Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer

The γ‐interferon‐induced enzymes indoleamine 2,3‐dioxygenase and GTP‐cyclohydrolase are key players in tumor immune escape mechanisms. We quantified serum levels of neopterin and tryptophan breakdown (tryptophan, kynurenine, and kynurenine‐to‐tryptophan ratio) in addition to prostate‐specific antigen (PSA) in newly diagnosed prostate cancer (PCa) patients (n = 100) before radical prostatectomy (RP) as well as at time of biochemical recurrence (BCR) after RP (n = 50) in comparison to healthy men (n = 49). Effects of biomarkers on the risk of PCa diagnosis on transrectal biopsy, worse histopathological characteristics of the RP specimens, and cancer‐specific survival (CSS) after BCR were investigated. Neopterin (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.08–5.61; P = 0.032) and kynurenine (HR, 2.93; 95% CI, 1.26–6.79; P = 0.012) levels were univariately associated with CSS. When adjusted for other biomarkers, only neopterin remained an independent predictor of CSS (HR, 2.56; 95% CI, 1.07–6.12; P = 0.035). Only PSA was associated with an increased risk of PCa diagnosis on biopsy, univariately (odds ratio, 3.14; 95% CI, 1.68–5.88; P < 0.001) as well when adjusted for other biomarkers (odds ratio, 3.29; 95% CI, 1.70–6.35; P < 0.001). Moreover, only preoperative PSA was able to predict positive surgical margin (area under the receiver operating characteristic curve [AUC] = 0.71; 95% CI, 0.59–0.82; P = 0.001), higher Gleason score (AUC = 0.75; 95% CI, 0.66–0.85; P < 0.001) and extraprostatic involvement (AUC = 0.79; 95% CI, 0.69–0.88; P < 0.001) at RP specimens, respectively. Although serum neopterin and tryptophan breakdown cannot be considered as biomarkers in detecting PCa or in predicting worse final pathological findings, neopterin levels are useful for stratifying patients into different prognostic groups after BCR.     

Survival benefit from S‐1 as compared to Fluorouracil in Asian patients with advanced gastrointestinal cancer: A meta‐analysis

Whether S‐1 could replace 5‐Fluorouracil (5‐Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta‐analysis was performed to compare the activity, efficacy and toxicity of S‐1‐based versus 5‐Fu‐based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S‐1‐based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09–2.70), but no significant progression‐free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72–1.06). Subgroup analyses revealed that S‐1‐based chemotherapy significantly improved OS and ORR in subgroups of patients with non‐platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S‐1‐based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S‐1‐based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S‐1, and S‐1‐based chemotherapy could be considered to replace 5‐Fu‐based therapy for the treatment of advanced GI cancer in Asian patients.     

Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX‐Lung 3

In LUX‐Lung 3, afatinib significantly improved progression‐free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation‐positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX‐Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut‐off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut‐off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment‐related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation‐positive lung adenocarcinoma patients and OS in Del19 but not L858R patients ( www.clinicaltrials.gov ; NCT00949650).     

Increased risk of cancer in patients with early‐onset cataracts: A nationwide population‐based study

Early‐onset cataracts are associated with insufficient antioxidative activity, and, therefore, a potential risk of cancer. This study investigated the risk of cancer after being diagnosed with early‐onset cataracts. Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. Study subjects were comprised of patients with early‐onset cataracts, aged 20–55 years (International Classification of Diseases, 9th Revision, Clinical Modification [ICD‐9‐CM] code 366.00, 366.01, 366.02, 366.03, 366.04, 366.09, 366.17 and 366.18) and newly diagnosed between 1997 and 2010 (n = 1281), and a comparison cohort without the disease (n = 5124). Both cohorts were followed up until 2010 to estimate the incidences of cancer. We used the Poisson regression model to compare incidence rate ratios and the 95% confidence interval (CI). Cox proportional hazards regression was used to assess the hazard ratio (HR) of cancer associated with early‐onset cataracts. The overall incidence rate of all cancers was 2.19‐fold higher in the early‐onset cataract cohort than in the comparison cohort (8.06 vs 3.68 per 1000 person‐years) with an adjusted HR of 2.13 (95% CI = 1.48, 3.07). The site‐specific analysis also showed a strong relationship, with adjusted HR of 3.24 ((95% CI = 1.30, 8.10) for head and neck cancer, 3.29 (95% CI 1.16, 9.31) for hepatoma and 3.19 (95% CI 1.34, 7.58) for breast cancer. The present study suggests that patients with early‐onset cataracts are at an increased risk of being diagnosed with cancer in subsequent years.     

Which is false: Oxaliplatin or fluoropyrimidine? An analysis of patients with KRAS wild‐type metastatic colorectal cancer treated with first‐line epidermal growth factor receptor monoclonal antibody

This meta‐analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin‐based chemotherapy treatment improves efficacy in KRAS wild‐type metastatic colorectal cancer (mCRC), and whether infusional 5‐fluorouracil (5‐FU) and oxaliplatin is a preferred combination for EGFR mAbs. Oxaliplatin (including treatment), EGFR mAbs, first‐line treatment, KRAS wild‐type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time‐to‐event outcomes of overall survival (OS) and progression‐free survival (PFS) were analyzed using HRs (hazard ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. A total of 1767 patients who were KRAS wild‐type were included in this meta‐analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin‐based chemotherapy in patients with KRAS wild‐type mCRC as first‐line treatment resulted in significant improvements in PFS (HR = 0.88; 95% confidence interval (CI), 0.79–0.99; P = 0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14–1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR = 0.96; 95% CI, 0.85–1.08; P = 0.48). However, the differences in OS and PFS were not significant when mAbs were added to bolus 5‐FU or capecitabine‐based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5‐FU and oxaliplatin combination (P = 0.06; PFS, HR = 0.76; 95% CI, 0.65–0.86; P = 0.0002), and even OS was marginally significant, which was consistent with the subgroup analysis of cetuximab and panitumumab. EGFR mAbs combined with oxaliplatin and an infusional 5‐FU regimen was associated with significantly improved RR, PFS and OS as first‐line treatment in KRAS wild‐type mCRC.     

A preclinical evaluation of a novel multikinase inhibitor,SKLB‐329, as a therapeutic agent against hepatocellular carcinoma

We previously reported that lower post‐diagnostic circulating 25‐hydroxyvitamin D [25(OH)D] concentrations were associated with higher risk of overall mortality and distant disease in stage I–IV postmenopausal breast cancer survivors. This association was now re‐examined in an extended dataset to investigate potential effect modification by tumor characteristics and lifestyle factors. A prospective cohort study was conducted in Germany including 2,177 incident stage I–IV postmenopausal breast cancer patients aged 50–74 years. Patients were diagnosed between 2001 and 2005 and median follow‐up time was 5.3 years. Cox proportional hazards models were stratified by age at diagnosis, study center and season of blood collection and adjusted for other prognostic factors. A meta‐analysis of studies on circulating 25(OH)D and mortality in breast cancer patients was performed to summarize evidence. Lower concentrations of 25(OH)D were significantly associated with higher risk of overall mortality [hazard ratio (HR) lowest vs. highest tertile = 1.86; 95% confidence interval (CI): 1.22, 2.82; p‐trend = 0.002] and distant disease (HR = 1.76; 95% CI: 1.24, 2.49; p‐trend = 0.003) in stage I–IIIa but not in stage IIIb–IV breast cancer patients. No significant interaction by lifestyle factors was observed (all p‐interaction > 0.05). The meta‐analysis yielded significant associations with overall and breast cancer‐specific mortality (lowest vs. highest quantile: HR = 1.52; 95% CI: 1.22, 1.88 and HR = 1.74; 95% CI: 1.23, 2.40, respectively). In conclusion, post‐diagnostic circulating 25(OH)D concentrations were associated with overall mortality and distant disease in stage I–IIIa postmenopausal breast cancer patients. This association was not strongly modified by lifestyle factors.     

Tumor‐infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer

Tumor‐infiltrating neutrophils (TIN) carry out quite significant but opposite functions in different cancers, and their function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TIN in biliary cancer, a training set (n = 118) and a validation set (n = 127) were involved in this study. TIN were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils <18/high‐power field [HPF]) vs high (neutrophils ≥18/HPF). Kaplan‐Meier curve, Cox proportional hazards models and receiver operating characteristic curve were used to assess the prognostic significance. TIN was identified as an independent prognostic factor for overall survival in the training set (HR: 4.720; 95% CI: 2.623‐8.493; P < .001) which was confirmed in the validation set (HR: 4.993; 95% CI: 2.626‐9.492; P < .001). Notably, among patients with stage III and IV disease, those with low TIN could benefit from adjuvant chemotherapy, with a reduced risk of compromised survival compared with those with high TIN (HR: 0.294; 95% CI: 0.099‐0.873; P = .047 in the training set; and HR: 0.100; 95% CI: 0.022‐0.462; P = .006 in the validation set). In addition, TIN were negatively related to biological pathways as regulation of activated T‐cell proliferation and lymphocyte‐mediated immunity, and showed a negative correlation with CD8 +  T cells (r = −.324, P < .001). Taken together, our results implicate TIN as an independent marker of prognosis and indicator of patients who would benefit from adjuvant chemotherapy in biliary cancer.     

Germline mutation in DNA‐repair genes is associated with poor survival in BRCA1/2‐negative breast cancer patients

BRCA1/2 genes are the most frequently germline mutated DNA‐repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non‐BRCA1/2 DNA‐repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA‐repair genes were determined using a multigene panel in 7657 BRCA1/2‐negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2‐negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA‐repair genes. The prevalence of DNA‐repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early‐onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA‐repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA‐repair gene mutation was an independent unfavorable factor for recurrence‐free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00‐1.91, P = 0.05) and disease‐specific survival (adjusted HR=1.63, 95% CI: 1.04‐2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2‐negative breast cancer patients carried germline mutations in the 16 DNA‐repair genes, and the DNA‐repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.     

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta‐analyses have been null for late‐life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p′‐DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p′‐DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population‐based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996–1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow‐up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer‐related. Using Cox regression models, we estimated the multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid‐adjusted organochlorine concentrations with all‐cause and breast cancer‐specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all‐cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer‐specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all‐cause and breast cancer‐specific mortality. Third tertile DDE concentrations were inversely associated with 15‐year all‐cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population‐based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.     

Joint associations of smoking and television viewing time on cancer and cardiovascular disease mortality

Excessive sitting time and smoking are pro‐inflammatory lifestyle factors that are associated with both cancer and cardiovascular disease (CVD) mortality. However, their joint associations have not been investigated. We examined the associations of television (TV) viewing time with cancer and CVD mortality, according to smoking status, among 7,498 non‐smokers (34% ex‐smokers) and 1,409 current‐smokers in the Australian Diabetes, Obesity and Lifestyle Study. During 117,506 person‐years (median 13.6 years) of follow‐up, there were 346 cancer and 209 CVD‐related deaths. Including an interaction between TV time and smoking status in the model significantly improved the goodness of fit for cancer (p = 0.01) but not CVD mortality (p = 0.053). In the multivariate‐adjusted model, every additional hr/d of TV time was associated with increased risk of cancer‐related (HR 1.23; 95% CI 1.08–1.40), but not CVD‐related mortality (HR 1.16; 95% CI 0.97–1.38) in current‐smokers. Elevated multivariate‐adjusted cancer mortality HRs were observed for current‐smokers watching 2 to <4 hr/d (HR 1.45; 95% CI 0.78–2.71) and ≥4 hr/d (HR 2.26; 95% CI 1.10–4.64), compared to those watching <2 hr/d. Current‐smokers watching 2 to <4 hr/d (HR 1.07; 95% CI 0.45–2.53) and ≥4 hr/d (HR 1.92; 95% CI 0.76–4.84) did not have a significantly higher risk of CVD mortality, compared to <2 hr/d. No associations were observed for non‐smokers. These findings show an association of TV, a common sedentary behavior, with cancer mortality in current‐smokers. The association with CVD mortality was less clear. Further exploration in larger data sets is warranted. Limiting TV viewing time may be of benefit in reducing cancer mortality risk in current‐smokers.     

Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft‐versus‐host disease and survival outcome

Delayed platelet recovery (DPR) despite prompt neutrophil engraftment is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT). However, few studies have evaluated the risk factors and long‐term outcome. Therefore, we retrospectively analysed 219 adult patients who underwent their first allogenic HSCT with neutrophil engraftment. Of these 219 patients, 50 (22.8%) had DPR that was defined as relapse‐free survival at day 60 after HSCT without primary platelet recovery despite neutrophil engraftment. The results of a multivariate analysis showed that a high‐risk underlying disease (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.04‐5.48; P = .041) and human leukocyte antigen–mismatched HSCT (OR, 2.63; 95% CI, 1.28‐5.43; P = .009) were associated with an increased risk of DPR. In univariate analyses, the occurrence of DPR was significantly associated with inferior overall survival, high nonrelapse mortality, and a low incidence of chronic graft‐versus‐host disease (GVHD), despite a comparable relapse rate. In multivariate analyses, DPR was associated with inferior overall survival (hazard ratio [HR], 2.00; 95% CI, 1.23‐3.27; P = .005) and a low incidence of chronic GVHD (HR, 0.42; 95% CI, 0.22‐0.78; P = .002). In conclusion, DPR was a strong predictor of shorter survival but also less frequent chronic GVHD.     

Methodological considerations for disentangling a risk factor's influence on disease incidence versus postdiagnosis survival: The example of obesity and breast and colorectal cancer mortality in the Women's Health Initiative

Often, studies modeling an exposure's influence on time to disease‐specific death from study enrollment are incorrectly interpreted as if based on time to death from disease diagnosis. We studied 151,996 postmenopausal women without breast or colorectal cancer in the Women's Health Initiative with weight and height measured at enrollment (1993–1998). Using Cox regression models, we contrast hazard ratios (HR) from two time‐scales and corresponding study subpopulations: time to cancer death after enrollment among all women and time to cancer death after diagnosis among only cancer survivors. Median follow‐up from enrollment to diagnosis/censoring was 13 years for both breast (7,633 cases) and colorectal cancer (2,290 cases). Median follow‐up from diagnosis to death/censoring was 7 years for breast and 5 years for colorectal cancer. In analyses of time from enrollment to death, body mass index (BMI) ≥ 35 kg/m² versus 18.5–<25 kg/m² was associated with higher rates of cancer mortality: HR = 1.99; 95% CI: 1.54, 2.56 for breast cancer (p trend <0.001) and HR = 1.40; 95% CI: 1.04, 1.88 for colorectal cancer (p trend = 0.05). However, in analyses of time from diagnosis to cancer death, trends indicated no significant association (for BMI ≥ 35 kg/m², HR = 1.25; 95% CI: 0.94, 1.67 for breast [p trend = 0.33] and HR = 1.18; 95% CI: 0.84, 1.86 for colorectal cancer [p trend = 0.39]). We conclude that a risk factor that increases disease incidence will increase disease‐specific mortality. Yet, its influence on postdiagnosis survival can vary, and requires consideration of additional design and analysis issues such as selection bias. Quantitative tools allow joint modeling to compare an exposure's influence on time from enrollment to disease incidence and time from diagnosis to death.     

Gender differences in colorectal cancer survival: A meta‐analysis

A meta‐analysis was conducted to determine the influence of gender on overall survival (OS) and cancer‐specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer‐specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85–0.89) and CSS (HR = 0.92; 95% CI = 0.89–0.95) than males after meta‐analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.     

A prospective,randomized study on hepatotoxicity of anastrozole compared with tamoxifen in women with breast cancer

Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty‐three Chinese postmenopausal women with hormone receptor‐positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end‐point was fatty liver disease, defined as a liver–spleen ratio <0.9 as determined using a computed tomography scan. The secondary end‐points included abnormal liver function and treatment failure during the 3‐year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21–0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20–0.37). The most commonly reported adverse events were ‘reproductive system disorders’ in the tamoxifen group (17.1%), and ‘musculoskeletal disorders’ in the anastrozole group (14.6%). Postmenopausal women with hormone receptor‐positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.     

Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer

PurposeThe aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed “wide resection of the pelvic peritoneum,” (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum.MethodsA total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining.ResultsWith respect to patients with stage IIIA–IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17–0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31–0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17–0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31–0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors.ConclusionThe present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA–IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.     

Impact of sustained viral response postcurative therapy of hepatitis C‐related hepatocellular carcinoma: a systematic review and meta‐analysis

Antiviral therapy with interferon based therapies (IBT) has shown potential in improving survival in patients who have undergone resection or locoregional therapy for hepatitis C‐associated hepatocellular carcinoma (HCV‐HCC). However, this benefit has not been definitively ascribed to sustained viral response (SVR). Since IBT has been replaced with new directly acting agents (DAA), which are more efficacious in the treatment of HCV, we sought to better determine the prognostic impact of SVR in HCV‐HCC. A systematic search of MEDLINE and EMBASE from inception through October 2015 was performed to identify studies that described the impact of presence of SVR in patients who underwent curative treatment of HCV‐HCC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated for recurrence‐free survival (RFS) and overall survival (OS) utilizing a random‐effects model. After reviewing 858 abstracts, ten studies which included a total of 1,794 patients were selected and data was extracted. Of these ten studies, the impact of SVR on RFS and OS was reported in eight and seven studies respectively. In a meta‐analysis which included 1,519 patients, SVR was associated with improved OS (HR 0.18; 95% CI 0.11–0.29, I² = 2%). We also found that SVR was associated with better RFS in a meta‐analysis (1,241 patients; HR 0.50; 95% CI 0.40–0.63, I² = 0). In conclusion, SVR is associated with improved OS and RFS in patients with HCV who have undergone resection or locoregional therapy for HCC. Newer DAA therapies which offer increased tolerability and viral eradication should be considered as adjunctive therapy.     

Prognostic value of programmed death‐ligand 1 expression in patients with stage III colorectal cancer

The programmed death‐1/programmed death‐ligand 1 (PD‐L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD‐L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD‐L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty‐five patients were included in the analysis. PD‐L1 expression on TC and tumor‐infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow‐up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD‐L1 expression on TC and 15.3% showed high PD‐L1 expression on TIMC. Patients with high PD‐L1 expression on TC had significantly shorter disease‐free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21–4.62; P = 0.012). In addition, patients with high PD‐L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16–0.98; P = 0.046). These findings suggest that PD‐L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD‐L1 expression on TC and TIMC separately in the tumor microenvironment.     

Prognostic factors in malignant ovarian germ cell tumours (The Surveillance,Epidemiology and End Results experience 1978–2010)

PurposeTo evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil status, residency) on cause specific survival (CSS) in patients with malignant ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors.Patients and methods2541 patients with MOGCT, reported to the Surveillance, Epidemiology and End Results programme (1978–2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan–Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI).ResultsFive-year CSS was 97% (95% CI, 96–98%), and 92% (95% CI, 91–93%), respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis and presence of metastases were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR), 1.59; 95% CI, 1.11–2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83–3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95% CI, 1.17–5.25). Second cancer was diagnosed in 10% of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group (p = .002).ConclusionsIncreased attention should be directed towards the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.