Clinicopathological Characteristics of Anastomotic Recurrence After Curative Resection for Colorectal Cancer: Comparison With Nonanastomotic Local Recurrences.

BACKGROUND: Anastomotic recurrence is thought to be caused by implantation of tumor cells to the anastomotic line; however, its risk factors and prognostic significance remain unclear. OBJECTIVE: This study aimed to clarify the risk factors for anastomotic recurrence in colorectal cancer and assess the prognosis in comparison to nonanastomotic local recurrence. DESIGN: A single-center retrospective observational study. SETTINGS: The medical records of the study participants were retrospectively collected from the Department of Surgical Oncology at the University of Tokyo Hospital database. PATIENTS: This study included 1584 patients with colorectal cancer who underwent surgical resection between January 2005 and December 2017. We focused on 15 patients who had an anastomotic recurrence. MAIN OUTCOME MEASURES: The main outcome measures were the risk factors of anastomotic recurrence at the primary resection and prognosis data in comparison to that of nonanastomotic local recurrence. RESULTS: There were 15 patients (0.95%) with anastomotic recurrence and 35 (2.21%) with nonanastomotic local recurrence. Univariate analysis revealed that lymph node metastasis and advanced T stage are the risk factors for anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that of those with nonanastomotic local recurrence who underwent resection. LIMITATIONS: The small number of patients with anastomotic recurrence is a major limitation of this study. Additionally, the retrospective study design may have increased the risk of selection bias. CONCLUSIONS: Lymph node metastasis and advanced T stage were associated with anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that with resected nonanastomotic local recurrence. Thus, surveillance should be carefully continued while considering the poor prognosis of patients with anastomotic recurrence. See Video Abstract at http://links.lww.com/DCR/C92 . CARACTERSTICAS CLINICOPATOLGICAS DE LA RECURRENCIA ANASTOMTICA DESPUS DE LA RESECCIN CURATIVA DEL CNCER COLORRECTAL COMPARACIN CON LAS RECURRENCIAS LOCALES NO ANASTOMTICAS: ANTECEDENTES:Se cree que la recurrencia anastomótica es causada por la implantación de células tumorales en la línea anastomótica; sin embargo, los factores de riesgo asociados y el significado en cuanto a pronóstico siguen sin estar claros.OBJETIVO:Este estudio tuvo como objetivo aclarar los factores de riesgo para la recurrencia anastomótica en el cáncer colorrectal y evaluar el pronóstico en comparación con la recurrencia local no anastomótica.DISEÑO:Un estudio observacional retrospectivo de un solo centro.ESCENARIO:Los registros médicos de los participantes del estudio se recopilaron retrospectivamente de la base de datos del Departamento de Cirugía Oncológica del Hospital de la Universidad de Tokio.PACIENTES:Este estudio incluyó a 1584 pacientes con cáncer colorrectal que se sometieron a resección quirúrgica entre enero de 2005 y diciembre de 2017. Nos enfocamos en 15 pacientes que tuvieron recurrencia anastomótica.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron los factores de riesgo de recurrencia anastomótica en la resección primaria y los datos de pronóstico en comparación con la recurrencia local no anastomótica.RESULTADOS:Hubo 15 pacientes (0.95%) con recurrencia anastomótica y 35 (2.21%) con recurrencia local no anastomótica. El análisis univariable reveló que la metástasis en los ganglios linfáticos y el estadio T avanzado son los factores de riesgo para la recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de aquellos con recidiva local no anastomótica sometidos a resección.LIMITACIONES:El pequeño número de pacientes con recurrencia anastomótica es una limitación importante de este estudio. Además, el diseño retrospectivo del estudio puede haber aumentado el riesgo de sesgo de selección.CONCLUSIONES:La metástasis en los ganglios linfáticos y el estadio T avanzado se asociaron con recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de la recidiva local no anastomótica resecada. Por lo tanto, la vigilancia debe continuarse cuidadosamente considerando el mal pronóstico de los pacientes con recurrencia anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C92 . (Traducción-Dr. Jorge Silva Velazco ).

Improvement in Surgical Outcomes Using 3-Dimensional Printed Models for Lateral Pelvic Lymph Node Dissection in Rectal Cancer.

BACKGROUND: Lateral pelvic lymph node dissection for rectal cancer is challenging due to the complexity of the pelvic wall anatomy, and incomplete lateral pelvic lymph node dissection may result in local recurrence in the lateral pelvis. Although 3-dimensional printed organ models are useful for understanding spatial anatomy, it is currently unclear whether they improve surgical outcomes. OBJECTIVE: We aimed to assess whether the surgical effectiveness of lateral pelvic lymph node dissection is increased by the use of individualized 3-dimensional printed pelvic models. DESIGN: This was a retrospective study using a propensity matching analysis. SETTINGS: This study was conducted at a university hospital in Japan. PATIENTS: In total, 115 patients comprising 184 pelvic sides (right, 85 sides; left, 99 sides) who underwent lateral pelvic lymph node dissection for colorectal adenocarcinoma between January 2012 and December 2019 were enrolled. INTERVENTIONS: We compared surgical outcomes using 3-dimensional printed pelvic models with control outcomes. MAIN OUTCOME MEASURES: The primary outcome was the number of harvested lateral pelvic lymph nodes on 1 pelvic side after the propensity matching analysis. RESULTS: After matching, 35 pelvic sides each were allocated to the 3-dimensional model and control groups, and no significant differences were observed in patient characteristics between the 2 groups. The number of harvested lateral pelvic lymph nodes was significantly higher in the 3-dimensional model group (median, 9; range, 3-16) than in the control group (median, 6; range, 0-22; p = 0.047). LIMITATIONS: This was a retrospective study using propensity score matching. However, historical backgrounds were not matched, and the majority of lateral pelvic lymph node dissection procedures in the 3-dimensional model group were recently performed. This limitation may have influenced surgical outcomes. CONCLUSION: The present study demonstrated that, by referring to individualized 3-dimensional printed pelvic models, colorectal surgeons harvested a larger number of lateral pelvic lymph nodes during lateral pelvic lymph node dissection. This result suggests that 3-dimensional printed models help surgeons to complete more detailed procedures. See Video Abstract at http://links.lww.com/DCR/B776. MEJORA DE LOS RESULTADOS QUIRRGICOS MEDIANTE EL USO DE MODELOS IMPRESOS EN D PARA LA DISECCIN LATERAL DE LOS GANGLIOS LINFTICOS PLVICOS EN EL CNCER DE RECTO: ANTECEDENTES:La disección lateral de los ganglios linfáticos de la pelvis en el cáncer de recto es un desafío debido a la complejidad de la anatomía de la pared pélvica; la disección incompleta de las mismas puede resultar en una recidiva local en dicha zona. Aunque la impresión tridimensional de modelos de órganos es útil para comprender la estructura anatómica espacial, actualmente no está claro si mejoran los resultados quirúrgicos.OBJETIVO:Nuestro objetivo fue evaluar si la efectividad quirúrgica de la disección de los ganglios linfáticos laterales de la pelvis aumenta mediante el uso individualizado de modelos pélvicos impresos en 3D.DISEÑO:Este fue un estudio retrospectivo que utilizó un análisis de coincidencia de propensión.AJUSTE:Este estudio se realizó en un hospital universitario de Japón.PACIENTES:En total, se enrolaron 115 pacientes que comprendían 184 lados pélvicos (85 de lado derecho; 99 de lado izquierdo) que fueron sometidas a disección lateral de ganglios linfáticos de la pelvis por adenocarcinoma colorrectal entre enero de 2012 y diciembre de 2019.INTERVENCIONES:Comparamos los resultados quirúrgicos mediante modelos pélvicos tridimensionales impresos con los resultados de control.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el número de ganglios linfáticos laterales pélvicos extraídos en un lado pélvico después del análisis de coincidencia de propensión.RESULTADOS:Después del emparejamiento, se asignaron 35 lados pélvicos cada uno, tanto al modelo tridimensional como al grupo de control; no se observaron diferencias significativas con respecto a las características de los pacientes entre los dos grupos. El número de ganglios linfáticos pélvicos laterales extraídos fue significativamente mayor en el grupo del modelo tridimensional (mediana, 9; rango 3-16) que en el grupo de control (mediana, 6; rango, 0-22) (p = 0.047).LIMITACIONES:Este fue un estudio retrospectivo que utilizó el emparejamiento por puntuación de propensión. Sin embargo, antecedentes históricos no fueron encontrados y la mayoría de los procedimientos de disección de los ganglios linfáticos laterales pélvicos en el grupo del modelo tridimensional se realizaron recientemente. Esta limitación pudo haber influido en los resultados quirúrgicos.CONCLUSIONES:El presente estudio demostró que al referirse a modelos pélvicos individualizados impresos en 3D, los cirujanos colorrectales recolectaron un mayor número de ganglios linfáticos laterales de la pelvis durante la disección lateral. Este resultado sugiere que los modelos tridimensionales impresos ayudan a los cirujanos a completar procedimientos más detallados. Consulte Video Resumen en http://links.lww.com/DCR/B776.

Laparoscopic vs open restorative proctectomy after total abdominal colectomy for ulcerative colitis or familial adenomatous polyposis.

PURPOSE: Randomized controlled trials (RCTs) demonstrated that a laparoscopic approach provides short-term benefits, such as reduced blood loss and a shorter hospital stay, in patients who undergo rectal surgery. On the other hand, a few RCTs investigating proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP) suggested limited advantages of laparoscopic surgery over open surgery. A substantial proportion of patients with UC or FAP may undergo staged operations with IPAA, but no study has compared the two approaches for proctectomy with IPAA after total abdominal colectomy. METHODS: We examined 61 consecutive patients with UC or FAP who underwent proctectomy with IPAA after colectomy in our hospital. Patients were divided into the Lap group (n = 37) or the Op group (n = 24) according to surgical approach. Patient background and outcomes, such as operative time, blood loss, first bowel movement, postoperative complications, and pouchitis, were compared between these groups. RESULTS: One patient required conversion to open surgery in the Lap group. The median volume of blood loss was 90 mL in the Lap group and 580 mL in the Op group (p < 0.0001). The Lap group showed a shorter time to first bowel movement than the Op group (median: 1 vs 2 days, p = 0.0003). The operative time, frequencies of postoperative complications, and accumulation rate of pouchitis were similar between the two groups. CONCLUSIONS: Laparoscopic surgery was beneficial for patients undergoing restorative proctectomy in terms of blood loss and bowel recovery without increasing the operative time or rate of complications.

Prediction model of Graves' disease in general clinical practice based on complete blood count and biochemistry profile.

Although untreated Graves' disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease. We built a GD prediction model based on information obtained from subjects regarding sex, age, a complete blood count, and a standard biochemistry profile. We built the model in the training set and evaluated the performance of the model in the test set by using the artificial intelligence software Prediction One. Our machine learning-based model showed high discriminative ability to predict GD in the test set (area under the curve [AUC] 0.99). The main contributing factors to predict GD included age and serum creatinine, total cholesterol, alkaline phosphatase, and total protein levels. We still found high discriminative ability even when we restricted the variables to these five most contributory factors in our prediction model (AUC 0.97) built by using artificial intelligence software showed high GD prediction ability based on information regarding only five factors.

Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

BACKGROUND: Although chemoradiotherapy followed by radical surgery without lateral lymph node dissection is the current standard treatment in patients with rectal cancer, recent studies have demonstrated the benefits of adding lateral lymph node dissection to total mesorectal excision in patients with suspected lateral lymph node metastasis. However, the optimal indication for lateral lymph node dissection after chemoradiotherapy has not been determined. OBJECTIVE: This study aimed to establish the optimal indication for lateral lymph node dissection after chemoradiotherapy in patients with rectal cancer. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a single referral hospital. PATIENTS: A total of 279 patients with rectal cancer who underwent chemoradiotherapy followed by radical surgery between 2007 and 2018 were retrospectively enrolled. MAIN OUTCOME MEASURES: The largest lateral lymph nodes on CT were retrospectively assessed and compared with the pathologic results of dissected lateral lymph nodes and recurrences in lateral lymph node areas. RESULTS: The incidence of lateral lymph node metastasis after chemoradiotherapy was estimated to be 9.3%. Although patients with lateral lymph node metastasis frequently developed distant recurrence, 40.4% survived for >5 years without recurrence. An analysis of the lateral lymph node sizes showed that lateral lymph node size ≥8 mm before chemoradiotherapy was the optimal criterion for lateral lymph node dissection, with a sensitivity and specificity of 92.3% and 78.7%. Using this criterion, 72.0% of the patients could be spared lateral lymph node dissection. LIMITATIONS: Because of the retrospective nature of the present study, the selection of patients who underwent lateral lymph node dissection was biased. CONCLUSIONS: The optimal indication for lateral lymph node dissection was lateral lymph node size ≥8 mm before chemoradiotherapy. Cancer could be eradicated in >30% of patients with lateral lymph node metastasis by dissecting metastatic lateral lymph nodes. See Video Abstract at http://links.lww.com/DCR/B428. CRITERIOS DE TAMAO PTIMO PARA LA DISECCIN DE GANGLIOS LINFTICOS LATERALES DESPUS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO: ANTECEDENTES:Aunque la quimiorradioterapia seguida por cirugía radical sin disección de ganglios linfáticos laterales es el tratamiento estándar actual en pacientes con cáncer de recto, estudios recientes han demostrado beneficios de agregar disección de ganglios linfáticos laterales a la escisión mesorrectal total en pacientes con sospecha de metástasis de ganglios linfáticos laterales. Sin embargo, no se ha determinado la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia.OBJETIVO:Este estudio tuvo como objetivo establecer la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo hospital de referencia.PACIENTES:Se inscribieron retrospectivamente un total de 279 pacientes con cáncer de recto que se sometieron a quimiorradioterapia seguida por cirugía radical entre 2007 y 2018.PRINCIPALES MEDIDAS DE VALORACION:Los ganglios linfáticos laterales más grandes en la tomografía computarizada se evaluaron retrospectivamente y se compararon con los resultados patológicos de los ganglios linfáticos laterales disecados y recidivas en las áreas de los ganglios linfáticos laterales.RESULTADOS:Se estimó que la incidencia de metástasis en los ganglios linfáticos laterales después de la quimiorradioterapia fue del 9,3%. Aunque los pacientes con metástasis en los ganglios linfáticos laterales con frecuencia desarrollaron recurrencia a distancia, el 40,4% sobrevivió durante más de 5 años sin recurrencia. Un análisis de los tamaños de los ganglios linfáticos laterales mostró que la mayor dimensión de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia eran el criterio óptimo para la disección de los ganglios linfáticos laterales, con una sensibilidad y especificidad del 92,3% y 78,7%, respectivamente. Utilizando este criterio, el 72,0% de los pacientes podría evitarse la disección de los ganglios linfáticos laterales.LIMITACIONES:Debido a la naturaleza retrospectiva del presente estudio, la selección de pacientes que fueron sometidos a disección de ganglios linfáticos laterales fue sesgada.CONCLUSIÓN:La indicación óptima para la disección de los ganglios linfáticos laterales fue la dimensión mayor de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia. El cáncer se podría erradicar en más del 30% de los pacientes con metástasis en los ganglios linfáticos laterales disecando los ganglios linfáticos laterales metastásicos. Consulte Video Resumen en http://links.lww.com/DCR/B428.

Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. METHODS: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6-12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios. RESULTS: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06-1.71], P = 0.015). The heterogeneity among studies was low (I2  = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. CONCLUSION: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.

Intestinal cancer in patients with Crohn's disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods. METHODS: We conducted a systematic review and meta-analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019. RESULTS: Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43-3.02) and 22.01 (9.10-53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow-up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries. CONCLUSION: Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences.

Does anti-tumor necrosis factor alpha prevent the recurrence of Crohn's disease? Systematic review and meta-analysis.

BACKGROUND AND AIM: Anti-tumor necrosis factor (TNF) α agents are now well known to function as effective treatments for Crohn's disease (CD). Several meta-analyses have revealed the efficacy of anti-TNF therapy for preventing recurrence after surgery; however, the efficacies reported in some prospective studies differed according to the outcomes. Moreover, adverse events (AEs) were not well evaluated. We conducted this systematic review and meta-analysis to evaluate both the efficacy of anti-TNF therapy after stratification by the outcome of interest and the AEs. METHODS: We performed a systematic literature review of studies investigating anti-TNF therapy, CD, and postoperative recurrence. Meta-analyses were performed for endoscopic and clinical recurrence and AEs. RESULTS: A total of 570 participants, including 254 patients in the intervention group and 316 patients in the control group, in eight studies, were analyzed for recurrence. Based on the results of the meta-analysis, the efficacies of anti-TNF therapy at preventing endoscopic and clinical recurrence were as follows: relative risk (RR) 0.34, 95% confidence interval (CI) 0.22-0.53 and RR 0.60, 95% CI 0.36-1.02, respectively. The RR of AEs with anti-TNF therapy was 1.75 (95% CI 0.81-3.79). CONCLUSIONS: Anti-TNF therapy after surgery for CD displays efficacy at preventing endoscopic recurrence for 1-2 years, without increasing the incidence of AEs. However, clinical recurrence was not significantly reduced. The efficacy of postoperative anti-TNF therapy may differ in terms of the outcomes, which include long-term prevention, the avoidance of further surgery, and cost-effectiveness.

A Polymorphism in Interleukin-1ß Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Major complications in patients with ulcerative colitis (UC) include UC-associated cancer (UCAC) and postoperative pouchitis. We aimed to identify SNPs associated with UCAC/high-grade dysplasia (HGD) and pouchitis. METHODS: Patients with UC who underwent ileal pouch-anal anastomosis (IPAA) with >2 years of follow-up after functioning pouches were included. Pouchoscopies were performed at least once to diagnose pouchitis according to the modified pouchitis disease activity index. SNP genotyping was performed for 8 SNPs reportedly associated with UCAC and pouchitis, namely: ELF1 (rs7329174), FCGR2A, (rs1801274), interleukin-1ß (IL-1B; rs1143627), ITLN1 (rs2274910), MHC (rs7765379), TNFα (rs1799964), TNFSF15 (rs3810936), and UHMK1 (rs768910), using TaqMan genotyping technologies. We investigated the association of these SNPs with UCAC/HGD and pouchitis. Patients' background data were retrospectively collected, including the presence of preoperative extraintestinal manifestation (EIM). RESULTS: A total of 91 Japanese patients with UC were included. None of the 8 SNPs were associated with UCAC/HGD in our cohort. Multivariable analyses proved that the presence of preoperative EIM (hazard ratio [HR] 3.313, 95% CI 1.325-8.289) and IL-1B (rs1143627) TT genotype (HR 2.425, 95% CI 1.049-5.61) were independent predictive factors for the development of overall pouchitis. The presence of preoperative EIM (HR 3.977, 95% CI 1.292-12.24) and IL-1B (rs1143627 TT genotype; HR 3.382, 95% CI 1.101-10.39) were also independent predictive factors for the development of chronic pouchitis. CONCLUSIONS: The IL-1B (rs1143627) TT genotype and preoperative EIM were statistically significant predictors of pouchitis development after IPAA in patients with UC.

Low preoperative maximum squeezing pressure evaluated by anorectal manometry is a risk factor for non-reversal of diverting stoma.

PURPOSE: A diverting stoma is created to prevent anastomotic leakage and related complications impairing sphincteric function in rectal surgery. However, diverting stoma may be left unclosed. This study is aimed to analyze preoperative factors including anorectal manometric data associated with diverting stoma non-reversal before rectal surgery. We also addressed complications related to diverting stoma in patients undergoing surgery for rectal malignant tumor. METHODS: A total of 203 patients with rectal malignant tumor who underwent sphincter-preserving surgery with diverting stoma were retrospectively evaluated. The risk factors for non-reversal of diverting stoma were identified by univariate and multivariate analyses. For these analyses, anorectal manometric data were measured before rectal surgery. The association between stoma-related complications and other clinicopathological features was also analyzed. RESULTS: During the median follow-up of 46.4 months, 24% (49 patients) did not undergo stoma reversal. Among parameters that were available before rectal surgery, age ≥ 75 years, albumin < 3.5 g/dl, tumor size ≥ 30 mm, tumor distance from the anal verge < 4 cm, and maximum squeezing pressure (MSP) < 130 mmHg measured by anorectal manometry (ARM) were independent factors associated with stoma non-reversal. The most common stoma-related complication was peristomal skin irritation (25%). Ileostomy was the only factor associated with peristomal skin irritation. CONCLUSION: The current study demonstrated that low preoperative MSP evaluated by ARM, old age, hypoalbuminemia, and a large tumor close to the anus were predictive of diverting stoma non-reversal. Stoma site should be well deliberated when patients have the aforementioned risk factors for diverting stoma non-reversal.

Elemental diet therapy plays a significant role in preventing surgical recurrence of Crohn's disease in the era of biologics.

PURPOSE: Most patients with Crohn's disease (CD) experience surgical recurrence. In this era of novel therapies, we conducted this study to clarify which treatments effectively decrease the risk of surgical recurrence in patients with CD. METHODS: The subjects of this retrospective study were 37 patients with CD. We created cumulative surgery rate curves and performed univariate and multivariate analyses. RESULTS: Univariate analysis revealed that patients who consumed an elemental diet (ED; ≥ 900 kcal/day), anti-tumor necrosis factor-alpha, and thiopurines had a significantly better prognosis than those who did not (p = 0.011, p = 0.025, and p = 0.0080, respectively). Multivariate analysis revealed that ED therapy and thiopurines were independent significant factors for controlling surgical recurrence (p = 0.046 and p = 0.032, respectively). Additional analyses showed that the most promising ED therapeutic dose was ≥ 1200 kcal/day, while an ED therapeutic dose of ≥ 900 kcal/day was acceptable. CONCLUSIONS: Although univariate analyses revealed that all three treatment strategies had significant effects on surgical recurrence in patients with CD, multivariate analysis revealed that only ED therapy was significantly associated with surgical recurrence rates. Thus, ED therapy plays an important role in the management of CD, even in the era of biological therapies.

Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.

Postoperative distant metastasis dramatically affects rectal cancer patients who have undergone neoadjuvant chemoradiotherapy (NACRT). Here, we clarified the association between NACRT-mediated mammalian target of rapamycin (mTOR) signaling pathway activation and rectal cancer metastatic potential. We performed immunohistochemistry for phosphorylated mTOR (p-mTOR) and phosphorylated S6 (p-S6) on surgical specimen blocks from 98 rectal cancer patients after NACRT (cohort 1) and 80 colorectal cancer patients without NACRT (cohort 2). In addition, we investigated the association between mTOR pathway activity, affected by irradiation, and the migration ability of colorectal cancer cells in vitro. Based on the results of the clinical study, p-mTOR was significantly overexpressed in cohort 1 (with NACRT) as compared to levels in cohort 2 (without NACRT) (P < .001). High p-mTOR and p-S6 levels correlated with the development of distant metastasis only in cohort 1. Specifically, high p-S6 expression (HR 4.51, P = .002) and high pathological T-stage (HR 3.73, P = .020) after NACRT were independent predictors of the development of distant metastasis. In vitro, p-S6 levels and migration ability increased after irradiation in SW480 cells (TP53 mutation-type) but decreased in LoVo cells (TP53 wild-type), suggesting that irradiation modulates mTOR signaling and migration through cell type-dependent mechanisms. We next assessed the expression level of p53 by immunostaining in cohort 1 and demonstrated that p-S6 was overexpressed in samples with high p53 expression as compared to levels in samples with low p53 expression (P = .008). In conclusion, p-S6 levels after NACRT correlate with postoperative distant metastasis in rectal cancer patients, suggesting that chemoradiotherapy might modulate the mTOR signaling pathway, promoting metastasis.

Rate of Reoperation Decreased Significantly After Year 2002 in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) can require multiple intestinal surgeries. We examined time trends and risk factors for reoperation in patients with CD who underwent intestinal surgery, focusing on the effects of postoperative medical treatments. METHODS: We performed a retrospective analysis of 1871 patients with CD who underwent initial intestinal resection at 10 tertiary care institutions in Japan, with an initial surgical date after May 1982. We collected data on the background characteristics of all patients, including Montreal Classification, smoking status, and medical therapy after surgery (tumor necrosis factor antagonists [anti-TNF] agents or immunomodulators). The primary outcome was requirement for first reoperation. Rate of reoperation was estimated using the Kaplan-Meier method, and risk factors for reoperation were identified using the Cox regression model. RESULTS: The overall cumulative 5- and 10-year reoperation rates were 23.4% and 48.0%, respectively. Multivariable analysis showed that patients who underwent the initial surgery after May 2002 had a significantly lower rate of reoperation than patients who underwent surgery before April 2002 (hazard ratio [HR], 0.72; 95% CI, 0.61-0.86). Preoperative smoking (HR, 1.40; 95% CI, 1.18-1.68), perianal disease (HR, 1.50; 95% CI, 1.27-1.77), and ileocolic type of CD (HR, 1.42; 95% CI, 1.20-1.69) were significant risk factors for reoperation. Postoperative use of immunomodulators (HR, 0.60; 95% CI, 0.44-0.81) and anti-TNF therapy (HR, 0.71; 95% CI, 0.57-0.88) significantly reduced the risk. Anti-TNF was effective in the bionaive subgroup. CONCLUSIONS: The rate of reoperation in patients with CD significantly decreased after May 2002. Postoperative use of anti-TNF agents might reduce the reoperation rate for bionaive patients with CD.

Utility of a three-dimensional printed pelvic model for lateral pelvic lymph node dissection.

PURPOSE: In patients with advanced lower rectal cancer, the complex pelvic anatomy renders lateral pelvic lymph node dissection to be challenging. Therefore, we evaluated the utility of printing a three-dimensional (3D) pelvic model for lateral pelvic lymph node dissection. METHODS: We included 22 patients who underwent lateral pelvic lymph node dissection for rectal cancer between June 2017 and February 2019. Using CT scans, 3D pelvic images and models were constructed and printed, respectively. Thirty colorectal surgeons subjectively evaluated the utility of 3D pelvic models based on a 5-point Likert scale questionnaire (1 = strongly disagree, 5 = strongly agree). RESULTS: The average Likert score for the question "Would a 3D model be useful for understanding pelvic anatomy?" was 4.68. Cases with clinically diagnosed metastatic lymph nodes (4.79 ± 0.44) scored higher than those without them (4.38 ± 0.77, p = 0.02). For spatial comprehension of pelvic anatomy, 3D models scored higher (4.83) than 3D images (4.36, p < 0.001). The ease of use of 3D models and images was scored 4.60 and 4.20, respectively (p = 0.015). With experience, the 3D image reconstruction time decreased from 900 to 150 min. CONCLUSION: The 3D pelvic models may be helpful for experienced surgeons to understand the pelvic anatomy in lateral pelvic lymph node dissection.

Risk factors and therapeutic significance of inguinal lymph node metastasis in advanced lower rectal cancer.

PURPOSE: This study aimed to clarify predictors and therapeutic significance of inguinal lymph node metastasis (ILNM) in patients with rectal cancer. METHODS: Patients with rectal adenocarcinoma invading the anal canal who underwent curative surgery between 2003 and 2019 were retrospectively reviewed. Synchronous and metachronous lymph node (LN) metastasis were collectively defined as final nodal metastasis (f-LNM). Factors associated with f-LNM were analyzed. Moreover, the "modified therapeutic value index," defined by multiplication of the frequency of f-LNM by the 5-year overall survival rate for patients who received treatment for f-LNM, was calculated for each LN area. RESULTS: A total of 145 patients were enrolled (16 patients with f-ILNM). To predict f-ILNM, the cutoff of the inguinal lymph node (ILN) diameter of 8.5 mm gave an area under the curve of 0.889. Dentate line involvement (odds ratio 33.4) and ILN larger than the cutoff of 8 mm (odds ratio 11.9) were independently associated with f-ILNM. The modified therapeutic value indices of the inguinal, lateral pelvic, and mesorectal LNs in the entire population were 6.1, 8.2, and 20.3 points, respectively. In patients with dentate line invasion by cancer, the index of the ILN increased to 11.7 points. In patients with an ILN > 8 mm, the index further increased to 21.1 points. CONCLUSION: Dentate line involvement and ILN > 8 mm predicted the development of ILNM in patients with rectal cancer invading the anal canal. Treatment of the ILN should be considered for patients with the above predictors given the significant therapeutic outcomes.

Postoperative chemotherapy is associated with prognosis of stage IV colorectal cancer treated with preoperative chemotherapy/chemoradiotherapy and curative resection.

PURPOSE: Advances in systemic chemotherapy have increased the resectability in colorectal cancer (CRC) associated with metastases even if it was initially unresectable. However, what determines the prognosis of stage IV CRC patients treated by preoperative therapy and surgery remains unclear. We attempted to identify prognostic factors in such CRC patients. METHODS: We reviewed stage IV CRC patients who underwent curative resection between December 2007 and May 2019. The patients who underwent conversion chemotherapy for initially unresectable disease and those who received neoadjuvant chemotherapy (NAC) for resectable synchronous metastases or neoadjuvant chemoradiotherapy (NACRT) for advanced lower rectal cancer with resectable metastases were included. Recurrence-free survival (RFS) and overall survival (OS) were examined by multivariate analyses using Cox proportional hazard models. The RFS and OS curves were analyzed according to postoperative adjuvant chemotherapy (AC). RESULTS: Among 70 patients who underwent curative surgery (34 men, mean age: 60 years old), 33 had initially unresectable disease, 23 received NAC, and 14 NACRT. By multivariate analyses, AC was an independent predictor for improved RFS and OS (hazard ratio = 0.29, p = 0.0002, and hazard ratio = 0.37, p = 0.025). Patients treated with AC showed improved RFS and OS than those without AC (2-year RFS rate = 30% vs 19%, p = 0.031, and 3-year OS rate = 87% vs 67%, p = 0.045). CONCLUSION: Because of its association with improved prognosis, AC should be considered for stage IV CRC patients after curative resection regardless of initial resectability status and preoperative therapy.

Loss of RUNX3 Immunoreactivity in Non-Neoplastic Rectal Mucosa May Predict the Occurrence of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND/AIMS: Runt-related transcription factor (RUNX) 3 is a tumor suppressor whose expression is reduced in non-neoplastic rectal mucosa of patients with ulcerative colitis (UC) with coexisting colitis-associated cancer (CAC). We aimed to evaluate RUNX3 utility as a predictive marker for CAC using immunohistochemistry (IHC) for non-neoplastic UC mucosa. METHODS: We retrospectively compared the RUNX3 expression detected by IHC between non-neoplastic rectal biopsy specimens from 20 cases with invasive cancer (CAC group) and 20 cases selected from 138 patients without CAC (non-CAC group) that were treated during the same period (2006-2017) and were matched for sex, duration, extension, and age. We validated the results using tissue microarrays (TMA) of 44 operated cases with CAC. The RUNX3 expression level was determined by calculating the percentage of RUNX3-positive-cells. RESULTS: The RUNX3 expression was lower in the CAC than that in the non-CAC group (35.6 vs. 70.7%, p = 0.03). For a cutoff value of 58%, the sensitivity and specificity for predicting CAC were 75.0 and 70.0% respectively. The immunostaining results for the TMA showed the same trend; 74% of cases with CAC were negative for the RUNX3 expression. CONCLUSION: RUNX3 immunostaining of non-neoplastic mucosa is useful for identifying UC patients at a high risk of developing CAC.

Anastomotic bleeding following ileocolic end-to-side anastomosis using a circular stapler: incidence and risk factors.

PURPOSE: To identify the incidence of and risk factors for postoperative bleeding after ileocolic end-to-side anastomosis using a circular stapler. METHODS: We analyzed, retrospectively, the risk factors for postoperative anastomotic bleeding in patients who underwent right-sided colectomy with end-to-side anastomosis done using a circular stapler during colon tumor surgery at our institute between January 2015 and March 2019. RESULTS: Anastomotic bleeding developed in 10 (3.6%) of the total 279 patients. Univariate analysis revealed that age ≥ 80 years (8.8% vs. 1.9%; P = 0.008) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 1 (12.5% vs. 2.8%; P = 0.014) were significant risk factors for anastomotic bleeding. Postoperative anticoagulation therapy was not a risk factor for anastomotic bleeding. Multivariate analysis revealed that only age ≥ 80 years was an independent risk factor (odds ratio 4.12, 95% confidence interval 1.02-16.68, P = 0.047). Six of the ten patients with anastomotic bleeding were treated conservatively, three were treated by colonoscopic clipping, and one required surgery. CONCLUSION: End-to-side anastomosis is safe and feasible, but must be performed carefully in the elderly, who are at higher risk of anastomotic bleeding.

Management of isolated para-aortic lymph node recurrence of colorectal cancer.

Isolated para-aortic lymph node recurrence (PALNR) after curative surgery for colorectal cancer (CRC) is rare and its optimal management is not defined clearly. This review investigates the best outcomes among published studies on the management of PALNR in the field of CRC. We searched the PubMed database for studies reporting on the management of isolated PALNR in CRC, published in English or Japanese from January, 2000 to December, 2018. Studies including patients with other metastases were excluded. A total of 24 retrospective studies including 227 patients with PALNR were evaluated. The 3-year overall survival (OS) ranged from 60 to 100%, with a median OS of 34-80 months for patients who underwent PALNR dissection, and 14-42 months for patients who received non-surgical treatment. No surgery-related mortality was reported and the incidence of surgical, mainly low-grade, complications ranged from 33 to 52%. The predictors of improved survival outcome included R0 resection margins. Dissection for PALNR from CRC is considered a feasible treatment option that may yield a better prognosis than non-surgical treatment alone. Preoperative chemotherapy or CRT should be considered for their potential benefits, including a reduction in cancer volume and improved R0 resection rates.

Adverse events associated with bidirectional endoscopy with midazolam and pethidine.

Same-day bidirectional endoscopy has been reported to reduce recovery time, and procedure-related cost. The safety of bidirectional endoscopy vs colonoscopy only, while using midazolam and pethidine, has never been evaluated. We reviewed 1,202 consecutive patients who underwent bidirectional endoscopy or colonoscopy only with administration of midazolam and pethidine in Toyoshima Ensdoscopy Clinic. We compared the clinical characteristics and adverse events associated with method of endoscopy (colonoscopy only vs bidirectional endoscopy). Furthermore, multivariate logistic regression analyses were conducted to study the role of age, sex, use of sedative, polypectomy, and bidirectional endoscopy in adverse events. In the bidirectional endoscopy group, the doses of pethidine and midazolam, and the incidence rates of hypoxia and posto-endoscopic nausea were significantly higher. On multivariate analysis, age (odds ratio = 1.061, p<0.001), use of pethidine (odds ratio = 4.311, p = 0.003), and bidirectional endoscopy (odds ratio = 3.658, p<0.001) were independently associated with hypoxia. On multivariate analysis, female sex (odds ratio = 10.25, p = 0.027) and bidirectional endoscopy (odds ratio = 6.051, p = 0.022) were independently associated with post-endoscopic nausea. In conclusion, bidirectional endoscopy could increase hypoxia in elderly patients using pethidine and post-endoscopic nausea in female patients.