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Background/Aim: We investigated the anti-proliferative effect of quercetin on liver cancer cell lines. Materials and Methods: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 μM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. Results: The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. Conclusion: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.

Tumor location and immunity play important roles in the progression of colorectal cancer (CRC). This study aimed to investigate the differences in the immunosurveillance pattern between right‐ and left‐sided CRC and analyze their association with clinicopathologic features, including mismatch repair (MMR) status. We included surgically resected stage II/III CRC cases and evaluated the immunohistochemical findings of HLA class I, HLA class II, programmed cell death‐ligand 1 (PD‐L1), PD‐1, CTLA‐4, CD3, CD4, CD8, TIA‐1, T‐bet, GATA3, RORγT, Foxp3, and CD163. A total of 117 patients were included in the analyses; of these, 30 and 87 had right‐ and left‐sided cancer, respectively. Tumor immunity varied according to the tumor location in the overall cohort. Analysis of the tumors excluding those with DNA mismatch repair (MMR) deficiency also revealed that tumor immunity differed according to the tumor location. In right‐sided colon cancer (CC), high expression of Foxp3 (P = .0055) and TIA‐1 (P = .0396) were associated with significantly better disease‐free survival (DFS). High CD8 (P = .0808) and CD3 (P = .0863) expression tended to have better DFS. Furthermore, in left‐sided CRC, only high PD‐L1 expression in the stroma (P = .0426) was associated with better DFS. In multivariate analysis, high Foxp3 expression in right‐sided CC was an independent prognostic factor for DFS (hazard ratio, 7.6445; 95% confidence interval, 1.2091‐150.35; P = .0284). In conclusion, the immunosurveillance pattern differs between right‐ and left‐sided CRC, even after adjusting for MMR deficiency. Comparison of Kaplan‐Meier curves of disease‐free survival (DFS) in each tumor location excluding DNA mismatch repair deficiency. In right‐sided colon cancer, high Foxp3 (P = .0055) and TIA‐1 expression (P = .0396) were associated with significantly better DFS. High CD8 (P = .0808) and CD3 (0.0863) expression showed a tendency towards better DFS. In left‐sided colorectal cancer, only high sPD‐L1 expression (P = .0426) was associated with better DFS.

Background Thrombocytopenia is a marked feature of chronic liver disease and cirrhosis. We tried to clarify whether an accumulation of platelets in the liver contributes to thrombocytopenia and liver fibrosis in chronic liver disease. Methods Thirty-eight patients who underwent hepatectomy for hepatocellular carcinoma (HCC) with hepatitis C virus infection were included. The locations of platelets and Kupffer cells and the expression of platelet-derived growth factor (PDGF) receptor-β and smooth muscle actin (SMA) were identified by immunohistochemistry. Perisinusoidal mesenchymal cells that express PDGF receptor-β and SMA were interpreted as transformed hepatic stellate cells (HSCs). Results Patients with cirrhosis had a more extensive platelet area in the liver compared to controls (5601 ± 5611 vs. 564 ± 361 μm 2 , p  = 0.02), although the blood platelet count significantly decreased along with the progression of liver fibrosis. In cirrhotic liver, most platelets were present in the sinusoidal space of the periportal area with inflammation, where HSCs expressing PDGF receptor-β were frequently observed. In addition, the platelet and Kupffer cell areas were significantly smaller in cancerous tissue than those in noncancerous tissues (platelet area: 492 ± 823 vs. 3643 ± 4055 μm 2 , p  = 0.001; Kupffer cell area: 450 ± 841 vs. 3012 ± 3051 μm 2 , p  = 0.001). Conclusions The accumulation of platelets in the liver with chronic hepatitis may be involved in thrombocytopenia and liver fibrosis through the activation of HSCs. In addition, our findings also indicate that both platelets and Kupffer cells decrease in HCC tissues.

Studies have indicated that liver mobilization during hepatectomy could cause the dissemination of tumor cells. However, the data are still limited in terms of the relationship between circulating tumor cells (CTCs) and surgical procedures. Fifteen patients who underwent hepatectomy for primary hepatocellular carcinoma (HCC) were included in the study. Blood samples were collected from the portal vein, central vein, and peripheral artery at three time points, namely, before mobilization (BM) of the liver, during transection (DT) of parenchyma, and after resection (AR) of the tumor. To detect CTCs, a real-time PCR assay was performed using primers for the epithelial cell adhesion molecule, cytokeratin 18, and glypican 3. Patients were divided into anterior approach (AA) and non-AA (NA) groups. In the AA group, patients underwent an initial hilar vascular dissection followed by a liver hanging maneuver during transection. Seven patients were allocated to the AA group, and eight to the NA group. In the NA group, CTC levels in the portal vein were significantly increased at DT and AR compared to BM. In cases with large HCC (>70 mm), CTC levels in central venous blood were significantly increased at DT and AR in the NA group. The AA liver resection technique may minimize CTC dissemination, improving the prognosis of patients with HCC.

The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Background Reactive lymphoid hyperplasia (RLH) of the liver is a benign disorder. It is usually observed in the skin, orbit, thyroid, lung, breast, or gastrointestinal tract, but rarely in the liver. Since the first report of RLH of the liver in 1981, only 75 cases have been described in the past literature. Herein, we report a case of RLH of the liver in a patient with autoimmune hepatitis (AIH), which was misdiagnosed as hepatocellular carcinoma (HCC) preoperatively and resected laparoscopically. Case presentation A 43-year-old Japanese woman with autoimmune hepatitis was followed up for 5 years. During her medical checkup, a hypoechoic nodule in segment 6 of the liver was detected. The nodule had been gradually increasing in size for 4 years. Abdominal ultrasound (US) revealed a round, hypoechoic nodule, 12 mm in diameter. Contrast-enhanced computed tomography (CT) demonstrated that the nodule was slightly enhanced in the arterial dominant phase, followed by perinodular enhancement in the portal and late phases. A magnetic resonance imaging (MRI) scan showed low signal intensity on the T1-weighted image (T1WI) and slightly high signal intensity on the T2-weighted image (T2WI). The findings of the Gd-EOB-DTPA-enhanced MRI were similar to those of contrast-enhanced CT. Tumor markers were all within the normal range. The preoperative diagnosis was HCC and a laparoscopic right posterior sectionectomy was performed. Pathological examination revealed that the nodular lesion was infiltrated by small lymphocytes and plasma cells, and germinal centers were present. Immunohistochemistry was positive for B cell and T cell markers, indicating polyclonality. The final diagnosis was RLH of the liver. Conclusions The pathogenesis of RLH of the liver remains unknown, and a definitive diagnosis based on imaging findings is extremely difficult. If a small, solitary nodule is found in female patients with AIH, the possibility of RLH of the liver should be considered.

The aim of this study was to examine the clinicopathological features of pancreatic adenosquamous carcinoma (PASC). Our study included seven patients who underwent resection of PASC. PASC is characterized by large tumors and strong infiltration into the major blood vessels and other organs, forcing many patients to undergo extended resections. In addition, all patients experienced liver metastasis recurrence following surgery, with a very poor prognosis. Histopathologically, a poorly differentiated sarcomatous component existed in all patients in addition to an adenocarcinoma component and squamous carcinoma component. Although P40 staining for the sarcomatous component was positive along with squamous carcinoma, E-cadherin expression disappeared while vimentin was expressed. It has been suggested that it is highly likely that these sarcomatous components are derived from squamous carcinoma and have an impact on prognosis. The sarcomatous component may be related to the biological malignancy of PASC.

The aim of this study was to examine the clinicopathological features of intraductal papillary neoplasm of the bile duct (IPNB) and investigate their relationships with intraductal papillary mucinous neoplasm (IPMN). Our study included 104 patients who underwent resection of tumors that showed papillary growth within the bile duct and pancreas. Comparisons were performed based on subtypes and histological grades. The presence of various histological grades was confirmed in both the IPNB group and the IPMN group, and statistical significance was found in the between-group comparisons of subtypes and histological grades. It was shown that while all patients who underwent IPNB resection did not match the classifications proposed by Nakanuma et al., they did reflect classification characteristics. IPNB and IPMN have common clinical histological features. Common features between IPNB subtype classifications were also identified, which may provide novel diagnostics.