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Surgical site infection is a source of significant morbidity after colorectal surgery. Previous efforts to develop models that predict surgical site infection have had limited accuracy. Machine learning has shown promise in predicting post-operative outcomes by identifying non-linear patterns within large datasets.We sought to use machine learning to develop a more accurate predictive model for colorectal surgical site infections.Patients who underwent colorectal surgery were identified in the American College of Surgeons National Quality Improvement Program database from years 2012-2019 and were split into training, validation, and test sets. Machine learning techniques included random forest, gradient boosting, and artificial neural network. A logistic regression model was also created. Model performance was assessed using area under the receiver operating characteristic curve.A national, multicenter dataset.Patients who underwent colorectal surgery.The primary outcome (surgical site infection) included patients who experienced superficial, deep, or organ-space surgical site infections.The dataset included 275,152 patients after application of exclusion criteria. 10.7% of patients experienced a surgical site infection. Artificial neural network showed the best performance with area under the receiver operating characteristic curve of 0.769 (95% CI 0.762 - 0.777), compared with 0.766 (95% CI 0.759 - 0.774) for gradient boosting, 0.764 (95% CI 0.756 - 0.772) for random forest, and 0.677 (95% CI 0.669 - 0.685) for logistic regression. For the artificial neural network model, the strongest predictors of surgical site infection were organ-space surgical site infection present at time of surgery, operative time, oral antibiotic bowel prep, and surgical approach.Local institutional validation was not performed.Machine learning techniques predict colorectal surgical site infections with higher accuracy than logistic regression. These techniques may be used to identify patients at increased risk and to target preventative interventions for surgical site infection. See Video Abstract at http://links.lww.com/DCR/C88.

Distribution of colorectal cancer cases according to SMAD4 expression status and immune response to the tumor in validation cohort

Kaplan-Meier graphs in the validation cohort with number of subjects at risk showing colorectal cancer-specific survival according to SMAD4 status.

Kaplan-Meier graphs with number of subjects at risk comparing recurrence-free survival (RFS) by (a) TIL status, or (b) PLA status, with arrows indicating patients whose tumors were also SMAD4 loss.

Clinical, pathological, and molecular characteristics of colorectal cancer cases according to SMAD4 expression status in validation cohort

Ordinal logistic regression analyses to assess the association of SMAD4 expression status with lymphocytic reaction patterns in validation cohort

Purpose:SMAD4 has shown promise in identifying patients with colorectal cancer at high risk of recurrence or death.Experimental Design: A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance.Results:The discovery cohort consisted of 364 patients with stage I–IV colorectal cancer. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3–8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL), and lower peritumoral lymphocyte aggregate (PLA) scores (all P < 0.04). SMAD4 loss was associated with worse RFS (P = 0.02). When stratified by SMAD4 and immune infiltrate status, patients with SMAD4 loss and low TIL or PLA had worse RFS (P = 0.002 and P = 0.006, respectively). Among patients receiving 5-fluorouracil (5-FU)-based systemic chemotherapy, those with SMAD4 loss had a median RFS of 3.8 years compared with 13 years for patients with SMAD4 retained. In xenografted mice, the SMAD4-lost tumors displayed resistance to 5-FU. An independent cohort replicated our findings, in particular, the association of SMAD4 loss with decreased immune infiltrate, as well as worse disease-specific survival.Conclusions:Our data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate, supporting its use as a prognostic marker in patients with colorectal cancer.

Kaplan-Meier graph with number of subjects at risk comparing (a) SMAD4, (b) TIL, and (c) PLA status, separately, as well as (d) SMAD4 and TIL, and (e) SMAD4 and PLA, together, with recurrence-free survival (RFS) among only the MMR-proficient patients.

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BACKGROUND AND OBJECTIVES: Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compare the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS: This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS: 444 locally advanced rectal cancer patients managed by 5 surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p=0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS: While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that amongst expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.

PURPOSE: To compare the characteristics and outcomes of rectal cancer patients with local recurrence at a perianastomotic site (PA), a surgical field (SF) site, or in lateral lymph nodes (LLN). METHODS: A total of 114 consecutive patients who underwent surgery for recurrent, non-metastatic rectal cancer at a single comprehensive cancer center between 1997 and 2012 were grouped on the basis of radiographic assessment of type of recurrence: PA, 76 (67%) patients; SF, 25 (22%) patients; LLN, 13 (11%) patients. Demographic, clinical, and pathological features were compared between the three groups, as were disease-free survival (DFS) and overall survival (OS). RESULTS: Recurrence type was associated with positive circumferential margin in the primary resection (PA, 4 [6%]; SF, 4 [19%]; LLN, 3 [25%]; P = 0.027), prior neoadjuvant therapy for the primary tumor (PA, 57 [75%]; SF, 18 [72%]; LLN, 4 [31%]; P = 0.007) and location of the primary tumor in the upper rectum (PA, 33 [45%]; SF, 5 [23%]; LLN, 1 [8%]; P < 0.001). Patients with PA had longer median DFS (PA, 5.1 years; SF, 1.5 years; LLN, 1.2 years; P = 0.036). There was a non-significant trend toward longer OS and higher rates of R0 resection for PA. CONCLUSION: Type of recurrence after salvage surgery for locally recurrent rectal cancer is associated with longer DFS in patients with PA recurrence.

Background Ureteral injury (UI) is a rare but devastating complication during colorectal surgery. Ureteral stents may reduce UI but carry risks themselves. Risk predictors for UI could help target the use of stents, but previous efforts have relied on logistic regression (LR), shown moderate accuracy, and used intraoperative variables. We sought to use an emerging approach in predictive analytics, machine learning, to create a model for UI. Methods Patients who underwent colorectal surgery were identified in the National Surgical Quality Improvement Program (NSQIP) database. Patients were split into training, validation, and test sets. The primary outcome was UI. Three machine learning approaches were tested including random forest (RF), gradient boosting (XGB), and neural networks (NN), and compared with traditional LR. Model performance was assessed using area under the curve (AUROC). Results The data set included 262,923 patients, of whom 1519 (.578%) experienced UI. Of the modeling techniques, XGB performed the best, with an AUROC score of .774 (95% CI .742-.807) compared with .698 (95% CI .664-.733) for LR. Random forest and NN performed similarly with scores of .738 and .763, respectively. Type of procedure, work RVUs, indication for surgery, and mechanical bowel prep showed the strongest influence on model predictions. Conclusions Machine learning-based models significantly outperformed LR and previous models and showed high accuracy in predicting UI during colorectal surgery. With proper validation, they could be used to support decision making regarding the placement of ureteral stents preoperatively.

Background For rectal cancer with unresectable metastases, current practice favors omitting interventions directed at the primary tumor in asymptomatic patients. Objective This study aimed to determine the proportion of patients with primary tumor-related complications, characterize salvage outcomes, and measure survival in patients with metastatic rectal cancer who did not undergo upfront intervention for their primary tumor. Design This is a retrospective analysis. Setting This study was conducted at a comprehensive cancer center. Patients Patients who presented between January 1, 2008, and December 31, 2015, with synchronous stage IV rectal cancer, an unresected primary tumor, and no prior primary tumor-directed intervention were selected. Main outcome measures The main outcome measured was the rate of primary tumor-related complications in the cohort that did not receive any primary tumor-directed intervention. The Kaplan-Meier method and Cox regression analysis were used to determine whether complications are associated with survival. Results The cohort comprised 358 patients with a median age of 56 years (22-92). Median follow-up was 26 months (range, 1-93 months). Among the 168 patients (46.9%) who eventually underwent elective resection of the primary tumor, the surgery was performed with curative intent in 66 patients (18.4%) and preemptive intent in 102 patients (28.5%). Of the 190 patients who did not undergo an upfront or elective intervention for the primary tumor, 68 (35.8%) experienced complications. Nonsurgical intervention for complications was attempted in 34 patients with an overall success rate of 61.8% (21/34). Surgical intervention was performed in 47 patients (including 13 patients for whom nonsurgical intervention failed): diversion in 26 patients and resection in 21 patients. Of those 47 patients, 42 (89.4%) ended up with a colostomy or ileostomy. Limitations This study was conducted at a single center. Conclusion A significant proportion of patients with metastatic rectal cancer and untreated primary tumor experience primary tumor-related complications. These patients should be followed closely, and preemptive intervention (resection, diversion, or radiation) should be considered if the primary tumor progresses despite systemic therapy. See Video Abstract at http://links.lww.com/DCR/B400. COMPLICACIONES RELACIONADAS CON EL TUMOR PRIMARIO Y RESULTADOS DE RESCATE EN PACIENTES CON CANCER DE RECTO METASTASICO Y UN TUMOR PRIMARIO NO TRATADO: Para el cancer de recto con metastasis no resecables, la practica actual favorece la omision de las intervenciones dirigidas al tumor primario en pacientes asintomaticos.Determinar la proporcion de pacientes con complicaciones relacionadas con el tumor primario, caracterizar los resultados de rescate y medir la supervivencia en pacientes con cancer rectal metastasico que no se sometieron a una intervencion inicial para su tumor primario.Analisis retrospectivo.Centro oncologico integral.Pacientes que se presentaron entre el 1 de enero de 2008 y el 31 de diciembre de 2015 con cancer de recto en estadio IV sincronico, un tumor primario no resecado y sin intervencion previa dirigida al tumor primario.Tasa de complicaciones relacionadas con el tumor primario en la cohorte que no recibio ninguna intervencion dirigida al tumor primario. Se utilizo el metodo de Kaplan-Meier y el analisis de regresion de Cox para determinar si las complicaciones estan asociadas con la supervivencia.La cohorte estuvo compuesta por 358 pacientes con una mediana de edad de 56 anos (22-92). La mediana de seguimiento fue de 26 meses (rango, 1 a 93 meses). Entre los 168 pacientes (46,9%) que finalmente se sometieron a reseccion electiva del tumor primario, la cirugia se realizo con intencion curativa en 66 pacientes (18,4%) y con intencion preventiva en 102 pacientes (28,5%). De los 190 pacientes que no se sometieron a una intervencion inicial o electiva para el tumor primario, 68 (35,8%) experimentaron complicaciones. Se intento una intervencion no quirurgica para las complicaciones en 34 pacientes con una tasa de exito global del 61,8% (21 de 34). La intervencion quirurgica se realizo en 47 pacientes (incluidos 13 pacientes en los que fallo la intervencion no quirurgica): derivacion en 26 pacientes y reseccion en 21 pacientes. De esos 47 pacientes, 42 (89,4%) terminaron con una colostomia o ileostomia.Unico centro.Una proporcion significativa de pacientes con cancer de recto metastasico y primario no tratado experimentan complicaciones relacionadas con el tumor primario. Se debe hacer un seguimiento estrecho de estos pacientes y considerar la posibilidad de una intervencion preventiva (reseccion, derivacion o radiacion) si el tumor primario progresa a pesar de la terapia sistemica. Consulte Video Resumen en http://links.lww.com/DCR/B400.

Background Because of increased risk of metachronous colorectal cancer (CRC), all patients with Lynch syndrome (LS) are offered a total colectomy. However, because metachronous CRC rate by mismatch repair (MMR) gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy. Study Design Single-center, retrospective cohort study in patients with an earlier colectomy for CRC and an MMR germline mutation in MLH1, MSH2, MSH6, or PMS2 followed prospectively in a hereditary CRC family registry. All patients underwent surveillance colonoscopy. Metachronous CRC was defined as one detected more than 1 year after index resection. Primary end point was cumulative incidence of metachronous CRC overall and by MMR gene. Results One hundred and ten patients were included: 35 with MLH1 likely pathogenic/pathogenic (LP/P) variants (32%), 42 MSH2 (38%), 20 MSH6 (18%), and 13 PMS2 (12%). Median follow-up 4.26 years (range 0.53 to 19.92 years). Overall, metachronous CRC developed in 22 patients (20%). At 10-year follow-up, incidence was 12% (95% CI 6% to 23%), with no metachronous CRC detected in patients with a PMS2 or MSH6 LP/P variant. Conclusions After index segmental resection, metachronous CRC is less likely to develop in LS patients with MSH6 or PMS2 LP/P variant than in MLH1 or MSH2 carriers. Our data support segmental resection and long-term colonoscopic surveillance rather than total colectomy in carefully selected, well-informed LS patients with MSH6 or PMS2 LP/P variant.

BACKGROUND A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach. OBJECTIVE The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision). DESIGN This was a retrospective case-control study using patient-reported outcomes. SETTINGS The study was conducted at a comprehensive cancer center. PATIENTS Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge. MAIN OUTCOME MEASURES Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. RESULTS Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001). LIMITATIONS The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion. CONCLUSIONS A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCION EVACUATORIA INFORMADA POR PACIENTES EN CANCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUES DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugia de preservacion del esfinter para pacientes con cancer rectal localmente avanzado que logran una respuesta clinica completa despues de la terapia neoadyuvante. Hay datos limitados sobre la funcion evacuatoria en pacientes sometidos a este abordaje para preservacion de organos.Evaluar la funcion evacuatoria en pacientes con cancer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugia de preservacion de esfinteres (escision mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncologico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugia de preservacion de esfinteres controlando por edad, sexo y la distancia del tumor al borde anal.Funcion evacuatoria utilizando un instrumento de valoracion del Centro de Cancer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor funcion evacuatoria en la escala general (puntuacion total media, 76 versus 55; p

Objective: In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread - MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT. Methods and materials: A PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed. Results: Individual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5 mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (p

Purpose: We aimed to investigate genomic correlates underlying extremes of survivorship in metastatic colorectal cancer and their applicability in informing survival in distinct subsets of patients with metastatic colorectal cancer. Experimental Design: We examined differences in oncogenic somatic alterations between metastatic colorectal cancer cohorts demonstrating extremes of survivorship following complete metastasectomy: ≤2-year (n = 17) and ≥10-year (n = 18) survivors. Relevant genomic findings, and their association with overall survival (OS), were validated in two independent datasets of 935 stage IV and 443 resected stage I–IV patients. Results: In the extremes-of-survivorship cohort, significant co-occurrence of KRAS hotspot mutations and TP53 alterations was observed in ≤2-year survivors (P < 0.001). When validating these findings in the independent cohort of 935 stage IV patients, incorporation of the cumulative effect of any oncogenic Ras/B-raf (i.e., either KRAS, NRAS, or BRAF) and TP53 alteration generated three prognostic clusters: (i) TP53-altered alone (median OS, 132 months); (ii) Ras/B-raf–altered alone (65 months) or Ras/B-raf- and TP53 pan-wild-type (60 months); and (iii) coaltered Ras/B-raf–TP53 (40 months; P < 0.0001). Coaltered Ras/B-raf–TP53 was independently associated with mortality (HR, 2.47; 95% confidence interval, 1.91–3.21; P < 0.001). This molecular profile predicted survival in the second independent cohort of 443 resected stage I–IV patients. Coaltered Ras/B-raf–TP53 was associated with worse OS in patients with liver (n = 490) and lung (n = 172) but not peritoneal surface (n = 149) metastases. Moreover, coaltered Ras/B-raf–TP53 tumors were significantly more likely to involve extrahepatic metastatic sites with limited salvage options. Conclusions: Genomic analysis of extremes of survivorship following colorectal cancer metastasectomy identifies a prognostic role for coaltered Ras/B-raf–TP53 and its association with distinct patterns of colorectal cancer metastasis.

Background The outcomes of robot-assisted mesorectal excision for rectal cancer, compared with open resection, have not been fully characterized. Methods A retrospective analysis of pathologic, short-term, and long-term outcomes in patients with rectal adenocarcinoma who underwent total or tumour-specific mesorectal excision at a high-volume cancer centre between 2008 and 2017 was conducted. Outcomes after robotic and open surgery were compared on an intention-to-treat basis. Results Out of 1048 resections performed, 1018 patients were reviewed, with 638 who underwent robotic surgery and 380 open surgery. Robotic surgery was converted to the open approach in 17 (2.7 per cent) patients. Patients who underwent robotic surgery were younger (median 54 (range 22–91) years versus median 58 (range 18–97) years; P < 0.001), had higher tumours (median 80 (range 0–150) mm from the anal verge versus median 70 (0–150) mm; P = 0.001), and were less likely to have received neoadjuvant therapy (64 per cent versus 73 per cent; P = 0.003). For patients who underwent a robotic total mesorectal excision, the operating time was longer (median 283.5 (range 117–712) min versus median 249 (range 70–661) min; P < 0.001). However, the rate of complications was lower (29 per cent versus 45 per cent; P < 0.001) and length of hospital stay was shorter (median 5 (range 1–32) days versus median 7 (range 0–137) days; P < 0.001). Median follow-up of survivors was 2.9 years. The proportion of patients with a positive circumferential resection margin did not differ between the groups, nor did the rate of local recurrence (robotic versus open: 3.7 per cent, 95 per cent c.i. 1.9 to 5.6 versus 2.8 per cent, 95 per cent c.i. 1.0 to 4.6; P = 0.400), systemic recurrence (robotic versus open: 11.7 per cent, 95 per cent c.i. 8.5 to 14.8 versus 13.0 per cent, 95 per cent c.i. 9.2 to 16.5; P = 0.300), or overall survival (robotic versus open: 97.8 per cent, 95 per cent c.i. 96.3 to 99.3 versus 93.5 per cent, 95 per cent c.i. 90.8 to 96.2; P = 0.050). The same results were documented in a subanalysis of 370 matched patients, including 185 who underwent robotic surgery and 185 open surgery, for the overall incidence of any postoperative complications, overall survival, disease-free survival, local recurrence, and systemic recurrence. Conclusion In patients with rectal cancer who are candidates for curative resection, robotic mesorectal excision is associated with lower complication rates, shorter length of stay, and equivalent oncologic outcomes, compared with open mesorectal excision., In patients with rectal cancer amenable to curative resection, robotic mesorectal excision was associated with lower complication rates, shorter length of stay, and equivalent oncologic outcomes, compared with open mesorectal excision. The results indicate that in high-volume centres, with institutional resources and support, the benefits of minimally invasive surgery can be extended to all rectal cancer patients without sacrificing oncological outcomes.

Background The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC). Methods Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided. Results In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P Conclusions EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.

Background Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. Materials and Methods This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. Results The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). Conclusions Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.

Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had received induction chemotherapy versus those who did not.We reviewed records of patients with locally advanced rectal cancer who were treated with CRT between September 2009 and October 2014, and who had completed ≥ 4 PRO assessments during treatment. Clinician- and patient-reported toxicities were collected each week during treatment. We fit binomial generalized linear models to maximum toxicity scores across all patients' visits.Of 123 patients with ≥ 4 PRO assessments, 87 (71%) patients reported a clinically meaningful PRO score of 3 or higher for diarrhea, and 91 (74%) patients reported a PRO score of ≥ 3 for urgency, during 1 or more weeks of treatment, corresponding to 'very frequent' or worse. Of 116 patients who had also completed ≥ 4 clinician-reported assessments for descriptive analysis, clinically significant diarrhea (Common Terminology Criteria for Adverse Events grade ≥ 2) was reported in 9% of patients, and grade 2 proctitis and cystitis were reported in 20% and 4%, respectively. Eighty-four (68%) patients had undergone induction chemotherapy prior to CRT. Patients who received induction chemotherapy had 68% lower odds of experiencing significant urgency (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.95; P = .04), 76% lower odds of bleeding (OR, 0.24; 95% CI, 0.1-0.62; P .01), and 75% lower odds of tenesmus (OR, 0.25; 95% CI, 0.11-0.6; P .01) versus those treated with upfront CRT.Based on PROs, a high proportion of patients experienced clinically significant symptoms during pelvic CRT, with diarrhea and urgency being most commonly reported. This appears to be under-reported on clinician-reported assessments. Delivery of induction chemotherapy was associated with lower odds of experiencing urgency, bleeding, and tenesmus on PROs during subsequent CRT, with no significant impact on diarrhea and rectal pain.

BACKGROUND AND PURPOSE: Comorbidity indices (CI) are widely used in retrospective studies. We investigated the value of commonly-used CIs in risk adjustment for postoperative complications after colorectal surgery. METHODS: Patients undergoing colectomy without stoma for colonic neoplasia at a single institution from 2009–2014 were included. Four CIs were calculated or obtained for each patient using administrative data: Charlson-Deyo (CCI-D), Charlson-Romano (CCI-R), Elixhauser Comorbidity Score (ECS) and American Society of Anesthesiology classification (ASA). Outcomes of interest in the 90-day postoperative period were: any surgical complication, surgical site infection (SSI), Clavien-Dindo (CD) grade 3 or higher complication, anastomotic leak or abscess and nonroutine discharge. Base models were created for each outcome based on significant bivariate associations. Logistic regression models were constructed for each outcome using base models alone, and each index as an additional covariate. Models were also compared using the Delong and Clarke-Pearson method for Receiver-Operator Characteristic curves (ROC), with the CCI-D as the reference. RESULTS: 1813 patients were included. Postoperative complications were reported in 756 (42%) patients. Only 9% of patients had a CD grade 3 or higher complication, and 22.8% of patients developed an SSI. Multivariable modeling showed equivalent performance of the base model and the base model augmented by the CIs for all outcomes. The ROC curves for the 4 indices were also similar. DISCUSSION AND CONCLUSIONS: The inclusion of CIs added little to the base models, and all CIs performed similarly well. Our study suggests that CIs do not adequately risk adjust for complications after colorectal surgery.

Increasing the interval from completion of neoadjuvant therapy to surgery beyond 8 weeks is associated with increased response of rectal cancer to neoadjuvant therapy. However, reports are conflicting on whether extending the time to surgery is associated with increased perioperative morbidity. Patients who presented with a tumor within 15 cm of the anal verge in 2009–2015 were grouped according to the interval between completion of neoadjuvant therapy and surgery

Purpose: SMAD4 has shown promise in identifying patients with colorectal cancer at high risk of recurrence or death. Experimental Design: A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance. Results: The discovery cohort consisted of 364 patients with stage I–IV colorectal cancer. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3–8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL), and lower peritumoral lymphocyte aggregate (PLA) scores (all P < 0.04). SMAD4 loss was associated with worse RFS (P = 0.02). When stratified by SMAD4 and immune infiltrate status, patients with SMAD4 loss and low TIL or PLA had worse RFS (P = 0.002 and P = 0.006, respectively). Among patients receiving 5-fluorouracil (5-FU)-based systemic chemotherapy, those with SMAD4 loss had a median RFS of 3.8 years compared with 13 years for patients with SMAD4 retained. In xenografted mice, the SMAD4-lost tumors displayed resistance to 5-FU. An independent cohort replicated our findings, in particular, the association of SMAD4 loss with decreased immune infiltrate, as well as worse disease-specific survival. Conclusions: Our data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate, supporting its use as a prognostic marker in patients with colorectal cancer.

BACKGROUND: The use of the da Vinci robotic platform for total colectomy has been limited by the need to reposition the patient-side surgical cart from one side of the patient to the other, which increases operative time. In this study we examined the feasibility of robotic total colectomy using the da Vinci Xi model, which offers a rotating boom-mounted system and laser-targeted trocar positioning. METHODS: The study cohort consisted of 23 patients who underwent minimally invasive total colectomy for cancer or polyposis syndromes at a comprehensive cancer center between 2015 and 2017. Of the 23 colectomies, 15 were robotic and 8 were laparoscopic. For the robotic colectomies, trocars were placed in the supraumbilical region and all four quadrants. The da Vinci Xi robot was placed between the patient’s legs, and the boom was rotated from left to right and then to the middle in order to work sequentially on the right colon, the left colon, and the pelvis. Operating time and short- term outcomes were compared between the patients who underwent robotic surgery and the patients who underwent laparoscopic surgery. RESULTS: The two groups of patients were comparable in age, gender, BMI, physical status, and disease types. In the robotic group, median length of stay (4 vs. 6 days, p = 0.047) was significantly shorter and median operative time (243 vs. 263 min, p = 0.97) and median estimated blood loss (50 vs. 100 ml; p = 0.08) were similar between the groups. CONCLUSIONS: With the da Vinci Xi boom-mounted system, total abdominal colectomy can be performed without the need to move the patient-side surgical cart, and is associated with shorter length of stay and similar operative time compared to the laparoscopic approach.

AIM: In 2014, Memorial Sloan Kettering Cancer Center was identified as an outlier for increased length of stay (LOS) after colorectal surgery. We subsequently implemented a comprehensive Enhanced Recovery After Surgery (ERAS) program in January 2016, which is continually monitored to target areas for improvement. The primary aim of this study was to evaluate the impact of a newly established ERAS program in a high-volume colorectal center over time. METHOD: This was a retrospective cohort study, comparing 3000 sequential cancer patients who underwent elective colorectal surgery before and after ERAS implementation. Patients were divided into three groups (Pre-, Early, and Late ERAS). Adherence to ERAS process measures and outcomes (LOS, complications, and 30-day readmission) were compared among the three time periods. RESULTS: Adherence to ERAS metrics significantly increased over time, from a median of 25% Pre-ERAS to 67% Early and 75% Late ERAS (p < 0.0001). Mean LOS decreased from 5.2 days Pre-ERAS to 4.5 Early and 4.0 Late ERAS (p < 0.0001). There were no differences in rates of complications or readmissions, and patients with shorter LOS had lower readmission rates. With ERAS, the readmission rate was 4.4% for patients discharged within 3 days, versus >10% for LOS ≥5 days (p < 0.0001). CONCLUSION: Initiation of an ERAS program at a high-volume colorectal center was associated with decreased LOS, without increasing morbidity. Increased ERAS adherence was associated with a further decrease in LOS. Multidisciplinary monitoring to promote protocol adherence is necessary for maintaining a safe and effective ERAS program.

Purpose: Evaluate response of mismatch repair–deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. Experimental Design: dMMR rectal tumors at Memorial Sloan Kettering Cancer Center (New York, NY) were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty patients with dMMR rectal cancer were identified by IHC and/or microsatellite instability analysis, with initial treatment response compared with a matched MMR-proficient (pMMR) rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. Results: Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), six (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors (P = 0.0001). Rectal cancer dMMR tumoroids reflected this resistance to chemotherapy. No genomic predictors of chemotherapy response were identified. Of 16 patients receiving chemoradiation, 13 (93%) experienced tumor downstaging; one patient had stable disease, comparable with 48 pMMR rectal cancers. Of 13 patients undergoing surgery, 12 (92%) had early-stage disease. Forty-two (84%) of the 50 patients tested positive for Lynch syndrome with enrichment of germline MSH2 and MSH6 mutations when compared with 193 patients with Lynch syndrome–associated colon cancer (MSH2, 57% vs 36%; MSH6, 17% vs 9%; P < 0.003). Conclusions: Over one-fourth of dMMR rectal tumors treated with neoadjuvant chemotherapy exhibited disease progression. Conversely, dMMR rectal tumors were sensitive to chemoradiation. MMR status should be performed upfront in all locally advanced rectal tumors with careful monitoring for response on neoadjuvant chemotherapy and genetic testing for Lynch syndrome in patients with dMMR rectal cancer.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation, and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic, or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients’ tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.

Aim:\ud Significant recent changes in management of locally advanced rectal cancer include preoperative staging, use of extended neoadjuvant therapies, and minimally invasive surgery (MIS). This study was aimed at characterizing those changes and associated short‐term outcomes.\ud \ud Method:\ud We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ locally advanced rectal cancer ≤15 cm from the anal verge who were evaluated at a comprehensive cancer center in 2009–2015.\ud \ud Results:\ud In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009‐2010, 2011, 2012, 2013, and 2014‐2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009‐2010 to 98% in 2014‐2015 (p < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (p < 0.001); and increased use of MIS, from 33% to 70% (p < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; p < 0.001), as did the rates of grade III‐V complications (from 13% to 7%; p < 0.05), surgical site infections (from 24% to 8%; p < 0.001), anastomotic leak (from 11% to 3%; p < 0.05), and positive circumferential resection margin (from 9% to 4%; p < 0.05). TNM downstaging increased from 62% to 74% (p = 0.002).\ud \ud Conclusion:\ud Shifts toward MRI‐based staging, total neoadjuvant therapy, and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

BACKGROUND Ovarian metastases from colorectal cancer (OM-CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are poorly characterized and optimal clinical management remains unclear. METHODS Women with a histopathological diagnosis of OM-CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched tumor pairs/trios. Regression models were used to analyze variables associated with progression-free survival and overall survival (OS). RESULTS Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM-CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with reduced OS. Matched multisite tumor sequencing did not identify OM-specific genomic alterations. Of the 195 patients who underwent oophorectomy for OM-CRC (median age, 49 years with a progression-free survival of 9.4 months and an OS of 23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In multivariable analysis, residual disease after surgery (R2 resection) was associated with worse survival. Patients with EOM were less likely to achieve R0/R1 surgical resection status (complete macroscopic resection without clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1 resection status was achieved, both patients with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114 patients with R0/R1 resection status, 23 (20%) had no disease recurrence, including 10 patients (9%) with > 3 years of follow-up. CONCLUSIONS Loss-of-function alterations in SMAD4 are frequent and predictive of worse survival in patients with OM-CRC. Similar to oligometastatic CRC to the lung or liver, surgical resection of OM-CRC is associated with a better outcome only if all macroscopic metastatic disease is resected. Cancer 2016. © 2016 American Cancer Society.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation, and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to individual patients. We established a biorepository of 32 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic, or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and theirex vivoresponses to clinically relevant chemotherapy and radiation treatment correlate well with responses noted in individual patients’ tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive rectal cancer followed by metastasis to lung and liver. Importantly, engrafted tumors closely reflected the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based,in vitroplatform coupled with endoluminal propagation in animals.

BackgroundThe Memorial Sloan Kettering Cancer Center (MSK) colon cancer recurrence nomogram is a risk calculator that provides patients and clinicians with individualized prediction of recurrence following curative resection of colon cancer. Although validated on multiple separate cohorts, the nomogram requires periodic updating as patient care changes over time. The aim of this study was to evaluate the nomogram’s accuracy in a contemporary cohort and modify the tool to reflect improvements in outcome related to advances in colon cancer therapy.MethodsA contemporary patient cohort was compiled, including consecutive colon cancer patients undergoing curative resection for stage I–III colon adenocarcinoma at MSK from 2007 to 2014. The nomogram’s predictive accuracy was assessed by concordance index and calibration plots of predicted vs actual freedom from recurrence at 5 years after surgery.ResultsData from a total of 999 eligible patients with complete records were used for validation. Median follow-up among survivors was 37 months. The concordance index was 0.756 (95% confidence interval = 0.707 to 0.805), indicating continued discriminating power, but the calibration plot revealed that the nomogram overestimated recurrence risk. Recalibration of the nomogram by estimating a new baseline freedom-from-recurrence function restored the nomogram’s accuracy.ConclusionThe updated nomogram retains the original nomogram’s variables but includes a lower baseline estimation of recurrence risk, reflecting improvements in outcomes for all stages of colon cancer, likely resulting from advances in imaging and integration of multiple treatment modalities.

Background and Objectives Achieving a pathologic complete response (pCR) after neoadjuvant therapy has been associated with better prognosis in rectal cancer patients. The objective of this study was to investigate the relationship between distance to the anal verge (DTAV) and pCR. Methods Review of a prospectively maintained database of patients with locally advanced rectal cancer who received neoadjuvant treatment was completed. Uni- and multivariate analysis assessed the association between DTAV and pCR after neoadjuvant therapy. Results Of 827 included patients, 20% had a pCR. We found that pCR rates were 11% for tumors 10 cm from the anal verge (P = 0.002). Multivariate analysis also showed a strong association between DTAV and pCR (P = 0.008). The bimodal distribution of pCR resulted in a lower odds ratio of pCR for tumors 8 cm from the anal verge. Conclusions Patients with low tumors ( 8 cm), were less likely to have a pCR. Further investigation is warranted to determine if these observations are related to tumor biology or possibly differences in radiation technique. J. Surg. Oncol. 2016;114:637–641. © 2016 Wiley Periodicals, Inc.

Incisional hernia (IH) is a common complication after colectomy, with impacts on both health care utilization and quality of life. The true incidence of IH after minimally invasive colectomy is not well described. The purpose of this study was to examine IH incidence after minimally invasive right colectomies (RC) and to compare the IH rates after laparoscopic (L-RC) and robotic (R-RC) colectomies. This is a retrospective review of patients undergoing minimally invasive RC at a single institution from 2009 to 2014. Only patients undergoing RC for colonic neoplasia were included. Patients with previous colectomy or intraperitoneal chemotherapy were excluded. Three L-RC patients were included for each R-RC patient. The primary outcome was IH rate based on clinical examination or computed tomography (CT). Univariate and multivariate time-to-event analyses were used to assess predictors of IH. 276 patients where included, of which 69 had undergone R-RC and 207 L-RC. Patient and tumor characteristics were similar between the groups, except for higher tumor stage in L-RC patients. Both the median time to diagnosis (9.2 months) and the overall IH rate were similar between the groups (17.4 % for R-RC and 22.2 % for L-RC), as were all other postoperative complications. In multivariable analyses, the only significant predictor of IH was former or current tobacco use (hazard raio 3.0, p = 0.03). This study suggests that the incidence of IH is high after minimally invasive colectomy and that this rate is equivalent after R-RC and L-RC. Reducing the IH rate represents an important opportunity for improving quality of life and reducing health care utilization after minimally invasive colectomy.

This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed. Prognostic accuracies for recurrence-free survival (RFS) were compared, and interobserver agreement among 3 pathologists was assessed. The study cohort consisted of 851 patients. Although all the histologic markers except WHO grade were significantly associated with RFS (PDCs, tumor budding, perineural invasion, and desmoplastic reaction: P

Importance Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. Objective To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC. Design, Setting, and Participants A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified. Exposures Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT). Main Outcomes and Measures Treatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK. Results Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. Conclusions and Relevance Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Previous reports on the surgical management of appendix cancer show high recurrence rates among patients initially presenting with localized disease. This study sought to characterize predictors of outcome among patients treated for stages 1-3 appendix cancer at the authors' institution.Patients with nonmetastatic appendix cancer undergoing definitive surgery at a single cancer center from 1994 to 2013 were retrospectively reviewed. Patients with appendiceal adenomas, cystadenomas, or classical carcinoids were excluded from the study. The median follow-up period was 5.2 years (interquartile range 2.9-6.7 years).The study identified 70 patients, 49 % of whom were women. The median age was 52 years (range 20-84 years). All were explored by an expert surgeon who had treated at least 20 appendiceal cancers. The procedures were appendectomy (n = 2), right hemicolectomy (n = 66), and diagnostic laparoscopy and placement of an intraperitoneal port (n = 2). The final pathology showed that transmural (30 T4, 32 T3, 4 T2, 4 T1) and node-negative disease (80 %) were common. Goblet cell carcinoid (GCC) features were identified in 54 % of the tumors. These were smaller and more likely to present as acute appendicitis than appendiceal adenocarcinoma (AA), but were otherwise similar in clinical presentation and outcome. The presence of lymph node (LN) metastasis was associated with a higher risk of recurrence than of stage 2 appendix cancer (78 vs. 4 % at 5 years; p0.0001). A total of 12 patients experienced recurrence (5 GCC, 7 AA): 9 in the peritoneum, 2 in mesenteric LNs, and 1 in the surgical incision.Stages 1-3 invasive AA and GCC behave similarly in terms of clinical presentation and outcome. Perforated appendix and T4 tumor stage were common but not associated with recurrence. Although uncommon, LN metastasis strongly predicted recurrence.

Evaluating patients for recurrent anal cancer after primary treatment can be difficult owing to distorted anatomy and scarring. Many institutions incorporate endoscopic ultrasound to improve detection, but the effectiveness is unknown.The aim of this study is to compare the effectiveness of digital rectal examination and endoscopic ultrasound in detecting locally recurrent disease during routine follow-up of patients with anal cancer.This study is a retrospective, single-institution review.This study was conducted at an oncologic tertiary referral center.Included were 175 patients with nonmetastatic anal squamous-cell cancer, without persistent disease after primary chemoradiotherapy, who had at least 1 posttreatment ultrasound and examination by a colorectal surgeon.The primary outcomes measured were the first modality to detect local recurrence, concordance, crude cancer detection rate, sensitivity, specificity, and predictive value.Eight hundred fifty-five endoscopic ultrasounds and 873 digital rectal examinations were performed during 35 months median follow-up. Overall, ultrasound detected 7 (0.8%) mesorectal and 32 (3.7%) anal canal abnormalities; digital examination detected 69 (7.9%) anal canal abnormalities. Locally recurrent disease was found on biopsy in 8 patients, all detected first or only with digital examination. Four patients did not have an ultrasound at the time of diagnosis of recurrence. The concordance of ultrasound and digital examination in detecting recurrent disease was fair at 0.37 (SE, 0.08; 95% CI, 0.21-0.54), and there was no difference in crude cancer detection rate, sensitivity, specificity, and negative or positive predictive values.The heterogeneity of follow-up timing and examinations is not standardized in this study but is reflective of general practice.Endoscopic ultrasound did not provide any advantage over digital rectal examination in identifying locally recurrent anal cancer, and should not be recommended for routine surveillance.

Perianal Paget's disease (intraepithelial adenocarcinoma) is rare and sometimes difficult to diagnose because symptoms are nonspecific. It is often noninvasive but frequently recurs locally. Invasive disease can metastasize to distant sites.The purpose of this work was to review the diagnosis, management, and outcomes of patients with perianal Paget's disease.Institutional databases were queried for all of the cases of perianal Paget's disease at Memorial Sloan-Kettering Cancer Center between 1950 and 2011. Clinicopathologic factors were investigated for association with recurrence and survival.The study was conducted at a tertiary care center.Sixty-five patients with perianal Paget's disease were included in the study (35 women [54%]; median age at diagnosis, 66 years [range, 60-72 years]; and 41 with invasive disease/24 with noninvasive disease). A total of 56% with invasive disease were men.Measures included median follow-up, disease status, local and distant recurrence, sites of recurrence, disease-specific survival, overall survival, and treatment modality.A total of 95% with invasive disease and 87% with noninvasive disease were symptomatic at presentation. The most common symptoms were pruritus and perianal bleeding. The duration of symptoms was longer in patients with invasive (12.0 months; range, 4.0-18.0 months) versus noninvasive (3.5 months; range, 1.0-10.0 months) disease. Synchronous malignancies unrelated to the primary disease were noted in 5 patients with invasive disease and 3 with noninvasive disease. Noninvasive disease was treated with a wide local excision and invasive disease with a wide local excision (n = 32, 78%) or abdominoperineal resection (n = 9, 22%). Forty-one patients (27 invasive and 14 noninvasive) required multiple operations for tumor clearance. In those with invasive disease, the median time to recurrence was 5 years, and the median tumor-specific survival rate was 10 years.This was a retrospective study, limited by selection bias.Perianal Paget's disease is associated with nonspecific symptoms, frequently delaying diagnosis. Wide local excision is the treatment of choice if negative margins can be obtained. Abdominoperineal resection should be considered for invasive disease. Local recurrence is common; follow-up includes periodic proctoscopy and digital examination. Invasive disease can metastasize to distant sites; follow-up should include the examination of inguinal lymph nodes and the imaging of liver and lungs.

Neoadjuvant radiation therapy (RT) downstages rectal cancer but may increase postoperative morbidity. This study aims to quantify 30-day complication rates after total mesorectal excision (TME) using current techniques and to assess for an association of these complications with neoadjuvant RT.Stage I-III rectal cancer patients who underwent TME from 2005 to 2010 were identified. Complications occurring within 30 days after TME were retrieved from a prospectively maintained institutional database of postoperative adverse events.The cohort consisted of 461 patients. Median age was 59 years (range 18-90), and 274 patients (59 %) were male. Comorbid conditions included obesity (n = 147; 32 %), coronary artery disease (n = 83; 18 %), diabetes (n = 65; 14 %), and inflammatory bowel disease (n = 19; 4 %). A low anterior resection (LAR) was performed in 383 cases (83 %), an abdominoperineal resection (APR) was performed in 72 cases (16 %), and a Hartmann's procedure was performed in 6 cases (1 %). Preoperative RT was delivered to 310 patients (67 %; median dose of 50.4 Gy, range 27-55.8 Gy). The 30-day incidence of postoperative mortality was 0.4 % (n = 2), any complication 25 % (n = 117), grade 3 or more complication 5 % (n = 24), intra-abdominal infection 3 % (n = 12), abdominal wound complication 9 % (n = 42), perineal wound complication after APR 11 % (n = 8/72), and anastomotic leak after LAR 2 % (n = 6/383). These events were not associated with neoadjuvant RT.In a cohort undergoing TME using current techniques, neoadjuvant RT was not associated with 30-day postoperative morbidity or mortality.

IMPORTANCE: The watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection. OBJECTIVE: To analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response to neoadjuvant therapy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018. EXPOSURES: Patients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136). MAIN OUTCOMES AND MEASURES: Kaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival. RESULTS: Compared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median [range], 67.2 [32.1-90.9] vs 57.3 [25.0-87.9] years, P

Patients with colorectal cancer (CRC) and renal cell carcinoma (RCC) may be at risk for additional primary malignancies. A review of 101 patients with these concurrent diagnoses was performed. Forty-two percent of patients had 1 or more additional malignancies; none appeared to be associated with Lynch syndrome (LS). This suggests the need for careful follow-up in these patients and further study.Small studies have demonstrated that patients who have both colorectal and renal cell carcinoma may be at increased risk for the development of additional malignancies. A possible genetic basis has been suggested. Our study describes the clinicopathologic features of these patients and clarifies the relationship of this cohort with Lynch syndrome (LS).Patients with primary CRC and RCC treated at our institution were identified. Medical records were reviewed for demographic and clinical information. Immunohistochemical staining for mismatch repair (MMR) proteins was performed on tumor tissue when possible.During the study period, 24,642 patients were treated for CRC and 7,366 were treated for RCC at our institution. One hundred seventy-nine patients had both diagnoses, with 101 patients eligible for inclusion in our cohort. Tumors were typically early stage. The 2 cancers presented as synchronous lesions in 42% of patients. Thirty-two patients had 1 additional primary malignancy, 7 patients had 2 additional primary malignancies, and 3 patients had 3 additional primary malignancies. No patient had a family history that met the Amsterdam II criteria (AC) for LS, but 50% had family members with 1 malignancy. One of 10 colorectal tumors analyzed for the absence of MMR protein expression demonstrated the absence of MSH6, but the corresponding RCC demonstrated intact expression of all 4 MMR proteins.It is rare for patients to be diagnosed with both CRC and RCC. The clinicopathologic features of this cohort and the results of immunohistochemical analysis performed on a sample of these patients do not suggest LS. However, the high rate of additional carcinomas suggests a need for careful follow-up. Multicenter longitudinal studies are warranted to further understand the natural history and possible genetic basis for this entity.

The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.Review of a single institution's prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and0.001, respectively).In this dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.

Robotic colorectal resection continues to gain in popularity. However, limited data are available regarding how surgeons gain competency and institutions develop programs. To determine the number of cases required for establishing a robotic colorectal cancer surgery program. Retrospective review. Cancer center. We reviewed 418 robotic-assisted resections for colorectal adenocarcinoma from January 1, 2009, to December 31, 2014, by surgeons at a single institution. The individual surgeon’s and institutional learning curve were examined. The earliest adopter, Surgeon 1, had the highest volume. Surgeons 2–4 were later adopters. Surgeon 5 joined the group with robotic experience. A cumulative summation technique (CUSUM) was used to construct learning curves and define the number of cases required for the initial learning phase. Perioperative variables were analyzed across learning phases. Case numbers for each stage of the learning curve. The earliest adopter, Surgeon 1, performed 203 cases. CUSUM analysis of surgeons’ experience defined three learning phases, the first requiring 74 cases. Later adopters required 23–30 cases for their initial learning phase. For Surgeon 1, operative time decreased from 250 to 213.6 min from phase 1–3 (P = 0.008), with no significant changes in intraoperative complication or leak rate. For Surgeons 2–4, operative time decreased from 418 to 361.9 min across the two phases (P = 0.004). Their intraoperative complication rate decreased from 7.8 to 0 % (P = 0.03); the leak rate was not significantly different (9.1 vs. 1.5 %, P = 0.07), though it may be underpowered given the small number of events. Our data suggest that establishing a robotic colorectal cancer surgery program requires approximately 75 cases. Once a program is well established, the learning curve is shorter and surgeons require fewer cases (25–30) to reach proficiency. These data suggest that the institutional learning curve extends beyond a single surgeon’s learning experience.