Prophylactic defunctioning stomas improve clinical outcomes of anastomotic leak following rectal cancer resections: An analysis of the US Rectal Cancer Consortium.

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes. METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did or did not receive DLI during LAR. Secondary outcomes included risk factors for AL, receipt of adjuvant therapy, 3-year overall survival, and 3-year recurrence. RESULTS: Of 815 patients, 38 (4.7%) suffered AL after LAR. Patients with AL were more likely to be male, have unintentional preoperative weight loss, and are less likely to undergo DLI. On multivariable analysis, DLI remained protective against AL (p < 0.001). Diverted patients were less likely to undergo future surgical procedures including additional ostomy creation, completion proctectomy, or pelvic washout for AL. Subgroup analysis of 456 patients with locally advanced disease showed that DLI was correlated with increased receipt of adjuvant therapy for patients with and without AL on univariate analysis (SHR:1.59; [95% CI 1.19-2.14]; p = 0.002), but significance was not met in multivariate models. CONCLUSION: Lack of DLI and preoperative weight loss was associated with anastomotic leak. Fecal diversion may improve the timely initiation of adjuvant oncologic therapy. The long-term outcomes following routine diverting stomas warrant further study.

Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium.

BACKGROUND AND OBJECTIVES: Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS: The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS: Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS: SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.

Discharge Prescribing Protocol Decreases Opioids in Circulation and Does Not Increase Refills After Colorectal Surgery.

BACKGROUND: Up to 10% of patients develop new, persistent opioid use after surgery. We aimed to assess our prescribing practices and patient utilization of opioids after colorectal surgery. OBJECTIVE: This study aimed to implement an opioid-prescribing protocol that will minimize the number of postoperative opioids to decrease community circulation and persistent use by patients. DESIGN: This was a single-institution, prospective study based on questionnaires of postoperative patients in 2019 and 2020 to determine opioid prescribing and usage patterns. Based on these preliminary results, a protocol was implemented in which patients were discharged with 5 or 15 oxycodone 5 mg equivalents based on opioid usage in the 24 hours before discharge. Patients were surveyed after protocol implementation. SETTINGS: Our institution is a large referral center for surgical treatment of colorectal disease. PATIENTS: Adults who underwent inpatient abdominal colorectal procedures. MAIN OUTCOME MEASURES: End points included the number of opioids prescribed, number of prescribed opioids taken, and refill rate. Nonparametric testing was used. RESULTS: Of 77 eligible patients, 61 were opioid naive. Preprotocol, opioid-naive patients (n = 29) were prescribed a median of 30 (interquartile range [IQR], 30-45) tablets but took only 10 (IQR, 0-10; p < 0.0001). Eighty-three percent took 20 or fewer tablets. After protocol implementation, opioid-naive patients (n = 32) were prescribed fewer tablets (median 15; IQR, 7-15; p < 0.0001) but took a similar number of tablets as the preprotocol group (median 10; IQR, 0-10; p = 0.21). The refill rate remained similar (13.8% vs 18.8%; p = 0.60). Protocol adherence was 90.6%. LIMITATIONS: This study is limited by sample size, cohort heterogeneity, and generalizability. CONCLUSIONS: Patients took significantly fewer opioids than were prescribed. Our protocol limited overprescribing and resulted in fewer opioids in the community without opportunity costs such as increased refills. Long-term studies are needed to assess the effects of persistent opioid use after surgery. See Video Abstract at http://links.lww.com/DCR/C93 .

ANTECEDENTES: Hasta el 10% de los pacientes desarrollan un nuevo uso persistente de opioides después de la cirugía. Nuestro objetivo fue evaluar nuestras prácticas de prescripción y la utilización de opioides por parte de los pacientes después de la cirugía colorrectal. OBJETIVO: Nuestro objetivo es implementar un protocolo de prescripción de opioides que minimice la cantidad de opioides posoperatorios para disminuir la circulación en la comunidad y el uso persistente por parte de los pacientes. DISEÑO: Estudio prospectivo, de una sola institución, basado en cuestionarios de pacientes postoperatorios en 2019 y 2020 para determinar los patrones de prescripción y uso de opioides. Con base en estos resultados preliminares, se implementó un protocolo en el que los pacientes eran dados de alta con 5 o 15 equivalentes de oxicodona de 5 mg según el uso de opioides en las 24 horas previas al alta. Los pacientes fueron encuestados después de la implementación del protocolo. AJUSTES: Nuestra institución es un gran centro de referencia para el tratamiento quirúrgico de la enfermedad colorrectal. PACIENTES: Adultos que se sometieron a procedimientos colorrectales abdominales con hospitalización. PRINCIPALES MEDIDAS DE RESULTADO: Los criterios de valoración incluyeron el número de opioides recetados, el número de opioides recetados tomados y la tasa de reabastecimiento. Se utilizaron pruebas no paramétricas. RESULTADOS: De 77 pacientes elegibles, 61 no habian recibido opioides. A los pacientes sin tratamiento previo con opioides antes del protocolo (n = 29) se les prescribió una mediana de 30 (rango intercuartilico [RIC] 30­45) comprimidos, pero solo tomaron 10 (RIC 0.10, p < 0,0001). El ochenta y tres por ciento tomo ≤20 comprimidos. Despues de la implementacion del protocolo, a los pacientes sin tratamiento previo con opioides (n = 32) se les prescribieron menos comprimidos (15; RIC 7.15, p < 0,0001), pero tomaron un numero similar antes de la intervención (10; RIC 0­10, p = 0,21). La tasa de reabastecimiento se mantuvo similar (13,8% frente a 18,8%, p = 0,60). La adherencia al protocolo fue del 90,6%. LIMITACIONES: Este estudio está limitado por el tamaño de la muestra, la heterogeneidad de la cohorte y la generalización. CONCLUSIONES: Los pacientes tomaron significativamente menos opioides de los prescritos. Nuestro protocolo limitó la prescripción excesiva y dio como resultados menos opioides en la comunidad sin costos de oportunidad, como el aumento de reabastecimiento. Se necesitan estudios a largo plazo para evaluar los efectos sobre el uso persistente de opioides después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C93 . (Traducción­Dr. Francisco M. Abarca-Rendon).

Management and Outcomes of Pathologic Upstaging of Clinical Stage I Rectal Cancers: An Exploratory Analysis.

BACKGROUND: Preoperative staging of clinical stage I rectal cancer can fail to diagnose T3 or nodal disease. Adjuvant treatment of these upstaged patients remains controversial. OBJECTIVE: The objective was to identify predictors of clinical stage I rectal cancer upstaging and quantify rates of local and systemic recurrence. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using data from the United States Rectal Cancer Consortium, a registry of 1881 rectal cancer resections performed at 6 academic medical centers. PATIENTS: There were a total of 94 clinical stage I rectal cancer patients who underwent proctectomy without preoperative therapy. MAIN OUTCOME MEASURES: The primary measures were incidence of pathologic upstaging, recurrence (local and systemic), and overall survival. RESULTS: Among 94 clinical stage I patients who underwent proctectomy without preoperative therapy, 23 (24.5%) were upstaged by surgical pathology. There were 6 pT3N0 patients, 8 pT1-2N+ patients, and 9 pT3N+ patients. There were no significant differences in demographic or clinical characteristics between upstaged and nonupstaged patients. Of the 6 patients who were upstaged to T3N0 disease, none received adjuvant therapy and none developed recurrence. Of the 17 patients who were upstaged to N+ disease, 14 (82%) received adjuvant chemotherapy and 6 (35%) received adjuvant chemoradiation. None developed a local recurrence, but 4 (24%) developed systemic recurrence, and 2 (12%) died of disease over a mean of 36 months of follow-up. Among the 9 pT3N+ patients, the systemic recurrence rate was 33%, despite 8 of 9 patients receiving adjuvant fluorouracil, leucovorin, and oxaliplatin. LIMITATIONS: Small sample size hinders the ability to draw significant conclusions. CONCLUSIONS: One in 4 patients with stage I rectal cancer had unrecognized T3 or nodal disease found on operative pathology. Occult nodal disease was associated with worse outcomes, despite receiving adjuvant therapy. Systemic recurrence was more common than local recurrence. See Video Abstract at http://links.lww.com/DCR/B885 . MANEJO Y RESULTADOS DEL AUMENTO DEL ESTADIO PATOLGICO DE LOS CNCERES DE RECTO EN ESTADIO CLNICO I UN ANLISIS EXPLORATORIO: ANTECEDENTES:El estadiaje pre-operatorio del cáncer de recto en fase clínica I puede ser erróneo en el diagnóstico T3 o en la diseminación ganglionar. El tratamiento adyuvante de estos pacientes sobre-estadificados ​​sigue siendo controvertido.OBJETIVO:El identificar los factores predictivos en fase clínica I del cáncer de recto y cuantificar las tasas de recurrencia local y sistémica.DISEÑO:Estudio de cohortes retrospectivo.AJUSTE:El estudio se realizó utilizando los datos del Consorcio del Cáncer de Recto de los Estados Unidos, con un registro de 1.881 resecciones oncológicas rectales realizadas en seis centros médicos académicos.PACIENTES:Un total de 94 pacientes con cáncer de recto en fase clínica I fueron sometidos a proctectomía sin terapia preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la incidencia del sobre-estadiaje histopatológico, la recurrencia (local y sistémica) y la sobrevida general.RESULTADOS:De 94 pacientes en fase clínica I que se sometieron a una proctectomía sin terapia preoperatoria, 23 (24,5%) fueron sobre-estadiados ​​por la histopatología quirúrgica. Hubieron 6 pacientes pT3N0, 8 pT1-2N + y 9 pT3N +. No hubo diferencias significativas en las características demográficas o clínicas entre los pacientes sobre-estadiados ​​y los no sobre-estadiados. De los 6 pacientes que fueron sobre-estadiados en la enfermedad T3N0, ninguno de ellos recibió terapia adyuvante y ninguno recidivó. De los 17 pacientes que fueron sobre-estadiados a la enfermedad N +, 14 (82%) recibieron quimioterapia adyuvante y 6 (35%) recibieron quimio-radioterapia adyuvante. Ninguno desarrolló recidiva local, pero 4 (24%) desarrollaron recidiva sistémica y 2 (12%) murieron a causa de la enfermedad durante el seguimiento medio de 36 meses. Entre los 9 pacientes con pT3N +, la tasa de recidiva sistémica fue del 33%, a pesar de que 8 de 9 pacientes recibieron fluorouracilo, leucovorina y oxaliplatino como quimio-adyuvantes.LIMITACIONES:El tamaño pequeño de la muestra dificulta la capacidad de obtener conclusiones significativas.CONCLUSIONES:Uno de cada cuatro pacientes con cáncer de recto en estadío I presentaba enfermedad ganglionar o T3 no descrita en la histopatología operatoria. La enfermedad ganglionar oculta se asoció con peores resultados, a pesar de recibir terapia adyuvante. La recidiva sistémica fue más común que la recidiva local. Consulte Video Resumen en http://links.lww.com/DCR/B885 . (Traducción-Dr. Xavier Delgadillo ).

Perioperative Complications After Proctectomy for Rectal Cancer: Does Neoadjuvant Regimen Matter?

OBJECTIVE: Investigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer. SUMMARY OF BACKGROUND DATA: Neoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated. METHODS: This single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed. RESULTS: Of 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome. CONCLUSION: In rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT.

Development and Assessment of a Clinical Calculator for Estimating the Likelihood of Recurrence and Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, and Surgery.

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed. Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score. Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using Cox proportional hazards and multivariable regression analyses with restricted cubic splines. Because patients with complete pathological response to neoadjuvant therapy had uniformly favorable outcomes, their predictions were obtained separately. The study included 1400 patients with stage II or III rectal cancer who received treatment with chemotherapy, radiotherapy, and surgery at 2 comprehensive cancer centers (Memorial Sloan Kettering [MSK] Cancer Center and Siteman Cancer Center [SCC]) between January 1, 1998, and December 31, 2017. Patients from the MSK cohort received chemoradiation, surgery, and adjuvant chemotherapy from January 1, 1998, to December 31, 2014; these patients were randomly assigned to either a model training group or an internal validation group. Models were externally validated using data from the SCC cohort, who received either chemoradiation, surgery, and adjuvant chemotherapy (chemoradiotherapy group) or short-course radiotherapy, consolidation chemotherapy, and surgery (total neoadjuvant therapy with short-course radiotherapy group) from January 1, 2009, to December 31, 2017. Data were analyzed from March 1, 2020, to January 10, 2021. Exposures: Chemotherapy, radiotherapy, chemoradiotherapy, and surgery. Main Outcomes and Measures: Recurrence-free survival and OS were the outcome measures, and the discriminatory performance of the clinical calculators was measured with concordance index and calibration plots. The ability of the clinical calculators to predict RFS and OS was compared with that of the AJCC staging system and the NAR score. The models for RFS and OS among patients with incomplete pathological response included postoperative pathological tumor category, number of positive lymph nodes, tumor distance from anal verge, and large- and small-vessel venous and perineural invasion; age was included in the risk model for OS. The final clinical calculators provided RFS and OS estimates derived from Kaplan-Meier curves for patients with complete pathological response and from risk models for patients with incomplete pathological response. Results: Among 1400 total patients with locally advanced rectal cancer, the median age was 57.8 years (range, 18.0-91.9 years), and 863 patients (61.6%) were male, with tumors at a median distance of 6.7 cm (range, 0-15.0 cm) from the anal verge. The MSK cohort comprised 1069 patients; of those, 710 were assigned to the model training group and 359 were assigned to the internal validation group. The SCC cohort comprised 331 patients; of those, 200 were assigned to the chemoradiotherapy group and 131 were assigned to the total neoadjuvant therapy with short-course radiotherapy group. The concordance indices in the MSK validation data set were 0.70 (95% CI, 0.65-0.76) for RFS and 0.73 (95% CI, 0.65-0.80) for OS. In the external SCC data set, the concordance indices in the chemoradiotherapy group were 0.71 (95% CI, 0.62-0.81) for RFS and 0.72 (95% CI, 0.59-0.85) for OS; the concordance indices in the total neoadjuvant therapy with short-course radiotherapy group were 0.62 (95% CI, 0.49-0.75) for RFS and 0.67 (95% CI, 0.46-0.84) for OS. Calibration plots confirmed good agreement between predicted and observed events. These results compared favorably with predictions based on the AJCC staging system (concordance indices for MSK validation: RFS = 0.69 [95% CI, 0.64-0.74]; OS = 0.67 [95% CI, 0.58-0.75]) and the NAR score (concordance indices for MSK validation: RFS = 0.56 [95% CI, 0.50-0.63]; OS = 0.56 [95% CI, 0.46-0.66]). Furthermore, the clinical calculators provided more individualized outcome estimates compared with the categorical schemas (eg, estimated RFS for patients with AJCC stage IIIB disease ranged from 7% to 68%). Conclusions and Relevance: In this prognostic study, clinical calculators were developed and validated; these calculators provided more individualized estimates of the likelihood of RFS and OS than the AJCC staging system or the NAR score among patients with rectal cancer who received multimodal treatment. The calculators were easy to use and applicable to both short- and long-course radiotherapy regimens, and they may be used to inform surveillance strategies and facilitate future clinical trials and statistical power calculations.

Travel Time to a High Volume Center Negatively Impacts Timing of Care in Rectal Cancer.

BACKGROUND: Regionalization of rectal cancer surgery may lead to worse disease free survival owing to longer travel time to reach a high volume center yet no study has evaluated this relationship at a single high volume center volume center. MATERIALS AND METHODS: This was a retrospective review of rectal cancer patients undergoing surgery from 2009 to 2019 at a single high volume center. Patients were divided into two groups based on travel time. The primary outcome was disease-free survival (DFS). Additional outcomes included treatment within 60 d of diagnosis, completeness of preoperative staging, and evaluation by a colorectal surgeon prior to initiation of treatment. RESULTS: A lower proportion of patients with long travel time began definitive treatment within 60 d of diagnosis (74.0% versus 84.0%, P= 0.01) or were seen by the treating colorectal surgeon before beginning definitive treatment (74.8% versus 85.4%, P < 0.01). On multivariable logistic regression analysis, patients with long travel time were significantly less likely to begin definitive treatment within 60 d of diagnosis (OR = 0.54; 95% CI = 0.31-0.93) or to be evaluated by a colorectal surgeon prior to initiating treatment (OR = 0.45; 95% CI = 0.25-0.80). There were no significant differences in DFS based on travel time. CONCLUSIONS: Although patients with long travel times may be vulnerable to delayed, lower quality rectal cancer care, there is no difference in DFS when definitive surgery is performed at a high volume canter. Ongoing research is needed to identify explanations for delays in treatment to ensure all patients receive the highest quality care.

Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer.

PURPOSE: Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. METHODS: Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. RESULTS: The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. CONCLUSION: This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.

Adenoma-like adenocarcinoma: clinicopathologic characterization of a newly recognized subtype of colorectal carcinoma.

The 5th edition of the World Health Organization (WHO) Classification of Tumours (Digestive System) recognizes a new subtype of colorectal adenocarcinoma, called adenoma-like adenocarcinoma. In this study, we sought to determine its clinicopathologic associations and how it is comparable with adenocarcinoma, of no special type (NOS). We retrospectively reviewed all available archival slides of stage I-III colonic adenocarcinoma resection specimens at our institution from 2013 to 2016.Ninety-one cases were classified as adenoma-like adenocarcinoma, and 251 cases were classified as adenocarcinoma, NOS. Of the adenoma-like adenocarcinoma cases, a majority (65 cases, 71%) were composed exclusively of adenoma-like features, designated as pure adenoma-like adenocarcinoma, whereas in the rest, the component of adenoma-like morphology was more than 50% but less than 100%, designated as mixed adenoma-like adenocarcinoma. Compared with adenocarcinoma, NOS, adenoma-like adenocarcinoma cases were significantly associated with the absence of tumor budding (P < 0.001), the absence of an immature/myxoid desmoplastic reaction (P < 0.001), the presence of intraepithelial tumor-infiltrating lymphocytes (P = 0.006), involvement of fewer lymph nodes ( P < 0.001), fewer tumor deposits (P = 0.042), lower pT stage (P = 0.047), lower pN stage (P < 0.001), and consequently the pTNM prognostic group (P < 0.001), as well as better recurrence-free survival (RFS), as per univariate analysis than adenocarcinoma, NOS cases (P = 0.026) but not as per multivariate analysis. However, mixed adenoma-like adenocarcinoma had a worse RFS than pure adenoma-like adenocarcinoma (hazard ratio = 1.639, 95% confidence interval = 0.494-5.437). Our findings not only support the importance of distinguishing this new subtype of colorectal adenocarcinoma but also raise the question whether mixed adenoma-like adenocarcinoma cases should be included in this category, and if so, whether 50% is an appropriate cutoff, as currently defined by the WHO.

Fragmented Care in the Treatment of Rectal Cancer and Time to Definitive Therapy.

BACKGROUND: The National Accreditation Program for Rectal Cancer (NAPRC) emphasizes a multidisciplinary approach for treating rectal cancer and has developed performance measures to ensure that patients receive standardized care. We hypothesized that rectal cancer patients receiving care at multiple centers would be less likely to receive timely and appropriate care. STUDY DESIGN: A single institution retrospective review of a prospectively maintained database was performed. All patients undergoing proctectomy and ≤1 other treatment modality (eg radiation and/or chemotherapy) for Stage II/III rectal adenocarcinoma were included. Unified care was defined as receiving all modalities of care at our institution, and fragmented care was defined as having at least 1 treatment modality at another institution. RESULTS: From 2009 to 2019, 415 patients met inclusion criteria, with 197 (47.5%) receiving fragmented care and 218 (52.5%) receiving unified care. The unified cohort patients were more likely to see a colorectal surgeon before starting treatment (89.0% vs 78.7%, p < 0.01) and start definitive treatment within 60 days of diagnosis (89.0% vs 79.7%, p = 0.01). On adjusted analysis, unified care patients were 2.78 times more likely to see a surgeon before starting treatment (95% CI 1.47-5.24) and 2.63 times more likely to start treatment within 60 days (95% CI 1.35-5.13). There was no difference in 90-day mortality or 5-year disease-free survival. CONCLUSIONS: This retrospective cohort study suggests patients with rectal cancer receiving fragmented care are at an increased risk of delays in care without any impact on disease-free survival. These findings need to be considered within the context of ongoing regionalization of rectal cancer care to ensure all patients receive optimal care, irrespective of whether care is delivered across multiple institutions.

Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical Function and Perioperative Complication in Major Abdominal Colorectal Operations.

BACKGROUND: Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) is a validated tool for capturing a patient's perception of their physical capacity. The goal of this study was to determine whether preoperative PF correlates with a risk of postoperative complications. STUDY DESIGN: Patients from a single-institution American College of Surgeons NSQIP database undergoing elective colorectal abdominal operations from January 2018 to June 2019 with a preoperative PROMIS-PF T-score were eligible for this retrospective study. Patients were divided into moderate to severe (score <40) and minimal to mild (score ≥40) physical disability cohorts. Primary outcomes were any complication and any Clavien-Dindo grade III or higher complication. Multivariate logistic regression was performed. RESULTS: In total, 249 patients were included: 78 (31%) with self-scored moderate to severe disability and 171 (69%) with minimal to mild disability. Patients who scored as moderate to severe disability had a higher frequency of comorbidities and an open operative approach compared with patients with minimal to mild disability. These patients then had higher rates of any complication (37.2% vs 19.9%; p = 0.0036) and Clavien-Dindo grade III or higher complications (14.1% vs 7.6%; p = 0.017). After adjusting for patient factors, surgical procedure, and approach, patients scoring as moderate to severe disability were 2.00 times more likely (95% CI, 1.05 to 3.84; p = 0.036) to have any complication and 2.76 times more likely (95% CI, 1.07 to 7.14; p = 0.036) to have a Clavien-Dindo grade III or higher complication. CONCLUSIONS: Moderate to severe PF disability score is associated with increased risk of postoperative complications among patients undergoing colorectal operations. PROMIS-PF T-score can be a useful tool to identify patients who would benefit from targeted preoperative interventions, such as patient education, nutritional optimization, and prehabilitation.

Patient-provider gender preference in colorectal surgery.

BACKGROUND: Preference for a gender concordant surgeon has been demonstrated when the chief complaint is perceived as private. We aimed to investigate this phenomenon among colorectal patients. METHODS: A 3-week prospective, observational, quality improvement study was performed. Schedulers recorded all new patient calls and factors influencing patient selection of surgeon. Demographic information was obtained. Descriptive statistics were performed. RESULTS: There were 60 new patients scheduled; 35 (58.3%) female. Ten(16.7%) chose a surgeon based on gender; 70% of those with gender requests (GR) were female (70%), and 80% were gender-concordant. Seven (70%) of those with GR had anorectal complaints. Of all patients with anorectal complaints, 20.6% had a GR vs. 11.5% non-anorectal (p = 0.49). CONCLUSIONS: A considerable percentage of patients make a GR when seeking treatment, especially for anorectal disease. Departments should be mindful of the sensitive nature of many colorectal diseases and strive to diversify accordingly in order to create safe environments for the optimal delivery of patient-centered care.

Clinicopathologic determinants of pathologic treatment response in neoadjuvant treated rectal adenocarcinoma.

Neoadjuvant treatment (NAT) followed by total mesorectal excision is currently considered the standard of treatment for rectal adenocarcinoma. The degree of pathologic treatment response (pTR) correlates significantly with the recurrence free survival and overall survival (OS). However, it remains unclear which clinical and pathologic factors are associated with a more robust response to NAT, including showing pathologic complete response (pCR). Chemokine receptor 4 (CXCR4) overexpression has been associated with unfavorable OS in some studies. In this study, we sought to evaluate the clinicopathologic determinants of pTR in neoadjuvant treated rectal adenocarcinoma (NAT-RA). We retrospectively identified 91 patients who underwent pre-treatment diagnostic biopsy, NAT, and surgical resection at our institution. The archival slides were reviewed for pathologic features in the pre-treatment biopsies and for assessment of pTR in the resection specimens according to the current College of American Pathologist (CAP)'s guidelines. pCR was obtained in 16.5% of the cases, whereas 20.9% had near pCR, 30.8% had partial response, and 31.9% had a poor/no response. CXCR4 immunohistochemical analysis was also performed on the pre-treatment biopsies. Lower pre-treatment cT-stage (p = 0.019) and pre-treatment AJCC cTNM stage groups (p = 0.004), longer time interval between completion of NAT and resection (p = 0.022), and presence of tumor-infiltrating lymphocytes in the pre-treatment biopsies (p = 0.019) were significantly associated with a better pTR. CXCR4 nuclear expression was associated with a lower percentage of residual tumor (p = 0.036). Pre-treatment CEA levels, tumor differentiation, CAP treatment response groups and lower percentage of residual tumor were associated with a better OS.

Increased efficiency of endocrine procedures performed in an ambulatory operating room.

BACKGROUND: Thyroid and parathyroid procedures historically have been viewed as inpatient procedures. Because of the advancements in surgical techniques, these procedures were transferred from the inpatient operating room (OR) to the outpatient OR at a single academic institution approximately 7 y ago. The goal of this study was to determine whether this change has decreased turnover times and maximized OR utilization. METHODS: We performed a retrospective review of 707 patients undergoing thyroid (34%) and parathyroid (66%) procedures by a single surgeon at our academic institution between 2005 and 2008. Inpatient and outpatient groups were compared using Student t-test, chi-square test, or the Kruskal-Wallis test where appropriate. Multiple regression analysis was used to determine how patient and hospital factors influenced turnover times. RESULTS: Turnover times were significantly lower in the outpatient OR (mean 18 ± 0.7 min) when compared with the inpatient OR (mean 36 ± 1.4 min) (P < 0.001). When compared by type of procedure, all turnover times remained significantly lower in the outpatient OR. Patients in both ORs were similar in age, gender, and comorbidities. However, inpatients had a higher mean American Society of Anesthesiologists score (2.30 versus 2.13, P < 0.001) and were more likely to have an operative indication of cancer (23.1% versus 9.2%, P < 0.001). Using multiple regression, the inpatient OR remained highly significantly associated with higher turnover times when controlling for these small differences (P < 0.001). CONCLUSIONS: Endocrine procedures performed in the outpatient OR have significantly faster turnover times leading to cost savings and greater OR utilization for hospitals.

Unilateral thyroidectomy for the treatment of benign multinodular goiter.

BACKGROUND: Benign multinodular goiter (MNG) is one of the most commonly treated thyroid disorders. Although bilateral resection is the accepted surgical treatment for bilateral MNG, the appropriate surgical resection for unilateral MNG continues to be debated. Bilateral resection generally has lower recurrence rates but higher complication rates than unilateral resection. Therefore, the purpose of this study was to define the recurrence and complication rates of unilateral and bilateral resections to determine the appropriate intervention for patients with unilateral, benign MNG. METHODS: We reviewed a prospectively maintained database of all patients who underwent a thyroidectomy for treatment of benign MNG at a single institution between May 1994 and December 2011. All patients with bilateral MNG were treated with bilateral resection. Surgical treatment for unilateral MNG was determined by surgeon preference, with all but one surgeon opting for unilateral resection to treat unilateral MNG. Data were reported as means ± standard error of the mean. Chi-squared analysis was used to determine statistical significance at a level of P < 0.05. RESULTS: A total of 683 patients underwent thyroidectomy for MNG. Of these patients, 420 (61%) underwent unilateral resection and 263 patients (39%) underwent total thyroidectomy. The mean age was 52 ± 17 y, and 542 patients (79%) were female. The mean follow-up time was 46.1 ± 1.9 mo. The rate of recurrent disease was similar between unilateral (2%, n = 10) and bilateral (1%, n = 3) resections (P = 0.248). Unilateral resection patients had a lower total complication rate than patients with bilateral resections (8% versus 26%, P < 0.001); however, there was no difference in the rate of permanent complications (0.2% versus 1%, P = 0.133). Thyroid hormone replacement was rare in unilateral resection patients but necessary in all patients with bilateral resection (19% versus 100%, P < 0.001). CONCLUSIONS: Patients that had unilateral resections endured less overall morbidities than those who had bilateral resections, and their risk of recurrent disease was similar. They were also significantly less likely to require lifelong hormone replacement therapy postoperatively. Although bilateral resection remains the recommended treatment for bilateral MNG, these data strongly support the use of unilateral thyroidectomy for the treatment of unilateral, benign MNG.

Hippocampus and medial prefrontal cortex contributions to trace and contextual fear memory expression over time.

Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion effects are observable within 30 d of training; (2) whether lesions of the ventral hippocampus (VH) produce temporally graded retrograde amnesia similar to DH lesions; and (3) whether the lesion-to-test interval critically contributes to these lesion deficits. In Experiment 1, excitotoxic lesions of the DH, VH, or mPFC were made at 1 or 30 d following trace fear conditioning. DH and VH lesioned animals showed a deficit in freezing to the tone at the recent, but not remote, timepoint. Medial PFC lesioned animals showed the opposite pattern. In Experiment 2, lesions to DH, VH, or mPFC were made 1 d following training, while testing occurred 30 d later. There were no deficits in freezing to the tone in any lesion condition compared to controls. These results suggest that systems consolidation of trace fear memory occurs within 30 d of acquisition, but does not depend on hippocampus-mPFC interactions during this period.

Synchronous and antecedent nonthyroidal malignancies in patients with papillary thyroid carcinoma.

BACKGROUND: There is a known association between the development of papillary thyroid cancer (PTC) after a primary nonthyroidal cancer (NTC). However, the prevalence of synchronous or antecedent NTCs in patients with PTC is undetermined, as are the clinicopathologic characteristics of PTC in these patients. STUDY DESIGN: A review was performed of our prospectively maintained PTC database between January 1995 and December 2010. Information collected included patient and tumor characteristics, medical history, PTC presentation, and treatment modality. RESULTS: Four hundred and thirty-three adult patients underwent thyroid resection and had PTC on final pathology. Sixty-seven cases of synchronous or antecedent NTCs were observed in 60 patients (13.9%). The most commonly associated antecedent NTCs were breast (n = 11), prostate (n = 8), and melanoma (n = 5), whereas renal cell carcinoma (n = 3) and melanoma (n = 3) were the synchronous NTCs most observed. Compared with patients without an NTC, those with an NTC were older (56.4 ± 15.5 years vs 44.9 ± 14.2 years; p < 0.0001), had experienced radiation exposure (35.0% vs 3.5%; p < 0.001), and more commonly presented with a thyroid mass incidentally on imaging (41.7% vs 9.1%; p ≤ 0.001). Papillary thyroid cancer tumor characteristics were similar between groups, except that NTC patients presented at a more advanced stage. However, when analyzed independently, primary tumor size, and nodal and distant metastases were comparable. CONCLUSIONS: The prevalence of synchronous or antecedent NTCs in patients surgically treated for PTC is 13.9%. These patients present with PTC tumor characteristics similar to those without additional NTCs, and should therefore be managed equivalently. In addition, surgeons should be aware of the frequency of synchronous PTC with these types of tumors and consider evaluation of the neck at the time of NTC diagnosis.