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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 -
Molecular Diagnosis & Therapy Mar 2024Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the... (Review)
Review
Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.
Topics: Humans; Biomarkers; Anus Neoplasms; Carcinoma, Squamous Cell; Genomics; Neoplasm Recurrence, Local
PubMed: 38267771
DOI: 10.1007/s40291-023-00692-9 -
Frontiers in Medicine 2023Intussusception refers to the invagination of a proximal loop of the bowel into an adjacent distal segment. This condition is rare in adults, especially when it involves...
Intussusception refers to the invagination of a proximal loop of the bowel into an adjacent distal segment. This condition is rare in adults, especially when it involves a complete folding of the ileocecal area out of the body cavity. Meanwhile, enterogenous cysts are congenital malformations that are largely identified in childhood following symptoms of bowel obstruction. While surgical treatment is ultimately required for both diseases, deciding on the type of surgery and the right time to operate can be a challenge for clinicians. It is especially difficult to decide on treatment for an adult with the coincidental occurrence of both conditions and no definitive pathologic diagnosis prior to surgery. Here, we present the case study of a 19-year-old female patient who presented with a prolapsed anus due to intussusception caused by a large ileocecal mass. The patient was admitted to the emergency department with a "massive anal mass." She remained symptomatic after receiving conventional conservative treatment and had to undergo emergency surgery after developing an intestinal obstruction. While the patient's intraoperative condition also confirmed the preoperative CT findings, the situation became more complicated during surgery. The postoperative pathological report indicated the presence of an enterogenous cyst. After recovery from surgery, the patient was successfully discharged. Intussusception or intestinal obstruction caused by an intestinal mass is a surgical indication, and removal is the only way to cure the condition. This case study provides a helpful reference for general surgeons, especially anorectal surgeons, imaging physicians, and pathologists, and informs the diagnosis and treatment of this patient population.
PubMed: 38249983
DOI: 10.3389/fmed.2023.1324792