Long-term Outcome in Patients With Anorectal Malformations

Background Anorectal malformations(ARM) are rare and cover congenital defective development of rectum.

ARM include a range of congenital conditions and may in varying degrees involve the anorectum. A significant part have malformations in other organs mainly the urinary tract.

In the vast majority ARM are recognized at birth by lack of a normal anus. The primary approach is construction of a stoma and subsequent reconstruction. Bowel continuity is typical restored after 4-6 months.

Many patients experience abnormal bowel function later on and affected quality of life(QoL).

Aim

The primary objective is to assess the patient-related outcome 10-30 years after surgery for ARM and to see if it related to existing damage to anorectum and bowel function. The secondary objective is to identify problems with bowel function which may be treated medically or by surgery to improve bowel function and QoL. To obtain the necessary knowledge the study is divided in the following sub-projects:

1. Assessment of bowel function and QoL through relevant questionnaires
2. Examine sphincter anatomy and function through rectal ultrasound, magnetic resonans(MR)-scan of the pelvis and anal manometry. Bowel function is assessed through colonic transit time. Screening for urinary tract problems with uroflowmetry.

Methods Participants are identified through relevant diagnostic codes(Q 42) and patients which underwent surgery for ARM in the years 1985-2005 are included if informed consent is obtained.

Relevant questionnaires regarding symptoms and QoL are completed before the following examinations:

* Anal manometry
* Anal ultrasound
* Pudenda conduction velocity
* Colonic transit time
* Magnetic resonans(MR)-scan of lower abdomen and pelvis
* Uroflowmetry

Bowel function and QoL is assessed in both children and adults with relevant validated questionnaires.

Perspective No danish studies and only a few foreign investigate the relationship between anatomy/physiology and quality of life after surgery for anorectal malformations.

The investigators believe the study and included comprehensive examinations will clarify the causes of functional problems after surgery for anorectal malformations. Results of questionnaires regarding symptoms, disease-specific-and general quality of life offer a unique opportunity for targeted treatment to improve symptoms and QoL in patients with ARM.

Aim

Endpoints The primary endpoints are outcome 10-30 years after surgery for anorectal malformations and to see if it is related to existing altered anatomy, anorectal function and intestinal passage.

The secondary endpoints is to identify bowel function problems which can be treated by medicine or surgery to improve patients bowel function and quality of life.

To obtain the necessary knowledge the study will be divided in the following

Sub-projects:

1. Evaluation of bowel function and quality of life with relevant questionnaire.
2. Examine anorectal anatomy and function with anal ultrasound, Magnetic resonans(MR)-scan of the small pelvis and anal manometry. Overall bowel function is examined with colonic transit time. Screening for urinary problems with urodynamic testing.

Background Anorectal malformations(ARM) cover a wide spectrum of congenital disorders seen in both sexes and may also involve the urinary tract and genitals. It occurs in 1/2500 of newborns with a slight predominance in boys and 2/3 have accompanying anomalies. ARM form as an abnormal development of the hindgut which later forms the descending colon, rectum, anus, bladder and urethra. This explains frequent recurrence of accompanying malformations in the urinary tract.

The reason for the development of ARM is unknown. The etiology is probably multifactorial including both heredity and environment. A chromosomal anomaly is found among 5% of patients with ARM and Trisomy 21 being most common. Possible risk factors is maternal fever in the first trimester, industrial exposure to solvents, paternal smoking, maternal obesity and diabetes.

Accompanying anomalies often involve more organ systems. The mortality among patients with ARM is 10-20 % and is primary seen with high malformations having most severe associated anomalies including cardiac.

Previously the classification of ARM was based upon sex and the position of rectum relative to the levator ani muscle in high, intermediate and low(Wingspread classification). Pena and colleagues suggested in the mid 90s a classification system based on the presence of a fistula. Later the Krickenbeck classification system was introduced which classify ARM based on appearance, surgical approach and symptoms.

The classic surgical approach consists of an early divergent stoma, later a surgical correction and finally closure of the stoma.The classic surgical treatment of intermediate and high ARM was an abdominoperineal pull-through technique. Later Pena and colleagues introduced posterior sagittal anorectal plasty(PSARP). PSARP was adapted at Odense University hospital in 1994 and still the preferred surgical approach. Last laparoscopic assisted anorectal pull-through(LAARP) has been introduced but has not gain common accept.

Functional problems after ARM is primary fecal incontinence for high and constipation for low malformations.Treatment is primary medical or dietetic regulation of the bowel and in treatment-resistent cases anal irrigation and appendicostomy and antegrade colonic irrigation. Sometimes a permanent stoma may be needed.

Different imaging techniques and physiological measures have been used to clarify the anatomy and bowel function after surgical correction of ARM.

MRI(magnetic resonance imaging) of the pelvis has shown differences in patients with constipation and fecal incontinence after surgery for ARM. MRI provides useful information regarding pelvic musculature, colonic anatomy and other accompanying disorders. Anal ultrasound and manometry are useful to evaluate the anatomy and function of the anal sphincter. Scar tissue formation and defects in the anal sphincter are correlated to pressure in the anal canal and fecal incontinence.

A recent technique to evaluate the anorectal neuromuscular function is High Resolution Anorectal Manometry(HRAM). HRAM has previously proven to be more accurate in displaying anorectal anatomy compared to water-perfused manometry. Colonic transit time provides information about motility disorders and in patient with constipation colonic hypomobility is observed.

Pudendal nerve conduction velocity can be useful in evaluating fecal incontinence and delayed conduction velocity observed.

An essential issue regarding ARM is quality of life(QoL). A literature review by Witvliet and colleagues showed that only 20% of published studies used validated questionnaires.(30) Nine of 30 included studies on QoL were performed on an adult population. Poyet and colleagues found Health Related Quality of Life(HRQoL) was affected among patient aged one to four years compared to a control group after surgery for ARM. Hartmann et al. found no changes during a period of three years in an adult population. Women, older patients, patients with other defects and patients with a stoma reported reduced QoL.

Statistics It is mainly a descriptive study and therefore power calculation is neither possible nor relevant. In recruitment period an average of 10 patients have undergone surgery annually at the University Hospital of Odense. The investigators expect more than 50% of patients will participate and the population would be one of the largest yet seen. It will be possible to prove clinical relevant differences(20%) or correlations between different operative techniques. Further more it is possible to prove correlations between symptoms and outcome of different imaging techniques, examinations and questionnaires.

Questionnaires Symptoms and QoL are assessed with questionnaires. Bowel function after surgery for anorectal malformations is evaluated with the Krickenbeck Classification. In adults also with Wexner's Incontinence score and Cleveland Clinic Constipation Score(CCCS).

Disease-specific QoL in adults is assessed with Fecal Incontinence QoL(FIQL) and general QoL with the EQ-5D-5L. In participants below 18 years of age general QoL is assessed with Strenght and Difficulties Questionnaire(SDQ).

Urinary function and impact on quality of life in adults is evaluated with International Consultation on Incontinence Modular Questionnaire - Female Lower Urinary Tract Symptoms(ICIQ-FLUTS) and International Consultation on Incontinence Modular Questionnaire - Male Lower Urinary Tract Symptoms(ICIQ-MLUTS).

Sexual function is assessed with International Index of Erectile Dysfunction(IIEF) and in women with Female Sexual Function Index(FSFI).

Only Danish version of questionnaires are used.

Course plan The project will run for three years(2014-2017) and it is intended that all subjects have completed examinations before July 2016. The participants will be asked to fill in the different questionnaire regarding bowel habits, symptoms and QoL. There are planned hospitalization for participants for two days and they may stay overnight at the patient hotel or at home. Initially medical history is obtained, clinical examination performed and questionnaires collected.

Perspective No danish studies and only a few foreign investigate the relationship between anatomy/physiology and quality of life after surgery for anorectal malformations.

The investigators believe the study and included comprehensive examinations will clarify the causes of functional problems after surgery for anorectal malformations. Results of questionnaires regarding symptoms, disease-specific-and general quality of life offer a unique opportunity for targeted treatment to improve symptoms and QoL in patients with ARM.

Eligibility Criteria:
Inclusion Criteria:

* Surgery for anorectal malformations

Exclusion Criteria:

* Severe mental disability