Publications by authors named "Keisuke Hata"

243 Publications

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

Dis Colon Rectum 2021 Oct 29. Epub 2021 Oct 29.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo.

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 three-dimensional printed organ models are useful for understanding spatial anatomy, it currently remains 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 three-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 three-dimensional printed pelvic models with control outcomes.

Main Outcome Measures: The primary outcome was the number of harvested lateral pelvic lymph nodes on one pelvic side after the propensity matching analysis.

Results: After matching, 35 pelvic sides each were allocated to the three-dimensional model and control groups, and no significant differences were observed in patient characteristics between the two groups. The number of harvested lateral pelvic lymph nodes was significantly higher in the three-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 three-dimensional model group were recently performed. This limitation may have influenced surgical outcomes.

Conclusion: The present study demonstrated that by referring to individualized three-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 three-dimensional printed models help surgeons to complete more detailed procedures. See Video Abstract at http://links.lww.com/DCR/B776.
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http://dx.doi.org/10.1097/DCR.0000000000002327DOI Listing
October 2021

Surgical outcomes of robot-assisted laparoscopic partial nephrectomy for cystic renal cell carcinoma.

J Robot Surg 2021 Aug 3. Epub 2021 Aug 3.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

To compare the surgical outcomes of robot-assisted partial nephrectomy (RAPN) between patients with cystic renal cell carcinoma (cRCC) and those with solid RCC (sRCC). We retrospectively analyzed 1065 patients who underwent RAPN between 2013 and 2020 for a pathological diagnosis of RCC. Patients were divided into two groups: cRCC and sRCC. cRCC was diagnosed according to the Bosniak classification system. To minimize selection bias between the two groups, patient variables (patient characteristics) and tumor factors (such as size and complexity) were adjusted using 1:1 propensity score matching. Of the 1065 patients, 94 (9%) were diagnosed with cRCC. Bosniak categories of IIF, III, and IV were noted in 4 (4.2%), 31 (33%), and 59 (63%) patients, respectively. After matching, 83 patients each were assigned to the cRCC and sRCC groups. The operation time in cRCC tended to be longer than in sRCC but not significantly different (164 vs. 150 min, P = 0.0767). Other surgical outcomes, such as change in estimated glomerular filtration rate ( - 5.2 vs.  - 7.2%, P = 0.1577), perioperative complications (14.5 vs. 15.7%, P = 0.9225), estimated blood loss (62 vs. 58 mL, P = 0.5613), or negative surgical margin status (100 vs 99%, P = 0.236), were not significantly different between the two groups. During the follow-up period of about 2 years, one and two patients showed recurrence in the cRCC and sRCC groups, respectively. The surgical outcomes of RAPN were similar between cRCC and sRCC, demonstrating the feasibility of RAPN for cRCC.
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http://dx.doi.org/10.1007/s11701-021-01292-7DOI Listing
August 2021

Risk factors for non-reaching of ileal pouch to the anus in laparoscopic restorative proctocolectomy with handsewn anastomosis for ulcerative colitis.

Intest Res 2021 Mar 12. Epub 2021 Mar 12.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aims: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis and handsewn anastomosis for ulcerative colitis requires pulling down of the ileal pouch into the pelvis, which can be technically challenging. We examined risk factors for the pouch not reaching the anus.

Methods: Clinical records of 62 consecutive patients who were scheduled to undergo RPC with handsewn anastomosis at the University of Tokyo Hospital during 1989-2019 were reviewed. Risk factors for non-reaching were analyzed in patients in whom hand sewing was abandoned for stapled anastomosis because of nonreaching. Risk factors for non-reaching in laparoscopic RPC were separately analyzed. Anatomical indicators obtained from presurgical computed tomography (CT) were also evaluated.

Results: Thirty-seven of 62 cases underwent laparoscopic procedures. In 6 cases (9.7%), handsewn anastomosis was changed to stapled anastomosis because of non-reaching. Male sex and a laparoscopic approach were independent risk factors of non-reaching. Distance between the terminal of the superior mesenteric artery (SMA) ileal branch and the anus > 11 cm was a risk factor for non-reaching.

Conclusions: Laparoscopic RPC with handsewn anastomosis may limit extension and induction of the ileal pouch into the anus. Preoperative CT measurement from the terminal SMA to the anus may be useful for predicting non-reaching.
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http://dx.doi.org/10.5217/ir.2020.00158DOI Listing
March 2021

Evidence-based clinical practice guidelines for inflammatory bowel disease 2020.

J Gastroenterol 2021 06 22;56(6):489-526. Epub 2021 Apr 22.

Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
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http://dx.doi.org/10.1007/s00535-021-01784-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137635PMC
June 2021

Clinical significance of CD8 and FoxP3 tumor-infiltrating lymphocytes and MFG-E8 expression in lower rectal cancer with preoperative chemoradiotherapy.

Mol Clin Oncol 2021 May 5;14(5):87. Epub 2021 Mar 5.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Preoperative chemoradiotherapy (CRT) for rectal cancer contributes to tumor down-staging and decreases locoregional recurrence. However, each patient shows a significantly different response to CRT. Therefore, the identification of predictive factors to CRT response would be beneficial to avoid unnecessary treatment. Cancer immunity in patients has been suggested to play an important role in the eradication of the tumor by CRT. In the present study, the utility of CD8 and forkhead box P3 (FoxP3) tumor-infiltrating lymphocytes (TILs) and the expression of a novel immuno-regulatory factor, lactadherin (MFG-E8), in predicting CRT effectiveness in patients with rectal cancer was examined. A total of 61 patients with rectal cancer, who underwent curative resection following CRT were included in the study. The numbers of CD8 and FoxP3 TILs in a biopsy taken before CRT and MFG-E8 expression level in the specimens obtained at the time of the surgery after CRT were examined using immunohistochemical staining, and their association with clinicopathological characteristics, including patient survival, was determined. The tumors with more CD8 TILs in the biopsy samples before CRT showed a significantly more favorable CRT response. The patients with tumors and a higher number of CD8 TILs before CRT also exhibited significantly longer disease-free and overall survival times. Higher MFG-E8 expression level in post-CRT specimens was significantly associated with favorable CRT response; however, no significant association was found with any other clinicopathological characteristics, including survival time. The number of CD8 TILs before CRT was a valuable predictor for CRT response and was associated with favorable prognosis in patients with lower rectal cancer and who were treated with CRT. High MFG-E8 expression level after CRT was also associated with a favorable CRT response.
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http://dx.doi.org/10.3892/mco.2021.2249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976375PMC
May 2021

Metachronous ileal cancer after surgery for ascending colon cancer in a patient with Lynch syndrome: A case report.

Int J Surg Case Rep 2021 Apr 27;81:105714. Epub 2021 Feb 27.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Introduction And Importance: Colorectal surveillance via colonoscopy in patients with Lynch syndrome reduces the mortality of colorectal cancer. On the other hand, it is unclear whether surveillance for other malignancies, including small bowel cancer, is beneficial. We report a patient with Lynch syndrome who developed ileal cancer after surgery for ascending colon cancer.

Case Presentation: A 47-year-old man visited our hospital for a check-up for positive fecal occult blood. He was diagnosed with ascending colon cancer and met the clinical criteria for the diagnosis of Lynch syndrome based on his past and family history. The Bethesda markers demonstrated high-frequent microsatellite instability. Laparoscopy-assisted right hemicolectomy was performed. He received follow-up colonoscopy the next year, which revealed ileal cancer near the anastomosis. He underwent resection of the second cancer via a laparoscopic approach, and has been free from recurrence for five years.

Clinical Discussion: Small bowel cancer has a dismal prognosis because a high percentage of patients were diagnosed at advanced stages. The diagnosis of metachronous ileal cancer by the first follow-up colonoscopy after surgery for ascending colon cancer offered a long disease-free survival in our patient.

Conclusion: The clinical course suggested the importance of inspecting the small bowel in Lynch syndrome patients, especially when colorectal cancer is diagnosed.
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http://dx.doi.org/10.1016/j.ijscr.2021.105714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941031PMC
April 2021

Establishment of deformable three-dimensional printed models for laparoscopic right hemicolectomy in transverse colon cancer.

ANZ J Surg 2021 Jul 26;91(7-8):E493-E499. Epub 2021 Feb 26.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Applications of three-dimensional (3-D) printed solid organ models for navigation and simulation were previously reported for abdominal surgeries, and their usefulness was shown by subjective evaluation. However, thus far, no study has examined the effect of intraoperative movements for tissue handling. Novel, deformable 3-D printed models of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) were created to optimize laparoscopic right hemicolectomy. The aim of this study was to establish a method using these individualized models for use in surgical practice.

Methods: Deformable 3-D models for laparoscopic right hemicolectomy were created using a 3-D printing flexible filamentous material (thermoplastic polyurethane). Five patients with transverse colon cancer who underwent laparoscopic right hemicolectomy with D3 lymphadenectomy between April 2017 and September 2019 were enrolled in this study. Then, the created patient-specific models were compared with the previously recorded intraoperative video views.

Results: Transverse colon mobilization changed the spatial arrangement of the branches of the SMA and SMV. The 3-D models reproduced the intraoperative view, although approaches to the dominant vessels to complete D3 lymphadenectomy may vary.

Conclusions: Deformable 3-D models of the SMA and SMV with added branches may aid in optimizing laparoscopic right hemicolectomy operations.
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http://dx.doi.org/10.1111/ans.16659DOI Listing
July 2021

A case of pulmonary tumor embolism diagnosed with respiratory distress immediately after FDG-PET/CT scan.

Radiol Case Rep 2021 Mar 15;16(3):718-722. Epub 2021 Jan 15.

Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Acute distress immediately following an F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan is an exceedingly rare event. We report a case whose condition was suddenly deteriorated in the nuclear medicine laboratory, and whose diagnosis was confirmed by FDG-PET/CT. A 67-year-old woman with left renal cell carcinoma (RCC) suddenly complained of dyspnea and tachycardia just after undergoing FDG-PET/CT. PET/CT images showed increased FDG uptakes in the left renal vein, inferior vena cava, right atrium, and bilateral hila. She was diagnosed with a massive tumor embolism from the inferior vena cava to both pulmonary arteries, and urgently underwent tumor embolectomy. FDG-PET/CT was helpful for diagnosing the tumor embolism and differentiating it from bland thromboembolism in this patient with RCC.
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http://dx.doi.org/10.1016/j.radcr.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817422PMC
March 2021

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

J Gastroenterol Hepatol 2021 Jul 3;36(7):1744-1753. Epub 2021 Feb 3.

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

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 (I  = 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.
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http://dx.doi.org/10.1111/jgh.15401DOI Listing
July 2021

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

Dis Colon Rectum 2021 03;64(3):274-283

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.1097/DCR.0000000000001866DOI Listing
March 2021

[The current status and future perspectives of the treatment for colitis-associated cancer].

Nihon Shokakibyo Gakkai Zasshi 2020 ;117(11):931-938

Department of Surgical Oncology, The University of Tokyo.

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http://dx.doi.org/10.11405/nisshoshi.117.931DOI Listing
December 2020

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

Langenbecks Arch Surg 2021 Feb 19;406(1):131-139. Epub 2020 Oct 19.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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.
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http://dx.doi.org/10.1007/s00423-020-02011-wDOI Listing
February 2021

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

J Gastroenterol Hepatol 2021 Apr 14;36(4):864-872. Epub 2020 Oct 14.

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/jgh.15288DOI Listing
April 2021

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

J Gastroenterol Hepatol 2021 Feb 30;36(2):329-336. Epub 2020 Sep 30.

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/jgh.15229DOI Listing
February 2021

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

Surg Today 2021 Feb 18;51(2):250-257. Epub 2020 Aug 18.

Yokoyama Memorial Hospital, Nagoya, Japan.

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.
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http://dx.doi.org/10.1007/s00595-020-02112-5DOI Listing
February 2021

Long-Term Follow-Up of Targeted Biopsy Yield (LOFTY Study) in Ulcerative Colitis Surveillance Colonoscopy.

J Clin Med 2020 Jul 18;9(7). Epub 2020 Jul 18.

Center for Advanced IBD Research and Treatment, Kitasato Institute Hospital, Kitasato University, 5-9-1 Shirokanedai, Minato-ku, Tokyo 108-8642, Japan.

We previously performed a randomized controlled trial (RCT) comparing targeted and random biopsy in neoplasia detection in patients with ulcerative colitis (UC), which showed the short-term effectiveness of targeted biopsy with one-time colonoscopy. In this retrospective cohort study, we investigated the long-term effectiveness of targeted biopsy in tertiary care hospitals, using the follow-up data from patients with UC for ≥ 8 years who had enrolled in the initial RCT. The primary outcome was death from colorectal cancer (CRC). Secondary outcomes were advanced neoplasia (CRC or high-grade dysplasia) and colectomy due to neoplasia after the RCT. We compared these outcomes between target and random groups. Data on 195 of the 221 patients (88.2%) enrolled in the previous RCT were collected from 28 institutions between 2008 and 2019. No patients died of CRC in either group, with a median 8.8-year follow-up demonstrating a robustness for targeted biopsy in terms of CRC death prevention. Advanced neoplasia was detected in four and three patients in the target and random groups, respectively. Colectomy was required due to neoplasia in three patients in each group. The chance of developing CRC in patients with a negative colonoscopy was low, and the targeted biopsy appeared effective in this population. Conversely, patients found with low-grade dysplasia at initial RCT have 10-fold higher risk of progression to high-grade dysplasia and/or CRC. Ten extracolonic malignancies were observed during the follow-up, resulting in four deaths. Panchromoendoscopy was used only in 4.6% and targeted biopsy was only performed in 59.1% of colonoscopies. We recommend targeted biopsy rather than > 33 random biopsies in real-world settings under adequate observation by specialists.
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http://dx.doi.org/10.3390/jcm9072286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408776PMC
July 2020

Colonoscopy using back brace support belt: A randomized, prospective trial.

JGH Open 2020 Jun 7;4(3):441-445. Epub 2019 Nov 7.

Department of Gastroenterology and Hepatology Tokai University School of Medicine Tokyo Japan.

Background And Aim: Looping is a major problem in colonoscopy, and it prolongs procedure time. We evaluated the efficacy and safety of an external abdominal compression device (back brace support belt; Maxbelt) with respect to cecal insertion time and other outcomes.

Methods: We performed a prospective study on outpatients undergoing elective colonoscopy in Toyoshima Endoscopy Clinic. Subjects were randomly assigned to groups and were subjected to either Maxbelt ( = 39) or no device (control, = 38) during colonoscopy. The colonoscopist was blinded to the study. The primary outcome that was observed was insertion time.

Results: The intubation time of the Maxbelt group was shorter than that of the no device group, but the difference was not significant (3.29 4.49 min, = 0.069). After stratifying by age, the use of Maxbelt significantly decreased cecal intubation time in elderly participants (age ≥ 45) compared to no device group (3.27 5.00 min, = 0.032). The use of the Maxbelt significantly decreased insertion difficulty encountered by the colonoscopist ( = 0.01). There was no difference in adenoma detection rate, manual pressure, position change, and adverse event.

Conclusions: The use of a back brace support belt could be a viable approach for colonoscopy in elderly patients. (University Hospital Medical Information Network: UMIN000029361).
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http://dx.doi.org/10.1002/jgh3.12276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273705PMC
June 2020

Expert endoscopists with high adenoma detection rates frequently detect diminutive adenomas in proximal colon.

Endosc Int Open 2020 Jun 25;8(6):E775-E782. Epub 2020 May 25.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan.

Adenoma detection rate (ADR) is an important quality indicator in colonoscopy, and improved ADR decreases the incidence of colorectal cancer. We investigated differences in polyp detection according to the endoscopist's ADR. We performed a propensity-score matching study using baseline patient characteristics of age, sex, body mass index, family history of colorectal cancer, smoking, drinking, indication for colonoscopy, bowel preparation, and colonoscope type. We compared polyp detection and colonoscopy procedures between patients who underwent colonoscopy by high-ADR endoscopists (high ADR group) and by low-ADR endoscopists (low ADR group). We matched 334 patients in the high ADR group with 334 in the low ADR group. The ADR was 44.0 % and 26.9 % for the high-ADR and low-ADR endoscopists, respectively. Proximal, nonprotruding, and diminutive adenomas were more frequently detected by high-ADR endoscopists than by low-ADR endoscopists (all  < 0.001); similarly, more high-risk adenomas were detected by high-ADR endoscopists (  = 0.028). Furthermore, more sessile serrated polyps detected by high-ADR endoscopists (  = 0.041). High-ADR endoscopists more frequently performed pancolonic chromoendoscopy (  < 0.001). Expert detectors often found nonprotruding and diminutive adenomas in the proximal colon along with increased detection rate of high-risk adenomas. Low-ADR endoscopists need to recognize the features of missed adenomas to improve their ADRs.
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http://dx.doi.org/10.1055/a-1136-9971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247898PMC
June 2020

Nodularity-like appearance in the cardia: novel endoscopic findings for infection.

Endosc Int Open 2020 Jun 25;8(6):E770-E774. Epub 2020 May 25.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

  -associated nodular gastritis, which is associated with follicular lymphoid hyperplasia, is mainly recognized in the antrum. However, we have also observed nodularity-like appearance in the cardia. This study aimed to investigate the clinical significance of cardiac nodularity-like appearance in -associated gastritis.  Patients who underwent esophagogastroduodenoscopy and were evaluated for infection for the first time were enrolled. A nodularity-like appearance in the cardia was defined as a miliary nodular appearance or scattered appearances of small circular whitish coloration. infection was diagnosed according to serum anti- antibody and the urea breath test or histology. Accuracy of the infection diagnoses based on nodularity-like appearance were assessed.  Among 265 patients, 42 patients (15.8 %) were diagnosed as positive for . Cardiac nodularity-like appearance and antral nodularity were recognized in 25 and 15 patients, respectively. In accuracy of predicting by cardiac nodularity-like appearance, specificity was 0.996, sensitivity was 0.571, positive predictive value was 0.960, negative predictive value was 0.925, and accuracy was 0.928. The sensitivity of cardiac nodularity-like appearance was significantly higher than that of antral nodularity (  = 0.0284).  Cardiac nodularity-like appearance had a high accuracy rate for infection diagnosis. Cardiac nodularity-like appearance was found more frequently than antral nodularity.
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http://dx.doi.org/10.1055/a-1136-9890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247899PMC
June 2020

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

Surg Today 2020 Nov 20;50(11):1368-1374. Epub 2020 May 20.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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.
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http://dx.doi.org/10.1007/s00595-020-02022-6DOI Listing
November 2020

Anal canal adenocarcinoma with pagetoid spread and inguinal lymph node metastasis treated with preoperative chemoradiotherapy: A case report.

Mol Clin Oncol 2020 Jun 16;12(6):529-532. Epub 2020 Mar 16.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread.
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http://dx.doi.org/10.3892/mco.2020.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179386PMC
June 2020

Clinical diagnosis of a double primary sigmoid colon cancer and metastatic tumour using a gene-targeted panel test: a case report.

ANZ J Surg 2020 11 25;90(11):E139-E140. Epub 2020 Apr 25.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/ans.15921DOI Listing
November 2020

Laparoscopic surgery for T4 colon cancer: a risk factor for peritoneal recurrences?

Surgery 2020 07 15;168(1):119-124. Epub 2020 Apr 15.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background: Although some preclinical studies have inferred that laparoscopic surgery for advanced cancer may increase the risk of peritoneal metastasis, this potential hazard has not been fully evaluated in the clinical setting. This study aimed to clarify whether laparoscopic surgery is associated with an increased risk of postoperative peritoneal recurrence after resection of T4 colon cancer.

Methods: This study included 272 patients who underwent curative resection for pathological T4a colon cancer without distant metastases at the University of Tokyo Hospital between 1997 and 2017. Multivariable Fine-Gray analysis was performed to evaluate whether the use of laparoscopy was an independent risk factor for postoperative peritoneal recurrence. Thereafter, oncological outcomes (overall and relapse-free survival, and organ-specific recurrence) were compared between laparoscopic colectomy and open colectomy using propensity score matching.

Results: Multivariable analysis found that laparoscopic surgery was a significant risk factor for postoperative peritoneal recurrence (hazard ratio: 1.89; 95% confidence interval: 1.01-3.65; P = .046). Comparison after propensity score matching revealed that the incidence of peritoneal recurrence was significantly higher after laparoscopic colectomy than after open colectomy (5-year cumulative incidence: 28.1% vs 12.1%; P = .003).

Conclusion: This study suggested that laparoscopic surgery may be related to an increased risk of peritoneal recurrence in patients with pathological T4a colon cancer. Clinicians should be fully aware of this potential risk and seek an optimal treatment plan for the prevention and early detection of peritoneal metastasis.
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http://dx.doi.org/10.1016/j.surg.2020.02.026DOI Listing
July 2020

Upfront Surgery for Small Intestinal Non-Hodgkin's Lymphoma.

Anticancer Res 2020 Apr;40(4):2373-2377

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: The clinical significance of surgery for secondary small intestinal non-Hodgkin's lymphomas (NHL) remains unknown. This study aimed to investigate the efficacy of resection for both primary and secondary small intestinal NHL.

Patients And Methods: Twenty patients with small intestinal lymphoma who underwent surgical resection at our Institute between 2009 and 2017 were retrospectively evaluated. The clinicopathological and surgery-related factors were reviewed. We also analyzed their surgical outcomes such as postoperative complications, perforation rate, and overall survival (OS).

Results: In total, 13 (65%) and 7 (35%) patients had primary and secondary lymphomas, respectively. A total of 70% of patients were diagnosed with aggressive-type lymphomas. A total of 15 (75%) patients had Lugano system stage IV. Only one (5%) patient experienced postoperative grade II deep vein thrombosis and pulmonary embolism. The 3-year OS rate after surgery was 59.6%.

Conclusion: Surgical resection prior to chemotherapy is a feasible and safe therapeutic strategy for small intestinal NHL.
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http://dx.doi.org/10.21873/anticanres.14206DOI Listing
April 2020

The Influence of Neoadjuvant Chemoradiation for Middle and Lower Rectal Cancer on Anorectal Function.

Anticancer Res 2020 Apr;40(4):2199-2208

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: To date, there is no clear understanding whether preoperative long-course chemoradiotherapy combined with surgery for rectal cancer is detrimental to anorectal function. The purpose of this study was to clarify the influence of preoperative chemoradiotherapy and surgery for middle and lower rectal cancer on postoperative anorectal function.

Patients And Methods: Data of 113 patients with middle or lower rectal cancer treated with preoperative chemoradiotherapy plus surgery or surgery alone between January 2013 and December 2016 were analyzed. A total of 84 and 29 patients underwent low anterior resection and intersphincteric resection, respectively. In patients with T3 or deeper and with any N stage cancer below peritoneal reflection, surgery plus lateral lymph node dissection or preoperative radiation (total: 50.4 Gy/28 fractions) to the pelvis with chemoradiotherapy plus surgery was treated. Anorectal function was assessed prior to treatment and 6 and 12 months postoperatively. Specifically, maximum resting pressure and maximum squeezing pressures were measured. The Wexner score was recorded prior to treatment and 12 months postoperatively.

Results: maximum resting pressure and maximum squeezing pressure decreased post-surgery in both groups. Maximum resting pressure and maximum squeezing pressure at 12 months and the Wexner score at 12 months post-surgery were comparable among patients treated with chemoradiotherapy plus surgery and those treated with surgery alone.

Conclusion: Preoperative chemoradiotherapy did not clearly impair postoperative anorectal function in patients who underwent low anterior resection and intersphincteric resection.
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http://dx.doi.org/10.21873/anticanres.14181DOI Listing
April 2020

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

Int J Colorectal Dis 2020 May 2;35(5):905-910. Epub 2020 Mar 2.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

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.
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http://dx.doi.org/10.1007/s00384-020-03534-wDOI Listing
May 2020

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

Int J Colorectal Dis 2020 Apr 3;35(4):655-664. Epub 2020 Feb 3.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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.
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http://dx.doi.org/10.1007/s00384-020-03520-2DOI Listing
April 2020

Adverse events associated with bidirectional endoscopy with midazolam and pethidine.

J Clin Biochem Nutr 2020 Jan 30;66(1):78-81. Epub 2019 Oct 30.

Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan.

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, <0.001), use of pethidine (odds ratio = 4.311,  = 0.003), and bidirectional endoscopy (odds ratio = 3.658, <0.001) were independently associated with hypoxia. On multivariate analysis, female sex (odds ratio = 10.25,  = 0.027) and bidirectional endoscopy (odds ratio = 6.051,  = 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.
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http://dx.doi.org/10.3164/jcbn.19-73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983442PMC
January 2020

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

Cancer Sci 2020 Apr 22;111(4):1291-1302. Epub 2020 Feb 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/cas.14332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156826PMC
April 2020

Assessment of the Changes in Mitochondrial Gene Polymorphism in Ulcerative Colitis and the Etiology of Ulcerative Colitis-associated Colorectal Cancer.

Anticancer Res 2020 Jan;40(1):101-107

Department of Surgical Oncology, the University of Tokyo, Tokyo, Japan.

Background: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer.

Materials And Methods: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared.

Results: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC.

Conclusion: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.
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http://dx.doi.org/10.21873/anticanres.13931DOI Listing
January 2020
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