Surgical decision for a young woman with familial adenomatous polyposis

Familial adnomatous polyposis (FAP) is a disease characterised by a multitude of polyps (hundreds to thousands), most often present in the colon, which have pre-malignant potential. The condition is due to a mutation in the adenomatous polyposis coli (APC) gene. Although the majority of these cases are inherited, a significant proportion arise due to a de novo mutation. The definitive treatment for the condition is surgery, but with multiple surgical options available, it is important to consider the trifecta of best evidence, clincial judgement and patient values in the selection process. In the present case report, a 36-year old woman diagnosed with FAP presented with a small bowel obstruction upstream of her stoma. Eight months previosuly, she underwent a panproctocolectomy and ileostomy with the creation of a ileal-pouch. The surgery was necessary as there was a suspected rectosigmoid cancer seen on CT. Reported is the information pertaining to her recent stay in hospital following the obstruction but the discussion explores the multi-faceted approach to determining which type of surgery was most suitable for


Abstract
Familial adnomatous polyposis (FAP) is a disease characterised by a multitude of polyps (hundreds to thousands), most often present in the colon, which have pre-malignant potential. The condition is due to a mutation in the adenomatous polyposis coli (APC) gene. Although the majority of these cases are inherited, a significant proportion arise due to a de novo mutation. The definitive treatment for the condition is surgery, but with multiple surgical options available, it is important to consider the trifecta of best evidence, clincial judgement and patient values in the selection process. In the present case report, a 36-year old woman diagnosed with FAP presented with a small bowel obstruction upstream of her stoma. Eight months previosuly, she underwent a panproctocolectomy and ileostomy with the creation of a ileal-pouch. The surgery was necessary as there was a suspected rectosigmoid cancer seen on CT. Reported is the information pertaining to her recent stay in hospital following the obstruction but the discussion explores the multi-faceted approach to determining which type of surgery was most suitable for this patient.

FAP -a summary
Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition in which there is a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5. The consequence of this mutation is characteristic polyp formation predominantly in the colon, but also at other sites such as the small bowel, which can develop into adenocarcinomas. Although named 'familial', it is believed that 10-30% of cases of FAP arise from de novo mutations 1 . FAP is a rare disease, with estimates of frequency from 1 in 6,850 to 29,000 people 2 . It is estimated that FAP is responsible for approximately 1% of colorectal cancer presentations 3 .

A brief history
The first reported case of polyposis was described in 1721 by Menzel 4 . This report was followed by many others in the subsequent decades, with an ill-defined suspected sequelae of events involving rectal haemorrhage leading to mucosal prolapse, inflammation, diarrhoea and rectal mucosal follicular hypertrophy 5 . At the beginning of the 20th century, the tendency for the polyp condition to have an inherited predisposition was illuminated5. Later that century, it was highlighted the pre-malignant potential of these adenoid polyps with surgery becoming an important treatment option. The first 3-stage proctocolectomy for the condition was performed in 1924 6 . A few years later, it was determined that the inheritance pattern for this condition was dominant 7 , and there began to appear the suggestion that offspring of affected individuals should undergo a prophylactic sigmoidectomy. The first proctocolectomy with a straight ileoanal anastamosis was successfully carried out in 1933. Later, Lloyd-Davies carried out the first colectomy and ileorectal anastomosis in St Mark's Hospital 8 . Much later, in 1978, another treatment option, called a restorative procotocolectomy was performed 22 . FAP does not just affect the colon, with extra-intestical features described by Gardner in 1951 which include desmoid tumours, cyst-like tumours and bone tumours 9 .

Aetiology and pathogenesis
The characteristic gene affected in FAP is APC. The role of this gene is as a tumour suppressor gene, which is involved in controlling the Wnt signal transduction pathway 10 . The possibility of an association of a chromosomal deletion in 5q and FAP was proposed in 1986 11 and confirmed to be 5q21-22 by two independent groups in 1987 12,13 .
The polyps which arise in FAP have malignant potential. There is a link between the site of mutation in Keywords: Familial adenomatous polyposis, surgical management.

Summary
In the present case report, there are two particular learning points which are crucial. The first is that we must take serious symptoms seriously, even in young people. In this case study, we had a young woman with a change in bowel habit, with cancer being a differential diagnosis which would usually be further down the list. However, due process was followed which led to the diagnosis being made swiftly. Furthermore, we must remember that spontaneous mutation is present in over a quarter of cases of FAP so, again, take serious symptoms seriously. Secondly, a point which is important for this case is the optimization of a patient's condition prior to surgery. In the present case, the patient was admitted for TPN to help her recover some weight and strength to prior to surgery, to maximize her chances of a successful surgical outcome.
the APC gene and the degree of disease severity. Mutations at the far 3' and 5' ends of the APC gene are associated with a milder phenotype whilst mutations between codons 1251 and 1309 are associated with an increased polyp burden, as well as the presentation of colorectal cancer earlier in life 14,15 . Furthermore, patients with a mutation 3' to codon 1400 have a significantly greater risk of intra-abdominal desmoid which is a serious cause of mortality in FAP patients 16 .

Presentation
The vast majority of patients with FAP are diagnosed prior to presentation as one of their parents will be affected the condition. Genetic testing is generally done around 12 years of age 17 . Surveillance plays a large role in preventing the onset of colorectal cancer. There have been numerous reports that centralised registration and prophylactic examination has improved the prognosis of FAP [18][19][20] . However, as mentioned, up to 30% of FAP cases are spontaneous mutations1. Therefore, it is possible for patients to present in their early middle age with nonspecific abdominal symptoms such as bowel changes, decreased appetite, increased flatulenece and intermittent per rectal bleeding 21 .

Treatment
The mainstay of treatment for FAP is surgical intervention. The rationale is to reduce the risk of colorectal cancer by removing the colon before any cancer can develop. From the late 1940's the only surgical options available were total proctocolectomy, where the colon, rectum and anus were removed or colectomy with ileorectal anastomosis (IRA), where the colon was removed and the ileum was joined to the rectum 5 . However, in 1978, another surgical option, restorative proctocolectomy, with an ileal pouch anal anastamosis (IPAA) was described and became widely used in FAP prophylaxis 22 .

History of Presenting Complaint
Whoopie has had a four week history of abdominal pain . She descibes it as being crampy 'like being in labour' every 10 minutes. The pain was worse on movement. In this time she has had variable stoma output but has been passing flatus. She has also had small amounts of PR discharge.
The patient had presented to the surgical emergency unit two weeks previously with similar, but less severe complaints. Then, it was determined that her obstructive picture was likely to be due to slow bowel transit. She was given buscopen and sent home.

Past Medical History
Chemotherapy 2018 (August)

Family History
There is no family history of note.

Examination
General Inspection: Alert and conversing. Cardiovascular System: Heart sound 1+2 present with no additional sounds. Respiratory System: Breath sounds clear. Abdominal System: Abdomen soft, no guarding, no rebound. However, there was noted discomfort medial to the stoma on the right side. Stoma filled with light brown mushy faeces.

Initial Impression
Taking in to account the above history and clinical findings, it was suspected that Whoopie was experiencing bowel obstruction (possibly intermittent?) upstream of her stoma.

Management
Day 1: On the probability of there being an intermittent small bowel obstruction, it was determined that the patient should be admitted with a view to ease her pain and discomfort. This was achieved by intubation of the stoma which 'instantly' alleviated the pain.
Furthermore, Prof Cunningham decided that it was timely to close the ileostomy. The patient was deemed to be very poorly and had lost a lot of weight. As such, the decision was made that she needed to be admitted and given TPN to build her up for surgery to make the join in two weeks.
Day 12: surgery -Incision: Laprascropy Findings: The surgical team undertook an examination under anaethetic and the pouch anal anastomosis was satisfactory. A sutured anastomoses was performed and the site of obstruction identified but this did not require resection when freed from the fascia.

Discussion
The decision to perform a panprotcocolectomy and ileostomy with the formation of an ileo-anal pouch was arrived at following the consideration of best evidence, clinical judgement and patient values.

Best evidence
There are a number of surgical options availabile to a patient with FAP, and a number of considerations to attend to each one.
The first option is that of a total proctocolectomy which results in the total removal of all large bowel mucosa. The benefit of this is that it is completely protective against colorectal cancer and is thus oncologically the best procedure. However, this is accompanied by profound emotiional and psychological consequences and is therefore less commonly performed in FAP patients, unless there is low rectal insult or sphincter dysfunction 23 .
Another option is a colectomy with ileo-rectal anastamosis (IRA). A majot benefit of this procedure is the ability to perform it laparoscopically 24 . Furthermore, a permanent ileostomy is not required, which is comparison to the total proctocolectomy 25 . A major drawback of this procedure is the fact that as some of the mucosa remains, there is a risk of the development of carcinomas in time and routine surveillance is required. However, even with surveillance, cancer risk rises around the age of 50 26,27 , which may require these patients to progress to a complete proctectomy.
The final surgucal procedure of interest is a restorative protcocolectomy with ileo-pouch anal anastamosis (IPAA). The major benefit of this procedure is the advantage of removing virtually all of the large bowel reducing the risk of future cancers but does require a pelvic dissection to do so. As a result, there is an increased risk of both erectile and ejactulatory function in males as well as ferility in females 25,28 . There is evidence to suggest that fertility in women can be halved following this procedure 29 . Like the IRA, this procedure requires further surveillance of the anorectal transition zone where polyps may arise. It has also been reported that adenomas, and even carcinomas can arise from the ileoanal puch which can subsequently lead to pouch removal 30, 31 .
A meta-analysis of the latter two surgeries included 12 studies including 1,002 patients with FAP 25 . The findings were that multiple post-operative procedures such as bowel frequency, night defecation and the requirement for incontinence pads were significantly less in the IRA-treated patients than the IPAA group. However, faecal urgency was more pronounced with IRA than IPAA. Rectal cancer was only seen in the IRA group (5%) and most likely accounts for the greater requirement for abdominal reoperation on the rectum (28%) compared to IPAA (3%). In a case series comparing patient outcomes for IRA v IPAA, there were fewer side effects such as increased frequency, bowel discomfort and passive discomfort presenting in IPAA cases 32 . However, this case series only included 27 patients so should be met with caution. Another study which assessed 184 patients found no difference in either mental health summary score of physical health summary score between groups of patients who had either undergone IRA or IPAA procedures 33 , suggesting the two procedures to be of equal merit as perceived by the patients. However, of the 184, only 32 were in the IRA group which could bias interpretation. Taken together, these analyses seem to suggest that there may be lesser side effects with the IRA procedure than the IPAA one, but this is accompanied by a greater risk of re-operation.

Clinical judgement
It was evident from the genetic testing and colonoscopy that FAP was the diagnosis for Whoopie. Therefore, an important next step was to consider which surgery might be best suited. Prof Cunningham is experienced in procotocolectomy, IRA and IPAA procedures, so all options were available to the patient. In this particular case, with such a young woman, Prof Cunningham was adament that a proctocolectomy with an permanent ileostomy was not necessary and would significantly impair the patient's quality of life.
Both colectomy with IRA and restorative proctocolectomy with IPAA were feasible options. However, with the polyp burden in the rectum of the patient as well as the tumour being present in the recto-sigmoid junction, IPAA was possibly more suitable. Therefore, Prof Cunningham believed that a restoratie proctocolectomy with IPAA was the best option to remove disease as well as maintain a good quality of life for the patient.

Patient values
At the time of presentation, Whoopie was a 35year old mother of a one year old son. She says that she was suspicious of the diagnosis of cancer in her bowel before it was delivered as she had had a long history of having blood in her stool and fluctuating bowel habits. When it came to attending the consulation with Prof Cunningham, the patient had done much research on the internet and was somewhat familiar with the options for surgery. She said that as a mother, her paramount responsibility was to do what she had to so she could be alive for her son. Therefore, she was willing to undertake whichever procedure was necessary, even if that meant the complete removal of the large bowel and a permanent stoma. However, Whoopie was convinced by Prof Cunningham's argument that the restorative procotcolectomy with IPAA would yield the best results for her in combination with a better quality of life. It would mean that she would have to maintain surveillance, but she was willing for this to be the case. There was of course the risk to her fertility, but Whoopie declared that she was not intending on having more children which removed the weight of this risk.

Conclusion
FAP is a condition in which 'cure' comes through surgery. There are a number of surgical options, and it is evident that there needs to be a consensus between best evidence, clinical judgement and patient values for the best option to be selected. In the current case, 36-year old Whoopie opted to have a panprocotocolectomy with an ileal pouch anal anatomosis. According to the best available evidence, it was possible she would be at greater risk of having undesirable side effects, and also an increased risk that her fertility would be affected. Howecer, Whoopie was willing to accept these risks on the basis that she had completed her family and that she was satisfied that IPAA, although with possible side effects, would allow her the best prognosis to ensure her future with her son.

Conflicts of interest
None.

Funding
None.

Consent
The patient has consented for the publication of this case study.