Evaluation of Urinalysis-Based Screening for Urothelial Carcinoma in Patients With Lynch Syndrome.

BACKGROUND: Approximately 5% to 10% of patients with Lynch syndrome develop urothelial carcinoma. Current screening recommendations vary and are based on expert opinion. Practices need to be evaluated for clinical effectiveness. Our program utilizes urinalysis as a screening test, followed by additional evaluation of microscopic hematuria. OBJECTIVE: This study aimed to determine the clinical utility of a urinalysis-based screening approach for urothelial cancers in patients with Lynch syndrome. DESIGN: This is a retrospective review of a prospectively maintained cohort. SETTING: Patients with Lynch syndrome were managed at a tertiary referral center. PATIENTS: All patients with a Lynch syndrome diagnosis who had a screening urinalysis done as part of our institutional screening protocol (N = 204) were included. MAIN OUTCOME MEASURES: A single-institution hereditary colorectal cancer syndrome registry was queried for patients with Lynch syndrome who had been screened for urothelial carcinomas by urinalysis. Demographics, genotype, family history of urothelial carcinoma, urinalysis results, and subsequent screenings and final diagnosis were gathered for patients between 2008 and 2017. RESULTS: Two hundred four asymptomatic patients underwent screening by urinalysis. Nineteen patients (9.3%) had microscopic hematuria and were further evaluated with urine cytology, imaging, cystoscopy, and/or Urology consultation. None of the 19 patients with microscopic hematuria had urothelial carcinoma. During the same study period, 5 of 204 (2.4%) patients with Lynch syndrome were diagnosed with urothelial cancer, and all presented with symptoms between screening intervals. LIMITATIONS: This is a retrospective study, and not all patients underwent the same secondary evaluation. CONCLUSIONS: No urothelial carcinomas were detected by screening urinalysis in our cohort of asymptomatic patients with Lynch syndrome. False-positive testing led to extensive, mostly uninformative, workups. If urothelial cancer screening is to continue, more effective screening approaches need to be identified. See Video Abstract at http://links.lww.com/DCR/B702. EVALUACIN DEL CRIBADO BASADO EN ANLISIS DE ORINA PARA CARCINOMA UROTELIAL EN PACIENTES CON SNDROME DE LYNCH: ANTECEDENTES:Aproximadamente el 5-10% de los pacientes con síndrome de Lynch desarrollan carcinoma urotelial. Las recomendaciones actuales de detección varían y se basan en la opinión de expertos. Las prácticas deben evaluarse para determinar su eficacia clínica. Nuestro programa utiliza el análisis de orina como prueba de detección, seguido de una evaluación adicional con hematuria microscópica.OBJETIVO:Determinar la utilidad clínica desde un enfoque de cribado basado en análisis de orina, para cánceres uroteliales en pacientes con síndrome de Lynch.DISEÑO:Revisión retrospectiva de una cohorte mantenida prospectivamente.ENTORNO CLINICO:Pacientes con síndrome de Lynch atendidos en un centro de referencia terciario.PACIENTES:Criterios de inclusión fueron todos los pacientes con diagnóstico de síndrome de Lynch realizándoles un análisis de orina de detección como parte de nuestro protocolo de detección institucional (N = 204).PRINCIPALES MEDIDAS DE VALORACION:Solicitando un registro de síndrome de cáncer colorrectal hereditario de una sola institución para pacientes con síndrome de Lynch previamente evaluados para carcinomas uroteliales mediante análisis de orina. Se recopilaron para los pacientes entre 2008 y 2017, datos demográficos, genotipo, antecedentes familiares de carcinoma urotelial, resultados del análisis de orina, posteriores exámenes de detección posteriores y diagnóstico final.RESULTADOS:Doscientos cuatro pacientes asintomáticos fueron sometidos a cribado mediante análisis de orina. Diecinueve pacientes (9,3%) tenían hematuria microscópica y fueron investigados más a fondo con citología de orina, imágenes, cistoscopia y / o consulta de urología. Ninguno de los 19 pacientes con hematuria microscópica tenían carcinoma urotelial. Durante el mismo período de estudio, 5 de 204 (2,4%) pacientes con síndrome de Lynch fueron diagnosticados con cáncer urotelial y todos presentaron presentando síntomas entre los intervalos de detección.LIMITACIONES:Estudio retrospectivo y no todos los pacientes sometidos a la misma evaluación secundaria.CONCLUSIONES:No se detectaron carcinomas uroteliales mediante análisis de orina de detección en nuestra cohorte de pacientes asintomáticos con síndrome de Lynch. Las pruebas de falsos positivos. Condujeron a estudios exhaustivos y en su mayoría poco informativos. Si se desea continuar con la detección del cáncer de urotelio, es necesario identificar enfoques de detección más efectivos. Consulte Video Resumen en http://links.lww.com/DCR/B702.

Guideline-Recommended Chemoradiation for Patients With Rectal Cancer at Large Hospitals: A Trend in the Right Direction.

BACKGROUND: Many patients with rectal cancer are treated at small, low-volume hospitals despite evidence that better outcomes are associated with larger, high-volume hospitals. OBJECTIVES: This study aims to examine trends of patients with rectal cancer who are receiving care at large hospitals, to determine the patient characteristics associated with treatment at large hospitals, and to assess the relationships between treatment at large hospitals and guideline-recommended therapy. DESIGN: This study was a retrospective cohort analysis to assess trends in rectal cancer treatment. SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Patterns of Care studies were used. PATIENTS: The study population consisted of adults diagnosed with stages II/III rectal cancer in 1990/1991, 1995, 2000, 2005, 2010, and 2015. MAIN OUTCOME MEASURES: The primary outcome was treatment at large hospitals (≥500 beds). The receipt of guideline-recommended preoperative chemoradiation therapy and postoperative chemotherapy was assessed for patients diagnosed in 2005+. RESULTS: Two thousand two hundred thirty-one patients were included. The proportion treated at large hospitals increased from 19% in 1990/1991 to 27% in 2015 (ptrend < 0.0001). Black race was associated with treatment at large hospitals (vs white) (OR, 1.73; 95% CI, 1.30-2.31), as was being 55 to 64 years of age (vs 75+), and diagnosis in 2015 (vs 1990/1991). Treatment in large hospitals was associated with twice the odds of preoperative chemoradiation, as well as younger age and diagnosis in 2010 or 2015 (vs 2005). LIMITATIONS: The study did not account for the change in the number of large hospitals over time. CONCLUSIONS: Results suggest that patients with rectal cancer are increasingly being treated in large hospitals where they receive more guideline-recommended therapy. Although this trend is promising, patients receiving care at larger, higher-volume facilities are still the minority. Initiatives increasing patient and provider awareness of benefits of specialized care, as well as increasing referrals to large centers may improve the use of recommended treatment and ultimately improve outcomes. See Video Abstract at http://links.lww.com/DCR/A994. QUIMIORRADIACIÓN RECOMENDADA EN GUÍAS PARA PACIENTES CON CÁNCER RECTAL EN HOSPITALES DE GRAN TAMAÑO: UNA TENDENCIA EN LA DIRECCIÓN CORRECTA: Muchos pacientes con cáncer rectal se tratan en hospitales pequeños y de bajo volumen a pesar de evidencia de que los mejores resultados se asocian con hospitales más grandes y de gran volumen. OBJETIVOS: Examinar las tendencias en los pacientes con cáncer rectal que reciben atención en hospitales de gran tamaño, determinar las características de los pacientes asociadas con el tratamiento en hospitales grandes y evaluar la relación entre el tratamiento en hospitales grandes y la terapia recomendada en guías. DISEÑO:: Este estudio fue un análisis de cohorte retrospectivo para evaluar las tendencias en el tratamiento del cáncer de recto. ESCENARIO: Se utilizaron datos de los estudios del programa Patrones de Atención, Vigilancia, Epidemiología y Resultados Finales (SEER) del Instituto Nacional de Cáncer (NIH). PACIENTES: La población de estudio consistió en adultos diagnosticados con cáncer rectal en estadio II / III en 1990/1991, 1995, 2000, 2005, 2010 y 2015. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue el tratamiento en hospitales grandes (≥500 camas). La recepción de quimiorradiación preoperatoria recomendada según las guías y la quimioterapia posoperatoria se evaluaron para los pacientes diagnosticados en 2005 y posteriormente. RESULTADOS: Se incluyeron 2,231 pacientes. La proporción tratada en los hospitales grandes aumentó del 19% en 1990/1991 al 27% en 2015 (ptrend < 0.0001). La raza afroamericana se asoció con el tratamiento en hospitales grandes (vs. blanca) (OR, 1.73; IC 95%, 1.30-2.31), al igual que 55-64 años de edad (vs ≥75) y diagnóstico en 2015 (vs 1990/1991). El tratamiento en los hospitales grandes se asoció con el doble de probabilidad de quimiorradiación preoperatoria, así como con una edad más temprana y diagnóstico en 2010 o 2015 (vs 2005). LIMITACIONES: El estudio no tomó en cuenta el cambio en el número de hospitales grandes a lo largo del tiempo. CONCLUSIONES: Los resultados sugieren que los pacientes con cáncer rectal reciben cada vez más tratamiento en hospitales grandes donde reciben terapia recomendada por las guías mas frecuentemente. Aunque esta tendencia es prometedora, los pacientes que reciben atención en hospitales más grandes y de mayor volumen siguen siendo una minoría. Las iniciativas que aumenten la concientización del paciente y del proveedor de servicios médicos sobre los beneficios de la atención especializada, así como el aumento de las referencias a centros grandes podrían mejorar el uso del tratamiento recomendado y, en última instancia, mejorar los resultados. Vea el Resumen en video en http://links.lww.com/DCR/A994.

Effect of BMI on outcomes in proctectomy.

BACKGROUND: The unique surgical challenges of proctectomy may be amplified in obese patients. We examined surgical outcomes of a large, diverse sample of obese patients undergoing proctectomy. OBJECTIVE: The purpose of this work was to determine whether increased BMI is associated with increased complications in proctectomy. DESIGN: This was a retrospective review. SETTINGS: The study uses the American College of Surgeons National Surgical Quality Improvement Program database (2010 and 2011). PATIENTS: Patients included were those undergoing nonemergent proctectomy, excluding rectal prolapse cases. Patients were grouped by BMI using the World Health Organization classifications of underweight (BMI <18.5); normal (18.5-24.9); overweight (25.0-29.9); and class I (30.0-34.9), class II (35.0-39.9), and class III (≥40.0) obesity. MAIN OUTCOME MEASURES: We analyzed the effect of preoperative and intraoperative factors on 30-day outcomes. Continuous variables were compared with Wilcoxon rank-sum tests and proportions with the Fisher exact or χ tests. Logistic regression controlled for the effects of multiple risk factors. RESULTS: Among 5570 patients, class I, II, and III obesity were significantly associated with higher rates of overall complications (44.0%, 50.8%, and 46.6% vs 38.1% for normal-weight patients; p < 0.05). Superficial wound infection was significantly higher in classes I, II, and III (11.6%, 17.8%, and 13.0% vs 8.0% for normal-weight patients; p < 0.05). Operative times for patients in all obesity classes were significantly longer than for normal-weight patients. On multivariate analysis, an obese BMI independently predicted complications; ORs (95% CIs) were 1.36 (1.14-1.62) for class I obesity, 1.99 (1.54-2.54) for class II, and 1.42 (1.02-1.96) for class III. LIMITATIONS: This study was a retrospective design with limited follow-up. CONCLUSIONS: Class I, II, and III obese patients were at significantly increased risk for morbidity compared with normal BMI patients. Class II obese patients had the highest rate of complications, a finding that deserves further investigation.

A matched case-control study of IBD-associated colorectal cancer: IBD portends worse outcome.

BACKGROUND AND OBJECTIVES: The effect of inflammatory bowel disease (IBD) on outcome in patients with colorectal cancer (CRC) remains unclear. Our objective is to evaluate oncologic outcomes of patients with IBD-associated CRC. METHODS: We retrospectively reviewed a prospectively maintained database to identify patients with IBD-associated CRC. Clinicopathologic variables and overall survival were compared to patients with sporadic CRC using a 2:1 matched-controlled analysis. RESULTS: Fifty-five patients with IBD and CRC were identified. On univariate analysis, CRC patients with IBD had a significantly shorter median overall survival (68.2 months vs. 204.3 months, P = 0.01) compared to patients with sporadic CRC. On multivariate analysis, after adjusting for N and M stage, IBD was associated with an increased risk of death compared to sporadic CRC (HR = 2.011, 95% CI 1.24-3.23, P = 0.004). Stage 3 CRC patients with IBD in particular showed significantly decreased survival (23.0 vs. 133.9 months, P = 0.008). CONCLUSIONS: In this study, patients with node-positive IBD-associated CRC had a significant increased risk of death and a shorter overall survival than those with sporadic disease and may require tailored adjuvant therapy and surveillance protocols. Continued investigation to elucidate the mechanisms that contribute to these observations is justified.

An initial experience with 85 consecutive robotic-assisted rectal dissections: improved operating times and lower costs with experience.

BACKGROUND: Data are limited about the robotic platform in rectal dissections, and its use may be perceived as prohibitively expensive or difficult to learn. We report our experience with the initial robotic-assisted rectal dissections performed by a single surgeon, assessing learning curve and cost. METHODS: Following IRB approval, a retrospective chart review was conducted of the first 85 robotic-assisted rectal dissections performed by a single surgeon between 9/1/2010 and 12/31/2012. Patient demographic, clinicopathologic, procedure, and outcome data were gathered. Cost data were obtained from the University HealthSystem Consortium (UHC) database. The first 43 cases (Time 1) were compared to the next 42 cases (Time 2) using multivariate linear and logistic regression models. RESULTS: Indications for surgery were cancer for 51 patients (60 %), inflammatory bowel disease for 18 (21 %), and rectal prolapse for 16 (19 %). The most common procedures were low anterior resection (n = 25, 29 %) and abdominoperineal resection (n = 21, 25 %). The patient body mass index (BMI) was statistically different between the two patient groups (Time 1, 26.1 kg/m(2) vs. Time 2, 29.4 kg/m(2), p = 0.02). Complication and conversion rates did not differ between the groups. Mean operating time was significantly shorter for Time 2 (267 min vs. 224 min, p = 0.049) and remained significant in multivariate analysis. Though not reaching statistical significance, the mean observed direct hospital cost decreased ($17,349 for Time 1 vs. $13,680 for Time 2, p = 0.2). The observed/expected cost ratio significantly decreased (1.47 for Time 1 vs. 1.05 for Time 2, p = 0.007) but did not remain statistically significant in multivariate analyses. CONCLUSIONS: Over the series, we demonstrated a significant improvement in operating times. Though not statistically significant, direct hospital costs trended down over time. Studies of larger patient groups are needed to confirm these findings and to correlate them with procedure volume to better define the learning curve process.

Characteristics and symptomatology of colorectal cancer in the young.

BACKGROUND: The incidence of colorectal cancer in patients <50 years has rapidly risen recently. Understanding the presenting symptoms may facilitate earlier diagnosis. We aimed to delineate patient characteristics, symptomatology, and tumor characteristics of colorectal cancer in a young population. METHODS: A retrospective cohort study was conducted evaluating patients <50 years diagnosed between 2005 and 2019 with primary colorectal cancer at a university teaching hospital. The number and character of colorectal cancer-related symptoms at presentation was the primary outcome measured. Patient and tumor characteristics were also collected. RESULTS: Included were 286 patients with a median age of 44 years, with 56% <45 years. Nearly all patients (95%) were symptomatic at presentation, with 85% having 2 or more symptoms. The most common symptoms were pain (63%), followed by change in stool habits (54%), rectal bleeding (53%), and weight loss (32%). Diarrhea was more common than constipation. More than 50% had symptoms for at least 3 months before diagnosis. The number and duration of symptoms were similar in patients older than 45 compared to those younger. Most cancers were left-sided (77%) and advanced stage at presentation (36% stage III, 39% stage IV). CONCLUSION: In this cohort of young patients with colorectal cancer, the majority presented with multiple symptoms having a median duration of 3 months. It is essential that providers be mindful of the ever-increasing incidence of colorectal malignancy in young patients, and that those with multiple, durable symptoms should be offered screening for colorectal neoplasms based on symptoms alone.

Surgical management of large, connected perineal and pelvic epidermal inclusion cysts mimicking a dumbbell-shaped lesion in an adult male.

INTRODUCTION AND IMPORTANCE: Epidermal inclusion cysts are a common benign finding, and they are predominantly asymptomatic. They can rarely form in the pelvis or abdomen, however, and may cause symptoms secondary to mass effect. This case highlights management of an anterectal epidermal inclusion cyst connected to the perineal cyst, mimicking a dumbbell-shaped lesion, found in a male. CASE PRESENTATION: This is a unique case of a 21-year-old Caucasian male with a palpable perineal mass, lower extremity hypoesthesia, and constipation who was found to have a complex-shaped cyst on computed tomography and magnetic resonance imaging. This was ultimately managed with a two-stage perineal and transabdominal resection. CLINICAL DISCUSSION: This case highlights that perineal epidermal inclusion cysts may have pelvic extension, especially in patients with additional new-onset neurologic, gastrointestinal, or urologic symptoms. These symptoms should completely resolve after resection. Additionally, resection is recommended to prevent complications including malignant degeneration and fistulization. CONCLUSION: This is the first reported case of an anterectal, epidermal inclusion cyst connected to a perineal cyst found in a male. Perineal and pelvic cysts may be synchronous and may be connected through the pudendal canal. These masses can be safely removed via a combined perineal and transabdominal resection. The connecting portion of lesions that have both pelvic and perineal components should be meticulously identified and dissected because even a thin, patent segment - if left unresected - may result in lesion recurrence.

Staged Approaches to Restorative Proctocolectomy with Ileoanal Pouch-When and Why?

Restorative proctocolectomy (RPC) with ileal pouch anal-anastomosis (IPAA) is commonly performed for patients with ulcerative colitis, familial adenomatous polyposis, and selected phenotypes of Crohn's disease (CD). Due to concerns about the effects of surgical complications on pouch functional outcomes, debate remains surrounding when and whether RPC with IPAA should be performed in a staged manner. Particularly debated are the timings of the IPAA, whether it is constructed at time of the proctocolectomy and whether to utilize temporary fecal diversion with a loop ileostomy. RPC with IPAA can be performed in one, two, or three stages, with each stage typically separated by 3-6 months. Proponents of a staged approach argue that poor pouch function, which is often a result of IPAA complications, including leak and infection, can be difficult to overcome and mandate additional, major surgeries, and that staging pouch creation and pairing with a protective ileostomy reduce those complications. However, subjecting patients to multiple surgeries and prolonging their time with an ileostomy present unique risks as well. Surgeons' experience and preference and patient characteristics need to be considered when determining operative planning. Highly selected patients with CD can be considered for RPC with IPAA, although with an acknowledgment of inherently higher pouch failure rates. Understanding the short- and long-term consequences of RPC with IPAA construction can help surgeons determine the appropriate approach.

Intra-abdominal and Anorectal Abscesses.

Intra-abdominal and anorectal abscesses are common pathologies seen in both inpatient and outpatient settings. To decrease morbidity and mortality, early diagnosis and treatment are essential. After adequate drainage via a percutaneous or incisional approach, patients need to be monitored for worsening symptoms or recurrence and evaluated for the underlying condition that may have contributed to abscess formation.

Teaching and Mentoring Early in Surgical Practice.

BACKGROUND: Transitioning from trainee to independent surgeon is challenging, with teaching and mentoring learners adding complexity. This study aimed to identify benefits and challenges of teaching and mentoring residents early in surgical practice. MATERIALS AND METHODS: A mixed-methods survey with multiple choice and open-ended questions was developed for early career (first 3 years) and experienced (more than 3 years) surgeons working with residents. The survey was initially piloted by 6 surgeons, revised according to feedback and distributed on Twitter. Quantitative and qualitative analyses were performed. RESULTS: Seventy-three valid responses were analyzed, 21 (25%) from early career surgeons and 53 (75%) from experienced surgeons. The majority were women (62%), practiced in academics (78%) and lived in the United States (76%). Most of the early career and experienced surgeons selected the operating room as the most teaching challenging location (62% early career; and 60% experienced). Top teaching challenges of early career surgeons were the need to focus on own skills (24%) and concern for patient safety/outcomes (24%), while experienced surgeons reported need to focus on own skills (23%) and difficulty giving up control (23%). Open-ended responses identified themes related to teaching and mentoring. Comments highlighted benefits of organizational support to facilitate teaching and mentoring and negative experiences due to resident learners not respecting early career surgeons. DISCUSSION: This pilot study explores an area not previously studied. Early career surgeons and experienced surgeons find many similar challenges and benefits of teaching and mentoring residents. Challenges and themes identified can guide early career surgeons and organizations with regard to teaching and mentoring.

Impact of routine mismatch repair screening on genetic counseling and surgical management in colorectal cancer patients.

BACKGROUND: Mismatch repair (MMR) deficiency in colorectal cancer (CRC) should prompt consideration of genetic counseling (GC) as a Lynch syndrome (LS) diagnosis may have several implications for the patient and family. The study aims were to examine how routine MMR testing influences the rate of GC and surgical resection extent. METHODS: A single-institution retrospective review was performed on CRC specimens (including colonoscopic biopsies) routinely screened for MMR deficiency from 2012 to 2018. MLH1-deficient cancers with mutated BRAF or MLH1-promoter hypermethylation were excluded. RESULTS: MMR deficiency was identified in 295 of 1139 CRC specimens. After exclusions, 57 patients remained. Forty-two patients (74%) were identified preoperatively, and 35 (83%) were referred to GC: 16 were seen preoperatively, 9 postoperatively. Eight patients were diagnosed with Lynch syndrome (LS) preoperatively: 2 had no resection, 2 underwent segmental resection and 4 underwent extended resection. CONCLUSIONS: Most MMR-deficient patients were identified and referred to GC preoperatively, though not all were seen. Of the preoperatively diagnosed LS patients, half underwent extended resection. Barriers to GC and decision-making around resection extent bears further study.

Male sex, ostomy, infection, and intravenous fluids are associated with increased risk of postoperative ileus in elective colorectal surgery.

BACKGROUND: Postoperative ileus is a common and costly complication after elective colorectal surgery. Effects of intravenous fluid administration remain controversial, and the effect of ostomy construction has not been fully evaluated. Various restrictive intravenous fluid protocols may adversely affect renal function. We aimed to investigate the impact of intestinal reconstruction and intravenous fluid on ileus and renal function after colorectal resection under an enhanced recovery protocol. METHODS: A retrospective study of a prospectively maintained institutional database for a tertiary academic medical center following National Surgical Quality Improvement Program standards was reviewed, analyzing elective colorectal resections performed under enhanced recovery protocol from 2015 to 2018. Postoperative ileus was defined as nasogastric decompression, nil per os >3 days postoperatively, or nasogastric tube insertion. Patients with and without ileus were compared. Intravenous fluid and different anastomoses and ostomies were investigated. Acute kidney injury was a secondary outcome, due to the potential of renal damage with restriction of intravenous fluid volume during and after surgery and controversy in current literature in this matter. RESULTS: Postoperative ileus occurred in 18.5% of patients (n = 464). Male sex (odds ratio 1.97, 95% confidence interval 1.12-3.52) and postoperative infection (odds ratio 2.13, 95% confidence interval 1.03-4.35) were associated with ileus. Compared to colorectal anastomosis, ileostomy/ileorectal anastomosis had the highest risk of ileus (odds ratio 4.9, 95% confidence interval 2.33-11.3), colostomy second highest (odds ratio 3.3, 95% confidence interval 1.35-8.39), while ileocolic anastomosis did not significantly differ (odds ratio 2.06, 95% confidence interval 0.69-5.85) on multivariate analysis. Each liter of intravenous fluid within the first 72 hours significantly correlated with postoperative ileus (odds ratio 1.41, 95% confidence interval 1.27-1.59). Rates of acute kidney injury did not differ (P = .18). CONCLUSION: Each additional liter of intravenous fluid given in the first 72 hours increased the risk of postoperative ileus 1.4-fold. There is substantially higher risk of ileus with male sex, infection, ileostomy/ileorectal anastomosis, and colostomy. Judicious use of intravenous fluid, as described in our enhanced recovery protocol, is not detrimental for renal function in the setting of normal baseline.

The Role of Multiagent Chemoradiation in the Management and Prognosis of Anal Squamous Cell Carcinoma.

INTRODUCTION: The standard treatment for anal squamous cell carcinoma (ASCC) is multiagent chemotherapy with radiation (CRT). This is based on several randomized trials demonstrating lower recurrence and colostomy-free survival rates with multiagent CRT; however, these studies could not confirm an overall survival (OS) benefit. We hypothesized that the lack of improved OS was due to limited sample sizes and follow-up, and that multiagent CRT is associated with higher OS. METHODS: The National Cancer Database was queried for patients diagnosed with stages I, II, and II ASCC and received between 45 and 59.4 Gy of radiation between 2004 and 2015. OS of patients receiving multiagent CRT compared to monoagent CRT and radiation alone was analyzed across stages. RESULTS: A total of 10,438 patients received multiagent CRT, 1163 had monoagent CRT and 446 received radiation alone. Compared to the other two groups, patients receiving multiagent CRT were younger, had fewer comorbidities, and more advanced disease (all p < 0.001). After adjusting for available confounders, multiagent CRT remained independently associated with higher OS for stages II and III ASCC. A subset analysis of patients ≥ 70 years demonstrated similar survival between monoagent versus multiagent CRT across all stages. CONCLUSION: Multiagent CRT is associated with an OS benefit compared to monoagent CRT or radiation alone for stages II and III, but not stage I ASCC. Monoagent CRT may represent an adequate treatment for selected patients ≥ 70 years. The benefit of multiagent CRT should be balanced against treatment-related toxicities depending on disease stage and patient physiology.

Prospective Validation of the Iowa Rectal Surgery Risk Calculator.

BACKGROUND: The Iowa Rectal Surgery Risk Calculator estimates risk for proctectomy procedures. The Iowa Calculator performed well on NSQIP 2010-2011 training and 2005-2009 validation datasets, but was not prospectively validated and did not include low anterior resections. This study sought to demonstrate validity on new independent data, to update the calculator to include low anterior resection, and to compare performance to other risk assessment tools. METHODS: Non-emergent ACS-NSQIP proctectomy and low anterior resection data from 2010 to 2015 (n = 65,683) were included. The Iowa Calculator generated risk estimates for 30-day morbidity using 2012-2015 data. An Updated Calculator used 2010-2011 training data to include low anterior resection, with validation on 2012-2015 data. NSQIP data provided NSQIP Morbidity Model predictions and a custom web-script collected ACS-NSQIP Online Surgical Risk Calculator predictions for all patients. RESULTS: Proctectomy morbidity (not including low anterior resection) decreased from 40.4% in 2010-2011 to 37.0% in 2012-2015. Low anterior resection had lower morbidity (22.4% in 2012-15). The Iowa Calculator demonstrated good discrimination and calibration using 2012-2015 data (C-statistic 0.676, deviance + 9.2%). After including low anterior resection, the Updated Iowa Calculator performed well during training (c-statistic 0.696, deviance 0%) and validation (C-statistic 0.706, deviance + 7.9%). The Updated Iowa Calculator had significantly better discrimination and calibration than morbidity predictions from the ACS Online Calculator (C-statistic 0.693, P < 0.001, deviance - 28.1%) and NSQIP General/Vascular Surgery Model (C-statistic 0.703, P < 0.05, deviance - 40.8%). CONCLUSION: When applied to new independent data, the Iowa Calculator supplies accurate risk estimates. The Updated Iowa Calculator includes low anterior resection, and both are prospectively validated. Risk estimation by the Iowa Calculators was superior to ACS-provided risk tools.

Single-incision robotic colectomy: are costs prohibitive?

BACKGROUND: The feasibility, safety, and costs of single-incision robotic colectomy (SIRC) are not known. METHODS: A retrospective review was conducted, comparing the initial 29 consecutive SIRC procedures performed to 36 multiport laparoscopic colectomies (MLC). RESULTS: The groups did not differ significantly on age, body mass index, gender, ASA classification, smoking status, steroid usage or rate of diabetes. Procedure time, conversion rate, infectious complications and length of stay did not differ significantly. The ratio of observed:expected direct hospital costs statistically favoured MLC, although there was no statistical difference between groups for contribution margin, or for observed and expected direct hospital costs. CONCLUSIONS: These results demonstrate safety and technical feasibility for SIRC in selected patients with short-term outcomes and hospital costs comparable to MLC. Contribution margin remained positive and expected costs exceeded observed for SIRC. Increased costs for SIRC are a concern. The comparable but relatively high mortality in both groups may represent an institutional approach to colectomy where significant comorbidity is not a contraindication to minimally invasive surgery. Copyright © 2015 John Wiley & Sons, Ltd.

Hospital Characteristics Associated with Stage II/III Rectal Cancer Guideline Concordant Care: Analysis of Surveillance, Epidemiology and End Results-Medicare Data.

BACKGROUND: Evidence suggests that high-volume facilities achieve better rectal cancer outcomes. METHODS: Logistic regression was used to evaluate association of facility type with treatment after adjusting for patient demographics, stage, and comorbidities. SEER-Medicare beneficiaries who were diagnosed with stage II/III rectal adenocarcinoma at age ≥66 years from 2005 to 2009 and had Parts A/B Medicare coverage for ≥1 year prediagnosis and postdiagnosis plus a claim for cancer-directed surgery were included. Institutions were classified according to National Cancer Institute (NCI) designation, presence of residency program, or medical school affiliation. RESULTS: Two thousand three hundred subjects (average age = 75) met the criteria. Greater proportions of those treated at NCI-designated facilities received transrectal ultrasound (TRUS) or magnetic resonance imaging (MRI)-pelvis (62.1 vs. 29.9 %), neoadjuvant chemotherapy (63.9 vs. 41.8 %), and neoadjuvant radiation (70.8 vs. 46.3 %), all p < 0.0001. On multivariate analysis, odds ratios (95 % confidence intervals) for receiving TRUS or MRI, neoadjuvant chemotherapy, or neoadjuvant radiation among beneficiaries treated at NCI-designated facilities were 3.51 (2.60-4.73), 2.32 (1.71-3.16), and 2.66 (1.93-3.67), respectively. Results by residency and medical school affiliation were similar in direction to NCI designation. CONCLUSIONS: Those treated at hospitals with an NCI designation, residency program, or medical school affiliation received more guideline-concordant care. Initiatives involving provider education and virtual tumor boards may improve care.

Disruption of thioredoxin metabolism enhances the toxicity of transforming growth factor ß-activated kinase 1 (TAK1) inhibition in KRAS-mutated colon cancer cells.

Transforming growth factor ß-activated kinase 1 (TAK1) is critical for survival of many KRAS mutated colorectal cancer cells, and TAK1 inhibition with 5Z-7-oxozeaenol has been associated with oxidative stress leading to tumor cell killing. When SW 620 and HCT 116 human colon cancer cells were treated with 5µM 5Z-7-oxozeaenol, cell viability, growth, and clonogenic survival were significantly decreased. Consistent with TAK1 inhibition being causally related to thiol-mediated oxidative stress, 10mM N-acetylcysteine (NAC) partially reversed the growth inhibitory effects of 5Z-7-oxozeaenol. In addition, 5Z-7-oxozeaenol also increased steady-state levels of H2DCFDA oxidation as well as increased levels of total glutathione (GSH) and glutathione disulfide (GSSG). Interestingly, depletion of GSH using buthionine sulfoximine did not significantly potentiate 5Z-7-oxozeaenol toxicity in either cell line. In contrast, pre-treatment of cells with auranofin (Au) to inhibit thioredoxin reductase activity significantly increased levels of oxidized thioredoxin as well as sensitized cells to 5Z-7-oxozeaenol-induced growth inhibition and clonogenic cell killing. These results were confirmed in SW 620 murine xenografts, where treatment with 5Z-7-oxozeaenol or with Au plus 5Z-7-oxozeaenol significantly inhibited growth, with Au plus 5Z-7-oxozeaenol trending toward greater growth inhibition compared to 5Z-7-oxozeaenol alone. These results support the hypothesis that thiol-mediated oxidative stress is causally related to TAK1-induced colon cancer cell killing. In addition, these results support the hypothesis that thioredoxin metabolism is a critical target for enhancing colon cancer cell killing via TAK1 inhibition and could represent an effective therapeutic strategy in patients with these highly resistant tumors.

Loss of SOD3 (EcSOD) Expression Promotes an Aggressive Phenotype in Human Pancreatic Ductal Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDA) cells are known to produce excessive amounts of reactive oxygen species (ROS), particularly superoxide, which may contribute to the aggressive and refractory nature of this disease. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide in the extracellular environment. This study tests the hypothesis that EcSOD modulates PDA growth and invasion by modifying the redox balance in PDA. EXPERIMENTAL DESIGN: We evaluated the prognostic significance of EcSOD in a human tissue microarray (TMA) of patients with PDA. EcSOD overexpression was performed in PDA cell lines and animal models of disease. The impact of EcSOD on PDA cell lines was evaluated with Matrigel invasion in combination with a superoxide-specific SOD mimic and a nitric oxide synthase (NOS) inhibitor to determine the mechanism of action of EcSOD in PDA. RESULTS: Loss of EcSOD expression is a common event in PDA, which correlated with worse disease biology. Overexpression of EcSOD in PDA cell lines resulted in decreased invasiveness that appeared to be related to reactions of superoxide with nitric oxide. Pancreatic cancer xenografts overexpressing EcSOD also demonstrated slower growth and peritoneal metastasis. Overexpression of EcSOD or treatment with a superoxide-specific SOD mimic caused significant decreases in PDA cell invasive capacity. CONCLUSIONS: These results support the hypothesis that loss of EcSOD leads to increased reactions of superoxide with nitric oxide, which contributes to the invasive phenotype. These results allow for the speculation that superoxide dismutase mimetics might inhibit PDA progression in human clinical disease.