Survival trends for left and right sided colon cancer using population-based SEER database: A forty-five-year analysis from 1975 to 2019.

BACKGROUND: Survival differences between left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. PURPOSE: We sought to assess the trends in colon cancer cause- specific survival (CSS) and overall survival (OS) based on sidedness. METHOD: Fine-Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population-based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975-1989, interval period A; 1990-2004, B; and 2005-2019, C). RESULTS: Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18-49, 64.6%; 50-64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975-1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow-up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86-0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. CONCLUSION: LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor.

The impact of COVID-19 on mortality, length of stay, and cost of care among patients with gastrointestinal malignancies: A propensity score-matched analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus 19 (COVID-19) pandemic have had a lasting impact on the care of cancer patients. The impact on patients with gastrointestinal (GI) malignancies remains incompletely understood. We aimed to assess the impact of COVID-19 on mortality, length of stay (LOS), and cost of care among patients with GI malignancies, and identify differences in outcomes based on primary tumor site. METHODS: We analyzed discharge encounters collected from the National Inpatient Sample (NIS) between March 2020 and December 2020 using propensity score matching (PSM) and COVID-19 as the treatment effect. RESULTS: Of the 87,684 patient discharges with GI malignancies, 1892 were positive for COVID-19 (C+) and eligible for matching in the PSM model. Following PSM analysis, C+ with GI tumors demonstrated increased incidence of mortality compared to their COVID-19-negative (C-) counterparts (21.3% vs. 11.9%, p < 0.001). C+ patients with colorectal cancer (CRC) had significantly higher mortality compared to those who were C- (40% vs. 24%; p = 0.035). In addition, C+ patients with GI tumors had a longer mean LOS (9.4 days vs. 6.9 days; p < 0.001) and increased cost of care ($26,048.29 vs. $21,625.2; p = 0.001) compared to C- patients. C+ patients also had higher odds of mortality secondary to myocardial infarction relative to C- patients (OR = 3.54, p = 0.001). CONCLUSIONS: C+ patients with GI tumors face approximately double the odds of mortality, increased LOS, and increased cost of care compared to their C- counterparts. Outcome disparities were most pronounced among patients with CRC.

Race, age, and sex differences on the influence of obesity on colorectal cancer sidedness and mortality: A national cross-sectional study.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) sidedness is recognized as a prognostic factor for survival; left-sided colorectal cancer is associated with better outcomes than right-sided colon cancer (RsCC). We aimed to evaluate the influence of obesity on CRC sidedness and determine how race, age, and sex affect mortality among overweight and obese individuals. METHODS: A survey-weighted analysis was conducted using data obtained from the National Inpatient Sample between 2016 and 2019. RESULTS: Of the 24 549 patients with a diagnosis of CRC and a reported body mass index (BMI), 13.6% were overweight and 49.9% were obese. The race distribution was predominantly non-Hispanic Whites (69.7%), followed by Black (15.6%), Hispanic (8.7%), and other race (6.1%). Overweight (BMI: 25-29.9) and obese (BMI: ≥30) individuals were more likely to have RsCC (adjusted OR [aOR] = 1.28; 95% CI: 1.17-1.39, p < 0.001 and aOR = 1.45; 95% CI: 1.37-1.54, p < 0.001, respectively). Obese Black individuals were more likely to have RsCC as compared to their White counterparts (aOR = 1.23; 95% CI: 1.09-1.38). CONCLUSIONS: Obesity is associated with an increased risk of RsCC. In addition, racial disparities in CRC sidedness and outcomes are most pronounced among obese patients.

Prognostic Factors and Survival in Gastrointestinal Extrapulmonary Small Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare, aggressive neuroendocrine tumor. Factors affecting survival, including the prognostic significance of primary tumor site, remain under investigation. METHODS: Data from the surveillance, epidemiology, and end results (SEER) program were extracted to identify patients diagnosed with GI EPSCCa between 2000 and 2018. Cox proportional hazard models were used to assess prognostic factors based on primary tumor site. RESULTS: A total of 1687 patients were included in the survival analysis. The distribution of the primary tumor location was as follows: 31.5% colorectum (CRC), 22.1% esophageal, 20.6% pancreatic, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Esophagogastric and SI EPSCCa were more common among Black individuals, whereas CRC, HB, and pancreatic EPSCCa were more common among White patients (p = 0.012). There were no racial differences in OS for GI EPSCCa. HB EPSCCa was associated with inferior OS compared with esophageal tumors (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.00-1.46; p = 0.048), and SI EPSCCa was associated with prolonged survival compared with esophageal EPSCCa (aHR 0.76, 95% CI 0.48-1.20; p = 0.237) but did not reach statistical significance. Surgical intervention and a treatment period after 2006 were associated with superior OS. CONCLUSIONS: The prognosis for GI ESPCCa varies based on site. Chemotherapy, radiation, and surgical resection are associated with improved outcomes; however, the prognosis for patients with EPSCCa remains dismal. Prospective studies are needed to guide therapy for this aggressive tumor.

Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival.

OBJECTIVES: Early-onset pancreatic cancer (EOPC) - defined as pancreatic cancer diagnosed before the age of 50 years - is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival. MATERIALS AND METHODS: Using PubMed and Medline, the following terms were searched and relevant citations assessed: "early onset pancreatic cancer," "late onset pancreatic cancer," "pancreatic cancer," "pancreatic cancer genes," and "pancreatic cancer targeted therapy." RESULTS: Mutations in CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC. CONCLUSIONS: Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management.

Factors Affecting Inpatient Mortality and Length of Stay in Nonmetastatic Colorectal Cancer: Insights from the National Inpatient Sample.

OBJECTIVE: The objective of this study was to assess the effect of opioid use and other factors on inpatient length of stay (LOS) and mortality among patients hospitalized with nonmetastatic colorectal cancer (NMCRC). MATERIALS AND METHODS: We analyzed discharge encounters collected from the 2016 to 2017 National Inpatient Sample (NIS) to evaluate the effect of long-term opioid use (90 d or longer) and cancer-related complications on LOS and mortality among hospitalized patients with NMCRC. RESULTS: A total of 94,535 patients with NMCRC were included in the analysis. Long-term opioid users had a shorter average LOS and reduced inpatient mortality as compared with nonopioid users (5.97±5.75 vs. 6.66±6.92 d, P<0.01; and adjusted odds ratio=0.72, 95% confidence interval: 0.56-0.93, respectively). Factors that significantly increased both LOS and mortality included infection, venous thromboembolism, and chemotherapy-induced neutropenia; the average LOS was 2.7, 2.6, and 0.7 days longer, and the adjusted odds ratio for risk of inpatient mortality was 3.7, 1.2, and 1.2, respectively (P<0.05), for patients admitted with these cancer-related complications. CONCLUSIONS: Long-term opioid use is associated with decreased LOS and inpatient mortality among patients with NMCRC. Individuals admitted for cancer-related complications face a longer LOS and increased mortality as compared with those admitted without these morbidities.

A review of the racial heterogeneity of breast cancer stem cells.

Breast Cancer Stem Cells has become the toast of many breast cancer investigators in the past two decades owing to their crucial roles in tumourigenesis, progression, differentiation, survival and chemoresistance. Despite the growing list of research data in this field, racial or ethnic comparison studies on these stem cells remain scanty. This study is a comparative racial analysis of putative breast cancer stem cells. Research articles on the clinicopathological significance of breast cancer stem cells within a period of 17 years (2003-2020) were reviewed across 5 major races (African/Black American, Asian, Caucasian/White, Hispanic/Latino, and American). The associations between the stem cells markers (CD44+/CD24-/low, BMI1, ALDH1, CD133, and GD2) and clinicopathological and clinical outcomes were analysed. A total of 40 studies were included in this study with 50% Asian, 25% Caucasian, 10% African, 5% American and 2.5% Hispanic/Latino, and 7.5% other mixed races. CD44+/CD24-/low has been associated with TNBC/Basal like phenotype across all races. It is generally associated with poor clinicopathological features such as age, tumour size, lymph node metastasis and lymphovascular invasion. In Asians, CD44+/CD24-/low was associated with DFS and OS but not in Caucasians. ALDH1 was the most studied breast CSC marker (40% of all studies on breast cancer stem cell markers) also associated with poor clinicopathological features including size, age, stage, lymph node metastasis and Nottingham Prognostic Index. ALDH1 was also associated with DFS and OS in Asians but not Caucasians. Racial variations exist in breast cancer stem cell pattern and functions but ill-defined due to multiple factors. Further research is required to better understand the role of breast CSC.

Apolipoprotein-AI and AIBP synergetic anti-inflammation as vascular diseases therapy: the new perspective.

Vascular diseases (VDs) including pulmonary arterial hypertension (PAH), atherosclerosis (AS) and coronary arterial diseases (CADs) contribute to the higher morbidity and mortality worldwide. Apolipoprotein A-I (Apo A-I) binding protein (AIBP) and Apo-AI negatively correlate with VDs. However, the mechanism by which AIBP and apo-AI regulate VDs still remains unexplained. Here, we provide an overview of the role of AIBP and apo-AI regulation of vascular diseases molecular mechanisms such as vascular energy homeostasis imbalance, oxidative and endoplasmic reticulum stress and inflammation in VDs. In addition, the role of AIBP and apo-AI in endothelial cells (ECs), vascular smooth muscle (VSMCs) and immune cells activation in the pathogenesis of VDs are explained. The in-depth understanding of AIBP and apo-AI function in the vascular system may lead to the discovery of VDs therapy.

Second primary malignancies in patients with melanoma in situ: Insights from the surveillance, epidemiology, and end results program.

BACKGROUND: Melanoma in situ (MIS) is among the most frequently diagnosed cancers in the United States. Emerging data suggest that MIS is associated with an increased risk of developing a second primary malignancy (SPM). OBJECTIVES: To determine trends in MIS-associated SPMs and identify MIS-specific features that increase SPM risk. METHODS: In this retrospective population-based study, we identified 90,075 patients who were diagnosed with MIS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results database. The risk of developing an SPM among these individuals was compared to individuals without a diagnosis of MIS. The risk of developing an SPM among patients with a diagnosis of MIS was also increased over time. RESULTS: Patients with a diagnosis of MIS had an increased relative risk (RR) of developing an SPM as compared to the general population with an identical age, sex, race, and follow-up period. The RR of a metachronous malignancy in MIS patients also increased over time, as follows: 1.16 (95 % CI: 1.07-1.26), 1.19 (95 % CI: 1.14-1.23), 1.30 (95 % CI: 1.27-1.33), and 1.52 (95 % CI: 1.49-1.56) in 1973-1982, 1983-1992, 1993-2002, and 2003-2015, respectively (P < 0.05). In addition, there was a direct correlation between the number of MIS lesions and SPM risk; ≥1, ≥2, and ≥3 tumors portended a 1.5-2, 2-3, and 4-5-fold increased risk of developing an SPM, respectively. CONCLUSIONS: MIS is associated with an increased risk of developing an SPM and therefore individuals with a history of MIS may benefit from close medical surveillance.

The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population.

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44+/CD24-/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes. METHOD: Tissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44+/CD24-/low/ALDH1+ and the clinicopathological phenotypes were also studied. RESULTS: A high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751-12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841-16.662, p = 0.001) but not associated with CD44+/CD24-/low (r = 0.134, OR- 2.720 95%CI- 0.959-7.710, p = 0.052). CD44+/CD24-/ALDH1+ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147-6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339-175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421-10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217-7.536). There was no association between CD44+/CD24-/ALDH1+ and the molecular subtypes. CONCLUSION: The high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44+/CD24-/ALDH1+ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.

Enhancing Matured Stem-Cardiac Cell Generation and Transplantation: A Novel Strategy for Heart Failure Therapy.

Heart failure (HF) remains one of the major causes of morbidity and mortality worldwide. Recent studies have shown that stem cells (SCs) including bone marrow mesenchymal stem (BMSC), embryonic bodies (EB), embryonic stem (ESC), human induced pluripotent stem (hiPSC)-derived cardiac cells generation, and transplantation treated myocardial infarction (MI) in vivo and in human. However, the immature phenotypes compromise their clinical application requiring immediate intervention to improve stem-derived cardiac cell (S-CCs) maturation. Recently, an unbiased multi-omic analysis involving genomics, transcriptomics, epigenomics, proteomics, and metabolomics identified specific strategies for the generation of matured S-CCs that may enhance patients' recovery processes upon transplantation. However, these strategies still remain undisclosed. Here, we summarize the recently discovered strategies for the matured S-CC generation. In addition, cardiac patch formation and transplantation that accelerated HF recuperation in clinical trials are discussed. A better understanding of this work may lead to efficient generation of matured S-CCs for regenerative medicine. Graphical abstract.

Prevalence of Themes Linked to Delayed Presentation of Breast Cancer in Africa: A Meta-Analysis of Patient-Reported Studies.

PURPOSE: The prevalence of themes linked to delay in presentation of breast cancer (BC) and their underlying factors vary considerably throughout Africa. Regional differences and trends are largely unreported. The purpose of this research was to provide summary estimates of the prevalence and distribution of the themes and underlying factors linked to delay in the presentation of BC, regional variation, and trends in an effort to identify targets for intervention. DESIGN: We screened articles found through PubMed/Medline, African Journal OnLine, Science Direct, Google/Google Scholar, and ResearchGate. We included patient-reported surveys on the reasons linked to delayed presentation under 6 previously identified themes: symptom misinterpretation, fear, preference for alternative care, social influence, hospital-related factors, and access factors. The meta-analytical procedure in MetaXL used the quality-effect model. RESULTS: Twelve of the 236 identified articles were eligible for this review. The overall summary estimate of late presentation (> 90 days) was 54% (95% CI, 23 to 85) and was worst in the eastern and central regions. Symptom misinterpretation was the most common theme (50%; 95% CI, 21 to 56), followed by fear (17%; 95% CI, 3 to 27), hospital-related theme (11%; 95% CI, 1 to 21), preference for alternative care (10%; 95% CI, 0 to 21), social influence (7%; 95% CI, 0 to 14), and access-related theme (6%; 95% CI, 0 to 13). The most common factor underlying symptom misinterpretation was mischaracterizing the breast lesion as benign (60%; 95% CI, 4 to 100) which surpassed lack of awareness in the last decade. Misdiagnosis and failure to refer were the dominant hospital-related factors. CONCLUSION: Modifiable factors such as mischaracterizing malignant masses as benign, fear, misdiagnosis, and failure to refer were the prevalent factors contributing to delays throughout Africa. These factors are promising targets for intervention.

Acute occlusive mesenteric ischemia in high altitude of southwestern region of Saudi Arabia.

BACKGROUND AND OBJECTIVES: Mesenteric ischemia which can be acute or chronic depending on the rapidity of compromised blood flow produces bowel ischemia, infarction, bacterial transmigration, endotoxemia, multisystem organ failure and death. High altitude can precipitate thrombosis because of hypobaric hypoxia and its effect on coagulation system. The objectives of this study are to determine the risk factors, clinical presentation, type and pattern of acute occlusive mesenteric ischemia in high-altitude of southwestern region of Saudi Arabia. MATERIALS AND METHODS: We reviewed the records of all the patients with acute occlusive mesenteric ischemia admitted to the Armed Forces Hospital, southern region, Kingdom of Saudi Arabia during the period of 2005 to 2010, and compiled data including demographics, clinical presentation, risk factors, preoperative investigations, management, histopathological examination, and complications. The cases of mesenteric ischemia resulting from conditions such as volvulus and strangulated hernias were excluded. RESULTS: Our study included 21 patients, 10 (48%) men and 11 (52%) women with a mean age of 56 years (SD 14). Abdominal pain was the most common presenting symptoms. CT angiography depicted occlusive arterial disease in 8 patients (38%) and venous thrombosis in 13 patients (62%). Diabetes mellitus was the most frequent risk factor for arterial mesenteric ischemia. Chronic liver disease particularly liver cirrhosis was the most prominent risk factor for venous mesenteric thrombosis. Intestinal ischemia was confirmed by histopathological examination. CONCLUSION: Acute occlusive mesenteric ischemia can mimic other more common intra-abdominal diseases clinically; therefore a high index of suspicion is required particularly for patients with relevant risk factors to prompt early diagnosis and intervention. Venous mesenteric thrombosis was more common than arterial mesenteric ischemia in our region.