Search

Bhupesh Pokhrel,1 Eun Kwang Choi,1 Omer Khalid,2 Kumar Sandrasegaran,3 Evan L Fogel,1 Lee McHenry,1 Stuart Sherman,1 James Watkins,1 Gregory A Cote,1 Henry A Pitt,4 Nicholas J Zyromski,4 Beth Juliar,1 Glen A Lehman11Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Department of Gastroenterology, St Louis University School of Medicine, St Louis, MO, 3Department of Radiology, 4Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USABackground: A preliminary study has shown increased pancreatic fat in patients with idiopathic pancreatitis and sphincter of Oddi dysfunction. In this study, we aimed to determine if an increased quantity of pancreatic fat is an independent risk factor for pancreatitis post-endoscopic retrograde cholangiopancreatography (ERCP).Methods: In this case control study, we retrospectively reviewed a local radiological and ERCP database to identify patients who had had abdominal magnetic resonance imaging (MRI) followed by ERCP no more than 60 days later between September 2003 and January 2011. Percentage of fat was determined by recording signal intensity in the in-phase (Sin) and out-of-phase (Sout) T1-weighted gradient sequences, and calculation of the fat fraction as (Sin - Sout)/(Sin) × 2 by an abdominal radiologist blinded to clinical history. Controls matched for age, gender, and other pancreatobiliary disease were selected from a group with no post-ERCP pancreatitis (before fat content of the pancreas was analyzed).Results: Forty-seven patients were enrolled. Compared with controls, subjects with post-ERCP pancreatitis were similar in terms of age (41.4 years versus 41.1 years), gender (21.2% versus 20.2% males), pancreatobiliary disease characteristics, and most ERCP techniques. Measurements of pancreatic head, body, and tail fat and body mass index were similar in patients and controls.Conclusion: Increased pancreatic fat on MRI criteria is not an independent predictor of post-ERCP pancreatitis.Keywords: magnetic resonance imaging, obesity, pancreatic fat, post-ERCP pancreatitis, sphincter of Oddi dysfunction

Routine drainage of the operative bed following elective pancreatectomy remains controversial. Data specific to distal pancreatectomy (DP) have not been examined in a multi-institutional collaborative. : Data from the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project were utilized. The impact of drain placement on development of pancreatectomy-related and overall morbidity were analyzed. Propensity scores for drain placement were calculated, and nearest neighbor matching was used to create a matched cohort. Groups were compared using bivariate and logistic regression analyses. : Over 14 months, 761 patients undergoing DP were accrued; 606 were drained. Propensity score matching was possible in 116 patients. Drain and no drain groups were not different with respect to multiple preoperative and operative variables. All pancreatic fistulas (p

BackgroundAccurate assessment of complications is critical in analysing surgical outcomes. The post-operative morbidity index (PMI), derived from the Modified Accordion Severity Grading System and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative measure of post-operative morbidity. This study utilizes PMI to establish the complication burden for a distal pancreatectomy (DP).MethodsFrom 2005–2011, nine centres contributed ACS-NSQIP complication data for 655 DPs. Each complication was assigned an Accordion severity weight ranging from 0.11 for grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity weights divided by the total number of patients.ResultsACS-NSQIP complications occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087. Bleeding/Transfusion and Organ Space Infection were the most common complications. Frequency and burden differed across Accordion grades. While grade 4–6 complications represented only 15.4% of complication occurrences, they accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI did not vary based on laparoscopic versus open approach or the performance of a splenectomy.DiscussionThis study uses two validated systems to quantitatively establish the morbidity of a DP. The PMI allows estimation of both the frequency and severity of complications and thus provides a more comprehensive assessment of risk.

The aim of this study was to determine if early recognition and treatment of delayed gastric emptying (DGE) can augment postoperative outcomes in patients undergoing pancreatectomy.The International Study Group of Pancreatic Surgery definition of DGE was used to identify patients at Indiana University Hospital who required supplemental nutrition for DGE after pancreatectomy. Outcomes were compared between those without DGE, those with DGE who received supplemental nutrition within 10 days after pancreatectomy (early intervention), and those treated after 10 days (late intervention).Between 2007 and 2012, the incidence of DGE was 15% (n = 163/1,089), 45% (n = 73) required supplemental nutrition, including 60% (n = 44/73) in the early intervention and 40% (n = 29/73) in the late intervention groups. Postoperative morbidity (62% vs 41%; P .01), duration of stay (16 vs 7 days; P .01), and readmissions (41% vs 17%; P .01) were greater among those with DGE. The early intervention group resumed a regular diet sooner (day 24 vs 36; P = .05) and were readmitted less often (25% vs 65%; P .01) than those in the late intervention group. Treatment-related complications occurred in 14% of patients.Patients with DGE can be managed with acceptable treatment-related morbidity. Outcomes are best when supplemental nutrition is started within 10 days of operation.

BACKGROUND Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. METHODS The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. RESULTS The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. CONCLUSIONS Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level.

Data on the effect of bile duct injuries (BDI) on health-related quality of life (HRQOL) are not well defined. We sought to assess long-term HRQOL after BDI repair in a large cohort of patients spanning a 23-year period.We identified and mailed HRQOL questionnaires to all patients treated for major BDI after laparoscopic cholecystectomy between January 1, 1990 and December 31, 2012 at Johns Hopkins Hospital.We identified 167 patients alive at the time of the study who met the inclusion criteria. Median age at BDI was 42 years (interquartile range 31 to 54 years); the majority of patients were female (n = 131 [78.4%]) and of white race (n = 137 [83.0%]). Most patients had Bismuth level 2 (n = 56 [33.7%]) or Bismuth level 3 (n = 40 [24.1%]) BDI. Surgical repair most commonly involved a Roux-en-Y hepaticojejunostomy (n = 142 [86.1%]). Sixty-two patients (37.1%) responded to the HRQOL questionnaire. Median follow-up was 169 months (interquartile range 125 to 222 months). At the time of BDI, mental health was most affected, with patients commonly reporting a depressed mood (49.2%) or low energy level (40.0%). These symptoms improved significantly after definitive repair (both p0.05). Limitations in physical activity and general health remained unchanged before and after surgical repair (both p0.05).Mental health concerns were more commonplace vs physical or general health issues among patients with BDI followed long term. Optimal multidisciplinary management of BDI can help restore HRQOL to preinjury levels.

Iatrogenic injuries of the biliary tract have increased in incidence over the past decade with the introduction of laparoscopic cholecystectomy. Although a number of factors have been identified with a higher risk of injury (male gender, complicated gallstone disease, aberrant anatomy) and a number of technical steps have been emphasized to avoid these injuries, the incidence of bile duct injuries has reached a steady-state at least double the rate observed with open cholecystectomy. Most patients sustaining a bile duct injury are recognized in the weeks following laparoscopic cholecystectomy. Careful preoperative preparation should include control of sepsis by draining any bile collections or fistulas and complete cholangiography. Long-term results are best achieved in specialized hepatobiliary centers performing biliary reconstruction with a Roux-en-Y hepaticojejunostomy. Success rates over 90% have been reported from several centers to date with intermediate follow-up.

Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 +/- 0.3 N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions was greater in the Fe+ group (34.7 +/- 2.9%) compared to the Fe- group (23.9 +/- 3.2%; P

The recent introduction of cryotherapy and radiofrequency ablation of liver metastasis has expanded the indications for treatment. As technology has advanced, a percutaneous approach has been developed. Percutaneous treatment, however, requires accurate preoperative imaging. From 1993 to 1999, 179 patients underwent operative exploration for treatment of suspected hepatic metastases from colorectal carcinoma. One hundred seventy-seven patients were staged by preoperative CT, two patients were staged by MRI, and complete data were available in 176. Hepatic tumor count by preoperative imaging was compared to intraoperative tumor count obtained by inspection, palpation, ultrasonographic examination using a 3.5/7.5 MHz T probe, and careful gross sectioning of the resected specimen. Post hoc analysis was performed on 35 CT scans by two radiologists who specialize in abdominal CT. These radiologists were blinded to the intraoperative findings. Their interpretations were compared to the intraoperative counts and to each other. Thirty-four (19%) of 179 patients were deemed untreatable at operation because of unsuspected overwhelming liver involvement in 11 (6%) or extrahepatic metastases in 23 (13%). For the group, CT was accurate in 80 patients (45%), showed more lesions than were found in 16 (9%), and showed fewer metastases than were found in 80 (45%). When the preoperative scan predicted a solitary metastasis, it was correct in 45 (65%) of 69 patients and underestimated disease in 24 (35%). In the post hoc analysis, the mean numbers of lesions reported by the two radiologists did not differ from the mean number of tumors found; however, the radiologists' counts agreed on 16 (59%) and disagreed on 11 (41%) of the scans. The accuracy of CT decreased with increasing numbers of lesions. Regardless of the type of preoperative imaging, intraoperative findings altered the course of the operation in 96 (55%) of 176 patients. Preoperative imaging is not sufficiently accurate to permit adequate percutaneous treatment of hepatic metastases from colorectal carcinoma.

The objective of this study was to evaluate the short-term and long-term outcome as well as quality of life in patients undergoing surgical management of chronic pancreatitis. Between January 1980 and December 1996, a total of 255 patients underwent surgery for chronic pancreatitis at The Johns Hopkins Hospital. The etiology of the disease, indications for surgery, patient characteristics, and long-term survival were analyzed. A visual analog quality-of-life questionnaire containing 23 items graded on a scale of 0 to 10 (0 = worst and 10 = best) was sent to patients postoperatively. Visual analog responses relating to before and after the chronic pancreatitis surgery were compared using a paired t test. During the17-year review period, 263 operations were performed for chronic pancreatitis in 255 patients. The most common presenting symptoms were abdominal pain (88%), weight loss (36%), nausea/vomiting (30%), jaundice (14%), and diarrhea (12%). The cause of the pancreatitis was resumed to be alcohol in 43%, idiopathic in 38%, pancreas divisum in 5%, ampullary abnormality in 4%, and gallstones in 3%. Pancreaticoduodenectomy was the most common procedure in 96 patients (37%), followed by distal pancreatectomy in 67 (25%), Puestow procedure in 52 (19%), sphincteroplasty in 37 (14%), and Duval procedure in five (2%). The overall mortality and morbidity rates were 1.9% and 35%, respectively. Two hundred twenty-seven (89%) of the 255 patients were alive at last follow-up. For the entire cohort of patients, the 5- and 10-year actuarial survivals were 88% and 82%, respectively. One hundred six (47%) of the 227 living patients responded to the visual analog quality-of-life questionnaire. Patients reported improvements in all aspects of the quality-of-life survey including enjoyment out of life, satisfaction with life, pain, number of hospitalizations, feelings of usefulness, and overall health (P < 0.005). In addition to improved quality of life after surgery, narcotic use was decreased (41% vs. 21%, P < 0.01) and alcohol use was decreased (59% vs. 33%, P < 0.001). However, patients often became insulin-dependent diabetics (12% vs. 41%, P < 0.0001) and required pancreatic enzyme supplementation (34% vs. 55%, P < 0.01) after surgical intervention. These data suggest that surgery for patients with chronic pancreatitis can be performed safely with minimal morbidity and excellent long-term survival. Moreover, this study evaluates quality of life in a standardized analog fashion, with highly significant improvement reported in all quality-of-life measures. We conclude that surgery remains an excellent option for patients with chronic pancreatitis.

It has been suggested that the placement of endoscopic or percutaneous biliary stents prior to pancreaticoduodenectomy increases postoperative morbidity. A retrospective review of a prospectively collected database was performed. Patients undergoing preoperative biliary stenting were compared with patients who did not undergo stenting. In addition, outcomes after endoscopic and percutaneous stenting were compared. Patients who had undergone operative biliary bypass prior to pancreaticoduodenectomy were excluded from the analysis. Between January 1994 and December 1997, 567 patients underwent pancreaticoduodenectomy without prior operative biliary bypass. Preoperative biliary stenting was performed in 408 patients (72%), whereas the remaining 159 patients (28%) did not undergo biliary stenting. In the stented group, 64% had stents placed via a percutaneous approach and 36% had stents placed endoscopically. The stented patients were older (mean 63.1 years vs. 61.4 years; P = 0.05) and were more likely to be white (92% vs. 82%; P = 0.005). Those who had stents placed were more likely to have jaundice (67% vs. 38%; P

Background: Pancreatic lymphoma is a rare neoplasm. The role of surgical resection in curing this disease is poorly defined. Study Design: From March 1983 to July 1997, eight patients with stage I or II primary pancreatic lymphoma were identified and retrospectively reviewed. All patients received chemotherapy, five patients received radiotherapy, and three patients also underwent surgical resection. A review of the published pancreatic lymphoma experience in the English-language literature was also undertaken. Results: Three patients underwent pancreaticoduodenectomy with successful resection of the lymphoma and are disease free at 64, 62, and 53 months followup. Five patients were treated with nonresectional therapy. Three are disease free at 128, 51, and 24 months. Two patients died of disease at 9 and 37 months. A review of the pancreatic lymphoma experience in the English- language literature identified 122 cases of pancreatic lymphoma. Fifty-eight of these cases represented stage I or II lymphoma, which was treated without surgical resection with a 46% cure rate. Fifteen patients who had surgical resection for localized disease have been reported with a 94% cure rate. Conclusions: Based on both our single institution experience and the literature, it is suggested that surgical resection may play a beneficial role in the treatment of localized pancreatic lymphoma, although selection factors cannot be absolutely excluded.

Background: Cystic pancreatic neoplasms may be benign, premalignant, or malignant. These lesions may remain asymptomatic for long periods and can be quite large at the time of presentation. Methods: A retrospective analysis was used to determine whether preoperative evaluation can predict pathology and determine resectability and outcome. Results: Over 12 years, 145 cystic pancreatic neoplasms, of which 24 (17%) were larger than 10 cm, were managed at the Johns Hopkins Hospital. Those 24 large tumors included 9 of 73 cystadenomas (12%), 7 of 27 cystadenocarcinomas (26%), 2 of 35 adenocarcinomas producing mucin or associated with a cyst (6%), 5 of 9 Hamoudi tumors (55%), and 1 dermoid cyst. Clinical symptoms, liver function tests, and computed tomographic scans did not distinguish benign from malignant pathology. On 18 angiograms, 2 malignant and 4 benign neoplasms demonstrated encasement or occlusion; however, 3 of these 6 tumors were resectable. Twenty of 22 patients (91%) who were explored underwent resection with no hospital mortality. For the entire series, 5-year survival for those with cystadenomas, cystadenocarcinomas, and cystic adenocarcinomas was 97%, 38%, and 9%, respectively. Three-year survival for those 7 with cystadenocarcinomas larger than 10 cm was 54%, compared with 51% for those 20 with smaller cystadenocarcinomas. Conclusions: Preoperative evaluation usually does not predict pathology, resectability, or outcome. Moreover, resectability is high and morbidity is low, irrespective of size. Large cystic pancreatic tumors should be explored to determine pathology, attempt resection, and provide an opportunity for long-term survival.

Background. Complex biliary surgery is associated with significant morbidity, prolonged hospital stay, and high cost. Clinical pathway implementation has the potential to standardize treatment and improve outcomes. Therefore the aim of this analysis was to determine whether clinical pathway implementation and/or feedback of outcome data would alter hospital stay, charges, and mortality rates for complex biliary surgery at an academic medical center. Methods. Pre- and postoperative length of stay, hospital charges, and mortality rates were monitored for 36 months before (period 1) and for 2 18-month periods (periods 2 and 3) after implementation of a clinical pathway for hepaticojejunostomy. Outcome data were provided to the surgeons 18 months after pathway implementation to determine whether further clinical practice improvement was possible. Results. From 1991 to 1997, 339 patients underwent hepaticojejunostomy at The Johns Hopkins Hospital for malignant and benign biliary obstruction. Total length of stay was 13.3 ± 0.9 days for period 1 compared with 12.5 ± 0.8 days for period 2 (not significant) and 10.1 ± 0.3 days for period 3 (P < .01 vs period 1; P

Background: Hepatic resection for colorectal metastases has been established as the best option for patients with 4 or less lesions meeting specified criteria. Recently, the use of intraoperative ultrasound has increased the detection of previously occult liver lesions, and cryotherapy has allowed the treatment of liver lesions in inaccessible areas with less destruction of normal liver in the case of multiple lesions. We prospectively performed hepatic resection or cryotherapy to test the hypothesis that more than 4 liver metastases could be safely and successfully treated with improved long-term survival. Methods: From August 1993 to January 1999, 137 patients with liver metastases from colorectal cancer were treated with hepatic resection or cryotherapy at the Medical College of Wisconsin. Preoperative and postoperative computed tomography scans, intraoperative assessments of lesion number and curability, number of blood transfusions administered, length of stay, complications experienced, and overall survival rates were reviewed. Results: One hundred thirty-seven patients were explored. Treatment consisted of resection alone in 34, cryotherapy alone in 20, both treatments in 52, and no treatment was possible in 31 patients. “Curability” was defined as complete resection or cryotherapy of all identifiable tumor at the conclusion of the operation. A Cox proportional hazards model demonstrated that survival was determined by the destruction of all identifiable metastases (P < .001) and was not statistically influenced by age, gender, type of therapy, or the number of metastases treated. Conclusions: Surgical treatment of colorectal liver metastases remains the best option for patients with this disease. A key factor in overall survival is the destruction or resection of all identifiable disease and not the number of tumors per se. Using cryotherapy as an addition to the surgical arsenal, patients previously deemed unresectable because of the number of lesions have a chance for long-term survival. This study demonstrates improved long-term survival for “cured” patients with more than 4 metastatic lesions, thereby extending the indications for resection/ablation. (Surgery 1999;126:766-74.)

Cholangiocarcinoma remains difficult to diagnose and is a major cause of death in patients with primary sclerosing cholangitis. Recently serum carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) levels have been reported to improve diagnostic accuracy in patients with cholangiocarcinoma and primary sclerosing cholangitis. We reviewed our experience with cholangiocarcinoma complicating primary sclerosing cholangitis to identify clinical factors associated with cholangiocarcinoma in patients with primary sclerosing cholangitis and to determine the appropriate management of patients with confirmed or suspected cholangiocarcinoma. Between 1984 and 1997, 25 patients (18%) were diagnosed with cholangiocarcinoma among 139 patients with primary sclerosing cholangitis. The diagnosis of primary sclerosing cholangitis was made coincident with the diagnosis of cholangiocarcinoma in 12 patients and preceded it by a mean of 62 months in the remaining 13 patients. The incidence of inflammatory bowel disease was higher (P

Background: Advances in the nonoperative staging and palliation of periampullary carcinoma have dramatically changed the management of this disease. Currently, surgical palliation is used primarily for patients found to be unresectable at the time of laparotomy performed for the purpose of determining resectability. Study Design: A review of all patients undergoing operative management for periampullary adenocarcinoma at a single, high-volume institution was performed. The review focused on patients found to be unresectable who, therefore, underwent surgical palliation. Results: Between December 1991 and December 1997, 256 patients with unresectable periampullary adenocarcinoma were operatively palliated. During the same time period, 512 patients underwent pancreaticoduodenectomy (PD) for periampullary carcinoma. Sixty-eight percent of patients were unresectable secondary to liver metastases or peritoneal metastases, and 32% were deemed unresectable because of local vascular invasion. Of the 256 patients, 51% underwent double bypass (hepaticojejunostomy [HJ] and gastrojejunostomy [GJ]), 11% underwent HJ alone, 19% underwent GJ alone, and 19% did not undergo any form of bypass. Celiac block was performed in 75% of patients. Palliated patients were significantly younger, with a mean age of 64.0 years compared with 65.8 years in the resected group (p = 0.04). Gender and race distributions were similar in the 2 groups, with 57% of palliated patients and 55% of resected patients being men (p = NS) and 91% of patients in each group being Caucasian (p = NS). Palliative procedures were performed with a mortality rate of 3.1%, compared to 1.9% in those successfully resected (p = NS). Those undergoing operative palliation had a significantly lower incidence of postoperative complications when compared with those undergoing pancreaticoduodenectomy (22% versus 35%, p Conclusions: Surgical palliation continues to play an important role in the management of periampullary carcinoma. In this high-volume center, 33% of patients undergoing operative management of this disease were unresectable. Surgical palliation can be accomplished with acceptable perioperative mortality (3.1%) and morbidity (22%), with excellent longterm results.

Background. Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. Materials and methods. Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. Results. Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90%). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25%). Four of seven tumors (57%) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. Conclusions. Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis-associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.

We observed a clustering of cholangiocarcinoma in a part of West Virginia. We analyzed the frequency and type of alterations in the p53 tumor-suppressor gene and the K-ras oncogene to determine whether cholangiocarcinomas from this high-incidence area differ from other cholangiocarcinomas at the molecular level. We studied 12 carcinomas of patients from the high-incidence area (West Virginia group), and 15 carcinomas of patients from nearby states (non-West Virginia group). Over-expression of the p53 gene product, accompanying most mutations in the p53 gene, was determined by immunohistochemistry. p53 sequence analysis of exons 5, 6, 7, and 8 of the p53-immunohistochemical-positive carcinomas was also performed. K-ras codon 12 mutations were detected by the polymerase chain reaction and allele-specific oligonucleotide hybridization. Significantly more cholangiocarcinomas from the West Virginia group were p53-immunohistochemical-positive than from the non-West Virginia group (67% vs. 20%; p < 0.05). p53 mutations did not differ in the 2 groups in respect to site or specific type. No differences were found between the 2 groups regarding K-ras mutations (17% vs. 27%). Although the higher frequency of p53-immunohistochemical positivity in the West Virginia group may reflect a different etiology of these cholangiocarcinomas, explaining the high incidence in this area, results of p53 sequence analysis were not different in the West Virginia group. The high incidence may be explained by difference in carcinogenic dose or a different etiology not reflected in p53 or K-ras alterations.

Reports of improved survival rates for patients with resected adenocarcinoma of the pancreas coincide with the adoption of adjuvant chemoradiation protocols. The impact of nodal micrometastases demonstrated by molecular assays and adjuvant therapy on survival of patients with stage I pancreatic cancer has not been adequately assessed.A retrospective analysis of postoperative chemoradiation on survival in 61 patients undergoing resection of pancreatic adenocarcinomas from 1984 to 1997 was performed. Archival tumors and regional nodes from 25 patients with stage I cancers were tested for a Kiras oncogene mutation using polymerase chain reaction and analysis for restriction fragment length polymorphisms (PCR/RFLP).Adjuvant chemoradiation was associated with improved survival for stage I (P.01), but not stage III, disease. Seventeen (68%) of 25 patients with stage I disease tested had evidence of mutant Kiras in one or more regional nodes. Survival did not differ for patients with molecular micrometastases. Six of 17 (35%) patients with micrometastases received adjuvant chemoradiation and had improved survival (P.05).The majority of patients with stage I pancreatic cancer have PCR/RFLP evidence of lymph node micrometastases. Adjuvant chemoradiation improves survival in these patients by treating micrometastases not detected by histology. Adjuvant chemoradiation should be used for patients with stage I pancreatic cancers.

As the population in the United States ages, an increasing number of elderly patients may be considered for pancreaticoduodenal resection. This high-volume, single-institution experience examines the morbidity, mortality, and long-term survival of 727 patients undergoing pancreaticoduodenectomy between December 1986 and June 1996. Outcomes of patients 80 years of age and older (n = 46) were compared to those of patients younger than 80 years. In these older patients, pancreaticoduodenectomy was performed for pancreatic adenocarcinoma (n = 25; 54%), ampullary adenocarcinoma (n = 9; 20%), distal bile duct adenocarcinoma (n = 5; 1 l%), duodenal adenocarcinoma (n = 2; 4%), cystadenocarcinoma (n = 2; 4%), cystadenoma (n = 1; 2%), and chronic pancreatitis (n = 2; 4%). When compared to the 681 concurrent patients younger than 80 years who were undergoing pancreaticoduodenectomy, the two groups were statistically similar with respect to sex, race, intraoperative blood loss, and type of pancreaticoduodenectomy performed. Patients 80 years of age or older had a shorter median operative time (6.4 hours vs. 7.0 hours; P = 0.02) but a longer postoperative length of stay (median = 15 days vs. 13 days; P = 0.01) and a higher complication rate (57% vs. 41%; P = 0.05) when compared to their younger counterparts. Pancreaticoduodenectomy in the older group resulted in a 4.3% perioperative mortality rate compared to 1.6% in the younger group (P = NS). In the subset of patients undergoing pancreati-coduodenectomy for periampullary adenocarcinoma (n = 495), patients 80 years of age or older (n = 41) had a median survival of 32 months and a 5-year survival rate of 19%, compared to 20 months and 27%, respectively, in patients younger than 80 years (n = 4.54; P = 0.77). These data demonstrate that pancreaticoduodenectomy can be performed safely in selected patients 80 years of age or older, with morbidity and mortality rates approaching those observed in younger patients. Based on these data, age alone should not be a contraindication to pancreaticoduodenectomy.

OBJECTIVE: The current study examines the results of extrahepatic biliary resection, nonoperative endoscopic biliary dilation with or without percutaneous stenting, and liver transplantation in the management of patients with primary sclerosing cholangitis (PSC). SUMMARY BACKGROUND DATA: Primary sclerosing cholangitis is a progressive inflammatory disease leading to secondary biliary cirrhosis. The most effective management of sclerosing cholangitis before the onset of cirrhosis remains unclear. METHODS: From 1980 to 1994, 146 patients with PSC were managed with either resection of the extrahepatic bile ducts and long-term transhepatic stenting (50 patients), nonoperative endoscopic biliary dilation with or without percutaneous stenting (54 patients), medical therapy (28 patients), and/or liver transplantation (21 patients). RESULTS: Procedure-related morbidity and mortality rates were similar between surgically resected and nonoperatively managed patients. In noncirrhotic patients, the serum bilirubin level was significantly (p < 0.05) reduced from preoperative levels (8.3+/-1.5 mg/dL) 1 (1.7+/-0.4 mg/dL) and 3 (2.7+/-0.9 mg/ dL) years after resection, but not after endoscopic or percutaneous management. For noncirrhotic PSC patients, overall 5-year survival (85% vs. 59%) and survival until death or transplantation (82% vs. 46%) were significantly longer (p < 0.05) after resection than after nonoperative dilation with or without stenting. For cirrhotic patients, survival after liver transplantation was longer than after resection or nonoperative dilation with or without stenting. Five patients developed cholangiocarcinoma, including three (6%) of the nonoperatively managed patients but none of the resected patients. CONCLUSIONS: In carefully selected noncirrhotic patients with PSC, resection and long-term stenting remains a good option. Patients with cirrhosis should undergo liver transplantation.

Background and Objectives: The 5-year survival rates after resection of pancreatic carcinoma have recently increased and are predicted by tumor size, DNA content, and lymph node metastases at the time of resection. However, whether the 10-year survival rates have also increased and are similarly predicted by these factors is not known. Methods The influence of preoperative imaging tests, alcohol consumption, cigarette smoking, K-ras mutations, anatomic location, details of surgical resection, pathologic findings, and tumor DNA content on survival was tested for 96 patients after a successful resection of a pancreatic carcinoma with 17 patients being followed for more than 5 years. Results The 5- and 10-year patient survival rates were 18% and 3%, respectively. Univariate and multivariable analyses showed that tumor DNA content, pathologic tumor size, and lymph node metastases were the strongest prognostic indicators for long-term patient survival, although the importance of tumor size may diminish 2 or more years after resection. Surprisingly, the 11 patients with diploid carcinomas ⩾4 cm had an estimated 10-year survival rate of 36%. Conclusion These results show that the 10-year survival rate for pancreatic carcinoma remains very low, although the subset of patients with biologically favorable tumors has a prolonged survival and possible cure after resection. J. Surg. Oncol. 1998;67:151–159. © 1998 Wiley-Liss, Inc.

This single-institution retrospective analysis reviews the management and outcome of patients with surgically treated adenocarcinoma of the duodenum. Between February 1984 and August 1996, fifty-five patients with adenocarcinoma of the duodenum underwent surgery at The Johns Hopkins Hospital. Univariate analysis was performed to identify possible prognostic indicators. Curative resection was performed in 48 patients (87%): 35 of these patients (73%) underwent a pancreaticoduodenectomy (PD), whereas 27% (n = 13) underwent a pancreas-sparing duodenectomy (PSD). Patients undergoing PD were comparable to those undergoing PSD with respect to demographic factors, presenting symptoms, and tumor pathology. The remaining 13% of patients (n = 7) were deemed unresectable at the time of surgery and underwent biopsy and/or palliative bypass. PD was associated with an increase in postoperative complications when compared to PSD (57% vs. 30%), but this difference was not statistically significant. One perioperative death occurred following PD (mortality 2.9%), The overall 5-year survival rate for the 48 patients undergoing potentially curative resection was 53 %. Negative resection margins (P

CA 19-9 has achieved a defined role in the diagnosis, prognosis, and monitoring of patients with pancreatic cancer. For diagnosis, a reference value above 200 u/mL in a nonjaundiced patient with a confirming CT scan has a very high predictive value. For prognosis, a low preoperative value and a normal value after resection predict a good outcome. Similarly, CA 19-9 levels have been used successfully in monitoring the response to neoadjuvant therapy.

OBJECTIVE: The authors reviewed the pathology, complications, and outcomes in a consecutive group of 650 patients undergoing pancreaticoduodenectomy in the 1990s. SUMMARY BACKGROUND DATA: Pancreaticoduodenectomy has been used increasingly in recent years to resect a variety of malignant and benign diseases of the pancreas and periampullary region. METHODS: Between January 1990 and July 1996, inclusive, 650 patients underwent pancreaticoduodenal resection at The Johns Hopkins Hospital. Data were recorded prospectively on all patients. All pathology specimens were reviewed and categorized. Statistical analyses were performed using both univariate and multivariate models. RESULTS: The patients had a mean age of 63 +/- 12.8 years, with 54% male and 91% white. The number of resections per year rose from 60 in 1990 to 161 in 1995. Pathologic examination results showed pancreatic cancer (n = 282; 43%), ampullary cancer (n = 70; 11%), distal common bile duct cancer (n = 65; 10%), duodenal cancer (n = 26; 4%), chronic pancreatitis (n = 71; 11%), neuroendocrine tumor (n = 31; 5%), periampullary adenoma (n = 21; 3%), cystadenocarcinoma (n = 14; 2%), cystadenoma (n = 25; 4%), and other (n = 45; 7%). The surgical procedure involved pylorus preservation in 82%, partial pancreatectomy in 95%, and portal or superior mesenteric venous resection in 4%. Pancreatic-enteric reconstruction, when appropriate, was via pancreaticojejunostomy in 71% and pancreaticogastrostomy in 29%. The median intraoperative blood loss was 625 mL, median units of red cells transfused was zero, and the median operative time was 7 hours. During this period, 190 consecutive pancreaticoduodenectomies were performed without a mortality. Nine deaths occurred in-hospital or within 30 days of operation (1.4% operative mortality). The postoperative complication rate was 41%, with the most common complications being early delayed gastric emptying (19%), pancreatic fistula (14%), and wound infection (10%). Twenty-three patients required reoperation in the immediate postoperative period (3.5%), most commonly for bleeding, abscess, or dehiscence. The median postoperative length of stay was 13 days. A multivariate analysis of the 443 patients with periampullary adenocarcinoma indicated that the most powerful independent predictors favoring long-term survival included a pathologic diagnosis of duodenal adenocarcinoma, tumor diameter

Cholesterol gallstones occur most commonly in multiparous women, but the causes for this phenomenon remain unclear. This same patient population is prone to chronic iron deficiency anemia. In addition, iron is known to play an important role in hepatic enzyme metabolism. Therefore, we tested the hypotheses that iron deficiency would alter hepatic cholesterol metabolism and enhance gallstone formation.Forty adult prairie dogs were fed either a control iron-supplemented (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron-supplemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. After 8 weeks gallbladder bile, serum, and liver were harvested. Gallbladder bile was examined for cholesterol crystals and gallstones. Bile lipids and hepatic enzymes were measured, and a cholesterol saturation index (CSI) was calculated.Animals receiving the iron-deficient diet were more likely to have cholesterol crystals in their bile than were animals on the control diet (80% vs. 20%; p0.05). Animals on the 0.4% cholesterol iron-deficient diet had more cholesterol crystals per high-powered field (79 +/- 10 vs. 49 +/- 9; p = 0.07), a higher molar % cholesterol (6.0 +/- 0.3 vs 4.4 +/- 0.5; p0.05), and a higher CSI (1.27 +/- 0.10 vs. 0.91 +/- 0.07; p0.05) compared to animals receiving the 0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylase levels were lower in the animals on the iron-deficient diet compared to those receiving the control diet (0.42 +/- 0.08 vs 1.17 +/- 0.40 pmol/mg per minute; p = 0.07).These data suggest that an iron-deficient diet (1) alters hepatic enzyme metabolism, which, in turn, (2) increases gallbladder bile cholesterol and promotes cholesterol crystal formation. We conclude that iron deficiency plays a previously unrecognized role in the pathogenesis of cholesterol gallstone formation in women.

Hepatic abscesses are being recognized with increasing frequency in immunocompromised patients and those with malignant diseases. Risk factors and treatment for patients with pure fungal abscesses and mixed fungal and pyogenic abscesses have not been well described. A retrospective review of patients with hepatic abscesses was undertaken at The Johns Hopkins Hospital from 1973 through 1993. Eight patients with pure fungal hepatic abscesses and 34 patients with mixed fungal/pyogenic abscesses were identified. Clinical presentation, diagnosis, management, and outcome were analyzed. In the group with pure fungal abscesses, fungemia was predictive of death; four patients in this group died, whereas the remaining four patients who received amphotericin B treatment before the onset of fungemia all survived. In the group with mixed fungal/pyogenic abscesses, 11 patients received amphotericin B, whereas 23 did not. Ten (43%) of these 23 patients died. However, only one of five patients who received more than 1000 mg of amphotericin B died. In patients with hematologic malignancies, who are known to be at risk for fungal infections, amphotericin B treatment should be instituted early. In patients with mixed fungal/pyogenic hepatic abscesses who fail to improve after drainage and broad-spectrum antibiotics, antimycotic therapy should be considered early, before the onset of fungemia.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently performed for suspected biliary tumors for diagnosis and staging but carries a theoretical risk of needle-track seeding. We aimed to evaluate the impact of preoperative EUS-FNA on long-term outcomes for patients with cholangiocarcinoma (CCA).In a retrospective single-center study of consecutive patients with CCA with preoperative EUS-FNA, main outcome measures were overall survival and progression-free survival.In 150 patients with confirmed CCA, 61 underwent preoperative FNA. Median overall survival was 18.5 months (95% confidence limits [CL] 15.4, 25.7): 111 patients died and 39 survived. Of the 150 patients, 119 underwent curative-intent surgical resection, with median progression-free survival of 17.8 months (95% CL 14.5, 22.8); 89/119 patients had tumor recurrence or died, and 30/119 remained alive and disease-free. On multivariable analysis, overall survival was associated with: undergoing curative-intent surgery (hazard ratio [HR] 5.79, P = 0.001), lack of lymph node involvement (HR 1.89, P = 0.011), younger age (HR 1.51 for every 10 years, P0.0015), and small tumor size (HR 1.11 for every 1 cm, P = 0.029). For patients undergoing curative-intent surgery, on multivariable analysis, improved progression-free survival was associated with: lack of lymph node involvement (HR 1.88, P = 0.010), smaller tumor size (HR 1.16 for every 1 cm smaller, P = 0.003), and younger age (HR 1.53 for every 10 years, P0.001). Number of needle passes showed no statistically significant impact on overall survival.Preoperative EUS-FNA in patients with CCA does not appear to adversely affect overall or progression-free survival.

Pancreaticoduodenectomy (PD) remains a challenging operation with a 40% postoperative complication rate. Pyogenic liver abscess (PLA) is an uncommon complication following PD with little information on its incidence or treatment. This study was done to examine the incidence, risk factors, treatment, and long-term outcome of PLA after PD.We retrospectively reviewed 1,189 patients undergoing PD (N = 839) or distal pancreatectomy (DP) (N = 350) at a single institution over a 14-year period (January 1, 1994-January 1, 2008). Pancreatic databases (PD and DP) were queried for postoperative complications and cross-checked through a hospital-wide database using ICD-9 codes 572.0 (PLA) and 006.3 (amebic liver abscess) as primary or secondary diagnoses. No PLA occurred following DP. Twenty-two patients (2.6%) developed PLA following PD. These 22 patients were matched (1:3) for age, gender, year of operation, and indication for surgery with 66 patients without PLA following PD.PLA occurred in 2.6% (22/839) of patients following PD, with 13 patients (59.1%) having a solitary abscess and 9 (40.9%) multiple abscesses. Treatment involved antibiotics and percutaneous drainage (N = 15, 68.2%) or antibiotics alone (N = 7, 31.8%) with a mean hospital stay of 12 days. No patient required surgical drainage, two abscesses recurred, and all subsequently resolved. Three patients (14%) died related to PLA. Postoperatively, patients with biliary fistula (13.6 vs. 0%, p = 0.014) or who required reoperation (18.2 vs. 1.5%, p = 0.013) had a significantly higher rate of PLA than matched controls. Long-term follow-up showed equivalent 1-year (79 vs.74%), 2-year (50 vs. 57%), and 3-year (38 vs. 33%) survival rates and hepatic function between patients with PLA and matched controls.Postoperative biliary fistula and need for reoperation are risk factors for PLA following PD. Antibiotics and selective percutaneous drainage was effective in 86% of patients with no adverse effects on long-term hepatic function or survival.

BackgroundThe factors associated with delayed gastric emptying (DGE) after a pancreaticoduodenectomy (PD) are not definitively known.MethodsFrom November 2011 through to May 2012, data were prospectively collected on 711 patients undergoing a pancreaticoduodenectomy or total pancreatectomy as part of the American College of Surgeons‐National Surgical Quality Improvement Program Pancreatectomy Demonstration Project. Bivariate and multivariate models were employed to determine the factors that predicted DGE.ResultsIn the 711 patients, the overall rate of DGE was 20.1%. In a bivariate analysis, intra‐operative factors such as pylorus‐preservation (47.1% versus 43.7%, P = 0.40), intra‐operative drain placement (85.5%, versus 85.1%, P = 0.91) and an antecolic compared with a retrocolic gastrojejunostomy (60.1% versus 65.1%, P = 0.26) were not different between the DGE and no DGE groups. Pancreatic fistula formation (31.2% versus 10.1%), post‐operative sepsis (21.7% versus 7.0%), organ space surgical site infection (SSI) (23.9% versus 7.9%), need for percutaneous drainage (23.0% versus 10.6%) and reoperation (10.6% versus 3.1%) were higher in patients with DGE (P < 0.0001). In a multivariable model, only pancreatic fistula, post‐operative sepsis and reoperation were independently associated with DGE.DiscussionIn this multicentre study, only post‐operative complications were associated with DGE. Neither pylorus preservation nor route of enteric reconstruction (antecolic versus retrocolic) was associated with delayed gastric emptying.

Obesity is an established risk factor for pancreatic adenocarcinoma. No study has examined specifically the influence of obesity on malignant risk in patients with intraductal papillary mucinous neoplasm (IPMN), a group at substantial risk of pancreatic adenocarcinoma. We hypothesize that obesity is associated with a greater frequency of malignancy in IPMN.Data on patients undergoing resection for IPMN between 1992 and 2012 at a high-volume university institution were collected prospectively. Clinicopathologic and demographic parameters were reviewed. Patients were classified according to World Health Organization categories of body mass index (BMI). Malignancy was defined as high-grade dysplastic or invasive IPMN.We collected data on 357 patients who underwent resection for IPMN. Of these, 274 had complete data for calculation of preoperative BMI and 31% had malignant IPMN. Of 254 patients with a BMI of35 kg/m(2), 30% had malignant IPMN versus 50% in patients with BMI of ≥35 (P = .08). In branch-duct IPMN, patients with a BMI of35 had 12% of malignant IPMN compared with 46% in severely obese patients (P = .01). Alternatively, in main-duct IPMN, no difference was found in the malignancy rate (48% vs 56%; P = .74).These findings suggest that obesity is associated with an increased frequency of malignancy in branch-duct IPMN. Obesity is a potentially modifiable risk factor that may influence oncologic risk stratification, patient counseling, and surveillance strategy.

While referring to the evidence adopted in the Tokyo Guidelines 2007 (TG07) as well as subsequently obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular, new findings have accumulated on the occurrence of symptoms in patients with gallstones, frequency of severe cholecystitis and cholangitis, onset of cholecystitis and cholangitis after endoscopic retrograde cholangiopancreatography and medications, mortality rate, and recurrence rate. The primary etiology of acute cholangitis/cholecystitis is the presence of stones. Next to stones, the most significant etiology of acute cholangitis is benign/malignant stenosis of the biliary tract. On the other hand, there is another type of acute cholecystitis, acute acalculous cholecystitis, in which stones are not involved as causative factors. Risk factors for acute acalculous cholecystitis include surgery, trauma, burn, and parenteral nutrition. After 2000, the mortality rate of acute cholangitis has been about 10 %, while that of acute cholecystitis has generally been less than 1 %. After the publication of TG07, diagnostic criteria and severity assessment criteria were standardized, and the distribution of cases according to severity and comparison of clinical data among target populations have become more subjective. The concept of healthcare-associated infections is important in the current treatment of infection. The treatment of acute cholangitis and cholecystitis substantially differs from that of community-acquired infections. Cholangitis and cholecystitis as healthcare-associated infections are clearly described in the updated Tokyo Guidelines (TG13). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07), diagnostic criteria and severity assessment criteria for acute cholangitis have been presented and extensively used as the primary standard all over the world. However, it has been found that there are crucial limitations in these criteria. The diagnostic criteria of TG07 do not have enough sensitivity and specificity, and its severity assessment criteria are unsuitable for clinical use. A working team for the revision of TG07 was organized in June, 2010, and these criteria have been updated through clinical implementation and its assessment by means of multi-center analysis. The diagnostic criteria of acute cholangitis have been revised as criteria to establish the diagnosis where cholestasis and inflammation demonstrated by clinical signs or blood test in addition to biliary manifestations demonstrated by imaging are present. The diagnostic criteria of the updated Tokyo Guidelines (TG13) have high sensitivity (87.6 %) and high specificity (77.7 %). TG13 has better diagnostic capacity than TG07. Severity assessment is classified as follows: Grade III: associated with organ failure; Grade II: early biliary drainage should be conducted; Grade1: others. As for the severity assessment criteria of TG07, separating Grade II and Grade I at the time of diagnosis was impossible, so they were unsuitable for clinical practice. Therefore, the severity assessment criteria of TG13 have been revised so as not to lose the timing of biliary drainage or treatment for etiology. Based on evidence, five predictive factors for poor prognosis in acute cholangitis––hyperbilirubinemia, high fever, leukocytosis, elderly patient and hypoalbuminemia––have been extracted. Grade II can be diagnosed if two of these five factors are present. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were first published in the Journal of Hepato-Biliary-Pancreatic Surgery. The fundamental policy of TG07 was to achieve the objectives of TG07 through the development of consensus among specialists in this field throughout the world. Considering such a situation, validation and feedback from the clinicians' viewpoints were indispensable. What had been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. In June 2010, we set up the Tokyo Guidelines Revision Committee for the revision of TG07 (TGRC) and started the validation of TG07. We also set up new diagnostic criteria and severity assessment criteria by retrospectively analyzing cases of acute cholangitis and cholecystitis, including cases of non-inflammatory biliary disease, collected from multiple institutions. TGRC held meetings a total of 35 times as well as international email exchanges with co-authors abroad. On June 9 and September 6, 2011, and on April 11, 2012, we held three International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines. Through these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria, and the new severity assessment criteria, new flowcharts of the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been added, new recommendations for gallbladder drainage and antimicrobial therapy, and the role of surgical intervention. Management bundles for acute cholangitis and cholecystitis were introduced for effective dissemination with the level of evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the grade of recommendations. TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The bundles for the management of acute cholangitis and cholecystitis are presented in a separate section in TG13. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

We propose a management strategy for acute cholangitis and cholecystitis according to the severity assessment. For Grade I (mild) acute cholangitis, initial medical treatment including the use of antimicrobial agents may be sufficient for most cases. For non-responders to initial medical treatment, biliary drainage should be considered. For Grade II (moderate) acute cholangitis, early biliary drainage should be performed along with the administration of antibiotics. For Grade III (severe) acute cholangitis, appropriate organ support is required. After hemodynamic stabilization has been achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. In patients with Grade II (moderate) and Grade III (severe) acute cholangitis, treatment for the underlying etiology including endoscopic, percutaneous, or surgical treatment should be performed after the patient's general condition has been improved. In patients with Grade I (mild) acute cholangitis, treatment for etiology such as endoscopic sphincterotomy for choledocholithiasis might be performed simultaneously, if possible, with biliary drainage. Early laparoscopic cholecystectomy is the first-line treatment in patients with Grade I (mild) acute cholecystitis while in patients with Grade II (moderate) acute cholecystitis, delayed/elective laparoscopic cholecystectomy after initial medical treatment with antimicrobial agent is the first-line treatment. In non-responders to initial medical treatment, gallbladder drainage should be considered. In patients with Grade III (severe) acute cholecystitis, appropriate organ support in addition to initial medical treatment is necessary. Urgent or early gallbladder drainage is recommended. Elective cholecystectomy can be performed after the improvement of the acute inflammatory process. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Background Risk factors for unplanned intubation have been delineated, but details regarding when and why reintubations occur as well as strategies for prevention have not been defined. Methods Over a 2-year period, 104 of 3,141 patients (3.3%) monitored via the American College of Surgeons-National Surgical Quality Improvement Program required unplanned intubation. These patients were compared to those who remained extubated and were characterized by (1) the operation performed; (2) the postoperative day when reintubation occurred; and (3) the underlying causes. Results Patients who required reintubation were significantly older (65.8 years) and were more likely to be male (55%) and to have several comorbidities, weight loss (16%), dependency (14%), or sepsis (9%). The operations complicated most commonly by unplanned intubation were gastrectomy (13%), nephrectomy (10%), colectomy (9%), pancreatectomy (8%), hepatectomy (7%), and enterectomy (6%). The most common causes and median postoperative days were sepsis (33%, day 8) and aspiration/pneumonia (31%, day 4). Sepsis was due most commonly to an abdominal or pelvic abscess (74%), which was frequently not recognized despite an inflammatory response. Aspiration occurred most commonly after upper abdominal operations (78%) despite signs of diminished bowel function. Conclusion Postoperative sepsis and aspiration/pneumonia account for two thirds of unplanned intubations. Opportunities for management of patients exist for the prevention of this deadly complication.

An aggressive operative approach to gallbladder cancer has been advocated because of improved long-term survival, but data on short-term outcomes are lacking. Therefore, the purpose of this study was to analyze the postoperative outcomes of patients undergoing operative management of gallbladder cancer.Data from the American College of Surgeons-National Surgical Quality Improvement Program (2005-2009) were queried for patients with a diagnosis of gallbladder cancer. Outcomes included serious morbidity, overall morbidity, and mortality.For the 613 patients identified, the median age was 67 years, and 64% were female. A potentially curative operation was performed in 424 (69%) patients, including cholecystectomy alone (n =150, 35%), partial hepatectomy (n = 249, 59%), and extensive hepatectomy (n = 25, 6%). Overall morbidity rates for these procedures were 21%, 19%, and 28%, respectively. Mortality was greater (P.001) in patients undergoing extensive hepatectomy (16%) compared with those undergoing cholecystectomy (7%) or partial hepatectomy (2%).Partial hepatectomy is the most common procedure performed for gallbladder cancer and is a safe operation. A small minority of younger, healthier patients undergoes an extensive hepatectomy, but the mortality of this operation is greater. This analysis suggests that patients with gallbladder cancer should be managed at high-volume centers.

Cholangiocarcinoma is an uncommon tumor that may occur anywhere along the intrahepatic or extrahepatic biliary tree. In the United States approximately 5,000 cholangiocarcinomas are diagnosed per year while many more biliary malignancies occur in Asia. The hepatic duct bifurcation is the most frequently involved site, and approximately 50–70 % of cholangiocarcinomas are found in this perihilar region [1]. The role of radiation therapy, chemoradiation and chemotherapy as adjuvants to surgical resection in patients with perihilar cholangiocarcinoma remains controversial. Aggressive surgical resection obtaining a negative microscopic margin offers the only chance for long-term survival. However, many patients will only be candidates for nonoperative stenting or palliative surgery aimed to provide biliary drainage and prevent cholangitis and hepatic failure. Radiation therapy, chemoradiation and/or chemotherapy also can be used in these patients with nonresectable disease in an attempt to palliate symptoms and extend survival.

Carcinoma of the pancreas remains a disease with a grim prognosis. The majority of patients are not resectable for cure at the time of presentation, with less than 20% of affected patients surviving 1 year after diagnosis. Because cure is unlikely for most patients, palliation of symptoms (obstructive jaundice, duodenal obstruction, and pain) is of primary importance. Obstructive jaundice is the most common presenting symptom for cancer of the pancreas and can be managed by both surgical and nonoperative techniques. Although prospective randomized studies support an early advantage to the nonoperative techniques, concern for late complications, including recurrent jaundice and duodenal obstruction, favor a surgical approach. The management of pain due to unresectable carcinoma of the pancreas remains a significant problem. A recent prospective randomized study has shown that intraoperative chemical splanchnicectomy with 50% alcohol significantly relieves or prevents pain when compared with a placebo treatment. For patients not undergoing surgery, a percutaneous celiac nerve block can be performed quickly with overall good results. The decision to perform nonoperative versus surgical palliation for pancreatic cancer is influenced by the patient's symptoms, overall health status, projected survival, and the expected procedure-related morbidity and mortality. The major advantage for surgical palliation is the ability of a single procedure to combine adequate long term palliation for all three primary symptoms of the disease. Most surgical series report acceptable hospital morbidity and mortality, and a reasonable postoperative length of hospital stay.

OBJECTIVE: The authors define the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma. BACKGROUND: Decreases in perioperative morbidity and mortality and improved long-term survival associated with pancreaticoduodenectomy for patients with pancreatic carcinoma have clearly established a role for this operation when performed with curative intent. However, most surgeons remain hesitant to perform pancreaticoduodenectomy unless surgical margins are widely clear, choosing rather to perform palliative biliary and gastric bypass. METHODS: A single-institution retrospective review was performed comparing the outcome of 64 consecutive patients undergoing pancreaticoduodenectomy for pancreatic carcinoma with gross or microscopic evidence of adenocarcinoma at the surgical resection margins, and 62 consecutive patients found to be unresectable at the time of laparotomy because of local invasion without evidence of metastatic disease (stage III). Combined biliary and gastric bypass were performed in 87% of patients not resected. RESULTS: The two groups were similar with respect to age, gender, race, and presenting symptoms. The hospital mortality rate was identical in both groups (1.6%). Fifty-eight percent of patients undergoing pancreaticoduodenectomy had an uncomplicated postoperative course compared with 68% of patients undergoing palliative bypass (not significant). The length of postoperative hospital stay after pancreaticoduodenectomy was 18.4 days, which was significantly longer (p < 0.05) than for patients undergoing palliative bypass (15.0 days). The overall actuarial survival (Kaplan-Meier) was improved significantly in patients undergoing pancreaticoduodenectomy (p < 0.02). Postoperative chemotherapy and radiation therapy improved survival in both groups. CONCLUSIONS: Pancreaticoduodenectomy can be performed with a similar perioperative morbidity and mortality and only a minimal increase in hospital stay when compared with traditional surgical palliation. Pancreaticoduodenectomy with postoperative chemotherapy and radiation therapy is associated with improved long-term survival when compared with patients treated with surgical bypass. These data support the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma and with local residual disease.