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.

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.

Anorectal Transplantation: The First Long-term Success in a Canine Model.

OBJECTIVE: Anorectal transplantation is a challenging procedure but a promising option for patients with weakened or completely absent anorectal function. SUMMARY BACKGROUND DATA: We constructed a canine model of anorectal transplantation, evaluated the long-term outcomes, and controlled rejection and infection in allotransplantation. METHODS: In the pudendal nerve function study, 6 dogs were randomly divided into 2 groups, transection and anastomosis, and were compared with a control using anorectal manometry, electromyography, and histological examination. In the anorectal transplantation model, 4 dogs were assigned to 4 groups: autotransplant, allotransplant with immunosuppression, allotransplant without immunosuppression, and normal control. Long-term function was evaluated by defecography, videography, and histological examination. RESULTS: In the pudendal nerve function study, anorectal manometry indicated that the anastomosis group recovered partial function 6 months postoperatively. Microscopically, the pudendal nerve and the sphincter muscle regenerated in the anastomosis group. Anorectal transplantation was technically successful with a 3-stage operation: colostomy preparation, anorectal transplantation, and stoma closure. The dog who underwent allotransplantation and immunosuppression had 2 episodes of mild rejection, which were reversed with methylprednisolone and tacrolimus. The dog who underwent allotransplantation without immunosuppression had a severe acute rejection that resulted in graft necrosis. Successful dogs had full defecation control at the end of the study. CONCLUSIONS: We describe the critical role of the pudendal nerve in anorectal function and the first long-term success with anorectal transplantation in a canine model. This report is a proof-of-concept study for anorectal transplantation as a treatment for patients with an ostomy because of anorectal dysfunction.

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.

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.

Ki67 expression and localization of T cells after neoadjuvant therapies as reliable predictive markers in rectal cancer.

Chemoradiotherapy (CRT) is the standard neoadjuvant therapy for locally advanced rectal cancer (RC). However, neoadjuvant chemotherapy (NAC) also shows favorable outcomes. Although the immunological environment of RC has been thoroughly discussed, the effect of NAC on it is less clear. Here, we investigated the immunological microenvironment, including T cell infiltration, activation, and topological distribution, of resected RC tissue after neoadjuvant therapies and evaluated the correlation between T cell subsets and patient prognosis. Rectal cancer patients (n = 188) were enrolled and categorized into 3 groups, namely CRT (n = 41), NAC (n = 46), and control (surgery alone; n = 101) groups. Characterization of residual carcinoma cells and T cell subsets in resected tissues was performed using multiplex fluorescence immunohistochemistry. The densities of total and activated (Ki67high ) T cells in tissues after NAC, but not CRT, were higher than in control. In both CRT and NAC groups, patients presenting with higher treatment effects showed aggressive infiltration of T cell subsets into carcinomas. Multivariate analyses of pathological and immunological features and prognosis revealed that carcinoma Ki67high CD4+ T cells after CRT and stromal Ki67high CD8+ T cells after NAC are important prognostic factors, respectively. Our results suggest that evaluation of T cell activation with Ki67 expression and its tumor localization can be used to determine the prognosis of advanced RC after neoadjuvant therapies.

Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells.

T315I mutation found in chronic myelogenous leukemia (CML) and Ph + ALL patients is the most serious one among resistance against BCR/ABL kinase inhibitors including imatinib and is only responsive to ponatinib (PNT). However, the novel strategy is required to reduce life-threatening adverse effects of PNT including ischemic cardiovascular disease. We examined the mechanism of PNT-induced cytotoxicity against a T315I(+) Ph + ALL cell line, TccY/Sr. PNT induced apoptosis (increased sub G1 cells, and cleaved caspase3 and PARP), and suppressed protein expression of MCL1, cyclin D2 and c-myc, which were reversed by a proteasome inhibitor, MG132, suggesting enhanced proteasomal degradation by PNT. Among BCL2 family inhibitors, MCL1 inhibitors (maritoclax and AZD5991) robustly induced cell death, showing the MCL1-dependent survival of TccY/Sr cells. Decreased MCL1 and c-myc expression by PNT was also observed in T315I(+) MEGA2/STIR cells. PNT suppressed PI3K activation followed by AKT inhibition and GSK3 dephosphorylation. PI3K/AKT inhibitors mimicked PNT, suggesting that PI3K/AKT signaling is important for survival of TccY/Sr cells. Moreover, GSK3 inhibitor (SB216763) reduced PNT-induced cytotoxicity and degradation of c-myc and MCL1. AZD5991 exhibited the synergistic action with PNT, anti-cancer drugs and venetoclax (BCL2 inhibitor), suggesting the utility of MCL1 inhibitor alone or in combination as a future clinical option for Ph + leukemia patients.

Prognostic Impact of Curative Resection for Peritoneal Recurrence of Colorectal Cancer.

BACKGROUND: Peritoneal recurrence (PR) of colorectal cancer is a poor prognostic factor but may be treatable by curative resection. We investigated the efficacy of this treatment and identified risk factors for postoperative recurrence. METHODS: The subjects were patients who underwent radical surgery for colorectal cancer between January 2006 and March 2014. Those with PR were retrospectively reviewed. Prognostic factors for overall survival (OS) and risk factors for postoperative recurrence were identified. RESULTS: Among 2256 patients, 66 had PR (2.9%). Surgical resection of PR was performed in 41 patients. Curative resection was achieved macroscopically in 38 cases without diffuse metastases in the peritoneum distant from the primary tumor and with a peritoneal cancer index < 10. In multivariate analysis, curative resection was a significant prognostic factor [hazard ratio (HR) 0.198] for better 5-year OS compared with cases without curative resection (68.7% vs. 6.3%, P < 0.001). In 28 cases with concurrent metastasis, curative resection significantly improved 5-year OS compared with no curative resection (78.7% vs. 0%, P = 0.008). In the 38 patients with curative resection, the 3-year recurrence-free survival rate was 21.4%. In multivariate analysis, concurrent metastasis was a significant risk factor [HR 3.394] for postoperative recurrence, and cases with concurrent metastasis more frequently had recurrence within 2 years after curative resection. CONCLUSIONS: Curative resection improved the prognosis in patients with limited and resectable PR of colorectal cancer with or without concurrent metastasis. However, recurrence after curative resection was common and concurrent metastasis was a risk factor for this recurrence.

Impact of intraoperative indocyanine green fluorescence angiography on anastomotic leakage after laparoscopic sphincter-sparing surgery for malignant rectal tumors.

PURPOSE: Whether indocyanine green fluorescence angiography (ICG-FA) during rectal surgery is effective in reducing anastomotic leakage remains unclear. This study aimed to investigate the effect of intraoperative ICG-FA on anastomotic leakage after sphincter-sparing surgery for malignant rectal tumors. METHODS: This was a retrospective, single-center cohort study conducted on 852 consecutive patients who underwent laparoscopic sphincter-sparing surgery from January 2007 to June 2017 at our institution. The incidence of anastomotic leakage was compared between patients who underwent ICG-FA to determine the proximal resection margin and those in whom this technique was not performed, using logistic regression analysis, including propensity score. RESULTS: A total of eight patients were excluded (one patient with previous low anterior resection and seven patients who underwent simultaneous resection for other primary cancers), resulting in 844 patients being analyzed. Before propensity score matching, 141 patients (16.7%) who underwent ICG-FA were compared with 703 patients (83.3%) in whom ICG-FA was not performed. The incidence of anastomotic leakage was 2.8% (4/141) in the ICG-FA group and 12.4% (87/703) in the control group (p = 0.001). After propensity score matching (n = 420), the patient characteristics between the two groups were well balanced, and the incidence of anastomotic leakage was 2.8% (4/141) in the ICG-FA group and 13.6% (38/279) in the control group (p = 0.001). Logistic regression analyses using propensity score showed that patients who underwent ICG-FA had significantly lower odds of anastomotic leakage. CONCLUSION: Intraoperative ICG-FA is a promising method to reduce anastomotic leakage after laparoscopic rectal surgery.

Forced expression of miR-143 and -145 in cardiomyocytes induces cardiomyopathy with a reductive redox shift.

BACKGROUND: Animal model studies show that reductive stress is involved in cardiomyopathy and myopathy, but the exact physiological relevance remains unknown. In addition, the microRNAs miR-143 and miR-145 have been shown to be upregulated in cardiac diseases, but the underlying mechanisms associated with these regulators have yet to be explored. METHODS: We developed transgenic mouse lines expressing exogenous miR-143 and miR-145 under the control of the alpha-myosin heavy chain (αMHC) promoter/enhancer. RESULTS: The two transgenic lines showed dilated cardiomyopathy-like characteristics and early lethality with markedly increased expression of miR-143. The expression of hexokinase 2 (HK2), a cardioprotective gene that is a target of miR-143, was strongly suppressed in the transgenic hearts, but the in vitro HK activity and adenosine triphosphate (ATP) content were comparable to those observed in wild-type mice. In addition, transgenic complementation of HK2 expression did not reduce mortality rates. Although HK2 is crucial for the pentose phosphate pathway (PPP) and glycolysis, the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) was unexpectedly higher in the hearts of transgenic mice. The expression of gamma-glutamylcysteine synthetase heavy subunit (γ-GCSc) and the in vitro activity of glutathione reductase (GR) were also higher, suggesting that the recycling of GSH and its de novo biosynthesis were augmented in transgenic hearts. Furthermore, the expression levels of glucose-6-phosphate dehydrogenase (G6PD, a rate-limiting enzyme for the PPP) and p62/SQSTM1 (a potent inducer of glycolysis and glutathione production) were elevated, while p62/SQSTM1 was upregulated at the mRNA level rather than as a result of autophagy inhibition. Consistent with this observation, nuclear factor erythroid-2 related factor 2 (Nrf2), Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) were activated, all of which are known to induce p62/SQSTM1 expression. CONCLUSIONS: Overexpression of miR-143 and miR-145 leads to a unique dilated cardiomyopathy phenotype with a reductive redox shift despite marked downregulation of HK2 expression. Reductive stress may be involved in a wider range of cardiomyopathies than previously thought.

Prospective multicenter study of reduced port surgery combined with transvaginal specimen extraction for colorectal cancer resection.

PURPOSE: The relevance of transvaginal specimen extraction (TVSE) combined with reduced port surgery (RPS) remains unknown. This study investigated the feasibility of TVSE with RPS according to short-term outcomes and cosmesis. METHODS: This prospective multicenter study enrolled ten patients at three institutions. For the semi-quantification of each parameter, we administered questionnaires to assess pain (visual analogue scale), subjective/objective wound healing esthetics [photo series questionnaires (PSQ)], and quality of life (QOL). RESULTS: No operative complications occurred, except one case of urinary tract infection, which was promptly cured with antibiotics. On day 0, pain was rated at 2.3 ± 0.67 at rest and 4.9 ± 0.82 during sneezing; these ratings gradually declined over time. The PSQ showed that the patient ratings of wound esthetics after TVSE were not inferior to ratings from patients after conventional laparoscopy or single incision laparoscopic surgery, and they were significantly higher than the patient ratings of wounds after laparotomy (P < 0.05). The QOL scores showed that, in comparison to before surgery, after surgery, patients reported significant deterioration of their physical function (96.67 ± 1.49 vs. 87.33 ± 2.71), emotional function (93.33 ± 2.72 vs. 86.67 ± 2.22), fatigue (7.78 ± 3.72 vs. 26.67 ± 8.31), and pain (6.67 ± 3.69 vs. 18.33 ± 4.61). CONCLUSION: TVSE with RPS for colorectal cancer was feasible and was associated with a low degree of postoperative pain.