Journal of Clinical Medicine

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12 pages, 1105 KiB

Open AccessArticle

Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis

by Xiaochen Zhang, Dai Ishikawa, Kei Nomura, Naoyuki Fukuda, Mayuko Haraikawa, Keiichi Haga, Tomoyoshi Shibuya, Toshihiro Mita and Akihito Nagahara

J. Clin. Med. 2022, 11(4), 1055; https://doi.org/10.3390/jcm11041055 - 17 Feb 2022

Cited by 3 | Viewed by 2128

Abstract

Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step [...] Read more.

Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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11 pages, 1559 KiB

Open AccessArticle

Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis

by Kei Nomura, Dai Ishikawa, Koki Okahara, Shoko Ito, Keiichi Haga, Masahito Takahashi, Atsushi Arakawa, Tomoyoshi Shibuya, Taro Osada, Kyoko Kuwahara-Arai, Teruo Kirikae and Akihito Nagahara

J. Clin. Med. 2021, 10(8), 1749; https://doi.org/10.3390/jcm10081749 - 17 Apr 2021

Cited by 64 | Viewed by 4471

Abstract

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC [...] Read more.

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger’s clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = −0.71, p = 2 × 10⁻⁹). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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12 pages, 1113 KiB

Open AccessArticle

Sequential Approach for a Critical-View COlectomy (SACCO): A Laparoscopic Technique to Reduce Operative Time and Complications in IBD Acute Severe Colitis

by Gianluca Matteo Sampietro, Francesco Colombo and Fabio Corsi

J. Clin. Med. 2020, 9(10), 3382; https://doi.org/10.3390/jcm9103382 - 21 Oct 2020

Cited by 6 | Viewed by 3119

Abstract

Acute severe colitis is the major indication for surgery in inflammatory bowel diseases (IBD), and in particular, in ulcerative colitis (UC). A laparoscopic approach for abdominal colectomy is recommended, due to better perioperative and long-term outcomes. However, costs, time-spending, and outcomes are still [...] Read more.

Acute severe colitis is the major indication for surgery in inflammatory bowel diseases (IBD), and in particular, in ulcerative colitis (UC). A laparoscopic approach for abdominal colectomy is recommended, due to better perioperative and long-term outcomes. However, costs, time-spending, and outcomes are still a topic of improvement. We designed a standardized 10-steps, sequential approach to laparoscopic colectomy, based on the philosophy of the “critical view of safety”, with the aim to improve perioperative outcomes (operative duration, estimated blood loss, complications, readmissions, reoperations, and length of postoperative stay). We performed a retrospective cohort study using data from a prospectively maintained clinical database. We included all the consecutive, unselected patients undergoing laparoscopic subtotal colectomy (SCo) for IBD between 2008 and 2019 in a tertiary IBD Italian Centre. Starting from 2015, we regularly adopted the novel Sequential Approach for a Critical-View Colectomy (SACCo) technique. We included 59 (40.6%) patients treated with different laparoscopic approaches, and 86 patients (59.4%) operated on by the SACCo procedure. The mean operating time was significantly shorter for the SACCo group (144 vs. 224 min; p < 0.0001). The SACCo technique presented a trend to fewer major complications (6.8% vs. 8.3%), less readmissions (2.3% vs. 13.5%; p = 0.01), and shorter postoperative hospital stay (7.2 vs. 8.8 days; p = 0.003). Laparoscopic SACCo-technique is a safe and reproducible surgical approach for acute severe colitis and may improve the outcomes of this demanding procedure. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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15 pages, 1227 KiB

Open AccessArticle

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

by Keisuke Hata, Soichiro Ishihara, Yoichi Ajioka, Keiichi Mitsuyama, Kenji Watanabe, Hiroyuki Hanai, Reiko Kunisaki, Hiroshi Nakase, Keiji Matsuda, Ryuichi Iwakiri, Nobuyuki Hida, Shinji Tanaka, Yoshiaki Takeuchi, Masaru Shinozaki, Noriyuki Ogata, Kentaro Moriichi, Fumihito Hirai, Kenichi Sugihara, Tadakazu Hisamatsu, Yasuo Suzuki, Mamoru Watanabe and Toshifumi Hibi Show full author list Hide full author list

J. Clin. Med. 2020, 9(7), 2286; https://doi.org/10.3390/jcm9072286 - 18 Jul 2020

Cited by 8 | Viewed by 2508

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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10 pages, 2618 KiB

Open AccessArticle

Effectiveness and Nephrotoxicity of Long-Term Tacrolimus Administration in Patients with Ulcerative Colitis

by Keiichi Haga, Tomoyoshi Shibuya, Kei Nomura, Koki Okahara, Osamu Nomura, Dai Ishikawa, Naoto Sakamoto, Taro Osada and Akihito Nagahara

J. Clin. Med. 2020, 9(6), 1771; https://doi.org/10.3390/jcm9061771 - 7 Jun 2020

Cited by 8 | Viewed by 2704

Abstract

Background: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and [...] Read more.

Background: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. Methods: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. Results: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. Conclusion: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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16 pages, 2003 KiB

Open AccessArticle

Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation

by Koki Okahara, Dai Ishikawa, Kei Nomura, Shoko Ito, Keiichi Haga, Masahito Takahashi, Tomoyoshi Shibuya, Taro Osada and Akihito Nagahara

J. Clin. Med. 2020, 9(6), 1650; https://doi.org/10.3390/jcm9061650 - 31 May 2020

Cited by 30 | Viewed by 6608

Abstract

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are [...] Read more.

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent–child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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Review

Jump to: Research

11 pages, 510 KiB

Open AccessEditor’s ChoiceReview

Clinical Manifestations of Leukocytoclastic Vasculitis, Treatment, and Outcome in Patients with Ulcerative Colitis: A Systematic Review of the Literature

by Ivana Pantic, Djordje Jevtic, Charles W. Nordstrom, Cristian Madrid, Tamara Milovanovic and Igor Dumic

J. Clin. Med. 2022, 11(3), 739; https://doi.org/10.3390/jcm11030739 - 29 Jan 2022

Cited by 12 | Viewed by 3644

Abstract

Leukocytoclastic vasculitis (LCV) is a rare extraintestinal manifestation (EIM) of ulcerative colitis (UC). Observations about its association with UC stem from case reports and small case series. Due to its rarity, more rigorous cross-sectional studies are scarce and difficult to conduct. The aim [...] Read more.

Leukocytoclastic vasculitis (LCV) is a rare extraintestinal manifestation (EIM) of ulcerative colitis (UC). Observations about its association with UC stem from case reports and small case series. Due to its rarity, more rigorous cross-sectional studies are scarce and difficult to conduct. The aim of this systematic review was to synthetize the knowledge on this association by reviewing published literature in the form of both case reports and case series; and report the findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In contrast to LCV in Chron disease (CD), which occurs secondary to biologic therapies used for its treatment, LCV in UC is a true reactive skin manifestation. Both genders are equally affected. Palpable purpura (41%) and erythematous plaques (27%) are the most common clinical manifestations. In 41% of patients, the rash is painful, and the lower extremities are most commonly involved (73%). Systemic symptoms such as fever, arthralgias, fatigue, and malaise are seen in 60% of patients. Unlike previous reports, we found that LCV more commonly occurs after the UC diagnosis (59%), and 68% of patients have active intestinal disease at the time of LCV diagnosis. Antineutrophil cytoplasmic antibody (ANCA) is positive in 41% of patients, and 36% of patients have other EIMs present concomitantly with LCV. The majority of patients were treated with corticosteroids (77%), and two (10%) required colectomy to control UC and LCV symptoms. Aside from one patient who died from unrelated causes, all others survived with their rash typically resolving without scarring (82%). Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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15 pages, 312 KiB

Open AccessReview

The Role of Biomarkers in Surgery for Ulcerative Colitis: A Review

by Jared Matson, Sonia Ramamoorthy and Nicole E. Lopez

J. Clin. Med. 2021, 10(15), 3362; https://doi.org/10.3390/jcm10153362 - 29 Jul 2021

Cited by 6 | Viewed by 2256

Abstract

Ulcerative colitis (UC) is an inflammatory condition that generally affects the rectum and extends proximally into the colon in a continuous, distal-to-proximal pattern. Surgical resection (total proctocolectomy) is the only cure for UC and is often necessary in managing complicated or refractory disease. [...] Read more.

Ulcerative colitis (UC) is an inflammatory condition that generally affects the rectum and extends proximally into the colon in a continuous, distal-to-proximal pattern. Surgical resection (total proctocolectomy) is the only cure for UC and is often necessary in managing complicated or refractory disease. However, recent advances in biologically targeted therapies have resulted in improved disease control, and surgery is required in only a fraction of cases. This ever-increasing array of options for medical management has added complexity to surgical decision-making. In some circumstances, the added time required to ensure failure of medical therapy can delay colectomy in patients who will ultimately need it. Indeed, many patients with severe disease undergo trials of multiple medical therapies prior to considering surgery. In severe cases of UC, continued medical management has been associated with a delay to surgical intervention and higher rates of morbidity and mortality. Biomarkers represent a burgeoning field of research, particularly in inflammatory bowel disease and cancer. This review seeks to highlight the different possible settings for surgery in UC and the role various biomarkers might play in each. Full article

(This article belongs to the Special Issue An Update on Ulcerative Colitis: From Pathophysiology to Clinical Management)

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