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Science Advances Sep 2023Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma...
Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn's disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.
Topics: Animals; Humans; Mice; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Sorting Nexins; Stem Cells
PubMed: 37647408
DOI: 10.1126/sciadv.adh5016 -
Journal of Translational Internal... Jul 2023The aim of this systemtic review is to introduce clinical applications (especially emerging) and potential mechanisms of sacral nerve stimulation (SNS) for treating...
BACKGROUND
The aim of this systemtic review is to introduce clinical applications (especially emerging) and potential mechanisms of sacral nerve stimulation (SNS) for treating various gastrointestinal diseases.
MATERIALS AND METHODS
PubMed and Web of Science were searched for studies published on SNS and its clinical applications in fecal incontinence (limited to systematic review and meta-analysis of clinical studies), constipation (limited to reviews and randomized control clinical studies), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and upper gastrointestinal motility disorders. The relevant studies were pooled, and their findings were summarized and discussed.
RESULTS
SNS is an approved method for treating fecal incontinence. Systematic review and meta-analysis demonstrated high efficacy of the SNS therapy for fecal incontinence. Increased anal sphincter pressure and improvement in rectal sensation were reported as major mechanisms involved in the SNS therapy. SNS has also been proposed for treating constipation, but the therapy has been shown ineffective. There is a lack in SNS methodological optimization and mechanistic research. A few basic and clinical studies have reported the potential of SNS for treating visceral pain in IBS. SNS seemed capable of improving mucosal barrier functions. Several case reports are available in the literature on the treatment of IBD with SNS. Several laboratory studies suggested therapeutic potential of a special method of SNS for IBD. Cholinergic anti-inflammatory mechanisms were reported. Due to a recently reported spinal afferent and vagal efferent pathway of SNS, a few preclinical studies reported the potential of SNS for upper gastrointestinal motility disorders. However, no clinical studies have been performed.
CONCLUSIONS
SNS for fecal incontinence is a well-established clinical therapy. However, the current method of SNS is ineffective for treating constipation. Further methodological development and randomized clinical trials are needed to explore potential applications of SNS for IBS and IBD.
PubMed: 37408571
DOI: 10.2478/jtim-2023-0086 -
Cureus Nov 2023Anorectal mucosal melanoma (AMM) is an infrequent and highly aggressive form of mucosal melanoma. Its rarity makes it challenging to clinically diagnose, and its initial...
Anorectal mucosal melanoma (AMM) is an infrequent and highly aggressive form of mucosal melanoma. Its rarity makes it challenging to clinically diagnose, and its initial symptoms are typically nonspecific such as rectal/anal bleeding (the most common symptom), anal pain, or the presence of an anal mass. The prognosis for this condition is generally poor, and its incidence appears to be increasing each year. AMMs often go undetected and/or are already metastasized at the time of diagnosis. We present a case report of a patient who initially presented with nonspecific symptoms of anemia and blood per rectum, and was later found to have stage IV melanoma of the anorectal region. There is a notable scarcity of literature on this disease, resulting in a lack of a comprehensive understanding of its nature. Most available information consists of isolated case reports rather than comprehensive studies. Although surgical resection remains the primary treatment approach, the majority of patients (over 80%) will die due to distant metastasis within five years after undergoing surgery. The five-year survival rate for anorectal melanoma is estimated to be between 6% and 22%.
PubMed: 38106750
DOI: 10.7759/cureus.48835 -
Emerging Infectious Diseases Oct 2023We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis...
We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis (syphilis contacts). All syphilis contacts had oral rinse and swab samples collected for testing. Men who have sex with men had anal swab and women had vaginal swab samples collected for testing, regardless of the presence of lesions. Of 407 persons tested, 42 (10%) had early syphilis diagnosed; of those, 19 (45%) tested positive by PCR from any anatomic site and had a positive serologic test. T. pallidum was positive from vaginal samples in 3 women, anal samples in 3 men, and oral cavity samples in 2 women and 3 men, without symptoms at those sites. Three women had no prior syphilis serologic test. T. pallidum detection at asymptomatic mucosal sites suggests early syphilis infections, particularly in cases that would conventionally be staged as latent syphilis of unknown duration.
Topics: Male; Adult; Female; Humans; Treponema pallidum; Syphilis; Homosexuality, Male; Sexual and Gender Minorities; Vagina
PubMed: 37703891
DOI: 10.3201/eid2910.230660 -
Techniques in Coloproctology Dec 2023Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive...
BACKGROUND
Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3.
METHODS
We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed.
RESULTS
Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period.
CONCLUSIONS
Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear.
TRIAL REGISTRATION
Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.
Topics: Humans; Young Adult; Adult; Middle Aged; Aged; Endoscopic Mucosal Resection; Papillomavirus Infections; Retrospective Studies; Feasibility Studies; Carcinoma in Situ; Anus Neoplasms
PubMed: 38102514
DOI: 10.1007/s10151-023-02896-x -
Journal of Clinical Medicine Dec 2023Inflammatory Bowel Diseases (IBD), mainly Ulcerative Colitis (UC) and Crohn's Disease (CD), are disorders characterized by chronic inflammation with severe morbidity and... (Review)
Review
Inflammatory Bowel Diseases (IBD), mainly Ulcerative Colitis (UC) and Crohn's Disease (CD), are disorders characterized by chronic inflammation with severe morbidity and long-term disabling quality of life outcomes. UC mainly affects the mucosal and sub-mucosal layers of the colon, without embracing the peri-intestinal structures. Considering the predominant mucosal location of UC inflammation, the implementation of transmural evaluation by cross-sectional imaging techniques, mainly Intestinal Ultrasound (IUS), has been left behind for ages, especially if compared to CD. Nevertheless, studies analyzing intestinal ultrasound parameters accuracy in disease activity detection reported a good-to-optimal correlation of IUS markers with colonic inflammation, suggesting comparable feasibility of IUS monitoring in UC as in CD. The easy-to-use, costless and point-of-care available status of IUS is therefore crucial in order to improve the diagnostic process and, according to the recent literature, to monitor the response to treatment leading to speeding up decision making and therapy adjustments. Recent studies have demonstrated the correlation between transmural healing in UC with favorable outcomes even in the long term. An evidence gap still exists in the assessment of the rectum, with trans-perineal ultrasound (TPUS) a potential answer to reach a more precise evaluation of rectal inflammation. Eventually, IUS is also increasingly showing promises in emergent or post-surgical UC settings, considering various efforts put in line to demonstrate its feasibility in predicting response to salvage therapy for surgery avoidance and in studying inflammation relapse after procto-colectomy with ileo-pouch-anal anastomosis (IPAA) creation.
PubMed: 38137644
DOI: 10.3390/jcm12247569 -
Medical Science Monitor : International... Jul 2023BACKGROUND The high recurrence rate of perianal fistula Crohn's disease (PFCD) increases the need to protect the anal sphincter during each surgical treatment of...
BACKGROUND The high recurrence rate of perianal fistula Crohn's disease (PFCD) increases the need to protect the anal sphincter during each surgical treatment of fistulas. We aimed to evaluate the safety and efficacy of internal orifice alloy closure in patients with PFCD. MATERIAL AND METHODS Fifteen patients with PFCD were enrolled in the study between July 6, 2021, and April 27, 2023. All patients underwent preoperative colonoscopy and anal magnetic resonance examination for diagnosis and evaluation. Internal orifice alloy closure (IOAC) was performed only when Crohn's disease was in remission. The external sphincter had not been severed. Perianal magnetic resonance imaging examination was used for postoperative evaluation after 6 months. Fistula cure rate, length of stay, perianal pain, and Wexner incontinence score were retrospectively compared between 15 patients treated with IOAC and 40 patients treated with other surgical methods. RESULTS Fifteen patients (male/female: 9/6, age: 23.6±14.3 years) with PFCD were included (follow-up: 24 months). In total, 20.0% (3) had multiple tracts, and 13.3% (2) had a high anal fistula. Among them, 10 patients received biologics for induction for mucosal healing before surgery. The fistula healed completely in 80.0% (12/15) and did not heal in 20.0% (3/15). Three patients who did not heal underwent fistulotomy and eventually recovered. IOAC is not superior in terms of fistula healing rates, length of stay, and anal pain, but its Wexner incontinence scores are significantly lower than with other surgical methods. CONCLUSIONS IOAC is a novel sphincter-saving surgery that is effective and safe for the treatment of PFCD.
Topics: Humans; Female; Male; Child; Adolescent; Young Adult; Adult; Crohn Disease; Retrospective Studies; Rectal Fistula; Alloys; Pelvic Pain
PubMed: 37434329
DOI: 10.12659/MSM.940873 -
Evaluation of the Incidence of Anal Fissures in Patients who Systemic Isotretinoin Therapy for Acne.Dermatology Practical & Conceptual Jul 2023Isotretinoin is an effective drug widely used in the treatment of severe acne. In this study, we tried to evaluate the incidence of anal fissures with clinical and...
INTRODUCTION
Isotretinoin is an effective drug widely used in the treatment of severe acne. In this study, we tried to evaluate the incidence of anal fissures with clinical and laboratory side effects associated with isotretinoin.
METHODS
The study evaluated 210 patients who received systemic isotretinoin treatment. Especially patients with constipation and anal bleeding were evaluated by the General Surgery clinic to arrange appropriate treatments.
RESULTS
Of 210 patients included in the study, 138 (65.7%) were female and 72 (34.3%) were male, with a mean age of 23.7 years. The most common adverse event was dry lips in 206 (98.1%) patients. The mucocutaneous side effects were constipation 36 (17.1%), anal bleeding 18 (8.6%), mucosal erosion 10 (4.7%), anal fissure 7 (3.3%). Treatment was discontinued due to elevated liver function tests in 5 patients (2.3%), and because anal bleeding could not be controlled in 1 patient.
CONCLUSIONS
Isotretinoin is the most effective acne medicine used today. Clarification of the patients about the rarely seen side effects such as dryness, erosion, fissure and bleeding in the anal mucosa in addition to the common mucocutaneous side effects will ensure that patients are more cautious and increase their tolerance to the treatment.
PubMed: 37557107
DOI: 10.5826/dpc.1303a133 -
Journal of Hematology Apr 2024Anorectal infections in neutropenic leukemia patients are a significant and potentially life-threatening complication. The pathogenesis of this condition is not entirely... (Review)
Review
Anorectal infections in neutropenic leukemia patients are a significant and potentially life-threatening complication. The pathogenesis of this condition is not entirely understood and believed to be multifactorial, including mucosal injury as a result of cytotoxic drugs, profound neutropenia and impaired host defense. Establishing an early diagnosis is key and often made clinically on the basis of signs and symptoms, but also from imaging studies demonstrating perianal inflammation or fluid collection. The management of anorectal infections in neutropenic leukemia patients is not straightforward, as there are no well-conducted studies on this entity. This review seeks to provide a framework into the pathophysiology and clinical presentation of anorectal infections in neutropenic leukemia patients, propose a diagnostic approach and to discuss controversies in the management of this condition.
PubMed: 38644983
DOI: 10.14740/jh1251