C-reactive Protein-to-Albumin Ratio: A Useful Predictor for Biliary Fistula After Hepatectomy.

Introduction Postoperative bile leakage (POBL) has emerged as a complication following hepatectomy. POBL is associated with an elevated risk of liver failure and surgical death. This study aimed to examine risk factors for POBL in primary hepatocellular carcinoma (HCC) patients. Methods A total of 296 patients who had surgical resection for a preoperative diagnosis of primary HCC from January 2013 to December 2022 at Ehime Prefectural Central Hospital were included in this study. The patients were categorized into two groups based on the presence of POBL. The preoperative, operative, and histopathological findings were analyzed between the two groups. Risk factors were determined using multivariable analysis. Results Regarding preoperative findings, statistically significant differences were observed in white blood cell count, platelet count, C-reactive protein (CRP) level, and CRP-to-Albumin ratio (CAR) between the two groups (p = 0.023, p = 0.025, p = 0.011, and p = 0.012, respectively). As for intraoperative variables, only operation time (p = 0.017) was statistically correlated with the risk of POBL. Regarding pathological variables, there were no statistically significant differences between the two groups. The optimal cut-off value of CAR, as determined by ROC curve analysis, was 0.053. This value had a sensitivity of 80.0% and a specificity of 72.8%. Multivariate logistic regression analysis indicated that CAR ≥ 0.053 (p = 0.030) and operation time ≥ 308 min (p = 0.023) were independent potential markers for POBL after hepatectomy. Conclusion A high CAR level can be an effective predictor for POBL following hepatectomy.

Vertical interval between hepatic segment of inferior vena cava and right atrium predicts intraoperative blood loss during hemi-hepatectomy.

BACKGROUND: Intraoperative bleeding is a major issue for hepatic surgeons because large intraoperative blood loss causes poor patient outcome. The aim of this study was to identify predictors of intraoperative bleeding during hemi-hepatectomy. Methods This study enrolled 45 living donors for liver transplantation (cohort 1) and 44 patients with various conditions (cohort 2) who underwent hemi-hepatectomy at Ehime University Hospital between January 2010 and March 2019 (Approval number: 1810024). The gap between the ventral horizontal line of the inferior vena cava (IVC) confluent with the right atrium (RA) and the dorsal horizontal line of the hepatic segment of the IVC (IVC-RA gap) was determined from preoperative images. Cardiopulmonary and liver functions were investigated as potential predictors of intraoperative estimated blood loss (iEBL). Results The IVC-RA gap positively correlated with iEBL in cohorts 1 and 2 (r = 0.453, P = 0.002 and r = 0.443, P = 0.003, respectively), and multivariate analysis selected the IVC-RA gap as an independent predictor of iEBL >400 ml in cohorts 1 and 2 (odds ratios 1.177 and 1.115; 95% confidence intervals 1.041-1.330 and 1.007-1.234; P = 0.009 and P = 0.036, respectively). Conclusions The IVC-RA gap is a novel and simple predictor of iEBL.

Wilson Disease With Giant Splenic Artery Aneurysms Caused by Fibromuscular Dysplasia During Living Donor Liver Transplantation: A Case Report.

Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT.

Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions.

Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31+/CD45- endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis.

Reconstruction of Middle Hepatic Vein Tributaries With Artificial Vascular Grafts in Living Donor Liver Transplant Using Right Lobe Grafts: A Case Series.

BACKGROUND: Congestion of the anterior section of the grafted liver might be a problem when performing living donor liver transplant using a right lobe graft without middle hepatic vein (MHV). This can be prevented by MHV tributary reconstruction. We report our procedure and results of reconstructing MHV tributaries using artificial vascular grafts (AVGs). METHODS: We consider venous reconstruction when the estimated territory of each MHV tributary of the transplanted liver is more than 100 mL. For tributaries distant from the stump of the right hepatic vein of the graft, we use heparin-bonded AVGs made of expanded polytetrafluoroethylene with circular rings as the interposition graft between the MHV tributary and the inferior vena cava. During donor surgery, the suturing margin of the MHV tributary is secured before cutting, and it is anastomosed to the AVG during back-bench surgery. After restoration of portal flow in the recipient, we anastomose the AVG at a new position on the inferior vena cava. RESULTS: The above procedure was performed for 4 cases. The estimated drainage territory of the vein that was reconstructed using the AVG ranged from 104 to 180 mL. The AVG patency was achieved for about 2 months in all cases. In terms of morbidity, biloma and pancreatic fistula were observed in 2 cases, although removal of the AVG was not required postoperatively in any of the cases. CONCLUSION: The heparin-bonded expanded polytetrafluoroethylene AVG with circular rings is a feasible option for MHV tributary reconstruction in living donor liver transplant using right liver lobe grafts without MHVs.

Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy.

AIM: The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC. METHODS: This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[-]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(-) groups. RESULTS: Serosal invasion was observed in 19 of the 161 patients (12%). The 5-year recurrence-free survival rate was lower for S(+) (13.0%) than for S(-) (28.7%, P = 0.006). The 5-year overall survival (OS) rate was lower for S(+) (24.7%) than for S(-) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α-fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3-year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(-) group (49.7%, P = 0.001). CONCLUSIONS: Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow-up or consideration of adjuvant treatment.

A Truncated form of CD200 (CD200S) Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages.

CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L) but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs) in C6-CD200S tumors displayed dendritic cell (DC)-like morphology with multiple processes and CD86 expression. Furthermore, CD3(+), CD4(+) or CD8(+) cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8(+) cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas.