Familial adenomatous polyposis (FAP): An Interview with Triantafyllos Doulias

An interview by Gloria Zaffaroni

GZ TDESCP dedicated this month to raising awareness for hereditary colorectal cancer syndromes and genetics.

Gloria Zaffaroni interviews Triantafyllos Doulias, Consultant Colorectal Surgeon, Colchester Hospital University NHS foundation Trust, and member of the ESCP Guidelines Committee for ESCP's monthly topic: Colorectal Genetics.

Familial adenomatous polyposis (FAP) is an autosomal inherited syndrome, which is responsible for 1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. The syndrome is caused by mutations in the APC gene.

Recent discoveries in the genetics of familial colorectal cancer and polyposis recognised new genes involved in the development of different forms of adenomatous polyposis, such as the MUTY gene, POLD1 and POLE.

The previous guideline for the clinical management of familial adenomatous polyposis were published in 2008 by the EHTG (European Hereditary Tumour Group).

Gloria Zaffaroni: Dear Triantafyllos, thank you for the opportunity to talk about the “Revised EHTG-ESCP guidelines for clinical management of FAP and other adenomatous polyposis syndromes”. As we can see from the title of the future guidelines, they will include also other rare adenomatous syndromes. What else is new in the updated guidelines?

Triantafyllos Doulias: Thank you for the interview and the opportunity to talk about this important ESCP EHTG collaboration.

In recent years, new genes leading to the development of adenomatous polyposis of the colon have been discovered using NGS techniques (such as POLE and POLD 1). Unfortunately, the literature and evidence on these syndromes is still in its infancy, but despite this we felt that the guideline update should include them. There will also be an additional section devoted to GAPPS (Gastric Adenocarcinoma and Proximal Polyposis of the Stomach): a disease also sustained by a mutation in the APC gene. The section on extra-colonic manifestations will be expanded, trying to direct the right attention. In addition to the already existing sections on Upper Gi and desmoid tumours, information will be given on other manifestations such as thyroid neoplasms, hepatoblastoma, CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium), fibromas and osteomas, incidentalomas, hepatobiliary neoplasia. We felt that this inclusion is crucial since patients have a longer life expectancy, thanks to the role of prophylactic surgery. Hence there is need of the clinician to have this knowledge in order to evaluate the appropriate indications for screening and treatment. Furthermore, these guidelines will respect the new concept promoted by the EHTGs of “dynamic guidance” format, meaning that the updating of the content is a rolling process as new evidence arises (for specific topics).

GZ: Can you tell us, what’s new in the colorectal surgery field for FAP patients?

TD: As already mentioned, genetics has given us new information in recent years, which could potentially change our surgical approach, in respect with the patient's clinical and phenotypic manifestations. This is particularly important when we explore surgical options for example what would the role of the near total colectomy with preservation of the sigmoid colon with subsequent ileo-sigmoid anastomosis as the potential surgical treatment of a-FAP patients. One of the classic debates in the surgical management of the FAP patient is the timing of the procedure. The new guidance suggests that the patients’ age is irrelevant for the timing of surgery and recommends the endorsement of the FAP colon polyposis staging system and stage-specific intervention the IPSS (InSiGHT polyposis staging system). A balance between right indication for surgery and the unique characteristics of each patient should play an important role on the decision making. Another hot topic in the new guidelines will be the role of surgery in patients of childbearing age and the role of surgical intervention on their fertility. The new guidance is in favour of a laparoscopic approach in restorative proctocolectomy with IPAA. Other topics of interest to colorectal surgeons will be on the surgical management of desmoids encountered during prophylactic surgery, what would be the treatment options and ways of reducing their formation, stressing the fact that trauma is a risk factor, and surgery must be considered as trauma.
Finally, the role of diverting ileostomy and the role of the surveillance post panproctocolectomy will be analysed in more detail since the risk of malignancy in the remaining part of the rectum is significantly raised in these particular groups of patients.

GZ: Why do you think a colorectal surgeon should also have knowledge of extracolonic manifestations?

TD: The surgeon should be aware of initial presentation being an extracolonic manifestation especially in children since the early diagnosis increases substantially the survival. The surgeon must have knowledge of the importance of screening protocols in detecting extracolonic manifestations and refer the patient to other specialties on time. While consenting FAP patients for a surgical procedure the risk of desmoids formation should be mentioned to the patient. Desmoid tumours are formed due to surgery related stress/trauma. They might influence the surgical plan during a repeat procedure. It is therefore essential to know what treatments are available, the possibility of chemoprevention and when they require surgical attention.

GZ: What do you think are the strengths of collaborative guideline writing between two societies, in this case EHTG and ESCP?

TD: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) have developed a multidisciplinary working group to conduct a graded evidence review. From the first joint Hereditary Colorectal Cancer symposium in Nice, 2018, this collaboration has shown its strong relations in the development and publication of various projects such as the updated version of the guidelines for Lynch syndrome and the educational Ileal pouch series. This collaboration on the development of the guidelines of FAP patients brings the experience, the expertise and the different voices of the members of the 2 societies aiming for best outcome in advancing the knowledge and the science.

GZ: What do you think are the lesser-known critical aspects for a the surgeon, but of which he should be aware?

TD: I would think that the surgeon should be aware of the role of chemoprevention in FAP patients in the terms of preventing the disease progression, delaying the need for colectomy and temporizing the development of extracolonic disease. So far surgical intervention and endoscopic surveillance are the major weapons in the treatment of FAP but even following a colectomy, patients remain at high risk for duodenal, gastric, thyroid cancer, in addition to desmoid tumours. Several chemo preventative agents have shown encouraging results. The surgeon should be aware of the new research outcomes and should be able to include them in the decision making.

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