Background We aimed to verify the role of hENT1 as a prognostic predictor for patients with resectable pancreatic ductal adenocarcinoma (PDAC) who underwent radical resection followed by intra-arterial infusion of gemcitabine-based regimen. Methods We collected surgical samples from 102 patients with resectable PDAC who received radical resection followed by intra-arterial infusion of gemcitabine-based regimen. The hENT1 expression with the help of immunohistochemistry was conducted using formalin-fixed and paraffin embedded tissues. The Kaplan–Meier analyses and Cox regression were used to evaluate the mortality hazard associated with the discrepancy between strong and weak of hENT1 expression. Patients’ clinical and pathological characteristics were compared between the two groups, then the role of hENT1 as a prognostic predictor was further explored. Results A total of 102 patients were included to assess the hENT1 expression. 50 patients were classified into high hENT1 expression group, the other 52 patients were attributed into low hENT1 expression group. High hENT1 expression was related to a significantly improved overall survival (OS) ( p = 0.014) and disease-free survival (DFS) ( p = 0.004). Both univariate ( p = 0.001) and multivariate analyses ( p < 0.001) indicated that high hENT1 expression was related to a decreased mortality. Conclusions High expression of hENT1 is positive prognostic factor for adjuvant intra-arterial gemcitabine-based chemotherapy in resectable PDAC.

Abstract Purpose Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy(NAC) in osteosarcoma(OS) is still without substantial evidence. Methods We retrospectively analyzed 256 OS patients who underwent standard NAC in our institute. Hb concentrations before/after NAC and changed Hb levels (dHb, Hb level before NAC minus that after NAC) were recorded to assess their prognostic value in DFS(disease-free survival) and tumor necrosis rate to NAC. Results There was higher percentage of pretreatment anemia in poor response group(87 out of 181) with a tumor necrosis rate < 90%, compared with those in good response group(36 out of 75). Besides, in patients with good response to NAC, the median dHb was 13, which was smaller than that(median dHb 18) in poor response to NAC. Further ROC analysis demonstrated that dHb had a significant role in prediction for the NAC response in OS patients.In survival analysis, patients with high dHb(≥ 12.5) had an inferior DFS(38 ± 2.44 months), compared with those with dHb below 12.5(47 ± 7.26 months). Conclusion In osteosarcoma, dynamic Hb decrease after NAC predicted poor survival and worse response to neoadjuvant chemotherapy. Pretreatment anemia might be a potential indicator to forecast response to NAC. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.

Objectives Pancreatic calcifications (PC) are considered specific for chronic pancreatitis (CP), but PC may also be present in non-CP diseases. The aims are to understand the pattern of calcifications in different diseases and to determine they were related to malignant diseases. Methods A retrospective study was performed including patients with PC or CP undergoing surgery in the Department of General Surgery of Ruijin Hospital from January 2003 to June 2018. Results PC were observed in 168 (4.5%) of the 3755 patients with pancreatic lesions treated during the study period. The majority of patients with PC had three kinds of CP (73.2%) while 26.8% had other five kinds of non-CP diseases. In patients with non-CP diseases, the incidence of PC in malignant intraductal papillary mucinous neoplasm (IPMN) was significantly higher than benign IPMN (8.3% vs. 0.7%, p = 0.004). In patients of CP with pancreatic mass (n = 81), PC (Odds ratio = 28.6, p = 0.000), advanced age (> 55 years) and parenchymal atrophy were independent predictors for malignancy. In patients of CP without pancreatic mass (n = 110), there were 82 cases (74.5%) with PC and 5 cases (4.5%) with pancreatic ductal adenocarcinoma. The regression model of risk factors was not successful. Conclusions The disease spectrum with PC was very diverse. PC may be related to malignant IPMN in non-CP diseases and is related to malignancy in the patients of CP with pancreatic mass and indications for resection.

Primary gallbladder neuroendocrine carcinomas (GB-NEC) are malignant neoplasms that remained to be studied. In this study we aimed to summarize their clinicopathological characteristics, effective treatment and prognostic factors for patients with GB-NEC. Patients with GB-NEC admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Renji Hospital, School of Medicine, Shanghai Jiao Tong University from October 2012 to August 2020 were enrolled. Clinicopathological characteristics of our patients and those reported in previous studies were recorded. The Kaplan-Meier method and univariate and multivariate Cox regression analyses were used for survival analysis. Altogether 15 patients from our hospitals and 47 patients from previous studies were included. A total of 55 patients who underwent surgical resection, including R 0 and non-R 0 resection, had significantly longer overall survival compared with the other seven patients. A univariate analysis indicated that patients aged 60 years or older, with jaundice, carcinoid syndrome, non-R 0 resection, and advanced stage were associated with worse survival. A multivariate analysis showed that patients aged 60 years or older, carcinoid syndrome and non-R 0 resection, but not lymphadenectomy and adjuvant chemotherapy, were independently related to reduced survival. R 0 resection should be the first-line treatment for GB-NEC. Older age, carcinoid syndrome and non-R 0 resection are independently associated with reduced survival after surgical resection.

TABLE S1 Sleep duration and risk of all-cause, cancer and CVD mortality in NHIS cohort Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract BACKGROUND: Epidemiological data regarding the regional differences in chronic pancreatitis (CP) from the mainland of China is lacking. We aimed to gather and combine the information concerning the regional distribution and the risk factors associated with pancreatic cancer (PaCa) and death from published articles. METHODSː:Case articles on CP published in seven databases from January 1979 to December 2018 were analysed. RESULTS: A total of 4,452 cases articles (containing 161,243 CP cases) were included. Since the mid-1990s, the number of published articles grew rapidly, which was significantly related to the gross domestic product of the region. In recent years, the number of CP cases of idiopathic etiology, those receiving endoscopic treatment, those with comorbid diabetes mellitus and the number of Science Citation Index (SCI) case articles have increased. Surgical treatment (37.4%) was closely associated to alcoholic CP (r = 0.55, P = 0.000), idiopathic CP (r = 0.52, P = 0.000), wasting (r = 0.21, P = 0.000), jaundice (r = 0.27, P = 0.000), PaCa and death detected during hospitalization and follow-up, and was more common in underdeveloped areas. Endoscopic therapy (27.9%) was mainly concentrated in developed areas, associated with non-alcoholic CP and a higher incidence of death (r = 0.48, P = 0.000) and PaCa (r = 0.3, P = 0.000) during follow-up. The total number of PaCa in CP cases was significantly related to the number of PaCa cases in each region (r = 0.94, P = 0.002). PaCa detected during hospitalization was mainly related to jaundice, pain, diabetes, biliary diseases, alcoholic CP, conservative treatment and surgical treatment. CONCLUSIONS: The distribution of clinical features and management treasures showed obvious regional characteristics, which closely related to the local detection level of CP and PaCa, showing that there were likely to be many cases of misdiagnosis or delayed diagnosis of CP and PaCa. The problem of uneven distribution of medical resources, which related to the imbalance of economic and social development, needs to be resolved.

Objectives: To examine the cross-sectional relationship between sleep duration and 11 chronic diseases (risk of obesity, depression, diabetes, asthma, COPD, arthritis, kidney, CHD, stroke, and cancer [excluding skin cancer]) by using data from Behavioral Risk Factor Surveillance System. Methods: Using data from the 2013, 2014 and 2016 Behavioral Risk Factor Surveillance System, a total sample consisted of 1,191,768 participants. Logistic regression models were constructed to calculate OR and 95% confidence intervals (CI) for the association between sleep duration and 11 chronic diseases. In addition, we also conducted subgroup analysis based on age and gender. Results: In multi-adjusted model, the positive association between extremely short or long sleep duration and risk of chronic diseases was significant (P <0.05) with the exception of skin cancer (P = 0.14 and P = 0.43). There are stronger association between extremely short or long sleep duration and obesity, diabetes, asthma, chronic obstructive pulmonary disease, arthritis, kidney, coronary heart disease, stroke, and cancer in women and aged 18-64 years old. Conclusions: Our results indicated a higher risk of common chronic diseases due to short or long sleep duration in women and aged 18-64 years. Further studies are needed to demonstrate these association. (C) 2020 Published by Elsevier B.V.

This study aimed to investigate whether the effects of sleep duration interacted with the presence of diabetes. We specifically sought to examine the relationship between sleep duration and all-cause and cause-specific mortality in people with type 2 diabetes across sex, age at diagnosis, duration of diabetes and treatment type. The sample consisted of 273,029 adults, including 248,817 without diabetes and 24,212 with type 2 diabetes, who participated in the National Health Interview Survey from 2004 to 2013 and whose data were linked to a mortality database up to 31 December 2015. Sleep duration was measured using self-report, whereby participants were asked ‘on average how long do you sleep each day (≤5, 6, 7, 8, 9 or ≥10 h/day)?’ The relationship between sleep duration and mortality risk was investigated using Cox proportional hazards regression model, with adjustments for demographics, BMI, lifestyle behaviours and clinical variables. Absolute mortality rate was higher in adults with diabetes and extremes of sleep duration (≤5 h/day, 215.0 per 10,000 person-years; ≥10 h/day, 363.5 per 10,000 person-years). There was a non-significant interaction between sleep duration and the presence of diabetes (p for interaction = 0.08). A J-shaped relationship existed between sleep duration and all-cause mortality risk in people with type 2 diabetes. Compared with the reference group (7 h/day), both shorter and longer sleep durations were associated with increased risk of all-cause mortality (≤5 h/day, HR 1.24 [95% CI 1.09, 1.40]; 6 h/day, HR 1.13 [1.01, 1.28]; 8 h/day, HR 1.17 [1.06, 1.30]; ≥10 h/day, HR 1.83 [1.61, 2.08]). Similar associations were also observed for mortality risk from CVD, cancer, kidney disease, Alzheimer’s disease and chronic lower respiratory diseases. Longer sleep duration in those with a younger age at diabetes onset was associated with greater risks of all-cause and CVD mortality. Shorter sleep duration in individuals treated with both insulin and oral glucose-lowering medication was also associated with higher risks of all-cause and CVD mortality. The associations between sleep duration and mortality risk may be different between diabetic and non-diabetic individuals. In people with type 2 diabetes, sleeping less or more than 7 h/day was associated with increased risk of all-cause and condition-specific mortality. The association was more prominent in those with a younger age at diabetes onset and receiving treatment with both oral glucose-lowering medication and insulin. This population may benefit from targeted sleep-related interventions to reduce the risks of adverse health outcomes.

Objective: The relationship between diabetes and all- and cause-specific mortality in individuals with common cancers (breast, colorectal, and prostate) remains both under-researched and poorly understood. Methods: Cancer survivors (N = 37,993) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between pre- and post-diabetes and all-cause and cause-specific mortality. Results: Over a median follow-up period of 13 years, 2,350 all-cause, 698 cancer, and 506 CVD deaths occurred. Among all cancer survivors, patients with diabetes had greater risk of: all-cause mortality [hazard ratio (HR) 1.35, 95% CI = 1.27-1.43], cancer-specific mortality (HR: 1.14, 95% CI = 1.03-1.27), CVD mortality (HR: 1.36, 95% CI = 1.18-1.55), diabetes related mortality (HR: 17.18, 95% CI = 11.51-25.64), and kidney disease mortality (HR: 2.51, 95% CI = 1.65-3.82), compared with individuals without diabetes. The risk of all-cause mortality was also higher amongst those with diabetes and specific types of cancer: breast cancer (HR: 1.28, 95% CI = 1.12-1.48), prostate cancer (HR: 1.20, 95% CI = 1.03-1.39), and colorectal cancer (HR: 1.29, 95% CI = 1.10-1.50). Diabetes increased the risk of cancer-specific mortality among colorectal cancer survivors (HR: 1.36, 95% CI = 1.04-1.78) compared to those without diabetes. Diabetes was associated with higher risk of diabetes-related mortality when compared to non-diabetic breast (HR: 9.20, 95% CI = 3.60-23.53), prostate (HR: 18.36, 95% CI = 6.01-56.11), and colorectal cancer survivors (HR: 12.18, 95% CI = 4.17-35.58). Both pre- and post-diagnosis diabetes increased the risk of all-cause mortality among all cancer survivors. Cancer survivors with diabetes had similar risk of all-cause and CVD mortality during the second 5 years of diabetes and above 10 years of diabetes as compared to non-diabetic patients. Conclusions: Diabetes increased the risk of all-cause mortality among breast, prostate, and colorectal cancer survivors, not for pre- or post-diagnosis diabetes. Greater attention on diabetes management is warranted in cancer survivors with diabetes.

Several studies have examined the relationship between smoking and mortality in cancer survivors. However, few have reported the relationships in several cancer sites (i.e., bladder, non-melanoma skin, uterine, melanoma, and lymphoma), and limited data exist on the dose-response relationship between number of cigarettes smoked per day or duration of smoking cessation and mortality. Cancer survivors (N = 35,093, 61% female, mean age = 47 years old) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between smoking status, all-cause, and disease-specific mortality. After a median follow-up of 13 years, 11,066 deaths occurred. Survivors who reported smoking at study entry had a 73%, 75%, 85% higher risk for cardiovascular disease, cancer, and all-cause mortality, respectively when compared to nonsmokers. Former smokers had a 31% and 37% higher risk of all-cause and cancer mortality, respectively when compared to nonsmokers. The observed relationships appeared to differ by the number of cigarettes smoked (i.e., ≥ 10 per day), especially for breast, cervix, lung, prostate, uterine and non-melanoma skin cancer survivors. Those who continued smoking post diagnosis were at greatest risk of all-cause and cancer mortality, but the associations varied substantially by cancer site. These data provide sufficient evidence of the health hazards associated with smoking for cancer survivors and provide further support for public health strategies designed to curb smoking in this vulnerable population.

BACKGROUND:Diabetes mellitus (DM) is a risk factor for pancreatic cancer (PC), but its prognostic value in PC is still unclear. To elucidate this issue, we systematically reviewed the evidence concerning the association between diabetes status and PC.METHODS:Medline and EMBASE databases were searched to identify the eligible studies. Overall and subgroup analyses were performed to detect the discrepancy of prognosis according to diabetes status. Hazard ratios (HRs) with 95% CI were used to estimate the effect size.RESULTS:Eighteen studies including 16,181 patients with sample size ranging from 113 to 4,658 were pooled in this meta-analysis. Results showed that patients with DM had worse survival (HR 1.19, 95% CI: 1.07-1.32). In view of the impact of diabetes duration and tumor stage on the outcomes, we classified the studies into different groups. The results indicated that DM was associated with survival in both long-standing diabetes (HR 1.26, 95% CI: 1.14-1.40) and recent-onset diabetes (HR 1.29, 95% CI: 1.09-1.51). Data regarding localized disease (HR 1.57, 95% CI: 1.00-2.46) and nonlocalized (locally advanced and metastatic) disease (HR 1.42, 95% CI: 1.16-1.73) verified that the prognostic value was independent of tumor stage.CONCLUSION:Our results suggested that patients with DM were associated with worse survival than those without DM. Diabetes may be a predictive factor of survival in patients with PC. Surveillance of diabetes status and antidiabetes medication administration after the diagnosis of PC is of clinical importance.

Gallbladder cancer (GBC) is the most common malignancy in biliary tract with poor prognosis. Due to its high chemoresistance, systemic chemotherapies have had limited success in treating GBC patients. MicroRNAs (miRNAs) are emerging novel regulators of chemoresistance, which modulate the expression of drug resistance-related genes. In this study, we investigated the association between miR-145 expression and cisplatin sensitivity by both in vivo and in vitro analysis. Quantitative PCR (q-PCR) analysis indicated an increased miR-145 expression in GBC tissues. In addition, studies on GBC cell lines suggested an increased cisplatin efficacy with miR-145 overexpression, whereas decreasing miR-145 expression reduced cisplatin sensitivity. Further, we found that miR-145 accelerated MRP1 mRNA degradation by directly targeting its 3′-UTR and therefore caused increased cisplatin toxicity in GBC cells. Moreover, lower miR-145 and higher MRP1 expression levels predicted poor prognosis in GBC patients who received chemotherapy. Collectively, our findings established a rationale for using miR-145 expression as a biomarker to identify cisplatin-resistant GBC patients and propose that treatment strategies increasing the expression of miR-145 could be a new therapeutic approach for GBC patients.

Introduction Approximately 5% of primary breast cancer patients present de novo stage IV breast cancer, for whom systematic therapy is the mainstream treatment. The role of surgical excision of the primary tumor has been controversial due to inconsistent results of relevant studies. Recently, with the reports of some relevant preclinical data, retrospective studies and randomized clinical trials, we've got more evidence to reexamine the issue. Based on those above, a literature review and meta-analysis was performed to determine whether surgery of the primary tumor could improve overall survival in the setting of stage IV breast cancer. Materials and Methods A comprehensive search of PubMed, OVID, American Society of Clinical Oncology (ASCO) symposium documents, European Society for Medical Oncology (ESMO) symposium documents and San Antonio Breast Cancer Symposium (SABCS) symposium documents was performed to identify published literature that evaluated survival benefits from excision of the primary tumor in the setting of stage IV breast cancer. Data were extracted in review of appropriate studies by the authors independently. The primary endpoint was overall survival following surgical removal of the primary tumor. Secondary endpoints were the impacts of surgery on progression free survival (PFS) and time to progression (TTP). Results Data from 19 retrospective studies showed a pooled hazard ratio of 0.65 (95% confidence interval (95% CI), 0.60-0.71, P < 0.01= for overall survival (OS), indicating a 35% reduction in risk of mortality in patients who underwent surgical excision of the primary tumor. Nevertheless, the analysis of 3 randomized clinical trials revealed a pooled hazard ratio of 0.85 (95% CI, 0.59–1.21, P = 0.359) for OS in the surgical group. According to the meta-regression, the survival benefit was independent of age, tumor size, site of the metastases, and PR or HER-2 status, acceptance of systematic therapies and radiotherapy and inversely correlated with the ER+ status of the population included. Conclusions This is the first meta-analysis that includes both retrospective and prospective studies regarding the impact of surgery of the primary tumor on survival in stage IV breast cancer patients. According to the analytical results, we do not recommend surgery of the primary tumor as routine therapy for stage IV breast cancer. However, for those who are supposed to have long life expectancy, physicians could discuss it with these patients, put forward surgery as a therapy choice and perform the operation under deliberation.