The protective effect of adipose-derived stem cells against liver injury by trophic molecules.

In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.


Regulatory T cells in the blood: a new marker of surgical stress.


Hand-assisted laparoscopic splenectomy for a huge splenic vascular lesion with aneurysms in a patient with impending Kasabach-Merritt syndrome-like phenomenon.

Splenic vascular lesions are relatively rare and are usually found incidentally. However, the vascular lesions associated with Kasabach-Merritt syndrome, such as hemangioma, can be life-threatening. We herein describe the case of a young adult female patient with a huge splenic vascular lesion, aneurysms of the splenic artery, and increased plasma levels of fibrin/fibrinogen degradation products and D-dimers. Hand-assisted laparoscopic splenectomy was performed, after which the coagulopathy was drastically improved. Minimally invasive surgical intervention such as hand-assisted laparoscopic splenectomy should be considered as the first treatment choice in such a case.

The Journal of Medical Investigation : JMI


Oxaliplatin-related sinusoidal obstruction syndrome mimicking metastatic liver tumors.

A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.


We originally developed a multi-capillary polyurethane foam packed-bed module as a hybrid-artificial liver support system (HALSS) and have applied for the permission of the clinical application to our institutional ethical committee. We summarized here the history, recent obstacles in clinical applications, and future prospects of HALSS, including our own.


Angiogenic switch as a molecular target of malignant tumors

In vivo progression to malignancy is characterized by the switch to an angiogenic phenotype. The angiogenic switch is a critical control point for tumor expansion. The ability of a tumor to become neovascularized permits rapid expansion of tumor growth and increases the likelihood of metastases. The genetic alterations that accompany the switch to the angiogenic phenotype are unknown. Discoveries of such genes lead to comprehension of molecular mechanisms of the tumor progression, as well as development of novel therapeutic tools. We have isolated a novel "angiogenic switch molecule," angiopoietin-2, upregulated specifically in hypervascular hepatocellular carcinoma (HCC). Angiopoietin family proteins have been originally identified as ligands of the vascular endothelial receptor of tyrosine kinase Tie2. Ectopic expression of angiopoietin-2 promotes the rapid development of human HCCs and produces hemorrhage within tumors in nude mice. These results suggest a role for angiopoietin-2 in the neovascularization of HCC. In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Angiopoietin protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells. Tumorigenicity with angiogenesis was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for angiopoietin/Tie2 signaling in the induction of HCC neovascularization and disease progression. More important, inhibition of the angiopoietin/Tie2 signal transduction cascade is a promising approach for HCC treatment.


[Novel molecularly targeted peptides interfering the specific signal transduction of cancer metastasis]

Nihon Rinsho. Japanese Journal of Clinical Medicine


The effect of polysaccharide k with S-1 based chemotherapy in advanced gastric cancer.

Polysaccharide K (PSK) is widely used in Japan as a biological response modifier for cancer patients. We investigated the effects of PSK with S-1 based chemotherapy for advanced gastric cancer patients in immune response. Nine advanced gastric cancer patients who underwent chemotherapy at the University of Tokushima were included in this study. In all patients, 3g PSK was received orally and S-1 based chemotherapy for 2 weeks alternately for 8 weeks. Serial changes in immunological parameters (Foxp3, Natural killer (NK), CD4/CD8) were monitored. The levels of Foxp3 at 8 weeks was significantly decreased compared with 2 weeks (4.26% vs. 3.11%). In NK activity at 8 weeks was significantly increased compared with 2 weeks (27% vs. 47%). These results of this study suggested that chemotherapy with PSK improved the immune response in advanced gastric cancer patients. Especially Foxp3 was concerned in this mechanism.


Effect of Kampo medicine "Dai-kenchu-to" on microbiome in the intestine of the rats with fast stress.

Diversity of gut microbiome has been recently reported to be lost in inflammatory bowel disease. We have previously reported that the Dai-kenchu-to (DKT) prevented the bacterial translocation through suppression of cytokine and apoptosis in rat's fast stress model. The aim of this study was to evaluate the effect of DKT on maintenance of microbial diversity in rat's intestine with inflammation. Wister rats were received the fast stress for 5 days. In DKT group, rats were administered with DKT (300 mg/kg/day) during the fast stress (DKT-group). The gut microbiomes were analyzed at before- and after- fast stress, and the effect of DKT for on microbial diversities of the gut were evaluated by the PCR-clone library method targeting the 16 S ribosomal RNA gene. In Control-group, Erysipelotrichaceae increased to 86% in after fast stress, OTU of before-fast stress was 111 and after fast stress was only 9 (changing rate: 58%). The diversity of microbiome was severely decreased. On the other hand, in DKT-group, diversity of microbiome was kept after fast stress (Lachnospiraceae: Ruminococcaceae: Coriobacteriales 54%, 22%, 5%), Operational taxonomic units of before fast stress was 52 and after fast stress was 55 (changing rate: 6%). Family Lachnospiraceae which includes butyrate-producing Clostridia (Clostridium IV and XIVa). DKT prevented the reduction of diversity of microbiome in rat's fast stress model. Our data suggested the new anti-inflammatory mechanism of DKT through gut microbiome.


Impact of C-reactive protein on prognosis of patients with colorectal carcinoma.

The aim of this study was to investigate the impact of preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with colorectal carcinoma (CRC). We investigated the correlation between preoperative CRP level and clinicopathological factors including prognosis of 167 patients who underwent resection for CRC retrospectively. Clinicopathological variables were compared between patients with serum CRP levels >1mg/dL (29 patients; high-CRP group) and patients with serum CRP levels <1mg/dL (138 patients; low-CRP group). In high-CRP group, 9 patients were stage I+II and 20 patients ware stage III+IV. In low-CRP group, 93 patients were stage I+II and 45 patients were stage III+IV. There were significant differences in the clinical stage, tumor diameter, curativity, final stage between the two groups (p<0.01). The overall survival and recurrence-free survival rates in high-CRP group were lower compared with the rates in low-CRP group (p<0.05 and p=0.14). In addition, the overall survival rate in stage I+II patients with high-CRP was significantly lower than that in patients with low-CRP (p<0.05). Using multivariate analysis, the preoperative elevation of serum CRP level was an independent prognostic factor in patients with CRC (p<0.05). We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.


Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer.

BACKGROUND: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. METHODS: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. RESULTS: Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. CONCLUSION: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.

International Journal of Clinical Oncology


A Modified liver-hanging maneuver focusing on the ligamentum venosum in left hepatic lobectomy

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.


Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma.

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.


Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in gallbladder carcinoma

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil, which have been examined as possible predictive markers. We conducted this study to clarify the role of TS and DPD expressions in gallbladder carcinoma (GBC). The subjects were 28 patients who underwent surgical resection of GBC. We examined intratumoral TS and DPD mRNA expressions, using the Danenberg tumor profile method. The expression levels were classified into two groups, based on median values. Clinicopathological variables, including prognosis, were then compared between the high and low expression groups. There was a significant difference in the incidence of lymph node metastasis between the high and low TS expression groups. The incidence of advanced clinical stage was higher in the low TS expression group than in the high TS expression group. However, no clear correlation was observed between the DPD mRNA expression and any clinicopathological variable. There was no significant difference in the postoperative survival rates between the groups, in accordance with the expression of TS or DPD genes. Low TS mRNA was correlated with a high incidence of lymph node metastasis and advanced clinical stage. Therefore, TS gene expression may help identify patients at increased risk of the progression of GBC.


Impact of a new refrigerator on the preservation of hepatic grafts.

Aim: Current medical transplantation methods focus on solutions for major problems such as the shortage of donors. To overcome these issues, expanding organ preservation time has become a major concern. A new refrigerating chamber has been recently developed, which can cool the inside of a material to the required temperature by frequently sensing the temperature of both inside and surface of the materials. The purpose of this study is to evaluate the usefulness of a new refrigerating system in hepatic preservation. Methods: The liver grafts were harvested from rats and divided into two groups. Group A consisted of grafts preserved in chilled University of Wisconsin solution (UW) solution (on ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW solution in a new refrigerator at 4°C. Results: In group B, aspartate aminotransferase released into effluent after cold storage for 72 h showed a marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate decreased significantly in group B (P < 0.05). In group B, the levels of adenosine triphosphate were significantly preserved after cold storage for 24 h and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive cells for heme oxygenase-1 were significantly increased in group B after cold storage. Conclusion: This new refrigerator can improve preservation injury of hepatic grafts and may provide an innovative technique for liver transplantation.


Irinotecan injures tight junction and causes bacterial translocation in rat.

Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation. Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution. In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05). Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.


Platelet-derived endothelial cell growth factor/thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer.

A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies. The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically. Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-β and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.


Effects of a whey peptide-based enteral formula diet on liver dysfunction following living donor liver transplantation.

BACKGROUND AND AIMS: Whey protein, a protein complex derived from milk is well known as a functional food with a number of health benefits. MEIN(®) (Meiji Dairies Co., Tokyo Japan) is a functional liquid-type nutritional diet containing whey-hydrolyzed peptide. In this study, we examined the effects of MEIN(®) on postoperative liver dysfunction in patients who underwent living donor-related liver transplantation (LDLT). METHODS: Sixteen adult patients transplanted between 2005 and 2011 at our institute were evaluated retrospectively. In MEIN group (n = 8), administration of MEIN(®) was started around 14 days after liver transplantation when serum liver enzymes were re-elevated, while MEIN(®) was not administered in the control group (n = 8) who did not have postoperative liver dysfunction. RESULTS: In the preoperative clinical characteristics, the model for end-stage liver disease score in the MEIN group was significantly lower than that in the control group. The graft-to-recipient body weight ratio in the MEIN group was lower than that in the control group. Elevation of enzymes in the liver function tests such as alanine aminotransferase and total bilirubin, and C-reactive protein in the MEIN group had significantly improved, and became almost normal values which were the same as those in the control group. CONCLUSION: These findings suggest that administration of whey-hydrolyzed peptide attenuates the post-transplant liver dysfunction and may avoid an unnecessary liver biopsy.


Surgical results of pancreatoduodenectomy in elderly patients.

To assess the safety and feasibility of pancreatoduodenectomy (PD) in elderly patients, we investigated the clinical characteristics of patients aged ≥75 years, who underwent this procedure at our hospital. Between November 2005 and December 2010, 84 patients underwent PD at Tokushima University Hospital. We analyzed the clinicopathological data and outcomes after PD in patients aged ≥75 years compared with those in patients <75 years. The preoperative characteristics of the elderly group (n = 28) were similar to those of the younger group (n = 56). The hemoglobin and albumin levels were significantly lower in the elderly patients (P < 0.05), who also had a higher rate of preoperative pulmonary dysfunction (P < 0.05). The operation time and intraoperative blood loss did not differ significantly between the groups, but the incidence of pneumonia was higher in the elderly group (P < 0.05). The overall survival rate did not differ significantly between the groups. Advanced age alone does not have an adverse effect on surgical outcomes, including postoperative complications and long-term prognosis. Therefore, PD may be justified for selected elderly patients.


Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein.

Aim: Lens culinaris agglutinin A-reactive fraction of α-fetoprotein (AFP-L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP-L3 to predict the recurrence and prognosis of HCC after curative hepatectomy. Methods: One hundred and forty-two HCC patients who underwent curative hepatectomy were examined for the correlation between preoperative tumor marker, including AFP, des-γ-carboxy prothrombin (DCP) and AFP-L3, and clinicopathological variables. The prognostic factors of disease-free survival rates and overall survival rates were also determined using clinicopathological variables including these three tumor markers. Results: There were similar tendencies in the relationship between these three markers and malignant behaviors including lower grade tumor differentiation or vascular invasion. In multivariate analysis, increased AFP-L3 value (P = 0.019) was found to be an independent prognostic factor of disease-free survival after curative hepatectomy. In addition, elevated DCP (P = 0.013) and AFP-L3 values (P = 0.012) were found to be independent prognostic factors. Furthermore, the preoperative AFP-L3 value in the patients with early recurrence (within 1 year after hepatectomy) was significantly higher than that in those without early recurrence (26.9 ± 19.5 % vs 14.2 ± 19.8 %, P = 0.047). Conclusion: Preoperative AFP-L3 value was strongly correlated to disease-free and overall survival rate and the timing of recurrence, so it appears that it would be useful to predict the recurrence and prognosis of HCC after curative hepatectomy.


The Impact of Pegylated-Interferon alpha-2b on Partial and Massive Hepatectomy Model in Rats.

The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. 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 (1.5 μg/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). 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. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 104/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. 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.


Significance of sonic hedgehog signaling after massive hepatectomy in a rat.

To clarify the functional involvement of hedgehog signaling, especially sonic hedgehog (Shh) and glioma-associated oncogene (Gli)-1 which are known to play an important role in embryonic development and cancer, in the regeneration of a hepatectomized rat liver. Six-week-old male Wistar rats were subjected to 70 or 90 % hepatectomy (Hx). Animals were killed at 24, 48 and 72 h after Hx. The liver/body weight ratio was measured as an index of regeneration. Formalin-fixed liver samples were embedded in paraffin, stained for immunohistochemistry with proliferating cell nuclear antigen (PCNA) antibody, and the labeling index was calculated. Immunohistochemistry was also performed with Shh and Gli-1 antibodies. The liver/body weight ratio gradually increased in both the 70 and 90 % Hx, groups. The hepatocytes were strongly stained for PCNA at 24 h after Hx. Non-parenchymal cells were gradually stained by PCNA from 24 to 72 h after Hx. Shh and Gli-1 expression in hepatocytes was higher after 24 h than at other times and then gradually decreased. Shh and Gli-1 expression in non-parenchymal cells increased gradually, and was found mainly in liver zone I at 72 h after 70 and 90 % Hx. The expression of both markers suggested that Shh signaling contributes to tissue reconstruction after Hx.


Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.

Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.


Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.

The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.

International Journal of Clinical Oncology


Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.


Successful case with hemophagocytic syndrome after living donor liver transplantation.

Hemophagocytic syndrome (HPS) is a rare but serious complication that is associated with hypercytokinemia caused by activated T lymphocytes and macrophages in immunologically compromised patients. Living donor liver transplantation (LDLT) between adults has been performed to compensate for the shortage of available organs. There have been some reports of HPS after LDLT but its prognosis is disappointingly poor. Herein, we report a case of HPS in a 53-year-old woman who underwent LDLT using a left lobe graft. HPS was diagnosed on postoperative day 6 and successfully treated with a steroid pulse. HPS is a fatal complication in immunologically compromised patients but its early diagnosis and appropriate treatment can lead to an improved outcome.


Huge focal nodular hyperplasia difficult to distinguish from well-differentiated hepatocellular carcinoma

We present a 43-year-old man with huge focal nodular hyperplasia (FNH) that was difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). He previously had abnormal portal vein circulation due to hypoplasia of the intrahepatic portal vein, which was treated with a superior mesenteric vein-inferior vena cava shunt. Laboratory findings included predominantly indirect hyperbilirubinemia with concomitant elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia. Serum α-fetoprotein and des-γ-carboxy prothrombin were slightly elevated. Multidetector-row computed tomography detected the primary tumor in the left liver lobe, which partially showed a central stellate scar. Gd ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed some low-intensity areas in the tumor in the hepatocyte phase. 99mTc-galactosyl human serum albumin scintigraphy showed normal intake of agent in the tumor. We could not rule out well-differentiated HCC. Extended left hepatectomy was performed. Final histopathological findings showed that most of the tumor was FNH against a background of portal vein hypoplasia with moderate atypia and hemorrhage. And immunohistochemical analysis revealed high expression of organic anion transporter (OATP) 1B3 and low expression of multidrug resistance-associated protein (MRP) 2 in a part of the tumor. The patient has remained alive with no hepatic lesion for 1 year after surgery. We describe a case of huge FNH that was difficult to distinguish from well-differentiated HCC even by current fully preoperative imaging technology and demonstrate the effectiveness of curative surgical resection.


Hepatic screlosed hemangioma which was misdiagnosed as metastasis of gastric cancer: report of a case

A screlosed hemangioma of the liver is rare among hepatic tumors. A 75 years old male was referred to our hospital for gastric cancer and a hepatic tumor. The histological finding of gastric cancer was revealed to be well differentiated adenocarcinoma. The liver tumor was 1.1×1.0 cm in size and located in segment 8 of the liver. Computed tomography (CT) showed it to be a tumor with ring enhancement. Magnetic resonance imaging (MRI) showed the tumor to have a low signal on T1-weighted and slightly high signal on T2-weighted images. Level of hemoglobin was 7.8 g/dl. It was thought to be persistent bleeding from gastric cancer. With diagnosis of liver metastasis from gastric cancer, chemotherapy is recommended. However, to control the bleeding from gastric cancer, we performed distal gastrectomy and wedge resection of liver (S8). The histological examination of the liver tumor revealed to be a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. We report herein a case of the rare tumor which was misdiagnosed as a liver metastasis of gastric cancer.

The Journal of Medical Investigation : JMI


Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection.

Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer. A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer. Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different. LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.


Clinicopathological analysis of distal margin for rectal cancer after preoperative chemoradiation therapy.

Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins ≥1 cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.


Preoperative radiotherapy combined with S-1 for advanced lower rectal cancer: phase I trial.

S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD). Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2). Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%). The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.


The effects of the Kampo medicine (Japanese herbal medicine) ``Daikenchuto'' on the surgical inflammatory response following laparoscopic colorectal resection.

The inflammatory response after surgery is associated with various postoperative complications. The aim of the present prospective study was to evaluate the effects of Daikenchuto (DKT) (a Japanese herbal medicine) on the inflammatory response in patients following laparoscopic colorectal resection. Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups: a DKT intake group (D group, n = 15) and a control group (C group, n = 15). The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day. The body temperature, heart rate, WBC count, lymphocyte count, C-reactive protein (CRP) level, β-D: -glucan level and Candida index were compared between the two groups. The patients' mean age in the D group was significantly younger than that in the C group. D3 lymph node dissection was performed more often in the D group. The time until first flatus was significantly shorter in the D group (1.8 ± 0.5 days) than in the C group (2.7 ± 0.5 days). The CRP level was significantly lower in the D group (4.6 ± 0.6 mg/dl) than in the C group (8.3 ± 1.1 mg/dl) on the 3rd postoperative day. Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus. DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer.


Hilar cholangiocarcinoma accompanied by pancreaticobiliary maljunction without bile duct dilatation 20 years after cholecystectomy: report of a case

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. From the perspective of carcinogenesis, the treatment for PBM is controversial. We herein report a case of hilar cholangiocarcinoma 20 years after the occurrence of gallbladder cancer. A 75-year-old man was referred to our hospital regarding an obstructive jaundice and bile duct tumor. A cholecystectomy was performed for cholelithiasis on this patient 20 years ago, and cancer in situ was detected. Computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a tumor of the portal hepatic region and PBM without dilatation of the bile duct. Adenocarcinoma was detected from bile cytology, and we diagnosed hilar cholangiocarcinoma. Despite the biliary decompression, jaundice was prolonged and the patient passed away. Our case suggests that not only cholecystectomy but also biliary diversion is needed for PBM regardless of the existence of bile duct dilatation.


The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.

The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.


Specific molecular signatures of non-tumor liver tissue may predict a risk of hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most common human cancers and a major cause of cancer-related death worldwide. The bleak outcomes of HCC patients even after curative treatment have been, at least partially, attributed to its multicentric origin. Therefore, it is necessary to examine not only tumor tissue but also non-tumor liver tissue to investigate the molecular mechanisms operating during hepatocarcinogenesis based on the concept of "field cancerization". Several studies previously investigated the association of molecular alterations in non-tumor liver tissue with clinical features and prognosis in HCC patients on a genome-wide scale. In particular, specific alterations of DNA methylation profiles have been confirmed in non-tumor liver tissue. This review focuses on the possible clinical value of array-based comprehensive analyses of molecular alterations, especially aberrant DNA methylation, in non-tumor liver tissue to clarify the risk of hepatocarcinogenesis. Carcinogenetic risk estimation based on specific methylation signatures may be advantageous for close follow-up of patients who are at high risk of HCC development. Furthermore, epigenetic therapies for patients with chronic liver diseases may be helpful to reduce the risk of HCC development because epigenetic alterations are potentially reversible, and thus provide promising molecular targets for therapeutic intervention.


日本医学会分科会における女性医師支援2015年 第3回アンケート調査

日本医学会分科会における女性医師支援2015年 第3回アンケート調査


Epithelial-mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation.

We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.


The beneficial effects of Kampo medicine Dai-Ken-Chu-To after hepatic resection: a prospective randomized control study.

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. 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, 2.5 g 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. 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). DKT suppressed inflammatory reaction, stimulated bowel movement and improved oral intake after hepatic resection, which may decrease serious morbidity after hepatic resection.


Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation.

Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters 3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial-mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA-mediated upregulation of hypoxia-inducible factor-1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia-inducible factor-1.


Liver regeneration after splenectomy in patients with liver cirrhosis.

Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration. Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups. Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy. Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed.


Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation.

Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred. J. Med. Invest. 63: 315-318, August, 2016.

The Journal of Medical Investigation : JMI


Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma.

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). 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. 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. The CD44 expressions in the non-tumor tissues may predict HCC recurrence.

International Journal of Clinical Oncology


Indoleamine 2,3-dioxygenase affects the aggressiveness of intraductal papillary mucinous neoplasms through Foxp3+CD4+CD25+ T cells in peripheral blood.

Intraductal papillary mucinous neoplasms (IPMNs) have a high malignant potential. We previously reported that peripheral Foxp3(+)CD4(+)CD25(+) T-cell (Foxp3(+) Treg) populations significantly increase with IPMN pathological aggressiveness. Dendritic cell-mediated induction of active Tregs from naive CD4(+) T cells requires indoleamine 2,3-dioxygenase (IDO). Here, we evaluated whether an IDO-Foxp3(+) Treg interaction plays a role in IPMN pathological aggressiveness. We evaluated peripheral blood samples and resected specimens from 12 patients with IPMN. We analyzed Foxp3(+)CD4(+)CD25(+) T cells in peripheral blood by fluorescence-activated cell sorting, evaluated the resected specimens by anti-IDO antibody staining, and compared them with the patients' clinicopathological factors. The pathological aggressiveness of IPMN was significantly associated with the number of peripheral Foxp3(+) Tregs (P < 0.05) and IDO-positive cells per high-power field (HPF) (P < 0.01). There was a significant correlation between the numbers of peripheral Foxp3(+) Tregs and IDO-positive cells/HPF (r = 0.625, P < 0.01). Patients with 7 or more IDO-positive cells/HPF had a significantly higher recurrence rate than those with less than 7 IDO-positive cells/HPF (P < 0.01, log-rank test). Peripheral Foxp3(+) Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3(+) Tregs can be induced by local IDO-positive cells in IPMN.


Modified hanging method for liver resection.

The liver hanging maneuver (LHM) is a useful technique to transect the liver parenchyma while lifting it with a tape passed between the anterior surface of the inferior vena cava (IVC) and the liver parenchyma. The original method was employed mostly for right hepatectomy with an "anterior approach" for huge liver tumors. The tape serves as a guide to the transection plane and facilitates the control of bleeding in the deeper parenchyma of the liver while protecting the anterior surface of the IVC. On the other hand, several recent studies have shown the feasibility and usefulness of modified LHM techniques. These methods can be applied to left hepatectomy with or without caudate lobectomy (segmentectomy 1), even for patients undergoing orthotopic liver transplantation. This report explains the methods and pitfalls of the original and modified LHM. In addition, important anatomical and technical aspects of the mobilization of hepatic lobes are also included.

Journal of Hepato-Biliary-Pancreatic Sciences