Downregulation of ABCC3 activates MAPK signaling through accumulation of deoxycholic acid in colorectal cancer cells.

ABCC3 (also known as MRP3) is an ATP binding cassette transporter for bile acids, whose expression is downregulated in colorectal cancer through the Wnt/ß-catenin signaling pathway. However, it remained unclear how downregulation of ABCC3 expression contributes to colorectal carcinogenesis. We explored the role of ABCC3 in the progression of colorectal cancer-in particular, focusing on the regulation of bile acid export. Gene expression analysis of colorectal adenoma isolated from familial adenomatous polyposis patients revealed that genes related to bile acid secretion including ABCC3 were downregulated as early as at the stage of adenoma formation. Knockdown or overexpression of ABCC3 increased or decreased intracellular concentration of deoxycholic acid, a secondary bile acid, respectively, in colorectal cancer cells. Forced expression of ABCC3 suppressed deoxycholic acid-induced activation of MAPK signaling. Finally, we found that nonsteroidal anti-inflammatory drugs increased ABCC3 expression in colorectal cancer cells, suggesting that ABCC3 could be one of the targets for therapeutic intervention of familial adenomatous polyposis. Our data thus suggest that downregulation of ABCC3 expression contributes to colorectal carcinogenesis through the regulation of intracellular accumulation of bile acids and activity of MAPK signaling.

Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

PURPOSE: The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. METHODS: Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. RESULTS: The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). CONCLUSIONS: Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Effect of abdominal aortic calcification on the prognosis and recurrence of colorectal cancer stages II-III: A retrospective cohort study.

PURPOSE: Abdominal aortic calcification (AAC) is a well-known risk marker for cardiovascular disease. However, its clinical effect on patients who underwent radical surgery for colorectal cancer (CRC) stages II-III is unclear. This study aimed to analyze the associations between AAC and prognosis of patients with stage II-III CRC. METHODS: To evaluate the effect of AAC on clinical outcomes, prognosis, and metastatic patterns of CRC, we analyzed 362 patients who underwent radical surgery for stage II-III CRC between 2010 and 2018. RESULTS: The high AAC group had significantly worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In the multivariate Cox regression analyses, a high AAC was an independent risk factor for poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.23-4.59; p = 0.01), poor CSS (HR, 5.22; 95% CI, 1.74-15.6; p < 0.01), and poor RFS (HR, 1.83; 95% CI, 1.19-2.83; p < 0.01). A high AAC was not associated with a risk of lung metastasis or local or peritoneal recurrence, but a risk for liver metastasis of CRC. CONCLUSION: A high AAC showed a strong relationship with poor OS, CSS, and RFS after curative resection for stage II-III CRC. A high AAC was also associated with a risk for liver metastasis, which may worsen the prognosis in stage II-III CRC. AAC could be a new clinical tool for predicting the prognosis for patients in stage II-III CRC.

Correlation between serum pro-inflammatory cytokine levels and the prognosis of the patients with acute liver failure.

BACKGROUND AND AIM: The prognosis of acute liver failure (ALF) remains poor, and liver transplantation is an alternative treatment option. Assessing the prognosis of ALF is important in determining treatment strategies. Here, we investigated clinical factors including serum pro-inflammatory cytokine levels that are associated with the prognosis of ALF. METHODS: Sixty-six patients who developed ALF were enrolled in this study. Serum concentrations of 12 pro-inflammatory cytokines were measured on admission. The prognosis and factors associated with survival and development of hepatic coma were analyzed. RESULTS: Of 66 patients, 4 patients underwent liver transplantation, and 49 patients were rescued without liver transplantation, while the remaining 13 patients died. Serum concentrations of interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-13, TNF, IFN -γ, IP-10, and G-CSF were significantly elevated in ALF patients. IL-4 and IL-8 levels were higher in patients who underwent liver transplantation or died than in rescued patients. Multivariable analysis identified age ≥ 55 years and IL-4 ≥ 1.2 pg/mL on admission as independent factors for mortality. Serum IL-8 levels were higher in patients with hepatic coma, and prothrombin-international normalized ratio ≥ 3.5 and IL-8 ≥ 77.2 pg/mL on admission were associated with development of hepatic coma after admission. CONCLUSION: Serum levels of several pro-inflammatory cytokines were elevated in ALF patients. IL-4 and IL-8 were correlated with survival and development of hepatic coma after admission, respectively. Measurement of serum pro-inflammatory cytokines seems to be useful for the management of ALF.

Prognosis of repeat hepatectomy for liver transplantable hepatocellular carcinoma recurrence after hepatectomy: a Retrospective Cohort Study with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO).

PURPOSE: Factors affecting the prognosis of repeat hepatectomy for transplantable hepatocellular carcinoma (HCC) recurrence after hepatectomy remain unclear. We aimed to clarify the prognostic factors for transplantable hepatocellular carcinoma recurrence after hepatectomy. METHODS: We included 1758 primary and 486 repeat hepatectomies out of 2244 for HCC performed between 2006 and 2017 using the Hiroshima Study Group for Clinical Oncology and Surgery database. We first compared survival rates of primary and repeat hepatectomy patients. Subsequently, prognostic factors were analyzed in patients who underwent a repeat hepatectomy for transplantable hepatocellular carcinoma recurrence after hepatectomy (defined as age < 70 years at the time of recurrence and recurrent tumor morphology that meets the Milan criteria). RESULTS: The 5-year overall survival rate (OS) after repeat hepatectomy was 63.2%, while the 5-year recurrence-free survival rate (RFS) was 23.7%. RFS demonstrated significant inferiority in the repeat hepatectomy group than in the primary hepatectomy group; however, OS did not present a notable difference between the two cohorts. In the transplantable recurrence group, mALBI grade 2b, max tumor size > 20 mm, and multiple tumors were independent prognostic risk factors for overall survival. Patients with two or more risk factors had a significantly lower survival rate (only 30.6% at 5 years) compared to those with one or fewer risk factors (81.8% at 5 years). CONCLUSIONS: We identified the risk factors involved in post-hepatectomy survival for patients with transplantable recurrence after hepatectomy. The results are a potential indicator of whether salvage liver transplantation should be considered during repeat hepatectomy.

Surgery-related disseminated intravascular coagulation predicts postoperative complications.

PURPOSE: The rate of postoperative morbidity, including infectious complications, is still high after major hepatobiliary pancreatic (HBP) surgery. Although surgery-related disseminated intravascular coagulation (DIC) occurs in some cases, its significance has not been elucidated in HBP surgery. This study aimed to evaluate the influence of surgery-related DIC on the complication severity after HBP surgery. METHODS: We analyzed the records of 100 patients with hepatectomy in two or more segments, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. The baseline characteristics and complications were compared between patients with and without surgery-related DIC on postoperative day 1 (POD1) after HBP surgery between 2010 and 2018. Complication severity was assessed using the Comprehensive Complication Index (CCI). RESULTS: The DIC group (surgery-related DIC on POD1) had predictive factors, such as larger bleeding volume and higher liver enzyme levels. The DIC group exhibited significantly elevated rates of surgical site infection, sepsis, prolonged intensive care unit stay, more frequent blood transfusions, and higher CCI. Furthermore, compared with and without adjustment of DIC, odds ratio (OR) of AST level and operation time for  the risk of high CCI decreased (OR of AST level: 1.25 to 1.19 and OR of operation time: 1.30 to 1.23) and the significant differences had vanished. CONCLUSIONS: Surgery-related DIC on POD1 could be a partial mediator between AST level, operation time and higher CCI. The prevention or proper management of surgery-related DIC on POD1 can be an important target to reduce the severity of postoperative complications.

Adoptive immunotherapy overcomes genetic susceptibility to bloodstream infections due to fc-gamma receptor polymorphisms after liver transplantation.

Single nucleotide polymorphisms (SNPs) in FCGR3A can predict the susceptibility of liver transplant (LT) recipients to bloodstream infections (BSI) and clinical outcomes following living-donor LT (LDLT). Here, we retrospectively analyzed the relationship of adoptive immunotherapy with activated natural killer (NK) cells from perfusate effluents of liver allografts against BSI following LDLT. Higher BSI incidence and lower survival were observed in LT recipients with FcγRIIIa (158F/F or F/V) (n = 81) who did not receive adoptive immunotherapy (n = 55) than in those who did (n = 26) (BSI frequency, 36.4% vs. 11.5%; p = .033; log-rank p = .047). After matching patient background using propensity score, similar results were obtained (BSI ratio, 41.7% vs. 12.5%; p = .049; log-rank p = .039). The predominant BSI pathogens in patients who did and did not receive adoptive immunotherapy were gram-negative rods (n = 3, 100%) and gram-positive cocci (GPC) (n = 15, 65.2%), respectively. The proportion of NK cells administered to patients with BSI was significantly lower than that administered to patients without BSI (Number: 80.3 (29.9-239.2) × 106 cells vs. 37.1 (35.6-50.4) × 106 ; p = .033, percentage; 14.1 (13.3-17.8)% vs. 34.6 (16.5-47)%, p = .0078). Therefore, adoptive immunotherapy with NK cells was associated with the reduced post-transplant BSI related to GPCs due to FcγRIIIa SNP in LT recipients.

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer.

The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interference-mediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.

Molecular Mismatch Predicts T Cell-Mediated Rejection and De Novo Donor-Specific Antibody Formation After Living Donor Liver Transplantation.

Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8+ T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.

Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E.

AIM: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. METHODS: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2 -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors. RESULTS: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion. CONCLUSIONS: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection.

Cognitive-Evaluative Dimension of Pain in Neuropathic Pain Relapse in Sciatica: A Case Report.

The cognitive-evaluative (C-E) dimension of pain is commonly observed in patients with a relatively long duration of pain. However, little is known about the effects of pain relapse on the C-E dimension of pain. Moreover, the improvement process of the C-E dimension of pain following treatment is unknown. The objective of this case report was to (a) demonstrate that the C-E dimension was affected in the acute phase of neuropathic pain in cases of pain relapse, and (b) demonstrate the improvement process of the C-E dimension of pain. A woman was diagnosed with low back pain (LBP) and sciatica. The patient had previously experienced symptoms of LBP and sciatica; thus, this episode was a case of pain relapse. At the beginning of rehabilitation, the C-E dimension of pain was present in addition to the sensory-discriminative (S-D) dimension of pain. It was observed that improvement of the C-E dimension of pain was delayed in comparison with that of the S-D dimension of pain. The C-E dimension of pain was observed with pain relapse even though it was in the acute phase of pain. This case provides a novel insight into the C-E dimension of pain. Moreover, the delay in improving the C-E dimension of pain indicates a difference in the improvement process for each pain dimension.

Everolimus enhances TRAIL-mediated anti-tumor activity of liver resident natural killer cells in mice.

In transplantation, innate immunity plays a pivotal role in immunosurveillance and host defence against microbes and neoplastic cells. Liver-resident NK cells express TNF-related apoptosis-inducing ligand (TRAIL), which distinguishes them from conventional NK cells. In this study, we investigated the impact of mTOR inhibition on liver-resident NK cells in comparison with that on splenic NK cells in a mouse model. In mice that received everolimus (EVR) for 7 days (range: 0.0125-0.25 mg/kg/day), the proportion of splenic NK cells was unchanged, whereas the number of liver NK cells including TRAIL+ NK subpopulation increased for all doses of EVR. Consistently, liver-resident NK cells from the EVR-treated mice displayed enhanced cytotoxicity against TRAIL-sensitive neoplastic cells. EVR treatment inhibited the transition of the immature subset of liver NK cells to a mature state. The negative regulator of NK cells FoxO1 was activated as a consequence of impaired mTORC2-dependent AKT phosphorylation. Activated FoxO1 both reduced T-bet expression and induced TRAIL expression, thereby inhibiting NK cell maturation and promoting the antitumour activity of the immature subset of liver NK cells in response to EVR treatment. These findings indicate that EVR treatment enhances the antitumour activity of immature liver-resident NK cells through TRAIL upregulation.

Impact on biliary complications of donor abdominal aortic calcification among living donor liver transplantation: a retrospective study.

Abdominal aortic calcification (AAC) was reported as a poor prognostic factor among liver transplantation. However, donor AAC is not enough discussed. We analyzed the impact of the donor AAC level on graft function on outcomes following living donor liver transplantation (LDLT). A total of 133 consecutive patients who had undergone LDLT were divided into two groups (non-AAC group and AAC group) according to their donor AAC level by plain computed tomography. The rate of postoperative biliary complications (BC) was significantly higher in AAC group (N = 17) than in non-AAC group (N = 116; HR, 2.77; 95% CI, 1.32-5.83; P = 0.0008). The Cox proportional hazards regression model revealed that donor AAC (HR, 4.15; 95% CI, 1.93-8.97; P = 0.0003) and right lobe graft (HR, 2.81; 95% CI, 1.41-5.61; P = 0.003) increased the risk of BC. Conversely, splenectomy (HR, 0.39; 95% CI, 0.16-0.92; P = 0.03) decreased the risk of BC after LDLT independently. The long-term survival was also significantly worse in AAC group than in non-AAC group (HR, 2.25; 95% CI, 1.04-4.89; P = 0.04). Donor AAC was an independent prognostic factor for BC among patients undergoing LDLT. Although further investigations are needed to verify our results, the levels of donor AAC could be a useful tool to identify the risks of BC and predict better outcomes following LDLT.

Impact of Abdominal Aortic Calcification Among Liver Transplantation Recipients.

Abdominal aortic calcification (AAC) is known as a risk factor of coronary artery disease, stroke, hyperphosphatemia, chronic inflammation, diabetes, and decreased estimated glomerular filtration rate. However, the clinical implications of incidental AAC findings in liver transplantation (LT) have not been evaluated in terms of posttransplantation survival and complications. Therefore, we analyzed the relationships between the AAC level and the outcomes following LT. A total of 156 consecutive patients who underwent LT between January 2007 and December 2014 were divided into 2 groups according to their AAC level (<100 mm3 or ≥100 mm3 ), as calculated using the Agatston method. Even after propensity matching, the survival time was significantly longer in the low-AAC group compared with that in the high-AAC group (median survival time, 4.5 versus 3.0 years; P < 0.01). A multivariate analysis identified high AAC level (hazard ratio, 2.2) and old donor age (hazard ratio, 2.2) as prognostic factors for overall survival. In conclusion, high AAC is an independent unfavorable prognostic factor in LT.

7-Ketocholesterol induces ROS-mediated mRNA expression of 12-lipoxygenase, cyclooxygenase-2 and pro-inflammatory cytokines in human mesangial cells: Potential role in diabetic nephropathy.

7-Ketocholesterol (7-KCHO) is a highly proinflammatory oxysterol and plays an important role in the pathophysiology of diabetic nephropathy (DN). Lipoxygenases (LOXs) and cyclooxygenases (COXs) are also involved in the development of DN. The aim of this study was to clarify the effects of 7-KCHO on mRNA expression of LOXs and COXs as well as pro-inflammatory cytokines in human mesangial cells (HMC). We evaluated cell viability by WST-8 assay and measured mRNA expression by reverse transcription-polymerase chain reaction. Intracellular reactive oxygen species (ROS) production was evaluated by flow cytometry. Although 7-KCHO did not affect cell viability of HMC, 7-KCHO stimulated significant increases in mRNA expression of 12-LOX, COX-2 and pro-inflammatory cytokines. 7-KCHO also induced an increase in ROS production, while N-acetylcysteine partially suppressed the increase. The 12-LOX and COX-2 inhibitors also suppressed mRNA expression of cytokines. These findings may contribute to the elucidation of the molecular mechanism of the pathophysiology of DN.

Fracture risk assessment tool (FRAX) and for the diagnosis of osteoporosis in Japanese middle-aged and elderly women: Chiba bone survey.

Osteoporosis not only increases bone fracture risk but also affects survival in postmenopausal women. Although osteoporosis is diagnosed based on low bone mineral density (BMD) determined by dual energy X-ray absorptiometry (DXA), BMD measurement is sometimes difficult because DXA is not widely available in the community. The Fracture Risk Assessment tool (FRAX) can predict 10-year major osteoporotic fracture risk and hip fracture risk with or without femoral neck BMD. The FRAX has not been investigated adequately in community-dwelling Japanese women. We administered the FRAX tool in 13,421 Japanese women who underwent DXA-based forearm BMD measurement in Chiba Bone Survey, a population-based, multicenter, cross-sectional study of postmenopausal osteoporosis conducted in Chiba, Japan. Mean age was 57.77 ± 9.24 years. Mean forearm BMD was 87.94 ± 17.00% of young adult mean (YAM). Mean FRAX major osteoporotic fracture risk without femoral neck BMD was 7.06 ± 5.22%. BMD decreased and percentage of osteoporosis increased from age 55 onward. Age distribution of percentage of subjects with FRAX major osteoporotic fracture risk >15% was similar to that of percentage of osteoporosis subjects. We identified the cutoff value of FRAX major osteoporotic fracture risk for diagnosis of osteoporosis as 7.2%. With this cutoff, the positive likelihood ratio was over 1.0 at age 55 and above but accuracy was low. In conclusion, FRAX without femoral neck BMD reflects bone status, and may be useful to diagnose osteoporosis in Japanese women aged 55 and above, although the sensitivity was low for osteoporosis screening, especially in middle-aged women.

Perforation of the gallbladder in a patient with acute cytomegalovirus cholecystitis shortly following renal transplantation.

A 74-year-old man with end-stage renal failure secondary to diabetes received a living donor renal transplant (cytomegalovirus [CMV]-seropositive recipient from a CMV-seropositive donor). Computed tomography scan revealed a gallbladder with hemorrhage. On postoperative day 27, cholecystography revealed gallbladder perforation; he underwent an emergency operation. Histological examination of the gallbladder wall was positive for multiple viral inclusion bodies. We report a very rare case of both hemorrhagic and perforated CMV cholecystitis within a month following renal transplantation.

Prediction of recurrence following hepatectomy in patients with hepatitis C virus infection-related hepatocellular carcinoma who achieved a sustained virological response.

AIM: The risk of hepatitis C virus infection-related hepatocellular carcinoma (HCC) is lower, with a better prognosis, in patients who achieve a sustained virological response (SVR) than in those who do not. We aimed to identify risk factors of post-hepatectomy HCC recurrence in patients who achieved a SVR. METHODS: This retrospective study included 349 HCC patients who underwent an initial radical hepatectomy at our institution between January 2005 and December 2014. Sixty-eight patients had achieved a SVR (the SVR group) and 281 patients had not (the non-SVR group). Clinical characteristics and long-term outcomes were compared between the two groups. Univariate and multivariate analyses identified variables associated with recurrence-free survival in the SVR group. RESULTS: Post-hepatectomy overall and recurrence-free survival rates were significantly higher in the SVR group than the non-SVR group (P < 0.01 and <0.05, respectively). Univariate analysis of post-hepatectomy recurrence-free survival in the SVR group revealed multiple significant factors: aspartate aminotransferase, 25 IU/L or more (P = 0.01); indocyanine green retention rate at 15 min, 20.0% or less (P < 0.05); hepatic vascular invasion (P < 0.05); and an interval of months or less between achieving a SVR and hepatectomy (P < 0.01). Multivariate analysis confirmed an interval of 30 months or less between achieving a SVR and hepatectomy as an independent prognostic factor of recurrence-free survival (hazard ratio, 2.30; 95.0% confidence interval, 1.04-5.13; P < 0.05). CONCLUSION: The interval between achieving a SVR and hepatectomy is an important predictor of recurrence in hepatitis C virus infection-related HCC patients who achieved a SVR.