Mac-2 binding protein glycosylation isomer as a novel predictor of early recurrence after resection for hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. METHODS: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. RESULTS: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31-2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05-1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). CONCLUSIONS: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

Cancer-associated fibroblasts promote tumor cell growth via miR-493-5p in intrahepatic cholangiocarcinoma.

The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs.

Prognostic significance for recurrence of fibroblast growth factor receptor 2 in intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection.

AIMS: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). METHODS AND RESULTS: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. CONCLUSION: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

A novel combined carbohydrate antigen 19-9 and lymphocyte-to-monocyte ratio score can predict early recurrence of resectable pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, which causes a poor prognosis. This study aimed to establish a scoring model to assess the optimal treatment in patients who underwent surgery for PDAC. METHODS: This single-center retrospective study included 127 patients who underwent radical resection for PDAC between 2005 and 2021. Early recurrence (ER) was defined as recurrence within 12 months after resection. The predictive effect for ER was evaluated using receiver operating characteristic (ROC) curves of preoperative parameters. RESULTS: ER occurred in 43 (33.9%) patients. The ER group had a significantly worse prognosis than the non-ER group (p < 0.0001). The carbohydrate antigen 19-9 (CA19-9) level and lymphocyte-to-monocyte ratio (LMR) were the strongest diagnostic factors (areas under the ROC curves: 0.74 and 0.68, respectively). The ER prediction score was calculated using optimal cutoff values. A higher CA19-9-LMR score was associated with a worse prognosis in terms of the overall and recurrence-free survival (p = 0.0017 and p < 0.0001, respectively). A multivariate analysis identified a high CA19-9-LMR score as an independent predictor of ER. CONCLUSIONS: The CA19-9-LMR scoring model can predict ER after surgery and is applicable for risk stratification in the assessment of patients with resectable PDAC.

Mac-2-Binding Protein Glycosylation Isomer as a Novel Predictor of Hepatocellular Carcinoma Recurrence in Patients with Hepatitis C Virus Eradication.

BACKGROUND: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. METHODS: This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. RESULTS: Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. CONCLUSIONS: Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

Impact of aspartate aminotransferase-to-platelet ratio index based score to assess posthepatectomy liver failure in patients with hepatocellular carcninoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF. METHODS: This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors. RESULTS: Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0-4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all). CONCLUSIONS: The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

A novel combined prognostic nutritional index and aspartate aminotransferase-to-platelet ratio index-based score can predict the survival of patients with hepatocellular carcinoma who undergo hepatic resection.

PURPOSE: Inflammation-, nutrition-, and liver fibrosis-related markers are recognized as prognostic for hepatocellular carcinoma (HCC) patients. This study, therefore, assessed the preoperative prognostic utility of the combination of these markers in patients with HCC. METHODS: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2004 and 2017. A total of 454 patients were divided into training (n = 334) and validation (n = 120) cohorts by random sampling. The predictive impact on surgical outcomes was evaluated using receiver operating characteristic (ROC) curves of these prognostic values in the training cohort. RESULTS: The prognostic nutritional index (PNI) and aspartate aminotransferase-to-platelet ratio index (APRI) were the strongest diagnostic values (areas under the ROC curves: 0.627 and 0.646, respectively). A scoring system (over 0-2 points) was developed using optimal cutoff values (for PNI < 46.5 scored as 1 point; for APRI > 0.98 scored as 1 point). An increased PNI-APRI score was an independent prognostic factor for both the overall and disease-free survival in HCC patients. Finally, the clinical feasibility of the PNI-APRI score was confirmed in the validation cohort. CONCLUSIONS: The PNI-APRI score is a useful marker for predicting surgical outcomes of HCC patients.

Prognostic impact of tumor microvessels in intrahepatic cholangiocarcinoma: association with tumor-infiltrating lymphocytes.

Tumor microvessel density (MVD) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (ICC). Tumor-infiltrating lymphocytes (TILs) are also key components of the tumor microenvironment that play important roles in ICC progression. This study aimed to clarify the relationships between the MVD and immune status and prognosis in patients with ICC. Immunohistochemical staining for cluster of differentiation 34 (CD34), cluster of differentiation 8 (CD8), forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) was performed. The relationships between the MVD and clinicopathological characteristics and outcomes were analyzed. Additionally, the correlations between the MVD, CD8+ and Foxp3+ TIL counts, and PD-L1 expression were evaluated. One hundred ICC patients were classified into high (n = 50) and low (n = 50) MVD groups. The serum platelet and carbohydrate antigen 19-9 levels were higher in the low MVD group than in the high MVD group (P = 0.017 and P = 0.008, respectively). The low MVD group showed a significantly larger tumor size (P = 0.016), more frequent microvascular invasion (P = 0.001), and a higher rate of intrahepatic (P = 0.023) and lymph node (P < 0.001) metastasis than the high MVD group. Moreover, the MVD showed a high positive correlation with CD8+ TILs (r = 0.754, P < 0.001) and a negative correlation with Foxp3+ TILs (r = -0.302, P = 0.003). In contrast, no significant correlation was observed between the MVD and PD-L1 expression in cancer cells (P = 0.817). Patients with low MVDs had a significantly worse prognosis than those with high MVDs. Furthermore, multivariable analyses revealed that a low MVD influenced recurrence-free survival. A decreased intratumoral MVD might predict ICC patient outcomes. Tumor microvessels might be associated with ICC progression, possibly by altering TIL recruitment.

Impact of Immune Response on Outcomes in Hepatocellular Carcinoma: Association With Vascular Formation.

BACKGROUND AND AIMS: We investigated the prognostic value of programmed death ligand 1 (PD-L1) expression, tumor-infiltrating CD8-positive T-cell status, and their combination in hepatocellular carcinoma (HCC). Their association with PD-L1 expression and vascular formation was further explored. APPROACH AND RESULTS: Using a database of 387 patients who underwent hepatic resection for HCC, immunohistochemical staining of PD-L1, CD8, and CD34 was performed. Additionally, we undertook an enzyme-linked immunosorbent assay for soluble PD-L1. Compared with patients with HCC and PD-L1-negative expression (n = 311), patients with HCC and PD-L1-positive expression (n = 76) showed significantly worse overall survival (OS; multivariate hazard ratio, 2.502; 95% confidence interval [CI], 1.716-3.649; P < 0.0001). The presence of tumor-infiltrating CD8-positive T cells was significantly correlated with longer OS (multivariate hazard ratio, 0.383; 95% CI, 0.274-0.537; P < 0.0001). Stratification based on PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status was also significantly associated with OS (log-rank, P < 0.0001). HCC with PD-L1-positive expression was significantly correlated with positivity for vessels that encapsulated tumor clusters. Serum PD-L1 levels were significantly higher in the group of patients who had PD-L1-positive expression than in the group of patients who had PD-L1-negative expression (P = 0.0158). CONCLUSIONS: PD-L1 expression in cancer cells was associated with a poor clinical outcome and vascular formation in patients with HCC. Additionally, the combination of PD-L1 expression with tumor-infiltrating CD8-positive T-cell status enabled further classification of patients based on their clinical outcome. Thus, PD-L1 expression in cancer cells and tumor-infiltrating CD8-positive T-cell status might serve as predictive tissue biomarkers.

Impact of Capicua on Pancreatic Cancer Progression.

BACKGROUND: The transcription factor capicua (CIC) regulates mammalian development and homeostasis. Growing evidence shows that CIC suppresses various human cancers by directly repressing the downstream cancer-related target genes. This study investigated the clinical and biologic significance of CIC expression in pancreatic cancer (PC). METHODS: The study reviewed 132 patients with PC who underwent curative resection. The patients were divided into two groups according to CIC immunoreactivity score by immunohistochemistry, and the associations between CIC expression, clinicopathologic characteristics, and postoperative prognosis were investigated. Moreover, the influence of CIC expression on the malignant potential of PC cells was assessed with cell proliferation, motility assays, and use of quantitative real time-polymerase chain reaction and Western blot on the downstream target genes of CIC in knockdown experiments. RESULTS: The low-CIC expression group showed a higher proportion of lymphatic invasion (72.9% vs. 53.1%; p = 0.024), intrapancreatic neural invasion (94.1% vs. 81.3%; p = 0.021), and extrapancreatic plexus invasion (30.9% vs. 7.8%; p = 0.0006) than the high-CIC expression group as well as significantly worse overall survival (p = 0.0002) and recurrence-free survival (p = 0.0041) rates. Low CIC expression was an independent risk factor for poor prognosis (p = 0.038). Pancreatic cancer cells with knockdown CIC significantly enhanced cell motilities and cell cycle progression, promoted expression levels of ETV4 and MMP-9, and induced EMT. CONCLUSIONS: The study elucidated the association of low CIC expression with a poor prognosis for patients with PC and suggested that the CIC-ETV4-MMP-9 axis might control PC progression.

Lymphocyte-C-reactive protein ratio as a prognostic marker associated with the tumor immune microenvironment in intrahepatic cholangiocarcinoma.

BACKGROUND: Changes in immune cell and inflammation-associated protein levels, either independently or in combination, are commonly used as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte-CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of LCR and its relationship to various aspects of the tumor immune microenvironment in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: This was a single-center, retrospective study of patients who underwent surgical resection for ICC between 1998 and 2018. Patients were dichotomized into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Tumor-infiltrating CD8+ and FOXP3s+ lymphocytes and tumor expression of CD34 and programmed death-ligand 1 were evaluated by immunohistochemical staining of resected tumors. RESULTS: A total of 78 ICC patients were enrolled and assigned to the high (n = 44)- and low (n = 34)-LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly higher serum CA19-9 level (median 20.6 vs. 77.3 U/mL, P = 0.0017) and larger tumor size (median 3.5 vs. 5.5 cm, P = 0.0018). LCR correlated significantly with tumor microvessel density (r = 0.369, P = 0.0009) and CD8+ T lymphocyte infiltration (r = 0.377, P = 0.0007) but not with FOXP3+ T lymphocyte infiltration or tumor PD-L1 expression. Low-LCR status was significantly associated with worse overall survival by multivariate analysis (P = 0.0348). CONCLUSIONS: Low-LCR status may reflect a poor anti-tumor immune response and predict worse outcomes in ICC patients.

Modulation of Nqo1 activity intercepts anoikis resistance and reduces metastatic potential of hepatocellular carcinoma.

The processing of intracellular reactive oxygen species (ROS) by nuclear factor erythroid-derived 2-like 2 (Nrf2) and NADPH quinone oxidoreductase 1 (Nqo1) is important for tumor metastasis. However, the clinical and biological significance of Nrf2/Nqo1 expression in hepatocellular carcinoma (HCC) remains unclear. We aimed to clarify the clinical importance of Nrf2/Nqo1 expression in HCC and evaluate the association of Nrf2/Nqo1 expression with HCC metastasis. We also evaluated the impact of Nqo1 modulation on HCC metastatic potential. We used spheroids derived from HCC cell lines. In anchorage-independent culture, HCC cells showed increased ROS, leading to the upregulation of Nrf2/Nqo1. Futile stimulation of Nqo1 by ß-lapachone induces excessive oxidative stress and dramatically increased anoikis sensitivity, finally diminishing the spheroid formation ability, which was far stronger than depletion of Nqo1. We analyzed 117 cases of primary HCC who underwent curative resection. Overexpression of Nrf2/Nqo1 in primary HCC was associated with tumor size, high α-fetoprotein, and des-γ-carboxy-prothrombin levels. Overexpression of Nrf2/Nqo1 was also associated with multiple intrahepatic recurrences (P = .0073) and was an independent risk factor for poor prognosis (P = .0031). NADPH quinone oxidoreductase 1 plays an important role in anchorage-independent survival, which is essential for survival for circulation and distant metastasis of HCC cells. These results suggest that targeting Nqo1 activity could be a potential strategy for HCC adjuvant therapy.

Surgical Indications for Hepatocellular Carcinoma with Non-hypervascular Hypointense Nodules Detected by Gd-EOB-DTPA-Enhanced MRI.

BACKGROUND: The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. METHODS: We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. RESULTS: There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). CONCLUSIONS: Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely.

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. RESULTS: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. CONCLUSIONS: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.

Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.

Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma.

PURPOSE: Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). METHODS: The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. RESULTS: The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. CONCLUSIONS: Our IS scoring system may predict long-term outcomes after surgery for MF-ICC.

Lymphocyte-to-Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma.

Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment.

A case of difficult-to-diagnose hepatic reactive lymphoid hyperplasia finally diagnosed by using PCR analysis of IgH-gene rearrangements: a case report.

Reactive lymphoid hyperplasia (RLH) of the liver is extremely rare. Despite advancements in diagnostic imaging technology, it is still difficult to distinguish from hepatocellular carcinoma (HCC). Herein, we present a case of hepatic RLH mimicking HCC that was postoperatively diagnosed using several imaging modalities. A 78-year-old female was referred to our hospital with a positive hepatitis C virus antibody (HCV Ab) test. Ultrasonography revealed a 13 mm isoechoic lesion in segment 8 of the liver. Contrast-enhanced computed tomography (CE-CT) demonstrated arterial hyperintensity and washout during the later phase. On ethoxybenzyl magnetic resonance imaging (EOB-MRI), the lesion was hyperenhanced in the arterial phase and of low intensity in the hepatocyte phase. Although the tumor markers were all within normal limits, the pattern of contrast enhancement of the tumor on CT and MRI was consistent with that of HCC. We performed S8 segmentectomy of the liver. Histological examination of the resected specimen revealed dense lymphoid tissue of variable sizes and shapes with expanded germinal centers. Immunohistochemical examination was positive for CD3, CD10 (germinal center), and CD20, and negative for B-cell lymphoma 2 (bcl-2) (germinal center) and Epstein-Barr virus (EBV). A polymerase chain reaction (PCR) analysis of IgH-gene rearrangements revealed polyclonality. Based on these findings, hepatic RLH was diagnosed. The postoperative course was uneventful, and the patient was discharged on the 10th postoperative day. She had a good quality of life after surgery and no liver nodule recurrence was detected at the 4-month medical follow-up. Hepatic RLH is an extremely rare disease and preoperative diagnosis is difficult. This should be considered in the differential diagnosis of single small hepatic tumors. An echo-guided biopsy and careful observation of imaging may help diagnose hepatic RLH, and a PCR analysis of IgH-gene rearrangements would be necessary for the definitive diagnosis of hepatic RLH.

Total pancreatectomy preserving the right gastroepiploic artery following proximal gastrectomy.

Total pancreatectomy (TP) after proximal gastrectomy (PG) requires more attention than ordinary TP during surgery in terms of the preservation of blood flow to the remnant stomach that was supplied via only the right gastric and gastroepiploic arteries. The current report presents the details of a case in which the remnant stomach was safely preserved when performing TP. A 74-year-old man who underwent PG for gastric cancer 17 years previously was diagnosed with pancreatic head cancer during follow-up for intraductal papillary mucinous neoplasm of the pancreatic body and tail. To preserve digestive function and reduce postoperative complications, TP preserving the right gastroepiploic artery and splenic vessels was performed. The remnant stomach and function were safely preserved without any complications after surgery.