Epidemiology of familial adenomatous polyposis in Sweden: changes over time and differences in phenotype between males and females

BACKGROUND: The Swedish Polyposis Registry was set up in Sweden in the late 1950s to promote screening of familial adenomatous polyposis (FAP). The aim of this study was to examine the epidemiology of FAP in Sweden, including the influence of screening on morbidity and mortality in colorectal cancer (CRC). METHODS: Four hundred and thirty-one patients (213 males and 218 females) with FAP from 145 families recorded by the Swedish Polyposis Registry were investigated. The effect of screening on morbidity and mortality in CRC was evaluated by comparing the 216 probands with the 215 call-up patients. Three different periods were studied: the pre-screening period (1912-1956), the first screening period (1957-1976), and the second screening period (1977-1996). RESULTS: The mean annual incidence rates during the three periods were 0.2, 1.38, and 0.86 per million, respectively. The birth frequency was calculated to be 1 in 18,000 between 1947 and 1966, and the prevalence was 32 per million at the end of 1996. The proportion of new mutants among the FAP patients born between 1927 and 1966 was estimated to be 11%. The median age at diagnosis of probands was 39 (range, 11-71) years and did not change over time, although an increase was seen in the subgroup with CRC at diagnosis (P = 0.02). In the call-up group the median age at diagnosis was 22 (range, 3-65) years. Sixty-seven per cent of the probands and 3.3% of the call-up patients had CRC at diagnosis, and the corresponding mortality figures were 44% and 1.9%. The risk among probands of having CRC at diagnosis decreased from 81% to 49% (P = 0.0006). Female probands were diagnosed with symptoms (P = 0.03) and CRC (P = 0.04) earlier than male probands. CONCLUSIONS: A nationwide screening program facilitates detection and early diagnosis of FAP. A decrease in CRC morbidity among probands contributed to the improved prognosis. An earlier onset of symptoms and CRC in females indicate that the course of FAP is influenced by sex.     

Impact of Screening Examinations on Survival in Familial Adenomatous Polyposis

Background: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). Methods: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. Results: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause ofdeath was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. Conclusion: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

Centralized Registration,Prophylactic Examination,and Treatment Results in Improved Prognosis in Familial Adenomatous Polyposis: Results from the Danish Polyposis Register

Background: Over the last few decades numerous regional and national registers have been established all over the world with the aim of improving survival in familial adenomatous polyposis (FAP). The Danish Polyposis Register was founded in 1971 and coordinates the screening and subsequent prophylactic colectomy of FAP patients. Methods: The crude cumulative survival in 321 patients (205 probands and 116 call-up cases) with verified FAP was calculated in accordance with the life-table method. Results: At the time of diagnosis of FAP only 2 of 116 (2%) had colorectal cancer versus 142 of 205 probands (69%). The 10-year cumulative survival was 94% (95% confidence limits, 89-99) in call-up cases compared with only 41% (34-49) in probands (p < 0.00001), and survival improved significantly (p < 0.00001) after the establishment of the Danish Polyposis Register. Conclusion: The establishment of a centralized polyposis register has resulted in a substantial improvement of the prognosis in FAP.     

Impact of screening examinations on survival in familial adenomatous polyposis

BACKGROUND: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). METHODS: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. RESULTS: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause of death was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. CONCLUSION: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

Results of national registration of familial adenomatous polyposis

BACKGROUND AND AIMS: The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival rate in FAP patients before and after the establishment of the Danish Polyposis Register. PATIENTS AND METHODS: The Danish Polyposis Register was established by collecting information on probands and construction of their pedigrees. Family members at risk were offered prophylactic endoscopic and molecular genetic examination, and affected individuals were treated by colectomy. RESULTS: At the end of 2001, the Danish Polyposis Register included 434 patients from 165 families. The incidence rate was 1.90x10(-6) and the prevalence rate 4.65x10(-5). Colorectal cancer on the basis of FAP constituted 0.07% of all colorectal cancers in the 1990s. Colorectal cancer was diagnosed in 170/252 probands (67%) and in 5/182 call-up patients (3%) (p<0.001). The cumulative crude survival was 94% in call-up patients compared with 44% in probands (p<0.0001). A comparison of two periods, 1900-1975 and 1976-2001, demonstrated a decreased prevalence of colorectal cancer from 60% to 27% (p<0.0001), and an increased use of colectomy from 52% to 93% (p<0.00001). The cumulative crude survival in FAP showed substantial improvement with time (p<0.00001). CONCLUSION: Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially. The work of the Danish Polyposis Register is probably the main cause of this improvement.     

Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival.

The incidence and prevalence rates of familial adenomatous polyposis (FAP) in Finland between 1961 and 1990 were estimated from Finnish polyposis registry data comprising 81 FAP families, including 251 affected patients. In addition, the effect of family screening on the occurrence of colorectal carcinoma was evaluated by comparing the call up and proband groups and calculating the proportion of FAP among all patients with colorectal carcinoma. The incidence of FAP was 0.62 to 2.38 per million and the prevalence increased steadily from 0.88 to 26.3 million during the study period suggesting improving prognosis. Altogether 76 of 116 probands (65.5%) had colorectal carcinoma compared with only five of 76 call up patients (6.6%). Consequently, the life expectancy of the call up patients was significantly better than that of the probands from the age of 31 years and above. However, at most, 0.53% of all colorectal carcinomas were associated with FAP in 1966-70, and the diminishing frequency of this proportion was more a result of an increase in sporadic colorectal carcinomas in Finland than of family screening for FAP. Family screening is very effective in FAP and must always be undertaken when a new proband is diagnosed.     

Clinical features in familial polyposis coli

Three hundred nineteen affected members of 94 Danish families with familial polyposis coli had been registered in the Danish Polyposis Register by the end of 1982. Of the 247 histologically verified cases, 168 were propositi and 79 were call-up patients. The frequency of colorectal cancer at the time of diagnosis of polyposis was 69 percent in propositi vs. 3 percent in call-up patients. The cumulative survival rate after ten years was 97 percent in call-up patients, as compared to 42 percent in propositi. The prognosis of polyposis patients has improved significantly since the establishment of the Danish Polyposis Register in 1971. Supported by grants from the Danish Cancer Society (809/71 and 87/80), “Max og Anna Friedmanns Legat,” “Ferdinand og Ellen Hindsgauls Fond,” and “Arkitekt Holger Hjortenberg og hustru, Dagmar Hjortenbergs Fond.” This work has been carried out with statistical aid from the Danish Medical Research Council (5521363/84).     

Causes of death in familial adenomatous polyposis.

BACKGROUND: The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer. METHODS: The material consisted of 328 patients (144 females and 184 males) registered from I January 1943 to 31 December 1992 in the Danish Polyposis Register. The standard mortality rate (SMR) was calculated for known major causes of death, using the entire Danish population as background population. The attributable risk was also calculated for selected death causes. RESULTS: One hundred and thirty-three patients had died, SMR being 4.98 (95% confidence limits, 4.17-5.90). There were significantly lower SMRs in the call-up group than in the proband group. The late cohort (1943-1992) had lower SMRs than the early group (1889-1942). SMR was significantly increased for death due to colorectal cancer (145), duodenal cancer (214), and ovarian cancer (30). No deaths due to desmoids were observed in the examination period. The attributable risk for colorectal cancer was 29% and for duodenal cancer only 0.6%. CONCLUSION: Colorectal cancer is the most frequent cause of death in polyposis patients, followed by duodenal/periampullary cancer, but the latter is still a rare cause of death in FAP.     

Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study

BACKGROUND & AIMS: Several randomized population-based studies have shown that screening for colorectal cancer (CRC) by fecal occult blood tests (FOBTs) can reduce CRC mortality. The aim of this French population-based study was to assess whether a similar benefit could be obtained in countries characterized by high performances in the diagnosis and management of CRC. METHODS: Small-sized geographic areas, including 91,199 individuals aged 45-74 years, were allocated to either FOBT screening or no screening. Six screening rounds were performed. The FOBT was performed without diet restriction and was sent to a central analysis center and processed without rehydration. Screening group participants who had a positive test result were offered a full colonoscopy. The entire population was followed up for 11 years after study entry. RESULTS: Acceptability of the test was 52.8% at the first screening round and varied between 53.8% and 58.3% in the successive rounds. Positivity rates were 2.1% initially and 1.4% on average in the successive rounds. CRC mortality was significantly lower in the screening population compared with the control population (mortality ratio, 0.84; 95% confidence interval, 0.71-0.99). The reduction in CRC mortality was more pronounced in those who participated at least once (mortality ratio, 0.67; 95% confidence interval, 0.56-0.81). CONCLUSIONS: Our findings, together with the results of other trials, suggest that biennial screening by FOBTs can reduce CRC mortality regardless of the quality of the health system and support attempts to introduce large-scale screening programs into the general population.     

Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: A meta-analysis

AIM: To conduct a systematic review and meta-analysis of published population-based randomized controlled trials (RCTs).METHODS: RCTs evaluating the difference in mortality and incidence of colorectal cancer (CRC) between a screening flexible sigmoidoscopy (FS) group and control group (not assigned to screening FS) with a minimum 5 years median follow-up were identified by a search of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled Trials through August 2013. Random effects model was used for meta-analysis.RESULTS: Four RCTs with a total of 165659 patients in the FS group and 249707 patients in the control group were included in meta-analysis. Intention-to-treat analysis showed that there was a 22% risk reduction in total incidence of CRC (RR = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63-0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR = 0.57, 95%CI: 0.45-0.72).CONCLUSION: This meta-analysis suggests that screening FS can reduce the incidence of proximal and distal CRC and mortality from distal CRC along with reduction in diagnosis of advanced CRC.     

Geographical variation and factors associated with colorectal cancer mortality in a universal health care system

OBJECTIVE:

To investigate the geographical variation and small geographical area level factors associated with colorectal cancer (CRC) mortality.

METHODS:

Information regarding CRC mortality was obtained from the population-based Manitoba Cancer Registry, population counts were obtained from Manitoba’s universal health care plan Registry and characteristics of the area of residence were obtained from the 2001 Canadian census. Bayesian spatial Poisson mixed models were used to evaluate the geographical variation of CRC mortality and Poisson regression models for determining associations with CRC mortality. Time trends of CRC mortality according to income group were plotted using joinpoint regression.

RESULTS:

The southeast (mortality rate ratio [MRR] 1.31 [95% CI 1.12 to 1.54) and southcentral (MRR 1.62 [95% CI 1.35 to 1.92]) regions of Manitoba had higher CRC mortality rates than suburban Winnipeg (Manitoba’s capital city). Between 1985 and 1996, CRC mortality did not vary according to household income; however, between 1997 and 2009, individuals residing in the highest-income areas were less likely to die from CRC (MRR 0.77 [95% CI 0.65 to 0.89]). Divergence in CRC mortality among individuals residing in different income areas increased over time, with rising CRC mortality observed in the lowest income areas and declining CRC mortality observed in the higher income areas.

CONCLUSIONS:

Individuals residing in lower income neighbourhoods experienced rising CRC mortality despite residing in a jurisdiction with universal health care and should receive increased efforts to reduce CRC mortality. These findings should be of particular interest to the provincial CRC screening programs, which may be able to reduce the disparities in CRC mortality by reducing the disparities in CRC screening participation.     

Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset

BACKGROUND & AIMS: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. METHODS: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. RESULTS: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%-66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0-46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%-66.1%). CONCLUSIONS: A markedly later age of onset for CRC at 61 y than previously reported (approximately 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before.     

Survival after colorectal cancer in patients with ulcerative colitis: a nationwide population-based Danish study

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Little is known about how UC impacts CRC prognosis. In a nationwide population-based study we examined the CRC prognosis in UC patients compared to CRC patients without UC. METHODS: From the Danish Cancer Registry and the Danish Hospital Discharge Registry, we identified all CRC patients and all patients with UC in Denmark from 1977 to 1999. We compared survival in 279 UC patients with CRC to all other 71,259 CRC patients and computed mortality rate ratios (MRR). We also compared stage distribution at time of cancer diagnosis. RESULTS: The mean age at time of CRC diagnosis was 62.6 yr in UC patients and 71.2 yr in patients without UC. Cancer stage distribution for localized cancer, regional spread, and distant metastasis were 46.6%, 30.1%, and 16.5% in UC patients compared to 44.0%, 28.3%, and 19.4% in CRC patients without UC. The overall MRR for UC patients with CRC compared with all other CRC patients were 1.24 (95% CI 1.02-1.51) in the first year and 1.17 (95% CI 1.01-1.36) after 5 yr of follow-up. CONCLUSION: UC patients with CRC have a stage distribution similar to patients with CRC without UC. The prognosis of CRC is poorer for UC patients than for patients without UC.     

Associations between the age at diagnosis and location of colorectal cancer and the use of alcohol and tobacco: implications for screening

BACKGROUND: Individualizing recommendations for colorectal cancer (CRC) screening intervals and modalities requires accurate risk assessment. Although hereditary predisposition is commonly used, the effect of exogenous risk factors has remained largely unexplored. To address this, we analyzed the age at presentation and location of CRC in relation to alcohol and tobacco use. METHODS: We queried the IMPAC Medical Registry Services Cancer Information Resource File for CRCs diagnosed between June 1, 1993, and December 31, 2003. Subjects were classified as current, past, or never users of alcohol and tobacco. A logistic regression model for location of CRC and a linear regression model for age at diagnosis were constructed using these explanatory variables along with gender, race, and insurance status. RESULTS: Our data set consisted of 161 172 patients with CRC. Current drinking, smoking, and smoking plus drinking were associated with younger ages at onset of CRC (adjusted age difference, 5.2, 5.2, and 7.8 years, respectively; P<.001 for all). A distal location of CRC was more likely to occur in current drinkers (odds ratio, 1.192; 95% confidence interval, 1.15-1.23) and smokers (odds ratio, 1.164; 95% confidence interval, 1.12-1.21). Colorectal cancer in men tended to occur earlier (adjusted age difference, 1.9 years; P<.001) and have a distal predominance (odds ratio, 1.42; P<.001) compared with women. The smoking but not the drinking effect size was greater in women than in men (adjusted age difference, 2.6 years; P<.001). CONCLUSIONS: Alcohol use, tobacco use, and male gender were associated with earlier onset and a distal location of CRC. If confirmed, these factors should guide recommendations regarding initiation of CRC screening and, possibly, choice of techniques.     

The metabolic syndrome and its components as prognostic factors in colorectal cancer: A meta-analysis and systematic review

Background and Aim

Metabolic syndrome (MetS) increases the risk of colorectal cancer (CRC), and the impact of MetS on CRC prognosis remains controversial after the diagnosis of CRC has been established. This study aimed to explore the impact of the individual components and synergies of MetS on the prognosis of patients with CRC.

Methods

We searched articles published before August 3, 2022, in four databases, including PubMed, Embase, Cochrane Library, and ScienceDirect. The random-effects model inverse variance method was used to estimate the summarized effect size.

Results

Patients with CRC with MetS were 1.342 times more likely to experience all-cause mortality than those without MetS, and the 95% confidence interval (CI) of hazard ratio (HR) was 1.107–1.627 (P = 0.003). CRC-specific mortality in patients with CRC with MetS was 2.122 times higher than in those without MetS, and the 95% CI of HR was 1.080–4.173 (P = 0.029). CRC-specific mortality exhibited an increasing trend of risk with increased metabolic risk factors. The HR of CRC-specific mortality for one, two, and three metabolic risk factors was 1.206 (95% CI, 1.034–1.407; P = 0.017), 1.881 (95% CI, 1.253–2.824; P = 0.002), and 2.327 (95% CI, 1.262–4.291; P = 0.007), respectively.

Conclusions

Metabolic syndrome increased all-cause and CRC-specific mortality in patients with CRC. As a single component of MetS, diabetes mellitus increased overall mortality in patients with CRC, while obesity increased CRC-specific mortality in patients with CRC, with a significant difference from non-MetS. Moreover, the risk of CRC-specific mortality increased with increasing number of metabolic risk factors.     

Colorectal cancer mortality in Inner Mongolia between 2008 and 2012

AIM: To determine the extent of colorectal cancer (CRC) mortality and the association between demographic characteristics and CRC mortality in Inner Mongolia.METHODS: Data were collected from the Death Registry System, maintained by the Inner Mongolia Centers for Disease Control and Prevention, from 2008 to 2012. Deaths were classified according to the International Classification of Disease, 10^th Revision. Years of life lost, average years of life lost (AYLL), and mortality were calculated over the five years between 2008 and 2012. A conditional logistic regression model was used to analyze the association between marital status, occupational status, education level, area of residence, and the risk of CRC.RESULTS: The AYLL of CRC was 17.39 years. The average mortality of CRC was 5.6/100000. People living in urban areas and having a higher education level had a significantly higher risk of CRC (OR = 1.74 and 95%CI: 1.29-2.35, P < 0.001 and OR = 2.39, 95%CI: 1.76-3.25, P < 0.001, respectively). People who were employed had a lower risk of CRC (OR = 0.64, 95%CI: 0.48-0.86, P = 0.003). The mortality of CRC was positively correlated with the education level (P < 0.001). No statistically significant association was observed between marital status and CRC risk (P = 0.259).CONCLUSION: Living in urban areas, higher education level and unemployment are associated with CRC mortality in Inner Mongolia.     

Risk factors for colorectal cancer in Crohn's colitis: a case-control study

BACKGROUND: Few data exist regarding exposures associated with colorectal cancer (CRC) in patients with Crohn's colitis. The aim of this study was to identify exposures that alter the risk of CRC in patients with Crohn's colitis. METHODS: The Research Patient Database Registry at Massachusetts General Hospital was searched to identify cases and controls. Cases had a confirmed diagnosis of Crohn's disease involving at least one third of the colon and a confirmed diagnosis of colorectal adenocarcinoma. Matched controls were randomly chosen from the same source population. Paired univariate analysis was performed to develop an odds ratio (OR) for each exposure. RESULTS: Twenty-seven patients were found to have Crohn's colitis and CRC. Colonoscopy performed for screening or surveillance was associated with an OR of 0.21 (95% CI 0.04-0.77; P=0.02). Nonsignificant trends for a protective effect included prior appendectomy (OR 0.30; 95% CI 0.05-1.17; P=0.10) and regular 5-aminosalicylate use (OR 0.30; 95% CI 0.05-1.17; P=0.10). Smoking history was associated with a 4-fold-increased risk for CRC, but this was not statistically significant (OR 4.00; 95% CI 0.80-38.67; P=0.11). CONCLUSIONS: We found that having a colonoscopy for an indication of surveillance or screening is associated with decreased risk of CRC in the setting of Crohn's colitis. These data underscore the importance of CRC surveillance for Crohn's colitis in addition to ulcerative colitis and should prompt further study in this area.     

Education and management of patients with familial adenomatous polyposis. Are we making progress? A case report

A 25-year-old male patient was admitted to our clinic for abdominal pain, diarrhea, intermittent rectal bleeding and weight loss. The family history revealed two deaths due to colorectal cancer (maternal grandmother and patient's mother). The colonoscopy showed hundreds of polyps throughout the colon, and an ulcerative rectosigmoidian tumor. The diagnosis was Familial Adenomatous Polyposis (FAP). Colectomy with ileorectal anastomosis was performed. Histopathological diagnosis revealed moderately differentiated adenocarcinoma. Adjuvant chemotherapy was carried out. The patient had three brothers, without clinical symptoms. They had a colonoscopic examination for screening. Two of them were diagnosed with adenomatous polyposis - the first with classic FAP and the other one with the attenuated type (AFAP). The diagnosis of FAP can be made on the basis of either clinical or genetic criteria. When the family history, clinical features, and pathological findings are classic, the diagnosis is straightforward. Screening and prophylactic surgery are effective to prevent colorectal cancer in patients with FAP. Lifelong regular surveillance is necessary to detect and manage extracolonic lesions.     

Family history and colorectal cancer screening: a survey of physician knowledge and practice patterns

OBJECTIVES: Risk stratification is essential to effective implementation of colorectal cancer (CRC) screening strategies. The objectives of this study were to assess and compare the current knowledge and practice patterns of gastroenterologists and primary care physicians regarding familial risk of CRC. METHODS: We conducted a survey of regional gastroenterologists and a sample of university- and community-based primary care physicians. The survey instrument assessed physician knowledge of screening recommendations and current practices for individuals with family histories of CRC, adenomatous polyps (APs), familial adenomatous polyposis (FAP), and hereditary nonpolyposis cancer (HNPCC). The instrument also elicited data about familial risk assessment, documentation, and notification of at-risk family members. RESULTS: Thirty-five gastroenterologists (65%) and 58 primary care physicians (92%) completed the survey. Most gastroenterologists and primary care physicians (85% vs 72%) chose age 40 as the appropriate age to begin screening for a family history of CRC, but relatively few (37% vs 36%) recommended screening at age 40 for a family history of APs. Gastroenterologists were significantly more likely to recommend screening for FAP at puberty (80% vs 27%, p < 0.001) and for HNPCC at age 25 (73% vs 50%, p = 0.04). Colonoscopy was the preferred screening strategy by both groups for family histories of CRC (97%), HNPCC (97%), and APs (77%); primary care physicians also preferred colonoscopy for family histories of CRC (72%) and HNPCC (76%) but flexible sigmoidoscopy plus fecal occult blood testing for a family history of APs (38%). Gastroenterologists were more likely to recommend genetic testing for persons at risk of FAP (91% vs 71%, p = 0.03) and HNPCC (72% vs 57%, p = 0.18), routinely inquire about a family history of CRC or APs (93% vs 63%, p < 0.001), and recommend notification of at-risk first-degree relatives with family histories of CRC (94% vs 55%, p < 0.001) or AP (53% v.s 6%, p < 0.001). CONCLUSION: Although gastroenterologists are more likely than primary care physicians to elicit a family history of colorectal neoplasia and implement appropriate screening strategies, overall compliance with recommended guidelines and notification of at-risk relatives are suboptimal. Novel approaches for improving awareness of the available screening guidelines are needed.     

Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test

BACKGROUND: Several randomized studies have shown that colorectal cancer (CRC) screening by faecal occult blood test (FOBT) reduces CRC mortality. These trials have different designs, especially concerning FOBT frequency and duration, as well as the length of follow-up after stopping FOBT campaigns. AIMS: To review the effectiveness of screening for CRC with FOBT, to consider the reduction in mortality during or after screening or to identify factors associated with a significant mortality reduction. METHODS: A systematic review of trials of FOBT screening with a meta-analysis of four controlled trials selected for their biennial and population-based design. The main outcome measurements were mortality relative risk (RR) and 95% confidence interval (CI) of biennial FOBT during short (10 years, i.e. five or six rounds) or long-term (six or more rounds) screening periods, as well as after stopping screening and follow-up during 5-7 years. The meta-analysis used the Mantel-Haenszel method with fixed effects when the heterogeneity test was not significant, and used 'intent to screen' results. RESULTS: Although the quality of the four trials was high, only three were randomized, and one used rehydrated biennial FOBT associated with a high colonoscopy rate (28%). A meta-analysis of mortality results showed that subjects allocated to screening had a reduction of CRC mortality during a 10-year period (RR 0.86; CI 0.79-0.94) although CRC mortality was not decreased during the 5-7 years after the 10-year (six rounds) screening period, nor in the last phase (8-16 years after the onset of screening) of a long-term (16 years or nine rounds) biennial screening. Whatever the design of the period of ongoing FOBT, CRC incidence neither decreased nor increased, although it was reduced for 5-7 years after the 10-year screening period. Neither the design nor the clinical or demographic parameters of these trials were independently associated with CRC mortality reduction. CONCLUSION: Biennial FOBT decreased CRC mortality by 14% when performed over 10 years, without evidence-based benefit on CRC mortality when performed over a longer period. No independent predictors of CRC mortality reduction have been identified in order to allow a CRC screening programme in any subgroups of subjects at risk.