension or oliguria). We then analyzed for an association between epidural dysfunction and surgical outcomes. RESULTS: Epidural dysfunction occurred in 49% after pancreatectomy - hypo-function in 35% and hyper-function in 14%. Epidural dysfunction was independently associated with the development of overall (P < 0.001), pancreas-related (P = 0.041), and non-pancreas-related complications (P = 0.001). Hypo-function alone was independently associated with both pancreas-related (P = 0.015) and non-pancreas-related complications (P = 0.004). Hyper-function was independently associated with non-pancreas-related complications (P = 0.002). CONCLUSIONS: Outcomes after pancreatic resection can be improved by increasing the success rate of epidural anesthesia.

Screening for Pancreatic Cancer.

Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.

A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

BACKGROUND: According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. METHODS: Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. RESULTS: PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015). CONCLUSIONS: A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.

When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery.

BACKGROUND: Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology. RESULTS: The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis. CONCLUSION: In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.

Clinical importance of Familial Pancreatic Cancer Registry in Japan: a report from kick-off meeting at International Symposium on Pancreas Cancer 2012.

Pancreatic cancer is still a highly lethal disease with a 5-year survival rate of approximately 5 %. Early detection offers one of the best hopes for improving survival. Previous cohort studies and case-control studies showed that 4-10 % of pancreatic cancers have a hereditary basis, and individuals with a family history have an increased risk of developing pancreatic and extra-pancreatic malignancies. Since individuals with a family history of pancreatic cancer and those with a known genetic syndrome that predisposes to pancreatic cancer will be the first to benefit from early detection tests as they become available, familial pancreatic cancer (FPC) registries have been established in the US and Europe, but not yet in Japan. Such registries form the basis for epidemiological studies, clinical trials, and basic research on familial pancreatic cancer. There is a need for FPC registries in Japan as cancer risk varies among different populations and discoveries made in Western populations may not translate to the Japanese population. These registries in Japan will align with ongoing international efforts and add to a better understanding of the natural history, risk factors, screening strategies, and responsible genes, for improving survival of this dismal disease.

Accordion severity grading system: assessment of relationship between costs, length of hospital stay, and survival in patients with complications after esophagectomy for cancer.

BACKGROUND: The ability to assess and compare the impact of postoperative complications in major cancer surgery is currently limited. The Accordion Severity Grading System provides the opportunity to categorize complications according to treatment responses and resource use. STUDY DESIGN: A retrospective review of patient demographics, perioperative outcomes, and costs was performed using a prospective IRB-approved database of patients undergoing esophagectomy from 2000 to 2008. RESULTS: This study included 285 consecutive patients, 83% were male, and mean age was 63.7 years. Histology was predominantly adenocarcinoma (80%). For patients with invasive cancer, overall survival at 5 years was 50%. Mean overall cost and length of stay were $23,419 and 10.4 days, respectively. Neoadjuvant therapy was used in 156 patients (54.7%) and operative mortality rate was 0.7%. Complications were documented in 144 patients (50.5%), with Accordion grades assigned as 1 (29%), 2 (59%), 3 (3%), 4 (6%), 5 (2%), and 6 (0.7%). Accordion grade was significantly related to costs and length of stay in univariate (p < 0.005) and multivariate analyses (p < 0.005). There was a statistically significant difference in survival between those patients who did and did not experience complications; however, no significant differences were noted among individual Accordion grades. Cox regression multivariate analysis demonstrated a significant relationship between overall survival and occurrence of postoperative complications. CONCLUSIONS: The Accordion Severity Grading System provides a meaningful approach to classifying complications according to resource use, which also directly correlates with treatment costs and length of stay. Survival is affected by overall occurrence of complications, but was not related to individual Accordion grades in this study. The Accordion Severity Grading System should be a component of prospective data collections and can be used in major cancer surgery to study areas appropriate for quality improvement and cost containment.

After distal pancreatectomy pancreatic leakage from the stump of the pancreas may be due to drain failure or pancreatic ductal back pressure.

HYPOTHESIS: The method to lower postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) involves controlling risk factors for leakage from the pancreatic stump. GOAL: The aim of this study was to identify controllable risk factors for POPF. METHODS: In order to promote homogeneity, we used a single surgeon case series and then calculated POPF with a public web-based tool based on the severity classification system of the International Study Group of Pancreatic Surgery (ISGPS). A total of 223 consecutive cases of DPs were reviewed. DP involved the same hand-sewn fish-mouth closure of the pancreatic stump. All received postoperative epidural anesthesia. Logistic regression analysis identified risk factors for clinically relevant POPF (grade B/C). RESULTS: Mortality was zero. ISGPS gradings were: no POPF 53%, grade A = 32%, B = 13.9%, and C = 0.9%. The clinical-relevant POPF (B/C) rate was 14.8% of which 24% represented surgical drain failure due to lack of patency and/or misplaced from their original location. Preoperative endoscopic ablation and/or stenting of Wirsung's duct was a significant risk factor to lower grade B/C leak (3%). Multivariate analysis identified two controllable risk factors-intraoperative blood loss >1,000 ml and those who did not undergo preoperative endoscopic interventions of Wirsung's duct. In the group with presumed intact pancreatic sphincters (no endoscopic intervention, n = 177), the use of postoperative intravenous opioids (with epidural failure) was a risk factor for B/C leak (34%). These findings suggest that increased back pressure in the pancreatic duct has a role in promoting pancreatic stump leakage. CONCLUSIONS: Using the ISGPS definition and its web-based tool, the incidence of clinically relevant leakage was 14.8% in 223 cases of DP. Opportunities to lower this rate are improving our surgical drain technology, limiting intraoperative blood loss, and avoiding postoperative intravenous narcotics with epidural analgesia.

Intraductal papillary mucinous neoplasms of the pancreas: making a disposition using the natural history.

The process of Intraductal papillary mucinous neoplasms (IPMN) follows the adenoma-to-carcinoma sequence. If it progresses to malignancy about 5 years is required. Even though the process is slow IPMN provides the clinician with the opportunity to avoid malignancy if the patient is at risk. The natural history as observed through Kaplan Meier event curves for occurrence of malignancy show the process to malignancy is much faster (50% within 2 years) if pancreatitis-like symptoms are present or if the main pancreatic duct (MPD) is involved. Almost all decisions to resect (95% in our experience) are based on the presence of symptoms or the MPD location. Cyst size is used infrequently. Every patient with an IPMN should always have a planned follow-up and the frequency depends on the perceived risk of malignancy-immediate imaging if becomes symptomatic to every 2 to 3 years if asymptomatic side branch lesions. The natural history provides modern guidelines for making decisions in patients with a newly discovered IPMN.

Afferent limb syndrome and delayed GI problems after pancreaticoduodenectomy for pancreatic cancer: single-center, 14-year experience.

BACKGROUND: There are limited data on the incidence of afferent limb syndrome and other delayed GI problems in pancreatic cancer (PaC) patients, especially among long-term survivors (>2 years). OBJECTIVE: To evaluate the incidence of afferent limb syndrome (chronic afferent limb obstruction resulting in pancreatobiliary obstruction) and delayed GI problems in PaC patients after pancreaticoduodenectomy (PD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: PaC patients treated with PD (N = 186) over a 14-year period (January 1995-October 2009). INTERVENTIONS: Endoscopic balloon dilation and stent placement, percutaneous biliary drainage. MAIN OUTCOME MEASUREMENTS: Incidence of afferent limb syndrome and delayed GI complications (marginal ulcers, radiation enteropathy, anastomotic strictures). RESULTS: Mean age was 63 ± 10 years; 55% of patients were male. Afferent limb syndrome was noted in 24 patients (13%). Median time to diagnosis was 1.2 years (range 0.03-12.3 years); obstruction was primarily caused by recurrent PaC (8 patients, 33%) and radiation enteropathy (9 patients, 38%). Afferent limb syndrome was more likely to develop in patients with 2 years or longer of follow-up (n = 71, [38%]) compared with patients with 2 years or less of follow-up, after controlling for age, sex, surgery type, and adjuvant treatment (adjusted odds ratio, 4.5; 95% CI, 1.8-11.7). Other delayed GI problems included radiation enteropathy (6%), marginal ulcers (5%), anastomotic strictures (4%), cholangitis/liver abscesses (5%), and GI bleeding (6%). LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: GI problems, including afferent limb syndrome, are relatively common in PaC patients after surgery and adjuvant therapy. Clinicians should recognize and effectively treat these delayed GI problems, especially in long-term survivors.

The duration of symptoms predicts the presence of malignancy in 210 resected cases of pancreatic intraductal papillary mucinous neoplasms.

INTRODUCTION: Using Kaplan-Meier curves, a 2006 study illustrated a shorter time interval between development of symptoms and detection of malignant IPMN in the main pancreatic duct versus a side-branch duct location. Of 93 cases, only 62 were confirmed histologically. To support these interesting findings, we examined a larger cohort of cases where the diagnosis was confirmed histologically and asked if symptoms by themselves, as well as main duct location, were associated with malignant detection. METHODS: Between 1989 and 2009, 210 IPMN cases meeting international criteria were resected and histologically examined. Actuarial rates of malignant detection over time were calculated from the first clinical symptom to malignant detection (resection). These rates of malignant detection over time were compared for main vs. side-branch duct location and symptomatic vs. asymptomatic cases. RESULTS: The most common indications for resection were symptoms (88%) and main pancreatic duct location (65%). The actuarial malignant detection rates were significantly shorter for main duct location and also for symptomatic cases, regardless of duct location. CONCLUSIONS: Presence of symptoms followed by main pancreatic duct location had a significantly shorter elapsed time to malignant detection. The visual depiction of these actuarial rates highlights the importance of the clinical history. To determine malignant risk, the primary determinants for resection were either symptoms or main duct location (but not cyst size), confirming the 2006 study with a larger cohort of histologically confirmed cases.

Pancreatic anastomotic failure rate after pancreaticoduodenectomy decreases with microsurgery.

BACKGROUND: We have observed that leakage from pancreaticojejunostomy is reduced when a surgical microscope is used to construct the pancreaticojejunostomy during pancreaticoduodenectomy. To validate our hypothesis that better vision improves the technical performance of pancreaticojejunostomy, we limited inclusion criteria to those patients at high risk for leak, performed more cases, and used the grading system of the International Study Group of Pancreatic Surgery. STUDY DESIGN: From 1988 through 2008, 507 consecutive pancreaticoduodenectomies were performed with pancreaticojejunostomy. A subset of 283 patients at risk for leak had a main pancreatic duct (MPD) ≤3 mm at the surgical margin. Pancreaticojejunostomy was completed with surgical loupes (n = 135) or surgical microscope (n = 148). Incidence of pancreaticojejunostomy leak and delayed gastric emptying was determined using a Web-based calculator for the severity grading scale of the International Study Group of Pancreatic Surgery. RESULTS: Within the 507 pancreaticoduodenectomies, the clinically relevant pancreaticojejunostomy leak for those with an MPD >3 mm (n = 224) was 4%, and with an MPD ≤3 mm (n = 283) it was 16% (p < 0.0001). For these 283 high-risk patients, outcomes were worse in the loupes versus microscope group, ie, clinically relevant pancreaticojejunostomy leak (21% versus 11%; p = 0.021), pancreas-related complications (31% versus 19%; p = 0.018), clinically relevant delayed gastric emptying (19% versus 9%; p = 0.016), and hospital length of stay (12.9 versus 9.5 days; p < 0.0001). CONCLUSIONS: In a subset of pancreaticoduodenectomy patients at high risk for pancreaticojejunostomy leak, the increased visual acuity of the surgical microscope reduced clinically relevant pancreatic anastomotic failure, delayed gastric emptying, and hospital length of stay.

Positive peritoneal lavage cytology is a predictor of worse survival in locally advanced pancreatic cancer.

BACKGROUND: Peritoneal lavage cytology in the staging of pancreatic cancer is not widely used given improvements in computed tomography (CT). The aim of this study was to determine the utility of peritoneal lavage cytology in predicting survival in locally advanced pancreatic cancer. METHODS: Between 2000 and 2008, 202 patients with biopsy-proven pancreatic cancer who were determined by pancreas protocol CT to be locally advanced and not currently resectable underwent diagnostic laparoscopy and peritoneal lavage for cytology (DL-PLC). RESULTS: DL-PLC upstaged 58 of 202 patients (29%) to stage IV, who had a significantly worse median survival of 11 months versus 16 months (P = .03). Positive cytology was an independent predictor of worse survival (P = .02). DISCUSSION: Positive peritoneal cytology (stage IV disease) in locally advanced pancreatic cancer is common and predicts worse survival. This survival difference suggests that peritoneal cytology status might be useful in deciding treatment regimens in patients with locally advanced disease based on CT.

Pancreatic exocrine function is preserved after distal pancreatectomy.

INTRODUCTION: Our objective was to measure human stool elastase-1 to determine the effect of distal pancreatectomy on exocrine function. METHODS: During a 72-month period, 115 patients underwent resection. Stool elastase values were measured preoperatively in 83 patients and repeated at 3, 12, and 24 months. The amount of pancreas resected was divided into two categories-limited to the left of the portal vein and those resections over or extended to the right of the vein. RESULTS: Elastase values were normal in 84% (n = 70) of cases prior to resection (33% if chronic pancreatitis, 70% if pancreatic adenocarcinoma). In the 70 patients with normal preoperative values, exocrine function was maintained in those with resection that was limited to the left of the portal vein at 3, 12, and, 24 months. If the resection was over or extended to right of the portal vein, then 88% maintained normal exocrine function at 3 months, 92% at 12 months, and 100% were normal at 24 months. CONCLUSION: Of patients undergoing distal pancreatectomy, one sixth will have preoperative pancreatic insufficiency, most commonly those with pancreatic adenocarcinoma or chronic pancreatitis. Postoperative pancreatic insufficiency was seen transiently in those with resection that extended to the portal vein or beyond.