Postoperative bleeding after percutaneous transhepatic gallbladder drainage and aspiration in patients receiving antithrombotic therapy.

This study aimed to investigate the bleeding risk associated with percutaneous transhepatic gallbladder interventions in patients with acute cholecystitis receiving antithrombotic therapy. In this retrospective study, 194 consecutive patients who underwent percutaneous transhepatic gallbladder interventions for acute cholecystitis between April 2011 and April 2021 were enrolled. Patients were sorted into four groups: no prior antithrombotic therapy, discontinued antithrombotic drugs, single antithrombotic drug continued perioperatively, and multiple antithrombotic drugs continued perioperatively. The risk of postoperative bleeding after percutaneous transhepatic gallbladder interventions was evaluated via multivariate logistic regression analysis. Of the 116 (59.8%) patients receiving antithrombotic therapy, 32 (16.5%) discontinued antithrombotic drugs before their respective procedure, 50 (25.8%) continued a single antithrombotic drug, and 34 (17.5%) continued multiple antithrombotic drugs during the perioperative period. The rates of significant and severe bleeding were 10.3% (20/194) and 3.1% (6/194), respectively. The rate of significant bleeding was significantly higher in patients who continued multiple antithrombotic drugs than in patients who received no prior antithrombotic therapy (P = 0.006). In the multivariate logistic regression analysis, the continuation of multiple antithrombotic drugs during the perioperative period was a risk factor for significant bleeding after percutaneous transhepatic gallbladder interventions. In conclusion, the perioperative continuation of multiple antithrombotic drugs is a risk factor for postoperative bleeding after percutaneous transhepatic gallbladder interventions.

Improved Liver Function After Sustained Virologic Response Enhanced Prognosis in Hepatitis C with Compensated Advanced Liver Fibrosis.

BACKGROUND AND AIM: Liver function can be improved in patients with chronic hepatitis C virus (HCV) infection who achieved sustained virologic response (SVR) with direct-acting antiviral (DAA) treatment. However, to our knowledge, the impact of liver function improvement after SVR on prognosis has not been investigated. METHODS: A total of 716 patients with chronic HCV infection and compensated advanced liver fibrosis who began receiving DAA treatment between September 2014 and August 2018 in 25 Japanese hospitals and achieved SVR were enrolled. RESULTS: The median age was 73 years, and 336 (47%) and 380 (53%) patients had albumin-bilirubin (ALBI) grade 1 and grade 2, respectively. Improvement to ALBI grade 1 at 1 year after the end of treatment (EOT) was observed in 76% of the patients with baseline ALBI grade 2. Among 380 patients with baseline ALBI grade 2, alanine aminotransferase (ALT) levels ≥ 40 U/L (p < 0.001) and modified ALBI (mALBI) grade 2a (p < 0.001) were significantly associated with improvement to ALBI grade 1 at 1 year after EOT in multivariate analysis. During the median observation period of 51.8 months, 4 and 10 patients with baseline ALBI grade 1 and 2, respectively, died. In patients with baseline ALBI grade 2, only the absence of improvement to ALBI grade 1 at 1 year after EOT was significantly associated with all-cause mortality in univariate analysis. CONCLUSIONS: Baseline ALT levels and mALBI grade were significantly associated with improvement in liver function after SVR. Patients whose liver function improved after SVR could have better prognosis.

Circulating Cell-Free DNA Profiling Predicts the Therapeutic Outcome in Advanced Hepatocellular Carcinoma Patients Treated with Combination Immunotherapy.

Combination immunotherapy with anti-programmed cell death1-ligand1 (PD-L1) and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for patients with unresectable HCC (u-HCC). However, limited patients obtain clinical benefits. Cell-free DNA (cfDNA) in peripheral blood contains circulating tumor DNA (ctDNA) that reflects molecular abnormalities in tumor tissue. We investigated the potential of cfDNA/ctDNA as biomarkers for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy. We enrolled a multicenter cohort of 85 HCC patients treated with atezolizumab and bevacizumab (Atezo/Bev) between 2020 and 2021. Pretreatment plasma was collected, and cfDNA levels were quantified. Ultradeep sequencing of cfDNA was performed with a custom-made panel for detecting mutations in 25 HCC-related cancer genes. We evaluated the association of cfDNA/ctDNA profiles and clinical outcomes. Patients with high plasma cfDNA levels showed a significantly lower response rate and shorter progression-free survival and overall survival (OS) than those with low cfDNA levels. ctDNA detected in 55% of HCC patients included the telomerase reverse transcriptase (TERT) promoter in 31% of these patients, tumor protein 53 (TP53) in 21%, catenin beta 1 (CTNNB1) in 13% and phosphatase and tensin homolog (PTEN) in 7%. The presence or absence of ctDNA did not predict the efficacy of Atezo/Bev therapy. Twenty-six patients with a TERT mutation had significantly shorter OS than those without. The presence of a TERT mutation and alpha-fetoprotein (AFP) ≥ 400 ng/mL were independent predictors of poor OS according to multivariate Cox proportional hazard analysis and could be used to stratify patients treated with Atezo/Bev therapy based on prognosis. In conclusion, pretreatment cfDNA/ctDNA profiling may be useful for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy.

Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C who achieved a sustained virological response through direct-acting antiviral agents among the working population in Japan.

Background and Aim: The development of hepatocarcinogenesis after a sustained virological response (SVR) remains an important issue affecting the balance between treatment and occupational life of workers with chronic hepatitis C virus (HCV) infection in Japan. Here, we aimed to evaluate the hepatocellular carcinoma (HCC) reducing effect and risk factors for developing HCC after SVR in patients treated with direct-acting antiviral agents (DAAs) among the working population. Methods: We studied 2579 working patients with chronic HCV infection who achieved SVR after antiviral treatment. We compared the difference in the cumulative incidence of post-SVR HCC between the interferon (IFN)-based n = 1615 and DAA (n = 964) groups. The risk factors for post-SVR HCC development were determined in the DAA group. Results: After propensity score matching (n = 644 in each group), the HCC development rates were not significantly different between the groups (P = 0.186). Multivariate Cox regression and the cutoff values determined by the receiver operating characteristic curve analyses revealed that age ≥61 years, diabetes, lower serum albumin levels <4.0 g/dL at 24 weeks after the end of treatment (EOT), and higher serum α-fetoprotein levels ≥4.1 ng/mL at 24 weeks after the EOT were associated with the development of HCC. Conclusion: The HCC suppressing effect after SVR through DAA treatment is equivalent to that of IFN treatment in patients in the working population. Intensive follow-up is required after SVR with DAA treatment in Japanese workers with these risk factors to ensure the promotion of health and employment support.

Prediction Model for Intrahepatic Distant Recurrence After Radiofrequency Ablation for Primary Hepatocellular Carcinoma 2 cm or Smaller.

BACKGROUND: Intrahepatic hepatocellular carcinoma (HCC) has a high recurrence rate after radiofrequency ablation (RFA). However, to date, no standalone predictive factors for intrahepatic distant recurrence after curative ablation have been reported. AIMS: The aim of this study was to investigate predictive factors for intrahepatic distant recurrence after curative treatment with RFA for HCCs. METHODS: This multicenter study consisted of 17 institutions that registered 821 patients. The risk factors for intrahepatic distant recurrence after complete ablation by RFA for primary HCC ≤ 2 cm in diameter were identified in a retrospectively collected training set (n = 636) and then validated in a prospectively collected validation set (n = 185). RESULTS: The cumulative intrahepatic distant and local recurrence rates (i.e., entire recurrence rate) in the training set were 23.6% and 53.7% at 1 and 3 years, respectively. The cumulative intrahepatic distant recurrence rates in the training set were 17.0% and 43.8% at 1 and 3 years, respectively. Multivariate analysis of the training set showed that tumor number and serum levels of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) were independent risk factors for both entire recurrence and intrahepatic distant recurrence. Intrahepatic distant recurrence risk in both the training and validation cohorts was stratified using a scoring system with three factors: tumor number (single or multiple), AFP (< 10 ng/ml or ≥ 10 ng/ml), and DCP (< 50 mAU/ml or ≥ 50 mAU/ml). CONCLUSION: The scoring system composed of tumor number, AFP, and DCP is useful for classifying the risk of intrahepatic distant recurrence after curative ablation for HCC.

Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy.

Atezolizumab/bevacizumab (Atezo/Bev) combination therapy has become a front-line therapy for advanced hepatocellular carcinoma (HCC), but approximately 20% of patients are nonresponders. We investigated circulating biomarkers to predict therapeutic outcomes. We performed simultaneous measurement of 34 proteins using a multiplex bead-based immunoassay in baseline plasma from 34 patients who underwent Atezo/Bev therapy as first- or second-line treatment. Logistic regression analysis showed that plasma IL-6 and interferon alpha (IFNα) levels were significant predictors of non-responders (odds ratio of 13.33 and FDR p = 0.021 for IL-6 and IFNα). The progression-free survival (PFS) and overall survival (OS) of patients with high IL-6 levels were significantly shorter than those of patients with low IL-6 levels. Next, we measured baseline plasma IL-6 levels in 64 HCC patients who underwent Atezo/Bev therapy by ELISA. The IL-6-high group showed higher female ratio, AST levels, tumor markers, Child-Pugh score, and vascular invasion ratio. The PFS and OS of the IL-6-high group were significantly shorter than those of the IL-6-low group. Multivariate Cox proportional hazards analysis showed that IL-6 level and age were independent risk factors for disease progression (hazard ratio of 2.785 and p = 0.015 for IL-6, and hazard ratio 0.306 and p = 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.

Hyperprogressive disease in patients with unresectable hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

BACKGROUND: Atezolizumab plus bevacizumab was approved for hepatocellular carcinoma (HCC) patients in 2020, but treatment outcomes of atezolizumab plus bevacizumab in real-world settings remain unclear. Hyperprogressive disease (HPD), an acceleration of tumor growth occurring in some types of malignancies treated with immune checkpoint inhibitors, was assessed in HCC patients receiving atezolizumab plus bevacizumab. METHODS: Tumor growth kinetics (TGK) and tumor growth rate (TGR) were calculated at pre- and post-treatment in 88 Japanese patients with HCC receiving atezolizumab plus bevacizumab. Hyperprogressive disease was defined as progressive disease (PD) with ≥ two-fold increase in TGK and TGR. The association of baseline characteristics with HPD was analyzed. RESULTS: The best objective responses were partial response, stable disease, and PD in 12 (13.6%), 51 (58.0%), and 25 (28.4%) patients, respectively. The median progression-free survival was 5.0 months. Eleven (12.5%) and 9 (10.2%) patients had a TGK ratio and a TGR ratio of ≥2, respectively. Hyperprogressive disease was observed in nine patients (10.2%) and they showed significantly shorter overall survival than patients without HPD (median, 4.3 months vs. not reached; p < 0.001). Patients with HPD had larger and more intrahepatic tumors, higher levels of α-fetoprotein and lactate dehydrogenase, and higher neutrophil-to-lymphocyte ratio (NLR) at baseline than patients without HPD. NLR of ≥3 at baseline was identified as the only independent factor associated with HPD in multivariate analysis. CONCLUSIONS: Hyperprogressive disease was observed in 10.2% of HCC patients receiving atezolizumab plus bevacizumab, and an elevated NLR at baseline had an increased risk of HPD.

Serum growth differentiation factor 15 predicts hepatocellular carcinoma occurrence after hepatitis C virus elimination.

BACKGROUND: After hepatitis C virus (HCV) elimination, patients should be followed up due to risk of hepatocellular carcinoma (HCC). Growth differentiation factor 15 (GDF15) is a cytokine induced by mitochondrial dysfunction or oxidative stress. Aim To evaluate the prognostic value of GDF15 for HCC occurrence after HCV elimination. METHODS: We measured GDF15 levels in stored serum from patients with chronic HCV infection without a history of HCC who had achieved sustained virological response with direct-acting antiviral agents (DAAs). The patients were randomly divided into derivation (n = 964) and validation (n = 642) cohorts. RESULTS: In the derivation cohort, serum GDF15 levels were higher in those with HCC occurrence after DAA treatment than in those without. Multivariate Cox proportional hazards analysis revealed baseline GDF15 (>1350 pg/mL, HR 2.54), AFP (>5 ng/mL, HR 2.00), and the FIB-4 index (>3.25, HR 2.69) to be independent risk factors for HCC. Scoring based on GDF15, AFP and the FIB-4 index stratified HCC occurrence risk. In the validation cohort, the cumulative HCC occurrence rate at 3 years was 0.64%, 3.27% and 15.3% in low-score (N = 171), medium-score (N = 300) and high-score (N = 166) groups, respectively. In the total cohort, scoring divided patients with a FIB-4 index ≤3.25, whose HCC occurrence rate was 2.0% at 3 years, into medium-score and low-score groups with HCC occurrence rates at 3 years of 3.76% and 0.24%, respectively. CONCLUSIONS: Serum GDF15 predicts de novo HCC occurrence. Scoring using GDF15, AFP, and the FIB-4 index can predict de novo HCC occurrence risk after HCV elimination.

Prediction model for hepatocellular carcinoma occurrence in patients with hepatitis C in the era of direct-acting anti-virals.

BACKGROUND: Several factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct-acting anti-virals (DAAs). AIMS: To develop a prediction model for HCC occurrence after DAA-mediated SVR and validate its usefulness. METHODS: We analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients). RESULTS: In the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2 , P = 0.024), baseline fibrosis-4 (FIB-4) index (≥3.25, P = 0.001), albumin level at SVR (<4.0 g/dL, P = 0.010) and alpha-foetoprotein level at SVR (≥5.0 ng/mL, P = 0.006) were significantly associated with HCC occurrence. We constructed a prediction model for HCC occurrence with these four factors (2 points were added for the FIB-4 index, and 1 point was added for each of the other three factors). Receiver operating characteristics curve analysis identified a score of 2 as the optimal cut-off value for the prediction model (divided into 0-1 and 2-5). In the validation set, the sensitivity and negative predictive value for HCC occurrence were 87.5% and 99.7%, respectively, at 2 years and 71.4% and 98.0%, respectively, at 3 years. CONCLUSION: A prediction model combining these four factors contributes to an efficient surveillance strategy for HCC occurrence after DAA-mediated SVR.

Efficacy of Ramucirumab Versus Sorafenib as Subsequent Treatment for Hepatocellular Carcinoma.

BACKGROUND/AIM: The present study aimed to examine the therapeutic efficacy of ramucirumab compared with that of sorafenib as subsequent systemic therapy for patients with hepatocellular carcinoma (HCC) and serum α-fetoprotein (AFP) levels ≥400 ng/ml. PATIENTS AND METHODS: In our prospectively registered, real-world cohort, 13 and 11 patients treated with ramucirumab or sorafenib, respectively, were analyzed. Progression-free survival (PFS) was primarily compared between the ramucirumab and sorafenib groups. RESULTS: The PFS was significantly longer in the ramucirumab group than in the sorafenib group (median, 2.7 vs. 0.9 months, respectively; p=0.005). There were no significant differences in the objective response rates or the disease control rates between the ramucirumab and sorafenib groups (9.1% and 54.5% vs. 0.0% and 22.2%, respectively). CONCLUSION: Subsequent systemic therapy with ramucirumab showed a better ability to control tumor progression than sorafenib in HCC patients with serum AFP levels ≥400 ng/ml.

Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment.

AIM: The aim of the present study was to investigate the clinical course in hepatitis C virus (HCV)-positive patients with decompensated liver cirrhosis after direct-acting antivirals (DAAs) have been used for HCV infection. METHODS: This multicenter study prospectively analyzed a registered cohort composed of 73 HCV-positive patients with decompensated cirrhosis who attended our 11 institutions between January 2018 and July 2018. Prognoses, including changes in the liver reserve, hepatocellular carcinoma (HCC), decompensation events, and survival, were analyzed up to July 2020, as was the initiation of DAA treatment. RESULTS: Sixty-four (87.7%) and nine (12.3%) patients had Child-Pugh class (C-P) B and C at baseline, respectively. Within 2 years after enrollment, 17 patients (23.3%) received treatment with DAAs, and 31 patients (42.5%) developed uncontrolled HCC, switched to palliative care, or died. Patients who received DAA treatment were significantly younger and had significantly higher alanine aminotransferase levels and lower platelet counts than the patients who did not receive DAA treatment. The rates of overall survival, cumulative HCC occurrence, and cumulative hospitalization for any hepatic decompensation event at 2 years were 64.8%, 13.1%, and 65.6%, respectively. Overall survival was significantly shorter and the HCC occurrence and hospitalization rates were significantly higher in C-P C patients than in C-P B patients. CONCLUSIONS: Among HCV-positive patients with decompensated cirrhosis, approximately one-fourth received DAA treatment, but more than 40% of the patients lost the opportunity for treatment with DAAs.

Clinical outcomes of direct-acting antiviral treatments for patients with hepatitis C after hepatocellular carcinoma are equivalent to interferon treatment.

AIM: It remains unclear how direct-acting antiviral (DAA) treatments influence hepatocellular carcinoma (HCC) recurrence and survival in comparison with interferon (IFN). METHODS: In total, 338 patients with chronic hepatitis C virus (HCV) infection and previous HCC treatments who initiated IFN (N = 88, IFN group) or DAA treatment (N = 250, DAA group) from January 2005 to November 2017 at 23 hospitals and achieved sustained virologic response (SVR) were analyzed. Cumulative HCC recurrence and survival rates were compared between the two groups using propensity score (PS) matching. RESULTS: After PS matching, 63 patients were selected for each group. The cumulative HCC recurrence rates at 1 and 3 years were 20.6% and 34.6% in the IFN group and 19.2% and 43.0% in the DAA group, respectively; the difference in cumulative HCC recurrence rates between the two groups was not significant (P = 0.332). No significant differences in HCC recurrence patterns were observed between the two groups. Overall survival rates at 1 and 3 years were 100% and 96.6% in the IFN group and 100% and 96.4% in the DAA group, respectively; the difference in overall survival rates between the two groups was not significant (P = 0.132). No significant differences in HCC recurrence and overall survival rates were observed between the two groups in subgroup analyses of patients receiving curative treatment (liver resection or radiofrequency ablation) for the most recent HCC before HCV treatment. CONCLUSIONS: The recurrence rates and patterns of HCC and overall survival rates do not differ between SVR patients receiving IFN and DAA treatments.

Therapeutic efficacy of lenvatinib in hepatocellular carcinoma patients with portal hypertension.

AIM: Preserved liver function may be an important factor affecting therapeutic efficacy in hepatocellular carcinoma patients treated with lenvatinib, but not all patients can be treated while preserving liver function. This study evaluated the therapeutic efficacy of lenvatinib in patients with poor liver function with and without portal hypertension. METHODS: This prospectively registered multicenter study analyzed 93 patients treated with lenvatinib. Progression-free survival was compared between patients with and without advanced portal hypertension according to baseline liver function. Advanced portal hypertension was defined as having both splenomegaly and any portosystemic collaterals. RESULTS: A total of 37 patients (40.7%) had advanced portal hypertension. Progression-free survival did not differ between patients with and without advanced portal hypertension in the entire cohort (median 7.6 vs. 4.1 months, respectively; P = 0.148), but was significantly longer in patients with advanced portal hypertension than in those without advanced portal hypertension in the albumin-bilirubin grade 2 or 3 group (median 7.6 vs. 2.1 months, respectively; P = 0.016). In a multivariate analysis, the presence of advanced portal hypertension was identified as the only significant predictor associated with prolonged progression-free survival in the albumin-bilirubin grade 2 or 3 group. CONCLUSIONS: Advanced portal hypertension was associated with the therapeutic efficacy of lenvatinib in controlling the progression of hepatocellular carcinoma in patients with poor liver function.

Pre-existing minor variants with NS5A L31M/V-Y93H double substitution are closely linked to virologic failure with asunaprevir plus daclatasvir treatment for genotype 1b hepatitis C virus infection.

BACKGROUND: L31 and Y93 in the NS5A region of the hepatitis C virus (HCV) are the most important substitution positions associated with resistance to direct-acting antiviral (DAA) treatment. METHODS: We analyzed the frequency of NS5A L31M/V and Y93/H in NS5A inhibitor-naive HCV genotype 1 patients who received asunaprevir plus daclatasvir combination treatment using a conventional sequencing method and a deep sequencing method that can distinguish a single substitution at either position and a double substitution at both positions with a 0.1% detection threshold. RESULTS: The frequency of substitutions at both sites using the conventional method was very low, with 1 in 14 non-responders and 0 in 42 randomly selected responder patients. On the other hand, for the deep sequencing method, cases with double substitutions in the tandem sequence were detected in 8/14 non-responders and 1/42 responders (p<0.0001). For the conventional method, substitutions were detected at any position in 6/14 non-responders and 2/42 responders (p = 0.0019), with a clear difference between the two groups. The difference was also clear with the deep sequencing method, with 11/14 non-responders and 8/42 responders. Interestingly, for the deep sequencing method, the single substitution of L31 was found in 6/14 non-responders and 7/42 responders, whereas single substitutions of Y93 or double substitutions were found in 7/14 vs. 1/42 and 8/14 vs. 1/42 patients, respectively. CONCLUSIONS: NS5A L31 and Y93 substitutions were detected in tandem by the deep sequencing methods in several genotype 1 patients, who may be more resistant to DAA treatment containing an NS5A inhibitor.

Hepatocellular carcinoma occurrence does not differ between interferon-based and interferon-free treatment with liver histological assessment.

AIM: Several studies have recently reported that hepatocellular carcinoma (HCC) occurrence does not differ between hepatitis C virus patients receiving interferon (IFN)-based and IFN-free treatments considering the patients' backgrounds. However, liver fibrosis was not directly considered in these studies. METHODS: In total, 3972 patients without a history of HCC who started IFN-based or IFN-free treatment between August 2002 and April 2017 at 30 Japanese hospitals and achieved a sustained virologic response were included. Propensity score matching considering liver histology was performed. RESULTS: The median age and percentage of patients with advanced liver fibrosis (F3/4) were 58 years and 11.4% in the IFN-based group, and 68 years and 18.9% in the IFN-free group, respectively. The HCC occurrence rates at 1 year and 2 years were 0.4% and 1.1% in the IFN-based group, and 1.6% and 4.1% in the IFN-free group, respectively, and HCC occurrence in the IFN-free group was significantly higher than that in the IFN-based group (P < 0.001). The characteristics of the HCC occurrence patterns did not differ between the two groups. After propensity score matching, among 764 patients, the HCC occurrence rates at 1 year and 2 years were 0.5% and 1.9% in the IFN-based group and 1.1% and 3.0% in the IFN-free group, respectively, and no significant difference was observed between the two groups (P = 0.489). CONCLUSIONS: HCC occurrence in sustained virologic response patients does not differ between IFN-based and IFN-free treatment considering liver fibrosis stage. The degree of its progress at diagnosis does not differ between the two groups.

[Endoscopic treatment for gastric carcinoid tumor in a patient with type A gastritis complicated with autoimmune polyendocrine syndrome: a case report].

A 42-year-old female developed type 1 diabetes mellitus at the age of 16 years and received insulin therapy. Esophagogastroduodenoscopy revealed an atrophic change localized in the gastric body and a small, protruding gastric lesion. Biopsy revealed that this lesion was gastric neuroendocrine tumor. Hence, the patient underwent en bloc resection by endoscopic submucosal resection with a ligation device. As the patient presented both autoimmune gastritis and type 1 diabetes mellitus, she was diagnosed with type 4 autoimmune polyendocrine syndrome. We report this case considering that only few cases of gastric neuroendocrine tumor with autoimmune gastritis (type A gastritis) complicated with autoimmune polyendocrine syndrome have been reported till date.

Efficacy of chemotherapy for older patients with gastric cancer: a multicenter retrospective cohort study.

BACKGROUND: Gastric cancer is one of the leading causes of malignant disease-related mortality, worldwide. With the use of recently developed anti-tumor agents, the prognoses of patients with unresectable gastric cancer are improving. However, the development of an aggressive treatment strategy for older patients (OPs) remains under debate due to concerns regarding treatment feasibility or patient frailty. We aimed to elucidate whether aggressive chemotherapy has survival benefits for OPs with advanced gastric cancer. METHODS: We analyzed consecutive patients diagnosed with inoperable advanced gastric cancer across seven hospitals from August 2007 to July 2015. We defined OPs as patients aged 75 years or older and compared their survival rates with those of non-older patients (NPs). RESULTS: A total of 256 OPs and 425 NPs were enrolled. Of the OPs, 152 patients received chemotherapy and 104 patients received best supportive care (BSC). In contrast, among the NPs, 375 patients received chemotherapy and 50 patients received BSC. There was no significant difference of the median survival time between OPs and NPs in the response to BSC (61 vs 43 days) or chemotherapy (312 vs 348 days). Combination chemotherapy significantly improved survival compared to monotherapy in both OPs and NPs groups (382 vs 253 days in OPs, 381 vs 209 days in NPs). Good performance status, combination therapy, and male, but not age, were significant independent prognostic factors. CONCLUSION: When the performance status of a gastric cancer patient is good, active chemotherapy may improve survival, regardless of age.

Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients.

AIM: Sofosbuvir (SOF) and ribavirin (RBV) combination therapy has improved the sustained virologic response (SVR) rate and shortened the treatment duration for patients with chronic hepatitis C virus (HCV) genotype 2 infection. Ribavirin-induced hemolytic anemia is one of the most troublesome side-effects of SOF/RBV therapy; however, factors associated with this condition have not been fully elucidated. We aimed to identify a safer way to complete treatment with SOF/RBV therapy by examining factors related to RBV-induced hemolytic anemia and identifying patients who did not develop anemia. METHODS: Two hundred and one patients with genotype 2 chronic hepatitis C treated with SOF/RBV therapy were studied. Significant factors associated with the decline in hemoglobin (Hb) levels from the baseline were analyzed. RESULTS: The SVR rate was 96.5% (194 out of 201 patients) based on intent-to-treat analysis. In multivariate analysis, inosine triphosphatase (ITPA) gene variation (P < 0.0001) and estimated glomerular filtration rate (eGFR) (0.001) were significantly associated with a decrease in Hb levels less than 2 g/dL. All patients were divided into four groups by ITPA and eGFR at baseline, and we identified patients with ITPA CA/AA and eGFR >75 as a group that did not develop anemia. CONCLUSIONS: The results presented here suggest that patients with ITPA CA/AA and eGFR >75 had no reduction in Hb levels during the treatment with SOF/RBV in HCV genotype 2-infected patients. Adding RBV to direct-acting antiviral therapy might not be problematic in certain patients, at least in terms of the occurrence of anemia.