Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). We reported the short-term outcomes of the VOLTAGE trial that investigated the safety and efficacy of preoperative CRT followed by nivolumab and surgery. Here, we present the 3-year outcomes of this trial. METHODS: Thirty-nine patients with microsatellite stable (MSS) LARC and five patients with microsatellite instability-high (MSI-H) LARC underwent CRT (50.4 Gy) followed by five doses of nivolumab (240 mg) and surgery. The 3-year relapse-free survival (RFS), overall survival (OS), and associations with biomarkers were evaluated. RESULTS: The 3-year RFS rates in patients with MSS and MSI-H were 79.5% and 100%, respectively, and the 3-year OS rates were 97.4% and 100%, respectively. Of the MSS patients, those with pre-CRT PD-L1 positivity, pre-CRT high CD8 + T cell/effector regulatory T cell (eTreg) ratio, pre-CRT high expression of Ki-67, CTLA-4, and PD-1 had a trend toward better 3-year RFS than those without. CONCLUSIONS: Three-year outcomes of patients with MSI-H were better than those of patients with MSS. PD-L1 positivity, elevated CD8/eTreg ratio, and high expression of Ki-67, CTLA-4, and PD-1 could be positive predictors of prognosis in patients with MSS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02948348.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Cytological Analysis of the Surgical Field During Transanal Total Mesorectal Excision for Rectal Cancer: A Prospective Study.

BACKGROUND: An unexpectedly large number of patients experienced local recurrence with transanal total mesorectal excision in Norway. This appears to be associated with cancer cell spillage during surgery. OBJECTIVE: To investigate the surgical field cytology during transanal total mesorectal excision. DESIGN: This was a prospective cohort study. SETTINGS: This study was conducted at a single center between June and December 2020. PATIENTS: Forty patients with rectal cancer underwent transanal total mesorectal excision. Following the irrigation of the surgical field, the water specimens were cytologically evaluated at six representative steps. The first sample was used as an initial control. The second, third, fourth, fifth, and sixth samples were collected after the 1st purse-string suture, rectotomy, the 2nd purse-string suture, specimen resection, and anastomosis, respectively. The clinicopathological features and intraoperative complications of the patients were reviewed. MAIN OUTCOME MEASURES: The primary outcome was to evaluate the presence of cancer cells in washing cytological samples. RESULTS: Of the 40 consecutive patients enrolled in this study, 18 patients underwent neoadjuvant chemoradiotherapy. Incomplete first pursestring suture and rectal perforation were observed in 4 (10.0%) and 3 (7.5%) cases, respectively. In the first sample, 31 (77.5%) patients had malignant cells. Malignant findings were detected in two patients (5.0%) from the second to fifth samples. None of the sixth sample exhibited any malignant findings. LIMITATIONS: This single center study had a small sample size. CONCLUSIONS: Cancer cells were initially detected by cytology, but only a few were observed throughout the procedure; however, cancer cells were not detected in the final surgical field. Further follow-up and novel studies are required to obtain clinically significant findings using cytology during transanal total mesorectal excision. See Video Abstract.

Development of a laparoscopic sigmoidectomy simulator: Sigmaster.

The sigmoid colon simulator was designed to accurately reproduce the anatomical layer structure and the arrangement of characteristic organs in each layer, and to have conductivity so that energy devices can be used. Dry polyester fibers were used to reproduce the layered structures, which included characteristic blood vessels, nerve sheaths, and intestinal tracts. The adhesive strength of the layers was controlled to allow realistic peeling techniques. The features of the Sigmaster are illustrated through a comparison of simulated sigmoidectomy using Sigmaster and actual surgery. We developed a laparoscopic sigmoidectomy simulator called Sigmaster. Sigmaster is a training device that closely reproduces the membrane structures of the human body and allows surgeons to experience the entire laparoscopic sigmoidectomy process.

Comparison between preoperative chemoradiotherapy and lateral pelvic lymph node dissection in clinical T3 low rectal cancer without enlarged lateral lymph nodes.

AIM: The standard strategy for clinical T3 rectal cancer without enlarged lateral lymph nodes is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) in Western countries and TME with bilateral lateral pelvic lymph node dissection (LPLND) in Japan. This study compared surgical, pathological and oncological results of these two strategies. METHOD: Patients who underwent preoperative CRT followed by TME in France (CRT + TME group) and those who underwent TME with LPLND in Japan (TME + LPLND group) for clinical T3 rectal adenocarcinoma without enlarged lateral lymph nodes from 2010 to 2016 were retrospectively analysed. RESULTS: In total, 439 patients were included in this study. The estimated local recurrence rate (LRR), disease-free survival and overall survival at 5 years post-surgery was 4.9%, 71% and 82% in the CRT + TME group, and 8.6%, 75% and 90% in the TME + LPLND group, respectively. Lateral LRR versus non-lateral LRR was 0.5% versus 4.2% in the CRT + TME group and 1.8% versus 6.2% in the TME + LPLND group. Obturator nerve injury and isolated pelvic abscess were shown only in the TME + LPLND group. Urinary complications were more frequent in the TME + LPLND group than in the CRT + TME group. CONCLUSION: Disease-free survival was not significantly different after TME with LPLND and after CRT followed by TME. LRR was not significantly different after both strategies; however, there was a trend for higher LRR after TME with LPLND than after CRT followed by TME. Obturator nerve injury, isolated lateral pelvic abscess and urinary complications should be noted when TME with LPLND is applied.

Two-team lateral lymph node dissection assisted by the transanal approach for locally advanced lower rectal cancer: comparison with the conventional transabdominal approach.

BACKGROUND: An optimal surgical approach to lateral lymph node dissection (LLND) remains controversial. With the recent popularity of transanal total mesorectal excision, a two-team procedure combining the transabdominal and transanal approaches was established as a novel approach to LLND. This study aimed to clarify the safety and feasibility of two-team LLND (2team-LLND) and compare its short-term outcomes with those of conventional transabdominal LLND (Conv-LLND). METHODS: Between April 2013 and March 2020, 463 patients diagnosed with primary locally advanced rectal cancer underwent a transanal total mesorectal excision; among them, 93 patients who underwent bilateral prophylactic LLND were included in this single-center, retrospective study. Among these patients, 50 and 43 patients underwent Conv-LLND (the Conv-LLND group) and 2team-LLND (the 2team-LLND group), respectively. The short-term outcomes, including the operation time, blood loss volume, number of complications, and number of harvested lymph nodes, were compared between the two groups. RESULTS: The intraoperative and postoperative complications in the 2team-LLND group were equivalent to those in the Conv-LLND group; furthermore, the incidence of postoperative urinary retention in the 2team-LLND group was acceptably low (9%). Compared with the Conv-LLND group, the 2team-LLND group had a significantly shorter operation time (P = 0.003), lower median blood loss (P = 0.02), and higher number of harvested lateral lymph nodes (P = 0.0005). CONCLUSION: The intraoperative and postoperative complications of 2team-LLND were comparable with those of Conv-LLND. Thus, 2team-LLND was safe and feasible for advanced lower rectal cancer. Moreover, it was superior to Conv-LLND in terms of the operation time, blood loss volume, and number of harvested lateral lymph nodes. Therefore, it can be a promising LLND approach.

Single-center comparative study of short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers.

BACKGROUND: Transanal total mesorectal excision is a promising surgical treatment for rectal cancer. However, evidence regarding the differences in outcomes between the transanal and laparoscopic total mesorectal excisions is scarce. We compared the short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers. METHODS: This retrospective study included patients who underwent low anterior or intersphincteric resection for middle (5-10 cm) or low (< 5 cm) rectal cancer at the National Cancer Center Hospital East, Japan, from May 2013 to March 2020. Primary rectal adenocarcinoma was confirmed histologically. Circumferential resection margins (CRMs) of resected specimens were measured; margins ≤ 1 mm were considered positive. The operative time, blood loss, hospitalization length, postoperative readmission rate, and short-term treatment results were compared. RESULTS: Four hundred twenty-nine patients were divided into two mesorectal excision groups: transanal (n = 295) and laparoscopic (n = 134). Operative times were significantly shorter in the transanal group than in the laparoscopic group (p < 0.001). The pathological T stage and N status were not significantly different. The transanal group had significantly lower positive CRM rates (p = 0.04), and significantly lower incidence of the Clavien-Dindo grade III (p = 0.02) and IV (p = 0.03) complications. Both groups had distal margin positivity rates of 0%. CONCLUSIONS: Compared to laparoscopic, transanal total mesorectal excision for low and middle rectal cancers has lower incident postoperative complication and CRM-positivity rates, demonstrating the safety and usefulness of local curability for middle and low rectal cancers.

Efficacy of transperineal minimally invasive surgery with laparoscopic abdominoperineal excision for lower rectal cancer.

PURPOSE: In abdominoperineal excision (APE), the advantages of the "down-to-up" approach are expected to be more obvious when performed as a two-team approach, including transperineal minimally invasive surgery (TpMIS). We investigated the efficacy of TpMIS with laparoscopic APE for lower rectal cancer. METHODS: Patients who underwent laparoscopic APE with (n = 20) or without (n = 30) TpMIS between December 2013 and April 2020 were retrospectively reviewed. Patient and tumor characteristics, intraoperative outcome, short-term outcome, and pathological findings were compared. Additional subgroup analyses were performed in technically challenging cases, including male patients, obese patients, and patients with tumors located at the anterior wall. RESULTS: There was no marked difference in the patient or tumor characteristics or short-term outcomes, including morbidity and mortality between the two groups. Pathological results were comparable, and the circumferential resection margin (CRM) positive rate was 10% in both groups. TpMIS achieved a significant reduction in operative time (p = 0.02). In a subgroup analysis, the amount of blood loss was also smaller in males (p = 0.02) and patients with a high BMI (> 25) (p = 0.005) than in others. CONCLUSION: Simultaneously performing TpMIS and laparoscopic APE is feasible owing to the favorable complication and CRM-positive rates. In terms of operative time and blood loss, TpMIS is expected to be advantageous in both easy and challenging cases.

Anastomosis-Related Complications After Stapled Anastomosis With Reinforced Sutures in Transanal Total Mesorectal Excision for Low Rectal Cancer: A Retrospective Single-Center Study.

BACKGROUND: The International Transanal Total Mesorectal Excision Registry group showed that transanal total mesorectal excision included clinical issues regarding anastomosis-related complications. OBJECTIVE: This study evaluated anastomotic complications in patients whose anastomoses were created with the stapler plus reinforced sutures procedure after transanal total mesorectal excision for low rectal cancer. DESIGN: This was a retrospective single-center study. SETTING: The study was conducted at the National Cancer Center Hospital East, Japan. PATIENTS: Between June 2016 and December 2019, 150 patients underwent transanal total mesorectal excision for low rectal cancer. Stapled anastomosis was performed for 55 patients, and coloanal handsewn anastomosis was performed for 95 patients. Blood perfusion of the colon was routinely evaluated with intraoperative indocyanine green fluorescence angiography. All patients who underwent stapled anastomosis received additional handsewn sutures on all rounds of the stapled line. Patients who underwent intersphincteric resection were excluded. MAIN OUTCOME MEASURES: The anastomosis-related complications were compared between the groups. RESULTS: Early anastomotic leakage was found in one (1.8%) and eight (8.4%) patients in the stapled group and handsewn group. Overall anastomosis-related complications, pelvic abscess, and anastomotic stenosis were significantly less frequent in the stapled group (p < 0.001, p < 0.048, and p < 0.032). Incomplete donuts after the stapled anastomosis were observed in 9 patients (16.4%); however, we reinforced all around the stapled line in these patients, and this reduced the subsequent occurrence of anastomotic leakage. LIMITATIONS: First, this was a retrospective single-center study that was not randomized or controlled. Second, there were chronological differences regarding the anastomotic method between the two groups. Third, our study included a relatively small number of patients who received preoperative chemoradiotherapy. CONCLUSIONS: Stapled anastomosis with reinforced handsewn sutures resulted in fewer anastomosis-related complications than did coloanal handsewn anastomosis after transanal total mesorectal excision for low rectal cancer; thus, the former may be superior and should be the preferred method, when technically possible. See Video Abstract at http://links.lww.com/DCR/B749.COMPLICACIONES RELACIONADAS CON LAS ANASTOMOSIS ENGRAMPADAS Y REFORZADAS CON SUTURAS EN LA EXCISIÓN TOTAL DEL MESORRECTO POR VÍA TRANSANAL EN CASOS DE CÁNCER DE RECTO BAJO: ESTUDIO RETROSPECTIVO UNICÉNTRICO. ANTECEDENTES: El grupo del Registro Internacional de Excisión Total del Mesorrecto por vía Transanal mostró que la excisión total mesorrectal transanal incluía problemas clínicos relacionados a las complicaciones involucradas con la anastomosis. OBJETIVO: Se evaluaron las complicaciones anastomóticas en pacientes cuyas anastomosis se realizaron con engrampadora reforzada de suturas después de la excisión total de l mesorrecto por vía transanal en casos de cáncer de recto bajo. DISEO: Estudio retrospectivo unicéntrico. AJUSTE: El Hospital del Centro Nacional del Cáncer del Este, Japón. PACIENTES: Entre junio de 2016 y diciembre de 2019, 150 pacientes se sometieron a excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo. Se realizó anastomosis con engrampadora en 55 y anastomosis coloanal suturada a mano en 95 pacientes. La perfusión tisular sanguínea del colon operado se evaluó de forma rutinaria con angiografía de fluorescencia con verde de indocianina intraoperatoria. Todos los pacientes que se sometieron a anastomosis con grapas recibieron suturas realizadas a mano adicionales sobre la totalidad de la línea de grapas. Se excluyeron los pacientes sometidos a resección interesfintérica. PRINCIPALES MEDIDAS DE RESULTADO: Las complicaciones relacionadas con la anastomosis se compararon entre los grupos. RESULTADOS: Se encontró fuga anastomótica temprana en 1 (1.8%) y 8 (8.4%) pacientes en el grupo de engrampado y en el grupo suturado a mano, respectivamente. En general, las complicaciones relacionadas con la anastomosis, el absceso pélvico y la estenosis anastomótica fueron significativamente menos frecuentes en el grupo con grapas (p < 0.001, p < 0.048, p < 0.032, respectivamente). Se observaron donas incompletas después de la anastomosis grapada en 9 pacientes (16,4%); sin embargo, reforzamos todo alrededor de la línea de grapas en estos pacientes, y esto redujo la aparición posterior de fugas anastomóticas. LIMITACIONES: Inicialmente, este fue un estudio retrospectivo de un solo centro que no fue aleatorizado ni controlado. En segundo lugar, hubo diferencias cronológicas con respecto al método anastomótico entre los dos grupos. En tercer lugar, nuestro estudio incluyó un número relativamente pequeño de pacientes que recibieron quimiorradioterapia preoperatoria. CONCLUSIONES: La anastomosis engrapada reforzada con suturas realizadas a mano dio como resultado menos complicaciones relacionadas con la anastomosis que la anastomosis coloanal suturada a mano después de la excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo; por tanto, el primero puede ser superior y debería ser el método preferido, cuando sea técnicamente posible. Consulte Video Resumen en http://links.lww.com/DCR/B749. (Traducción-Dr. Xavier Delgadillo).

Trans-anal surgery with the taTME technique for rectal gastrointestinal stromal tumors: a retrospective study.

PURPOSE: Rectal gastrointestinal stromal tumors (GISTs) surgery is often challenging owing to the anatomical constraints of the narrow pelvis and tumor hugeness. Despite the increasing number of patients undergoing trans-anal total mesorectal excision (taTME) globally, the feasibility of trans-anal surgery with the taTME technique for rectal GISTs remains unclear. We aimed to evaluate the feasibility of trans-anal surgery with the taTME technique for rectal GISTs. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical findings, surgical outcomes, pathological outcomes, urinary and anal functions, and prognoses of patients who underwent trans-anal surgery with the taTME technique for primary rectal GISTs at the National Cancer Center Hospital East from September 2014 to March 2020. RESULTS: Twenty-one patients with primary rectal GISTs were included in this study. The median distance from the anal verge to the lower edge of the tumor was 40 mm (range, 15-60 mm), and the median tumor size was 59 mm (range, 11-175 mm). Moreover, seven and 14 patients underwent one-team and two-team surgeries, respectively, with curative intent. Nineteen patients (90.5%) underwent anus-preserving surgery, and the urinary tracts were preserved in all cases. Two-team surgery showed a significantly lower blood loss volume and shorter operation time than one-team surgery (58 vs. 222 mL, P = 0.017; 184 vs 356 min, P = 0.041, respectively). The pathological negative-margin resection rate was 100%. During the follow-up period, no patient developed local GIST recurrence and one (4.8%) developed distant metastasis. CONCLUSION: Trans-anal surgery with the taTME technique is feasible for rectal GISTs, and two-team surgery may be more advantageous than one-team surgery in terms of operation time and blood loss.

Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG).

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain 'equipoise' between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer.

BACKGROUND: Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical significance using the mAb. METHODS: A total of 157 patients (86 men and 71 women; median age 63.0 years) with stage III CRC who underwent curative surgery were analyzed for TMEM180 expression as a retrospective cohort design. Immunohistochemistry with anti-TMEM180 mAb was conducted on frozen sections, and the data were evaluated for any correlation with clinicopathological indices or prognosis. SW480 CRC cells were examined to investigate the relationship between the expression of TMEM180 and tumourigenesis of xenografts. RESULTS: In total, 92 cases had low TMEM expression and 65 had high TMEM180 expression. For disease-free survival, hazard ratio in high-TMEM180 cases was 1.449 (95% confidential interval = 0.802-2.619) higher than in low-TMEM180 cases, but the difference was not significant (p = 0.219). For cancer specific survival, hazard ratio in high-TMEM180 cases was 3.302 (95% confidential interval = 1.088-10.020), significantly higher than in low-TMEM180 cases (p = 0.035). In an assay examining in vitro colony-forming activity in soft agar, SW480-WT cells clearly formed colonies, but neither KD1 nor KD2 cells did. The in vivo tumour-initiating activity of SW480 cell lines was positively correlated with the level of TMEM180 expression. CONCLUSION: These results indicate that TMEM180 is a useful marker for clinical prognosis in patients with CRC. We believe that these fundamental data warrant further basic and translational studies of TMEM180, and its mAb, for development of therapeutics against CRC.

Radiologic Factors and Areas of Local Recurrence in Locally Advanced Lower Rectal Cancer After Lateral Pelvic Lymph Node Dissection.

BACKGROUND: Identifying preoperative risk factors of local recurrence and patterns of treatment failure resulting after rectal cancer management is important for planning treatment strategies and improving the results of multidisciplinary care. OBJECTIVE: The purpose of this study was to analyze the associations between the preoperative factors and local recurrence and to investigate the local recurrence areas in patients with locally advanced lower rectal cancer who underwent lateral pelvic lymph node dissection. DESIGN: The study used a retrospective cohort design. SETTINGS: It was conducted at a single institution. PATIENTS: Overall 469 patients with locally advanced lower rectal adenocarcinoma located below the peritoneal reflex who received curative resection with lateral pelvic lymph node dissection during 2010 to 2018 were included. MAIN OUTCOME MEASURES: Independent risk factors for local recurrence were assessed using multivariate Cox regression. Local recurrence was classified into 3 areas using follow-up images. RESULTS: A total of 286 patients underwent upfront surgery, 132 patients received neoadjuvant chemotherapy followed by surgery, and 51 patients received preoperative chemoradiotherapy followed by surgery. Eighty-six patients (18.3%) were extramural venous invasion positive, and 113 patients (24.1%) were circumferential resection margin positive. The median follow-up period was 46 months. Local recurrence showed significant association with extramural venous invasion positive (HR = 2.596 (95% CI, 1.321-5.102); p = 0.006) or circumferential resection margin positive (HR = 2.298 (95% CI, 1.158-4.560); p = 0.017). The incidence of local recurrence was observed in 51 patients (10.8%), with the pelvic plexus and internal iliac area being the most frequent (6.6%), followed by the central pelvis area (3.8%), and was markedly low in the obturator area (0.4%). LIMITATIONS: This was a retrospective, single-institution design. CONCLUSIONS: Extramural venous invasion status and circumferential resection margin status were associated with a high local recurrence rate in patients who underwent lateral pelvic lymph node dissection. In addition, local recurrence in the obturator area was low compared with that in other areas. See Video Abstract at http://links.lww.com/DCR/B683. FACTORES RADIOLGICOS Y REAS DE RECURRENCIA LOCAL EN EL CNCER DE RECTO INFERIOR LOCALMENTE AVANZADO DESPUS DE LA DISECCIN GANGLIONAR PLVICA LATERAL: ANTECEDENTES:El identificar los factores de riesgo preoperatorios para recurrencia local y los patrones de fracaso del tratamiento que resultan del manejo del cáncer de recto es importante para planificar las estrategias de tratamiento y mejorar los resultados de la atención multidisciplinaria.OBJETIVO:Analizar las asociaciones entre los factores preoperatorios y la recidiva local, e investigar las áreas de recidiva local en pacientes con cáncer de recto inferior localmente avanzado que se sometieron a disección de ganglios linfáticos pélvicos laterales.DISEÑO:Un diseño de cohorte retrospectivo.ENTORNO CLÍNICO:Una sola institución.PACIENTES:Un total de 469 pacientes con adenocarcinoma rectal inferior localmente avanzado ubicado debajo del reflejo peritoneal que recibieron resección curativa con disección de ganglios linfáticos pélvicos laterales durante 2010-2018.PRINCIPALES MEDIDAS DE RESULTADO:Los factores de riesgo independientes de recurrencia local se evaluaron mediante regresión de Cox multivariante. La recurrencia local se clasificó en 3 áreas utilizando imágenes de seguimiento.RESULTADOS:Doscientos ochenta y seis pacientes se sometieron a cirugía inicial, 132 pacientes recibieron quimioterapia neoadyuvante seguida de cirugía y 51 pacientes recibieron quimiorradioterapia preoperatoria seguida de cirugía. Ochenta y seis pacientes (18,3%) fueron positivos para invasión venosa extramural y 113 pacientes (24,1%) fueron positivos para el margen de resección circunferencial. La mediana del período de seguimiento fue de 46 meses. La recidiva local mostró una asociación significativa con la invasión venosa extramural positiva (cociente de riesgo: 2,596; intervalo de confianza del 95%: 1,321-5,102; p = 0,006) o el margen de resección circunferencial positivo (cociente de riesgo: 2,298; intervalo de confianza del 95%: 1,158-4,560; p = 0,017). La incidencia de recidiva local se observó en 51 pacientes (10,8%), siendo el plexo pélvico y el área ilíaca interna los más frecuentes (6,6%), seguidos del área pélvica central (3,8%), y fue marcadamente baja en el área del obtudador (0.4%).LIMITACIONES:Un diseño retrospectivo de una sola institución.CONCLUSIONES:El estado de invasión venosa extramural o el estado del margen de resección circunferencial se asociaron con una alta tasa de recurrencia local en pacientes que se sometieron a disección de ganglios linfáticos pélvicos laterales. Además, la recurrencia local en el área del obturador fue baja en comparación con la de otras áreas. Consulte Video Resumen en http://links.lww.com/DCR/B683.

Association between urinary function and resected pattern of the autonomic nerve system after transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal excision (TaTME) is expected to improve the quality of total mesorectal excision as well as preserve urinary function. We aimed to study the frequency and risk factors of urinary dysfunction in rectal cancer patients after TaTME. Moreover, we analysed the association between urinary function and resected pattern of the autonomic nerve system (ANS) in TaTME. METHOD: We retrospectively analysed 231 patients who underwent TaTME at our hospital from 2013 to 2018. Independent risk factors for urinary dysfunction were assessed by multivariate analysis. Urinary dysfunction was defined as a condition that requires urethral catheterisation. We intraoperatively judged and classified the preserved or resected pattern of ANS into four categories. RESULTS: The rate of urinary dysfunction after TaTME was 12.1% at discharge. Multivariate analysis revealed that beyond TME and ANS resection were the two major independent risk factors for urinary dysfunction. Total ANS preservation had reduced rates of urinary dysfunction, and all patients were free from catheterisation 6 months post-surgery. There was a higher rate of urinary dysfunction in total ANS resection than in partial ANS resection at 6 months post-surgery. CONCLUSION: This study showed that urinary function after TaTME was associated with resection of the ANS. Furthermore, the rate of urinary dysfunction and recovery time were closely related to the pattern of ANS resection.

Potential benefit of laparoscopic surgery for rectal cancer on postoperative male sexual function.

AIM: The aim of this retrospective study was to evaluate the incidence of male sexual dysfunction after mid to low rectal cancer surgery and to identify factors associated with postoperative erectile and ejaculatory dysfunction. METHODS: The subjects were 410 consecutive male patients who underwent surgery for mid to low rectal cancer from 2009 to 2015. Two questionnaires on sexual function were administered: the International Index of Erectile Function, and an original questionnaire on ejaculatory status. Erectile and ejaculatory dysfunction were examined before and 3, 6, 12 months after surgery. In patients without preoperative dysfunction, multivariate regression analyses were performed to identify factors associated with the incidence of erectile and ejaculatory dysfunction at 12 months after surgery. RESULTS: Of 410 patients, 234 (57%) gave complete responses to the questionnaires, of whom 108 (46%) and 155 (66%) had severe erectile dysfunction, while 115 (49%) and 168 (72%) had severe ejaculatory dysfunction before and 12 months after surgery, respectively. Of the patients who maintained sexual function preoperatively, the incidence of erectile and ejaculatory dysfunction at 12 months after surgery was 51% (64/126) and 49% (58/119), respectively. In multivariate analysis, age >60 years (P = 0.02), laparotomy (P = 0.002), and creation of a diverting ileostomy (P = 0.003) were independent factors associated with postoperative erectile dysfunction, while age >60 years (P = 0.005), laparotomy (P = 0.04), and lateral lymph node dissection (P = 0.001) were independent factors associated with postoperative ejaculatory dysfunction. CONCLUSION: Sexual dysfunction occurred in almost half of patients after rectal cancer surgery, and was independently associated with several factors, including laparotomy.

A multicentre confirmatory single-arm trial of the safety and efficacy of a transanal drain for prevention of anastomotic leakage after surgery for rectal cancer.

AIM: Recent reports have described the use and efficacy of several types of transanal tube (TAT) for preventing anastomotic leakage by reducing intraluminal pressure. The aim of this study was to evaluate the safety and efficacy of a newly developed TAT for the prevention of anastomotic leakage after low anterior resection (LAR) for rectal cancer. METHOD: A multicentre confirmatory single-arm trial was designed to evaluate the safety and efficacy of a new TAT after LAR for rectal cancer. A total of 115 patients were registered in the trial at several cancer centres and other hospitals. All patients initially received reconstruction with a stapled anastomosis, but 18 then underwent creation of a diverting stoma. Of the remaining 97 patients, the first 96 were included in the protocol-defined primary analysis set. The primary outcome was the incidence of symptomatic leakage and the secondary endpoint was the incidence of complications associated with use of the TAT. The TAT was placed during LAR without creating a covering stoma and the drain was removed 4 or 5 days postoperatively. RESULTS: The rate of symptomatic leakage was 5.2% (95% confidence interval 1.7-11.7), which was significantly lower than the predetermined threshold value of 15.8% (one-sided p-value 0.0013). Only one patient had Grade 3 rectal bleeding that might have been related to use of the TAT. CONCLUSION: This nonrandomized study shows that the TAT appears to be safe and results in lower rates of anastomotic leakage in LAR compared with previous studies.

Sacral neuromodulation for the prevention of a permanent stoma in patients with severe defecation disorder following intersphincteric resection.

PURPOSE: Severe defecation disorder occurs frequently in coloanal anastomosis for low rectal cancer, and may affect quality of life. Sacral neuromodulation (SNM) has been reported to be successful after rectal resection, but there are no results for patients treated with intersphincteric resection (ISR). METHODS: A retrospective single-center study of SNM was performed for patient with defecation disorder following ISR. Pre- and post-treatment bowel frequencies, fecal incontinence episodes, and Wexner, LARS and FIQL scores were assessed to evaluate the efficacy. A good response was defined as ≥ 50% reduction of bowel frequency per day or fecal incontinence episodes per week. RESULTS: 10 patients (7 males, mean age 67.5 years) underwent SNM. All patients had severe fecal incontinence with a median Wexner score of 15 (13-20) and a median LARS score of 41 (36-41). The Wexner score improved after SNM, but not significantly (p = 0.06). LARS and FIQL scores significantly improved after SNM (p = 0.02, p = 0.01). At the end of follow-up, the good response rate was 40%. Three cases without a good response required creation of a permanent stoma. CONCLUSION: Seven out of 10 patients did not require a permanent colostomy after SNM. SNM should be considered before performing a permanent colostomy.

Delorme surgery for colonic mucosal prolapse after intersphincteric resection.

PURPOSE: Mucosal prolapse at the site of anastomosis is a long-term complication unique to ISR. It reduces the QOL of patients due to a worsened anal function and local symptoms around the anus. We herein sought to assess the surgical outcomes after Delorme surgery for these patients. METHODS: ISR was performed in 720 patients with low rectal cancer between January 2001 and March 2019 at the National Cancer Center Hospital East. Among these patients, the 33 (4.5%) who underwent initial Delorme surgery for postoperative colonic mucosal prolapse were identified from the medical records and then were analyzed retrospectively. We estimated the anal function using Wexner's incontinence score and assessed whether local anal symptoms due to the prolapse improved postoperatively. RESULTS: Stoma closure was performed before Delorme surgery in 15 (45.5%) patients, and we compared the preoperative and postoperative anal function in these patients. The average Wexner's incontinence score changed from 15.1 before to 12.9 after Delorme surgery. Local symptoms around the anus improved in all 33 (100%) patients. Recurrence of colonic mucosal prolapse occurred in 5 patients (15%), and Delorme surgery was reperformed in these cases. CONCLUSION: Delorme surgery for colonic mucosal prolapse following ISR has clinical benefits for both improving anal local symptoms and slightly improving the anal function.

Essential anatomy for total mesorectal excision and lateral lymph node dissection, in both trans-abdominal and trans-anal perspective.

BACKGROUND AND PURPOSE: Total Mesorectal Excisions (TME) is the standard treatment of rectal cancer. It can be performed under laparoscopic, robotic or transanal approach. Inadvertent injury to surrounding structure like autonomic nerves is avoidable, no matter which approach is adopted. Lateral lymph node dissection (LLND) is a less commonly performed pelvic operation involving dissection in an unfamiliar area to most general surgeons. This article aims to clarify all the essential anatomy related to these procedures. METHODS: We performed thorough literature search and revision on the pelvic anatomy. Our cases of TME and LLND, under either laparoscopic or transanal approach, were reviewed. We integrated the knowledge from literatures and our own experience. The result was presented in details, together with original figures and intra-operative photos. MAIN FINDINGS: Anatomy of pelvic fascia, autonomic nerve system, anal canal and sphincter complex are core knowledge in performing TME and LLND. CONCLUSIONS: Thorough understanding of the pelvic anatomy enables colorectal surgeons to master these procedures, avoid complication and perform extended resection. On the other hand, surgeons can appreciate the complex pelvic anatomy easier by seeing the pelvis in opposite angles (transabdominal and transaanal view).

The series of smooth muscle structures in the pelvic floors of men: Dynamic coordination of smooth and skeletal muscles.

INTRODUCTION: Recent studies have revealed the extended nature of smooth muscle structures in the pelvic floor, revising the conventional understanding of the "perineal body." Our aim was to clarify the three-dimensional configuration and detailed histological properties of the smooth muscle structures in the region anterior to the rectum and anal canal in men. MATERIALS AND METHODS: Four male cadavers were subjected to macroscopic and immunohistological examinations. The pelvis was dissected from the perineal side, as in the viewing angle during transperineal surgeries. Serial transverse sections of the region anterior to the rectum and anal canal were stained with Masson's trichrome and immunohistological stains to identify connective tissue, smooth muscle, and skeletal muscle. RESULTS: There was a series of smooth muscle structures continuous with the longitudinal muscle of the rectum in the central region of the pelvic floor, and three representative elements were identified: the anterior bundle of the longitudinal muscle located between the external anal sphincter and bulbospongiosus; bilateral plate-like structures with transversely-oriented and dense smooth muscle fibers; and the rectourethral muscle located between the rectum and urethra. In addition, hypertrophic tissue with smooth muscle fibers extended from the longitudinal muscle in the anterolateral portion of the rectum and contacted the levator ani. CONCLUSIONS: The series of smooth muscle structures had fiber orientations and densities that differed among locations. The widespread arrangement of the smooth muscle in the pelvic floor suggests a mechanism of dynamic coordination between the smooth and skeletal muscles.