Adenocarcinoma is a common histological type of ulcerative colitis-associated cancer (UCAC), whereas neuroendocrine carcinoma (NEC) is extremely rare. UCAC is generally diagnosed at an advanced stage, even with regular surveillance colonoscopy. A 41-year-old man with a 17-year history of UC began receiving surveillance colonoscopy at the age of 37 years; 2 years later, dysplasia was detected in the sigmoid colon, and he underwent colonoscopy every 3 to 6 months. Approximately 1.5 years thereafter, a flat adenocarcinoma lesion occurred in the rectum. Flat lesions with high-grade dysplasia were found in the sigmoid colon and surrounding area. The patient underwent laparoscopic total proctocolectomy and ileal pouch-anal anastomosis with ileostomy. Adenocarcinoma was diagnosed in the sigmoid colon and NEC in the rectum. One year postoperation, recurrence or metastasis was not evident. Regular surveillance colonoscopy is important in patients with long-term UC. A histological examination of UCAC might demonstrate NEC.

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential.

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.

No abstract available.
Carcinosarcoma*

BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). METHODS: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. RESULTS: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. CONCLUSIONS: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
6-Mercaptopurine ; Asian Continental Ancestry Group* ; Azathioprine ; Clinical Coding ; Hair ; Humans ; Inflammatory Bowel Diseases* ; Leukopenia

Fecal microbiota transplantation (FMT) is a treatment designed to correct gut dysbiosis by administration of feces from a healthy volunteer. It is still unclear whether FMT for children with ulcerative colitis (UC) is effective or hazardous. Here we describe a young patient to have received FMT for UC. A three-year-old girl was admitted to our hospital with severe active UC, and treated with aminosalicylates and various immunosuppressive drugs. As remission was not achieved, we decided to try FMT before colectomy. We administered donor fecal material a total of six times by retention enema (×2) and via a nasoduodenal tube (×4) within 10 days. The patient developed abdominal pain and pyrexia after each FMT session. Analyses revealed the transferred donor fecal microbiota had not been retained by the patient, who ultimately underwent colectomy. The severity of the UC and/or timing of FMT may have partly accounted for the poor outcome.
Abdominal Pain ; Child* ; Colectomy ; Colitis, Ulcerative* ; Dysbiosis ; Enema ; Fecal Microbiota Transplantation* ; Feces ; Female ; Fever ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Inflammatory Bowel Diseases ; Microbiota ; Tissue Donors ; Ulcer*

Objective To investigate the etiological and epidemiological characteristics of fungal keratitis in Jilin province of China and to establish a rapid and specific method for molecular identification of the prevalent fungal pathogens.Methods Corneal scrapings were collected from 225 patients with suspected fungal keratitis.Fungal strains were isolated and identified based on their morphology and physiological characteristics.The epidemiological characteristics of all isolated strains causing fungal keratitis were statistically analyzed.Species-specific primers of Fusarium solani (F.solani) were designed and used together with the universal fungal primers to establish a multiplex PCR assay for identification of F.solani in corneal scrapings.Results 156 out of 225 patients (69.3％) were diagnosed as fungal keratitis by fungal culture followed by the examination of morphological and physiological characteristics.A total of 168 pathogenic fungi strains were isolated,most of which were Fasarium spp.(49.4％),followed by Aspergillus spp.(17.9％) and Candida spp.(14.3％).F.solani was the predominant pathogen accounting for 34.5％ in all patients.Most of the patients (87.5％) were farmer and male patients (57.1％) accounted for the majority of 156 patients as well.Corneal trauma (38.5％) was considered as the main predisposing factor.The established multiplex PCR could specifically amplify a 300 bp nucleotide fragment of F.solani.It could be used for a rapid identification of F.solani in corneal scrapings.Conclusion Fusarium genus,particularly the species of F.solani,was the predominant pathogen for fungal keratitis in Jilin province of China.Corneal trauma was the most important predisposing factor.The established multiplex PCR could identify fungal infection from corneal scrapings rapidly and specifically.These findings are very important for the early diagnosis and treatment of fungal keratitis.

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.
Adsorption ; Arm ; Blood Component Removal ; Colitis, Ulcerative ; Extracorporeal Circulation ; Humans ; Inflammatory Bowel Diseases ; Prednisolone ; Prospective Studies ; Recurrence ; Remission Induction ; Salicylamides ; Ulcer

BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.
Antibodies ; Antibodies, Monoclonal ; Chemokine CCL2 ; Chemokine CCL5 ; Chemokines ; Crohn Disease ; Cytokines ; Humans ; Immune System ; Interferons ; Interleukin-10 ; Interleukin-13 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Lymphocytes ; Macrophages ; Mesalamine ; Remission Induction ; T-Lymphocytes, Regulatory ; Tumor Necrosis Factor-alpha ; Infliximab

The promotion of clinical research in Japan requires the establishment of a formal and systematic education and training program for clinicians to ensure they become effective clinician investigators. The first of its kind in Japan, a formal 1-year masters-degree-level training program (MCR course) was started at Kyoto University School of Medicine and Public Health. The first 28 students graduated in 2008, with most returning to their original clinical institutions.
1) As follow-up, we conducted a self-administered questionnaire survey of all 28 graduates (response rate, 86%) concerning the current status of clinical research and problems encountered at their institutions.
2) Almost 40% of respondents (n=24) reported "no time" or "no research collaborators" for clinical research.
3) Twenty respondents (83%) have attempted to promote clinical research at their hospital or workplace, but only 1 has received institutional support.
4) Over half of the respondents (54%) would like to be working in both clinical research and clinical practice at their hospital in the future (10-year timescale). Forty-two percent of respondents had a concrete image of the clinical researcher's career path.
5) Although open to improvement, the MCR program presents a concrete model for the education of clinical researchers. These findings suggest that promoting the conduct of clinical research requires the implementation of a support system and adjustment of personal and physical infrastructure.