-
Trials Feb 2024Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a...
Efficacy of amoxicillin/clavulanic acid after surgical drainage of perianal abscess in the prevention of the development of anal fistula (PERIQxA study): study protocol for a multicenter randomized, double-blind clinical trial.
BACKGROUND
Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a fistula after incision and drainage of an anal abscess is seen in approximately 26-37%. Its treatment is a relevant topic, and the role of the use of antibiotic therapy in its prevention remains controversial, after the publication of several studies with contradictory results and several methodological limitations. Our hypothesis is that the combination of amoxicillin and clavulanic acid will reduce the incidence of anal fistula.
METHOD
The aim of this study is to evaluate the efficacy of antibiotherapy after surgical drainage of perianal abscess in the development of perianal fistula. The PERIQxA study is a multicenter, randomized, double-blind controlled trial. The study has been designed to include 286 adult patients who will be randomly (1:1) assigned to either the experimental (amoxicillin/clavulanic acid 875/125 mg TDS for 7 days) or the control arm (placebo). The primary outcome measure is the percentage of patients that develop perianal fistula after surgery and during follow-up (6 months).
DISCUSSION
This clinical trial is designed to evaluate the efficacy and safety of amoxicillin/clavulanic in the prevention of perianal fistula. The results of this study are expected to contribute to stablish the potential role of antibiotherapy in the therapeutics for anal abscess.
TRIAL REGISTRATION
EudraCT Number: 2021-003376-14. Registered on November 26, 2021.
Topics: Adult; Humans; Abscess; Amoxicillin-Potassium Clavulanate Combination; Anus Diseases; Rectal Fistula; Drainage; Skin Diseases; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38355562
DOI: 10.1186/s13063-024-07922-3 -
DEN Open Apr 2024A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum....
A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.
PubMed: 38343421
DOI: 10.1002/deo2.340 -
Cureus Feb 2024Background Intrasphincteric injection of botulinum toxin is an alternative treatment for anal fissures, which may present less risk of fecal incontinence than more...
Background Intrasphincteric injection of botulinum toxin is an alternative treatment for anal fissures, which may present less risk of fecal incontinence than more invasive procedures, such as lateral internal sphincterotomy. The aim is to compare cure and complication rates between these two treatments. Methods We conducted a retrospective audit of patients who underwent treatment of anal fissures with intrasphincteric botulinum toxin or lateral internal sphincterotomy from 2016 to 2020 at the Colorectal Surgery Unit of Monash Health, Melbourne, Australia, excluding those who had previously had either procedure. Results Fifty-one patients received intrasphincteric botulinum toxin, and 40 patients underwent lateral internal sphincterotomy. Most patients in the botulinum group had a total dose of either 80 (53%; n=27) or 100 units (37%; n=19) and had the dose administered bilaterally at the 3 o'clock and 9 o'clock positions (n=41; 80%). Thirty-one patients in the botulinum group (61%) had complete resolution of symptoms, with a mean time to cure of two months, compared to 36 patients (90%) in the sphincterotomy group with a mean time to cure of 1.5 months. In most cases, postoperative incontinence was transient, although one patient in the botulinum group had persistent incontinence of flatus, and two patients in the sphincterotomy group had persistent fecal incontinence. Conclusion Intrasphincteric botulinum injection is an effective, less-invasive alternative to sphincterotomy for the treatment of anal fissures, with incontinence usually temporary when it occurs. Further research is needed to optimize the dose and location of injection and guide future recommendations.
PubMed: 38327720
DOI: 10.7759/cureus.53668 -
BJS Open Jan 2024
Topics: Humans; Cohort Studies; Lateral Internal Sphincterotomy; Fissure in Ano; Botulinum Toxins
PubMed: 38323879
DOI: 10.1093/bjsopen/zrad156 -
Australian Journal of General Practice 2024Anal fissure (AF) is the second most common anorectal complaint in healthcare settings. The presentation might be acute or chronic, characterised by severe pain with...
BACKGROUND
Anal fissure (AF) is the second most common anorectal complaint in healthcare settings. The presentation might be acute or chronic, characterised by severe pain with defaecation that persists for one to two hours. Non-surgical and surgical interventions are available based on the severity and persistence of the fissure.
OBJECTIVE
The aim of this article is to review the pathophysiology, clinical presentation and management of AF under current guidelines.
DISCUSSION
The aetiology of AF is unclear, although it is commonly associated with local trauma or associated chronic conditions. Acute AF is first treated with conservative therapy, including dietary fibre and sitz baths. Addition of topical nitrates, topical calcium channel blockers or botulinum toxin injection is indicated with failure of conservative treatment or at medical discretion. Surgical options are considered if AF persists despite treatment. Most present as hypertonic, but special consideration is needed for hypotonic or secondary presentations.
Topics: Humans; Fissure in Ano; Calcium Channel Blockers; Nitrates; Pain; Conservative Treatment
PubMed: 38316476
DOI: 10.31128/AJGP/05-23-6843 -
Journal of Medical Genetics Apr 2024Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and...
BACKGROUND
Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics.
METHODS
We screened and variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS.
RESULTS
We identified five novel and two reported pathogenic/likely pathogenic (P/LP) variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring.
CONCLUSION
This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.
Topics: Humans; Mutation; Transcription Factors; Syndrome; Hearing Loss, Sensorineural; Phenotype; Nuclear Proteins; Adaptor Proteins, Signal Transducing; Abnormalities, Multiple; Anus, Imperforate; Thumb
PubMed: 38296632
DOI: 10.1136/jmg-2023-109579 -
European Journal of Preventive... Jun 2024Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association...
AIMS
Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL-lowering, overall and through PCSK9 drug targets, on congenital malformations.
METHODS AND RESULTS
Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1 320 016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted, respectively, from a GWAS on 10 186 individuals and from the genotype-tissue expression project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n = 342 499) for eight categories of congenital malformations affecting multiple systems. Genetically proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems [OR 2.70, 95% confidence interval (CI) 1.30-5.63, P = 0.018], the skin (OR 2.23, 95% CI 1.33-3.75, P = 0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal, and limb association (VACTERL) (OR 1.51, 95% CI 1.16-1.96, P = 0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive of horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations.
CONCLUSION
These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.
Topics: Humans; Cholesterol, LDL; Female; Genome-Wide Association Study; Proprotein Convertase 9; PCSK9 Inhibitors; Mendelian Randomization Analysis; Pregnancy; Risk Factors; Abnormalities, Drug-Induced; Biomarkers; Risk Assessment; Serine Proteinase Inhibitors; Genetic Predisposition to Disease; Phenotype; Polymorphism, Single Nucleotide; Anticholesteremic Agents
PubMed: 38294056
DOI: 10.1093/eurjpc/zwad402 -
Journal For Immunotherapy of Cancer Jan 2024Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers...
BACKGROUND
Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.
METHODS
This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).
RESULTS
In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response.
CONCLUSIONS
Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.
Topics: Humans; Retrospective Studies; Prospective Studies; Programmed Cell Death 1 Receptor; Papillomavirus Infections; Carcinoma, Squamous Cell; Anus Neoplasms; DNA; Antibodies, Monoclonal, Humanized
PubMed: 38272561
DOI: 10.1136/jitc-2023-008436 -
Clinical and Translational... Apr 2024High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial...
INTRODUCTION
High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation).
METHODS
A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated.
RESULTS
The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00.
DISCUSSION
The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.
Topics: Humans; Deep Learning; Anus Neoplasms; Female; Male; Middle Aged; Squamous Intraepithelial Lesions; Carcinoma, Squamous Cell; Staining and Labeling; Proctoscopy; Aged; Algorithms; Neural Networks, Computer; Acetic Acid; Adult; Sensitivity and Specificity; Precancerous Conditions; Anal Canal; Predictive Value of Tests
PubMed: 38270249
DOI: 10.14309/ctg.0000000000000681