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Masaki Nishi,
Mitsuo Shimada,
Hideaki Uchiyama,
Toru Ikegami,
Yusuke Arakawa,
Jun Hanaoka,
Hirofumi Kanemura,
Yuji Morine,
Satoru Imura, Hidenori Miyake,
Toru Utsunomiya
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ABSTRACT: Key Words: Dai-ken-chu-to; Hepatic resection. Abbreviations: Alanine Aminotransferase (ALT); C-Reactive Protein (CRP); Dai-Ken- Chu-To (DKT); Postoperative Day (POD); Prothrombin Time-International Normalized Ratio (PT-INR); Total Bilirubin (TBil); Total Protein (TP); White Blood Cell (WBC). Background/Aims: After hepatic resection, delayed flatus and impaired bowel movement often cause problematic postoperative ileus. Kampo medicine, Dai-kenchu- to (DKT), is reported to have a various beneficial effects on bowel systems. The aim of this study was to prospectively evaluate effects of DKT after hepatic resection. Methodology: Thirty-two patients who underwent hepatic resection between July 2007 and August 2008 in Tokushima University Hospital were prospectively divided into DKT group (n=16) and control group (n=16). In DKT group, 2.5g of DKT was administered orally three times a day from postoperative day (POD) 1. Blood was examined on POD 1, 3, 5 and 7. Postoperative first flatus, bowel movement and full recovery of oral intake, hospital stays and complications were checked. Results: In DKT group, levels of c-reactive protein and beta-(1-3)-D-glucan on POD 3 were significantly decreased (p<0.05). Moreover, postoperative periods for the first flatus, bowel movement and the full recovery of oral intake were significantly shortened in DKT group (p<0.05). Conclusions: DKT suppressed inflammatory reaction, stimulated bowel movement and improved oral intake after hepatic resection, which may decrease serious morbidity after hepatic resection.
Hepato-gastroenterology 10/2012; 59(119):2290-4. · 0.66 Impact Factor
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Hiroki Mori,
Mitsuo Shimada,
Tohru Ikegami,
Tohru Utsunomiya,
Satoru Imura,
Yuji Morine,
Tetsuya Ikemoto,
Jun Hanaoka,
Shuichi Iwahashi,
Yu Saito,
Michihito Asanoma,
Shinichiro Yamada, Hidenori Miyake
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ABSTRACT: Key Words: Pegylated-interferon α-2b; Partial hepatectomy; Liver regeneration; Massive hepatectomy; Small-forsize graft. Abbreviations: 2'5' Oligoadenylate Synthetase (OAS); Aspartate Aminotransferase (AST); Blood Platelet (PLT); Choline-Deficient Ethionine-Supplemented (CDE); dsRNA-Dependent Protein Kinase (PKR); Hepatectomy (Hx); Hepatitis C Virus (HCV); Interferon (IFN); Labeling Index (LI); Liver Transplantation (LT); Liver weight to Body weight ratio (Lw/Bw ratio); Living Donor Liver Transplantation (LDLT); Ornithine Decarboxylase (ODC); Pegylated- Interferon (PEGIFN); Proliferating Cell Nuclear Antigen (PCNA); Standard Deviation (SD); White Blood Cell (WBC).Background/Aims: The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. Methodology: Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). Results: In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x104/mm3), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters. Conclusions: Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.
Hepato-gastroenterology 10/2012; 59(119):2300-4. · 0.66 Impact Factor
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Lkhagva-Ochir Tovuu,
Satoru Imura,
Tohru Utsunomiya,
Yuji Morine,
Tetsuya Ikemoto,
Yusuke Arakawa,
Hiroki Mori,
Jun Hanaoka,
Mami Kanamoto,
Koji Sugimoto,
Shuichi Iwahashi,
Yu Saito,
Shinichiro Yamada,
Michihito Asanoma, Hidenori Miyake,
Mitsuo Shimada
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ABSTRACT: BACKGROUND: CD44 is well known to be one of the cancer stem cell markers and is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and cell migration. We investigated the role of CD44 expression in both tumor and non-tumor tissues on recurrence of hepatocellular carcinoma (HCC). METHODS: Forty-eight patients with HCC who underwent hepatic resection at our institution were enrolled in this study. CD44 expressions in both tumor and non-tumor tissues were examined using real time reverse transcription-polymerase chain reaction. The patients were divided into two groups: high and low gene-expression group, based on the CD44 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. RESULTS: In the tumor tissues, the gene-expression levels of CD44 did not correlate with any clinicopathological parameters. The disease-free survival rate showed no significant difference between the two groups. In non-tumor tissues, although there was no significant relationship between the CD44 expression levels and clinicopathological factors, disease-free survival rate in the CD44 low expression group was significantly better than that in the CD44 high expression group (P < 0.05). In multivariate analysis, the risk factors in tumor recurrence were presence of microscopic portal invasion and high expression level of CD44. CONCLUSION: The CD44 expressions in the non-tumor tissues may predict HCC recurrence.
International Journal of Clinical Oncology 06/2012; · 1.41 Impact Factor
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ABSTRACT: Histone deacetylase (HDAC) plays an important role in chromatin remodeling and gene expression, and in regulating cell cycle progression and differentiation. Furthermore, hypoxic conditions in the malignant tumor enhance HDAC function and increased HDAC activity is closely involved in worse malignant behavior through hypoxia inducible factor (HIF) activation. The aim of this study was to elucidate the correlation between HDAC expression and tumor malignant behavior including HIF-1α expression in intrahepatic cholangiocarcinoma (IHCC).
Thirty-five patients with IHCC who underwent hepatic resection were evaluated. HDAC1 and HIF-1α expressions were determined immunohistochemically, and the patients were divided into 2 groups: the HDAC1 positive group (n = 21) and the HDAC1 negative group (n = 14). Clinicopathologic variables including HIF-1α expression were compared between the 2 groups.
HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 78% vs 8%, P = .001). Furthermore, disease free survival rate in the HDAC1 positive group had significantly worse than that in the HDAC1 negative group (P = .0003). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, P = .0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1α expression (P = .007).
These findings suggested that HDAC1 positive expression was a potential new prognostic indicator of IHCC, and a possible promising molecular target through the regulation of HIF-1α.
Surgery 03/2012; 151(3):412-9. · 3.10 Impact Factor
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Shinichiro Yamada,
Mitsuo Shimada, Hidenori Miyake,
Tohru Utsunomiya,
Yuji Morine,
Satoru Imura,
Tetsuya Ikemoto,
Hiroki Mori,
Jun Hanaoka,
Shuichi Iwahashi,
Yu Saito
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ABSTRACT: Aim: The aim of this study was to investigate the characteristics of super-elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super-elderly groups. Results: Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group. Conclusions: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.
Hepatology Research 02/2012; 42(5):454-8. · 2.20 Impact Factor
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ABSTRACT: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil and possible predictive markers. We conducted this study to clarify if TS and DPD gene expressions are a prognostic indicator for intrahepatic cholangiocarcinoma (IHCC).
The subjects of this study were 21 patients with IHCC who had undergone surgical resection. Intratumoral TS and DPD mRNA expressions were examined using the Danenberg tumor profile method and classified into two groups according to the median value of each. We then compared the clinicopathological variables, including prognosis, between the high and low expression groups.
Low DPD expression was correlated with macroscopic type, namely, mass-forming + infiltrative (P = 0.08). Postoperative survival rates in the low DPD expression group were significantly lower than those in the high DPD expression group. Multivariate analysis revealed macroscopic type to be an independent prognostic factor, whereas TS mRNA expression did not correlate with any clinicopathological variables, including prognosis.
Low DPD mRNA expression was related to macroscopic type and associated with poor prognosis. DPD mRNA expression in tumor cells is suggested to be an important regulator of malignant behavior in IHCC.
Surgery Today 12/2011; 42(2):135-40. · 1.22 Impact Factor
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ABSTRACT: To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations.
Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis.
Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups.
Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.
Surgery Today 11/2011; 42(2):147-51. · 1.22 Impact Factor
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ABSTRACT: The liver-hanging maneuver (LHM) is a useful technique in major hepatectomy. We made modifications to this technique with special reference to the ligamentum venosum for performing a left hepatectomy (LH). The aim of this study was to clarify the usefulness of our new technique.
Between August 2007 and May 2009, five patients underwent LH using our modified LHM and 12 patients underwent LH using a conventional procedure. The two groups were compared in terms of the patient characteristics, preoperative hepatic functions, surgical records, and outcomes.
The characteristics and preoperative hepatic function tests were similar between the modified LHM and non-LHM groups. Intraoperative blood loss was significantly reduced in the modified LHM group compared with the non-LHM group (193 ± 133 vs. 375 ± 167 ml, P < 0.05). The lengths of the operations and time required to perform a parenchymal transection did not differ significantly between the two groups (duration of operations 273 ± 37 vs. 337 ± 70 min; transection times 29 ± 10 vs. 28 ± 13 min). The postoperative complications and hospital stays did not differ significantly between the two groups.
Our modified LHM can reduce the intraoperative blood loss during LH, and our results have shown the usefulness of this modified technique for LH.
Surgery Today 11/2011; 42(8):720-3. · 1.22 Impact Factor
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ABSTRACT: We describe a new technique of ultrasound (US)-guided microwave coagulation (MC) of the Glissonean pedicle, performed before transection to control the inflow and select the resection area. This report introduces our procedure and evaluates the outcomes of patients treated using this technique.
The Glissonean pedicles feeding the segment or cone unit were coagulated by US-guided MC, after which transection was performed. We used this US-guided MC technique to perform anatomical resections in 12 patients with hepatocellular carcinoma (MC group). We compared the outcomes of this group with those of a historical group of 10 patients who underwent conventional hepatectomy (control group). The two groups were well matched for age, tumor size, location, and type of hepatectomy.
The mean operative times were similar, but the mean blood loss was significantly lower the in MC group than in the control group. Recurrence developed in four patients from the MC group, but local recurrence was not observed. Bile leakage occurred in one patient from the MC group, but the incidences of postoperative complications did not differ between the groups.
Our procedure allows anatomical resection to be performed safely and easily, and helps prevent intrahepatic metastasis via portal flow during the transection.
Surgery Today 11/2011; 42(1):35-40. · 1.22 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinoma (IHCC) is known to be one of the most malignant tumors. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions. The aim of this study was to elucidate the role of HIF-1 in IHCC.
Thirty-five patients with IHCC who underwent hepatic resection were enrolled in this study. The expression of HIF-1a was determined immunohistochemically and the patients were divided into two groups: HIF-1a positive group (n=22) and HIF-1a negative group (n=13). Clinicopathological variables including prognosis were compared between the two groups. The prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model.
HIF-1a expression correlated significantly with higher stage, and tended to correlate with tumor diameter (>4cm), vessels infiltration and intrahepatic metastasis. The prognosis in HIF-1a positive group was poorer than that in HIF-1a negative group (5-year survival: 62.9% vs. 18.3%). Furthermore, HIF-1a positive expression was identified as an independent prognostic factor for both overall and disease free survival.
The findings suggested that the intratumoral HIF-1a regulated malignant behavior and was a new prognostic indicator of IHCC.
Hepato-gastroenterology 07/2011; 58(110-111):1439-44. · 0.66 Impact Factor
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ABSTRACT: Aim: In patients with liver cirrhosis, abnormal energy metabolism induces low health-related quality of life (HRQOL) scores. However, late-evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long-term LES on HRQOL in cirrhotic patients, using the 36-item Short Form (SF-36) health survey. Methods: Thirty-nine cirrhotic patients classified as Child-Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non-LES group and 15 to the LES group. SF-36 scores, anthropometric data and serum biochemical parameters were examined in the non-LES and LES groups at 0, 6 and 12 months. Results: Neither anthropometric data nor laboratory data showed significant differences between the non-LES and the LES groups at 0, 6 and 12 months. The role-emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non-LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non-LES group. Conclusion: Long-term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.
Hepatology Research 04/2010; 40(5):470-6. · 2.20 Impact Factor
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ABSTRACT: Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats.
A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP.
Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage.
Journal of Gastrointestinal Surgery 09/2008; 13(1):66-73. · 2.83 Impact Factor
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ABSTRACT: Angiomyolipoma (AML) is a rare benign tumor that occurs most commonly in the kidney. Lesions in the liver are usually solitary and multiple AMLs of the liver are extremelyrare. Furthermore, extra renal or hepatic AML are rarely found. We report an unusual case of a 34-year-old man with a solitary omental AML and multiple hepatic AMLs. At the age of 23, the patient underwent right nephrectomy and enucleation of a left renal tumor because of bilateral AMLs. At the age of 34, more than 6 lesions in the liver and an enlarged solitary omental AML were discovered. The omental tumor, 50 x 40mm, 49g, was extirpated; it was well-defined and encapsulated a soft elastic mass. Histologically it was an epithelioid AML and positive for the melanogenesis-related marker HMB-45, the same as the earlier right renal tumor. We describe the first case of a solitary omental AML, which had metastasized, and with more than 6 hepatic AMLs.
The Journal of Medical Investigation 09/2005; 52(3-4):218-22.
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ABSTRACT: We report a patient with duodenal varices oozing blood who had undergone low anterior resection of the rectum and resection of the liver tumor because of multiple liver metastasis from rectal cancer 80 months previously. Although endoscopic variceal ligation (EVL) was carried out for the ruptured duodenal varices, their bleeding persisted and hepatic encephalopathy also appeared. Finally, balloon occluded retrograde transvenous obliteration (BRTO) with percutaneous transhepatic obliteration (PTO) was carried out for the duodenal varices. Percutaneous transhepatic portography revealed detailed hemodynamics. Following PTO, the duodenal varices were stagnated by BRTO, and no complications were recognized. No re-bleeding episode has been observed since the treatment. In addition, the hepatic encephalopathy was also improved.
The Journal of Medical Investigation 09/2005; 52(3-4):212-7.
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ABSTRACT: This study aimed to investigate regulatory mechanisms of hepatocyte proliferation by comparing liver regeneration of the remnant lobe after 70% partial hepatectomy (PH) and portal vein branch ligation (PBL) in rat.
Expressions of activins betaA, betaC, and betaE and their receptors were investigated after PH and PBL. The proliferating cell nuclear antigen (PCNA) labeling index was used to monitor hepatocyte proliferation.
The PCNA labeling index in the regenerative lobe of PBL rats reached a peak at 48 h, a delay of 24 h compared with the remnant lobe in PH rats. In the postoperative early stage, the expression of activin betaA, betaC, and betaE mRNAs was stronger in PBL than PH. At 72 h the expression of activin receptor type IIA mRNA reached a peak in PH but was significantly lower in PBL.
Hepatocyte proliferation, and the regulated expression of activins and their receptors, differs during liver regeneration after PH and PBL in the rat. Thus, regulation of activin signaling through receptors is one of the factors determining liver regeneration after PH and PBL.
Journal of Surgical Research 07/2005; 126(1):3-11. · 2.25 Impact Factor
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ABSTRACT: A superoxide-producing enzyme, NADPH oxidase 1 (Nox1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. Immunohistochemistry showed that Nox1 was constitutively expressed in surface mucous cells. Adenomas and well differentiated adenocarcinomas up-regulated Nox1 expression. Ki-67-negative, well differentiated tumor cells contained abundant Nox1, whereas Ki-67-positive, proliferating cells did not express it. This differentiation-dependent expression in normal as well as tumor tissues suggests distinct roles of Nox1 besides mitogenic function. Nuclear factor (NF)-kappaB was predominantly activated in adenoma and adenocarcinoma cells expressing abundant Nox1, suggesting that Nox1 may stimulate NF-kappaB-dependent antiapoptotic pathways in colon tumors.
Cancer Letters 05/2005; 221(1):97-104. · 4.24 Impact Factor
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ABSTRACT: Activin A is an autocrine inhibitor of cell growth in the liver. The biological activity of activin A is mediated by a heteromeric receptor complex. Follistatin (FS) binds to activin and inhibits its biological effects, and acts as a negative regulator of muscle cells. The role of activin receptors during liver regeneration following a hepatectomy has not been fully assessed. This study investigates the mechanism underlying how activin receptors regulate hepatocyte growth, and the effects of intravenous administration of FS during liver regeneration.
The expression of both activins and activin receptors in the liver after a 70% partial hepatectomy (HT) was assessed by RT-PCR and immunohistochemistry. FS 315 or 288 was infused for different periods of time based on changes in hepatocyte activin receptor expression after HT.
Activin receptor expression peaked between 48 and 72 hours after HT. 72 hours after HT, an injection of FS 315 resulted in a more potent stimulation of DNA synthesis and produced a greater increase in body weight compared with the control rats.
The expression of activin receptors after peak DNA synthesis might be a key component in the downregulation of DNA synthesis. Intravenous administration of FS 315 might promote liver regeneration and have anabolic actions.
Hepato-gastroenterology 04/2005; 52(61):60-6. · 0.66 Impact Factor
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ABSTRACT: During epithelial morphogenesis, adherens junctions (AJs) and tight junctions (TJs) undergo dynamic reorganization, whereas epithelial polarity is transiently lost and reestablished. Although ARF6-mediated endocytic recycling of E-cadherin has been characterized and implicated in the rapid remodeling of AJs, the molecular basis for the dynamic rearrangement of TJs remains elusive. Occludin and claudins are integral membrane proteins comprising TJ strands and are thought to be responsible for establishing and maintaining epithelial polarity. Here we investigated the intracellular transport of occludin and claudins to and from the cell surface. Using cell surface biotinylation and immunofluorescence, we found that a pool of occludin was continuously endocytosed and recycled back to the cell surface in both fibroblastic baby hamster kidney cells and epithelial MTD-1A cells. Biochemical endocytosis and recycling assays revealed that a Rab13 dominant active mutant (Rab13 Q67L) inhibited the postendocytic recycling of occludin, but not that of transferrin receptor and polymeric immunoglobulin receptor in MTD-1A cells. Double immunolabelings showed that a fraction of endocytosed occludin was colocalized with Rab13 in MTD-1A cells. These results suggest that Rab13 specifically mediates the continuous endocytic recycling of occludin to the cell surface in both fibroblastic and epithelial cells.
Journal of Biological Chemistry 02/2005; 280(3):2220-8. · 4.77 Impact Factor
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ABSTRACT: In the special occasion that the physiological lymphatic flow is obstructed, gallbladder carcinoma (GBC) may spread into the liver via lymphatic route. Therefore, this study was conducted to find out the direct lymphatic route draining into the liver from the gallbladder using pigs with ligated cystic ducts. After injecting the carbon particle suspension (CH40) or the contrast medium (Lipiodol) into the subserosal layer of the gallbladder, the lymphatic route into the liver was examined both macroscopically and histologically. In controls, CH40 or Lipiodol drained along the cystic duct toward the hepatoduodenal ligament. After occlusion of cystic duct, CH40 was interrupted at the ligated point, and then spread into the liver nearby the gallbladder bed, running off to the liver hilus, toward the hepatoduodenal ligament. This route was confirmed by the Lipiodol drainage into the right median lobe of the liver, equivalent to the segments V and IV a in humans. We presented for the first time the emergence of lymphatic drainage from the gallbladder into the liver after the occlusion of physiological lymphatic route using pigs. This implies that the direct spread into the segments V and IV a of liver should be considered in the surgical treatment of advanced GBC.
The Journal of Medical Investigation 09/2004; 51(3-4):210-7.
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ABSTRACT: The allogeneic islets transplantation is an ideal therapeutic strategy for patients with diabetes mellitus. However, it has been difficult to induce immunological tolerance against islets grafts. The CD4+CD25+ regulatory T-cells (Treg) play a role in suppressing T-cell activation. Thus, we evaluated whether Treg can regulate donor-specific T-cell tolerance that received allogeneic islets into the hepatic parenchyma (ITxHP) along with Treg.
C3H/He mice were used as donors; and streptozotocin-induced diabetic BALB/c mice were recipients. The protocol included three groups: Group A recipients received only 300 IE islets; Group B was given 300 IE islets and whole splenocytes; Group C was given 300 IE islets and Treg purified from peripheral lymph nodes.
For all mice in Groups A and B, the fasting blood sugar exceeded 250mg/dl and graft rejection was observed. GVHD was observed earlier in Group B than in Group A. In contrast graft survival exceeded 30 days for two mice in Group C (50%, mean POD 28.5 +/- 24.0, P<0.05). Mixed lymphocyte reaction showed that T-cells from tolerant mice had very weak responses against spleen cells from C3H mice.
The simultaneous ITxHP with CD4+CD25+ T-cells administration prolonged islet graft survivals and induced donor-specific hyporesponsiveness.
The Journal of Medical Investigation 09/2004; 51(3-4):178-85.
