The aim of this study was to evaluate the correlation between the histologic status of accompanying chronic hepatitis and the recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy by multivariate analysis.Recent studies have suggested that a considerable number of intrahepatic recurrence of HCC after hepatectomy might be the results of metachronous multicentric hepatocarcinogenesis. The authors hypothesized that the incidence of recurrence due to metachronous multicentric hepatocarcinogenesis would depend on the histologic status of accompanying chronic viral liver disease, which is a main promoter of HCC.One hundred ten patients with HCC who underwent curative resection were studied. Histologic status of accompanying chronic hepatitis was classified into the three categories: 1) normal liver or chronic persistent hepatitis (CPH, n = 13), 2) chronic aggressive hepatitis (CAH, n = 50), and 3) liver cirrhosis (LC, n = 47).The Cox multivariate proportional hazard model showed that the accompanying chronic viral hepatitis status (p = 0.0133), extent of hepatectomy (p = 0.0078), and number of tumors (p = 0.0475) were significantly predictive variables for recurrence-free survival. By the log-rank test, recurrence-free survival rate in patients with CPH was significantly higher than those in patients with CAH (p = 0.0005) and LC (p = 0.0075). Patients with CAH had the lowest recurrence-free survival rate (vs. LC, p = 0.028).The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.
The recurrence of autoimmunity and allograft rejection act as major barriers to the widespread use of islet transplantation as a cure for type 1 diabetes. The aim of this study was to evaluate the feasibility of immunoisolation by use of an agarose microcapsule to prevent autoimmune recurrence after islet transplantation.Highly purified islets were isolated from 6- to 8-week-old prediabetic male nonobese diabetic (NOD) mice and microencapsulated in 5% agarose hydrogel as a semipermeable membrane. Islet function was evaluated by a syngeneic islet transplantation model, in which islets were transplanted into spontaneously diabetic NOD mice.The nonencapsulated islet grafts were destroyed and diabetes recurred within 2 weeks after transplantation in all 12 mice. In contrast, 13 of the 16 mice that underwent transplantation with microencapsulated islets maintained normoglycemia for more than 100 days after islet transplantation. Histologic examination of the nonencapsulated islet grafts showed massive mononuclear cellular infiltration with beta-cell destruction. In contrast, the microencapsulated islets showed well-granulated beta cells with no mononuclear cellular infiltration around the microcapsules or in the accompanying blood capillaries between the microcapsules.Agarose microcapsules were able to completely protect NOD islet isografts from autoimmune destruction in the syngeneic islet transplantation model.
The long-term durability of agarose microencapsulated islets against autoimmunity was evaluated in NOD mice. Islets were isolated from 6-8-week-old prediabetic male NOD mice and microencapsulated in 5% agarose hydrogel. Microencapsulated or nonencapsulated islets were transplanted into the omental pouch of spontaneously diabetic NOD mice. Although the diabetic NOD mice that received nonencapsulated islets experienced a temporary reversal of their hyperglycemic condition, all 10 of these mice returned to hyperglycemia within 3 weeks. In contrast, 9 of 10 mice transplanted with microencapsulated islets maintained normoglycemia for more than 100 days. Islet grafts were removed at 100, 150, 200, 300, and 400 days posttransplantation. A prompt return to hyperglycemia was observed in the mice after graft removal, indicating that the encapsulated islet grafts were responsible for maintaining euglycemia. Histological examination revealed viable islets in the capsules at all time points of graft removal. In addition, β-cells within the capsules remained well granulated as revealed by the immunohistochemical detection of insulin. No immune cells were detected inside the microcapsules and no morphological irregularities of the microcapsules were observed at any time point, suggesting that the microcapsules successfully protected the islets from cellular immunity. Sufficient vascularization was evident close to the microcapsules. Considerable numbers of islets showed central necrosis at 400 days posttransplantation, although the necrotic islets made up only a small percentage of the islet grafts. Islets with central necrosis also showed abundant insulin production throughout the entire islets, except for the necrotic part. These results demonstrate the long-term durability of agarose microcapsules against autoimmunity in a syngeneic islet transplantation model in NOD mice.
The purpose of this study was to evaluate bacterial infection in bile juice in 18 cases undergoing biliary tract operation. Bile juice was taken from a drainage tube of the biliary tract during the operation procedure and as time elapsed after the operation, and was cultured to define the bacterial infection. The bile juice was highly contaminated with bacteria during examination, in which enterococcus and Gram-negative rod were frequently detected. The incidence of infection with enterococcus, E. coli or Klebsiella tended to increase after the operation, taking part in plural bacterial infection. Infection of bile juice was closely related with obstruction of the bile tract before operation and operative procedures. No preservation of papilla Vater function and plural bacterial infection, including anaerobic bacterial infection, might participate in the occurrence of biliary tract infection after the operation. Therefore, it was suggested that different preventive measure was necessary based on the degree of bacterial infection in each case.
Background. Vascular endothelial growth factor (VEGF), a major angiogenic factor, mediates a variety of disease conditions through promotion of angiogenesis. It also plays a critical role as a potent proinflammatory cytokine in a variety of physiologic and pathologic immune responses. In the present study, we evaluated the expression of VEGF in hepatic warm ischemia-reperfusion (I/R) injury and examined the effect of recombinant human (rh)VEGF administration in an established murine model. Method. The expression of VEGF in the liver was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry during I/R injury using 70% partial hepatic ischemia model. The effect of rhVEGF administration on I/R injury was evaluated by measuring liver function and histology. In addition, local inducible nitric oxide synthase (iNOS) and endothelial NO synthase expressions were examined to address the underlying mechanisms. Results. The local expression of VEGF was significantly up-regulated at 2 hours after reperfusion after 60 minutes of ischemia compared with that in the naïve liver. VEGF was expressed predominantly in CD11b+ cells infiltrating into the ischemic liver. The administration of rhVEGF had a significant protective effect on ischemic injury in the liver. This effect was associated with the up-regulation of iNOS expression in the rhVEGF-treated liver. Conclusion. We demonstrate a dual role of VEGF in hepatic warm I/R injury. Although endogenous VEGF is expressed and functional to initiate hepatic I/R injury, exogenous rhVEGF has a beneficial effect on the ischemic liver. These data may provide new insights into the role of VEGF as well as pathophysiology of hepatic I/R injury.
Solid pseudopapillary neoplasms of the pancreas are rare. Moreover, pancreatoduodenectomy (PD) and postoperative care are not common in pediatric surgery. Herein, we report a case of PD and nonalcoholic fatty liver disease (NAFLD) after PD and present a literature review.A 10-year-old girl with a suspected liver tumor was referred to our hospital. Echography, enhanced computed tomography and magnetic resonance imaging showed that the tumor coexisted with the solid and cystic parts of the pancreatic head. Since the patient was a young woman and the imaging findings were consistent with that of pancreatic solid pseudopapillary neoplasms (SPNs), we diagnosed her with pancreatic SPN. Thereafter, PD was performed, and she was discharged 10 days after the operation. Although her postoperative course was mostly uneventful, she experienced few episodes of abdominal pain and diarrhea before hospital discharge. These symptoms subsequently became more frequent and severe. The patient was urgently readmitted to the hospital for watery steatorrhea and lower abdominal colic pain. Her serum aspartate aminotransferase and alanine aminotransferase levels were elevated, and a fatty liver was detected on echography. The patient was diagnosed with steatorrhea, peristaltic pain, and NAFLD after PD. Pancrelipase (containing pancreatic digestive enzymes), antidiarrheal agents, and probiotics were started. Dosage increase of these drugs reduced the defecation frequency and abdominal pain and switched diarrhea to loose stools. However, more lipids in meals or more meals caused diarrhea and abdominal pain. Therefore, the doses of these drugs were further increased, and another antidiarrheal agent, loperamide hydrochloride, was added. Exocrine pancreatic enzymes supplementation and careful follow-up should prevent NAFLD progression after PD. At present, the patient has occasional abdominal pain, but has tangible soft stools once or twice a day. Although echography still shows a mottled fatty liver, her hepatic enzymes are only mildly elevated.Pediatric PD is rare, and residual pancreatic function is usually sufficient, unlike in adult cases. However, we experienced a case of NAFLD after PD for a pediatric pancreatic SPN, in which pancreatic enzyme supplementation effectively improved this condition. Further attention must be paid to worsening of NAFLD that can develop nonalcoholic steatohepatitis.
