Deprivation and Rurality Mediate Income Inequality's Association with Colorectal Cancer Outcomes.

INTRODUCTION: Income inequality is associated with poor health outcomes, but its association with colorectal cancer is not well-studied. The authors aimed to determine the association between income inequality and colorectal cancer incidence/mortality in U.S. counties, and hypothesized that this association was mediated by deprivation. METHODS: The authors performed a cross-sectional study of U.S. counties from 2015-2019 using statewide cancer registries and the Centers for Disease Control and Prevention WONDER database. Generalized linear negative binomial regression was performed in 2024 to estimate the association between Gini coefficient (income inequality) and colorectal cancer incidence/mortality using incidence rate ratios (IRRs) for the entire cohort and stratified by rurality. RESULTS: A total of 697,981 colorectal cancer cases were diagnosed in the 5-year study period. On adjusted regression, for every 0.1 higher Gini coefficient, there was an 11% higher risk of both colorectal cancer incidence and mortality (IRR 1.11, 95%CI 1.03,1.19 and IRR 1.11, 95%CI 1.05, 1.18 respectively). The association between income inequality and incidence/mortality peaked in more rural counties, however there was not an overall dose-dependent relationship between rurality and these associations. Deprivation mediated the association between income inequality and colorectal cancer incidence (indirect effect B coefficient 0.088, p<0.001) and mortality (B coefficient 0.088, p<0.001). The magnitude and direction of the direct, indirect, and total effects differed in each rurality strata. CONCLUSIONS: Much of income inequality's association with colorectal cancer outcomes operates through deprivation. Rural counties have a stronger association between higher income inequality and higher mortality, which works in tandem with deprivation.

Feasibility of a Tungsten-181 HDR brachytherapy source: Analysis of isotope production and source dosimetry.

BACKGROUND: Interest in Intensity Modulated Brachytherapy (IMBT) for High Dose Rate Brachytherapy (HDR) treatments has steadily increased in recent years. However, intensity modulation is not best optimized for currently used HDR sources since they emit high energy photons. To that end, the focus on IMBT has moved to middle energy sources, such as Ytterbium-169; yet even Yb-169 emits some high energy photons at a low yield. We present an alternative isotope, Tungsten-181 (T1/2 = 121 days) that is interesting due to its complete lack of high energy photon emissions. (Eavg = 58.9 keV, Emed = 57.5 keV) making it potentially favorable as high dose rate brachytherapy source from both a medical physics and health physics perspective. PURPOSE: The purpose of this study was to determine the feasibility of using W-181 as an HDR brachytherapy source; in this study we focused on W-181's production, dosimetric properties, and intensity modulation capabilities. METHODS: We determined the isotope production kinetics, its Dose Rate Constant, Radial Dose Function, photon self-absorption, and the shielding intensity modulation capabilities for a W-181 pellet source geometry using the MCNP6.2 Computer Simulations Code. All simulations were performed using a personal computer running an AMD Ryzen 5 3600 6-Core Processor 3.59 GHz. The number of histories run for each study were selected to produce relative simulation convergence errors in the MCNP tally output of less than 2%. Dosimetric calculations were made using the MCNP6.2 computer simulations code and activation analyses were determined mathematically using a Catenary kinetics analysis (also known as a Bateman Analysis) of W-181 and Tantlum-182 production from the neutron activation of a pure Tungsten-180 stable target. Since W-181 emits middle energy photons and has a high density, we also assessed the effects of photon self-absorption within a tungsten pellet. RESULTS: From our analysis, we determined that a 3.5 mm long and 0.6 mm in diameter is feasible for clinical applications. Our activation analyses found that these pellets can achieve W-181 activities up to 7.9Ci and 13Ci using neutron fluence rates of 4E14 cm-2 s-1 and 1E15 cm-2 s-1 respectively, which then would provide a dose rate of 1.84 ± 0.01 cG y/Ci/min at a depth of 1 cm from the source. Using our resulting Monte Carlo simulated Dose Rate Constant of 1.24 ± 0.02 cGy h-1∙U-1, a W-181 source in this geometry would require a source activity upwards of 10Ci for use in HDR treatments. In the intensity modulation analysis, only 0.1 mm of gold shielding was found to reduce a pellet's absorbed dose by over 50% while 0.3 mm of gold shielding, which is thin enough to theoretically fit between an HDR pellet and the inner catheter wall, was found to reduce the pellet's absorbed dose by over 85%. CONCLUSIONS: While W-181 has a lower specific activity than Ir-192 and Yb-169, it shows great promise as an isotope for use in Intensity Modulated Brachytherapy due to its easily shielded photons. We therefore expect that W-181 may lend itself best for use as a multi-pellet configuration in IMBT.

Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis.

PURPOSE: Surgery for anal fistulas can result in devastating complications, including reoperations and fecal incontinence. There is limited contemporary evidence comparing outcomes since the adoption of the ligation of intersphincteric fistula tract procedure into mainstream practice. The purpose of this study is to compare recurrence rates and long-term outcomes of anal fistula following repair. METHODS: Data was collected from the electronic medical records or patient reported outcomes from patients aged 18 or older with a primary or recurrent cryptoglandular anal fistula. Primary outcome was recurrence defined as the identification of at least one fistula os or a high clinical suspicion of anal fistula. Secondary outcomes included fecal incontinence and postoperative quality of life. RESULTS: A total of 171 patients underwent definitive surgical repairs for their anal fistula. So 66.5% had a simple fistula, and 33.5% had a complex fistula. Of the 171 patients, 12.5% had a recurrence. The recurrence rates were 5.9% for simple fistula and 25.4% for complex fistula. Predictors of recurrence included diabetes mellitus, history of anorectal abscess, complex fistula, and sphincter sparing surgery. LIFT or plug/biologic procedures were both associated with a 50% or greater recurrence rate. No significant differences were found in fecal incontinence or associated quality of life between sphincter sparing or non-sphincter sparing surgical resections. CONCLUSION: The study provides insights into the long-term outcomes of surgical repair for anal fistula. We demonstrate that sphincter sparing operations are associated with increased recurrence, meanwhile, non-sphincter sparing surgeries did not increase the risk of fecal incontinence or worsen quality of life.

Drainage of anorectal abscesses in the operating room is associated with a decreased risk of abscess recurrence and fistula formation.

BACKGROUND: Timely incision and drainage (I&D) is first line management for anorectal abscesses. We aimed to define current practices in anorectal abscess management and identify factors associated with abscess recurrence and fistula formation. METHODS: Index episodes of anorectal abscesses treated with I&D in 2014-2018 at a multi-hospital healthcare system were included. Association with one-year abscess recurrence or fistula formation was evaluated using Cox proportional hazard regression. Fistulae were captured only among patients without fistulae at the index operation. RESULTS: A total of 458 patients met study criteria. One-year rate of abscess recurrence or fistula formation was 20.3%. When compared to bedside procedures, drainage in the operating room was associated with a reduced risk of either recurrence or fistula formation (aHR 0.20 [95%CI 0.114-0.367]). CONCLUSIONS: Improved exposure and patient comfort in the operating room may allow more complete drainage contributing to decreased rates of abscess recurrence or fistula formation.

DNA Mismatch Repair-deficient Rectal Cancer Is Frequently Associated With Lynch Syndrome and With Poor Response to Neoadjuvant Therapy.

We evaluated 368 consecutively resected rectal cancers with neoadjuvant therapy for DNA mismatch repair (MMR) protein status, tumor response to neoadjuvant therapy, histopathologic features, and patient survival. Nine (2.4%) rectal cancers were mismatch repair-deficient (MMRD): 8 (89%) Lynch syndrome-associated tumors and 1 (11%) sporadic MLH1-deficient tumor. Of the 9 MMRD rectal cancers, 89% (8/9) had a tumor regression score 3 (poor response) compared with 23% (81/359) of MMR proficient rectal cancers ( P <0.001). Patients with MMRD rectal cancer less often had downstaging after neoadjuvant therapy compared with patients with MMR proficient rectal cancer (11% vs. 57%, P =0.007). In the multivariable logistic regression analysis, MMRD in rectal cancer was associated with a 25.11-fold increased risk of poor response to neoadjuvant therapy (tumor regression score 3) (95% confidence interval [CI]: 3.08-44.63, P =0.003). In the multivariable Cox regression analysis, the only variables significantly associated with disease-free survival were pathologic stage III disease (hazard ratio [HR]=2.46, 95% CI: 1.54-3.93, P <0.001), College of American Pathologists (CAP) tumor regression score 2 to 3 (HR=3.44, 95% CI: 1.76-6.73, P <0.001), and positive margins (HR=2.86, 95% CI: 1.56-5.25, P =0.001). In conclusion, we demonstrated that MMRD in rectal cancer is an independent predictor of poor response to neoadjuvant therapy and infrequently results in pathologic downstaging following neoadjuvant therapy. We also confirmed that MMRD in rectal cancer is strongly associated with a diagnosis of Lynch syndrome. Our results suggest that MMR status may help to provide a more patient-centered approach when selecting neoadjuvant treatment regimens and may help predict tumor response to neoadjuvant therapy.

Readmission After Surgical Resection for Colon and Rectal Cancers: A Retrospective Cohort Study.

BACKGROUND: Colorectal adenocarcinoma is a leading cause of cancer mortality worldwide, often requiring patients to undergo anatomy-altering surgical interventions leading to increased postoperative readmission. Hospital readmission rates have been correlated with increased mortality. Therefore, it is important to understand the association between 30-day readmission rates and mortality as well as the factors associated with increased readmission rates. STUDY DESIGN: This is a retrospective review utilizing data from the National Cancer Database. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: Between 2010 and 2016, 207 299 patients underwent surgery for rectal cancer and 754 895 for colon cancer. The readmission rates within 30 days of discharge were 5.4% and 5.5% for patients after surgery for rectal or colon cancer, respectively. 30-day readmission was not associated with 30-day mortality, but it was independently associated with increased 90-day mortality and inferior long-term survival for both cohorts (P = .001). Independent risk factors significantly associated with increased readmission included race, non-private insurance, and low income. CONCLUSION: This study provides a large, up-to-date, and comprehensive analysis of readmission rates for colon and rectal cancers. We demonstrate that socioeconomic factors are associated with increased 30-day readmission. 30-day readmission is also independently associated with increased 90-day mortality as well as lower overall survival rates. Our study supports the need for implementation of programs that support patients of lower socioeconomic status undergoing surgery to further decrease readmission rates and mortality.

Transanal excision with adjuvant therapy for pT1N0 rectal tumors with high-risk features offers equivalent survival to radical resection: A National Cancer Database analysis.

BACKGROUND: Current guidelines favor transabdominal radical resection (RR) over transanal local excision (TAX) followed by adjuvant therapy (TAXa) for pT1N0 rectal tumors with high-risk features. Comparison of oncologic outcomes between these approaches is limited, although the former is associated with increased postoperative morbidity. We hypothesize that such treatment strategies result in equivalent long-term survival. METHODS: A retrospective cohort study was conducted using the National Cancer Database (2010-2016) to identify patients with pT1N0 rectal adenocarcinoma with high-risk features who underwent TAX or RR for curative intent. The primary outcome was 5-year overall survival (OS), evaluated with log-rank and Cox-proportional hazards testing. RESULTS: A total of 1159 patients (age 67.4 ± 12.9 years; 56.6% male; 83.3% White) met study criteria, of which 1009 (87.1%) underwent RR and 150 (12.9%) underwent TAXa. Patients undergoing TAXa had shorter lengths of stay (RR = 6.5 days, TAXa = 2.7 days, p < 0.001). The 5-year OS was equivalent between groups. TAX without adjuvant therapy was associated with an increased risk of mortality (hazard ratio 1.81, 95% confidence interval 1.17-2.78, p = 0.01). CONCLUSIONS: This is the largest study to demonstrate equivalent 5-year OS between TAXa and RR for T1N0 rectal cancer with high-risk features. These findings may guide the development of prospective, randomized trials and influence changes in practice recommendations for early-stage rectal cancer.

The Role of Adjuvant Chemotherapy Following Right Hemicolectomy for Non-metastatic Mucinous and Nonmucinous Appendiceal Adenocarcinoma.

BACKGROUND: Appendiceal adenocarcinoma (AA) represents a heterogenous group of neoplasms with distinct histologic features. The role and efficacy of adjuvant chemotherapy (AC) in non-metastatic disease remain controversial. The aim of this study was to ascertain the role of AC in non-metastatic AA in a national cohort of patients. METHODS: The National Cancer Database (NCDB) was queried to identify patients diagnosed with stage I-III mucinous and nonmucinous AA who underwent right hemicolectomy between 2006 and 2016. Kaplan-Meier and Cox regression analyses were used to evaluate the impact of AC on overall survival (OS) stratified by each pathologic stage. RESULTS: A total of 1433 mucinous and 1954 nonmucinous AA were identified; 578 (40%) and 722 (40%) received AC respectively. In both AC groups, there was a higher proportion of T4 disease, lymph node metastasis, pathologic stage III, and poorly/undifferentiated grade (all P<0.05). On unadjusted analysis, there was no significant association between AC and OS for stage I-III mucinous AA. For nonmucinous AA, AC significantly improved OS only for stage II and III disease. On adjusted analysis, AC was independently associated with an improved OS for stage III nonmucinous AA (HR: 0.61, 95%CI 0.45-0.84, P=0.002), while for mucinous AA, AC was associated with worse outcomes for stage I/II disease (HR: 1.4, 95%CI 1.02-1.91, P=0.038) and had no significant association with OS for stage III disease. CONCLUSION: This current analysis of a national cohort of patients suggests a beneficial role for AC in stage III nonmucinous AA and demonstrates no identifiable benefit for stage I-III mucinous AA.

Developing Opioid Prescription Guidelines After Anorectal Surgery: Do Patient-Reported Outcomes and Risk Factors Influence Consumption?

BACKGROUND: Opioids prescribed to address postoperative pain drive opioid-related deaths in the United States. Prescribing guidelines have been developed for many general surgical procedures, which have decreased opioid prescription and consumption. The literature on opioids after anorectal surgery is lacking. OBJECTIVE: We analyzed our data on opioid prescription and consumption to create opioid-prescribing guidelines for anorectal procedures. DESIGN: We designed a prospectively collected postoperative survey given to consecutive patients undergoing anorectal surgery by colorectal surgeons. SETTINGS: Patients had surgery at 2 academic, university-affiliated hospitals. PATIENTS: Patients undergoing anorectal surgery from May 3, 2018, to December 18, 2019, were included in the study. Patients were excluded if they were <18 years of age, had a concurrent abdominopelvic surgery, consumed opioids in the week before their operation, or were without follow-up at 3 months postoperatively. MAIN OUTCOME MEASURES: The primary outcome of this study was the number of opioid pills needed to fulfill consumption of 80% of patients. Secondary outcome measures were patient, operative, and postoperative factors associated with increasing pill consumption. RESULTS: Eighteen 5-mg oxycodone tablets were needed to fulfill the needs of 80% of patients. An overall median of 8 pills was consumed. Pill prescription was independently predictive of increased consumption. The only patient factor associated with increased consumption was race; no other patient or operative factors were predictive of consumption. LIMITATIONS: Limitations of this study include its partially retrospective nature, use of self-reported data, and lack of racial diversity among our cohort. CONCLUSIONS: Without any clinical factors predictive of increased consumption, prescription guidelines can be standardized to ≤18 5-mg oxycodone tablets across anorectal surgery patients. As prescription is correlated with consumption, further work is needed to determine whether lesser quantities of opioids prescribed offer similar postoperative pain relief for patients undergoing anorectal surgery. See Video Abstract at http://links.lww.com/DCR/B821 .DESARROLLO DE PAUTAS PARA LA PRESCRIPCIÓN DE OPIOIDES DESPUÉS DE CIRUGÍA ANORRECTAL: ¿INFLUYEN EN EL CONSUMO LOS RESULTADOS INFORMADOS POR EL PACIENTE Y LOS FACTORES DE RIESGO? ANTECEDENTES: Los opioides recetados para tratar el dolor posoperatorio provocan muertes relacionadas con los opioides en los Estados Unidos. Se han desarrollado pautas de prescripción para muchos procedimientos quirúrgicos generales y estas han conducido a una disminución de la prescripción y el consumo de opioides. Hay una carencia de literatura sobre el uso de opioides después de cirugía anorrectal. OBJETIVO: Analizamos nuestros datos sobre prescripción y consumo de opioides para crear pautas de prescripción de opioides para procedimientos anorrectales. DISEO: Diseñamos una encuesta postoperatoria recopilada prospectivamente que se administró a pacientes consecutivos sometidos a cirugía anorrectal por cirujanos colorrectales. AJUSTES: Los pacientes fueron operados en dos hospitales académicos afiliados a la universidad. PACIENTES: Se incluyeron en el estudio pacientes sometidos a cirugía anorrectal desde el 3/05/2018 hasta el 18/12/2019. Se excluyó a los pacientes que tenían menos de 18 años, a los que se sometieron a cirugía abdominopélvica concurrente, a los que consumieron opioides en la semana anterior a la operación, o si no tenían seguimiento a los 3 meses del postoperatorio. PRINCIPALES MEDIDAS DE DESENLACE: El desenlace principal de este estudio fue el número de píldoras de opioides necesarias para satisfacer el consumo del 80% de los pacientes. Las medidas de desenlace secundarias fueron los factores del paciente, operatorios y posoperatorios asociados con el aumento del consumo de píldoras. RESULTADOS: Fueron necesarios dieciocho comprimidos de oxicodona de 5 mg para cubrir las necesidades del 80% de los pacientes. Se consumió una mediana general de 8 píldoras. La prescripción de la píldora fue un predictor independiente de un mayor consumo. El único factor del paciente asociado con un mayor consumo fue la raza; ningún otro paciente o factores operativos fueron predictivos del consumo. LIMITACIONES: Las limitaciones de este estudio incluyen su naturaleza parcialmente retrospectiva, el uso de datos autoinformados y la falta de diversidad racial entre nuestra cohorte. CONCLUSIONES: Sin ningún factor clínico que prediga un aumento del consumo, las pautas de prescripción se pueden estandarizar a dieciocho o menos comprimidos de oxicodona de 5 mg en pacientes sometidos a cirugía anorrectal. Como la prescripción se correlaciona con el consumo, se necesita más trabajo para determinar si cantidades menores de opioides prescritos ofrecen un alivio del dolor posoperatorio similar para los pacientes sometidos a cirugía anorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B821 . (Traducción-Juan Carlos Reyes ).

Intensity modulated high dose rate ocular brachytherapy using Se-75.

PURPOSE: We propose an alternative to LDR brachytherapy for the treatment of ocular melanomas by coupling intensity modulation, through the use of a gold shielded ring applicator, with a middle energy HDR brachytherapy source, Se-75. In this study, we computationally test this proposed design using MCNP6. METHODS AND MATERIALS: An array of discrete Se-75 sources is formed into a ring configuration within a gold shielded applicator, which collimates the beam to a conical shape. Varying this angle of collimation allows for the prescription dose to be delivered to the apex of various sized targets. Simulations in MCNP6 were performed to calculate the dosimetric output of the Se-75 ring source for various sized applicators, collimators, and target sizes. RESULTS: The prescription dose was delivered to a range of target apex depths 3.5-8 mm in the eye covering targets 10-15 mm in diameter by using various sized applicators and collimators. For a 16 mm applicator with a collimator opening that delivers the prescription dose to a depth of 5 mm in the eye, the maximum percent dose rate to critical structures was 30.5% to the cornea, 35.7% to the posterior lens, 33.3% to the iris, 20.1% to the optic nerve, 278.0% to the sclera, and 267.3% to the tumor. CONCLUSIONS: When using Se-75 in combination with the proposed gold shielded ring applicator, dose distributions are appropriate for ocular brachytherapy. The use of a collimator allows for the dose to more easily conform to the tumor volume. This method also reduces treatment time and cost, and it eliminates hand dose to the surgeon through the use of a remote afterloader device.

Shielded high dose rate ocular brachytherapy using Yb-169.

Purpose.We propose an approach for treating ocular melanoma using a new type of brachytherapy treatment device. This device couples Yb-169, a middle-energy high dose rate (HDR) brachytherapy source, with a gold shielded ring applicator to better conform radiation exposures to the tumor. In this study, we computationally test the dosimetric output of our proposed shielded ring applicator design using MCNP6 and validate it against an I-125 COMS plaque.Methods.The proposed Yb-169 ring applicator consists of an assembly of discrete sources delivered into an applicator with a conical collimated opening; this opening is tangent to the outside of the source tube. Using MCNP6, we simulated the dosimetric output of a ring of Yb-169 pellets placed within the collimator at various conical diameters and angles to demonstrate the dosimetric distribution for various prescription dose depths and target sizes using static intensity modulation.Results.Using various angles of collimation, the prescription dose was delivered to target apex depths of 3.5-8.0 mm into the eye covering target sizes ranging from 10 to 15 mm in diameter. This proposed device reduced the maximum absorbed dose to critical structures relative to I-125 by 5.2% to the posterior lens, 9.3% to the iris, 13.8% to the optic nerve, and 1.3% to the sclera.Conclusions.This proposed eye plaque design provides a more conformal dose distribution to the ocular tumor while minimizes dose to healthy ocular structures. In addition, the use of a middle-energy HDR brachytherapy source allows the use of a remote afterloader to expose the tumor after the plaque is sutured in place. This system is inherently safer and eliminates dose to the surgeon's hands.

Patient Factors Limit Colon Cancer Survival at Safety-Net Hospitals: A National Analysis.

BACKGROUND: Safety-net hospitals serve a vital role in society by providing care for vulnerable populations. Existing data regarding oncologic outcomes of patients with colon cancer treated at safety-net hospitals are limited and variable. The objective of this study was to delineate disparities in treatment and outcomes for patients with colon cancer treated at safety-net hospitals. METHODS: This retrospective cohort study identified 802,304 adult patients with colon adenocarcinoma from the National Cancer Database between 2004-2016. Patients were stratified according to safety-net burden of the treating hospital as previously described. Patient, tumor, facility, and treatment characteristics were compared between groups as were operative and short-term outcomes. Cox proportional hazards regression was utilized to compare overall survival between patients treated at high, medium, and low burden hospitals. RESULTS: Patients treated at safety-net hospitals were demographically distinct and presented with more advanced disease. They were also less likely to receive surgery, adjuvant chemotherapy, negative resection margins, adequate lymphadenectomy, or a minimally invasive operative approach. On multivariate analysis adjusting for patient and tumor characteristics, survival was inferior for patients at safety-net hospitals, even for those with stage 0 (in situ) disease. CONCLUSION: This analysis revealed inferior survival for patients with colon cancer treated at safety-net hospitals, including those without invasive cancer. These findings suggest that unmeasured population differences may confound analyses and affect survival more than provider or treatment disparities.

Time to Surgery and Colon Cancer Survival in the United States.

PURPOSE: Time to surgery (TTS) is of concern to patients diagnosed with cancer and their physicians. Controversy surrounds the impact of TTS on colon cancer survival. There are limited national data evaluating the association; thus, our aim was to estimate the overall survival (OS) impact from increasing TTS for patients with colon cancer. METHODS: Using the National Cancer Data Base (NCDB), we assessed OS as a function of time between diagnosis and surgery by evaluating intervals encompassing <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days in length. All patients were diagnosed with nonmetastatic colon cancer and underwent surgery as initial treatment. Our main outcome was OS as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors using Cox regression models and propensity score-based weighting. RESULTS: A total of 514,103 patients diagnosed between 1998 and 2012 were included. Individuals having <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days between diagnosis and surgery comprised 35.4%, 45%, 15.1%, 2.9%, 1%, and 0.6% of the patients, respectively. There was a steady increase in median TTS across the years. On multivariable analysis, TTS >30 days or within the first week independently increased mortality risk. There was a significant increase in mortality with TTS 31 to 60 [hazard ratio (HR) 1.13], 61 to 90 (HR 1.49), <7 (HR 1.56), 91 to 120 (HR 2.28), and 121 to 180 (HR 2.46) compared to surgery performed 7 to 30 days after diagnosis (P < 0.001). CONCLUSIONS: TTS is independently associated with OS and this represents a public health issue that should be addressed at a national level. Although time is required for evaluation before surgery, efforts to reduce TTS should be pursued.

Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma.

Tumor budding and CD8-positive (+) T-cells are recognized as prognostic factors in colorectal adenocarcinoma. We assessed CD8+ T-cell density and intratumoral budding in pretreatment rectal cancer biopsies to determine if they are predictive biomarkers for response to neoadjuvant therapy and survival. Pretreatment biopsies of locally advanced rectal adenocarcinoma from 117 patients were evaluated for CD8+ T-cell density using automated quantitative digital image analysis and for intratumoral budding and correlated with clinicopathological variables on postneoadjuvant surgical resection specimens, response to neoadjuvant therapy, and survival. Patients with high CD8+ T-cell density (≥157 per mm2) on biopsy were significantly more likely to exhibit complete/near complete response to neoadjuvant therapy (66% vs. 33%, p = 0.001) and low tumor stage (0 or I) on resection (62% vs. 30%, p = 0.001) compared with patients with low CD8+ T-cell density. High CD8+ T-cell density was an independent predictor of response to neoadjuvant therapy with a 2.63 higher likelihood of complete response (95% CI 1.04-6.65, p = 0.04) and a 3.66 higher likelihood of complete/near complete response (95% CI 1.60-8.38, p = 0.002). The presence of intratumoral budding on biopsy was significantly associated with a reduced likelihood of achieving complete/near complete response to neoadjuvant therapy (odds ratio 0.36, 95% CI 0.13-0.97, p = 0.048). Patients with intratumoral budding on biopsy had a significantly reduced disease-free survival compared with patients without intratumoral budding (5-year survival 39% vs 87%, p < 0.001). In the multivariable model, the presence of intratumoral budding on biopsy was associated with a 3.35-fold increased risk of tumor recurrence (95% CI 1.25-8.99, p = 0.02). In conclusion, CD8+ T-cell density and intratumoral budding in pretreatment biopsies of rectal adenocarcinoma are independent predictive biomarkers of response to neoadjuvant therapy and intratumoral budding associates with patient survival. These biomarkers may be helpful in selecting patients who will respond to neoadjuvant therapy and identifying patients at risk for recurrence.

Time-Dependent Displacement of Commensal Skin Microbes by Pathogens at the Site of Colorectal Surgery.

BACKGROUND: Although the healthy human skin microbiome has been the subject of recent studies, it is not known whether alterations among commensal microbes contribute to surgical site infections (SSIs). Our objective in this study was to characterize temporal and spatial variation in the skin microbiota of patients undergoing colorectal surgery and determine if dysbiosis contributes to SSIs. METHODS: Sixty one adults scheduled to undergo elective colon or rectal resection were identified by convenience sampling. By analyzing bacterial 16S rRNA gene sequences isolated from clinical samples, we used a culture-independent strategy to monitor perioperative changes in microbial diversity of fecal samples and the skin. RESULTS: A total of 990 samples from 61 patients were analyzed. Alpha diversity on the skin decreased after surgery but later recovered at the postoperative clinic visit. In most patients, we observed a transient postoperative loss of skin commensals (Corynebacterium and Propionibacterium) at the surgical site, which were replaced by potential pathogens and intestinal anaerobes (eg, Enterobacteriaceae). These changes were not observed on skin that was uninvolved in the surgical incision (chest wall). One patient developed a wound infection. Incisional skin swabs from this patient demonstrated a sharp postoperative increase in the abundance of Enterococcus, which was also cultured from wound drainage. CONCLUSIONS: We observed reproducible perioperative changes in the skin microbiome following surgery. The low incidence of SSIs in this cohort precluded analysis of associations between dysbiosis and infection. We postulate that real-time monitoring of the skin microbiome could provide actionable findings about the pathogenesis of SSIs.

Monte Carlo dosimetric characterization of a new high dose rate 169 Yb brachytherapy source and independent verification using a multipoint plastic scintillator detector.

PURPOSE: A prototype 169 Yb source was developed in combination with a dynamic rotating platinum shield system (AIM-Brachy) to deliver intensity modulated brachytherapy (IMBT). The purpose of this study was to evaluate the dosimetric characteristics of the bare/shielded 169 Yb source using Monte Carlo (MC) simulations and perform an independent dose verification using a dosimetry platform based on a multipoint plastic scintillator detector (mPSD). METHODS: The TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles ( 0 ∘ , 9 0 ∘ , 18 0 ∘ , and 27 0 ∘ ). RESULTS: The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5-10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6-6.2%) for BCF-10, 1.7% (0.9-2.9%) for BCF-12, and 2.2% (0.3-4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8 ± 1.2%, compared to 83.5 ± 0.5% as calculated by MC. CONCLUSIONS: The dose distribution for the bare/shielded 169 Yb source was independently verified using mPSD with good agreement in regions close to the source. The 169 Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.

Impact of Enhanced Recovery Pathways and early urinary catheter removal on post-operative urinary retention.

BACKGROUND: Post-operative urinary retention (POUR) is a common complication after colorectal surgery. Enhanced recovery pathways (ERP) typically include early catheter removal but may place patients at risk for POUR. METHODS: This is a retrospective cohort analysis of patients undergoing colorectal surgery at a single institution between April 2014 and November 2017. Patients were stratified into non-ERP and ERP cohorts and post-operative outcomes were compared. RESULTS: Of 284 patients studied, ERP was applied to 161 (57%) while the remaining 123 (43%) recovered under standard care. Median duration of indwelling Foleys was 1 day for ERP and 2 days for non-ERP patients (p < 0.001). ERP patients experienced higher rates of straight catheterization (22% vs 12%,p = 0.036), Foley reinsertion (14% vs 7%,p = 0.07), and initiation of alpha antagonists (12% vs 5%,p = 0.04). Significant independent predictors of POUR were age (OR 1.03, p = 0.002), male gender (OR 2.79, p = 0.001), surgery duration (OR 1.27, p = 0.027), and ERP (OR 1.96, p = 0.025). CONCLUSION: ERP following colorectal surgery that include routine early Foley catheter removal on post-operative day one is associated with increased rates of POUR; however, this did not lead to increased rates of catheter-associated urinary tract infections during the index admission in the population studied.

Refusal of cancer-directed treatment by colon cancer patients: Risk factors and survival outcomes.

AIM: Surgery with or without chemotherapy represent the only curative option for patients with colon cancer. However, some patients refuse treatment despite the recommendation. This study aims to identify the incidence, risk factors and impact on survival associated with refusal. METHODS: A National Cancer Data Base (NCDB) analysis between 1998 and 2012 was performed. We identified 924,290 patients with potentially treatable colon cancer. Patients who underwent treatment were compared with patients that refused. RESULTS: 7152 patients refused surgery. On multivariable analysis, patients were more likely to refuse if they were older (OR = 1.14; 95% CI 1.14-1.15), female (OR = 1.20; 95% CI 1.12-1.28), African American (vs White, OR = 2.30; 95% CI 2.10-2.51) or on Medicaid (vs private, OR = 3.06; 95% CI 2.49-43.77). Overall survival was worse in patients that refused surgery [median survival 6.8 vs 24 months, Cox hazard ratio (HR) 3.41; 95%CI 3.12-3.60]. Furthermore, 11,334 patients with path. stage III disease refused adjuvant chemotherapy. CONCLUSIONS: Refusal of treatment affects survival and is independently associated with several variables (gender, race, insurance status), therefore raising the concern that socioeconomic factors may drive decisions.

Postoperative nausea and vomiting in patients undergoing colorectal surgery within an institutional enhanced recovery after surgery protocol: comparison of two prophylactic antiemetic regimens.

BACKGROUND: Enhanced recovery protocols (ERP) provide optimal perioperative care for surgical patients. Postoperative nausea and vomiting (PONV) is common after colorectal surgery (CRS). We aim to compare the efficacy of aprepitant to a cost-effective alternative, perphenazine, as components of triple antiemetic prophylaxis in ERP patients. METHODS: Patients who underwent ERP CRS at a single institution from July 2015 to July 2017 were evaluated retrospectively. Only subjects who received aprepitant (Group 1) or perphenazine (Group 2) preoperatively for PONV prophylaxis were included. Patient characteristics, simplified Apfel PONV scores, perioperative medications, and PONV incidence were compared between the groups. PONV was defined as the need for rescue antiemetics on postoperative days (POD) 0-5. RESULTS: Five hundred ninety-seven patients underwent CRS of which 498 met the inclusion criteria. Two hundred thirty-one (46.4%) received aprepitant and 267 (53.6%) received perphenazine. The incidence of early PONV (POD 0-1) was comparable between the two groups: 44.2% in Group 1 and 44.6% in Group 2 (P = 0.926). Late PONV (POD 2-5) occurred less often in Group 1 than Group 2, respectively (35.9% vs. 45.7%, P = 0.027). After matching the groups for preoperative, procedural, and anesthesia characteristics (164 pairs), no difference in early or late PONV could be demonstrated between the groups. CONCLUSIONS: The incidence of PONV remains high despite most patients receiving three prophylactic antiemetic medications. Perphenazine can be considered a cost-effective alternative to oral aprepitant for prophylaxis of PONV in patients undergoing CRS within an ERP.