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.

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 ).

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.

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.

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.

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.

Comparison of methods to estimate water-equivalent diameter for calculation of patient dose.

Modern CT systems seek to evaluate patient-specific dose by converting the CT dose index generated during a procedure to a size-specific dose estimate using conversion factors that are related to patient attenuation properties. The most accurate way to measure patient attenuation is to evaluate a full-field-of-view reconstruction of the whole scan length and calculating the true water-equivalent diameter (Dw ) using CT numbers; however, due to time constraints, less accurate methods to estimate Dw using patient geometry measurements are used more widely. In this study we compared the accuracy of Dw values calculated from three different methods across 35 sample scans and compared them to the true Dw . These three estimation methods were: measurement of patient lateral dimension from a pre-scan localizer radiograph; measurement of the sum of anteroposterior and lateral dimensions from a reconstructed central slice; and using CT numbers from a central slice only. Using the localizer geometry method, 22 out of 35 (62%) samples estimated Dw within 20% of the true value. The middle slice attenuation and geometry methods gave estimations within the 20% margin for all 35 samples.

Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial.

BACKGROUND: Local excision is an organ-preserving treatment alternative to transabdominal resection for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared with transabdominal rectal resection. We investigated the oncological and functional outcomes of neoadjuvant chemoradiotherapy and local excision for patients with stage T2N0 rectal cancer. METHODS: We did a multi-institutional, single-arm, open-label, non-randomised, phase 2 trial of patients with clinically staged T2N0 distal rectal cancer treated with neoadjuvant chemoradiotherapy at 26 American College of Surgeons Oncology Group institutions. Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge, and with an Eastern Cooperative Oncology Group performance status of at least 2 were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m(2) twice daily on days 1-14 and 22-35), oxaliplatin (50 mg/m(2) on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m(2) twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The primary endpoint was 3-year disease-free survival for all eligible patients (intention-to-treat population) and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumours, and negative resection margins (per-protocol group). This study is registered with ClinicalTrials.gov, number NCT00114231. FINDINGS: Between May 25, 2006, and Oct 22, 2009, 79 eligible patients were recruited to the trial and started neoadjuvant chemoradiotherapy. Two patients had no surgery and one had a total mesorectal excision. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Thus, the per-protocol population consisted of 72 patients. Median follow-up was 56 months (IQR 46-63) for all patients. The estimated 3-year disease-free survival for the intention-to-treat group was 88·2% (95% CI 81·3-95·8), and for the per-protocol group was 86·9% (79·3-95·3). Of 79 eligible patients, 23 (29%) had grade 3 gastrointestinal adverse events, 12 (15%) had grade 3-4 pain, and 12 (15%) had grade 3-4 haematological adverse events during chemoradiation. Of the 77 patients who had surgery, six (8%) had grade 3 pain, three (4%) had grade 3-4 haemorrhage, and three (4%) had gastrointestinal adverse events. INTERPRETATION: Although the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection. FUNDING: National Cancer Institute and Sanofi-Aventis.

Dosimetric characterization of the M-15 high-dose-rate Iridium-192 brachytherapy source using the AAPM and ESTRO formalism.

The Source Production & Equipment Co. (SPEC) model M-15 is a new Iridium-192 brachytherapy source model intended for use as a temporary high-dose-rate (HDR) brachytherapy source for the Nucletron microSelectron Classic afterloading system. The purpose of this study is to characterize this HDR source for clinical application by obtaining a complete set of Monte Carlo calculated dosimetric parameters for the M-15, as recommended by AAPM and ESTRO, for isotopes with average energies greater than 50 keV. This was accomplished by using the MCNP6 Monte Carlo code to simulate the resulting source dosimetry at various points within a pseudoinfinite water phantom. These dosimetric values next were converted into the AAPM and ESTRO dosimetry parameters and the respective statistical uncertainty in each parameter also calculated and presented. The M-15 source was modeled in an MCNP6 Monte Carlo environment using the physical source specifications provided by the manufacturer. Iridium-192 photons were uniformly generated inside the iridium core of the model M-15 with photon and secondary electron transport replicated using photoatomic cross-sectional tables supplied with MCNP6. Simulations were performed for both water and air/vacuum computer models with a total of 4 × 109 sources photon history for each simulation and the in-air photon spectrum filtered to remove low-energy photons belowδ = 10 keV. Dosimetric data, including D·(r,θ), gL(r), F(r,θ), φan(r), and φ-an, and their statistical uncertainty were calculated from the output of an MCNP model consisting of an M-15 source placed at the center of a spherical water phantom of 100 cm diameter. The air kerma strength in free space, SK, and dose rate constant, Λ, also was computed from a MCNP model with M-15 Iridium-192 source, was centered at the origin of an evacuated phantom in which a critical volume containing air at STP was added 100 cm from the source center. The reference dose rate, D·(r0,θ0) ≡ D· (1cm,π/2), is found to be 4.038 ± 0.064 cGy mCi-1 h-1. The air kerma strength, SK, is reported to be 3.632 ± 0.086 cGy cm2 mCi-1 g-1, and the dose rate constant, Λ, is calculated to be 1.112 ± 0.029 cGy h-1 U-1. The normalized dose rate, radial dose function, and anisotropy function with their uncertainties were computed and are represented in both tabular and graphical format in the report. A dosimetric study was performed of the new M-15 Iridium-192 HDR brachytherapy source using the MCNP6 radiation transport code. Dosimetric parameters, including the dose-rate constant, radial dose function, and anisotropy function, were calculated in accordance with the updated AAPM and ESTRO dosimetric parameters for brachytherapy sources of average energy greater than 50 keV. These data therefore may be applied toward the development of a treatment planning program and for clinical use of the source.

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.

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.

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.

A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial.

PURPOSE: We designed American College of Surgeons Oncology Group (ACOSOG) Z6041, a prospective, multicenter, single-arm, phase II trial to assess the efficacy and safety of neoadjuvant chemoradiation (CRT) and local excision (LE) for T2N0 rectal cancer. Here, we report tumor response, CRT-related toxicity, and perioperative complications (PCs). METHODS: Clinically staged T2N0 rectal cancer patients were treated with capecitabine and oxaliplatin during radiation followed by LE. Because of toxicity, capecitabine and radiation doses were reduced. LE was performed 6 weeks after CRT. Patients were evaluated for clinical and pathologic response. CRT-related complications and PCs were recorded. RESULTS: Ninety patients were accrued; 6 received nonprotocol treatment. The remaining 84 were 65% male; median age 63 years; 83% Eastern Cooperative Oncology Group performance score 0; 92% white; mean tumor size 2.9 cm; and average distance from anal verge 5.1 cm. Five patients were considered ineligible. Therapy was completed per protocol in 79 patients, but two patients did not undergo LE. Among 77 eligible patients who underwent LE, 34 patients achieved a pathologic complete response (44%) and 49 (64%) tumors were downstaged (ypT0-1), but 4 patients (5%) had ypT3 tumors. Five LE specimens contained lymph nodes; one T3 tumor had a positive node. All but one patient had negative margins. Thirty-three (39%) of 84 patients developed CRT-related grade ≥3 complications. Rectal pain was the most common PC. CONCLUSIONS: CRT before LE for T2N0 tumors results in a high pathologic complete response rate and negative resection margins. However, complications during CRT and after LE are high. The true efficacy of this approach will ultimately be assessed by the long-term oncologic outcomes.

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.

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.

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.

Dependence of Yb-169 absorbed dose energy correction factors on self-attenuation in source material and photon buildup in water.

PURPOSE: Absorbed dose energy correction factors, used to convert the absorbed dose deposited in a LiF thermoluminescent dosimeter (TLD) into the clinically relevant absorbed dose to water, were obtained for both spherical volumetric sources and for the model 4140 HDR Yb-169 source. These correction factors have a strong energy dependence below 200 keV; therefore, spectral changes were quantified as Yb-169 photons traveled through both source material (Yb2O3) and water with the corresponding absorbed dose energy correction factors, f(r, theta), calculated as a function of location in a phantom. METHODS: Using the MCNP5 Monte Carlo radiation transport simulation program, the Yb-169 spectrum emerging from spherical Yb2O3 sources (density 6.9 g/cm3) with radii between 0.2 and 0.9 mm were analyzed and their behavior compared against those for a point-source. The absorbed dose deposited to both LiF and H2O materials was analyzed at phantom depths of 0.1-10 cm for each source radius and the absorbed dose energy correction factor calculated as the ratio of the absorbed dose to water to that of LiF. Absorbed dose energy correction factors for the Model 4140 Yb-169 HDR brachytherapy source similarly were obtained and compared against those calculated for the Model M-19 Ir-192 HDR source. RESULTS: The Yb-169 average spectral energy, emerging from Yb2O3 spherical sources 0.2-0.9 mm in radius, was observed to harden from 7% to 29%; as these photons traveled through the water phantom, the photon average energy softened by as much as 28% at a depth of 10 cm. Spectral softening was dependent on the measurement depth in the phantom. Energy correction factors were found to vary both as a function of source radius and phantom depth by as much as 10% for spherical Yb2O3 sources. The Model 4140 Yb-169 energy correction factors depended on both phantom depth and reference angle and were found to vary by more than 10% between depths of 1 and 10 cm and angles of 0 degrees and 180 degrees. This was in contrast to that of the Model M-19 Ir-192 source which exhibited approximately 3.5%-4.4% variation in its energy correction factors from phantom depths of 0.5-10 cm. The absorbed dose energy correction factor for the Ir-192 source, on the other hand, was independent of angle to within 1%. CONCLUSIONS: The application of a single energy correction factor for Yb-169 TLD based dosimetry would introduce a high degree of measurement uncertainty that may not be reasonable for the clinical characterization of a brachytherapy source; rather, an absorbed dose energy correction function will need to be developed for these sources. This correction function should be specific to each source model, type of TLD used, and to the experimental setup to obtain accurate and precise dosimetric measurements.