Upper Gastrointestinal Polyps and Cancer

Duodenal Neoplasia

After the colon and rectum, the duodenum is the second most commonly affected site of polyp development in FAP [2,3]. Duodenal adenomas can be found in 30-70% of patients [2-4] and the lifetime risk of

Table 1. Extra-colonic manifestations of familial polyposis

Upper gastrointestinal tract:

Stomach: fundic gland polyps, adenomatous polyps, cancer

Duodenum and small bowel: duodenal adenomas, periampullary cancer, small-bowel adenomas, cancer, lymphoid polyps of ileum Gallbladder, bile duct, pancreas: adenomas, cancer

Desmoid tumors: abdominal wall, mesentery, retroperi-toneum, extremities

Bone and dental abnormalities: osteomas, unerupted teeth, supernumerary teeth, dentigerous cyst, odontomas

Cutaneous lesions: epidermoid cysts, sebaceous cysts, fibromas and lipomas

Ocular: pigmented ocular fundus lesions (POFLs)

Other neoplasia: adrenal adenomas, nasal angiofibromas, thyroid papillary adenocarcinoma, CNS tumors (glio-blastoma multiforme, cerebellar medulloblastoma), hepa-toblastoma these lesions approaches 100% [4-6]. Duodenal/peri-ampullary adenocarcinoma is a leading cause of cancer death in FAP patients following colectomy.

Duodenal cancer is rare in the general population, with an incidence of 0.01-0.04% [7]. Compared with the general population, FAP patients have a 100-330-fold higher risk of duodenal cancer [8, 9]. The estimated cumulative lifetime risk of developing duodenal cancer in FAP range from 4 to 10% [4,10,11]. The median age of duodenal cancer development is 52 years (range 26-58) [4]. Therefore, although most patients eventually develop duodenal polyps, these lesions occur at a later age and have lower potential for malignant change compared with colonic polyps.

Polyps can be found throughout the duodenum, but the second and third portion and the peri-ampullary region are the most commonly affected sites. This pattern suggests a role for exposure of duodenal mucosa to bile acids in duodenal carcinogenesis [12,13]. Data on the relationship between the severity of duodenal polyposis and specific mutations in the APC are inconsistent [14-16]. However, most reports indicate that mutations in exon 15 of the APC gene, particularly distal to codon 1400, give rise to a severe duodenal phenotype [11,17,18-20].

The adenoma-carcinoma sequence has been also observed in the setting of duodenal carcinogenesis in patients with both FAP and sporadic disease. Spigel-man et al. showed that villous histology, moderate or severe dysplasia, and the presence of stage IV duodenal polyps were associated with malignant change [21].

The most useful system for rating the severity of duodenal polyposis was developed by Spigelman et al. This classification describes five (0-IV) stages. Points are accumulated for number, size, histology, and severity of dysplasia of polyps (Table 2). Approximately 70-80% of FAP patients have stage II or stage III duodenal disease, and 20-30% have stage I or stage IV disease [12, 22]. However, the estimated cumulative incidence of stage IV duodenal disease is 50% at age 70 years [4, 23]. The Spigelman classification correlates with risk of duodenal malignancy. Stages II, III, and IV disease are associated with a 2.3, 2.4, and 36% risk of duodenal cancer, respectively [22].

Duodenal polyposis slowly progresses in size, number, and histology, and eventually in Spigelman stage [24]. Heiskanen et al. reported worsening poly-

Table 2. Spigelman classification for duodenal polyposis in familial adenomatous polyposis





Polyp number




Polyp size (mm)












Stage 0, 0 points; stage I, 1-4 points; stage II, 5-6 points; stage III, 7-8 points; stage IV, 9-12 points

Stage 0, 0 points; stage I, 1-4 points; stage II, 5-6 points; stage III, 7-8 points; stage IV, 9-12 points

Table 3. Recommendations for management of duodenal polyposis in familial adenomatous polyposis adjusted to the Spigelman stage of duodenal polyposis [6]









4 years




2-3 years




2-3 years




6-12 months




6-12 months



posis in 73% of 71 FAP patients followed for 11 years [5]. The median interval for progression by one stage was 4-11 years. The risk of developing stage III or IV disease exponentially increases after 40 years of age [25]. Endoscopic surveillance of the upper gastrointestinal tract for the development of neoplasia is recommended by most authorities. Screening for upper gastrointestinal disease should start at the time of FAP diagnosis [26]. The guidelines for continued endoscopic surveillance after baseline examination are according to the Spigelman stage (Table 3) [6, 22].


Endoscopic treatment options for duodenal lesions include snare excision, thermal ablation, argon plasma coagulation, and photodynamic therapy (PDT). Most reports of endoscopic therapy use snare excision. However, endoscopic treatment is usually insufficient in guaranteeing a polyp-free duodenum and might cause complications. Recurrence rates of adenomatous tissue in the duodenum of FAP patients treated endoscopically range from 50 to 100% [26, 27-29]. Surgical procedures to treat duodenal polyposis include local excision (duodenotomy with polypectomy and/or ampullectomy), pancreas preserving duodenectomy, and pancreaticoduo-denectomy. There are no randomized studies published to help guide surgical selection.

Local surgical treatment with duodenotomy has proven insufficient in guaranteeing a polyp-free duodenum, with most studies reporting high recurrence rates in patients with severe duodenal adenomatosis [5, 26-28, 30-33]. Farnell and colleagues found a lower recurrence rate of duodenal polyps of 32 and 43% at 5 and 10 years of follow up, respectively [34]. Nevertheless, duodenotomy may be indicated in patients with one or two dominant worrisome duodenal lesions in otherwise uninvolved or minimally involved intestine.

More radical surgery, in the form of pancreatico-duodenectomy, or pancreas preserving duodenecto-my, has been indicated for patients with severe polyposis (stage III-IV), failed endoscopic or local surgical treatment, and carcinoma. [26-28, 31-39]. Low recurrence rates of polyposis have been reported with these procedures.

Pharmacological Treatment. Duodenal adenomas seem less responsive to chemoprevention with NSAIDs than colonic counterparts. The results of NSAID, COX 2 inhibitors and other compounds on regression or prevention of duodenal adenomas in FAP appear disappointing [40-42]. The response of earlier Spigelman stages might be better [43]. Suggested guidelines for chemoprevention are presented in Table 3.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment