Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Prognostic value of preoperative geriatric nutritional risk index in intrahepatic cholangiocarcinoma after hepatectomy: a single­center retrospective cohort study.

AIM: Patients with malignant tumors are prone to develop nutritional disorders. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for assessing the nutritional status. This study was performed to evaluate whether the preoperative GNRI can serve as a prognostic factor in patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative surgery. METHODS: This study included 123 consecutive patients with ICC who were treated with curative surgery. Kaplan-Meier analysis was performed to calculate the recurrence-free survival (RFS) and overall survival (OS), and Cox regression analysis was used to evaluate prognostic factors. RESULTS: Of the 123 patients, 82 were male and 41 were female. The median age of the patients was 70 years, and the median follow-up period was 37.0 months (interquartile range, 16.2-71.7 months). The patients were classified by the median GNRI into a low GNRI group (GNRI < 105) and high GNRI group (GNRI ≥ 105). The patients in the low GNRI group had a significantly poorer prognosis in terms of RFS and OS than the patients in the high GNRI group (RFS, p = 0.0201; OS, p < 0.0001). Lymph node metastasis [hazard ratio (HR), 4.66; 95% confidence interval (CI), 2.46-8.85], postoperative complications (HR, 2.38; 95% CI, 1.32-4.31), and a low GNRI (HR, 2.53; 95% CI, 1.42-4.50) were independent poor prognostic factors for OS. CONCLUSION: The GNRI may be a useful prognostic indicator in patients with ICC undergoing curative hepatectomy.

Patient vulnerability is associated with poor prognosis following upfront hepatectomy for colorectal liver metastasis.

BACKGROUND: With the rapid aging of populations worldwide, the number of vulnerable patients with liver metastasis from colorectal cancer has increased. This study aimed to examine the association between vulnerability and clinical outcomes in patients with colorectal liver metastasis (CRLM). METHODS: Consecutive 101 patients undergoing upfront hepatectomy for CRLM between 2004 and 2020 were included. The preoperative vulnerability was assessed using the Clinical Frailty Scale (CFS) score ranging from one (very fit) to nine (terminally ill), and frailty was defined as a CFS score of ≥ 4. A multivariable Cox proportional hazard regression model was utilized to investigate associations of frailty with disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Of the 101 patients, 12 (12%) had frailty. Associations between frailty and surgical outcomes, namely, the incidence of 90-day mortality and postoperative complications, were not statistically significant (P > 0.05). In the multivariable analyses, after adjusting for clinical risk scores calculated using six factors (timing of liver metastasis, primary tumor lymph node status, number of liver tumors, size of the largest tumor, extrahepatic metastatic disease, and carbohydrate antigen 19-9 level) to predict recurrence following hepatectomy for CRLM, preoperative frailty was found to be an independent risk factor for DFS (hazard ratio [HR]:2.37, 95% confidence interval [CI] 1.06-4.72, P = 0.036), OS (HR:4.17, 95% CI 1.43-10.89, P = 0.011), and CSS (HR:3.49, 95% CI 1.09-9.60, P = 0.036). CONCLUSION: Preoperative frailty was associated with worse DFS, OS, and CSS after upfront hepatectomy for CRLM. Assessment and improvement of patient vulnerability may provide a favorable prognosis for patients with CRLM.

Perioperative disabilities in activities of daily living are associated with worse prognosis after hepatectomy for colorectal liver metastasis.

BACKGROUND: The number of vulnerable patients with colorectal liver metastasis (CRLM) has increased. This study aimed to clarify the relationship between perioperative activities of daily living (ADL) and clinical outcomes after hepatectomy for CRLM. METHODS: Consecutive patients undergoing resection of CRLM from 2004 to 2020 were included. Pre- or postoperative ADL was evaluated according to Barthel index (BI) scores, which range from 0 to 100. Higher scores represent greater level of independence in ADL. Pre- or postoperative BI scores of ≤85 were defined as perioperative disabilities in ADL. Multivariable Cox proportional hazard regression models were utilised to estimate adjusted hazard ratios (HRs) and confidence interval (CI). RESULTS: A total of 218 patients were included, 16 (7.3%) revealed preoperative BI scores of ≤85, and 32 (15%) revealed postoperative BI scores of ≤85. In multivariate analyses, the perioperative disabilities in ADL were independently associated with shorter overall survival (HR, 1.96; 95% CI, 1.10-3.31; P = 0.023) and cancer-specific survival (HR, 2.31; 95% CI, 1.29-3.92; P = 0.006). CONCLUSION: Perioperative disabilities in ADL were associated with poor prognosis following hepatectomy for CRLM. Improving preoperative vulnerability and preventing functional decline after surgery may provide a favourable prognosis for patients with CRLM.

Hyperglycaemia induces metabolic reprogramming into a glycolytic phenotype and promotes epithelial-mesenchymal transitions via YAP/TAZ-Hedgehog signalling axis in pancreatic cancer.

BACKGROUND: Hyperglycaemia is a well-known initial symptom in patients with pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming in cancer, described as the Warburg effect, can induce epithelial-mesenchymal transition (EMT). METHODS: The biological impact of hyperglycaemia on malignant behaviour in PDAC was examined by in vitro and in vivo experiments. RESULTS: Hyperglycaemia promoted EMT by inducing metabolic reprogramming into a glycolytic phenotype via yes-associated protein (YAP)/PDZ-binding motif (TAZ) overexpression, accompanied by GLUT1 overexpression and enhanced phosphorylation Akt in PDAC. In addition, hyperglycaemia enhanced chemoresistance by upregulating ABCB1 expression and triggered PDAC switch into pure basal-like subtype with activated Hedgehog pathway (GLI1 high, GATA6 low expression) through YAP/TAZ overexpression. PDAC is characterised by abundant stroma that harbours tumour-promoting properties and chemoresistance. Hyperglycaemia promotes the production of collagen fibre-related proteins (fibronectin, fibroblast activation protein, COL1A1 and COL11A1) by stimulating YAP/TAZ expression in cancer-associated fibroblasts (CAFs). Knockdown of YAP and/or TAZ or treatment with YAP/TAZ inhibitor (K975) abolished EMT, chemoresistance and a favourable tumour microenvironment even under hyperglycemic conditions in vitro and in vivo. CONCLUSION: Hyperglycaemia induces metabolic reprogramming into glycolytic phenotype and promotes EMT via YAP/TAZ-Hedgehog signalling axis, and YAP/TAZ could be a novel therapeutic target in PDAC.

Disability in perioperative activities of daily living is associated with worse survival outcomes following hepatic resection in patients with intrahepatic cholangiocarcinoma.

AIM: Intrahepatic cholangiocarcinoma (ICC) is a rare disease; however, its incidence and mortality are increasing worldwide. The rapid aging of populations around the world is leading to an increased number of patients with cancer who develop disability in activities of daily living (ADL). This study was conducted to investigate the associations of perioperative ADL with patient survival after hepatic resection for ICC. METHODS: We included 70 consecutive patients who underwent hepatectomy for ICC from 2010 to 2021 in the current study. Preoperative and postoperative ADL were evaluated based on the Barthel index, which yields a score of 0-100 points, with higher scores indicating greater independence. A preoperative or postoperative Barthel index score of <100 was defined as disability in perioperative ADL. Cox proportional hazards regression was used to calculate hazard ratios after adjusting for potential confounders. RESULTS: Among the 70 patients, seven (10%) had a preoperative Barthel index score of <100, and 23 (33%) showed a postoperative Barthel index score of <100. Multivariate analyses revealed that disability in perioperative ADL was associated with shorter recurrence-free survival (multivariable hazard ratios 2.38, 95% confidence interval 1.22-4.57; p = 0.011) and overall survival (multivariable hazard ratio 2.49, 95% confidence interval 1.09-5.70; p = 0.031). CONCLUSIONS: Disability in perioperative ADL is associated with shorter recurrence-free and overall survival after hepatic resection for ICC. Upon validation, perioperative measurement of ADL may improve risk assessment, and improvement of perioperative ADL may lead to favorable clinical outcomes in patients with ICC.

Distinct approaches (antecolic and retrocolic) according to tumor location in laparoscopic and endoscopic cooperative surgery for non-ampullary duodenum tumors.

AIM: Laparoscopic and endoscopic cooperative surgery for early non-ampullary duodenum tumors (D-LECS) is now noted because of its safety and lower invasiveness. Here, we introduce two distinct approaches (antecolic and retrocolic) according to the tumor location during D-LECS. METHODS: From October 2018 to March 2022, 24 patients (25 lesions) underwent D-LECS. Two (8%), two (8%), 16 (64%), and five (20%) lesions were located in the first portion, in the second portion to Vater's papilla, around the inferior duodenum flexure, and in the third portion of the duodenum, respectively. The median preoperative tumor diameter was 22.5 mm. RESULTS: Antecolic and retrocolic approaches were employed in 16 (67%) and 8 (33%) cases, respectively. LECS procedures, such as two-layer suturing after full-thickness dissection and laparoscopic reinforcement by seromuscular suturing after endoscopic submucosal dissection (ESD), were performed in five and 19 cases, respectively. Median operative time and blood loss were 303 min and 5 g, respectively. Intraoperative duodenal perforations occurred in three of 19 cases during ESD; however, they were successfully laparoscopically repaired. Median times until start diet and postoperative hospital stay were 4.5 and 8 days, respectively. Histological examination of the tumors revealed nine adenomas, 12 adenocarcinomas, and four GISTs. Curative resection (R0) was achieved in 21 cases (87.5%). In a comparison of the surgical short outcomes between antecolic and retrocolic approaches, there was no significant difference. CONCLUSION: D-LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors, and two distinct approaches according to the tumor location are feasible.

Comparison of Slow-Infusion Magnetic Resonance Angiography with Sequential K-Space Filling and Computed Tomography Angiography to Detect the Adamkiewicz Artery.

BACKGROUND: Radiographic detection of the Adamkiewicz artery (AKA) before aortic surgery helps to avoid spinal cord ischemia (SCI). We applied magnetic resonance angiography (MRA) using gadolinium enhancement (Gd-MRA) by means of the slow-infusion method with sequential k-space filling and compared AKA detectability with that of computed tomography angiography (CTA). METHODS: A total of 63 patients with thoracic or thoracoabdominal aortic disease (30 with aortic dissection [AD] and 33 with aortic aneurysm) who underwent both CTA and Gd-MRA to detect AKA were evaluated. The detectability of the AKA using Gd-MRA and CTA were compared among all patients and subgroups based on anatomical features. RESULTS: The detection rates of the AKAs using Gd-MRA and CTA were higher in all 63 patients (92.1% vs. 71.4%, P = 0.003). In AD cases, the detection rates using Gd-MRA and CTA were higher in all 30 patients (93.3% vs. 66.7%, P = 0.01) as well as in 7 patients whose AKA originated from false lumens (100% vs. 0%). In aneurysm cases, the detection rates using Gd-MRA and CTA were higher in 22 patients whose AKA originated from the nonaneurysmal parts (100% vs. 81.8%, P = 0.03). In clinical, SCI was observed in 1.8% of cases after open or endovascular repair. CONCLUSIONS: Despite the longer examination time and more complicated imaging techniques compared to those of CTA, the high spatial resolution of slow-infusion MRA may be preferable for detecting AKA before performing various thoracic and thoracoabdominal aortic surgeries.

Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial.

BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

[The Usefulness of RFA as a Conversion Therapy after Molecular Targeted Therapy for Advanced Hepatocellular Carcinoma-A Case of Long-Term Survival with Multidisciplinary Treatment].

In this study, we report a case in which molecular-targeted agents have been shown to be effective in the treatment of unresectable hepatocellular carcinoma(HCC), which has enabled a radical treatment, conversion therapy, and long-term survival with multimodality treatment including RFA. Case: A 61-year-old male, abdominal ultrasonography revealed a large liver tumor and multiple lesions mainly in the right lobe of the liver. He was diagnosed as having unresectable HCC, and treatment with sorafenib was initiated. After treatment, the tumor was clearly reduced in size and the lung metastases disappeared. Five years later, recurrence was observed at the treated site of S7/8, and RFA was performed again after TACE. The patient has survived for 8 years without recurrence.

Survival impact of immune cells infiltrating peritumoral area of hepatocellular carcinoma.

Inflammatory and immune cells in the tumor microenvironment are reported to be associated with tumor progression in several cancers. In total, 225 patients who underwent initial and curative hepatectomy for hepatocellular carcinoma (HCC) from 2004 to 2013 were enrolled in this study. Tumor-associated neutrophils (TANs), M2 macrophages (TAMs; tumor-associated macrophages), CD8+ T cells, and regulatory T cells (Tregs) were evaluated by immunohistochemistry (IHC), and their relationships with patient clinicopathological characteristics and prognosis were evaluated. IHC was performed focusing on TANs first. We could not find a relationship between intratumoral and peritumoral TANs and clinicopathological features except for the fibrous capsule and infiltration of tumors into capsule. Next, TAMs, CD8+ cells and Tregs were evaluated by IHC. At the peritumoral area, TANs and TAMs (r = 0.36, p = 0.001) or Tregs (r = 0.16, p = 0.008) showed a positive correlation, whereas TANs and CD8+ cells showed a negative correlation (r = -0.16, p = 0.02). As for survival outcomes, at the peritumoral area, high TANs (p = 0.0398), low CD8+ cells (p = 0.0275), and high TAMs (p = 0.001) were significantly associated with worse overall survival (OS). In addition, high TANs (p = 0.010), and high TAMs (p = 0.00125) were significantly associated with worse disease-free survival (DFS). Finally, we established a risk signature model by combining the expression patterns of these cells. The high-risk signature group had significantly worse OS (p = 0.0277) and DFS (p = 0.0219) compared with those in the low-risk signature group. Our risk signature based on immune cells at the peritumoral area of the HCC can predict patient prognosis of HCC after curative hepatectomy.

Vascular imaging of patients with refractory Takayasu arteritis treated with tocilizumab: post hoc analysis of a randomized controlled trial.

OBJECTIVES: Tocilizumab, an anti-IL-6 receptor antibody, was investigated in patients with refractory Takayasu arteritis (TAK) in a phase 3 randomized controlled trial. In this post hoc analysis, we investigated whether tocilizumab treatment inhibited the progression of vascular lesions caused by TAK in these patients. METHODS: Included patients received at least one dose of tocilizumab and underwent CT at baseline and at week 48 after tocilizumab initiation. Three radiologists not involved in the original trial independently evaluated the CT images. Twenty-two arteries from each patient were assessed for change from baseline in wall thickness (primary endpoint), dilatation/aneurysm, stenosis/occlusion or wall enhancement for at least 96 weeks after tocilizumab initiation. Patient-level assessments were also conducted. RESULTS: In 28 patients, 86.7% of 22 arteries had improved or stable wall thickness at week 96. Proportions of patients with improved or stable, partially progressed or newly progressed lesions were 57.1%, 10.7% and 28.6%, respectively, for wall thickness; proportions with improved or stable lesions were 92.9% for dilatation/aneurysm, and 85.7% for stenosis/occlusion. Patients with newly progressed lesions, reflecting more refractory disease, were prescribed glucocorticoids at dosages that could not be reduced below 0.1 mg/kg/day at week 96. CONCLUSIONS: Approximately 60% of patients with TAK did not experience progression in wall thickness within 96 weeks after initiation of tocilizumab treatment. Few patients experienced progressed dilatation/aneurysm, or stenosis/occlusion. Wall thickness progression likely resulted from refractory TAK. Patients who experience this should be monitored regularly by imaging, and additional glucocorticoid or immunosuppressive treatment should be considered to avoid vascular progression. TRIAL REGISTRATION: Japan Pharmaceutical Information Centre number, JapicCTI-142616.

The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification. RESULTS: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-γ-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors. CONCLUSIONS: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.

High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study.

BACKGROUND: Bloom syndrome helicase (BLM) is overexpressed in multiple types of cancers and its overexpression may induce genomic instability. This study aimed to determine the function of BLM expression in pancreatic cancer. METHODS: BLM messenger RNA (mRNA) expression was analyzed using public datasets to determine its relationship with pancreatic cancer prognosis. Overall, 182 patients with pancreatic cancer who underwent radical resection at our institution were enrolled. BLM expression was evaluated by immunohistochemistry (IHC). We explored the effect of BLM on the proliferation, invasion, migration, and chemoresistance of pancreatic cancer cells via small-interfering RNAs and performed pathway analysis using gene set enrichment analysis. RESULTS: BLM mRNA expression was higher in tumor tissue than in normal tissue and had a prognostic effect on overall survival (OS) and recurrence-free survival. The same results were validated by IHC. Multivariate analysis showed that high BLM expression was an independent poor prognostic factor for OS (hazard ratio [HR] 1.678, p = 0.029). In subgroup analysis, the effect of high BLM expression was more significant on OS in patients with younger age (HR 2.27, p = 0.006), male sex (HR 2.39, p = 0.002), high cancer antigen 19-9 level (HR 2.44, p = 0.001), advanced tumor stage (HR 2.25, p = 0.001), lymph node metastasis (HR 2.51, p = 0.001), nerve invasion (HR 2.07, p = 0.002), and adjuvant chemotherapy (HR 2.66, p < 0.001). In vitro, BLM suppression resulted in reduced tumor proliferation, invasion, migration, and chemoresistance. Mechanistically, BLM expression may be associated with E2F1 and E2F2. CONCLUSION: BLM expression is a prognostic factor for patients with pancreatic cancer, especially in those with advanced malignancies and receiving chemotherapy.

Impairment of perioperative activities of daily living is associated with poor prognosis following hepatectomy for hepatocellular carcinoma.

BACKGROUND: The number of cancer patients with impairment of activities of daily living (ADLs) has increased. This study aimed to examine associations of perioperative Barthel index score, a validated measure of ADLs, with survival outcomes following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We analyzed data of 492 consecutive patients who underwent hepatectomy for HCC between 2010 and 2018. Pre- and postoperative ADLs were assessed using the Barthel index (range, 0-100; higher scores indicate greater independence). Preoperative Barthel index score ≤85 or postoperative Barthel index score ≤85 was defined as impairment of perioperative ADLs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) after adjusting for potential confounders. RESULTS: Among the 492 patients, 26 (5.2%) had a preoperative Barthel index score ≤85 and 95 (19%) had a postoperative Barthel index score ≤85. Impairment of perioperative ADLs was independently associated with shorter overall survival (multivariable HR: 1.75, 95% confidence interval [CI]: 1.06-2.81, p = 0.028). The association of impairment of perioperative ADLs with recurrence-free survival was not statistically significant. CONCLUSION: Impairment of perioperative ADLs is associated with poor prognosis following hepatectomy for HCC. Maintenance and improvement of perioperative ADLs would be important to provide favorable long-term outcomes in patients with HCC.

Major postoperative complications are associated with early recurrence of hepatocellular carcinoma following hepatectomy.

BACKGROUND AND AIM: Early recurrence (ER) is a strong predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. The aim of this study was to examine manageable factors associated with ER. METHODS: Overall, 475 consecutive patients with primary HCC who underwent curative hepatectomy were included (R0/R1). We defined ER as recurrence within 2 years after hepatectomy and analyzed predictors for ER. We also defined postoperative complication as Clavien-Dindo classification grade III or IV. RESULTS: ER after hepatectomy was observed in 209 cases (44.0%). Patients with ER had a significantly poor prognosis compared with those with late recurrence (log-rank p < 0.0001) and were more likely to be diagnosed with extrahepatic metastasis (p = 0.009). Significant predictors for ER were des-γ-carboxyprothrombin > 40 mAU/mL (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.36-3.14, p = 0.001), multiple tumors (OR 2.80 95%CI 1.83-4.32, p < 0.0001), cirrhosis (OR 1.53, 95%CI 1.01-2.32, p = 0.043), and postoperative complications (OR 1.72, 95% CI 1.05-2.85, p = 0.032). Blood loss (OR 1.09, 95%CI 1.05-1.13, p < 0.0001) and cirrhosis (OR 1.74, 95%CI 1.05-2.86, p = 0.031) were significant predictors for postoperative complications. CONCLUSIONS: We should pay close attention to surgical associated- and disease-specific factors in hepatectomy for HCC to prevent ER.

Clinical significance of preoperative inflammation-based score for the prognosis of patients with hepatocellular carcinoma who underwent hepatectomy.

PURPOSES: The present study investigated the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. METHODS: In total, 493 patients diagnosed HCC using the Milan criteria who underwent hepatic resection were retrospectively analyzed. Patients were evaluated according to several prognostic nutrition indices. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with the overall survival (OS). RESULTS: According to a univariate analysis, higher values in the Glasgow Prognostic Score [GPS] (hazard ratio [HR] = 1.99, p = 0.002), modified GPS [mGPS] (HR = 2.26, p < 0.001), C-reactive protein [CRP]-to-albumin ratio [CAR] (HR = 1.86, p = 0.0012), and CONUT (HR = 1.65, p = 0.008) and a lower value of prognostic nutritional index [PNI] (HR = 2.36, p < 0.001) were significantly associated with a poor OS. A multivariate analysis showed that a CAR ≥ 0.037 (HR = 1.67, 95% CI 1.06-2.64, p = 0.03), FIB4-index > 3.25 (HR = 1.98, 95% confidence interval [CI] 1.25-3.14, p = 0.004) and PIVKA-II > 40 mAU/ml (HR = 1.72, 95% CI 1.14-2.61, p = 0.01) were independent prognostic factors. CONCLUSIONS: This study demonstrated that the CAR was an independent prognostic score in patients with HCC and superior to other inflammation-based prognostic scores in terms of the prognosis.

Is Portal Vein Embolization Followed by Hepatectomy for Hepatocellular Carcinoma Justified in Patients with Impaired Liver Function?

BACKGROUND: Portal vein embolization (PVE) was developed for patients with insufficient future liver remnant volume and function and has gained relevant support worldwide before major hepatectomy. However, the efficacy of preoperative PVE for hepatocellular carcinoma (HCC) patients with impaired liver function remains uncertain. PATIENTS AND METHODS: Ninety-seven HCC patients who were scheduled for PVE followed by hepatectomy were enrolled in this study. Their short- and long-term outcomes were investigated, according to the liver damage classification defined by the Liver Cancer Study Group of Japan. RESULTS: Of 97 patients who underwent preoperative PVE, 30 (32.4%) could not undergo subsequent hepatectomy. Dropout rate from treatment strategy was significantly higher in patients with liver damage B (n = 13, 61.5%) than in those with liver damage A (n = 84, 26.2%) (P = 0.014). Among the 67 patients who underwent planned hepatectomy after PVE, 53 were categorized to liver damage A, and 14 were categorized to liver damage B at the point of hepatectomy. Although major complication and mortality rates were comparable between the two groups, the cumulative overall survival (OS) and disease-free survival (DFS) after hepatectomy were markedly worse in patients with liver damage B than in those with liver damage A (5-year OS rate: 23.1% vs 74.6%, P = 0.014, 5-year DFS rate: 7.8% vs 33.5%, P = 0.054, respectively). CONCLUSIONS: The treatment strategy of PVE followed by hepatectomy might be a contraindication for HCC patients with impaired liver function categorized as liver damage B because of the higher dropout rate and poorer long-term outcomes after hepatectomy.

High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer.

BACKGROUND: Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort. METHODS: We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis. RESULTS: We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression. CONCLUSIONS: High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.

MicroRNA-25 Exerts an Oncogenic Function by Regulating the Ubiquitin Ligase Fbxw7 in Hepatocellular Carcinoma.

BACKGROUND: MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin-proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated. METHODS: Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro. RESULTS: miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro. CONCLUSION: miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.