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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 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029 -
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 -
Dermatologic Surgery : Official... Jan 2017Hidradenitis suppurativa (HS) is a chronic inflammatory disease that frequently involves the perineal and perianal regions. The association between HS and malignant... (Review)
Review
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that frequently involves the perineal and perianal regions. The association between HS and malignant transformation is a rare but under recognized phenomenon.
OBJECTIVE
This systematic review aims to summarize all available cases of vulvar and perianal/perineal cancer emerging in patients with HS, describing clinical and therapeutic particularities of these coexisting conditions in female patients.
MATERIALS AND METHODS
This systematic review and pooled analysis was performed in accordance with the PRISMA guidelines; end-of-search date was June 15, 2015.
RESULTS
A total of 13 eligible articles were identified; 7 cases of vulvar cancer and 6 cases of perineal/perianal carcinomas in patients with HS were noted. A majority of published cases pertained to rather advanced carcinomas; only occasionally early stage carcinomas were identified. The optimal modifications in the treatment scheme of vulvar, perianal, and perineal cancer in patients with HS have not been established; detailed reporting of recurrence- and survival-related aspects is advised.
CONCLUSION
Vulvar, perianal, and perineal cancer represent a rare but serious complication of HS.
Topics: Buttocks; Carcinoma, Squamous Cell; Female; Hidradenitis Suppurativa; Humans; Perineum; Skin Neoplasms; Vulvar Neoplasms
PubMed: 27755170
DOI: 10.1097/DSS.0000000000000944 -
Ultraschall in Der Medizin (Stuttgart,... Jun 2017Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying... (Comparative Study)
Comparative Study Meta-Analysis Review
Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying perianal fistulae and abscesses. The National Library of Medicine and Embase were searched for articles on TPUS for the assessment of idiopathic and Crohn's perianal fistulae and abscesses. Two reviewers independently reviewed eligible studies and rated them for quality using the QUADAS tool. The primary outcome measure was the accuracy of TPUS as measured by its sensitivity and positive predictive value (PPV) in detecting and classifying perianal fistulae, internal openings and perianal abscesses. We included 12 studies (565 patients). Overall, the methodological quality of the studies was suboptimal. 3 studies were retrospective and 4 showed significant risks of bias in the application of the reference standard. The sensitivity of TPUS in detecting perianal fistulae on a per-lesion basis was 98 % (95 % CI 96 - 100 %) and the PPV was 95 % (95 % CI 90 - 98 %). The detection of internal openings had a sensitivity of 91 % (95 % CI 84 - 97 %) with a PPV of 87 % (95 % CI 76 - 95 %). The classification of fistulae yielded a sensitivity of 92 % (95 % CI 85 - 97 %) and a PPV of 92 % (95 % CI 83 - 98 %). TPUS had a sensitivity of 86 % (95 % CI 67 - 99 %) and PPV of 90 % (95 % CI 76 - 99 %) in the detection of perianal abscesses. The current literature on TPUS illustrates good overall accuracy in the assessment of perianal fistulae and abscesses. However, many studies had methodological flaws suggesting that further research is required.
Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anus Diseases; Child; Child, Preschool; Endosonography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Rectal Fistula; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome; Young Adult
PubMed: 28399604
DOI: 10.1055/s-0043-103954 -
International Journal of Colorectal... May 2015Perianal fistulas, and specifically high perianal fistulas, remain a surgical treatment challenge. Many techniques have, and still are, being developed to improve... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Perianal fistulas, and specifically high perianal fistulas, remain a surgical treatment challenge. Many techniques have, and still are, being developed to improve outcome after surgery. A systematic review and meta-analysis was performed for surgical treatments for high cryptoglandular perianal fistulas.
METHODS
Medline (Pubmed, Ovid), Embase and The Cochrane Library databases were searched for relevant randomized controlled trials on surgical treatments for high cryptoglandular perianal fistulas. Two independent reviewers selected articles for inclusion based on title, abstract and outcomes described. The main outcome measurement was the recurrence/healing rate. Secondary outcomes were continence status, quality of life and complications.
RESULTS
The number of randomized trials available was low. Fourteen studies could be included in the review. A meta-analysis could only be performed for the mucosa advancement flap versus the fistula plug, and did not show a result in favour of either technique in recurrence or complication rate. The mucosa advancement flap was the most investigated technique, but did not show an advantage over any other technique. Other techniques identified in randomized studies were seton treatment, medicated seton treatment, fibrin glue, autologous stem cells, island flap anoplasty, rectal wall advancement flap, ligation of intersphincteric fistula tract, sphincter reconstruction, sphincter-preserving seton and techniques combined with antibiotics. None of these techniques seem superior to each other.
CONCLUSIONS
The best surgical treatment for high cryptoglandular perianal fistulas could not be identified. More randomized controlled trials are needed to find the best treatment. The mucosa advancement flap is the most investigated technique available.
Topics: Bioprosthesis; Case-Control Studies; Fecal Incontinence; Female; Fibrin Tissue Adhesive; Humans; Ligation; Male; Prognosis; Randomized Controlled Trials as Topic; Rectal Fistula; Recurrence; Risk Assessment; Stem Cell Transplantation; Surgical Flaps; Treatment Outcome; Video-Assisted Surgery; Wound Healing
PubMed: 25487858
DOI: 10.1007/s00384-014-2091-8 -
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 -
Colorectal Disease : the Official... Apr 2016Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide,... (Review)
Review
AIM
Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high-quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research.
METHOD
MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two-thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence-based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/) or insufficient.
RESULTS
Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence.
CONCLUSION
Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.
Topics: Consensus; Evidence-Based Medicine; Humans; Practice Guidelines as Topic; Rectal Fistula
PubMed: 26847796
DOI: 10.1111/codi.13286 -
Journal of Crohn's & Colitis Oct 2016Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects.
METHODS
A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age ≥ 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated.
RESULTS
We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57].
CONCLUSIONS
Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly.
Topics: Age of Onset; Aged; Aged, 80 and over; Combined Modality Therapy; Disease Progression; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Middle Aged; Models, Statistical; Phenotype; Prognosis
PubMed: 26928965
DOI: 10.1093/ecco-jcc/jjw054