Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer.

BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

MRI-based radiomic score increased mrTRG accuracy in predicting rectal cancer response to neoadjuvant therapy.

PURPOSE: To develop a magnetic resonance imaging (MRI)-based radiomics score, i.e., "rad-score," and to investigate the performance of rad-score alone and combined with mrTRG in predicting pathologic complete response (pCR) in patients with locally advanced rectal cancer following neoadjuvant chemoradiation therapy. METHODS: This retrospective study included consecutive patients with LARC who underwent neoadjuvant chemoradiotherapy followed by surgery from between July 2011 to November 2015. Volumes of interest of the entire tumor on baseline rectal MRI and of the tumor bed on restaging rectal MRI were manually segmented on T2-weighted images. The radiologist also provided the ymrTRG score on the restaging MRI. Radiomic score (rad-score) was calculated and optimal cut-off points for both mrTRG and rad-score to predict pCR were selected using Youden's J statistic. RESULTS: Of 180 patients (mean age = 63 years; 60% men), 33/180 (18%) achieved pCR. High rad-score (> - 1.49) yielded an area under the curve (AUC) of 0.758, comparable to ymrTRG 1-2 which yielded an AUC of 0.759. The combination of high rad-score and ymrTRG 1-2 yielded a significantly higher AUC of 0.836 compared with ymrTRG 1-2 and high rad-score alone (p < 0.001). A logistic regression model incorporating both high rad-score and mrTRG 1-2 was built to calculate adjusted odds ratios for pCR, which was 4.85 (p < 0.001). CONCLUSION: Our study demonstrates that a rectal restaging MRI-based rad-score had comparable diagnostic performance to ymrTRG. Moreover, the combined rad-score and ymrTRG model yielded a significant better diagnostic performance for predicting pCR.

Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Rectal stimulation with prebiotics and probiotics before ileostomy reversal: a study protocol for a randomized controlled trial.

BACKGROUND: Ileostomy closure is associated with a high rate of postoperative morbidity, and adynamic ileus is the most common complication, with an incidence of up to 32%. This complication is associated with delayed initiation of oral diet intake, abdominal distention, prolonged hospital stay, and more significant patient discomfort. The present study aims to evaluate the rectal stimulus with prebiotics and probiotics before ileostomy reversal. METHODS: This is a protocol study for an open-label randomized controlled clinical trial. Ethical approval was received (CAAE: 56551722.6.0000.0071). The following criteria will be used for inclusion: adult patients with rectal cancer stages cT3/4Nx or cTxN+ that underwent loop protection ileostomy, patients treated with neoadjuvant chemoradiotherapy, and patients who underwent laparoscopic or robotic total mesorectal excision. Patients will be randomized to one of two groups. The intervention group (with rectal stimulus): the patients will apply 500 ml of saline solution with 6 g of Simbioflora® rectally, once a day, for 15 days before ileostomy closure. The control group (without rectal stimulation): the patients will close the ileostomy with no previous rectal stimulus. The primary outcomes will be the adynamic ileus (need for postoperative nasogastric tube insertion; nausea/vomiting; or intolerance to oral feedings within the first 72 h) and intestinal transit (time to first evacuation/flatus). RESULTS: The patient's enrollment starts in January 2023. We expect to finish in July 2025. DISCUSSION: The findings of this randomized clinical study may have important implications for managing patients undergoing ileostomy reversal. TRIAL REGISTRATION: This study is registered in the Brazilian Trial Registry (ReBEC) under RBR-366n64w. Registration date: 19/07/2022.

Outcomes of redo for failed colorectal or coloanal anastomoses: a systematic review and meta-analysis.

PURPOSE: This study aimed to review the outcomes of redo procedures for failed colorectal or coloanal anastomoses. METHODS: A systematic review was performed using the PubMed, Embase, Cochrane, and LILACS databases. The inclusion criteria were adult patients undergoing colectomy with primary colorectal or coloanal anastomosis and studies that assessed the postoperative results. The protocol is registered in PROSPERO (No. CRD42021267715). RESULTS: Eleven articles met the eligibility criteria and were selected. The studied population size ranged from 7 to 78 patients. The overall mortality rate was 0% (95% confidence interval [CI], 0%-0.01%). The postoperative complication rate was 40% (95% CI, 40%-50%). The length of hospital stay was 13.68 days (95% CI, 11.3-16.06 days). After redo surgery, 82% of the patients were free of stoma (95% CI, 75%-90%), and 24% of patients (95% CI, 0%-39%) had fecal incontinence. Neoadjuvant chemoradiotherapy (P=0.002) was associated with a lower probability of being free of stoma in meta-regression. CONCLUSION: Redo colorectal and coloanal anastomoses are strategies to restore colonic continuity. The decision to perform a redo operation should be based on a proper evaluation of the morbidity and mortality risks, the probability of remaining free of stoma, the quality of life, and a functional assessment.

The impact of the institutional abdominoperineal resections volume on short-term outcomes and expenses: a nationwide study.

BACKGROUND: The aim of this study was to evaluate the influence of the institutional volume of abdominoperineal resections (APR) on the short-term outcomes and costs in the Brazilian Public Health system. METHODS: This population-based study evaluated the number of APRs by institutions performed in the Brazilian Public Health system from January/2010 to July/2022. Data were extracted from a public domain from the Brazilian Public Health system. RESULTS: Four hundred and twelve hospitals performed APRs and were included. Only 23 performed at least 5 APRs per year on average and were considered high-volume institutions. The linear regression model showed that the number of hospital admissions for APRs was negatively associated with in-hospital mortality (Coef. = - 0.001; p = 0.013) and length of stay in the intensive care unit (Coef. = - 0.006; p = 0.01). The number of hospital admissions was not significantly associated with personnel, hospital, and total costs. The in-hospital mortality in high-volume institutions was significantly lower than in low-volume institutions (2.5 vs. 5.9%; p: < 0.001). The mean length of stay in the intensive care unit was shorter in high-volume institutions (1.23 vs. 1.79 days; p = 0.021). In high-volume institutions, the personnel (R$ 952.23 [US$ 186.64] vs. R$ 11,129.04 [US$ 221.29]; p = 0.305), hospital (R$ 4078.39 [US$ 799.36] vs. R$ 4987.39 [US$ 977.53]; p = 0.111), and total costs (R$ 5030.63 [US$ 986.00] vs. R$ 6116.71 [US$ 1198.88]; p = 0.226) were lower. CONCLUSIONS: Higher institutional APR volume is associated with lower in-hospital mortality and less demand for intensive care. The findings of this nationwide study may affect how Public Health manages APR care.

Timing of resection of synchronous colorectal liver metastasis: A systematic review and meta-analysis.

INTRODUCTION: The resection of the primary colorectal tumor and liver metastases is the only potentially curative strategy. In such cases, there is no consensus on whether the resection of the primary tumor and metastases should be performed simultaneously or whether a staged approach should be performed (resection of the primary tumor and after, hepatectomy, or the "liver first" approach). The aim of this study is to evaluate the results of hepatectomy associated with colectomy in colorectal neoplasms, comparing simultaneous and staged resection. METHODS: A systematic literature review was performed in PubMed, Embase, Cochrane, Lilacs, and manual reference search. The last search was in July/2021. Inclusion criteria were: studies that compared simultaneous and staged hepatectomy for colorectal liver metastasis; studies that analyze short and/or long-term outcomes. Exclusion criteria were reviews, letters, editorials, congress abstract, and full-text unavailability. Perioperative outcomes and overall survival were evaluated and, for staged resections, the outcomes associated with each procedure were added. The ROBINS-I and GRADE tools were used to assess the risk of bias and quality of evidence. Synthesis was performed using Forest plots. The PRISMA criteria (PROSPERO: CRD42021243762) were followed. RESULTS: The initial search collected 5655 articles and, after selection, 33 were included, covering 6417 patients. Simultaneous resection was associated with shorter length of stay (DR: -3.48 days [95% confidence interval {CI}: -5.64, -1.32]), but with a higher risk of postoperative mortality (DR: 0.02 [95% CI: 0.01, 0.02]). There was no difference between groups for blood loss (risk difference [RD]: -141.38 ml [95% CI: -348.84, 66.09]), blood transfusion (RD: -0.06 [95% CI: -0.14, 0.03]) and general complications (RD: 0.01 [95% CI: -0.06, 0.04]). The longest operating time in staged surgery was not statistically significant (RD: -50.44 min [95% CI: -102.38, 1.49]). Regarding overall survival, there is no difference between groups (hazard ratio: 0.88; 95% CI: 0.71-1.04). CONCLUSION: Patients must be well selected for each strategy. Simultaneous approach to patients at high surgical risk should be avoided due to increased perioperative mortality. However, when the patient presents a low surgical risk, the simultaneous approach reduces the hospital stay and guarantees long-term results equivalent to staged surgery.

Outcomes of Patients With Local Regrowth After Nonoperative Management of Rectal Cancer After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Clinical complete responders after chemoradiation for rectal cancer are increasingly being managed by a watch-and-wait strategy. Nonetheless, a significant proportion will experience a local regrowth, and the long-term oncological outcomes of these patients is not totally known. OBJECTIVE: The purpose of this study was to analyze the outcomes of patients who submitted to a watch-and-wait strategy and developed a local regrowth, and to compare these results with sustained complete clinical responders. DESIGN: This was a retrospective study. SETTING: Single institution, tertiary cancer center involved in alternatives to organ preservation. PATIENTS: Patients with a biopsy-proven rectal adenocarcinoma (stage II/III or low lying cT2N0M0 at risk for an abdominoperineal resection) treated with chemoradiation who were found at restage to have a clinical complete response. INTERVENTIONS: Rectal cancer patients treated with chemoradiation who underwent a watch-and-wait strategy (without a full thickness local excision) and developed a local regrowth were compared to the remaining patients of the watch-and-wait strategy. MAIN OUTCOME MEASURES: Overall survival between groups, incidence of regrowth' and results of salvage surgery. RESULTS: There were 67 patients. Local regrowth occurred in 20 (29.9%) patients treated with a watch-and-wait strategy. Mean follow-up was 62.7 months. Regrowth occurred at mean 14.2 months after chemoradiation, half of them within the first 12 months. Patients presented with comparable initial staging, lateral pelvic lymph-node metastasis, and extramural venous invasion. The regrowth group had a statistically nonsignificant higher incidence of mesorectal fascia involvement (35.0% vs 13.3%, p = 0.089). All regrowths underwent salvage surgery, mostly (75%) a sphincter-sparing procedure. 5-year overall survival was 71.1% in patients with regrowth and 91.1% in patients with a sustained complete clinical response (p = 0.027). LIMITATIONS: This study was limited by its retrospective evaluation of patient selection for a watch-and-wait strategy and outcomes, as well as its small sample size. CONCLUSIONS: Local regrowth is a frequent event when following a watch-and-wait policy (29.9%); however, patients could undergo salvage surgical treatment with adequate pelvic control. In this series, overall survival showed a statistically significant difference from patients managed with a watch-and-wait strategy who experienced a local regrowth compared to those who did not. See Video Abstract at http://links.lww.com/DCR/B773.RESULTADOS DE LOS PACIENTES CON REBROTE LOCAL, DESPUÉS DEL MANEJO NO QUIRÚRGICO DEL CÁNCER DE RECTO, DESPUÉS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTEANTECEDENTES:Los respondedores clínicos completos, después de la quimiorradiación para el cáncer de recto, se tratan cada vez más mediante una estrategia de observación y espera. No obstante, una proporción significativa experimentará un rebrote local y los resultados oncológicos a largo plazo de estos pacientes, no se conocen por completo.OBJETIVO:El propósito de este estudio, fue analizar los resultados de los pacientes sometidos a una estrategia de observación y espera, que desarrollaron un rebrote local, y comparar estos resultados con respondedores clínicos completos sostenidos.DISEÑO:Este fue un estudio retrospectivo.ENTORNO CLINICO.Institución única, centro oncológico terciario involucrado en alternativas a la preservación de órganos.PACIENTES:Pacientes con un adenocarcinoma de recto comprobado por biopsia (estadio II / III o posición baja cT2N0M0, en riesgo de resección abdominoperineal), tratados con quimiorradiación, y que durante un reestadiaje, presentaron una respuesta clínica completa.INTERVENCIONES:Los pacientes con cáncer de recto tratados con quimiorradiación, sometidos a una estrategia de observación y espera (sin una escisión local de espesor total) y que desarrollaron un rebrote local, se compararon con los pacientes restantes de la estrategia de observación y espera.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia global entre los grupos, incidencia de rebrote y resultados de la cirugía de rescate.RESULTADOS:Fueron 67 pacientes. El rebrote local ocurrió en 20 (29,9%) pacientes tratados con una estrategia de observación y espera. El seguimiento medio fue de 62,7 meses. El rebrote se produjo a la media de 14,2 meses después de la quimiorradiación, la mitad de ellos dentro de los primeros 12 meses. Los pacientes se presentaron con una estadificación inicial comparable, metástasis en los ganglios linfáticos pélvicos laterales e invasión venosa extramural. El grupo de rebrote tuvo una mayor incidencia estadísticamente no significativa de afectación de la fascia mesorrectal (35,0 vs 13,3%, p = 0,089). Todos los rebrotes se sometieron a cirugía de rescate, en su mayoría (75%) con procedimiento de preservación del esfínter. La supervivencia global a 5 años fue del 71,1% en pacientes con rebrote y del 91,1% en pacientes con una respuesta clínica completa sostenida (p = 0,027).LIMITACIONES:Evaluación retrospectiva de la selección de pacientes para una estrategia y resultados de observar y esperar, tamaño de muestra pequeño.CONCLUSIONES:El rebrote local es un evento frecuente después de la política de observación y espera (29,9%), sin embargo los pacientes podrían someterse a un tratamiento quirúrgico de rescate con un adecuado control pélvico. En esta serie, la supervivencia global mostró una diferencia estadísticamente significativa de los pacientes manejados con una estrategia de observación y espera que experimentaron un rebrote local, en comparación con los que no lo hicieron. Consulte Video Resumen en http://links.lww.com/DCR/B773. (Traducción-Dr. Fidel Ruiz Healy).

Surgical technique and considerations about transanal transection and single-stapled (TTSS) anastomosis: the search for a perfect anastomosis

The evaluation of preventivemeasures and risk factors for anastomotic leakage has been a constant concern among colorectal surgeons. In this context, the description of a new way to perform a colorectal, coloanal or ileoanal anastomosis, known as transanal transection and single-stapled (TTSS) anastomosis, deserves an appreciation of its qualities, and a discussion about its properties and technical details. In the present paper, the authors review themost recent efforts aiming to reduce anastomotic dehiscence, and describe the TTSS technique in a patient submitted to laparoscopic total proctocolectomy with ileal pouch-anal anastomosis for familial adenomatous polyposis. Surgical perception raises important advantages such as distal rectal transection under visualization, elimination of double-stapling lines (with cost-effectiveness and potential protection against suture dehiscence), elimination of dog ears, and the opportunity to be accomplished via a transanal approach after open, laparoscopic, or robotic colorectal resections. Future studies to confirm these supposed advantages are needed. (AU)