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JAMA Oncology Apr 2022Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and...
IMPORTANCE
Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.
OBJECTIVE
To develop recommendations for the care of adults with EMPD.
EVIDENCE REVIEW
A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.
FINDINGS
The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.
CONCLUSIONS AND RELEVANCE
Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.
Topics: Aged; Humans; Imiquimod; Paget Disease, Extramammary; Prospective Studies; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 35050310
DOI: 10.1001/jamaoncol.2021.7148 -
Stem Cell Research & Therapy Apr 2023Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future.
SHORT CONCLUSION
MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.
Topics: Humans; Quality of Life; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Mesenchymal Stem Cells; Rectal Fistula; Crohn Disease
PubMed: 37101285
DOI: 10.1186/s13287-023-03331-6 -
Intestinal Research Apr 2022Perianal fistulas are a debilitating manifestation of Crohn's disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management...
BACKGROUND/AIMS
Perianal fistulas are a debilitating manifestation of Crohn's disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.
METHODS
A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
RESULTS
A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%-37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%-47.7%) with high heterogeneity (I2=67.1%).
CONCLUSIONS
In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.
PubMed: 35124951
DOI: 10.5217/ir.2021.00091 -
Diagnostics (Basel, Switzerland) May 2023(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for... (Review)
Review
(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for less than 0.2% of all BCC cases. There have been only a few reported cases of the disease, with fewer than 200 cases reported in total. Given the diagnostic challenges and potential for misdiagnosis, we conducted a systematic review of perianal basal cell carcinoma using real-world data to provide comprehensive and detailed information on the disease. (2) Methods: The study was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020. Patients' clinical pathologic features, tumor characteristics, treatment modalities, and outcomes were presented. (3) Results: The results of 41 studies involving 140 patients were analyzed. The most common symptoms reported by patients at presentation were anorectal bleeding, pain, and pruritus. Ulceration was the most frequently observed tumor characteristic. The majority of patients underwent local excision as their primary treatment, with only eight patients experiencing a recurrence. Our analysis did not reveal any statistically significant differences in the outcomes of different treatment modalities. (4) Conclusions: Identifying perianal BCC poses a significant challenge as it closely resembles other anal diseases, thereby making it difficult to differentiate between the different conditions. However, a wide local excision with clear margins is considered an effective treatment option for most patients. Alternative treatments, such as radiotherapy, may be recommended for patients who are unable to undergo surgery.
PubMed: 37175041
DOI: 10.3390/diagnostics13091650 -
Techniques in Coloproctology Oct 2022Most patients with perianal fistulizing Crohn's disease (pfCD) present with complex types of perianal fistulas and need repetitive repair operations, resulting in a high... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most patients with perianal fistulizing Crohn's disease (pfCD) present with complex types of perianal fistulas and need repetitive repair operations, resulting in a high risk of sphincter injury. Fistula-tract Laser Closure (FiLaC™) is a novel sphincter-saving technique that obliterates the fistula tract with a photothermal effect. The aim of the present systematic review and meta-analysis was to evaluate the efficacy and safety of FiLaC in pfCD.
METHODS
This study was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases, including PubMed, Embase, Cochrane Library and Wanfang Data were searched for published articles from January 2000 to June 2021. The clinicaltrials.gov website was searched for completed or ongoing trials on pfCD and FiLaC™. The references of each article were also searched for eligible data. The main outcome was the primary healing rate of the FiLaC™ procedure. Additionally, fecal incontinence was analyzed as the secondary outcome to evaluate the safety of FiLaC™.
RESULTS
Six studies met the eligibility criteria and were included in the final analysis. All studies were published within the past 6 years and came from European countries. There were 50 pfCD patients recruited, and 31 patients' fistulas were healed after FiLaC™. The pooled primary healing rate was 68% (95% CI 53.0-84.0%, I = 27%, p = 0.23). There was no major fecal incontinence after surgery.
CONCLUSIONS
These data suggest that FiLaC™ may be an effective and safe procedure for pfCD patients. However, the evidence is poor and there is a need for more high-quality prospective controlled studies with long-term follow-up before this minimally invasive technique is recommended for surgical treatment of pfCD.
Topics: Crohn Disease; Fecal Incontinence; Humans; Lasers; Prospective Studies; Rectal Fistula; Treatment Outcome
PubMed: 35962294
DOI: 10.1007/s10151-022-02682-1 -
JGH Open : An Open Access Journal of... Jun 2020Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While... (Review)
Review
Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI clinical healing was 0.10 (95% confidence interval [CI], 0.02-0.39) and 0.43 (95% CI, 0.26-0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long-term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice.
PubMed: 32514434
DOI: 10.1002/jgh3.12295 -
Cancers Mar 2021Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of... (Review)
Review
Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn's disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn's disease. The incidence rate of SCC related to perianal fistula was very low (<1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron's disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer.
PubMed: 33809997
DOI: 10.3390/cancers13061445 -
Posterior compartment prolapse and perineal descent: systematic review of available support devices.International Urogynecology Journal Nov 2023The aim of our study is to systematically review the literature about available devices facilitating perineal support during defecation in patients with obstructive... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of our study is to systematically review the literature about available devices facilitating perineal support during defecation in patients with obstructive defecation syndrome (ODS) and posterior pelvic organ prolapse (POP).
METHODS
We searched for the terms "defecat/ion or ODS" and" pessar/ies or device/aid/tool/perineal/perianal/prolapse and support" in MEDLINE, PubMed and Web of Science. Data abstraction was performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. A two-stage inclusion was performed, selecting first on title and abstract and secondly the full text. For variables with sufficient data, a meta-analysis was performed using a random-effects model. Other variables were descriptively reported.
RESULTS
Ten studies out of 1332 were included for systematic review. The devices could be categorized into three groups: pessaries (n = 8), vaginal stent (n = 1) and external support device (n = 1). Methodology and data reporting is heterogeneous. Meta-analysis could be performed for the Colorectal-Anal Distress Inventory (CRADI-8) and Impact Questionnaire (CRAI-Q-7) in three pessary studies which showed a significant mean change. Significant improvement of stool evacuation was seen in two other pessary studies. The vaginal stent significantly decreases ODS. Subjective perception of constipation improved significantly using the posterior perineal support device.
CONCLUSION
All reviewed devices seem to improve ODS in patients with POP. There are no data on their efficacy with regard to perineal descent-associated ODS. There is a lack of comparative studies between devices. Studies are difficult to compare due to different inclusion criteria and evaluation tools.
Topics: Female; Humans; Pelvic Organ Prolapse; Constipation; Vagina; Anal Canal; Perineum; Pessaries
PubMed: 37074368
DOI: 10.1007/s00192-023-05508-2 -
Inflammatory Bowel Diseases Oct 2022Perianal Crohn's disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Perianal Crohn's disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk factors, and outcomes of pCD in population-based cohort studies.
METHODS
Through a systematic literature review through March 1, 2021, we identified population-based inception cohort studies reporting cumulative incidence of perianal disease (primarily abscess and/or fistula) in patients with CD. We estimated the cumulative incidence of pCD at presentation and 1-, 5-, and 10-year follow-up, and risk factors for perianal disease and outcomes including risk of major (bowel resection, proctectomy, ostomy) and minor perianal (incision and drainage, seton placement, etc.) surgery.
RESULTS
In 12 population-based studies, prevalence of pCD was 18.7% (95% confidence interval [CI], 12.5%-27.0%) with 1-, 5-, and 10-year risk of perianal disease being 14.3% (95% CI, 7.9%-24.6%), 17.6% (95% CI, 11.3%-26.5%), and 18.9% (95% CI, 15.0%-23.4%), respectively. Approximately 11.5% of patients (95% CI, 6.7%-19.0%) had perianal disease at or before CD diagnosis. Colonic disease location and rectal involvement were associated with higher risk of pCD. Overall, 63.3% of patients (95% CI, 53.3-72.3) required minor perianal surgery and 6.4% of patients (95% CI, 1.8%-20.6%) required major abdominal surgery for pCD. Use of biologic therapy for pCD is common and has steadily increased throughout the years.
CONCLUSIONS
Approximately 1 in 5 patients with CD develops perianal disease within 10 years of CD diagnosis, including 11.5% who have perianal disease at presentation. Approximately two-thirds of patients require perianal surgery, with a smaller fraction requiring major abdominal surgery.
Topics: Cohort Studies; Crohn Disease; Humans; Incidence; Proctectomy; Rectal Fistula; Treatment Outcome
PubMed: 34792604
DOI: 10.1093/ibd/izab287 -
Journal of Pediatric Surgery Jul 2023Perianal abscesses and anal fistulas are common. The principle of intention-to-treat has not been considered in previous systemic reviews. Thus, the comparison between... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perianal abscesses and anal fistulas are common. The principle of intention-to-treat has not been considered in previous systemic reviews. Thus, the comparison between primary and post-recurrence management was confused, and the recommendation of primary treatment is obscure. The current study aims to identify the optimal initial treatment for pediatric patients.
METHODS
Using PRISMA guidelines, studies were identified from MEDLINE, EMBASE, PubMed, Cochrane Library, and Google Scholar without any language or study design restriction. The inclusion criteria include original articles or articles with original data, studies of management for a perianal abscess with or without anal fistula, and patient age of <18 years. Patients with local malignancy, Crohn's disease, or other underlying predisposing conditions were excluded. Studies without analyzing recurrence, case series of <5, and irrelevant articles were excluded in the screening stage. Of the 124 screened articles, 14 articles had no full texts or detailed information. Articles written in a language other than English or Mandarin were translated by Google Translation first and confirmed with native speakers. After the eligibility process, studies that compared identified primary managements were then included in the qualitative synthesis.
RESULTS
Thirty-one studies involving 2507 pediatric patients met the inclusion criteria. The study design consisted of two prospective case series of 47 patients and retrospective cohort studies. No randomized control trials were identified. Meta-analyses for recurrence after initial management were performed with a random-effects model. Conservative treatment and drainage revealed no difference (Odds ratio [OR], 1.222; 95% Confidential interval [CI]: 0.615-2.427, p = 0.567). Conservative management had a higher risk of recurrence than surgery without statistical significance (OR 0.278, 95% CI: 0.109-0.707, p = 0.007). Compared with incision/drainage, surgery can prevent recurrence remarkably (OR 4.360, 95% CI: 1.761-10.792, p = 0.001). Subgroup analysis of different approaches within conservative treatment and operation was not performed for lacking information.
CONCLUSION
Strong recommendations cannot be made due to the lack of prospective or randomized controlled studies. However, the current study based on real primary management supports initial surgical intervention for pediatric patients with perianal abscesses and anal fistula to prevent recurrence.
LEVEL OF EVIDENCE
Type of study: Systemic review; Evidence level: Level II.
Topics: Adolescent; Child; Humans; Abscess; Anus Diseases; Drainage; Rectal Fistula; Retrospective Studies; Treatment Outcome
PubMed: 36894443
DOI: 10.1016/j.jpedsurg.2023.01.055