Search

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 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.

The majority of cases of inherited colorectal cancer (CRC) are accounted for by two syndromes: Lynch syndrome and familial adenomatous polyposis (FAP). In the management of FAP, the role of prophylactic surgery is clearly defined, although the optimal procedure for an individual patient depends on a number of factors. In the management of Lynch syndrome, the indications for prophylactic procedures are emerging. The authors address the clinical evaluation, investigation findings, medical and surgical therapy, and extracolonic diseases of FAP, attenuated form of FAP (AFAP), MYH-associated polyposis, Lynch syndrome, familial colorectal cancer type X (FCCTX), hyperplastic polyposis syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. AFAP has been described that is associated with fewer adenomas and later development of CRC compared with classic FAP. The AFAP phenotype occurs in less than 10% of FAP patients. The clinical criteria for AFAP are no family members with more than 100 adenomas before the age of 30 years and (1) at least two patients with 10 to 99 adenomas at age over 30 years or (2) one patient with 10 to 99 adenomas at age over 30 years and a first-degree relative with CRC with few adenomas. Given that polyposis has a later onset and the risk of CRC is less well established in AFAP, some authors question whether prophylactic colectomy is necessary in all AFAP patients. This review contains 26 tables and 173 references Keywords: Colorectal cancer, Lynch syndrome, hyperplastic polyp, Peutz-Jeghers syndrome, juvenile polyposis syndrome, familial adenomatous polyposis

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.

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.

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.

Anatomically, the rectum extends from the point at which the three taenia coli fuse into a single longitudinal smooth muscle layer (rectosigmoid junction) to the anal canal. However, from an oncologic perspective, it corresponds to the distal 12 cm of the large bowel measured from the anal verge. According to this definition, most of the rectum is located below the anterior peritoneal reflection. Cancers that occur proximal to this level in the average patient behave more like colon cancers and are treated accordingly.

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.

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.

SUMMARY Patients with Lynch syndrome and rectal cancer present a unique clinical challenge. Management of the primary rectal cancer and prophylactic removal of the colon should be considered. In patients requiring a mesorectal excision, a combined prophylactic colon removal can be considered. Although surveillance of the colon with frequent colonoscopies is an alternative, concerns of metachronous colon cancer development support prophylactic removal of the colon as an alternative. Since data are not available to confirm superiority of either approach, the final decision is greatly dependent upon a patient's wishes and preferences. Patients interested in pursuing simultaneous prophylactic colon removal can be offered total proctocolectomy with either ileal pouch anal-anastomosis as a sphincter-preserving alternative or a total proctocolectomy with end ileostomy.

Background Patients with adenomatous polyposis may be at increased risk for developing thyroid cancer (TC). However, screening guidelines for TC in these patients are not well established. Methods Patients with a diagnosis of familial adenomatous polyposis, attenuated familial adenomatous polyposis, and gene mutation-negative adenomatous polyposis enrolled in our Hereditary Colorectal Cancer Family Registry were eligible for a screening thyroid ultrasound (US). Findings were reviewed by the study endocrinologist and intervention and/or follow-up determined. Results Fifty patients underwent screening thyroid US. Thirty-four (68%) patients had abnormal findings on US, including 27 (79%) with thyroid nodules. In 7 patients, US-detected thyroid nodules met established criteria for fine-needle aspiration. Of the 6 patients who underwent fine-needle aspiration, 2 (4%) were diagnosed with papillary TC. Both of these patients were female. Conclusions A large proportion of adenomatous polyposis patients will have abnormal results on thyroid US, including suspicious-appearing thyroid nodules that when biopsied are malignant. Female patients have an apparently greater risk of developing TC. Polyposis patients, especially women, should be offered participation in a thyroid US screening program.

The widespread implementation of screening colonoscopy has led to a parallel increase in the detection of early staged rectal cancer including T1N0M0 lesions. Rectal cancers at this stage have invaded into the submucosal layer of the rectal wall without metastasis to lymph nodes and other organs and have been traditionally managed with a transabdominal radical resection (RR). However, since a RR is associated with significant postoperative morbidity, local excisional approaches (LE) such as transanal excision (TAE), transanal endoscopic microsurgery (TEM), and transanal minimally invasive surgery (TAMIS), have been adopted. Whether the oncological results of a less morbid LE approach is comparable to a more morbid RR approach for T1N0M0 rectal cancer is the essential question of this chapter.

BACKGROUND Serrated polyposis syndrome is a rare syndrome associated with an increased risk for colorectal cancer. The World Health Organization criteria were established to standardize the diagnosis and management of patients afflicted with serrated polyposis. Although useful, the criteria may not be ideal for the initial screening of at-risk populations. OBJECTIVE The aim of this study was to examine the use of a minimal cutoff point of serrated lesions to increase the yield of serrated polyposis cases. DESIGN This was a retrospective review of colonoscopy and pathology reports to identify patients who met the World Health Organization criteria for serrated polyposis. SETTING This study was conducted at a tertiary cancer care referral center. PATIENTS Five hundred patients who had at least 2 pathologically confirmed hyperplastic polyps and/or sessile serrated adenomas/polyps diagnosed between 1999 and 2009 were assessed. MAIN OUTCOME MEASURES The primary outcome measure was the number of serrated polyposis cases. RESULTS Forty of the 500 (8%) patients met the World Health Organization criteria for serrated polyposis syndrome. Patients underwent a median of 4 colonoscopies (range, 1-23) before satisfying the criteria, and only 1 (3%) patient met the criteria for diagnosis during the initial colonoscopy. All 16 patients with a history of colorectal cancer were only diagnosed with serrated polyposis either at the time of their cancer diagnosis or during postoperative colonoscopies. Only 5 of the 40 (13%) patients were enrolled in our institutional Hereditary Colorectal Cancer Family Registry before our study for prospective serrated lesion tracking and colorectal cancer screening. LIMITATIONS This tool requires validation in a prospective setting. CONCLUSIONS The cutoff point of at least 2 pathologically confirmed serrated lesions can serve as a screening tool for identifying patients meeting the World Health Organization criteria for serrated polyposis syndrome who would otherwise go undetected.

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

Objective To prospectively compare the ability of flourodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) to identify a pathological complete response (pCR) in patients with rectal cancer treated by chemoradiation. Background A major obstacle in pursuing nonoperative management in patients with rectal cancer after chemoradiation is the inability to identify a pCR preoperatively. Methods A total of 121 patients with rectal cancer were prospectively enrolled. FDG-PET scans and helical CT scans were obtained before and after neoadjuvant chemoradiation. Consensus readings of PET and CT scans were used to classify certainty of disease (5-point confidence rating scale). The ability of PET and CT scans to accurately distinguish a pCR (ypT0) from an incomplete response (ypT1-4) was estimated using the area under the receiver operating characteristic curve (AUC). Results Of the 121 patients, 26 (21%) had a pCR. PET and CT scans were equally inadequate at distinguishing a pCR from an incomplete response (AUC = 0.64 for both, P = 0.97). Among the 26 patients with a pCR, 14 (54%) and 5 (19%) were classified as complete responders on PET and CT scans, respectively. Among the 95 patients with an incomplete pathological response, 63 (66%) and 90 (95%) were classified as incomplete responders on PET and CT scans, respectively. None of the individual PET parameters, including visual response score, mean standard uptake value (SUVmean), maximum SUV (SUVmax), and total lesion glycolysis, accurately distinguished a pCR (AUCs = 0.57-0.73). Conclusions Neither PET nor CT scans have adequate predictive value to be clinically useful in distinguishing a pCR from an incomplete response and, therefore, should not be obtained for the purpose of attempting to predict a pCR after neoadjuvant chemoradiation for rectal cancer.

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.

Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations.Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis.Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P .01).Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures.

Objective Extent of distal resection margins in rectal cancer surgery remains controversial. We set out to determine the long-term oncologic impact of resection margins in patients with locally advanced rectal cancer using a comprehensive pathologic whole-mount section analysis. Background It has been demonstrated that there is minimal disease beyond the gross tumor margin after neoadjuvant combined modality therapy (CMT) for rectal cancer. Although this suggests that close resection margins may be used for sphincter preservation, the long-term oncologic impact of this approach is unclear. Methods We prospectively enrolled 103 patients with locally advanced rectal cancer after neoadjuvant CMT. Whole-mount pathologic analysis was performed, and clinicopathologic variables were correlated with disease-specific survival (DSS). Result : Sphincter preservation was achieved in 80% of patients, and the median distal margin was 2 cm (0.1 to 10 cm). There were 22 patients (21%) with distal margins 1 cm or less and no patient had a positive distal margin. Median radial margin was 1 cm and 4 patients (4%) had a margin of 1 mm or less. Viable distal intramural tumor spread was found in 3 patients (2.7%) and in all cases was limited to 1 cm or less from the gross tumor edge. At a median follow-up of 68 months, 5-year DSS was 86% and 1 patient experienced a local recurrence. Factors predictive of worse DSS included advanced tumor (T) and nodal (N) stage, tumor progression on neoadjuvant CMT, lack of a complete pathologic response, tumor location of 5 cm or less from the anal verge, and neurovascular invasion. The extent of the distal and radial margins of resection was not associated with DSS. Conclusions These results suggest that carefully selected patients with locally advanced rectal cancers who undergo neoadjuvant CMT can achieve excellent local control and DSS with a sphincter-sparing rectal resection and a margin distal clearance of 1 cm.

OBJECTIVE To characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation + total mesorectal excision + adjuvant chemotherapy. METHODS A total of 593 consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging) who received CMT were analyzed for patterns of recurrence. RESULTS After median 44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%) recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had multiple-organ recurrence. The most common site of distant recurrence was lung (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen patients (2.4%) recurred locally. Pulmonary metastases were most commonly identified by computed tomographic scan versus abnormal positron emission tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated with pulmonary recurrence were the following: pathologic stage, tumor distance from anal verge, lymphovascular or perineural invasion. Five-year freedom from pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%, 61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence underwent lung metastasectomy; 3-year freedom from recurrence was 37%. CONCLUSIONS Unlike colon cancer, which most frequently recurs in the liver, locally advanced rectal cancer treated with CMT relapses most frequently in the lung. Pulmonary metastasis was associated with advanced pathologic stage, low-lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of pulmonary metastasis usually requires serial imaging because metastases are often small when initially detected, well below the resolution of PET, and not necessarily associated with elevated CEA. Individualized risk-based surveillance strategies are recommended in this patient population.

Background En bloc resection of adjacent pelvic organ(s) may be needed to achieve clear surgical margins in rectal cancer surgery. An institutional experience is reported with perioperative morbidity and oncological outcomes. Methods Patients were identified retrospectively from a prospectively collected institutional database (1992–2010). Outcomes, and clinical and pathological factors were determined from medical records. Estimated overall survival, overall recurrence and local recurrence were compared using the log rank method and Cox regression analysis. Results Among 1831 patients with rectal cancer, 124 (6·8 per cent) underwent en bloc resection of part or all of an adjacent organ (vagina/uterus/ovary 90, prostate/seminal vesicle 23, bladder/ureter 15, small bowel/appendix 7). Five-year overall survival and local recurrence rates were 53·3 and 18·8 per cent respectively. There was one postoperative death, from multiple organ failure in a patient with liver cirrhosis. Fifty-two patients underwent sphincter-preserving surgery and three (6 per cent) developed an anastomotic leak. On univariable analysis, the only factor associated with local recurrence was completeness of resection (local recurrence rate 15 per cent versus 69 per cent for R0 versus R1 resection; P < 0·001). On multivariable analysis, factors associated with overall survival were sphincter-preserving surgery, absence of metastatic disease and R0 resection. Conclusion Multiple organ resection for locally advanced primary rectal cancer had good oncological outcomes when clear resection margins were achieved.

BACKGROUND: The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC. METHODS: Consecutive patients with SLMRC (disease-free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor-related variables, and treatment-related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence. RESULTS: In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5-year disease-specific survival rate was 51% for the entire cohort with a median follow-up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001). CONCLUSIONS: Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Cancer 2012. © 2012 American Cancer Society.

Background Lynch syndrome (LS), defined by a deleterious (pathogenic) germline mutation in a mismatch repair (MMR) gene, is characterized by early age-of-onset colorectal cancer (CRC). Because clinical criteria for LS, such as the Amsterdam II Criteria, may miss cases, reflex tumor tissue testing of all CRC patients for LS has been proposed. Our study describes the impact of routine immunohistochemistry (IHC) analysis of tumor tissue for loss of MMR protein expression in early age-of-onset CRC patients undergoing resection. Study Design A prospective institutional program was established to perform IHC analysis on all early age-of-onset (≤50 years) CRC patients undergoing resection. Patients with abnormal IHC analysis were referred to the Clinical Genetics Service for further evaluation. The study cohort excluded patients with other polyposis syndromes and inflammatory bowel disease. Results IHC was performed on 198 patients from July 2006 to June 2010. The median age was 42.8 years (range 23.1 to 50.6 years). Abnormal IHC was reported in 38 (19.1%) patients, and 22 (57.8%) with abnormal IHC analysis had germline genetic testing. Seventeen (77.2%) had an alteration detected in an MMR gene: 10 were known to be deleterious mutations and 7 were variants of uncertain significance. Overall, LS was detected in 5.1% of patients. Only 2 of the 10 (20%) with a deleterious mutation actually met the Amsterdam II Criteria. Conclusions Reflex IHC testing for LS on early age-of-onset CRC patients undergoing resection is feasible at the institutional level. This strategy identifies a substantial number of LS patients who would have been missed if genetic testing was based on the Amsterdam II Criteria alone.

To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer.In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K(trans), k(ep), v(e), AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant.Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K(trans) (mean 0.5 min(-1) vs. 0.2 min(-1), P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone.After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR.Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours. These objective quantitative measures may be more helpful than subjective imaging alone Some parameters differed markedly between completely responding and incompletely responding rectal cancers. Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.

Transanal endoscopic microsurgery is an alternative to transanal excision or radical surgery for benign and carefully selected malignant rectal tumors. Advantages over transanal excision include better visualization, access to more proximal lesions, higher likelihood of negative margins, and lower recurrence rates. Compared to radical resection, patients experience lower rates of morbidity and mortality but may have higher rates of local recurrence. A review of a prospectively maintained database of patients scheduled for transanal endoscopic microsurgery was performed. Ninety-three patients underwent 96 procedures for 13 carcinoid tumors, 1 submucosal mass, 46 adenomas, 12 in situ adenocarcinomas, and 21 invasive adenocarcinomas. Of these cases, 81.2% was successfully completed. There were nine complications (11.5%). Final pathology demonstrated 33 in situ and invasive adenocarcinomas. The mean follow-up was 25.9 months. The four recurrences (12.1%) occurred in: one tubulovillous adenoma, two in situ carcinomas, and one T2 lesion. Transanal endoscopic microsurgery is appropriate for benign lesions such as carcinoid tumors and adenomas and can also be curative in carefully selected patients with early-stage invasive rectal cancer. In cases of invasive adenocarcinoma, it should be reserved for low-risk cancers in patients who accept the possible increased risk of recurrence.

Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT. A total of 27 prospectively accrued patients with locally advanced rectal cancer (T3–4/N1) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8–14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUVmax, SUVavg, and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as

Data from randomized controlled trials support use of a diverting stoma in rectal cancer patients with low anastomoses, but there is little data on how this impacts patient quality of life (QOL). This study prospectively evaluates QOL in stage I-III rectal cancer patients undergoing sphincter-preserving surgery (SPS) with a temporary diverting stoma.Patents were identified from a prospective single-institution study of stage I-III rectal cancer patients undergoing SPS. Patients completed the EORTC C30/CR38 QOL scale preoperatively, at stoma closure, and at 6 months. The Stoma Quality of Life (SQOL) was administered at stoma closure. Subscales of the EORTC hypothesized to be affected by a diverting stoma were identified a priori. Longitudinal trends were analyzed using repeated measures ANOVA. Frequencies for responses on specific SQOL items were tabulated, and correlations between SQOL subscales and EORTC Global QOL assessed with Pearson correlation coefficient.Global QOL was reportedly good (mean score 70.2) and did not change with a temporary stoma (P = .83). Physical (P = .33), role (P = .07), and social function (P = .48) were also stable. Decreased body image was observed (P = .03). Stoma-related difficulties identified by the SQOL included sexual activity (53%), leakage (39%), discomfort in clothing (34%), concerns regarding privacy to empty pouch (32%), and feeling unattractive (31%). "Overall satisfaction with life," Work/social function (P.001), sexuality/body image (P = .01), and stoma function (P = .01) subscales of the SQOL correlated strongly with the EORTC Global QOL score (P.001).In this longitudinal study of QOL in rectal cancer patients with a temporary stoma, Global QOL was good despite significant stoma-related difficulties. Use of alternative research methodology is necessary to provide insight into why this contradiction exists.

Adenomatous polyps are found on screening colonoscopy in 22.5% to 58.2% of the adult population and therefore represent a common problem. 1 Patients with multiple adenomatous polyps are of unique interest because a proportion of these patients have an inheritable form of colorectal cancer. Patients with adenomatous polyps are categorized into 6 groups. The first 2 groups are autosomal dominant syndromes, namely, familial adenomatous polyposis (FAP) and its less virulent subtype, attenuated FAP (AFAP). The third group is Lynch syndrome, which is also transmitted in an autosomal dominant fashion and caused by a mutation in a mismatch repair (MMR) gene. Another group is familial colorectal cancersyndromeX(FCCX),whichincludespatientswithastrongfamilyhistoryofcolorectal cancer, also transmitted in anapparent autosomal dominant fashion, but whodo not have a detectable mutation. The fifth group, MUTYH-associated polyposis (MAP), is transmitted in an autosomal recessive manner and is caused by mutations in the MUTYHgene.Somepatientsmaynotmeetthecriteriaforaknownpolyposissyndrome

Evaluation of patients for Lynch syndrome includes assessment of age and family cancer history as well as testing for microsatellite instability and alterations in mismatch repair (MMR) genes. We examined the value of routine immunohistochemistry (IHC) for MMR proteins in patients with colorectal cancer (CRC) undergoing resection at a single institution.Beginning in July 2006, all patients aged50 years who were undergoing resection of primary CRC had their specimens routinely examined by IHC for MMR proteins. Patients aged 50-60 years were examined if histopathology suggestive of Lynch syndrome was reported, and patients of any age were examined if strong clinical suspicion was present. Family cancer history was analyzed and fulfillment of Amsterdam II criteria determined.Over an 18-month period, 96 patients aged50 years underwent CRC resection. Out of these, 72 patients (75%) had immunohistochemical testing, with an overall MMR protein loss rate of 19%. In selected patients aged 50-60 years and60 years, loss rates were 26% and 65%, respectively. Of all patients with MMR protein loss, 10 (32%) had reported histopathology, and 3 (10%) had family histories suggesting Lynch syndrome.We demonstrate the feasibility of routine immunohistochemical testing for MMR proteins in patients with CRC. As only a minority of patients with MMR protein loss met Amsterdam II criteria or had suggestive histopathology reported, routine IHC may identify patients with Lynch syndrome who might otherwise be missed.

Increased local recurrence after total mesorectal excision (TME) in obese rectal cancer patients has been attributed to technical difficulties associated with adiposity. In this study, we evaluate whether higher body mass index (BMI) compromises surgical resection in patients with locally advanced, mid-to-low rectal cancer after neoadjuvant therapy, adversely affecting long-term oncologic outcomes.Five-hundred and ninety-six patients with uT3/4 and/or uN1 rectal adenocarcinoma were treated from 1998 to 2007 with neoadjuvant therapy, followed by radical resection using TME. Outcomes were analyzed according to BMI: obese (BMIor=30) and nonobese (BMI30). Median follow-up was 39 months.In all, 26.7% of patients were obese. The rate for positive circumferential margin in nonobese was 4.9% versus 2.5% in obese (p = 0.21). The sphincter-sparing rate in nonobese was 79.5% versus 80.5% in obese (p = 0.77). Five-year overall survival for nonobese was 84% versus 90% for obese (p = 0.92). Five-year disease-free survival for nonobese was 76% versus 73% for obese (p = 0.75). Operative time was longer in obese than nonobese; 4.3 versus 3.7 hours, respectively (p0.01). Length of stay was longer in obese than nonobese; 8 versus 7 days, respectively (p0.01). Similar results were obtained in analysis stratified by gender.After neoadjuvant therapy for mid-to-low rectal cancer, higher BMI did not compromise sphincter preservation or complete resection or negatively affect long-term outcomes. These findings might be related to the fact that resection was performed in a specialty center with dedicated oncologic surgeons. However, higher BMI was associated with longer operative time, indicating a more technically demanding procedure and longer hospital stay.