Unresectable colorectal liver metastases: the safety and efficacy of conversion therapy using hepatic arterial infusion immunochemotherapy with 5-fluorouracil and polyethylene glycol-interferon α-2a.

BACKGROUND: Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy. METHODS: Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors. RESULTS: With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09). CONCLUSIONS: Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.

Laparoscopic cholecystectomy and common bile duct exploration for cholecystocholedocholithiasis with a left-sided gallbladder: report of a case.

A 75-year old woman was admitted to our hospital with right upper quadrant pain, vomiting, and jaundice. Laboratory findings showed elevated total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, and C-reactive protein levels. Abdominal ultrasonography (US) and drip infusion cholangiographic computed tomography (DIC-CT) showed not only cholecystocholedocholithiasis, but a gallbladder located left of the round ligament and close to the lateral segments of the liver. We performed laparoscopic cholecystectomy (LC) with choledocholithotomy for suspected cholecystocholedocholithiasis with a left-sided gallbladder. Routine ports were inserted in the American configuration for LC. The gallbladder was normogradely separated from the gallbladder fossa, and the fundus of the gallbladder was lifted ventrally and toward to the patient's right shoulder. These procedures provided the usual view for laparoscopic choledochotomy. The patient recovered uneventfully and was discharged on postoperative day 10. To our knowledge, this is the first report of laparoscopic common bile exploration in a patient with a left-sided gallbladder.

Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis.

BACKGROUND: Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein. METHODS: In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated. RESULTS: Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction. CONCLUSIONS: Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.

Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid.

OBJECTIVES: Clinical studies have shown that administration of eicosapentaenoic acid (EPA) to patients who have unresectable pancreatic cancer induces marked attenuation of cachexia. However, the exact mechanisms of the beneficial effect of EPA on pancreatic cancer are unknown. This examined the effect of EPA on proliferation of human pancreatic cancer cell lines and sought to clarify its mechanisms. METHODS: The effects of EPA on proliferation of three human pancreatic cancer cell lines (SW1990, AsPC-1, and PANC-1) were assessed. Induction of apoptosis and expressions of apoptosis-related proteins were measured. The effect of EPA on cyclo-oxygenase-2 expression in these cell lines was determined. RESULTS: EPA inhibited proliferation of all three human pancreatic cancer cell lines in a dose-dependent fashion. Simultaneously, EPA treatment induced apoptosis and this was associated with caspase-3 activation. EPA treatment was also associated with a decrease in intracellular levels of cyclo-oxygenase-2 protein. CONCLUSION: We have demonstrated that EPA inhibits human pancreatic cancer cell growth due at least in part to the induction of apoptotic cell death. Such apoptosis is associated with activation of caspase-3 and suppression of cyclo-oxygenase-2 expression. Greater understanding of the molecular events associated with the biological activity of EPA should enhance the therapeutic potential of administration of EPA to patients who have pancreatic cancer.

Carcinoid tumor of the extrahepatic bile duct: report of a case.

We report a rare case of carcinoid tumor of the extrahepatic bile duct. A 69-year-old woman with a history of hyperthyroidism was diagnosed to have a tumor of the extrahepatic bile duct. Laparotomy, for presumed cholangiocarcinoma, revealed a 2.5-cm-long, firm mass of the hilar-upper bile duct. The extrahepatic bile duct resection and lymphadenectomy was performed. Her postoperative course was uneventful and has been asymptomatic without recurrent tumor during 2 years of follow-up. Primary carcinoid tumors of the extrahepatic bile duct are very rare. Herein we report this rare case with a review of the literature.

Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx.

OBJECTIVE: To present the first reported case of a simultaneous squamous cell carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and the 9-month follow-up results. STUDY DESIGN: Case study. METHODS: Review of diagnostic studies, the operative technique, and the patient's chart for the 9-month period after treatment. RESULTS: A case with double laryngeal tumors with simultaneous evolution but different histological patterns is described. The squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the anterior commissure. A partial laryngectomy was performed, and the patient has been free of disease for 9 months. CONCLUSIONS: Multiple laryngeal tumors are exceedingly rare. To our knowledge, no previous reports of a simultaneous squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported. Both tumors were not invasive in this case, so conservation surgery was feasible.

Reconstruction of a large duodenal defect created by resection of a duodenal tubulovillous adenoma using a double-tract anastomosis to a retrocolic roux-en-y loop: report of a case.

Adenomas arising in the duodenum are uncommon. The surgical approach to adenoma of the duodenum remains controversial. We herein report the successful closure of a large defect after a partial duodenectomy for an adenoma. A 60-year-old man developed duodenal adenoma. An upper gastrointestinal roentgenographic series and endoscopy revealed a 2.5-cm tumor located adjacent to the duodenal papilla. The tumor was too large to be removed endoscopically, and therefore it was resected en bloc by a partial duodenectomy. Histology confirmed the diagnosis of benign tubulovillous adenoma. The large duodenal defect created by resection of the tumor was closed with double-tract anastomosis to a retrocolic Roux-en-Y loop. Large duodenal defects represent difficult surgical problems. Closure by direct anastomosis to a Roux-en-Y loop side-to-side is thus considered to be the procedure of choice.