Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts.

The effects of ethanol extracts from Thai plants belonging to the families of Annonaceae, Rutaceae, and Zingiberaceae on P-glycoprotein (P-gp) function and multidrug resistance were examined in paclitaxel-resistant HepG2 (PR-HepG2) cells. All the extracts tested, significantly increased the accumulation of [3H]paclitaxel, a P-gp substrate, in the cells. Among nine extracts, Z01 and Z02, extracts from Curcuma comosa and Kaempferia marginata (Zingiberaceae family), respectively, potently increased the accumulation. In addition, Z01 and Z02 increased the accumulation of other P-gp substrates, rhodamine 123 and doxorubicin, in PR-HepG2 cells in a concentration-dependent manner. Increased accumulation of rhodamine 123 and doxorubicin by Z01 and Z02 was also confirmed by confocal laser scanning microscopy. The effect of Z01 and Z02 pretreatment on the expression of MDR1 mRNA was also examined. The expression of MDR1 mRNA was not affected by the treatment of PR-HepG2 cells with these extracts for 48 hours. Cytotoxicity of paclitaxel was examined by XTT and protein assays in the absence and presence of Z02. Z02 potentiated the cytotoxicity of paclitaxel in PR-HepG2 cells. These results suggest that Curcuma comosa and Kaempferia marginata belonging to Zingiberaceae are useful sources to search for new P-gp modulator(s) that can be used to overcome multidrug resistance of cancer cells.

Peritoneal tuberculosis with gastric cancer: a case report / Tuberculosis peritoneal con cáncer gástrico: reporte de caso

This is a report of a case with both peritoneal tuberculosis and gastric cancer. Physicians should have a high index of suspicion of peritoneal tuberculosis if the patient is febrile with a past history of tuberculosis.

Este es el reporte de un caso con tuberculosis peritoneal y cáncer gástrico a la vez. Los médicos debáan tener un alto índice de sospecha de tuberculosis peritoneal si se trata de un paciente febril con antecedentes de tuberculosis.

Peritoneal tuberculosis with gastric cancer: a case report.

This is a report of a case with both peritoneal tuberculosis and gastric cancer. Physicians should have a high index of suspicion of peritoneal tuberculosis if the patient is febrile with a past history of tuberculosis.

Changes in the caudate lobe that is transplanted with extended left lobe liver graft from living donors.

BACKGROUND: Caudate lobe transplantation with an extended left lobe graft is an innovative and promising method for increasing the graft volume in living donor liver transplantation. However, little is known about the fate of the caudate lobe after transplantation. METHODS: Eight extended left lobe grafts with the caudate lobe were included in this study. No attempt was made to reconstruct the short hepatic veins. On the basis of the computed tomography scans that were obtained before the operation and 1 month after the transplantation, the increase in the graft volume by the addition of the caudate lobe and the changes in the transplanted caudate lobe were evaluated. RESULTS: The addition of the caudate lobe increased the graft volume by 25 +/- 2 g, corresponding to a 2% increase in graft volume/standard liver volume ratio. One month after the transplantation, the caudate lobe volume increased in all patients but 1. The regeneration rate of the caudate lobe and other segments (segments II-IV) 1 month after transplantation was 62% +/- 24% (24 +/- 4 mL- 37 +/- 4 mL) and 152% +/- 35% (374 +/- 45 mL-930 +/- 65 mL), respectively (P <.01). CONCLUSIONS: This technique affords a modest increase in liver volume with living donor left liver procurement.

Living-related auxiliary partial orthotopic liver transplantation for primary sclerosing chonangitis--subsequent removal of the native liver.

In Japan, living-related auxiliary partial orthotopic liver transplantation (APOLT) is mainly indicated for small-for-size grafts. We present the case of a 24 year-old patient with primary sclerosing cholangitis (PSC) who underwent a living-related auxiliary partial orthotopic liver transplantation for a small-for-size graft, that was subsequently excised. During the transplantation procedure, the native liver was freed from the surrounding tissues, and was only connected to the body by the right hepatic artery and right hepatic vein. The auxiliary extended left lobe graft, corresponding to 22% of the estimated recipient liver volume, was orthotopically transplanted after extended left lobectomy of the recipient native liver. Post-transplant CT-volumetry showed rapid increase of the graft volume with atrophy of the native liver, and GSA scintigraphy showed dominant function of the graft. Although hyper-bilirubinemia was prolonged by the removal of the native liver on the 18th post-transplantation day, it gradually subsided after plasmapheresis was performed twice, and the patient was discharged on the 77th post-transplantation day. We conclude, based on this case, that subsequent removal of the native liver is necessary in APOLT for patients with potential hepatic malignancies. The optimal timing of the removal of the remnant native liver should be determined based on CT-volumetry, GSA scintigraphy, and the liver biopsy specimen of the graft.

Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats.

BACKGROUND: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation. METHODS: Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups. RESULTS: The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group. CONCLUSION: dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats.

[Japan Surgical Society recertification: the viewpoint of surgeons in a local area].

The system of recertification is evaluated from the view point of the surgeons in a local area. The system only requires attendance at the national meeting of the Japan Surgical Society and/or meetings that are designated by the Japan Surgical Society for recertification. Half of such meetings have been held in the Kanto area over the past 10 years, resulting in an imbalance in the status of recertification between surgeons in the Kanto area and in local areas. In questionnaires about surgical recertification in local areas, many respondents pointed out this imbalance and the necessity for changing the conditions of recertification. The aim of recertification must be clarified and a new system of recertification investigated based upon the purpose of certification without imbalances between areas.

Rectal expander-assisted transanal endoscopic microsurgery in rectal tumors.

Rectal expander-assisted transanal endoscopic microsurgery (RE-TEM) was performed for two cases of early rectal cancer and a case of villous tumor under saddle block anesthesia. RE-TEM is the new technique for local excision of rectal tumors with a rectal expander that we developed. The rectal expander expands the rectum after insertion through the anus and provides adequate vision for microsurgery with standard video monitors. Tumors were located 8, 8, and 5 cm from the anal verge, and all of them were excised completely with no difficulty. Minor bleeding was noted in all cases and was controlled by electric coagulation and/or sutures. Average operative time for the three cases was 105 min. We conclude that RE-TEM is useful for rectal tumors and/or early rectal cancer that cannot be removed by endoscopy.

[Frequent chemolipiodolization and prostaglandin E1 administration for hepatocellular carcinoma with advanced liver cirrhosis].

"Frequent Chemolipiodolization & Prostaglandin E1 administration Therapy (FCPT)" which performed frequent chemolipiodolization to Hepatocellular carcinoma (HCC) and Prostaglandin E1 (PGE1) intra-hepatic arterial administration for avoiding serious liver damage by using reservoir was carried out for 7HCC cases with severe liver cirrhosis. Chemolipiodolization was performed every 4 weeks to 6 cases. PGE1 was given to all cases with 10 or 20 micrograms/4 hours every week after 7 days administration. In 6 cases that carried out Chemolipiodolization, FCPT demonstrated complete response in a case and partial response in 3 cases. Two other cases showed the progression of HCC in spite of the frequent chemolipiodolization. The serum hepaplastin levels were stable or improved in 5 cases. Improvement of the serum total protein levels was seen in the long survival cases. The general malaise of all cases was disappeared after FCPT. In 5 cases who had ascites before FCPT, the ascites was gradually decreased. We concluded that the FCPT was useful to treat HCC with advanced liver cirrhosis, and also the intra-hepatic arterial administration of PGE1 might have the possibility that is contributing to the liver function improvement of a liver cirrhosis.

Chemolipiodolization and prostaglandin E1 administration with use of hepatic arterial infusion port for the treatment of hepatocellular carcinoma and liver cirrhosis.

Frequent chemolipiodolization and prostaglandin E1 (PGE1) administered through a hepatic arterial infusion port were used for treatment in 2 cases of hepatocellular carcinoma (HCC) with liver cirrhosis. Chemolipiodolization was performed every 4 weeks with 6 ml lipiodol, 3 ml Optilay and 30 mg Epirubicin or 10 mg Mytomycin C. PGE1 (10 ug) was administrated to the hepatic artery once every week after the first 7 days administration. The treatment resulted in a decrease of the AFP level, an arrest of HCC growth and a reduction in ascites with an improvement of clinical and biochemical parameters in both cases. These encouraging preliminary results show that frequent lipiodolization is effective for unresectable HCC and frequent PGE1 administration via the hepatic artery is a safe and efficient treatment for liver cirrhosis.

Tolerance of the cirrhotic liver to cold ischemia: ex vivo analysis in rats.

We investigated the viability of rat cirrhotic livers preserved cold using an isolated rat liver perfusion model. Cirrhosis was induced by intravenous thioacetamide injection. Normal and cirrhotic livers were reperfused immediately or following 6 h of preservation through the portal vein with Krebs-Henseleit buffer and hyaluronic acid added. Cirrhotic livers with short cold ischemia showed higher portal venous resistance than their normal counterparts (p < 0.05), while cirrhotic livers preserved for 6 h exhibited marked elevation of the portal venous resistance as compared with their fresh counterparts or normal liver preserved cold for 6 h (p < 0.05). Similarly, the oxygen consumption of cirrhotic livers with short cold preservation was lower than that of normal livers (p < 0.05), which was further reduced by 6 h of cold preservation (p < 0.05). The bile output was not different between normal and cirrhotic livers. The sinusoidal endothelial cell function of cirrhotic livers as assessed by the clearance of hyaluronic acid was impaired even after a short period of cold ischemia. Histologically, cirrhotic livers showed severe sinusoidal endothelial cell damage, hepatocellular swelling, and marked septal edema which became more prominent by cold preservation. We conclude that the viability of the cirrhotic liver is impaired even by a short cold exposure, and that the prolongation of cold ischemia of the cirrhotic liver leads to further deterioration of the viability.

Partial hepatic grafting: porcine study on critical volume reduction.

BACKGROUND: The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. METHODS: Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). RESULTS: Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. CONCLUSIONS: Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.

Endoscopic findings and clinical manifestation of gastric anisakiasis.

OBJECTIVES: To identify the endoscopic findings and clinical manifestations of anisakiasis, we studied 87 cases of gastric anisakiasis. METHODS: Patient information was analyzed by means of patient records. The interval between the day of intake of Anisakis and endoscopic examination was determined in 86 cases. Then the endoscopic findings of each interval were elucidated. RESULTS: Moderate to severe gastric mucosal edema tends to occur within 1 or 2 days after Anisakis infection, accompanied by leukocytosis. As to the sites of penetration of Anisakis, 55% of cases were found in the greater curvature with severe mucosal edema. Among 87 cases, four patients experienced anisakiasis twice during the interval examined, and six patients had past histories of anisakiasis before the investigated interval. CONCLUSIONS: Gastric anisakiasis may be caused by an allergic reaction to the Anisakis antigen. There is a classic relationship between clinical and endoscopic findings and the interval after Anisakis administration. Anisakis usually is found in the greater curvature.

Percutaneous transhepatic portacaval shunt for high-risk esophageal varices.

Percutaneous transhepatic portacaval shunt (PTPS) was performed in a patient with high-risk esophageal varices prior to sclerotherapy. PTPS was accomplished with the aid of two catheters. The first catheter was placed in the right hepatic vein under ultrasonographic guidance, and the second was placed in the portal vein. The two catheters were then connected together. The color of the esophageal varices changed from blue to white, and serum protein levels were increased 8 weeks after PTPS. Sclerotherapy was then performed without any difficulty. PTPS is the easy and quick method of performing a portacaval shunt and may have importance for the management of patients with high-risk esophageal varices prior to the treatment of sclerotherapy or liver transplantation.

Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation.

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.