Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study.

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.

Comparison of etiological and physiological characteristics of fecal incontinence in men and women.

Fecal incontinence (FI) is often underreported and underestimated in men. Our aims were to clarify the causes and the physiological characteristics of FI in men and to underline the differences between etiological and physiological factors in men and women diagnosed with FI. The study cohort encompassed 200 men and 200 women who underwent anatomical and physiological evaluation for FI in a tertiary referral center specializing in pelvic floor disorders. All patients underwent endoanal ultrasound and anorectal manometry. Evacuation proctography was performed in some patients. Demographic, medical, anatomical, and physiological parameters were compared between the two study groups. Urge incontinence was the most frequent type of FI in both genders. In men, anal fistula, history of anal surgeries, rectal tumors, and pelvic radiotherapy were common etiologic factors, whereas history of pelvic surgeries was more common in women. Associated urinary incontinence was reported more frequently by women. External anal sphincter defects, usually anterior, were more common in women (M: 1.5%, F: 24%, P < 0.0001), whereas internal anal sphincter defect prevalence was similar in men and women (M: 6%, F: 12%, P = 0.19). Decreased resting and squeeze pressures were less common in men (M: 29%, F: 46%, P < 0.0001: M: 44%, F: 66%, P < 0.0001). The incidence of rectal hyposensitivity was higher in men (M: 11.1%, F: 2.8%, P < 0.0001), whereas rectal hypersensitivity was higher in women (M: 5.8%, F: 10.8%, P < 0.0001). Anorectal dyssynergia was more common in men (M: 66%, F: 37%, P < 0.0001). Significantly different etiological factors and physiological characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options.NEW & NOTEWORTHY Fecal incontinence (FI) in men has different etiological factors when compared with women. The prevalence of internal anal sphincter defect among men with FI was similar to women. Different manometric measurements were found among men with FI: decreased anal pressures were less common among men, whereas rectal hyposensitivity and anorectal dyssynergia were more common among men.

Mutational Signature Changes in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: We examined the concordance of genetic mutations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (SCCA) and assessed the impact of therapy on this concordance. METHODS: We analyzed next-generation sequencing reports from pretreatment tumor tissue and posttreatment ctDNA in 11 patients with metastatic SCCA treated at Vanderbilt University Medical Center between 2017 and 2021. RESULTS: Among the mutations identified in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Four patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 7 patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue. CONCLUSION: Patients with SCCA demonstrate a high degree of temporal mutational heterogeneity. This supports the hypothesis that ctDNA can serve as a real-time tracking mechanism for solid tumors' molecular evolution in response to therapy. Our findings highlight the potential of ctDNA in identifying emerging actionable mutations, supplementing information from tissue-based genomic assessments. Further research, ideally with larger and multi-institutional cohorts, is needed to validate our findings in this relatively rare tumor type.

A Predictive Model to Identify the Effects of Transcutaneous Sacral Nerve Stimulation With Pelvic Floor Exercises in Fecal Incontinence After Surgery for Anorectal Malformation.

INTRODUCTION: Although the combination of transcutaneous sacral nerve stimulation (tSNS) and pelvic floor exercises (PFEs) has shown significant effectiveness in treating fecal incontinence (FI) after surgery for congenital anorectal malformation (CARM), not all patients achieve satisfactory continence. Therefore, identifying which individuals will benefit from this method is crucial. METHODS: A prospective cohort study enrolled 92 children with FI. All patients underwent tSNS with PFE treatment, and an improved outcome was defined as a Wexner score ≤4. A predictive model to identify the effects of tSNS with PFEs in FI was developed based on the analysis of magnetic resonance imaging and high-resolution anorectal manometry with area under the receiver-operating characteristic curve to evaluate the predictive value of external anal sphincter (EAS) thickness index and anal squeezing pressure (ASP). RESULTS: tSNS with PFEs improved outcomes in 72 patients and led to poor outcomes in 20 (4 had their rectums deviate from the puborectalis muscle center or puborectal muscle ruptures while 16 lacked EAS with a lower ASP). The areas under the receiver-operating characteristic curve for EAS thickness index and ASP in predicting the effects of tSNS with PFEs were 0.915 (95% confidence interval 0.846-0.983, P = 0.000) and 0.886 (95% confidence interval 0.819-0.952, P = 0.000), respectively. By applying cutoff values of 0.076 for EAS thickness index and 21.95 mm Hg for ASP, tSNS with PFEs was found to be ineffective. DISCUSSION: tSNS with PFEs is effective for most patients with FI after CARM surgery, except when the rectum deviates from the puborectal muscle center, puborectal muscle rupture occurs, or EAS is absent with a low ASP.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study.

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service.

OBJECTIVES: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. METHODS: We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. CONCLUSIONS: POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.

Determinants of Type-Specific Human Papillomavirus Concordance Across Anatomic Sites in Young Men Who Have Sex With Men and Transgender Women, 3 U.S. Cities, 2016-2018.

BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections.

Pyoderma Gangrenosum of the Genitalia, Anus, and Perineum: Two Case Reports and a Review of Published Cases.

ABSTRACT: Pyoderma gangrenosum is an inflammatory skin disease that presents with rapidly progressive ulcers with violaceous, undermined borders. Despite most commonly affecting the lower extremities, pyoderma gangrenosum can rarely present in the genital, anal, and perineal regions. We describe 2 cases and report a review of published cases.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Substantial incidence of bladder dysfunction in patients with VACTERL association: Implications for surveillance.

VACTERL association is defined as the nonrandom co-occurrence of a minimum of three of the following six key components: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Patients presenting with two components may also belong in the same spectrum. Additional components have been associated with VACTERL defects, including single umbilical artery, tethered spinal cord (TSC), and genital malformations. We observed a significant proportion of patients with bladder dysfunction (often called neurogenic bladder in the medical record) when reviewing a cohort of patients with VACTERL defects at our clinical center. Our finding calls attention to bladder dysfunction as an additional VACTERL phenotypic component. The prevalence of bladder dysfunction is greatest in those with genital anomalies, anorectal malformations, sacral dysplasia, renal anomalies, and TSC. We propose that patients with two or more VACTERL malformations be monitored for symptoms of bladder dysfunction if one or more of the identified risk factors are present until the achievement of urinary continence.

Assisted vaginal birth in 21st century: current practice and new innovations.

Assisted vaginal birth rates are falling globally with rising cesarean delivery rates. Cesarean delivery is not without consequence, particularly when carried out in the second stage of labor. Cesarean delivery in the second stage is not entirely protective against pelvic floor morbidity and can lead to serious complications in a subsequent pregnancy. It should be acknowledged that the likelihood of morbidity for mother and baby associated with cesarean delivery increases with advancing labor and is greater than spontaneous vaginal birth, irrespective of the method of operative birth in the second stage of labor. In this article, we argue that assisted vaginal birth is a skilled and safe option that should always be considered and be available as an option for women who need assistance in the second stage of labor. Selecting the most appropriate mode of birth at full dilatation requires accurate clinical assessment, supported decision-making, and personalized care with consideration for the woman's preferences. Achieving vaginal birth with the primary instrument is more likely with forceps than with vacuum extraction (risk ratio, 0.58; 95% confidence interval, 0.39-0.88). Midcavity forceps are associated with a greater incidence of obstetric anal sphincter injury (odds ratio, 1.83; 95% confidence interval, 1.32-2.55) but no difference in neonatal Apgar score or umbilical artery pH. The risk for adverse outcomes is minimized when the procedure is conducted by a skilled accoucheur who selects the most appropriate instrument likely to achieve vaginal birth with the primary instrument. Anticipation of potential complications and dynamic decision-making are just as important as the technique for safe instrument use. Good communication with the woman and the birthing partner is vital and there are various recommendations on how to achieve this. There have been recent developments (such as OdonAssist) in device innovation, training, and strategies for implementation at a scale that can provide opportunities for both improved outcomes and reinvigoration of an essential skill that can save mothers' and babies' lives across the world.

Pelvic floor injury during vaginal birth is life-altering and preventable: what can we do about it?

Pelvic floor disorders after childbirth have distressing lifelong consequences for women, requiring more than 300,000 women to have surgery annually. This represents approximately 10% of the 3 million women who give birth vaginally each year. Vaginal birth is the largest modifiable risk factor for prolapse, the pelvic floor disorder most strongly associated with birth, and is an important contributor to stress incontinence. These disorders require 10 times as many operations as anal sphincter injuries. Imaging shows that injuries of the levator ani muscle, perineal body, and membrane occur in up to 19% of primiparous women. During birth, the levator muscle and birth canal tissues must stretch to more than 3 times their original length; it is this overstretching that is responsible for the muscle tear visible on imaging rather than compression or neuropathy. The injury is present in 55% of women with prolapse later in life, with an odds ratio of 7.3, compared with women with normal support. In addition, levator damage can affect other aspects of hiatal closure, such as the perineal body and membrane. These injuries are associated with an enlarged urogenital hiatus, now known as antedate prolapse, and with prolapse surgery failure. Risk factors for levator injury are multifactorial and include forceps delivery, occiput posterior birth, older maternal age, long second stage of labor, and birthweight of >4000 g. Delivery with a vacuum device is associated with reduced levator damage. Other steps that might logically reduce injuries include manual rotation from occiput posterior to occiput anterior, slow gradual delivery, perineal massage or compresses, and early induction of labor, but these require study to document protection. In addition, teaching women to avoid pushing against a contracted levator muscle would likely decrease injury risk by decreasing tension on the vulnerable muscle origin. Providing care for women who have experienced difficult deliveries can be enhanced with early recognition, physical therapy, and attention to recovery. It is only right that women be made aware of these risks during pregnancy. Educating women on the long-term pelvic floor sequelae of childbirth should be performed antenatally so that they can be empowered to make informed decisions about management decisions during labor.

The prevention of perineal trauma during vaginal birth.

Perineal trauma after vaginal birth is common, with approximately 9 of 10 women being affected. Second-degree perineal tears are twice as likely to occur in primiparous births, with a incidence of 40%. The incidence of obstetrical anal sphincter injury is approximately 3%, with a significantly higher rate in primiparous than in multiparous women (6% vs 2%). Obstetrical anal sphincter injury is a significant risk factor for the development of anal incontinence, with approximately 10% of women developing symptoms within a year following vaginal birth. Obstetrical anal sphincter injuries have significant medicolegal implications and contribute greatly to healthcare costs. For example, in 2013 and 2014, the economic burden of obstetrical anal sphincter injuries in the United Kingdom ranged between £3.7 million (with assisted vaginal birth) and £9.8 million (with spontaneous vaginal birth). In the United States, complications associated with trauma to the perineum incurred costs of approximately $83 million between 2007 and 2011. It is therefore crucial to focus on improvements in clinical care to reduce this risk and minimize the development of perineal trauma, particularly obstetrical anal sphincter injuries. Identification of risk factors allows modification of obstetrical practice with the aim of reducing the rate of perineal trauma and its attendant associated morbidity. Risk factors associated with second-degree perineal trauma include increased fetal birthweight, operative vaginal birth, prolonged second stage of labor, maternal birth position, and advanced maternal age. With obstetrical anal sphincter injury, risk factors include induction of labor, augmentation of labor, epidural, increased fetal birthweight, fetal malposition (occiput posterior), midline episiotomy, operative vaginal birth, Asian ethnicity, and primiparity. Obstetrical practice can be modified both antenatally and intrapartum. The evidence suggests that in the antenatal period, perineal massage can be commenced in the third trimester of pregnancy to increase muscle elasticity and allow stretching of the perineum during birth, thereby reducing the risk of tearing or need for episiotomy. With regard to the intrapartum period, there is a growing body of evidence from the United Kingdom, Norway, and Denmark suggesting that the implementation of quality improvement initiatives including the training of clinicians in manual perineal protection and mediolateral episiotomy can reduce the incidence of obstetrical anal sphincter injury. With episiotomy, the International Federation of Gynecology and Obstetrics recommends restrictive rather than routine use of episiotomy. This is particularly the case with unassisted vaginal births. However, there is a role for episiotomy, specifically mediolateral or lateral, with assisted vaginal births. This is specifically the case with nulliparous vacuum and forceps births, given that the use of mediolateral or lateral episiotomy has been shown to significantly reduce the incidence of obstetrical anal sphincter injury in these groups by 43% and 68%, respectively. However, the complications associated with episiotomy including perineal pain, dyspareunia, and sexual dysfunction should be acknowledged. Despite considerable research, interventions for reducing the risk of perineal trauma remain a subject of controversy. In this review article, we present the available data on the prevention of perineal trauma by describing the risk factors associated with perineal trauma and interventions that can be implemented to prevent perineal trauma, in particular obstetrical anal sphincter injury.

A novel genotype-phenotype between persistent-cloaca-related VACTERL and mutations of 8p23 and 12q23.1.

The mechanism underlying anorectal malformations (ARMs)-related VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, and renal and limb abnormalities) remains unclear. Copy number variation (CNV) contributed to VACTERL pathogenicity. Here, we report a novel CNV in 8p23 and 12q23.1 identified in a case of ARMs-related VACTERL association. This 12-year-old girl presented a cloaca (urethra, vagina, and rectum opening together and sharing a single tube length), an isolated kidney, and a perpetuation of the left superior vena cava at birth. Her intelligence, growth, and development were slightly lower than those of normal children of the same age. Array comparative genomic hybridization revealed a 9.6-Mb deletion in 8p23.1-23.3 and a 0.52-Mb duplication in 12q23.1 in her genome. Furthermore, we reviewed the cases involving CNVs in patients with VACTERL, 8p23 deletion, and 12q23.1 duplication, and our case was the first displaying ARMs-related VACTERL association with CNV in 8p23 and 12q23.1. These findings enriched our understanding between VACTERL association and the mutations of 8p23 deletion and 12q23.1 duplication. IMPACT: This is a novel case of a Chinese girl with anorectal malformations (ARMs)-related VACTERL with an 8p23.1-23.3 deletion and 12q23.1 duplication. Cloaca malformation is presented with novel copy number variation in 8p23.1-23.3 deletion and 12q23.1 duplication.

Anatomy of muscle connections in the male urethra and anorectal canal.

OBJECTIVES: To elucidate the male urethral muscular structure and its relationship with the anorectal canal muscles, as establishing an anatomical foundation for urethral function will contribute to the prevention, diagnosis, and treatment of urinary incontinence. METHODS: Eight male cadavers were used. Using a multifaceted approach, we performed macroscopic anatomical examination, histological analysis of wide-range serial sectioning and immunostaining, and three-dimensional (3D) reconstruction from histological sections. In the macroscopic anatomical examination, pelvic halves were meticulously dissected in layers from the medial aspect. In the histological analysis, the tissue, including the urethra and anorectal canal, was serially sectioned in the horizontal plane. The muscular structures were reconstructed and visualised in 3D. RESULTS: The membranous portion of the urethra had three muscle layers: the longitudinal and circular muscles (smooth muscle) and the external urethral sphincter (skeletal muscle). The circular muscle was connected posteriorly to the longitudinal rectal muscle. The external urethral sphincter had a horseshoe shape, with its posterior ends continuing to the external anal sphincter, forming a 3D ring-like sphincter. CONCLUSION: This study revealed skeletal and smooth muscle connections between the male urethra and anorectal canal, enabling urethral compression and closure. These anatomical muscle connections suggest a functional linkage between them.

Functional Disorders of the Ileal-Anal Pouch: A Systematic Review.

BACKGROUND: The IPAA is a boon to patients needing proctocolectomy but maintains per anal function through anatomic and physiologic compromises. The state of pouch function is hard to define because pouch anatomy is not normal and pouch physiology is a distortion of normal defecation. Patients with pouches develop multiple symptoms: some are expected, some are disease related, and some are the result of surgical complications. It is important to understand the cause of pouch-related symptoms so that appropriate management is offered. OBJECTIVES: The study aimed to review pouch symptoms and discuss their likely cause, review the literature on pouch function and dysfunction, and provide clarity to clear the confusion. DATA SOURCES: PubMed and Cochrane databases were searched using the terms "ileoanal pouch function" and "ileoanal pouch dysfunction." STUDY SELECTION: From 1983 to 2023, 553 articles related to "ileoanal pouch function" and 178 related to "ileoanal pouch dysfunction" were reviewed. Nine studies appeared under both headings. Case studies, duplicate publications, and articles concerning pouch diseases were excluded. MAIN OUTCOME MEASURES: Definitions of pouch function and dysfunction, methods of describing and scoring symptoms, and understanding of expected changes in pouch function given the nature of the surgery. RESULTS: Twenty-seven studies were reviewed from the ileoanal pouch dysfunction search and 38 from ileoanal pouch function. Three studies tried to define normal pouch function, 10 attempted to measure pouch function, and 4 aimed to score pouch function. Only 3 studies addressed pouch physiology. LIMITATIONS: A full discussion of pouch dysfunction is limited by the lack of studies focussing on the anatomic and physiologic consequences of turning the terminal ileum into an organ of storage. CONCLUSIONS: Most studies of pouch function and dysfunction do not consider expected changes in the physiology of defecation that follow restorative proctocolectomy. Thus, most studies of pouch function produce conclusions that lack an important dimension. See video from symposium.

Dilip's Transmucosal Internal Sphincterotomy: A Simplified Approach to Lateral Internal Sphincterotomy for Fissure in Ano.

BACKGROUND: Fissure in ano is a prevalent and painful condition, typically treated by lateral internal sphincterotomy after conservative measures fail. Dilip's transmucosal internal sphincterotomy introduces a simplified approach that reduces the risk of damaging the external sphincter, making it particularly suitable for less experienced surgeons. This innovation offers a less invasive method with minimal risk of incontinence, providing a safer, more accessible option. IMPACT OF INNOVATION: Transmucosal internal sphincterotomy simplifies the internal sphincterotomy process, offering a tailored approach that eliminates the need for extensive dissection. This method allows surgeons complete control over the internal sphincter bundle, facilitating a precise, customizable cut without the risks associated with traditional internal sphincterotomy, especially in obese patients where the intersphincteric groove is not visible, leading to potentially harmful blind incisions. TECHNOLOGY, MATERIALS, AND METHODS: The procedure is performed under saddle block anesthesia with the patient in the lithotomy position. A distinctive approach involving the use of retractors and stay sutures allows the internal sphincter to be made prominent and secured without extensive dissection. The division of the internal sphincter is achieved through a minimal mucosal incision, requiring no closure and significantly reducing postoperative pain and complications. PRELIMINARY RESULTS: Between December 2020 and February 2022, 124 patients received transmucosal internal sphincterotomy, showing significant benefits with a median operative time of 7 minutes and low postoperative pain. With a 2.5% infection rate effectively managed and a 3% transient incontinence rate, the majority healed within 9 weeks. Recurrence was rare at 1.6%. CONCLUSIONS AND FUTURE DIRECTIONS: Transmucosal internal sphincterotomy presents significant advantages over traditional internal sphincterotomy, including reduced pain, lower risk of complications, such as hematoma, abscess, or fistula formation, and the absence of painful postoperative nodules. The success of transmucosal internal sphincterotomy suggests that it should be incorporated into surgical education, offering a less daunting and more reproducible method for treating fissure in ano that is especially beneficial for junior surgeons and improving patient outcomes.