Spigelman Stage Research Articles

Gastric Tubular Adenomas Five Years After Total Proctocolectomy in Familial Adenomatous Polyposis

Familial Adenomatous Polyposis (FAP) is an autosomal dominant syndrome caused by mutations in the Adenomatous polyposis c (APC) gene. The prevalence of FAP ranges from 1 in 6, 850 to 1 in 31,250 births.Guidelines suggest FAP patients should start the surveillance process for colorectal cancer around age 10-12.However, endoscopy to look for FAP-like extra-colonic manifestations is recommended to start at age 25-30. Patients with FAP frequently have gastric polyps which could be fundic gland polyps and tubular adenomas, however it is uncommon to have mostly gastric tubular adenomas. A 23-yearold female with a past medical history of FAP presented for gastrointestinal surveillance. The patient's mother had FAP and thus the patient was screened for APC gene mutation which turned out to be positive. She underwent endoscopic surveillance of the gastrointestinal tract at age 18 when she found to have multiple colonic tubulovillous adenomas and subsequently had a total proctocolectomy with a J-pouch ileoanal anastomosis. She also had an abdominal wall desmoid tumor that was removed. The patient's first endoscopy was at age 19. The first three endoscopies (age 19, 20, and 21) showed fundic gland polyps in the stomach and tubular adenomas in the small bowel. The patient's most recent endoscopy showed multiple diminutive fundic gland like gastric polyps (figure 1, A) which turned to be tubular adenomas on histology. She also was noted to have duodenal tubular adenomas, figure 1, B. The prevalence of gastric adenomas is estimated to be about 9.2%- 23% in FAP. The risk for gastric cancer in FAP patients is 0.6% and seems to be more common in attenuated FAP than in FAP. Although we do not have a true estimate for the rate of transformation from gastric adenoma to malignancy, endoscopic surveillance is still recommended. Endoscopic surveillances have better metric measures in small bowel tubular adenomas than in gastric adenomas using the Spigelman staging system. This case had gastric and duodenal polyps at a much earlier age (19) than the recommended age of screening endoscopy (25-30). This case reminds us of the importance of surveillance EGDs in FAP patients and taking multiple biopsies from polyps which may look like fundic gland polyps on endoscopic evaluation but may be tubular adenomas on histology.Figure 1Figure 2

Frequency and Features of Duodenal Adenomas in Patients WithMUTYH-Associated Polyposis.

MUTYH-associated polyposis (MAP) is similar to familial adenomatous polyposis (FAP), in that it increases the risk for duodenal adenomas and cancer. Almost all patients with FAP develop duodenal adenomas and 5% develop duodenal cancer. Little is known about the prevalence of duodenal adenomas and cancer in patients with MAP, but current surveillance recommendations are the same for patients with FAP-they should begin surveillance when they are 25 years old. We aimed to assess the prevalence, extent, and progression of duodenal adenomas in patients with MAP and evaluate upper gastrointestinal tract surveillance recommendations. In a retrospective study, we collected data on all patients (n= 92) with MAP undergoing surveillance esophagogastroduodenoscopy from registries at St Mark's Hospital (London, UK) and the Academic Medical Center (Amsterdam, The Netherlands) from 2002 through 2014. We collected information on adenoma development, age at adenoma detection, interventions, and disease progression. Duodenal adenomas were detected in 31 patients (34%), at a median age of 50 years. When duodenal polyposis first was detected, it was Spigelman stages I or II in 84% of patients; most had few small polyps, without high-grade dysplasia or villous features. Subsequent esophagogastroduodenoscopy evaluation of 18 of these patients found that 14 (78%) had Spigelman stages 0 to II disease (median follow-up period, 7.8 y). Disease progressed in stage in 6 patients, over 9.5 years, because of lesion size or villous features (2 reached stage IV disease). Adenomas were down-staged in 8 patients after biopsy or polypectomy analyses, and were unchanged for 3 patients. In a data analysis from 92 patients with MAP, duodenal polyposis seemed to develop less frequently than in patients with FAP, and developed at a later age. Increasing lesion size and villous change appear to promote adenoma progression, rather than polyp number or dysplasia. It may be time to consider a new staging system for patients with MAP, to better determine disease severity and surveillance strategies.

Su1771 Ampullary Adenoma in Children With Familial Adenomatous Polyposis

Duodenal adenomas are found in the majority of adult patients with familial adenomatous polyposis (FAP) and contribute to a cumulative lifetime risk of duodenal cancer of approximately 5% (Vasen et al 1997). A much higher risk of 36% has been associated with Spigelman stage III and IV adenomatosis scored by size, number, histology, and grade of dysplasia of adenomas. While most of the duodenum can be examined by a forward-viewing endoscope (FVE), accurate inspection and biopsy of the ampulla requires use of a side-viewing endoscope (SVE). Ampullary disease does not correlate with the severity of non-ampullary duodenal involvement (Burke et al 1999) and ampullary cancers may represent approximately 50% of duodenal cancers in FAP patients (Latchford et al 2009). High-grade dysplasia and carcinoma of the ampulla has been reported in children with FAP (Attard et al 2004, Hinder et al 1980) but systematic examination of the ampulla using a SVE has not been reported. The primary aim of this study was to characterize the prevalence and stage of ampullary adenoma in children with FAP.

Recurrences are common after endoscopic ampullectomy for adenoma in the familial adenomatous polyposis (FAP) syndrome

Endoscopic ampullectomy is increasingly performed in patients with familial adenomatous polyposis (FAP)-associated ampullary adenomas. We sought to define the procedure-associated morbidities and long-term outcomes. We performed a retrospective chart review of patients with FAP who underwent endoscopic ampullectomy at two tertiary institutions between 1999 and 2010. The severity of duodenal polyposis was classified according to Spigelman's classification. Of 26 FAP patients who underwent endoscopic ampullectomy, 21 arose in the setting of Spigelman's stage II duodenal polyposis. Adverse events associated with endoscopic ampullectomy included acute pancreatitis (19.2%), abdominal pain (7.6%), and bleeding (3.8%). The mean resected adenoma size was 0.99 ± 0.34 cm. Three adenomas (12.0%) contained foci of high-grade dysplasia. Follow-up data were available for 24 patients. The mean follow-up duration was 84.5 ± 36.2 months. Adenoma recurrence was observed in 14 patients (58.3%; 14/24) at a mean of 38.3 months after initial ampullectomy. Adenomas ≥10 mm recurred more frequently than smaller adenomas (76.9 vs. 36.4%; p = 0.002). Positive margins were not associated with higher recurrence rates. No cancers were observed during long-term follow-up. Three patients underwent a Whipple procedure, but none was performed for a recurrent ampullary adenoma. Endoscopic ampullectomy in FAP can be performed safely. Because ampullary adenomas frequently recur after endoscopic ampullectomy, close surveillance is essential. Smaller tumors are less likely to recur, suggesting a benefit for early recognition of these lesions.

Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines

J. Balmana1, F. Balaguer2, A. Cervantes3 & D. Arnold4, on behalf of the ESMO Guidelines Working Group* Department of Medical Oncology, Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona; Department of Gastroenterology, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona; Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain; Department of Medical Oncology, Tumor Biology Clinic, Albert Ludwigs University, Freiburg, Germany;

The role of high-resolution endoscopy and narrow-band imaging in the evaluation of upper GI neoplasia in familial adenomatous polyposis

The Spigelman classification stratifies cancer risk in familial adenomatous polyposis (FAP) patients with duodenal adenomatosis. High-resolution endoscopy (HRE) and narrow-band imaging (NBI) may identify lesions at high risk. To compare HRE and NBI for the detection of duodenal and gastric polyps and to characterize duodenal adenomas harboring advanced histology with HRE and NBI. Prospective, nonrandomized, comparative study. Retrospective image evaluation study. Tertiary-care center. Thirty-seven FAP patients undergoing surveillance upper endoscopies. HRE endoscopy was followed by NBI. The number of gastric polyps and Spigelman staging were compared. Duodenal polyp images were systematically reviewed in a learning and validation phase. Number of gastric and duodenal polyps detected by HRE and NBI and prevalence of specific endoscopic features in duodenal adenomas with advanced histology. NBI did not identify additional gastric polyps but detected more duodenal adenomas in 16 examinations, resulting in upgrades of the Spigelman stage in 2 cases (4.4%). Pictures of 168 duodenal adenomas (44% advanced histology) were assessed. In the learning phase, 3 endoscopic features were associated with advanced histology: white color, enlarged villi, and size ≥1 cm. Only size ≥1 cm was confirmed in the validation phase (odds ratio 3.0; 95% confidence interval, 1.2-7.4). Nonrandomized study, scant number of high-grade dysplasia adenomas. Inspection with NBI did not lead to a clinically relevant upgrade in the Spigelman classification and did not improve the detection of gastric polyps in comparison with HRE. The only endoscopic feature that predicted advanced histology of a duodenal adenoma was size ≥1 cm.

Prospective enteroscopic evaluation of jejunal polyposis in patients with familial adenomatous polyposis and advanced duodenal polyposis

Duodenal cancer originating from duodenal adenomas is an important cause of death in patients with familial adenomatous polyposis (FAP). Small intestinal adenomas also occur distal to the duodenum, and literature suggests that they mainly occur in the proximal jejunum in patients with severe duodenal polyp burden. We recently reported on 3 FAP-patients with a jejunal adenocarcinoma, all also harbouring advanced duodenal polyposis. Therefore we questioned whether FAP patients should also be submitted to endoscopic surveillance of the jejunum. The aim of this study was to determine the incidence and burden of jejunal adenomas in patients with FAP and advanced duodenal disease. All patients with FAP and advanced duodenal polyposis (Spigelman stage IV) at our academic centre were invited to undergo antegrade single balloon enteroscopy (Olympus SIF-Q180) with propofol-sedation. Patient characteristics, procedural characteristics (success, depth of insertion) and enteroscopic findings (number, size and pathology) are described. We identified 18 patients with FAP and duodenal polyposis Spigelman stage IV. Thirteen participated in the study with a mean age of 54 (30-64) years. SBE was successfully performed in 10 patients, with a mean depth of insertion of 72 cm beyond the ligament of Treitz. Adenomatous polyps were detected in 9 patients. Only one of them had extensive polyposis beyond Treitz, with large polyps covering up to one-third of the jejunal circumference. No cancers or adenomas with high-grade dysplasia were detected. Clinically significant jejunal polyposis in FAP is rare, even in high-risk patients with advanced duodenal disease. Routine jejunoscopy does not seem warranted in patients with FAP.

Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development. Follow up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included the χ(2) test, actuarial method and Kaplan-Meier analysis. Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9-17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84-93), and of Spigelman stage IV was 35% (95% CI, 25-45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44-82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8-28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P < 0.0001). The median overall survival was 6.4 years (95% CI, 1.7 to not estimated): 8 years after a screen-detected cancer vs 0.8 years (95% CI, 0.03-1.7) after a symptomatic cancer (P < 0.0001). The location of the mutation in the APC gene did not influence the risk of developing Spigelman stage IV (P = 0.46) or duodenal cancer (P = 0.83). The risk of duodenal cancer in familial adenomatous polyposis is considerable, and regular surveillance and cancer prophylactic surgery result in a significantly improved prognosis.

Advanced duodenal disease in familial adenomatous polyposis: how frequently should patients be followed up after successful therapy?

Duodenal polyposis is found in the majority of patients with familial adenomatous polyposis. Endoscopic surveillance programmes grade the severity of duodenal disease according to the Spigelman classification (stages 0-IV) to identify patients at risk of developing adenocarcinoma. To evaluate the progression of duodenal polyposis in patients with a previous diagnosis of Spigelman stage IV disease who have been downstaged by endoscopic or pharmacological means. A database search of a large polyposis registry identified patients who had been downstaged from stage IV disease and had further opportunity for disease progression. These patients were divided into three groups according to their new Spigelman stage. A measure of a patient's disease progression was obtained by the increase in stage over the recommended follow up time period for their new, reduced, Spigelman stage. Group 1 (n=16) were downstaged to stage III disease, with 50% progressing back to stage IV over the recommended 1-year follow up period. Group 2 (n=19) were downstaged to stage II disease, with 84% progressing over the recommended 3-year follow up period. Group 3 (n=6) were downstaged to stage I disease, with 100% progressing over the recommended 5-year follow up period. Patients downstaged from Spigelman stage IV demonstrate an increased rate of disease progression in comparison to reported rates of primary disease progression. An amendment to the current endoscopic surveillance protocol is recommended to ensure that once a patient has been diagnosed with stage IV disease they are treated as a high-risk patient in perpetuity.

Simultaneous Laparoscopic Subtotal Colectomy and Pancreaticoduodenectomy for Colonic FAP and Ampullary Cancer

Laparoscopic surgery has extended its applications to resection of malignancies with favorable results. We report the first successful simultaneous laparoscopic subtotal colectomy and pancreaticoduodenectomy (PD) in a patient with familial adenomatous polyposis (FAP). A 37-year-old man presented with obstructive jaundice. Gastroscopy and biopsies revealed a large ampullary tubulovillous adenoma with mild dysplasia (Spigelman stage III). A colonoscopy for suspicion of FAP revealed numerous right-sided polyps with left-sided sparing. Computed tomography showed a double duct sign. A simultaneous laparoscopic subtotal colectomy and PD was performed successfully. The operative time was 225 minutes for the colectomy and 390 minutes for the PD. Histology showed an R0 resection of ampullary adenocarcinoma (20 negative nodes) and colonic polyps with low-grade dysplasia. Genetic screening confirmed a diagnosis of FAP. A simultaneous laparoscopic subtotal colectomy and PD in patients with FAP and ampullary neoplasia seems safe with favorable clinical and oncologic outcomes.

Laparoscopic Pancreas-preserving Total Duodenectomy for Familial Adenomatous Polyposis

Patients with duodenal polyps associated with familial adenomatous polyposis (FAP) have a considerable risk of developing duodenal carcinoma. Prophylactic resection of the duodenum for Spigelman stage III disease is the treatment of choice to prevent progression to cancer. Pancreaticoduodenectomy and pancreas-preserving total duodenectomy (PPTD) are the techniques that have been described for the surgical treatment of duodenal polyposis. We report the first case of laparoscopic PPTD in a patient with previous total colectomy for FAP and Spigelman stage III duodenal polyposis. A laparoscopic total dissection of the duodenum was carried out and the restoration was achieved performing pancreatico-biliary-jejunostomy and gastrojejunostomy. The postoperative period was uneventful. Laparoscopic PPTD can be performed safely in selected cases for the management of FAP.

Pancreas‐preserving total duodenectomy: a 10‐year experience

Traditionally, severe pathology of the duodenum has been treated by a pancreaticoduodenectomy using Whipple's operation. Pancreas-preserving total duodenectomy (PPTD) was introduced in the late 1990s as an alternative to Whipple's operation for selected diseases of the duodenum. We report our 10 years' experience with this operation. In the period from 1999 to 2010 13 patients (mean age 50 years) underwent PPTD. Ten patients had duodenal adenomatosis (Spigelman stage IV). Two patients had large solitary tubulovillous adenomas, and one patient had multiple duodenal gastrointestinal stromal tumor lesions. No mortality was observed. Six patients (46%) had a total of ten postoperative complications. Three patients (23%) had leakage of the ampullo-jejunostomy anastomosis, and one patient (8%) had leakage of the duodeno-jejunostomy anastomosis; all were treated conservatively with good results. One patient had recurrent episodes of pancreatitis, which disappeared spontaneously 3 months after operation. Three patients suffered from wound dehiscence, and two patients had postoperative pneumonia. Mean hospital admittance was 19 days (range 9-50 days). All patients were well at a mean follow-up of 56 months (range 2-134 months). Pancreas-preserving total duodenectomy appears to be a safe and valuable treatment option for patients with selected diseases of the duodenum.

Progression of duodenal adenomatosis in familial adenomatous polyposis: due to ageing of subjects and advances in technology

Familial adenomatous polyposis patients are at risk of duodenal cancer. Surveillance is indicated and the extent of duodenal polyposis is quantified by the Spigelman staging system. We noticed an impressive increase in high Spigelman stages over the years and therefore decided to investigate whether this increase might be due to the time-lapse since the inception of surveillance or related to improvements in endoscopic imaging and/or changes in dysplasia-reporting. Patients who were investigated by the same endoscopist since 1980 in at least 2 different episodes of technical improvements were eligible. The period 1980–2009 was divided into 4 episodes using the following landmarks: replacement of fibre-endoscopes by video-endoscopes in 1987, change in processors in 1995, change in image resolution in 2000, and change in dysplasia-reporting in 2006. An increase in Spigelman stages from low stages (0–II 100%) to high stages (III 28.1%, IV 43.8%) was seen (median follow-up: 19.5 years). In patients who progressed, a median of 4 years elapsed before progression by one stage occurred and 7 years to progress by two stages. In a mixed-model analysis, both time-lapse and technical improvements were determinant factors for duodenal disease progression. When both factors were introduced in the model, the time-lapse as well as the change in image resolution and dysplasia-ranking contributed consistently in increasing Spigelman scores and stages. The impressive increase in severity of duodenal polyposis is determined by time-lapse, technological advances and change in dysplasia-reporting. These results might call for a revised Spigelman classification.

Recurrence of severe duodenal disease after endoscopic downstaging in familial adenomatous polyposis

Introduction Duodenal polyposis is found in the majority of patients with familial adenomatous polyposis. Endoscopic surveillance programmes grade the severity of duodenal disease according to the Spigelman classification (stages 0–IV) to identify patients at risk of developing adenocarcinoma. Duodenoscopy can also be used therapeutically to remove polyps and thus reduce a patient9s Spigelman stage. This study aims to evaluate the progression of duodenal polyposis in patients with a previous diagnosis of Spigelman stage IV disease who have been downstaged by endoscopic or pharmacological means. Methods This retrospective cohort study used a database search of a large prospective polyposis registry to identify patients who had been downstaged from stage IV disease and had further opportunity for disease progression. These patients were divided into three groups according to their new Spigelman stage. A measure of a patient9s disease progression was obtained by the increase in stage over the recommended follow-up time period for their new, reduced, Spigelman stage. Results A total of 41 patients were indentified. Group 1 (n = 16) were downstaged to stage III disease, with 50% progressing back to stage IV over the recommended 1-year follow-up period. Group 2 (n = 19) were downstaged to stage II disease, with 84% undergoing progression over the recommended 3-year follow-up period. Group 3 (n = 6) were downstaged to stage I disease, with 100% undergoing progression over the recommended 5-year follow-up period. No patients were downstaged to stage 0. Conclusion Patients downstaged from Spigelman stage IV demonstrate an increased rate of disease progression back to severe disease in comparison to reported rates of primary disease progression. An amendment to the current endoscopic surveillance protocol is recommended to ensure that once a patient has been classified as having stage IV disease they are treated as a high-risk patient in perpetuity.

Cost-Effectiveness of Prophylactic Surgery for Duodenal Cancer in Familial Adenomatous Polyposis

Duodenal cancer is the leading cause of cancer death in familial adenomatous polyposis after colorectal cancer. The lifetime risk for developing duodenal cancer is 4% to 10%. Current treatment guidelines recommend endoscopic surveillance with a prophylactic pancreaticoduodenectomy in advanced duodenal polyposis, defined using the Spigelman staging system. Because no clinical trials have assessed this recommendation, a modeling approach was used to evaluate the cost-effectiveness of various treatment strategies. A Markov model was constructed to estimate the life expectancy and cost of three different strategies: pancreaticoduodenectomy at Spigelman stage III, pancreaticoduodenectomy at Spigelman stage IV, and pancreaticoduodenectomy at cancer diagnosis. A cohort of 30-year-old familial adenomatous polyposis patients with total colectomies was simulated until age 80. The analysis was from a societal perspective. Extensive sensitivity analysis was performed to assess the impact of model uncertainty on results. At all stages of polyposis and all ages <80 years, prophylactic surgery at Spigelman stage IV resulted in the greatest life expectancy. Surgery at stage IV was more effective and more expensive than surgery at cancer diagnosis, with an incremental cost of $3,200 per quality-adjusted life year gained. Surgery at stage III was not a viable option. The results were robust to wide variation in model parameters but were sensitive to the post-pancreaticoduodenectomy quality of life score. Prophylactic pancreaticoduodenectomy at stage IV duodenal polyposis in familial adenomatous polyposis is a cost-effective approach that results in greater life expectancy than surgery at either stage III or cancer diagnosis.

High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis

Duodenal polyposis occurs in approximately 90 % of patients with familial adenomatous polyposis (FAP) and 5 % - 10 % develop duodenal cancer. Novel imaging techniques may improve evaluation of duodenal polyposis using the Spigelman classification. We aimed to analyze the value of high resolution endoscopy (HRE) and the additional value of chromoendoscopy in the evaluation of duodenal polyposis in FAP. 43 FAP patients scheduled for surveillance endoscopy in two academic centers underwent gastroduodenoscopy with HRE forward- and side-viewing devices. After number and size of adenomas had been scored, indigo carmine 0.5 % was sprayed onto the mucosa, polyps were scored again and biopsies taken from the larger lesions. Subsequently, Spigelman classifications were assessed for pre- and post-staining. Before staining, a median of 16 adenomas per patient were detected compared with 21 adenomas after staining ( P = 0.02). Staining led to upgrading of Spigelman stage in 5/43 patients (12 %). Using the side-viewing endoscope, ampullary enlargement was detected in 22 patients (51 %) of whom 18 (42 %) had histologically confirmed ampullary adenomas. HRE has raised the quality of endoscopic imaging considerably. Consequently, re-evaluation of the original Spigelman classification system seems advisable. Chromoendoscopy further increases detection of duodenal adenomas in FAP but without considerable change in Spigelman stage. Ampullary adenomas are commonly found in FAP and are best visualized using a side-viewing endoscope. Therefore, a combination of forward-viewing HRE and chromoendoscopy with side-viewing endoscopy for the periampullary region seems useful for surveillance of duodenal adenomatosis in FAP.

Aggressive Phenotype of MYH-Associated Polyposis with Jejunal Cancer and Intra-Abdominal Desmoid Tumor

MYH-associated polyposis is an inherited autosomal recessive disease, linked to biallelic germline MYH mutations, which predisposes to the development of multiple colorectal adenomas and cancer. The colonic and extracolonic phenotype of this syndrome is very heterogeneous. We report the case of a young male patient with an aggressive MYH-associated polyposis phenotype. He presented at aged 30 years with more than 100 colonic polyps and 4 colonic adenocarcinomas. At aged 35 years, Spigelman Stage IV duodenal adenomatosis was detected. When he was 39 years old, he developed three synchronous jejunal adenocarcinomas and a mesenteric desmoid tumor. Based on this report, we believe that screening of the entire small bowel should be recommended in MYH-associated polyposis patients, especially in those with duodenal adenomas. Similar to patients with familial adenomatous polyposis, desmoid tumors also may be part of the clinical spectrum of MYH-associated polyposis and may prove to be a significant clinical problem in patients submitted to prophylactic colectomy.

Features of Duodenal Cancer in Patients With Familial Adenomatous Polyposis

Most patients with familial adenomatous polyposis (FAP) develop duodenal adenomas; duodenal cancer is a major cause of mortality in this patient group. We reviewed cases of duodenal cancer in patients with FAP to identify factors that determine long-term cancer risk. Twenty FAP patients (12 male) were identified from a registry database search. Data from registry and medical notes and endoscopic and histopathologic reports were evaluated. Of the cancers that developed in these patients, 11 were ampullary and 9 were duodenal. The median age at cancer diagnosis was 53 years. Seventeen patients died (median age at death, 57 y; median survival from diagnosis, 11 mo); the cause of death was metastatic or duodenal/ampullary cancer in 14 patients. Fifteen patients presented symptomatically (including 3 interval cancers while on surveillance). Two were diagnosed at surveillance and 3 were diagnosed during surgery performed for endoscopic features of advanced benign disease. Duodenal cancers were associated with a significantly lower mean colonic polyp count than ampullary cancers (496 +/- 282 vs 1322 +/- 735; P = .025); there appeared to be familial clustering of this cancer. When endoscopic data were available (n = 11 of 20), all ampullary cancers arose from ampullas greater than 1 cm. The Spigelman stage did not predict risk of ampullary cancer but did predict duodenal cancer (median stage 2 vs stage 4 for duodenal cancer). Once cancer arises in patients with FAP, prognosis is poor, so cancer prevention should be the main goal. Surveillance intervals should reflect both Spigelman staging and ampullary disease.

&lt;I&gt;COX-2&lt;/I&gt; Polymorphisms in Patients With Familial Adenomatous Polyposis

Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation, and angiogenesis. COX-2 has been found overexpressed in (pre)malignant tissues and may be relevant to cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on duodenal adenomatosis in patients with familial adenomatous polyposis (FAP). Blood from 85 patients with FAP and 218 age- and sex-matched healthy subjects was investigated for the presence of two functional promoter region polymorphisms (-1195G-->A and -765G-->C) in COX-2. Logistic regression analysis revealed an overrepresentation of the -1195GG genotype compared to the -1195AA genotype in patients with FAP (odds ratio = 2.81; 95% CI = 1.00-7.91, p = 0.042). No associations between single COX-2 polymorphisms or COX-2 haplotype were found when patients were evaluated according to their Spigelman stage. The predicted low COX-2 expression genotype -1195GG was found overrepresented in the patients with FAP. The COX-2 genotypes showed no association with the severity of duodenal adenomatosis.

Wireless capsule endoscopy in detecting small-intestinalpolyps in familial adenomatous polyposis

To detect the prevalence of small bowel polyps by wireless capsule endoscopy (WCE) in patients with familial adenomatous polyposis (FAP). We examined prospectively 14 patients with FAP to assess the location, size and number of small-intestinal polyps. Patients' age, sex, years of observation after surgery, type of surgery, duodenal polyps and colorectal cancer at surgery were analyzed. During WCE, polyps were detected in 9/14 (64.3%) patients. Duodenal adenomatous polyps were found in nine (64.3%) patients, and jejunal and ileal polyps in seven (50%) and eight (57.1%), respectively. The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps. Identification of the ampulla of Vater was not achieved with WCE. Importantly, the findings of WCE had no immediate impact on the further clinical management of FAP patients. No procedure-related complications were observed in the patients. WCE is a promising noninvasive new method for the detection of small-intestinal polyps. Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.