Publications by authors named "Takahide Shinagawa"

16 Publications

  • Page 1 of 1

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

Digestion 2021 31;102(3):489-498. Epub 2019 Oct 31.

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

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-1β (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.
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http://dx.doi.org/10.1159/000503283DOI Listing
August 2021

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

Clin Gastroenterol Hepatol 2020 04 20;18(4):898-907.e5. Epub 2019 Jul 20.

Department of Internal Medicine, Sakura Medical Centre, Toho University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1016/j.cgh.2019.07.025DOI Listing
April 2020

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Minim Invasive Ther Allied Technol 2020 Aug 22;29(4):202-209. Epub 2019 May 22.

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

Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear. We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups. Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes. Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.
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http://dx.doi.org/10.1080/13645706.2019.1619583DOI Listing
August 2020

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

Digestion 2020 14;101(2):156-164. Epub 2019 Feb 14.

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

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.
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http://dx.doi.org/10.1159/000497272DOI Listing
November 2020

Pine-cone and villi patterns are endoscopic signs suggestive of ulcerative colitis-associated colorectal cancer and dysplasia.

Gastrointest Endosc 2019 03 13;89(3):565-575.e3. Epub 2018 Oct 13.

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

Background And Aims: The appropriate site for targeted biopsy during surveillance colonoscopy for ulcerative colitis (UC) is still unclear. We aimed to clarify key endoscopic findings suggestive of neoplastic lesions for targeted biopsy in UC.

Methods: First, we created 769 stereomicroscopic pictures (509 neoplastic, 260 non-neoplastic) mimicking magnifying colonoscopic images from surgically resected specimens, including areas surrounding 25 neoplastic lesions in 15 patients with colitis-associated cancer at a single referral center. Second, we validated the results by using 113 magnifying endoscopic images (64 neoplastic, 49 non-neoplastic) from 39 lesions in 26 patients. Two evaluators, blinded to the pathologic diagnosis, independently classified them according to Kudo's pit pattern and surface morphology, such as pine-cone/villi patterns. The correlation between stereomicroscopic and pathologic findings (neoplastic vs non-neoplastic) for each image was investigated. The interobserver agreement was assessed using kappa statistics.

Results: In the stereomicroscopic analysis, neoplastic pit patterns (types III-V) were significantly correlated with the presence of neoplasia (sensitivity 77.4%, specificity 89.5%, kappa value 0.677). Pine-cone/villi patterns also showed high specificity (96.8%) but low sensitivity (21.4%, kappa value 0.625) for neoplasia. Endoscopic validation showed similar trends. A revision of the endoscopic findings of flat dysplasia with non-neoplastic pit patterns revealed that a reddish area may facilitate the identification of such lesions.

Conclusions: Targeted biopsies are recommended, especially for lesions showing pine-cone/villi patterns in addition to neoplastic pit patterns. For flat "non-neoplastic pit patterns," a reddish area may be an indication for a biopsy.
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http://dx.doi.org/10.1016/j.gie.2018.09.037DOI Listing
March 2019

Comparison of the guidelines for colorectal cancer in Japan, the USA and Europe.

Ann Gastroenterol Surg 2018 Jan 19;2(1):6-12. Epub 2017 Dec 19.

Department of Surgical Oncology The University of Tokyo Tokyo Japan.

Colorectal cancer (CRC) is one of the most common cancers globally as well as in Japan and has shown a pattern of increasing incidence and mortality rates. Therefore, guidelines for CRC are considered to be crucial for establishing standard medical treatment not only in Japan but also around the world. In this article, we explain the features of the representative guidelines in Japan (Japanese Society for Cancer of the Colon and Rectum [JSCCR]), the USA (National Comprehensive Cancer Network [NCCN]) and Europe (European Society for Medical Oncology [ESMO]) and review the differences among these guidelines for CRC. We focus, in particular, on the descriptions of local treatments, including endoscopic treatment for CRC and transanal excision for lower rectal cancer; surgical treatments with lymph node dissection, including management of lower rectal cancer with lateral lymph node metastasis and laparoscopic surgery; and chemotherapy. Although the guidelines share basic principles, some details are different. Consulting the guidelines of various regions from around the world may aid in more precise and effective examination of the details and backgrounds of our own native guidelines.
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http://dx.doi.org/10.1002/ags3.12047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881304PMC
January 2018

Protrusion on the Depressed Surface of Non-polypoid T1 Colorectal Cancer Is Associated with Venous Invasion.

Anticancer Res 2018 02;38(2):993-1002

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

Aim: The treatment strategies for T1 colorectal cancer (CRC) include both surgical and endoscopic resection. Surgical resection is indicated if lymphovascular invasion is present; however, the endoscopic prediction of lymphovascular invasion has not been reported. We aimed to correlate endoscopic morphology with pathological findings, including lymphovascular invasion, in non-polypoid T1 CRC.

Materials And Methods: We retrospectively investigated 63 patients with non-polypoid T1 CRC surgically resected between 2008 and 2016. Four typical endoscopic findings related to deep submucosal invasion, namely protrusion from a depressed surface, fold convergence, fullness and hardness, were assessed to elucidate their association with pathological findings.

Results: Protrusion was the only finding significantly correlated with positive venous invasion (67.9% of the lesions with protrusion vs. 34.3% of those without protrusion, p=0.01), which was also confirmed by a multivariable analysis (odds ratio(OR)=3.72, 95% confidence interval(CI)=1.24-11.2, p=0.02).

Conclusion: The endoscopic finding of protrusion on a depressed surface may be a sign indicating venous invasion in non-polypoid T1 CRC.
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http://dx.doi.org/10.21873/anticanres.12314DOI Listing
February 2018

Laparoscopic surgery in colon cancer patients treated with chronic anti-thrombotic therapy.

Surg Endosc 2018 08 16;32(8):3509-3516. Epub 2018 Jan 16.

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

Background: Anti-thrombotic medications are commonly used for the treatment and prevention of cardiovascular diseases. Laparoscopic resection of colon cancer has generally been accepted with favorable outcomes being reported in randomized control trials. However, the safety and efficacy of laparoscopic surgery for colon cancer patients receiving chronic anti-thrombotic therapy (AT) remain unclear.

Methods: We identified 951 patients who underwent elective resection for colon cancer between 2009 and 2016 from our database. Patients were classified according to the surgical approach and chronic AT. Clinicopathological factors and surgical outcomes were analyzed between patient groups. Patients' backgrounds were matched using propensity scores in laparoscopic surgery.

Results: Anti-thrombotic drugs were chronically used in 135 patients. Among 714 patients who underwent laparoscopy-assisted surgery, 96 received AT. The laparoscopic approach was superior to open surgery in terms of bleeding, surgical site infections, and hospital stay in patients receiving AT. In laparoscopy-assisted surgery, the AT group patients were older and showed lower hemoglobin and albumin levels than those not receiving AT (non-AT group), and were predominantly male. After propensity score matching, estimated blood loss and operative times were similar between the two groups (93 matched patients). The frequencies of postoperative bleeding (2.2%) and thrombotic complications (0%) in the AT group did not significantly differ from those in the non-AT group (1.1 and 0%, respectively). Moreover, AT did not affect survivals.

Conclusion: Laparoscopic approach appears to be safer and beneficial for colonic cancer patients receiving long-term AT. Bleeding and thrombotic events associated with laparoscopic surgery were not significantly affected by AT.
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http://dx.doi.org/10.1007/s00464-018-6071-xDOI Listing
August 2018

Application of Convolutional Neural Networks in the Diagnosis of Helicobacter pylori Infection Based on Endoscopic Images.

EBioMedicine 2017 Nov 16;25:106-111. Epub 2017 Oct 16.

Tada Tomohiro Institute of Gastroenterology and Proctology, Japan; Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Japan.

Background And Aims: The role of artificial intelligence in the diagnosis of Helicobacter pylori gastritis based on endoscopic images has not been evaluated. We constructed a convolutional neural network (CNN), and evaluated its ability to diagnose H. pylori infection.

Methods: A 22-layer, deep CNN was pre-trained and fine-tuned on a dataset of 32,208 images either positive or negative for H. pylori (first CNN). Another CNN was trained using images classified according to 8 anatomical locations (secondary CNN). A separate test data set (11,481 images from 397 patients) was evaluated by the CNN, and 23 endoscopists, independently.

Results: The sensitivity, specificity, accuracy, and diagnostic time were 81.9%, 83.4%, 83.1%, and 198s, respectively, for the first CNN, and 88.9%, 87.4%, 87.7%, and 194s, respectively, for the secondary CNN. These values for the 23 endoscopists were 79.0%, 83.2%, 82.4%, and 230±65min (85.2%, 89.3%, 88.6%, and 253±92min by 6 board-certified endoscopists), respectively. The secondary CNN had a significantly higher accuracy than endoscopists (by 5.3%; 95% CI, 0.3-10.2).

Conclusion: H. pylori gastritis could be diagnosed based on endoscopic images using CNN with higher accuracy and in a considerably shorter time compared to manual diagnosis by endoscopists.
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http://dx.doi.org/10.1016/j.ebiom.2017.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704071PMC
November 2017

Efficacy of a Surveillance Endoscopy After an Ileorectal Anastomosis in Patients With Ulcerative Colitis.

Clin Gastroenterol Hepatol 2018 01 1;16(1):150-151. Epub 2017 Sep 1.

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

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http://dx.doi.org/10.1016/j.cgh.2017.08.036DOI Listing
January 2018

Results of a 36-year surveillance program for ulcerative colitis-associated neoplasia in the Japanese population.

Dig Endosc 2018 Mar 2;30(2):236-244. Epub 2017 Nov 2.

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

Background And Aim: Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia.

Methods: We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups.

Results: Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96).

Conclusions: Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.
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http://dx.doi.org/10.1111/den.12955DOI Listing
March 2018

Colitis-associated cancer in inflammatory bowel disease and effective endoscopic surveillance programs.

Nihon Rinsho 2017 Mar;75(3):471-476

Patients with longstanding inflammatory bowel disease, such as ulcerative colitis and Crohn's disease are well known to have at high risk of developing colorectal cancer. Oxidative stress-induced DNA damage from chronic inflammation is considered to cause various genomic and epigenomic changes in the intestinal mucosa (e.g., TP53 mutation, microsatellite instability and the methylation of the CpG islands) and the accumulation of such changes may lead to the development of dysplasia in the normal mucosa, which finally grows to become carcinoma. This model of carcinogenesis is called "the dysplasia- carcinoma sequence" of colitis-associated cancer. Surveillance colonoscopy with random biopsy has previously been recommended for the detection of early-phase tumors, which are generally faint and difficult to identify. However, targeted biopsy with chromoendo- scopy has been proposed because of its less invasive nature and cost effectiveness. A randomized controlled trial comparing random and targeted biopsy methods was conducted in Japan and targeted biopsy was shown to be almost comparable to random biopsy in terms of the rate of dysplasia detection. To enable more effective surveillance colonoscopy, the appropriate selection of high-risk patients and biopsy methods are important to allow lesions to be correctly detected.
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March 2017

Small colorectal cancers resembling submucosal tumor with massive submucosal invasion and lymph node metastasis: A report of two cases and review of the literature.

Clin Res Hepatol Gastroenterol 2017 Mar 3;41(2):e19-e23. Epub 2016 Sep 3.

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

Colorectal cancer resembling submucosal tumor (SMT) is very rare. We herein report two cases of small colon carcinoma resembling SMT (80-year-old female and 67-year-old male), which massively invaded into the submucosal layer and accompanied marked lymphatic invasion and lymph node metastasis. We also reviewed the reported cases of colorectal carcinoma resembling SMT (SMT-like group, n=70) and analyzed the clinicopathological characteristics of this group compared with typical colorectal carcinoma cases operated at our institution (control group, n=1723). Tumors in the SMT-like group were significantly smaller in size compared with the control group; the median diameter measured 22mm vs. 37mm (P<0.01), respectively. Histologically, although the tumors in the SMT-like group were small in diameter, they almost all invaded into the submucosal (T1) or deeper layer (T2-4), and the rate of poorly differentiated adenocarcinoma or mucinous adenocarcinoma was significantly higher than that in the control group (48.6% vs. 7.7%; P<0.01). In the subgroup analysis of T1 tumors, the rate of lymphatic invasion in the SMT-like group was also significantly higher than that in the control group (43.8% vs. 15.4%; P<0.01). Carcinoma resembling SMT appears to be invasive and has a high risk of lymphatic invasion even if small in size. Therefore, surgical treatment with dissection of the regional lymph nodes might be necessary in cases with any signs of massive submucosal invasion.
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http://dx.doi.org/10.1016/j.clinre.2016.07.007DOI Listing
March 2017

Hereditary gastrointestinal cancer.

Surg Today 2016 Oct 16;46(10):1115-22. Epub 2015 Dec 16.

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

Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.
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http://dx.doi.org/10.1007/s00595-015-1283-3DOI Listing
October 2016

Hepatic Portal Venous Gas After Colonoscopy for Ulcerative Colitis: A Case Report.

J Crohns Colitis 2015 Nov 17;9(11):1058-9. Epub 2015 Jul 17.

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

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http://dx.doi.org/10.1093/ecco-jcc/jjv125DOI Listing
November 2015

Surveillance colonoscopy for colitis-associated dysplasia and cancer in ulcerative colitis patients.

Dig Endosc 2016 Apr 26;28(3):260-5. Epub 2015 Jul 26.

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

Long-standing ulcerative colitis patients are known to be at high risk for the development of colorectal cancer. Therefore, surveillance colonoscopy has been recommended for these patients. Because colitis-associated colorectal cancer may be difficult to identify even by colonoscopy, a random biopsy method has been recommended. However, the procedure of carrying out a random biopsy is tedious and its effectiveness has also not yet been demonstrated. Instead, targeted biopsy with chromoendoscopy has gained popularity in European and Asian countries. Chromoendoscopy is generally considered to be an effective tool for ulcerative colitis surveillance and is recommended in the guidelines of the British Society of Gastroenterology and the European Crohn's and Colitis Organisation. Although image-enhanced endoscopy, such as narrow-band imaging and autofluorescence imaging, has been investigated as a potential ulcerative colitis surveillance tool, it is not routinely applied for ulcerative colitis surveillance in its present form. The appropriate intervals of surveillance colonoscopy have yet to be determined. Although the Japanese and American guidelines recommend annual or biannual colonoscopy, the British Society of Gastroenterology and the European Crohn's and Colitis Organisation stratified their guidelines according to the risks of colorectal cancer. A randomized controlled trial comparing random and targeted biopsy methods has been conducted in Japan and although the final analysis is still ongoing, the results of this study should address this issue. In the present review, we focus on the current detection methods and characterization of dysplasia/cancer and discuss the appropriate intervals of colonoscopy according to the stratified risks.
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http://dx.doi.org/10.1111/den.12505DOI Listing
April 2016
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