Familial adenomatous polyposis : screening, surgery and desmoid tumours

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, which is characterized by the development of hundreds or thousands of polyps in the colon and rectum. The first representative of the family (proband) is usually found because he/she presents with the symptoms that usually arise from multiple polyps or from cancer in the large intestine. After this diagnosis family members of that proband are called for screening. The prevention of otherwise inevitable colorectal cancer by prophylactic surgery should preferably be performed in early adulthood. The main surgical options are colectomy with ileorectal anastomosis and proctocolectomy with an ileal pouch-anal anastomosis or ileostomy. The screening of FAP has been shown to be effective in terms of diminishing the number of deaths from colorectal cancer, but the reduction in overall mortality remains unclear. Patients with FAP also carry an elevated risk of desmoid tumours, which are histologically benign proliferations of myofibroblasts, but are often difficult to treat. Desmoid tumours of FAP patients may also act more aggressively than their sporadic counterparts. The aims of this PhD study were to analyse the short-term and long-term outcomes of the two different surgical procedures: colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). Further analysis was done on the need and the results of secondary proctectomies after IRA. The authors aimed to determine, whether familial screening reduces the overall mortality. The causes of death among Finnish FAP patients were studied. The risk of FAP among desmoid tumour patients was also studied. The disease outcome of patients with FAP-related tumours was compared with that of sporadic desmoid tumours in the Finnish population. Patient files of all 421 Finnish FAP patients archived since the year 1963 were studied. There were a total of 228 patients who had undergone IRA or IPAA between years 1963-2012. During the same period, 39 secondary proctectomies were performed for IRA patients. All the Finnish FAP patients until April 30th 2015 were included in the study for which the effect of screening was evaluated. Patients with a diagnosis of sporadic desmoid tumours between years 2000-2012 in Helsinki University Hospital district were invited to the FAP screening. They were offered both endoscopic screening and gene mutation testing. All 221 desmoid tumour patients from the year 1980 were included into the comparison of treatment between FAP associated and sporadic desmoid tumour. There were no significant differences in short term complications between IRA and IPAA. In the long run, however, more patients in the IRA group ended up with ileostomy than in the IPAA group. The total cumulative survival was better after IPAA than IRA, but if the analysis only took into account IRA performed after the IPAA era (from the year 1992 onwards) there were no significant difference between the groups. Secondary proctectomy was performed on 28% of IRA patients. The cumulative risk for secondary proctectomy at 30 years was 53%. The majority of operations were performed for cancer or suspicion of cancer. The risk of rectal cancer after IRA was 13% and the risk of rectal cancer death was 7%. The crude mortality ratio of probands was 34.9 per 1000 person years and 8.3 among call-ups. The relative survival of probands was significantly lower than for their call-up counterparts, and 20 year relative survival for the call-ups was as high as 94%. Over two-thirds of all deaths were FAP related. Among sporadic desmoid tumour patients the prevalence of FAP was 4.8%. FAP diagnosis of these patients was evident by endoscopy. No cases of AFAP, which could sometimes be detectable only by gene mutation testing, were found. There were more intra-abdominal desmoids in the FAP desmoid tumour group, and the desmoid tumours were bigger and more often multiple than those in the sporadic desmoid tumour group. Majority of sporadic desmoid tumour patients were women, whereas among the FAP-related desmoid tumour population the gender distribution was equal and the FAP related desmoid tumour patients were younger. The treatment of FAP-related desmoids was more difficult, intralesional resections were more common and there are desmoid-related deaths (14% of all deaths) among FAP patients in contrast to sporadic desmoids. Patients who underwent IPAA did not have more postoperative complications than patients with IRA. Substantial risk of rectal cancer remains after colectomy and IRA, so the IPAA procedure should be favored for the FAP patients with intermediate or severe polyposis. The risk of permanent stoma is also higher when proctectomy was performed in the second phase. The survival of probands is significantly lower than that of the general population whereas that of call-ups was comparable to the general population for up to 20 years after diagnosis. This is why the screening effort for the family members of the proband must be done. Desmoid tumour patients carry an elevated risk of FAP and therefore screening is usually indicated. Only asymptomatic patients with desmoid tumours situated in the extra truncal region may not need to be routinely screened. Desmoid tumours among FAP patients carry a more complex course of disease compared to patients with a sporadic desmoids, and thus the treatment of FAP-related desmoids is also more complex. If R0 resection is not achieved, the wait-and-see strategy might be a better choice than resection with involved margins.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-2411-1
Electronic ISBNs978-951-51-2412-8
Publication statusPublished - 2016
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3126 Surgery, anesthesiology, intensive care, radiology

Cite this

@phdthesis{7805f2ce242b480c9a196247184d2f6d,
title = "Familial adenomatous polyposis : screening, surgery and desmoid tumours",
abstract = "Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, which is characterized by the development of hundreds or thousands of polyps in the colon and rectum. The first representative of the family (proband) is usually found because he/she presents with the symptoms that usually arise from multiple polyps or from cancer in the large intestine. After this diagnosis family members of that proband are called for screening. The prevention of otherwise inevitable colorectal cancer by prophylactic surgery should preferably be performed in early adulthood. The main surgical options are colectomy with ileorectal anastomosis and proctocolectomy with an ileal pouch-anal anastomosis or ileostomy. The screening of FAP has been shown to be effective in terms of diminishing the number of deaths from colorectal cancer, but the reduction in overall mortality remains unclear. Patients with FAP also carry an elevated risk of desmoid tumours, which are histologically benign proliferations of myofibroblasts, but are often difficult to treat. Desmoid tumours of FAP patients may also act more aggressively than their sporadic counterparts. The aims of this PhD study were to analyse the short-term and long-term outcomes of the two different surgical procedures: colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). Further analysis was done on the need and the results of secondary proctectomies after IRA. The authors aimed to determine, whether familial screening reduces the overall mortality. The causes of death among Finnish FAP patients were studied. The risk of FAP among desmoid tumour patients was also studied. The disease outcome of patients with FAP-related tumours was compared with that of sporadic desmoid tumours in the Finnish population. Patient files of all 421 Finnish FAP patients archived since the year 1963 were studied. There were a total of 228 patients who had undergone IRA or IPAA between years 1963-2012. During the same period, 39 secondary proctectomies were performed for IRA patients. All the Finnish FAP patients until April 30th 2015 were included in the study for which the effect of screening was evaluated. Patients with a diagnosis of sporadic desmoid tumours between years 2000-2012 in Helsinki University Hospital district were invited to the FAP screening. They were offered both endoscopic screening and gene mutation testing. All 221 desmoid tumour patients from the year 1980 were included into the comparison of treatment between FAP associated and sporadic desmoid tumour. There were no significant differences in short term complications between IRA and IPAA. In the long run, however, more patients in the IRA group ended up with ileostomy than in the IPAA group. The total cumulative survival was better after IPAA than IRA, but if the analysis only took into account IRA performed after the IPAA era (from the year 1992 onwards) there were no significant difference between the groups. Secondary proctectomy was performed on 28{\%} of IRA patients. The cumulative risk for secondary proctectomy at 30 years was 53{\%}. The majority of operations were performed for cancer or suspicion of cancer. The risk of rectal cancer after IRA was 13{\%} and the risk of rectal cancer death was 7{\%}. The crude mortality ratio of probands was 34.9 per 1000 person years and 8.3 among call-ups. The relative survival of probands was significantly lower than for their call-up counterparts, and 20 year relative survival for the call-ups was as high as 94{\%}. Over two-thirds of all deaths were FAP related. Among sporadic desmoid tumour patients the prevalence of FAP was 4.8{\%}. FAP diagnosis of these patients was evident by endoscopy. No cases of AFAP, which could sometimes be detectable only by gene mutation testing, were found. There were more intra-abdominal desmoids in the FAP desmoid tumour group, and the desmoid tumours were bigger and more often multiple than those in the sporadic desmoid tumour group. Majority of sporadic desmoid tumour patients were women, whereas among the FAP-related desmoid tumour population the gender distribution was equal and the FAP related desmoid tumour patients were younger. The treatment of FAP-related desmoids was more difficult, intralesional resections were more common and there are desmoid-related deaths (14{\%} of all deaths) among FAP patients in contrast to sporadic desmoids. Patients who underwent IPAA did not have more postoperative complications than patients with IRA. Substantial risk of rectal cancer remains after colectomy and IRA, so the IPAA procedure should be favored for the FAP patients with intermediate or severe polyposis. The risk of permanent stoma is also higher when proctectomy was performed in the second phase. The survival of probands is significantly lower than that of the general population whereas that of call-ups was comparable to the general population for up to 20 years after diagnosis. This is why the screening effort for the family members of the proband must be done. Desmoid tumour patients carry an elevated risk of FAP and therefore screening is usually indicated. Only asymptomatic patients with desmoid tumours situated in the extra truncal region may not need to be routinely screened. Desmoid tumours among FAP patients carry a more complex course of disease compared to patients with a sporadic desmoids, and thus the treatment of FAP-related desmoids is also more complex. If R0 resection is not achieved, the wait-and-see strategy might be a better choice than resection with involved margins.",
keywords = "Adenomatous Polyposis Coli, +diagnosis, +mortality, +surgery, Anastomosis, Surgical, +adverse effects, +methods, Colectomy, Colonic Pouches, Colorectal Neoplasms, +prevention & control, Endoscopy, Gastrointestinal, Fibroma, Fibromatosis, Abdominal, Genes, APC, Ileostomy, Ileum, Mass Screening, Mutation, Proctocolectomy, Restorative, Proportional Hazards Models, Rectum, Risk Assessment, Risk Factors, Survival Rate, Treatment outcome, 3126 Surgery, anesthesiology, intensive care, radiology",
author = "Laura Koskenvuo",
note = "M1 - 91 s. + liitteet Helsingin yliopisto Volume: Proceeding volume:",
year = "2016",
language = "English",
isbn = "978-951-51-2411-1",
publisher = "[L. Koskenvuo]",
address = "Finland",

}

Familial adenomatous polyposis : screening, surgery and desmoid tumours. / Koskenvuo, Laura.

Helsinki : [L. Koskenvuo], 2016. 91 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Familial adenomatous polyposis : screening, surgery and desmoid tumours

AU - Koskenvuo, Laura

N1 - M1 - 91 s. + liitteet Helsingin yliopisto Volume: Proceeding volume:

PY - 2016

Y1 - 2016

N2 - Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, which is characterized by the development of hundreds or thousands of polyps in the colon and rectum. The first representative of the family (proband) is usually found because he/she presents with the symptoms that usually arise from multiple polyps or from cancer in the large intestine. After this diagnosis family members of that proband are called for screening. The prevention of otherwise inevitable colorectal cancer by prophylactic surgery should preferably be performed in early adulthood. The main surgical options are colectomy with ileorectal anastomosis and proctocolectomy with an ileal pouch-anal anastomosis or ileostomy. The screening of FAP has been shown to be effective in terms of diminishing the number of deaths from colorectal cancer, but the reduction in overall mortality remains unclear. Patients with FAP also carry an elevated risk of desmoid tumours, which are histologically benign proliferations of myofibroblasts, but are often difficult to treat. Desmoid tumours of FAP patients may also act more aggressively than their sporadic counterparts. The aims of this PhD study were to analyse the short-term and long-term outcomes of the two different surgical procedures: colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). Further analysis was done on the need and the results of secondary proctectomies after IRA. The authors aimed to determine, whether familial screening reduces the overall mortality. The causes of death among Finnish FAP patients were studied. The risk of FAP among desmoid tumour patients was also studied. The disease outcome of patients with FAP-related tumours was compared with that of sporadic desmoid tumours in the Finnish population. Patient files of all 421 Finnish FAP patients archived since the year 1963 were studied. There were a total of 228 patients who had undergone IRA or IPAA between years 1963-2012. During the same period, 39 secondary proctectomies were performed for IRA patients. All the Finnish FAP patients until April 30th 2015 were included in the study for which the effect of screening was evaluated. Patients with a diagnosis of sporadic desmoid tumours between years 2000-2012 in Helsinki University Hospital district were invited to the FAP screening. They were offered both endoscopic screening and gene mutation testing. All 221 desmoid tumour patients from the year 1980 were included into the comparison of treatment between FAP associated and sporadic desmoid tumour. There were no significant differences in short term complications between IRA and IPAA. In the long run, however, more patients in the IRA group ended up with ileostomy than in the IPAA group. The total cumulative survival was better after IPAA than IRA, but if the analysis only took into account IRA performed after the IPAA era (from the year 1992 onwards) there were no significant difference between the groups. Secondary proctectomy was performed on 28% of IRA patients. The cumulative risk for secondary proctectomy at 30 years was 53%. The majority of operations were performed for cancer or suspicion of cancer. The risk of rectal cancer after IRA was 13% and the risk of rectal cancer death was 7%. The crude mortality ratio of probands was 34.9 per 1000 person years and 8.3 among call-ups. The relative survival of probands was significantly lower than for their call-up counterparts, and 20 year relative survival for the call-ups was as high as 94%. Over two-thirds of all deaths were FAP related. Among sporadic desmoid tumour patients the prevalence of FAP was 4.8%. FAP diagnosis of these patients was evident by endoscopy. No cases of AFAP, which could sometimes be detectable only by gene mutation testing, were found. There were more intra-abdominal desmoids in the FAP desmoid tumour group, and the desmoid tumours were bigger and more often multiple than those in the sporadic desmoid tumour group. Majority of sporadic desmoid tumour patients were women, whereas among the FAP-related desmoid tumour population the gender distribution was equal and the FAP related desmoid tumour patients were younger. The treatment of FAP-related desmoids was more difficult, intralesional resections were more common and there are desmoid-related deaths (14% of all deaths) among FAP patients in contrast to sporadic desmoids. Patients who underwent IPAA did not have more postoperative complications than patients with IRA. Substantial risk of rectal cancer remains after colectomy and IRA, so the IPAA procedure should be favored for the FAP patients with intermediate or severe polyposis. The risk of permanent stoma is also higher when proctectomy was performed in the second phase. The survival of probands is significantly lower than that of the general population whereas that of call-ups was comparable to the general population for up to 20 years after diagnosis. This is why the screening effort for the family members of the proband must be done. Desmoid tumour patients carry an elevated risk of FAP and therefore screening is usually indicated. Only asymptomatic patients with desmoid tumours situated in the extra truncal region may not need to be routinely screened. Desmoid tumours among FAP patients carry a more complex course of disease compared to patients with a sporadic desmoids, and thus the treatment of FAP-related desmoids is also more complex. If R0 resection is not achieved, the wait-and-see strategy might be a better choice than resection with involved margins.

AB - Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, which is characterized by the development of hundreds or thousands of polyps in the colon and rectum. The first representative of the family (proband) is usually found because he/she presents with the symptoms that usually arise from multiple polyps or from cancer in the large intestine. After this diagnosis family members of that proband are called for screening. The prevention of otherwise inevitable colorectal cancer by prophylactic surgery should preferably be performed in early adulthood. The main surgical options are colectomy with ileorectal anastomosis and proctocolectomy with an ileal pouch-anal anastomosis or ileostomy. The screening of FAP has been shown to be effective in terms of diminishing the number of deaths from colorectal cancer, but the reduction in overall mortality remains unclear. Patients with FAP also carry an elevated risk of desmoid tumours, which are histologically benign proliferations of myofibroblasts, but are often difficult to treat. Desmoid tumours of FAP patients may also act more aggressively than their sporadic counterparts. The aims of this PhD study were to analyse the short-term and long-term outcomes of the two different surgical procedures: colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). Further analysis was done on the need and the results of secondary proctectomies after IRA. The authors aimed to determine, whether familial screening reduces the overall mortality. The causes of death among Finnish FAP patients were studied. The risk of FAP among desmoid tumour patients was also studied. The disease outcome of patients with FAP-related tumours was compared with that of sporadic desmoid tumours in the Finnish population. Patient files of all 421 Finnish FAP patients archived since the year 1963 were studied. There were a total of 228 patients who had undergone IRA or IPAA between years 1963-2012. During the same period, 39 secondary proctectomies were performed for IRA patients. All the Finnish FAP patients until April 30th 2015 were included in the study for which the effect of screening was evaluated. Patients with a diagnosis of sporadic desmoid tumours between years 2000-2012 in Helsinki University Hospital district were invited to the FAP screening. They were offered both endoscopic screening and gene mutation testing. All 221 desmoid tumour patients from the year 1980 were included into the comparison of treatment between FAP associated and sporadic desmoid tumour. There were no significant differences in short term complications between IRA and IPAA. In the long run, however, more patients in the IRA group ended up with ileostomy than in the IPAA group. The total cumulative survival was better after IPAA than IRA, but if the analysis only took into account IRA performed after the IPAA era (from the year 1992 onwards) there were no significant difference between the groups. Secondary proctectomy was performed on 28% of IRA patients. The cumulative risk for secondary proctectomy at 30 years was 53%. The majority of operations were performed for cancer or suspicion of cancer. The risk of rectal cancer after IRA was 13% and the risk of rectal cancer death was 7%. The crude mortality ratio of probands was 34.9 per 1000 person years and 8.3 among call-ups. The relative survival of probands was significantly lower than for their call-up counterparts, and 20 year relative survival for the call-ups was as high as 94%. Over two-thirds of all deaths were FAP related. Among sporadic desmoid tumour patients the prevalence of FAP was 4.8%. FAP diagnosis of these patients was evident by endoscopy. No cases of AFAP, which could sometimes be detectable only by gene mutation testing, were found. There were more intra-abdominal desmoids in the FAP desmoid tumour group, and the desmoid tumours were bigger and more often multiple than those in the sporadic desmoid tumour group. Majority of sporadic desmoid tumour patients were women, whereas among the FAP-related desmoid tumour population the gender distribution was equal and the FAP related desmoid tumour patients were younger. The treatment of FAP-related desmoids was more difficult, intralesional resections were more common and there are desmoid-related deaths (14% of all deaths) among FAP patients in contrast to sporadic desmoids. Patients who underwent IPAA did not have more postoperative complications than patients with IRA. Substantial risk of rectal cancer remains after colectomy and IRA, so the IPAA procedure should be favored for the FAP patients with intermediate or severe polyposis. The risk of permanent stoma is also higher when proctectomy was performed in the second phase. The survival of probands is significantly lower than that of the general population whereas that of call-ups was comparable to the general population for up to 20 years after diagnosis. This is why the screening effort for the family members of the proband must be done. Desmoid tumour patients carry an elevated risk of FAP and therefore screening is usually indicated. Only asymptomatic patients with desmoid tumours situated in the extra truncal region may not need to be routinely screened. Desmoid tumours among FAP patients carry a more complex course of disease compared to patients with a sporadic desmoids, and thus the treatment of FAP-related desmoids is also more complex. If R0 resection is not achieved, the wait-and-see strategy might be a better choice than resection with involved margins.

KW - Adenomatous Polyposis Coli

KW - +diagnosis

KW - +mortality

KW - +surgery

KW - Anastomosis, Surgical

KW - +adverse effects

KW - +methods

KW - Colectomy

KW - Colonic Pouches

KW - Colorectal Neoplasms

KW - +prevention & control

KW - Endoscopy, Gastrointestinal

KW - Fibroma

KW - Fibromatosis, Abdominal

KW - Genes, APC

KW - Ileostomy

KW - Ileum

KW - Mass Screening

KW - Mutation

KW - Proctocolectomy, Restorative

KW - Proportional Hazards Models

KW - Rectum

KW - Risk Assessment

KW - Risk Factors

KW - Survival Rate

KW - Treatment outcome

KW - 3126 Surgery, anesthesiology, intensive care, radiology

M3 - Doctoral Thesis

SN - 978-951-51-2411-1

PB - [L. Koskenvuo]

CY - Helsinki

ER -