Menahem Ben-Haim

Endoscopic sphincterotomy and temporary internal stenting for bile leaks following complex hepatic trauma

Biliary leak secondary to blunt or penetrating hepatic trauma and damage to the intrahepatic biliary tree remains a challenging problem. The role and safety of endoscopic retrograde cholangiopancreatography (ERCP) and stenting in this setting were studied.

Is There a Survival Benefit to Neoadjuvant Versus Adjuvant Chemotherapy, Combined with Surgery for Resectable Colorectal Liver Metastases?

BackgroundThe benefits of adding chemotherapy to surgery in patients with hepatic colorectal metastases at moderate and high risk for recurrence and the optimal sequence of administration are undetermined.MethodsWe followed the overall-survival and event-free survival rates after operation in patients with resectable colorectal metastases confined to the liver. The adjuvant patients first underwent surgery and then treatment, whereas the neoadjuvant patients underwent treatment, surgery, and re-treatment. Assignment was by oncologist and patient preferences. Chemotherapy was oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) based.ResultsFifty-six of 105 patients who underwent liver resections for colorectal metastases (2002–2005) are included. The two groups were comparable for demographics, characteristics of disease (including recurrence risk), treatment protocols, and follow-up. The respective 1-, 2-, and 3-year overall survival rates were 91%, 91%, and 84%, and the event-free survival rates were 63%, 49%, and 49% for the 19 adjuvant patients, and 95%, 91%, and 70%, and 94%, 50%, and 50% for the 37 neoadjuvant patients.ConclusionsThe midterm overall survival and disease-free survival rates in this group of patients with resectable colorectal metastases to the liver, who were treated with combination of resection and chemotherapy, were similar, regardless of the sequence of treatment.

High-Throughput Mutation Profiling in Intraductal Papillary Mucinous Neoplasm (IPMN)

BackgroundSpecific mutations leading to the development of various histological grades of intraductal papillary mucinous neoplasm (IPMN) have been partially characterized.MethodsAnalysis of 323 oncogenic mutations in 22 tumor-related genes was conducted, using a chip-based matrix-assisted laser desorption time-of-flight mass spectrometer of DNA extracted from microdissected cells of low-grade (n = 14), borderline (n = 6), and invasive IPMN (n = 7). Additional assays were performed on the DNA extracted from dyplastic cells found in the background of the adenocarcinoma.ResultsWe identified 9 K-ras mutations (low grade, 2/14; borderline, 1/6; invasive, 6/7), 3 p53 mutations (low grade, 1/14; invasive 2/7), and 2 PIK3CA mutations (low grade, 1/14; invasive, 1/7). K-ras, p53, and PIK3CA mutations present in the invasive cancer were absent in the adjacent precursor cells in 50% of the cases. In one patient, K-ras mutation was present in the precursor lesion and absent in the adjacent invasive lesion.ConclusionsOf the 22 screened tumor-related genes, only K-ras, p53, and PIK3CA mutations were found in IPMN. K-ras mutations are more prevalent in invasive than premalignant IPMN. The variable coexistence of mutations in the invasive cancer and in the adjacent precursor cells may point to the heterogeneous nature of this tumor.

Pancreatic cancer: Surgery is a feasible therapeutic option for elderly patients

BackgroundCompromised physiological reserve, comorbidities, and the natural history of pancreatic cancer may deny pancreatic resection from elderly patients. We evaluated outcomes of elderly patients amenable to pancreatic surgery.MethodsThe medical records of all patients who underwent pancreatic resection at our institution (1995-2007) were retrospectively reviewed. Patient, tumor, and outcomes characteristics in elderly patients aged ≥ 70 years were compared to a younger cohort (<70y).ResultsOf 460 patients who had surgery for pancreatic neoplasm, 166 (36%) aged ≥ 70y. Compared to patients < 70y (n = 294), elderly patients had more associated comorbidities; 72% vs. 43% (p = 0.01) and a higher rate of malignant pathologies; 73% vs. 59% (p = 0.002). Operative time and blood products consumption were comparable; however, elderly patients had more post-operative complications (41% vs. 29%; p = 0.01), longer hospital stay (26.2 vs. 19.7 days; p < 0.0001), and a higher incidence of peri-operative mortality (5.4% vs. 1.4%; p = 0.01). Multivariable analysis identified age ≥ 70y as an independent predictor of shorter disease-specific survival (DSS) among patients who had surgery for pancreatic adenocarcinoma (n = 224). Median DSS for patients aged ≥ 70y vs. < 70y were 15 months (SE: 1.6) vs. 20 months (SE: 3.4), respectively (p = 0.05). One, two, and 5-Y DSS rates for the cohort of elderly patients were 58%, 36% and 23%, respectively.ConclusionsProperly selected elderly patients can undergo pancreatic resection with acceptable post-operative morbidity and mortality rates. Long term survival is achievable even in the presence of adenocarcinoma and therefore surgery should be seriously considered in these patients.

Intraductal papillary mucinous neoplasm of the pancreas: associated cancers, family history, genetic predisposition?

BACKGROUND High rates of extrapancreatic malignancies (EPM) have been observed in patients with intraductal papillary mucinous neoplasm (IPMN). IPMN in patients with familial pancreatic cancer have also been reported. Our purpose was to evaluate the association of IPMN with EPM, malignancies in family members, and germline BRCA1 and BRCA2 mutations. METHODS Using retrospective analysis on prospectively collected data from 82 patients with IPMN and direct contact for familial cancer history, data were compared with those of 150 patients with pancreatic ductal adenocarcinoma (PDAC). The common germline mutations in the BRCA1 and BRCA2 genes were evaluated on available IPMN patients. RESULTS EPM rates were greater in IPMN than PDAC patients (P = .002). Malignancies in first-degree relatives, specifically pancreatic cancer, were more common among IPMN than PDAC patients (P = .028). IPMN patients with EPM had high rates of relatives with colorectal cancer (31%). Two of the 51 genetically tested patients (4%) were BRCA2 mutation carriers, and both had first-degree relatives with pancreatic cancer. One patient fulfilled the Amsterdam criteria for hereditary nonpolyposis colon cancer; however, the neoplasm was microsatellite stable. CONCLUSION Our results demonstrated high rates of EPM among IPMN patients. There was an increased rate of cancer in families of IPMN patients, specifically pancreatic cancer. A high rate of colorectal cancer in families of IPMN patients who have EPM was also observed. These findings suggest a genetic component in the pathogenesis of IPMN. Possible genetic changes include BRCA2 mutations, which are found in 25% of IPMN patients with a family history of pancreatic cancer.

Clinical presentation can predict disease course in patients with intraductal papillary mucinous neoplasm of the pancreas.

BackgroundPreoperative diagnosis of malignancy within intraductal papillary mucinous neoplasm of the pancreas (IPMN) solely by clinical or radiological findings is not always possible. We sought a correlation between preoperative clinico-radiological findings and outcome.MethodsA prospective database of pancreatic resections for IPMN (2002–2008) and a retrospective pathological revision of all pancreatic cancer specimens (1995–2001) were analyzed. The patients were grouped into asymptomatic with preoperative diagnosis of IPMN (group 1), symptomatic with a preoperative diagnosis of IPMN (group 2), and those with a preoperative diagnosis of pancreatic cancer whose specimen revealed a background of IPMN (group 3). The groups were compared for demographics, clinical presentation, pathological findings, and outcome.ResultsOf the 62 patients with IPMN, 19 were in group 1, 23 in group 2, and 20 in group 3. Their median age (range) was 65.6 (46–80), 67 (50–84), and 73.4 (57–86) years, respectively. The clinical presentation for groups 2 and 3 included abdominal pain (56% vs. 32 %), weight loss (8% vs. 52%), obstructive jaundice (4% vs. 57%), pancreatitis (22% and 5%), and new onset of diabetes (14% and 44%). Invasive cancer was found in one patient in group 1 (5.2%), two patients in group 2 (8.7%), and all patients in group 3. IPMN was present in 23 of 217 (10.6%) of all resected pancreatic cancer specimens. Five year survival for patients with invasive disease was 47% and 92% for patients with noninvasive disease (mean follow-up 37.6 months).ConclusionsBenign IPMN can usually be differentiated from adenocarcinoma preoperatively. The clinical presentation is highly indicative of disease course.

Budd-Chiari Syndrome and Acute Portal Vein Thrombosis: Management by a Transjugular Intrahepatic Portosystemic Shunt (TIPS) and Portal Vein Interventions via a TIPS

Acute portal vein thrombosis (PVT) is a devastating complication of Budd-Chiari syndrome (BCS). Con-servative approach, anticoagulation, systemic or transarterial thrombolysis, and urgent liver transplanta-tion were applied in this scenario but with poor results. We present and discuss an approach to treat BCS complicated by acute PVT. Two young female patients presented with acute liver failure, rapidly pro-gressive tense ascites, renal- and respiratory failure. The diagnosis of chronic BCS complicated by acute PVT was confirmed with ultrasound Doppler. Initial treatment was supportive. Right portal vein local-ization was by transarterial portogram or by computed tomography-guided microcoil placement. Trans-jugular intrahepatic portosystemic shunt (TIPS) was performed and included Wallstents and a Jograft in one case and Viatorr stentgraft that was extended later with a Hemobahn stentgraft in another. Mechan-ical clot removal from the portal system was performed in the primary procedure and in a revision pro-cedure in the following few days. Stents were placed precisely with no extension into the inferior vena cava or deeply into the main portal vein. Patients were fully anticoagulated and patency was assessed by ultrasound Doppler. The procedures were performed on days 5 and 10 following admission. In both cases, successful thrombectomies were reveised and maintained. Partial occlusion of the TIPS and reaccumulation of ascites were reversed with repeated procedure. Both patients were discharged without ascites and normal liver function. In conclusion, urgent TIPS and portal vein thrombectomy via TIPS are emerging therapeutic options that offer a safe and effective treatment to patients with BCS complicated by acute portal vein thrombosis.

Redefining Late Acute Graft Pancreatitis : Clinical Presentation, Radiologic Findings, Principles of Management, and Prognosis

Objective:To define the incidence, clinical presentation, radiologic findings and principles of diagnosis, and management of acute graft pancreatitis occurring more than 3 months after transplantation. Summary Background Data:Acute graft pancreatitis is a frequent late complication after simultaneous pancreas-kidney transplantation (SPKT) with enteric drainage that is not well understood. Methods:We performed a retrospective analysis of data from patients who underwent SPKT with enteric drainage at our institution. All recipients who experienced episodes that met the clinical criteria for late graft pancreatitis were included. We excluded events proven to be anastomotic or duodenal stump leaks. Clinical presentation, laboratory findings, radiologic imaging, course of management, and graft and patient outcome were evaluated and analyzed. Results:Of 79 SPKTs (1995–2007), 11 (14%) recipients experienced 31 episodes of late graft pancreatitis (average number per patient, 3; range, 1–13), occurring an average of 28 months after transplantation (range, 3 months to 8 years). All patients presented with right lower quadrant abdominal peritonitis, fever, and findings compatible with pancreas graft inflammation on computed tomography or ultrasound imaging. Mild hyperamylasemia (>110 IU/L) was found in 82% of cases. Treatment was conservative, including bowel rest, antibiotics, and percutaneous sampling and drainage of abscesses as necessary. Excellent graft and patient survival were achieved. Conclusion:The diagnosis of late acute graft pancreatitis is clinical, with confirmatory computed tomography or ultrasound imaging. Conservative treatment yields excellent graft and patient survival.

PANCREAS Transplantation 120: Late Intra-Abdominal Surgical Complications after Pancreas Transplantation With Roux-en-Y Enteric Drainage

tions or peri-operative mortalities. Twelve patients (43%) underwent a Whipple procedure and required a concomitant portal or SMV resection due to venous involvement. Operative time and blood loss was increased in the venous resection group. Peri-operative complications were observed in three of 12 patients who also underwent portal or SMV resection and 5 of 16 patients who underwent Whipple alone. Four of the 12 patients in the venous resection group and 3 of 16 in the Whipple alone group succumbed to recurrent disease at one-year follow-up. Four previously published series also support similar survival rates for patients undergoing Whipple procedure alone or concommitant venous resection. Conclusion: Adding portal or SMV resection to a Whipple procedure may be performed safely and allows a significantly greater number of patients with periampullary malignancies to benefit from surgical resection.