Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications

Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.

Survival in bladder and upper urinary tract cancers in Finland and Sweden through 50 years

Survival has improved in bladder cancer but few studies have considered extended periods or covered populations for which medical care is essentially free of charge. We analyzed survival in urothelial cancer (UC, of which vast majority are bladder cancers) in Finland and Sweden over a 50-year period (1967–2016) using data from the NORDCAN database. Finland and Sweden are neighboring countries with largely similar health care systems but higher economic resources and health care expenditure in Sweden. We present results on 1- and 5-year relative survival rates, and additionally provide a novel measure, the difference between 1- and 5-year relative survival, indicating how well survival was maintained between these two periods. Over the 50-year period the median diagnostic age has increased by several years and the incidence in the very old patients has increased vastly. Relative 1- year survival rates increased until early 1990s in both countries, and with minor gains later reaching about 90% in men and 85% in women. Although 5-year survival also developed favorably until early 1990s, subsequent gains were small. Over time, age specific differences in male 1-year survival narrowed but remained wide in 5-year survival. For women, age differences were larger than for men. The limitations of the study were lack of information on treatment and stage. In conclusion, challenges are to improve 5-year survival, to reduce the gender gap and to target specific care to the most common patient group, those of 70 years at diagnosis. The most effective methods to achieve survival gains are to target control of tobacco use, emphasis on early diagnosis with prompt action at hematuria, upfront curative treatment and awareness of high relapse requiring regular cystoscopy follow up.

Exploring the Association between Demographics and Cancer

Objective: We explore the association between demographics and the most prevalent cancers in the United States by analyzing empirical data from the Centers for Disease Control and Prevention, with indicators like cancer site, cancer incidence rate, relative survival rate, death rate, and demographic and lifestyle factors. Identifying cancer-related factors can contribute to improvements in treatment and management of the disease. Method: We use visual analytics to show behavioral factors and age to be associated with increasing incidence rates. Principal Results: Females are more susceptible to breast and males to prostate cancer. As a preventive measure, national healthcare entities, insurance companies and the government should consider both gender and age factors and monitor behavioral health measures like drugs and diet, in evaluating cancer treatment/mitigation. Main conclusions: Preventive care combined with improved outcomes and reduced costs is necessary. We offer implications for all developed countries in identifying key areas to target and manage public health.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study

Background: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. Methods: Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population–based cancer registries from 10 countries (Benin, Congo, Cote d’Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients (“traced patients”). Excess hazards of death by therapy use were modeled in a relative survival context. Results: A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I–III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. Conclusions: Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.

Primary Central Nervous System Lymphoma High Incidence And Poor Survival In Finnish Population-Based Analysis

Background: We report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. Methods: Finnish Cancer Registry data by histological diagnosis and tumor location (2007-2017) for cases with diffuse large B-cell lymphoma.Results: During 2007–2017, 392 new cases of PCNSL were reported (195 males, 197 females). The average age-adjusted incidence was 0.68/100.000 person-years. Incidence for males was 0.74/100.000 and for females 0.63/100.000, respectively. The incidence was highest, 2.93/100.000, among people aged 75–79 years. Concerning all cases in 2007-2017 the 2-year age-adjusted relative survival rate was 35% and the corresponding 5-year survival rate was 28%. Among patients under the age of 70, the age-adjusted 5-year relative survival rate increased from 36% in 2007-2012 to 43% for 2013-2017. Among patients aged 70+ the corresponding survival rates were poor, 7% and 9%.Conclusions: PCNSL incidence in Finland is among the highest reported in the world. The annual increase in incidence was 2.4%. The prognosis is still dismal, especially in elderly patients.

Trends in Incidence and Survival of Patients with Pancreatic Neuroendocrine Neoplasm, 1987–2016

Background. Pancreatic neuroendocrine neoplasm (pNEN), with the lowest 5-year survival rates in neuroendocrine tumors (NETs), exerts great threat to human health. Because large-scale population research aimed at pNEN is rare, we aimed to explore the tendencies and differences of changes in incidences and survival rates of pNEN in each decade from 1987 to 2016 and evaluate the impacts of age, sex, race, socioeconomic status (SES), and grade. Methods. Data on pNEN cases from 1987 to 2016 were extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan–Meier, Cox proportional hazards regression analyses, and relative survival rates (RSRs) were used to identify risk factors for pNEN. Results. The incidence and survival duration of pNEN increase every decade due to medical developments. The disparities of long-term survival in different age, sex, and grade groups expanded over time while that in race and SES groups narrowed. Older age and higher grade are independent risk factors for poorer survival. Females have lower incidence and longer survival than males. Prognosis of Black patients and poor (medium and high poverty) patients improved. Conclusions. This study depicted changes in incidence and survival rates of pNEN over the past three decades and evaluated potential risk factors related to pNEN, benefiting future prediction of vulnerable and clinical options.

Immune cell mediated cabozantinib resistance for patients with renal cell carcinoma

Renal cell carcinoma (RCC) is the third most common genitourinary cancer in the USA. Despite recent advances in the treatment for advanced and metastatic clear cell RCC (ccRCC), the 5-year relative survival rate for the distant disease remains at 12%. Cabozantinib, a tyrosine kinase inhibitor (TKI), which is one of the first-line therapies approved to treat advanced ccRCC as a single agent, is now being investigated as a combination therapy with newer immunotherapeutic agents. However, not much is known about how cabozantinib modulates the immune system. Here, we present a high throughput tri-culture model that incorporates cancer cells, endothelial cells, and patient-derived immune cells to study the effect of immune cells from patients with ccRCC on angiogenesis and cabozantinib resistance. We show that circulating immune cells from patients with ccRCC induce cabozantinib resistance via increased secretion of a set of pro-angiogenic factors. Using multivariate partial least square regression modeling, we identified CD4+ T cell subsets that are correlated with cabozantinib resistance and report the changes in the frequency of these populations in ccRCC patients who are undergoing cabozantinib therapy. These findings provide a potential set of biomarkers that should be further investigated in the current TKI-immunotherapy combination clinical trials to improve personalized treatments for patients with ccRCC.

Carotid endarterectomy in asymptomatic octogenarians: Outcomes at 30 days and 5 years

Background The following study investigated the 30-day and 5-year relative survival rate and freedom from neurological events in asymptomatic carotid stenosis (ACS) octogenarians who had undergone elective carotid endarterectomy (CEA). Methods Between January 2008 and June 2014, a retrospective review was conducted on ACS patients who had undergone elective CEA. The patients’ sample was divided into two groups: Group A (GA) included octogenarians and Group B (GB) included younger patients. The GA patients were subjected to a risk-scoring system and follow-up. The two groups were compared analysing the following primary endpoints: 30-day mortality, stroke, stroke/death and acute myocardial infarction (AMI); GA patients’ survival rate and freedom from neurological events at 5 years. The 30-day secondary endpoints included carotid shunting, redo surgical, need for general anaesthesia with preserved consciousness (GAPC) conversion and length of hospital stay. Results We identified 620 patients with ACS, of them 144 (23.2%) belonged to the GA and 476 (76.8%) belonged to the GB. No statistical difference between the two groups was found regarding the primary and secondary endpoints. One hundred nineteen of 144 GA patients (82.6%) underwent the follow-up; the median follow-up was 78.3 months. The GA patients’ 5-year survival rate was 62%, while freedom from cerebral events was 94.9%. Analysis regarding GA patients’ 5-year survival rate revealed a significantly lower percentage among the patients with a severe risk score compared with those with a moderate risk score (respectively, 29.5% vs 67.7%; p = .005). The multivariate analysis showed that chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were independently associated with lower survival. Conclusions The 30-day outcomes of CEA in octogenarians are comparable to those in younger patients. Comprehensive life expectancy and preoperative score, rather than age alone, should be taken into account before performing CEA on octogenarian patients, considering the short- and long-term efficacy in stroke prevention.

Period Analysis of Intraracial Differences in Incidence and Survival Rates in Epithelial Ovarian Cancer

Background. To explain the difference in the incidence and relative survival in a population-based cohort of women with epithelial ovarian cancer (EOC) postdiagnosis in the last forty years. EOC is the most common type of all ovarian cancers, but there is inadequate information about the variations related to long-term EOC survival. Methods. We acquired the incidence and relative survival rate data from the Surveillance, Epidemiology, and End Results (SEER) registries to analyze the epidemiological variations from 1974 to 2013 in EOC-affected individuals. The survival disparities in EOC-specific individuals due to age, race, and socioeconomic status (SES) were performed by Kaplan-Meier analysis. The Results. The overall incidence of EOC progressively declined to 9.0 per 100,000 from 11.4 in the last forty years. The median survival rate improved to 48 months in the first decade from a previous of 27 months in the fourth decade. The 5-year relative survival rate (RSR) increased to 44.3% that was previously 32.3% at the same time. However, between whites and blacks, an increase from 11 to 18 months was observed in the median survival differences. Between the low and high poverty groups, it was increased from 7 months to 12 months, respectively. Conclusions. The incidence rate of RSR and EOC-specific individuals in the last forty years was improved. However, the survival rates among different races and SES differed over time.