Incidence of prostate, colorectal and male breast cancers in relation with statins and testosterone replacement therapy: SEER-Medicare 2007-2015.

INTRODUCTION: Statins and testosterone replacement therapy (TTh) have been inconsistently associated with a reduced risk of hormone-related cancers (HRCs, prostate [PCa], colorectal [CRC], and male breast cancers [BrCa]). Yet, the joint association of statins and TTh with the incidence of these cancers, and whether these associations vary by race, remains poorly understood. The objective of this retrospective cohort study is to examine the independent and joint effects of pre-diagnostic use of statins and TTh on the risk of HRCs, including PCa, CRC, and male BrCa. MATERIALS: and Methods: In 105,690 men (≥65 yrs) identified using the SEER-Medicare 2007-2015 data, we identified 82,578 White and 10,256 Black men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and categorized into four groups (Neither users, statins alone, TTh alone and Dual users). Multivariable Time-varying Cox proportional hazards and Accelerated Failure Time (AFT) models were performed. RESULTS: We found inverse joint associations of statins and TTh with incident HRCs before (aHR: 0.39; 95 % CI: 0.35-0.44) and after 3 years of follow-up (aHR: 0.74; 95 % CI: 0.67-0.82). This included a lower risk for advanced stage HRC (only <3 years follow-up). Similar joint associations were identified with incident PCa, aggressive PCa, incident CRC, and its specific right- and left-sided CRC (only <3 years follow-up). In general, the inverse associations persisted among White (mainly <3 years follow-up) and Black men (high-grade HRC and <3 years follow-up). Findings from the AFT analysis were similar. DISCUSSION: Pre-diagnostic use of statins and TTh were, independently and jointly, associated with reduced risks of HRC and specific cancer sites at three years of follow-up overall, and among White and Black men. Greatest associations of HRCs risk reduction were observed among dual users (statins plus TTh). Further studies are needed to validate these findings, including larger samples of Black men, and male BrCa sites.

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

BACKGROUND: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. OBJECTIVE: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. METHODS: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. RESULTS: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. CONCLUSION: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

The incremental yield of adenoma detection with I-Scan versus high-definition white light colonoscopy-a systematic review and meta-analysis of randomized studies.

INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.

Self-expanding metal stents for the treatment of malignant colon obstruction from extra-colonic malignancy versus intra-colonic malignancy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The relative utility of self-expanding metal stent (SEMS) insertion for malignant colon obstruction (MCO) due to extra-colonic malignancy (ECM) versus intra-colonic malignancy (ICM) is understudied. METHODS: A systematic search was done from inception-April 2021 to identify reports of safety and efficacy of SEMS insertion for the treatment of MCO-ECM versus MCO-ICM. A meta-analysis of proportions, comparative meta-analysis to compute relative risks (RR), and mean differences (MD) was performed. Subgroup analyses and influence analyses were conducted. The certainty in estimates of effect(s) was assessed using the GRADE approach. RESULTS: Eight non-randomized studies were identified; 46% (39-53%) and 63% (59-67%) of patients in the ECM and ICM groups were male. Most obstructions were in the rectosigmoid colon in both ECM and ICM groups. SEMS insertion in MCO-ECM was associated with an increased risk of technical failure compared to MCO-ICM (RR 2.92; 1.13-7.54; Certainty: Very Low). Risk of clinical failure of SEMS was higher in MCO-ECM compared to MCO-ICM (RR 2.88; 1.58-2.52; Certainty: Very Low). The risk of clinical failure remained significant throughout the influence analysis, as well as on subgroup analysis. There was no significant difference in the risk of adverse events or luminal perforation with SEMS insertion among patients with MCO-ECM and MCO-ICM. On influence analysis, removal of one study unveiled a significant increase in the risk of luminal perforation in MCO-ECM (RR 3.22; 1.44-7.19; p = 0.004). CONCLUSION: SEMS for MCO-ECM may have a technical success rate comparable to or questionably worse than MCO-ICM, with low certainty in estimate of effects. SEMS deployment in MCO-ECM carries a higher risk of clinical failure, with a questionably higher risk of luminal perforation.

Factor Xa inhibitors versus low molecular weight heparin for the treatment of cancer associated venous thromboembolism; A meta-analysis of randomized controlled trials and non-randomized studies.

INTRODUCTION: We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). METHODS: A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. RESULTS: Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. CONCLUSION: Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

The Impact of Postoperative Complications on Long-Term Oncological Outcomes Following Curative Resection of Colorectal Cancer (Stage I-III): A Systematic Review and Meta-Analysis.

Background and objective The incidence of post-surgical complications (PSCs) after curative resection of non-metastatic colorectal cancer (CRC) is very widespread and evident. Some studies suggest that PSCs often predict poor long-term oncological outcomes. However, the available data on the topic is often controversial. The aim of this systematic review and meta-analysis was to study the effect of postoperative complications (POCs) on long-term oncological outcomes following curative resection of non-metastatic (stage I-III) CRC. Methods A comprehensive search of MEDLINE® and Excerpta Medica dataBASE (EMBASE) databases was performed via the Ovid platform, by using controlled vocabulary as well as natural language terms for POCs, outcomes, and CRC. Two authors independently screened the studies and extracted data. Conflicts were resolved by discussion among authors and also independently with the help of a third author. Meta-analysis was performed using a random-effects model (REM) to calculate pooled estimates for overall survival (OS), disease-free survival (DFS), and overall recurrence. Results Overall, 3,836 studies were initially screened, and 16 studies involving 37,192 patients were ultimately selected for final inclusion in the analysis. Meta-analysis of these studies showed that PSCs following non-metastatic CRC surgery predicted worse OS rates [hazard ratio (HR): 1.36; 95% CI: 1.15-1.61; p<0.00001], DFS (HR: 1.41; 95% CI: 1.11-1.80; p<0.00001), and overall recurrence (HR: 1.19; 95% CI: 1.04-1.37; p=0.01). Conclusion Based on our findings, PSCs predict poor OS rates, DFS, and overall recurrence following curative resection of non-metastatic CRC.

Cognitive disability in adult patients with brain tumors.

Cognitive dysfunction is common among patients with intracranial tumors. Most cognitive deficits are subtle, lack specificity, may mimic depression or other neurological disorders and may be recognized in retrospect by the physician. In certain cases, distinguishing between tumor recurrence and cognitive deficits that arise as a consequence of the treatment becomes challenging. Late treatment effects have also become an area of focus as the overall survival and prognosis of patients with brain tumors increases. New data has highlighted the importance of less toxic adjuvant therapies owing to their positive impact on prognosis and quality of life. Various experimental therapies and genetic influences on individual sensitivity towards injury are promising steps towards a better management strategy for cognitive dysfunction. In this literature review, we discuss cognitive dysfunction as a manifestation of intracranial tumors, treatment modalities such as radiotherapy, chemotherapy, surgery and their impact on cognition and patients' quality of life. We also discuss management options for cognitive dysfunction and emerging therapies.