Ultrasound Assessment After Surgery for Chronic Anal Fissure

BACKGROUND AND RATIONALE

Chronic anal fissure is a persistent, longitudinal tear in the anoderm that commonly causes severe pain during or after defecation, rectal bleeding, and a substantial reduction in quality of life. Increased resting pressure and persistent of the internal anal sphincter, reduced local blood flow, and repeated mechanical trauma during defecation contribute to persistence of the fissure. Initial management generally consists of measures intended to improve stool consistency, reduce trauma, and promote chemical relaxation of the internal anal sphincter. However, some patients continue to experience symptoms despite an adequate course of conservative treatment.

Lateral internal sphincterotomy is an established surgical treatment for chronic anal fissure that has not responded to conservative management. The procedure reduces internal anal sphincter pressure by dividing part of the distal internal sphincter. Although lateral internal sphincterotomy achieves high healing rates, the optimal extent of sphincter division remains uncertain. Division of an insufficient amount of muscle may fail to relieve sphincter hypertonia and may contribute to persistence or recurrence of the fissure. Conversely, excessive sphincter division may impair continence and lead to postoperative leakage of gas, liquid stool, or solid stool, or to faecal soiling.

The anatomical extent of sphincter division cannot always be accurately determined from the operative description alone. Endoanal ultrasonography permits direct postoperative assessment of the internal and external anal sphincters. Three-dimensional endoanal ultrasonography additionally enables longitudinal reconstruction of the anal canal and measurement of both the total length of the internal anal sphincter and the length of the postoperative sphincterotomy defect. The proportion of the internal sphincter divided can therefore be calculated for each participant and related to subsequent clinical outcomes.

The central hypothesis of this study is that there is a measurable range of internal anal sphincter division that is sufficient to promote fissure healing while limiting deterioration in anal continence. Identification of this relationship could contribute to a more anatomically tailored surgical approach rather than relying on a uniform division length for patients with different sphincter anatomy.

OBJECTIVES

The principal objective is to determine the minimum proportion of the internal anal sphincter divided during lateral internal sphincterotomy that is associated with fissure healing without clinically relevant postoperative deterioration in anal continence.

The study will also evaluate the impact of chronic anal fissure on quality of life before surgery, changes in generic and disease-specific quality of life during the first postoperative year, and clinical, anatomical, and surgical factors associated with fissure persistence, recurrence, faecal soiling, and anal incontinence.

Additional analyses will investigate the anatomical characteristics of the sphincterotomy defect, the integrity of the external anal sphincter, differences between complete, incomplete, or sonographically absent sphincter division, and the reproducibility of measurements obtained from stored three-dimensional ultrasound volumes.

STUDY DESIGN AND SETTING

This is a prospective, longitudinal, single-centre observational cohort study conducted in the Colorectal Surgery Unit of the Department of General and Digestive Surgery at Hospital Clínico Universitario de Valencia, Spain.

Consecutive adults with primary chronic anal fissure that has not responded to an adequate course of conservative treatment and who are scheduled for open or closed lateral internal sphincterotomy will be considered for participation. The study plans to include 66 participants. Recruitment began on 1 November 2024, and completion of follow-up is anticipated by 1 May 2028.

Participation in the study will not determine whether surgery is performed or which surgical technique is selected. All therapeutic decisions will be made by the treating clinical team according to routine clinical practice, the clinical characteristics of the participant, and the surgeon's judgement. The study is therefore observational: participants are not assigned to open or closed sphincterotomy, a specific type of anaesthesia, a predetermined length of sphincter division, or any other treatment strategy by the research protocol.

BASELINE ASSESSMENT

Before surgery, demographic characteristics, relevant comorbidities, current medication, cardiovascular risk factors, and previous anorectal disease or surgery will be recorded. In women, the obstetric history will also be documented, including information relevant to possible previous sphincter injury.

The clinical assessment will characterise the duration, location, appearance, and chronic features of the fissure. Information will be collected on bowel habit, stool consistency, straining, pain, bleeding, use of laxatives and analgesics, and previous medical or procedural treatment for the fissure. Baseline symptoms and their effect on daily life will be assessed before surgery.

Anal continence will be evaluated using the Jorge-Wexner score. This instrument assesses the frequency of incontinence to gas, liquid stool, and solid stool, as well as the use of pads and the effect of continence symptoms on lifestyle. Higher scores indicate greater impairment. Faecal soiling will be assessed separately because minor staining or leakage may not be fully represented by general continence scores.

Generic health-related quality of life will be evaluated using the 36-Item Short Form Health Survey, and condition-related quality of life will be assessed using the Faecal Incontinence Quality of Life questionnaire. Pain will be measured using the prespecified pain scale. The same instruments will be repeated during postoperative follow-up to evaluate changes over time.

SURGICAL MANAGEMENT

Open or closed lateral internal sphincterotomy will be performed by, or under the supervision of, surgeons from the Colorectal Surgery Unit. Participants may be positioned in lithotomy or in the prone jackknife position. Anaesthesia may consist of local anaesthesia, with or without sedation, or spinal anaesthesia, according to clinical judgement.

For open lateral internal sphincterotomy, the intersphincteric groove will be identified and a lateral incision will be made. The internal anal sphincter will be separated from the submucosal plane and from the distal external anal sphincter before controlled division of the selected internal sphincter fibres.

For closed lateral internal sphincterotomy, a scalpel will be introduced through a lateral intersphincteric approach, and the distal fibres of the internal anal sphincter will be divided towards the anal lumen. Wound closure or open drainage will be decided by the operating surgeon.

The operative record will document fissure morphology, the open or closed technique, type of anaesthesia, operating surgeon, and intraoperative estimate of the length or extent of internal sphincter division. Treatment will not be modified for research purposes, and the research ultrasound findings will be used for anatomical assessment rather than to direct the original surgical procedure.

ENDOANAL ULTRASONOGRAPHY

At the 3-month postoperative visit, participants will undergo two-dimensional followed by three-dimensional endoanal ultrasonography. No specific bowel preparation is planned. The examination will be performed in the knee-chest position using a B&K Medical Systems Pro Focus 2202 ultrasound platform with a B-K 2050 rotating probe. The probe permits 360-degree real-time transverse acquisition and multifrequency imaging. Acquisition will be performed at 10 MHz, with ultrasound settings standardised across examinations.

The probe will be introduced into the upper anal canal, identified by the level of the puborectalis muscle, and progressively withdrawn to acquire the complete anal canal volume. Examinations will be performed by colorectal surgeons experienced in endoanal ultrasonography. The acquired three-dimensional volumes will be stored to permit subsequent reconstruction, measurement, and independent review.

The ultrasonographic assessment will include the total longitudinal length of the internal anal sphincter, the longitudinal length of the sphincterotomy defect, the proportion of the internal anal sphincter divided, completeness of the division, and the angle of separation between the divided internal sphincter ends. The integrity of the external anal sphincter will also be assessed, and the location and extent of any external sphincter defect will be recorded.

The proportion of the internal anal sphincter divided will be calculated by dividing the longitudinal length of the sphincterotomy defect by the total longitudinal length of the internal anal sphincter. This relative measurement is intended to account for anatomical variation in sphincter length between participants and to provide a more individualised measure than the absolute defect length alone.

Stored ultrasound volumes will be evaluated separately by two independent observers experienced in endoanal ultrasonography. Each observer will record the prespecified measurements independently. Agreement between observers will be assessed using statistical methods appropriate to the type and distribution of each variable. Disagreements will be documented, and the analysis will distinguish between measurements obtained by each observer and any derived value used for the main outcome analyses.

FOLLOW-UP

Clinical follow-up is scheduled at 3, 6, and 12 months after surgery. At each visit, the investigators will assess fissure healing, persistence or recurrence, bowel habit, pain, bleeding, use of laxatives and analgesics, postoperative complications, hospital readmission, faecal soiling, and anal continence. Digital rectal examination will be performed when clinically feasible. The Jorge-Wexner score, soiling score, pain scale, SF-36, and Faecal Incontinence Quality of Life questionnaire will be repeated at each scheduled time point.

Fissure healing will be based on complete epithelialisation with no visible residual fissure and resolution of the associated clinical symptoms. Fissure persistence will be defined as failure of the fissure and its associated symptoms to resolve after surgery. The 3-month assessment will be used as the principal postoperative time point for identifying persistent disease.

Recurrence will be defined as the reappearance of a symptomatic fissure after previously documented healing and an intervening symptom-free period. The minimum symptom-free interval required for classification as recurrence will be prespecified in the statistical analysis plan before database lock.

The clinical status of the fissure at 12 months will be classified as healed without recurrence or as persistent or recurrent fissure. Anal continence will be evaluated by comparing the postoperative Jorge-Wexner score with the baseline score. Changes in individual continence components and the presence of faecal soiling will also be examined. Any threshold used to define clinically relevant deterioration in continence will be prespecified before the final analysis.

SAMPLE-SIZE RATIONALE

The sample-size calculation was performed using GRANMO and preliminary endosonographic data derived from the doctoral research of Ángel Sanahuja under the supervision of García-Granero. The calculation was based on comparison of two paired proportions and assumed an increase in the proportion of patients with anal incontinence from 0 at baseline to 13.6% after surgery.

Using a two-sided alpha level of 0.05 and 80% statistical power, 60 evaluable participants were required. Allowing for an anticipated loss to follow-up of approximately 10%, the target sample was increased to 66 participants.

Because the primary research question includes associations with potentially infrequent events, particularly recurrence and clinically relevant deterioration in continence, the effective number of observed events may limit the complexity of multivariable and predictive models. The number of candidate predictors and the degree of model flexibility will therefore be restricted according to the observed event count. Estimates will be reported with confidence intervals to reflect their precision.

STATISTICAL ANALYSIS

Analyses will follow a prespecified statistical analysis plan finalised before database lock. Participant flow, recruitment, availability of ultrasound examinations, and completeness of clinical follow-up will be reported. Baseline characteristics will be described for the complete cohort and, where appropriate, according to fissure and continence outcomes.

Continuous variables will be summarised using the mean and standard deviation or the median and interquartile range, depending on their observed distribution. Categorical variables will be presented as frequencies and percentages. Distributional assumptions will be assessed graphically and using appropriate diagnostic methods rather than relying solely on significance tests.

Changes in the Jorge-Wexner score, pain, SF-36, and Faecal Incontinence Quality of Life scores across baseline and the 3-, 6-, and 12-month assessments will be analysed using longitudinal mixed-effects models when supported by the data. These models will account for repeated measurements within the same participant and may allow the inclusion of participants with incomplete repeated observations under a missing-at-random assumption.

The association between the ultrasonographically measured proportion of internal anal sphincter division and the binary fissure outcome will be examined using logistic regression. Change in continence will be analysed using an appropriate generalised linear or ordinal model according to the observed distribution and properties of the outcome. Effect estimates will be accompanied by 95% confidence intervals.

The possibility of a non-linear association between the proportion of sphincter division and the clinical outcomes will be explored using restricted cubic splines only if the available sample size and number of events permit a reliable analysis. Candidate adjustment variables will be selected according to clinical relevance and prior knowledge rather than solely on the basis of univariable statistical significance.

Potential explanatory variables may include participant characteristics, baseline bowel habit and continence, fissure characteristics, previous anorectal or obstetric history, surgical technique, type of anaesthesia, operating surgeon, intraoperative estimate of sphincter division, ultrasonographic defect measurements, completeness of division, angle of separation, and external anal sphincter integrity. The final number of variables included in any model will depend on the amount and quality of the available data.

Exploratory analyses will compare participants with complete, incomplete, or sonographically absent internal sphincter division, provided that the number of participants in each category permits meaningful estimation. Open and closed surgical techniques may also be compared descriptively and analytically. These comparisons will be interpreted cautiously because the surgical technique is not randomly assigned and may be influenced by participant or surgeon characteristics.

Interobserver agreement for the ultrasonographic measurements will be quantified using agreement statistics selected according to whether the variable is continuous, ordinal, or categorical. The magnitude and clinical relevance of disagreement will be considered in the interpretation of associations between ultrasound findings and outcomes.

Missing data will be described by variable and follow-up time point. Patterns and possible reasons for missingness will be examined. If the amount and structure of missing data justify it, multiple imputation may be used for selected analyses under clearly stated assumptions. Complete-case or other sensitivity analyses will be performed where appropriate to assess the robustness of the findings.

All statistical tests will be two-sided, with a significance level of 0.05. Results will be interpreted using effect sizes, confidence intervals, and clinical relevance rather than statistical significance alone. The analyses will be conducted using RStudio.

POTENTIAL SOURCES OF BIAS

Consecutive recruitment is intended to reduce selective inclusion of participants. Nevertheless, the single-centre design may limit the generalisability of the findings to other hospitals, populations, surgical practices, or ultrasound protocols.

Because the study is observational and treatment decisions are made according to routine clinical practice, comparisons between open and closed sphincterotomy or between different operative approaches may be affected by confounding by indication and other measured or unmeasured factors. Relevant clinical and surgical characteristics will therefore be recorded and considered in adjusted analyses when the number of outcome events permits.

Standardisation of the ultrasound acquisition procedure and separate review of stored volumes by two independent observers are intended to reduce measurement variability. Interobserver agreement will be reported so that the reproducibility of the anatomical measurements can be considered when interpreting the results.

Loss to follow-up and incomplete questionnaires may introduce attrition bias. Participant flow and completeness of each assessment will therefore be reported, and the characteristics of participants with and without complete follow-up will be compared descriptively when feasible.

DATA MANAGEMENT AND CONFIDENTIALITY

Study information will be entered into a coded research database. Participants will be identified in the analytical dataset using a study code rather than directly identifying information. The correspondence between participant identity and study code will be stored separately with restricted access.

Data-quality procedures will include review of completeness, range, internal consistency, and temporal coherence. Any correction to the database will be traceable. Access to identifiable data will be limited to authorised members of the research team. Study documentation and data will be retained for at least 25 years in accordance with applicable institutional requirements.

ETHICAL CONSIDERATIONS

The study was reviewed and approved by the Clinical Research Ethics Committee of Hospital Clínico Universitario de Valencia on 12 October 2024, with reference number 2024/339. The study will be conducted in accordance with the Declaration of Helsinki and applicable Spanish and European data-protection legislation.

Participants will receive oral and written information about the study objectives, procedures, foreseeable burdens, potential risks, voluntary nature of participation, and right to withdraw. Written informed consent will be obtained before any study-specific procedure. Refusal to participate or subsequent withdrawal will not affect the participant's clinical care.

The principal study-specific burden is the endoanal ultrasonographic examination performed at 3 months after surgery. All surgical treatment and other clinical decisions will remain part of usual care. No experimental drug, device, or surgical intervention will be assigned by the study protocol.

Any substantial amendment affecting eligibility, outcomes, follow-up, sample size, or the analysis plan will be submitted to the ethics committee when required, documented with its date and rationale, communicated to the research team, and reflected in the ClinicalTrials.gov record and subsequent publications.

Inclusion criteria

• Age 18 years or older.
• Primary chronic anal fissure, defined as symptoms lasting more than 6-8 weeks and failure of complete conservative treatment, irrespective of the presence of anatomical signs of chronicity.
• Clinical indication for open or closed LIS.
• Capacity to understand the study, complete the questionnaires and provide written informed consent.

Exclusion criteria

• Acute anal fissure of less than 6-8 weeks' duration.
• Secondary anal fissure associated with Crohn's disease, ulcerative colitis, tuberculosis, HIV infection, anal malignancy or another identified secondary cause.
• Neurological or neuromuscular disease that may affect continence.
• Moderate or severe anal incontinence at baseline.
• Concomitant anorectal disease requiring another procedure, including symptomatic haemorrhoids or anal fistula.
• Previous or current circumstances that prevent reliable completion of patient-reported measures.
• Anticipated inability to attend postoperative follow-up.
• Incomplete conservative treatment before the decision for surgery.
• Participants may withdraw consent at any time without affecting their care. Investigators may discontinue study follow-up if eligibility was incorrectly assigned or if a clinical event prevents completion of study procedures. Data collected before withdrawal will be handled in accordance with the consent form and applicable legislation.