Falciform ligament in pancreatoduodenectomy for protection of skeletonized and divided vessels

Background/purpose  Pancreatic fistula, which is one of the main causes of late postpancreatectomy hemorrhage (PPH), is a common complication of pancreatoduodenectomy (PD). It may erode the anastomosis site and vascular wall in its vicinity, resulting in pseudoaneurysm formation and/or the rupture of major vessels. To protect the vessels near the area for pancreaticojejunostomy from potential pancreatic fistula, we have adopted a surgical option by which such vessels are separated from the pancreaticojejunostomy using a pedicled falciform ligament. We reviewed 36 patients who underwent PD that included this option. Methods  After the PD was completed (before reconstructions), the pedicled falciform ligament was spread widely on the major vessels exposed during resection, and was fixed to the surrounding retroperitoneal connective tissue. These procedures enabled the complete separation of these vessels from the pancreaticojejunostomy. Results  The mobilization and placement of the falciform ligament in the space between the pancreaticojejunostomy and the major vessels were successfully carried out without any complications. Although ten (28%) patients developed pancreatic fistula and three (8%) developed intraabdominal infection, none of the patients developed late PPH. Conclusions  The present surgical option is technically simple and easy, and may be an effective prophylactic measure against late PPH following PD.     

Synthetic bioabsorbable stent material for duct-to-duct biliary reconstruction

Biliary stricture remains a significant cause of morbidity after liver transplantation. We performed duct-to-duct biliary anastomosis by using an absorbable stent tube with a diameter equal to that of pig common bile duct as an internal stent. The stent tube was constructed using a synthetic biodegradable material-a lactic glycolic acid and epsilon-caprolactone copolymer. Three pigs were alive without cholestasis for 180 d; however, 1 pig died on the 65th postoperative d, and autopsy revealed no cholestasis or biliary sledge in the biliary stent tube. The 3 pigs were euthanized for histological examinations 180 d after surgery; the biliary stent tube was completely absorbed by this time. These experimental results showed the good patency of the absorbable biliary stent tube. In the future, the absorbable biliary stent tube is expected to be clinically developed as a biliary stent for biliary anastomosis, which may protect the biliary anastomotic stricture.     

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer

Background and aims Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia.Materials and Methods The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration200 mol/l, was evaluated.Results The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia.Conclusions Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.     

Effects of intravenous adenosine 5′-triphosphate on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery: a double-blind placebo-controlled study

Purpose  We conducted a double-blind placebo-controlled study to investigate the effects of the intraoperative intravenous infusion of adenosine 5′-triphosphate (ATP) on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery. Methods  Thirty patients (age, 16–42 years; 16 males/14 females) scheduled for sagittal split ramus osteotomy were assigned in a double-blind fashion to receive intraoperative intravenous infusion of ATP (n = 15) or saline (n = 15). Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Local anesthesia was added for intraoperative analgesia. In the ATP group, ATP was infused at a rate of 160 μg·kg⁻¹·min⁻¹ throughout surgery. Postoperative pain was managed with intravenous patient-controlled analgesia (PCA) with morphine. The intensity of postoperative pain was assessed with a verbal numeric rating scale (NRS). Morphine consumption was also assessed. Results  There were no differences in demographic, anesthetic, and surgical data between the ATP and placebo groups. Intraoperatively, ATP effectively suppressed responses of blood pressure and heart rate to painful surgical stimuli. There were no differences in postoperative NRS scores between the two groups. However, postoperative morphine consumption was significantly less in the ATP group, compared with the placebo group, throughout the 72-h postoperative observation period. Cumulative morphine consumption for 72 h postoperatively was 47% less with ATP, compared with placebo. No adverse effect of ATP was observed. Conclusion  Our data suggest that intraoperative ATP infusion can blunt hemodynamic responses to surgical stimuli and produce prolonged analgesia in patients undergoing major orofacial surgery.     

Inhibition of Autophagy by 3-MA Enhances the Effect of 5-FU-Induced Apoptosis in Colon Cancer Cells

Background  5-fluorouracil-(5-FU)-based adjuvant chemotherapy is widely used for the treatment of colorectal cancer. However, 5-FU resistance in the course of treatment has become more common. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored. Methods  Two colon-cancer-derived cell lines, colon26 and HT29, were used to investigate the effect of 5-FU, 3-methyladenine (3-MA, an autophagy inhibitor), or their combination on apoptotic cell death and autophagy. MTT assay, Hochest plus propidium iodide (PI) staining, and DNA fragmentation assay were used to observe apoptosis. Meanwhile, monodansylcadaverine (MDC) was used to detect autophagy. Finally, immunoblotting assay was used to explore the molecular change that occurred. Results  We observed the apoptosis induced by 5-FU in colon cancer cells. Meanwhile, autophagy was also stimulated. The combination treatment of 3-MA and 5-FU significantly increased the apoptotic cell death. By isolating the subcellular fractions of mitochondria and cytosol, we observed that the release of cytochrome c was increased in combination-treated cells. Cytochrome c resulted in the activation of caspase-3, thus activating PARP. Moreover, the anti-apoptotic protein, Bcl-xL, was significantly downregulated by 3-MA. Conclusions  Our results suggest that 5-FU-induced apoptosis in colon cancer cells can be enhanced by the inhibitor of autophagy, 3-MA. Autophagy might play a role as a self-defense mechanism in 5-FU-treated colon cancer cells, and its inhibition could be a promising strategy for the adjuvant chemotherapy of colon cancer.     

Indications of partial hepatectomy for transplantable hepatocellular carcinoma with compensated cirrhosis

BACKGROUND: The appropriate treatment strategy for transplantable hepatocellular carcinoma (HCC) patients with compensated cirrhosis remains controversial. METHODS: Surgical outcomes were reviewed in 136 cirrhotic patients with transplantable HCC who had undergone partial hepatectomy. Transplantable HCC was defined as that corresponding to Milan's criteria. RESULTS: The adverse prognostic factors for both survival and disease-free survival were histologic surgical margin of 5 mm or less, Child-Pugh B, and the presence of hepatitis C virus infection. The overall 5-year survival and disease-free survival rates of patients with 1 or none of the adverse prognostic factors were 73% and 33%, respectively, whereas those of patients with 2 or 3 adverse prognostic factors were 36% and 17%, respectively. CONCLUSIONS: Transplantable HCC patients with 2 or 3 adverse prognostic factors should be considered candidates for liver transplantation, whereas patients with only 1 or none of the adverse prognostic factors are good candidates for partial hepatectomy.     

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.