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).

Does Tri-Staple™ technology reduce the risk of anastomotic leakage in colorectal surgery? A propensity score matching analysis.

BACKGROUND AND OBJECTIVES: This study evaluates the Tri-Staple™ technology in colorectal anastomosis. METHODS: Patients who underwent rectosigmoidectomy between 2016 and 2022 were retrospectively evaluated and divided into two groups: EEA™ (EEA) or Tri-Staple™ (Tri-EEA). The groups were matched for age, sex, American Society of Anesthesiologists (ASA), and neoadjuvant radiotherapy using propensity score matching (PSM). RESULT: Three hundred and thirty-six patients were included (228 EEA; 108 Tri-EEA). The groups were similar in sex, age, and neoadjuvant therapy. The Tri-EEA group had fewer patients with ASA III/IV scores (7% vs. 33%; p < 0.001). The Tri-EEA group had a lower incidence of leakage (4% vs. 11%; p = 0.023), reoperations (4% vs. 12%; p = 0.016), and severe complications (6% vs. 14%; p = 0.026). There was no difference in complications, mortality, readmission, and length of stay. After PSM, 108 patients in the EEA group were compared with 108 in the Tri-EEA group. The covariates sex, age, neoadjuvant radiotherapy, and ASA were balanced, and the risk of leakage (4% vs. 12%; p = 0.04), reoperation (4% vs. 14%; p = 0.014), and severe complications (6% vs. 15%; p = 0.041) remained lower in the Tri-EEA group. CONCLUSION: Tri-Staple™ reduces the risk of leakage in colorectal anastomosis. However, this study provides only insights, and further research is warranted to confirm these findings.

Penis metastasis in colon cancer: A case report of an unusual site of dissemination.

INTRODUCTION AND IMPORTANCE: Colorectal cancer is a leading cause of cancer-related deaths worldwide. It is estimated that approximately 1.93 million new cases of colorectal cancer were diagnosed and almost one million global colorectal cancer-caused deaths in 2020. The incidence of colorectal cancer has been dramatically rising at alarming rates worldwide in the last decades. The most often sites of metastases are lymph nodes, liver, lung, and peritoneum. CASE PRESENTATION: We present a rare case of a 63-year-old male patient presenting with a nodule in the penis after being treated for cancer in the hepatic flexure of the colon. Biopsy showed colorectal cancer recurrence in the penis. CLINICAL DISCUSSION: Metastasis from colorectal cancer to the penis is rare and poorly discussed, with scarce data in the literature. CONCLUSION: A high level of suspicion should be adopted for the correct diagnosis and early treatment.

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.

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.

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.

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.