A novel triple secured technique for pancreatic reconstruction following pancreaticoduodenectomy for a soft pancreas.

BACKGROUND/AIMS: Soft pancreases are susceptible to developing pancreatic fistula following pancreaticoduodenectomy. To reduce the incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a soft pancreas, we developed a triple secured technique. In this study, we describe the details of this technique and also report on the postoperative outcomes. METHODOLOGY: The triple secured technique employed an ultrasonic dissector for pancreatic transection with skeletonizing and ligating of the small pancreatic branch ducts, duct-invagination or duct-to-mucosa anastomosis for main pancreatic duct management, and, finally, four large stitches between the pancreatic stump parenchyma and the jejunal seromuscular layer to prevent minor pancreatic leakage. A total of 28 consecutive patients with a soft pancreas who underwent pancreaticoduodenectomy using our technique were included in this study. RESULTS: Postopetrative complications occurred in 16 patients. Grade B pancreatic fistula developed in 6 patients. However, no grade C pancreatic fistula occurred in this series. Neither any reoperation nor in-hospital mortality was observed in this series. CONCLUSIONS: Our triple secured technique after pancreaticoduodenectomy was feasible and safe, with an acceptable rate of grade B pancreatic fistula and no grade C pancreatic fistula for patients with a soft pancreas.

Evolution and dynamics of pancreatic cancer progression.

Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patient's tumor are also discussed.

Prediction of posthepatectomy hepatic functional reserve by serum hyaluronate.

BACKGROUND: Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function and hepatic fibrosis. This study was designed to clarify the clinical significance of the serum hyaluronate level as a parameter of functional reserve. METHODS: The study included 283 patients undergoing hepatectomy. Liver function parameters were examined before surgery and compared with outcomes. Patients were retrospectively grouped according to the presence or absence of postoperative hepatic dysfunction. RESULTS: Preoperative serum hyaluronate levels were significantly raised in parallel with the degree of severity of the underlying chronic liver disease. Regression analysis revealed serum hyaluronate level to be an independent predictor of portal hypertension. In 131 patients undergoing major hepatectomy, preoperative hyaluronate levels were significantly higher in patients with poor outcome. Multivariable logistic regression analysis demonstrated serum hyaluronate and total bilirubin levels to be independent variables associated with postoperative hepatic dysfunction. Patients with high indocyanine green retention rate at 15 min (over 15 per cent) showed significantly higher morbidity and mortality rates when their serum hyaluronate levels were over 180 ng/ml. CONCLUSION: Serum hyaluronate is a simple clinical marker for portal venous pressure and a reliable auxiliary parameter of hepatic functional reserve in combination with other liver function tests.

The role of prostaglandins in liver ischemia-reperfusion injury.

Ischemia reperfusion (IR) of the liver is a multifactorial process that, at least in part, is responsible for the morbidity associated with major liver surgery under occlusion of the portal triad with the Pringle maneuver, total vascular exclusion or after liver transplantation. Surgeons are confronted with IR injury (IRI) more often than they anticipate. Although the human body has its own defense system, understanding the pathophysiology of IRI is essential for the surgeon in preventing and/or treating the reperfusion injury in common clinical practice. Several endogenous mechanisms exist to overcome IRI and a large number of pharmacological agents have also been found to confer protection against ischemic injury in the liver. They either blocked the injurious pathways directly or they subjected the liver to preconditioning. Prostaglandins (PGs) are a group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase (COX) pathway. They are short-lived, hormone-like chemicals that regulate cellular activities on a moment-to-moment basis and are produced in most tissues of the body, although the liver has emerged as the major organ participating in the synthesis, degradation and elimination of arachidonate products of systemic origin. PGs are released through the prostaglandin transporter on the cell's plasma membrane. During the last decade intensive work on the cytoprotective effects of PGs on livers suffering from IRI have been well documented. Prostaglandins confer their protective effects on IR-injured livers mainly by inhibiting the generation of reactive oxygen species, preventing leukocyte migration, reducing the synthesis or production of membrane degradation products, improving hepatic insulin and lipid metabolism, and regulating the production of inflammatory cytokines and cell adhesion molecules. Production of PGs have been found essential also soon after partial hepatectomy for hepatocyte proliferation.

Significance of fluorodeoxyglucose PET imaging in the diagnosis of malignancies in patients with biliary stricture.

AIM: This study was performed to evaluate the significance of positron emission tomography using fluorodeoxyglucose (FDG-PET) in diagnosing malignancy in patients with biliary stricture by comparing the sensitivity and specificity of FDG-PET with those of CT scans and cytological examination of the bile. METHODS: Thirty patients who underwent FDG-PET for differential diagnosis of the disease causing biliary stricture were included in this study. The sites of the strictures were as follows: in the intrahepatic bile duct in five patients, in the peripheral extrahepatic bile duct in 17 patients, and in the distal extrahepatic bile duct in eight patients. The sensitivity and specificity (%) of FDG-PET in diagnosing malignancies were evaluated and compared with those of CT scans and cytological examination using obtained bile. Final diagnoses were based on surgical or biopsy findings. Data was collected and analysed in a retrospective fashion. RESULTS: Malignant diseases were diagnosed in 21 patients, as follows: cholangiocarcinoma including Klatskin tumour in 10 patients, gallbladder cancer in eight, duodenal and ampulla cancer in two, and pancreatic cancer in one. In diagnosing malignancy in patients with biliary stricture, overall sensitivity and specificity were 85.7 (18/21) and 55.6 (5/9), respectively, for CT, 64.7 (11/17) and 100 (7/7), respectively, for cytological examination of the bile, and 90.5 (19/21) and 77.8 (7/9), respectively, for FDG-PET. CONCLUSIONS: In diagnosing malignant diseases in patients with biliary stricture, FDG-PET was superior to CT examination in both sensitivity and specificity, and superior to cytological examination of the bile in sensitivity. However, in patients with inflammatory disease, such as primary sclerosing cholangitis and cholecystitis, false positive rates were found. Therefore, a multidisciplinary diagnostic approach using FDG-PET in conjunction with conventional modalities seems essential to a precise differential diagnosis.

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.

Long-term survival after resection for small cell carcinoma of the esophagus.

We describe the rare case of a patient with esophageal small cell carcinoma who was completely cured. A 77-year-old man had small cell carcinoma of the esophagus with extensive lymph node metastases. Treatment comprised a subtotal esophagectomy and extended lymph node dissection. He has survived for more than 7 years with no evidence of recurrent disease. We suggest that radical operations should be considered for future patients if curative resection can be expected.

Endoscopically demonstrable esophageal changes after Helicobacter pylori eradication in patients with gastric disease.

BACKGROUND AND AIMS: An increased prevalence of reflux esophagitis has been reported following Helicobacter pylori (H. pylori) eradication in patients with duodenal ulcers in Western countries. However, it has remained unknown whether this might also appertain to individuals with other diseases. We therefore carried out this study to determine the effect of eradicating H. pylori infection in a series of Japanese patients. METHODS: Of a total of 203 H. pylori-positive patients successfully cured of infection, 82 cases (58 males, 24 females) with gastric disease, but not duodenal ulcers, were included in the present study; median age 56 years (range 18-80) and median follow up of 24 months (range 6-65). The patients were investigated clinically and endoscopically at regular intervals. RESULTS: Mild reflux esophagitis developed after eradication in three of 55 (5.5%) patients formerly without this condition, while it improved after eradication in five of 27 (18.5%) patients, with the disease endoscopically diagnosed prior to eradication. The estimated incidence of esophagitis within 3 years was 4.8% after cure of infection. Short segment Barrett's esophagus developed after eradication in six of 58 (10.3%) patients who did not have it prior to the therapy, while the condition did not improve in 24 patients affected before eradication. CONCLUSIONS: Endoscopic esophageal changes after H. pylori eradication in the present series of Japanese patients were relatively infrequent and mild. This therapeutic approach thus appears to be safe and unproblematic.

Preventive effect of preoperative portal vein ligation on endotoxin-induced hepatic failure in hepatectomized rats is associated with reduced tumour necrosis factor alpha production.

BACKGROUND: Preoperative portal vein embolization successfully reduces the incidence of postoperative hepatic failure in which endotoxin is postulated to be involved. To identify the mechanism of this preventive effect, the relationship of endotoxin-induced liver injury with tumour necrosis factor (TNF) alpha and nitric oxide production in the peripheral blood, liver and spleen of rats subjected to preoperative portal vein branch ligation (PVL) was compared with that in rats undergoing sham operation. METHODS: Rats with PVL and those that underwent sham operation were subjected to resection of ligated liver lobes (PVL-Hx rats) and two-thirds hepatectomy (noPVL-Hx rats) respectively at day 5, followed by intravenous administration of endotoxin 200 microgram/kg body-weight at day 7. At various time intervals after endotoxin injection, the peripheral blood, liver and spleen tissues were harvested and analysed for TNF-alpha and nitric oxide production. RESULTS: The survival rates of noPVL-Hx and PVL-Hx rats at 48 h after endotoxin administration were 40 and 100 per cent respectively. The former rats showed more extensive liver injury as represented by higher serum aminotransferase and hyaluronate levels than the latter. Plasma concentrations of TNF-alpha at 1.5 h after endotoxin treatment were significantly higher in noPVL-Hx rats (mean(s.e.m.) 22 125(2175) pg/ml; n = 6) than PVL-Hx rats (8344(4076) pg/ml; n = 6) (P < 0.01). Consistent with this, expression of TNF-alpha messenger RNA in the liver and spleen was suppressed in PVL-Hx rats. In two-thirds hepatectomized rats, plasma TNF-alpha concentrations after endotoxin administration at 1, 2 and 3 days (14 350(2186), 26 375(2478) and 23 000(3745) pg/ml respectively; n = 6 each) were significantly higher than that before operation (9067(1559) pg/ml; n = 6) (P < 0.05), whereas those at 5 and 7 days (10 102(3616) and 8580(1427) pg/ml respectively; n = 6 each) showed no significant increase. Furthermore, nitric oxide production in peripheral blood and liver was suppressed by preoperative PVL. CONCLUSION: Prevention of endotoxin-induced liver failure by preoperative PVL is associated with reduced production of TNF-alpha in the later phase of liver regeneration.

Measurement of serum hyaluronate as a predictor of human liver failure after major hepatectomy.

Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function. This study was designed to evaluate its application as a predictor of liver failure after major hepatectomy. Thirty-six patients who underwent right liver lobectomy after percutaneous transhepatic right branch portal vein embolization were divided into two groups based on their postoperative clinical course (groups 1 and 2, with and without postoperative liver failure, n = 6 and n = 30, respectively). We serially measured serum hyaluronate levels using a sandwich binding protein assay system before and after hepatectomy and determined relations with progression of the underlying chronic liver disorder, portal venous pressure, and liver growth of the left lobe after portal embolization. Serum hyaluronate levels were significantly elevated, in line with the degree of severity of the underlying chronic liver disorder, and correlated well with the portal venous pressure and the hypertrophic ratio of the left lobe subsequent to portal embolization. Serum hyaluronate levels in group 1 were significantly higher than those in group 2 before surgery and increased steeply during the early period after hepatectomy. These results suggest that the serum hyaluronate reflects the hepatic functional reserve, and serial measurement of this parameter after hepatectomy can serve as a simple indicator for early detection of posthepatectomy liver failure.

Indications for portal vein embolization combined with major hepatic resection for advanced-stage hepatocellular carcinomas. A preliminary clinical study.

BACKGROUND: Criteria for selection of patients for portal vein embolization (PVE) before major hepatectomy for advanced-stage hepatocellular carcinoma (HCC) have not been clarified in detail. This study was aimed at defining those benefiting from this therapy in a retrospective fashion. PATIENTS AND METHODS: Firstly, to determine liver functional criteria for applying this approach 26 patients with stage III (17 patients) or IV (9 patients) disease, who underwent major hepatectomies after PVE, were divided into those without major complications (20 patients) and a postoperative liver failure group (6 patients). Clinical, analytical, and hemodynamic parameters obtained before and after PVE were compared between the groups. Secondly, to define the application of this approach with regard to tumor progression survival rates of patients were also obtained, taking into account factors which affect tumor development, i.e. lesion size, intrahepatic metastasis and vascular invasion. RESULTS: With regard to liver function 4 nonindications were obtained: (1) a portal pressure measured right after PVE >25 cm H(2)O; (2) post-PVE serum hyaluronate >200 ng/ml; (3) pre-PVE serum cholinesterase <150 U/l; (4) post-PVE serum cholinesterase <150 U/l. In view of the tumor progression in patients with HCCs featuring intrahepatic metastasis spread to more than 3 segments (IM3) 1-, 3- and 5-year survival rates were low (42.9, 28.6 and 0%) with a statistical significance, compared to those in patients with intrahepatic metastasis limited in the same lobe (76.9, 46.2 and 24.6%). CONCLUSIONS: When laboratory data fulfill 3 or more of the criteria, the extent of hepatic resection may have to be carefully reconsidered. Patients with HCCs featuring IM3 intrahepatic metastasis may not benefit from the aggressive approach described here.

Morphological and functional alterations to sinusoidal endothelial cells in the early phase of endotoxin-induced liver failure after partial hepatectomy in rats.

Liver failure following major hepatectomy is characterized pathologically by massive hepatic necrosis, which is thought to begin with injury of sinusoidal endothelial cells (SECs). To examine the early events of SECs leading to hepatic damage, we performed time-course analyses of the morphological and functional perturbation of SECs after endotoxin administration to hepatectomized rats. At 1.5 h after endotoxin injection, when hepatocellular damage was not yet evident, SECs showed augmented expression of intercellular adhesion molecule-1, with frequent adherence of infiltrating leucocytes and ultrastructural features of defenestration and hypertrophied cytoplasm enriched with cell organelles. The serum level of hyaluronate, as an indicator of the functional state of SECs, was significantly elevated. At 3 h, SECs underwent necrosis and disruption, accompanied by fibrin deposits with concomitant hepatocellular necrosis. The morphological and functional alterations of SECs precede necrotic changes in hepatocytes and SECs in endotoxin-induced liver failure after partial hepatectomy.

Protective effects of antithrombin III supplementation on warm ischemia and reperfusion injury in rat liver.

The effect of antithrombin III (AT III) supplementation on energy status, microcirculation, cytoprotection, and prostacyclin (PGI2) production during and after a period of warm ischemia of the rat liver was investigated. AT III supplementation (250 units/kg) stimulate prostaglandin I2 (PGI2) production from 1 hour after administration, with maximal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were continued for 60 minutes after reperfusion. The rats received AT III (250 units/kg IC) 30 minutes before induction of liver ischemia (AT III group). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by 31P nuclear magnetic resonance showed significant improvement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control group). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0. 05). Ultrastructural alterations of sinusoidal endothelial cells were markedly reduced in the AT III group. The PGI2 level at the end of reperfusion was significantly elevated (p < 0.01) in the AT III group compared to the control group. The results of this study indicated that pretreatment with AT III significantly improved the energy status and microcirculation, as well as histologic damage, after liver ischemia and reperfusion. One of the fundamental effects of AT III might be mediated through the production of prostacyclin.

Further characterisation of a variant type of turkey herpesvirus which releases large quantities of cell-free viruses into culture medium.

A variant type of turkey herpesvirus (HVT/VT) which releases large quantities of cell-free virus into its culture medium was compared with the prototype of the FC 126 strain of HVT (HVT/WT) as to the biological and serological characteristics. The lack of replication-defective HVT/VT in chickens was considered to be due to the inability of the virus to infect and replicate in lymphocytes and not to temperature-sensitive defects at 41 degrees C. No obvious antigenic differences were found between HVT/VT and HVT/WT in agar gel precipitation and neutralisation tests using four specific antisera prepared in chickens hyperimmunised with cells infected with HVT/WT or HVT/VT and cultural supernatants of cells infected with HVT/WT or HVT/VT. Group-specific (gs) A and gs B antigens were released into the culture medium from cells infected with HVT/VT.

A comparison of the biological properties of type 2 plaque-producing agent derived from the Cal-1 strain of Marek's disease virus with other related viruses.

The serological and biological properties of the type 2 plaque-producing agent (PPA) derived from the Cal-1 strain of Marek's disease virus (MDV) were compared with those of reference strains of the three serotypes of MDV and herpesvirus of turkeys (HVT) groups; namely JM, HPRS-24 strains of MDV and the FC-126 strain of HVT for serotype 1, 2, and 3, respectively. By agar gel precipitation (AGP), indirect fluorescent antibody and virus neutralization tests, type 2 PPA was related but not identical to the FC-126 strain. By the AGP test, type 2 PPA showed a poor ability to synthesize B antigen and the A antigen was different from that of strain FC-126. To compare the virological characteristics of type 2 PPA with the reference strains, the release of cell-free virus into supernatants of infected cell cultures and titers of cell-free virus extracted sonically from infected cell cultures were examined. Cell-free type 2 PPA virus was easily detected in the supernatants and extracted from infected cell cultures. These properties were similar to reference strains of serotype 2 and 3. Next, the structural similarities of viral DNAs of type 2 PPA and strain FC-126 were examined by Southern blot hybridization. The restriction endonuclease-cleavage patterns of DNA of type 2 PPA were very similar but not identical to those of the FC-126 strain. In chickens inoculated with type 2 PPA, splenic lymphocytes supported a non-productive latent infection as did also those from chickens inoculated with the FC-126 or HPRS-24 strains. From these results, type 2 PPA appears to belong to serotype 3 of MDV and HVT groups. The origin of type 2 PPA is discussed.

In ovo interference of embryo non-lethal avian infectious bronchitis viruses (IBV) with velogenic Newcastle disease virus and embryo adapted IBV.

Avian infectious bronchitis virus (IBV) interfered with the lethal effects of velogenic Newcastle disease virus (NDV) and embryo adapted IBV in eggs previously inoculated with non-lethal IBV. Greater interference was noted in eggs superinfected with embryo adapted IBV than velogenic NDV. The interference could be eliminated by treating the initial IBV with homologous anti-IBV serum.