[Show abstract][Hide abstract] ABSTRACT: Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads to its primary disease outcomes including fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Mechanisms that mediate this inflammation are of major interest. We previously showed that overload of saturated fatty acids, such as that which occurs with metabolic syndrome, induced Sphingosine Kinase 1, an enzyme that generates sphingosine-1-phosphate. While data suggest beneficial roles for sphingosine-1-phosphate in some contexts, we hypothesized that it may promote hepatic inflammation in the context of obesity. Consistent with this, we observed 2-fold elevation of this enzyme in livers from humans with non-alcoholic fatty liver disease and also in mice with high saturated fat-feeding, which recapitulated the human disease. Mice exhibited activation of NFκB, elevated cytokine production, and immune cell infiltration. Importantly, sphingosine kinase 1 null mice were protected from these outcomes. Studies in cultured cells demonstrated saturated fatty acid induction of sphingosine kinase 1 message, protein, and activity, and also a requirement of the enzyme for NFκB signaling and increased mRNA encoding TNFα and MCP-1. Moreover, saturated fat-induced NFκB signaling and elevation of TNFα and MCP-1 mRNA in HepG2 cells was blocked by targeted knockdown of sphingosine-1-phosphate receptor 1, supporting a role for this lipid signaling pathway in inflammation in non-alcoholic fatty liver disease.
The Journal of Lipid Research 10/2015; DOI:10.1194/jlr.M063511 · 4.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatic ischemia/reperfusion (l/R) injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS) over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS) was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.
PLoS ONE 03/2014; 9(3):e93304. DOI:10.1371/journal.pone.0093304 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer mortality rates are significantly greater in AA than in EA individuals, and the disparity is worsening. We investigated the relationship between race and metastatic CRC (mCRC) survival in younger and older patients.
Using data from the Hollings Cancer Center (Charleston, SC), we studied the role of clinical, pathologic, and treatment-related factors on the disparity in survival. We carried out a retrospective cohort study of 82 mCRC patients (26 AA, 56 EA). The data source was medical record data from June 1, 2004 through May 31, 2008 with follow-up through June 30, 2010. Using Kaplan-Meier methods, we generated median survival time according to race and age (< 61, ≥ 61 years). Cox proportional hazards regression models were used to model the risk of death according to race.
The median age was 56.7 years for AA and 61.6 years for EA patients. Compared with EA, median survival in AA patients was 59% worse in younger patients (12.7 vs. 31.0 months) and 29% worse in older patients (11.7 vs. 16.4 months). The risk of death among younger AA compared with EA patients was 2.45 (95% confidence interval [CI], 1.15-5.23) and among older patients was 1.16 (95% CI, 0.49-2.73).
Our results highlight the importance of considering younger age, clinical prognostic markers, and tumor phenotypes as potential sources of the disparity in advanced stage CRC.
Clinical Colorectal Cancer 12/2013; 12(4):287-93. DOI:10.1016/j.clcc.2013.08.001 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival.
The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI.
We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years.
Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.
Cancer Causes and Control 01/2013; 24(3). DOI:10.1007/s10552-012-0133-5 · 2.74 Impact Factor
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2011; 10(9):e75-6. DOI:10.1016/j.cgh.2011.12.024 · 7.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Platinum-based doublet chemotherapy is the traditional treatment of choice for advanced non-small cell lung cancer (NSCLC); however, the efficacy of these regimens has reached a plateau. Increasing evidence demonstrates that patients with sensitizing mutations in the epidermal growth factor receptor (EGFR) experience improved progression-free survival and response rates with first-line gefitinib or erlotinib therapy relative to traditional platinum-based chemotherapy, while patients with EGFR-mutation negative tumors gain greater benefit from platinum-based chemotherapy. These results highlight the importance of molecular testing prior to the initiation of first-line therapy for advanced NSCLC. Routine molecular testing of tumor samples represents an important paradigm shift in NSCLC therapy and would allow for individualized therapy in specific subsets of patients. As these and other advances in personalized treatment are integrated into everyday clinical practice, pulmonologists will play a vital role in ensuring that tumor samples of adequate quality and quantity are collected in order to perform appropriate molecular analyses to guide treatment decisions. This article provides an overview of clinical trial data supporting molecular analysis of NSCLC, describes specimen acquisition and testing methods currently in use, and discusses future directions of personalized therapy for patients with NSCLC.
[Show abstract][Hide abstract] ABSTRACT: Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility, invasion, and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, noninvasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development.
For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin-resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 d, tumors were harvested and tissue was analyzed.
Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm(3)) compared with only 1/10 (10%) with empty DLD-1 cells.
Slug mediates EMT with enhanced in vivo rectal tumor formation. Our noninvasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer.
Journal of Surgical Research 03/2011; 170(1):56-63. DOI:10.1016/j.jss.2011.02.012 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Epithelial-to-mesenchymal transition
(EMT) is a series of molecular changes allowing epithelial
cancer cells to acquire properties of mesenchymal
cells: increased motility, invasion, and protection from
apoptosis. Transcriptional regulators such as Slug mediate
EMT, working in part to repress E-cadherin transcription.
We report a novel, noninvasive in vivo rectal
cancer model to explore the role of Slug in colorectal
cancer (CRC) tumor development.
Journal of Surgical Research 02/2011; 165(2):336-336. DOI:10.1016/j.jss.2010.11.198 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: On-site evaluation of fine-needle aspiration (FNA) specimens by a pathologist is essential to obtain adequate samples and provide a preliminary diagnosis. Distance from the laboratory can make this difficult. The authors present their experience with on-site evaluation using telecytopathology.
Dynamic images of cytology smears were captured and processed with a Nikon digital camera system for microscopy and transmitted via Ethernet. A pathologist accessed the real-time images on a computer and interpreted them while communicating with on-site operators over the telephone. Sample adequacy and accuracy of preliminary diagnosis were compared with those obtained by regular on-site evaluation.
A total of 429 telecytopathology cases and 363 conventional on-site cases were compared. Specimens were mainly from the pancreas, gastrointestinal tract, liver, and lymph nodes. Adequacy rate was 94.0% for telecytopathology and 97.7% for conventional cases. Preliminary diagnoses of unsatisfactory, adequate (defer), negative/benign, atypical, neoplasm, suspicious, and positive for malignancy were 6.3%, 13.5%, 14.9%, 17.9%, 7.2%, 8.6%, and 31.5% for telecytopathology and 3.9%, 30.6%, 21.5%, 9.6%, 5.0%, 5.2%, and 24.2% for conventional cases. Preliminary and final diagnoses were discrepant in 7 (1.8%) of 371 telecytopathology cases, and in 8 (3.1%) of 252 conventional cases. Difficulty was encountered in some cases in distinguishing pancreatic endocrine neoplasm from lymphoid proliferations, and low grade pancreatic tumors from chronic pancreatitis via telecytopathology.
On-site evaluation of FNA specimens via telecytopathology assures sample adequacy and accurate preliminary diagnosis compared with the conventional method. It allows pathologists to use their time more efficiently and makes on-site evaluations at remote locations possible.
Cancer Cytopathology 06/2010; 118(3):119-26. DOI:10.1002/cncy.20074 · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adhesions are common after conventional surgery; natural orifice transluminal endoscopic surgery (NOTES) avoids peritoneal disruption and may reduce adhesions.
To determine whether adhesions (and peritoneal contamination) are less common with NOTES transgastric colon injury and repair (TGCR) than with laparoscopic colon repair (LCR).
Porcine survival study.
After colon preparation and administration of antibiotics, forty 25-kg male pigs were randomly assigned to either TGCR or LCR. TGCR involved an endoscopic gastrotomy (needle-knife plus balloon dilation), CO(2) pneumoperitoneum, and a 2-cm needle-knife transmural incision of spiral colon. Colotomies were repaired with clips; gastrotomies were closed with clips and a detachable snare.
Adhesions were assessed at necropsy at 21 days; biopsy specimens were blindly reviewed. A 9-point adhesion score (density/vascularity, width, and extent) was averaged from 3 reviewers. Peritoneal lavage was sent for cell count and culture.
Two of 20 TGCR pigs died immediately (unrecognized preoperative autopsy-proven pneumonia). The median procedure times were 70.5 and 19.0 minutes for TGCR and LCR, respectively; weight gains were 7.1 and 8.2 kg, respectively. The median adhesion scores were 4.3 and 3.7, respectively (P = .26); subscores were similar (1.9, 1.5, 1.3 vs 1.7, 1.1, 1.0, respectively (P = .3-.6)). Peritoneal lavage bacterial growth was nonsignificantly lower after TGCR than after LCR (38.9% vs 60.0%, respectively; P = .30); administration of intragastric antibiotics did not decrease contamination. Three TGCR (vs no LCR) pigs had histologic peritonitis.
Animal model, colon prepped, injury immediately recognized.
NOTES colon repair is feasible after transmural injury. Adhesions, histologic peritonitis, and contamination were similar to those with laparoscopy and were not helped by intragastric antibiotics.
[Show abstract][Hide abstract] ABSTRACT: Lymphovascular invasion (LVI) in colorectal cancer (CRC) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors. However, the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown. This study was undertaken to examine such interobserver variability, and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement.
Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected; mucinous, medullary, and other recognized special subtypes were excluded. Fifty hematoxylin and eosin (H&E) slides (1 from each case) were circulated to 6 gastrointestinal pathologists, who independently assessed small and large vessel invasion. No diagnostic guidelines were given to the participating pathologists; each was instructed to apply the criteria for LVI that he or she used in daily practice. Immunohistochemistry (IHC) for D2-40 and CD31 was performed on corresponding paraffin blocks. The IHC slides were randomized, recirculated, and rescored for LVI. Results were analyzed by kappa (kappa) statistics, which correct for agreement by chance, and for percentage agreement.
The average kappa values were determined for the H&E slides (large and small vessel), CD31 (small vessel), and D2-40 (small vessel) (Fig. 1). Agreement was fair for H&E small vessel invasion [kappa=0.28; 95% confidence interval (CI): 0.22-0.34]. The least agreement was seen in interpretation of H&E large vessel invasion (kappa=0.18; 95%CI: 0.11-0.26). Agreement was not improved by use of immunohistochemical stains: CD31 (large vessel, kappa=0.42, 95%CI: 0.20-0.63, small vessel, kappa=0.26, 95%CI: 0.10-0.42) and D2-40 (kappa=0.32, 95%CI: 0.21-0.42).
Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC. Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone. This study highlights the need for criteria in evaluation of LVI, as this assessment may impact patient prognosis and thus change the course of clinical treatment.
The American journal of surgical pathology 09/2008; 32(12):1816-21. DOI:10.1097/PAS.0b013e3181816083 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One of the most common complications after distal pancreatectomy is a fistula from the pancreatic remnant. Factors influencing the development of a pancreatic fistula after distal pancreatectomy have not been clearly elucidated. The records of 91 patients who underwent distal pancreatectomy for chronic pancreatitis between 1995 and 2003 were retrospectively reviewed and analyzed. Average daily volume and amylase concentration between postoperative days 2 and 20 from drains located at the pancreatic resection site were compared to clinical variables. Out of 137 pre- and intraoperative clinical variables, multivariate analysis showed serum creatinine (t = 3.05, p = 0.004), history of intraabdominal operation (t = -2.68, p = 0.01), right-sided pancreatic duct dilation (t = 2.65, p = 0.01), synchronous cholecystectomy (t = 2.53, p = 0.02), and serum albumin (t = -2.19, p = 0.04) to be independently associated with drain volume. Drain amylase concentration was linked to serum creatinine (t = 8.55, p < 0.001), blood urea nitrogen (t = -3.43, p = .001), preoperative parenteral nutrition (t = 2.56, p = .01), and serum alkaline phosphatase (t = 2.51, p = 0.01). There was no correlation between the degree of fibrosis and drain output. Technique of pancreatic transection and presence of suture closure of the pancreatic duct did not affect drain output. In conclusion, the amount and amylase concentration of postsurgical drainage after distal pancreatectomy for chronic pancreatitis is dependent on markers of renal dysfunction, malnutrition, biliary disease, and possibly inflammation. These factors, if medically reversible, should be addressed in patients who are candidates for distal pancreatectomy for chronic pancreatitis.
Journal of Gastrointestinal Surgery 08/2007; 11(8):991-7. DOI:10.1007/s11605-007-0187-y · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Operative treatment of chronic pancreatitis is indicated for patients with intractable pain after failed medical and endoscopic treatment, or for the presence of complications of the disease. This study evaluates a single-center experience with operative management of chronic pancreatitis.
The records of 372 consecutive patients who underwent lateral pancreaticojejunostomy (n = 184), pancreaticoduodenectomy (n = 97), or distal pancreatectomy (n = 91) for chronic pancreatitis between 1995 and 2003 were retrospectively reviewed and analyzed. Longterm outcomes were assessed by patient survey, with a median followup of 5.5 +/- 0.2 years.
Primary indication for operative treatment included intractable pain (n = 215), pancreatic duct disruption (n = 109), inflammatory mass (n = 42), or biliary obstruction (n = 6). Perioperative morbidity was 22%, 51%, and 29% after lateral pancreaticojejunostomy, pancreaticoduodenectomy, and distal pancreatectomy, respectively, with a perioperative mortality rate of 1%. Two hundred twenty-eight patients were available for longterm followup. Fifty-eight patients (25%) died in the followup period. Twenty-four percent of the remaining 170 patients were pain free, and 25% had good pain control after the procedure. On multivariate analysis, risk factors for poor pain control were pancreaticoduodenectomy (p < 0.01), preoperative narcotic dependence (p < 0.02), earlier abdominal operations (p < 0.02), and an absent history of gallstone pancreatitis (p < 0.05). Sixty-two percent returned to work. Quality of life assessed by SF-36 version 2 questionnaire showed norm-based scores between the 35th and 46th percentile and slightly below, but not substantially different from, a general population. New onset of endocrine and exocrine insufficiency was present in 35% and 29% of patients, respectively.
Operative management of chronic pancreatitis can be performed with low mortality and acceptable morbidity. Surgical treatment can provide good pain control, return patients to work, and achieve a satisfactory quality of life in the majority of patients. Longterm mortality is high in a subset of patients.
Journal of the American College of Surgeons 06/2007; 204(5):1039-45; discussion 1045-7. DOI:10.1016/j.jamcollsurg.2006.12.045 · 5.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: EUS has been proposed as a minimally invasive and accurate test to detect chronic pancreatitis (CP).
To investigate the correlation between EUS criteria and histopathology grading in patients with presumed CP.
Patients who received pancreatic surgery according to presumed CP from the Medical University of South Carolina surgical database between 1995 and 2003 were identified and included if EUS was performed within 1 year before surgery. The number of EUS criteria for CP was compared with a histologic fibrosis score (FS).
Sensitivity and specificity of number of EUS criteria compared with FS.
Seventy-one patients were identified (38 women). Median FS was 7 (range, 0-12). Of the patients with calcifications: calcifications were detected by EUS in 30 (42%), 14 (47%) had calcifications missed by other imaging modalities, and 28 (93%) were confirmed to have abnormal histology (FS > or = 2). Of the patients without calcifications: in the 41 patients without calcifications on EUS, 36 (88%) had FS > or = 2; median FS was 5 (range, 0-12); the correlation between the number of EUS criteria and FS was low but statistically significant (r = 0.40; P = .01). Three or more EUS criteria provided the best balance of sensitivity (83.3%) and specificity (80.0%) for predicting abnormal histology.
Retrospective study. All patients were believed to need surgery.
A threshold of 3 or more EUS criteria provides the best balance of sensitivity and specificity for histologic pancreatic fibrosis. Calcifications seen by EUS but missed by other imaging are common in this group of patients.
[Show abstract][Hide abstract] ABSTRACT: To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined," the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29), 92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in 3 samples for which the initial cytological diagnosis was "suspicious" and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis.
International Journal of Cancer 04/2007; 120(7):1511-7. DOI:10.1002/ijc.22487 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autoimmune sclerosing pancreatitis (ASP) is a recently recognized cause of chronic pancreatitis. The role of operative intervention in this disease is controversial. A single center experience with 161 consecutive pancreatic resections for chronic pancreatitis was retrospectively reviewed. Operative specimens were reanalyzed and assessed for histological features of ASP. Long-term outcome was assessed by patient survey. Eight patients were identified with histological changes consistent with ASP. The pancreatic anatomic configuration according to intraoperative findings and preoperative radiographic evaluation was categorized into (1) diffusely enlarged pancreas (n = 4), (2) localized mass (n = 2), or (3) refractory pancreatic duct disruption without pancreatic enlargement (n = 2). Five patients underwent pancreaticoduodenectomy and three patients underwent distal pancreatectomy. Perioperative morbidity, operative time, and intraoperative estimated blood loss were similar to the same operation for other etiologies of chronic pancreatitis. Biliary obstruction occurred in two patients. Seven patients were alive 5 +/- 0.4 years after operation. Good quality of life measured by the SF-36 questionnaire was present in 4 of 7 patients surveyed. Good pain control was achieved with return to work in 5 of 7 patients. Two patients with poor pain control received glucocorticosteroids therapy without improvement in symptoms. Patients with ASP and a mass suspicious for malignancy or refractory duct disruption require operative intervention. Early postoperative outcome, long-term pain control, and improvement in quality of life appear to be good.
Journal of Gastrointestinal Surgery 02/2007; 11(1):56-8. DOI:10.1007/s11605-006-0043-5 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammatory myofibroblastic tumor is a rare benign entity formerly known as inflammatory pseudotumor. Involvement of the liver is extremely rare. There are controversies about the optimal treatment of this benign entity. Newer reports suggest an association with autoimmune sclerosing pancreatitis and primary sclerosing cholangitis. We present a case of an 18-year-old patient with biliary obstruction from a perihilar mass of the liver requiring hepatic resection. Division of the hepatic bile duct resulted in drainage of yellow, thick, gelatinous material in the presence of benign margins and absence of cholangitis. Histological examination showed a mass with fibroblastic and myofibroblastic cells set in a loose myxoid matrix containing scattered lymphocytes, consistent with an inflammatory myofibroblastic tumor. One-year recovery was uneventful. This report discusses the presentation, diagnosis, and controversies in management of this disease.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2007; 14(4):421-3. DOI:10.1007/s00534-006-1176-3 · 1.60 Impact Factor