It's Not About the Money: Continued Treatment and Survival Outcome Disparities in Minority Rectal Cancer Patients After Controlling for Socioeconomic Factors.

BACKGROUND: While the disparities for minority patients with cancer have been well established, few studies have illustrated disparities in cancer outcomes while controlling for potential confounding factors. The current study was designed to address these confounding variables and how they influence the treatment and survival time for patients with rectal cancer. METHODS: Using the Surveillance, Epidemiology, and End Results database, black and Hispanic patients were compared with white patients with rectal cancer for the rates of chemotherapy, radiation, and surgery in addition to survival time after diagnosis. Following this analysis, confounding variables were controlled for and analysis was repeated with groups of comparable demographic variables. RESULTS: Before controlling for confounding variables, there were significant differences in treatment and survival for both Hispanic and black patients compared with white. Following matching, black patients continued to have lower rates of treatment and shorter survival times. CONCLUSIONS: These differences in treatment methods and survival outcomes for minorities, particularly black patients, highlight the need for more advocacy and focus on these underrepresented populations with rectal cancer.

Malate-aspartate shuttle promotes l-lactate oxidation in mitochondria.

Metabolism in cancer cells is rewired to generate sufficient energy equivalents and anabolic precursors to support high proliferative activity. Within the context of these competing drives aerobic glycolysis is inefficient for the cancer cellular energy economy. Therefore, many cancer types, including colon cancer, reprogram mitochondria-dependent processes to fulfill their elevated energy demands. Elevated glycolysis underlying the Warburg effect is an established signature of cancer metabolism. However, there are a growing number of studies that show that mitochondria remain highly oxidative under glycolytic conditions. We hypothesized that activities of glycolysis and oxidative phosphorylation are coordinated to maintain redox compartmentalization. We investigated the role of mitochondria-associated malate-aspartate and lactate shuttles in colon cancer cells as potential regulators that couple aerobic glycolysis and oxidative phosphorylation. We demonstrated that the malate-aspartate shuttle exerts control over NAD+ /NADH homeostasis to maintain activity of mitochondrial lactate dehydrogenase and to enable aerobic oxidation of glycolytic l-lactate in mitochondria. The elevated glycolysis in cancer cells is proposed to be one of the mechanisms acquired to accelerate oxidative phosphorylation.

How Soon Should Patients With Colon Cancer Undergo Definitive Resection?

BACKGROUND: Timing of surgery has been shown to affect outcomes in many forms of cancer, but definitive national data do not exist to determine the effect of time to surgery on survival in colon cancer. OBJECTIVE: This study aimed to determine whether a delay in definitive surgery in colon cancer significantly affects survival. DATA SOURCES: A retrospective cohort study using 2 independent population-based databases, The Surveillance, Epidemiology, and End Results Medicare-linked database and the National Cancer Database, was performed. STUDY SELECTION: All patients had American Joint Committee on Cancer stage 1 through 3 colon cancer. Patients were more than 18 years of age in the National Cancer Database cohort and older than 66 years of age in the Medicare cohort. Patients had a minimum of 3 years of follow-up. MAIN OUTCOME MEASURES: The main outcome was overall survival as a function of time between diagnosis and surgery in 4 intervals (1-2, 3-4, 5-6, >6 weeks). RESULTS: The Medicare cohort demonstrated an adjusted 5-year survival of 8% to 14% higher in patients with a surgical delay between 3 and 6 weeks, with significantly lower hazard ratios in that interval. The National Cancer Database cohort demonstrated an adjusted 5-year survival of 9% to 16% higher in patients with surgery 3 to 6 weeks after diagnosis, with comparatively similar improvements in survival hazard. LIMITATIONS: Because this was a retrospective study of administrative databases, with Medicare data limited to billing data, the causality of outcomes must be interpreted with caution. CONCLUSIONS: The ideal timing of definitive resection in colon cancer is between 3 and 6 weeks after initial diagnosis. All efforts should be made for patients to obtain definitive surgery within this interval to achieve a modest but significant improvement in overall survival. See Video Abstract at http://links.lww.com/DCR/B76. ¿CUÁNDO DEBEN SOMETERSE LOS PACIENTES CON CÁNCER DE COLON A UNA RESECCIÓN DEFINITIVA?: Se ha demostrado que el momento de la cirugía afecta los resultados en muchas formas de cáncer, pero no existen datos nacionales definitivos para determinar el efecto del tiempo hasta la cirugía en la supervivencia en el cáncer de colon.Determinar si un retraso en la cirugía definitiva en el cáncer de colon afecta significativamente la supervivencia.Un estudio de cohorte retrospectivo que utiliza dos bases de datos independientes basadas en la población; Se realizó la base de datos vinculada a la vigilancia, la epidemiología y los resultados finales y la base de datos nacional del cáncer.Pacientes con cáncer de colon en estadíos 1 a 3 del Comité Estadounidense Conjunto sobre el Cáncer. Los pacientes tenían más de 18 años en la cohorte de la National Cancer Database y más de 66 años en la cohorte de Medicare. Los pacientes tuvieron un mínimo de 3 años de seguimiento.El resultado principal fue la supervivencia general en función del tiempo entre el diagnóstico y la cirugía en 4 intervalos (1-2, 3-4, 5-6, y mas de 6 semanas).La cohorte de Medicare demostró una supervivencia ajustada de 5 años de 8 a 14% más en pacientes con un retraso quirúrgico entre 3 a 6 semanas, con razones de riesgo significativamente más bajas en ese intervalo. La cohorte de la National Cancer Database demostró una supervivencia ajustada a 5 años de 9 a 16% más en pacientes con cirugía de 3 a 6 semanas después del diagnóstico, con mejoras comparativamente similares en el riesgo de supervivencia.Dado que este fue un estudio retrospectivo de bases de datos administrativas, con datos de Medicare limitados a datos de facturación, la causalidad de los resultados debe interpretarse con precaución.El momento ideal para la resección definitiva en el cáncer de colon es entre tres y seis semanas después del diagnóstico inicial. Se deben hacer todos los esfuerzos para que los pacientes obtengan una cirugía definitiva dentro de este intervalo para lograr una mejora modesta pero significativa en la supervivencia general. Consulte Video Resumen en http://links.lww.com/DCR/B76.

Industry Payments in Colon and Rectal Surgery: A Cross-Sectional Analysis of Open Payments Data.

BACKGROUND: The Physician Payments Sunshine Act of 2010 mandated publication of all financial relationships between companies and physicians on the Centers for Medicare and Medicaid Services' Open Payments Data to elucidate potential conflicts of interest. This study seeks to illuminate the financial relationships that the pharmaceutical, medical device, biologics, and medical supply industries maintained with colon and rectal surgeons across the United States from 2014 to 2018. MATERIALS AND METHODS: We extracted and analyzed all colon and rectal surgeon data from the Open Payments Data for 2014-2018 using Microsoft Excel 2018 and JMP PRO 13.2.0 (SAS Institute). We calculated descriptive statistics and displayed prominent trends in the data. RESULTS: From 2014 to 2018, totals of $26,841,274 in general payments and $7,492,822 in research payments were made to 1935 and 150 colorectal surgeons, respectively. Intuitive Surgical, Inc paid the most money in general payments every year, ranging from 39.0% to 58.8% of the total payment amount. Intuitive Surgical, Inc's product, da Vinci Surgical System, had the greatest number of payments, totaling 21,191 general payments. The year with the highest amount paid for research was 2017, in which a total of $2,810,558 was paid to colorectal surgeons. CONCLUSIONS: Companies across industries paid millions of dollars to colorectal surgeons from 2014 to 2018. However, further research is required to determine the causal effects of these surgeons' financial relationships with the industry on research, prescription, and technology adoption practices.

Considerations and Changes in the Evaluation, Management, and Outcomes in the Management of Diverticular Disease: The Diagnosis, Pathology, and Treatment of Diverticular Colitis.

Diverticular colitis, also known as segmental colitis associated with diverticulosis, is a colonic inflammatory disorder on the spectrum of inflammatory bowel disease (IBD). The disease consists of macroscopic and microscopic inflammation affecting inter-diverticular mucosa, sparing peri-diverticular mucosa, with inflammation confined to the descending and sigmoid colon. The disease likely arises from the altered immune response of an individual, genetically susceptible to the IBD spectrum of diseases. Patients with segmental colitis associated with diverticulosis (SCAD) are typically older, and likely represent a subgroup of IBD-susceptible patients who lacked an environmental trigger until that point in their life. Most patients remain in remission with initial treatments of mesalamine or topical steroids, and maintenance mesalamine afterwards. Only the most severe form of the disease necessitates immunomodulatory therapy and the consideration of surgery.

Condyloma Acuminatum, Anal Intraepithelial Neoplasia, and Anal Cancer in the Setting of HIV: Do We Really Understand the Risk?

BACKGROUND: The gold standard for surveillance of patients with anal lesions is unclear. OBJECTIVE: The aim of this study was to stratify patients for risk of progression of disease and to determine appropriate intervals for surveillance of patients with anal disease. DESIGN: This was a retrospective chart review for patients treated for anal lesions between 2007 and 2014. Only patients with ≥1 year of follow-up from index evaluation, pathology, documented physical examination, and anoscopy findings were included for analysis. SETTINGS: The study was conducted at an urban university hospital. PATIENTS: HIV-positive patients with anal lesions treated with excision and fulguration were included. MAIN OUTCOME MEASURES: Recurrence of anal lesions, progression of disease, and progression to cancer were measured. RESULTS: Ninety-one patients met inclusion criteria. The mean age was 41.6 years, and mean follow-up was 38.6 months (range, 11.0-106.0 mo). On initial pathology, 8 patients (8.8%) had a diagnosis of condyloma acuminatum without dysplasia, 20 patients (22%) had anal intraepithelial neoplasia I, 32 (35.2%) had anal intraepithelial neoplasia II, and 31 (34.1%) had anal intraepithelial neoplasia III. Sixty-nine patients (75.8%) had repeat procedures. Seven (87.5%) of 8 patients with condyloma and 6 (30%) of 20 patients with anal intraepithelial neoplasia I progressed to high-grade lesions. Five (15.6%) of 32 patients progressed from anal intraepithelial neoplasia II to III, and 2 patients with anal intraepithelial neoplasia III (6.5%) developed squamous cell carcinoma (2.3% for the entire cohort). LIMITATIONS: This was a single institution study. High-resolution anoscopy was not used. CONCLUSIONS: All of the HIV-positive patients with condyloma or anal intraepithelial neoplasia, regardless of the presence of dysplasia, should be surveyed at equivalent 3-month time intervals, because their risk of progression of disease is high. Video Abstract at http://links.lww.com/DCR/A389.

Body mass index predicts operative time in elective colorectal procedures.

BACKGROUND: Obesity currently affects more than a third of the United States population and is associated with increased surgical complications. Compared to all other subspecialties, colorectal surgery is the most affected by the increasing trend in obese surgical patients. Operative time has been found to have the greatest impact on hospital costs and physician workload. This study was conducted to determine whether obesity has a direct impact on operative time in elective colorectal procedures using a high-powered, nationally representative patient sample. METHODS: A retrospective analysis was conducted on 45,362 patients who underwent open and laparoscopic ileocolic resections, partial colectomies, and low pelvic anastomoses using American College of Surgeons National Surgical Quality Improvement Program data from 2005-2009. Operative time was the main outcome variable, whereas body mass index (BMI) was the main independent variable. BMI was divided into three classes as follows: normal (<25), overweight and/or obese (25-35), and morbidly obese (>35). A univariate linear model was used to analyze the relationship while controlling for confounding factors such as demographics and preoperative conditions. Statistical significance was established at P ≤ 0.05. RESULTS: Morbidly obese patients were found to have longer operative times than did normal patients across each individual colorectal procedure (P < 0.001), ranging from a mean difference of 17.8 min for open ileocolic resections to 56.6 min for laparoscopic low pelvic anastomoses with colostomies. CONCLUSIONS: BMI, as an objective measure of obesity, is a direct, statistically significant independent predictor of operative time across elective colorectal procedures.

Mitochondria membrane transformations in colon and prostate cancer and their biological implications.

Mitochondria have emerged as important determinants in cancer progression and malignancy. However, the role of mitochondrial membranes in cancer onset and progression has not been thoroughly investigated. This study compares the structural and functional properties of mitochondrial membranes in prostate and colon cancer cells in comparison to normal mitochondria, and possible therapeutic implications of these membrane changes. Specifically, isolation of cell mitochondria and preparation of inverted sub-mitochondrial particles (SMPs) illuminated significant cancer-induced modulations of membrane lipid compositions, fluidity, and activity of cytochrome c oxidase, one of the key mitochondrial enzymes. The experimental data further show that cancer-associated membrane transformations may account for mitochondria targeting by betulinic acid and resveratrol, known anti-cancer molecules. Overall, this study probes the relationship between cancer and mitochondrial membrane transformations, underlying a potential therapeutic significance for mitochondrial membrane targeting in cancer.

Cardiolipin mediates curcumin interactions with mitochondrial membranes.

Curcumin, the main molecular ingredient of the turmeric spice, has been reported to exhibit therapeutic properties for varied diseases and pathological conditions. While curcumin appears to trigger multiple signaling pathways, the precise mechanisms accounting for its therapeutic activity have not been deciphered. Here we show that curcumin exhibits significant interactions with cardiolipin (CL), a lipid exclusively residing in the mitochondrial membrane. Specifically, we found that curcumin affected the structures and dynamics of CL-containing biomimetic and biological mitochondrial membranes. Application of several biophysical techniques reveals the CL-promoted association and internalization of curcumin into lipid bilayers. In parallel, curcumin association with CL containing bilayers increased their fluidity and reduced lipid ordering. These findings suggest that membrane modifications mediated by CL interactions may play a role in the therapeutic functions of curcumin, and that the inner mitochondrial membrane in general might constitute a potential drug target.

Racial Disparities and the Effect of County Level Income on the Incidence and Survival of Young Men with Anal Cancer.

Purpose: Prior studies have identified a racial disparity in incidence and survival of squamous cell carcinoma of the anus (SCCA) in the young African American male population. We aim to determine whether racial disparities are independent of income and urban location. Methods: The National Cancer Institute's Surveillance of Epidemiology and End Results database was queried for data on patients with SCCA for the years of 2000-2013. Cox regression was used to determine the effect of race, county median family income, rural-urban continuum, and stage of disease on overall survival. Results: The incidence rate of SCCA was significantly higher in black men <50 years old than in white men. Black race had a hazard ratio of 1.55 (confidence interval [CI] 1.33-1.81) when controlling for age, stage, income, and urban-rural status. Each $10,000 increase in county median family income was protective with a hazard ratio of 0.90 (CI 0.86-0.94). Residence in a metropolitan area did not significantly affect survival. Conclusions: The lower survival of black men <50 years old with SCCA is independent of income, urban location, and stage of disease. Further efforts are needed to target this at-risk population and the authors suggest wide application of previously validated screening programs for anal dysplasia.

Are Prophylactic Antibiotic Agents Indicated in Anorectal Surgery for Patients with Human Immunodeficiency Virus?

BACKGROUND: With increased survival among patients with human immunodeficiency virus (HIV), surgeons have been seeing more cases of anal dysplasia and cancer. There is, however, no data on the incidence of surgical site infections (SSIs) in HIV-positive patients undergoing elective anorectal procedures, nor on the administration of prophylactic antibiotic agents. We reviewed a HIV-positive population that has undergone elective anorectal biopsy of areas of dysplasia observed on office anoscopy to assess the need for antibiotic prophylaxis. PATIENTS AND METHODS: A retrospective chart review was performed of all HIV-positive patients seen as outpatients in the Colorectal Surgery Division from 2007-2016. Demographics, dates of surgery and follow-up, antibiotic prophylaxis, and pre-operative CD4 count and HIV viral load were recorded for 229 patients. Post-operative examination notes were reviewed to determine the presence of SSIs. The proportion of patients who received prophylaxis was assessed and the SSI rate was calculated. RESULTS: Surgical site infections occurred in 2 of 237 (0.8%) cases without antibiotic prophylaxis and in none of the 38 cases with prophylaxis. This infection rate was found to be lower than that of the general surgery population, with no statistical difference from hemorrhoidectomy patients without HIV. One SSI occurred in a 51-year-old male with a pre-operative CD4 count of 612 per microliter and viral load of zero. Another occurred in a 57-year-old female with an unknown CD4 count and viral load. A χ2 analysis showed the incidence of SSIs in the groups with and without prophylaxis was not significantly different (p = 0.563). CONCLUSION: Surgical site infection rates in HIV-positive patients undergoing biopsies for anal dysplasia were similar to patients without HIV undergoing similar minor anorectal procedures, and no difference was noted in the rate of SSI with the administration of prophylactic antibiotic agents. We do not recommend routine use of prophylactic antibiotic agents in this population.

Nursing home status is an independent risk factor for adverse 30-day postoperative outcomes after common, nonemergent inpatient procedures.

BACKGROUND: Nursing home residents undergoing surgery have a higher rate of postoperative adverse outcomes than nonnursing home patients. This study seeks to determine what contribution nursing home status makes to theses occurrences, independent of comorbid conditions. METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database, the 30-day postoperative outcomes of the 5 commonest nonemergent inpatient procedures performed on nursing home residents were compared with those in nonnursing home residents using logistic regression analysis. RESULTS: Nursing home status was found to be an independent risk factor for septic complications in all procedures, for blood transfusion requirement after lower leg amputation, for pneumonia and stroke/cerebrovascular accident after thromboendarterectomy, and for mortality after partial colectomy with primary anastomosis. CONCLUSIONS: These data suggest that, in addition to serving as a surrogate indicator of health status and current morbidity, residence in a nursing home makes an independent contribution to adverse postoperative outcomes.

Patient-specific risk factors are predictive for postoperative adverse events in colorectal surgery: an American College of Surgeons National Surgical Quality Improvement Program-based analysis.

BACKGROUND: Pay-for-performance measures incorporate surgical site infection rates into reimbursement algorithms without accounting for patient-specific risk factors predictive for surgical site infections and other adverse postoperative outcomes. METHODS: Using American College of Surgeons National Surgical Quality Improvement Program data of 67,445 colorectal patients, multivariable logistic regression was performed to determine independent risk factors associated with various measures of adverse postoperative outcomes. RESULTS: Notable patient-specific factors included (number of models containing predictor variable; range of odds ratios [ORs] from all models): American Society of Anesthesiologists class 3, 4, or 5 (7 of 7 models; OR 1.25 to 1.74), open procedures (7 of 7 models; OR .51 to 4.37), increased body mass index (6 of 7 models; OR 1.15 to 2.19), history of COPD (6 of 7 models; OR 1.19 to 1.64), smoking (6 of 7 models; OR 1.15 to 1.61), wound class 3 or 4 (6 of 7 models; OR 1.22 to 1.56), sepsis (6 of 7 models; OR 1.14 to 1.89), corticosteroid administration (5 of 7 models; OR 1.11 to 2.24), and operation duration more than 3 hours (5 of 7 models; OR 1.41 to 1.76). CONCLUSIONS: These findings may be used to pre-emptively identify colorectal surgery patients at increased risk of experiencing adverse outcomes.

Unique risks for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery.

BACKGROUND: The aim of this study was to identify unique risk factors for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery. METHODS: A multivariate logistic regression model predicting 30-day mortality was constructed for patients with end-stage renal disease undergoing nonemergent colorectal procedures. Data were obtained from the National Surgical Quality Improvement Program (2005-2010). RESULTS: Among the 394 patients analyzed, those with serum creatinine levels >7.5 mg/dL had .07 times the adjusted mortality risk of those with levels <3.5 mg/dL. For colorectal surgery patients, the average serum creatinine level was 5.52 ± 2.6 mg/dL, and mortality was 13% (n = 50). CONCLUSIONS: High serum creatinine was associated with a lower risk for mortality in patients with end-stage renal disease, even though creatinine is often considered a risk factor for surgery. These results show how variables from a patient-centered subpopulation can differ in meaning from the general population.