Number of polyps
Polyp size (mm)
Degree of dysplasia
A surgical approach needs to be considered for patients with stage III/IV tumors. Treatment with celecoxib had been shown to be effective in reducing duodenal polyposis, but the drug has been taken off the market.
220.127.116.11 Surgery for Duodenal Adenomas
Both endoscopic and open surgical excision of duodenal adenomas allows down-staging of the polyposis, but it is associated with a high risk of recurrence. The only chance of a permanent cure for patients with advanced duodenal polyposis is a duodenal resection. The operation of choice is a pylorus-preserving pancreaticoduodenectomy or a pancreas-preserving duodenectomy in selected cases when there is no concern about malignancy . In specialist centers the outcome is good, with low recurrence rates and acceptable morbidity. Duodenal polyposis seems to follow the adenoma-carcinoma sequence. Therefore surgery should be discussed with patients with progressive and severe duodenal polyposis because invasive disease carries a poor prognosis, even when treated by radical surgery (Whipple procedure).
24.2.5 Desmoid Tumor
Desmoid tumors are histologically benign but locally invasive monoclonal proliferations of fibroblasts. They are only occasionally seen in the general population but affect 10–15 % of all patients with FAP. Desmoid tumors, together with duodenal polyposis/cancer, are the major cause of morbidity and mortality after proctocolectomy; they lead to death in approximately 10 %. Desmoid tumors arise either within the abdominal cavity, in particular within the small-bowel mesentery or on the abdominal wall, and occasionally on the extremities (Figs. 24.1 and 24.2). Their natural history shows great variation, with episodes of rapid and destructive growth as well as spontaneous regression. Intra-abdominal desmoid tumors can cause small-bowel and ureteric obstruction. Occasionally, a desmoid tumor arising within the small-bowel mesentery, thereby shortening it, makes a restorative procedure with IPAA impossible.
Desmoid tumor of the abdominal wall (MRI)
Giant desmoid tumor arising from the mesentery and fistulized through the abdominal wall (CT scan)
Risk factors for desmoid tumors have been identified among the FAP population: a germ-line mutation beyond the codon 1444, a family history of desmoid tumor, and a personal history of abdominal surgery [23, 24].
Medical treatment options include NSAIDs, antiestrogens, and chemotherapy and are used in an attempt to stabilize the tumor and induce regression. Several small studies have reported success for treatment with sulindac and/or tamoxifen , but evidence from randomized controlled studies is lacking. Cytotoxic therapy with vinblastine and methotrexate has shown some response. A more aggressive regimen combining dacarbazine with doxorubicin seems to be effective in rapidly expanding desmoid tumors. For stable intra-abdominal desmoid tumors, sulindac alone may be used. For slowly growing or symptomatic tumors, tamoxifen can be added. Chemotherapy is reserved for rapidly growing tumors; the rate of growth determines the drug regimen .
Surgery is recommended as the first-line treatment for desmoid tumors in the abdominal wall. Morbidity and mortality rates are low, but even with a 1-cm excision, margin recurrence is common. The abdominal wall may require reconstruction with prosthetic material. Surgery for intra-abdominal desmoid tumors is associated with a high risk of major complications (including hemorrhage, recurrence, and long-term parenteral nutrition) and therefore should be avoided whenever possible, unless the rare situation occurs where complete resection of the tumor can be performed easily. Intestinal ischemia and perforation resulting in peritonitis may, however, require an emergency laparotomy. In the future, small-bowel transplantation may become a treatment option for intra-abdominal desmoid tumors.
24.3 Hereditary Nonpolyposis Colorectal Cancer Syndrome
24.3.1 Molecular Screening
Following a careful personal and family history of cancer, some patients fulfill the Amsterdam I or II criteria or some of the Bethesda criteria (Table 24.2). However, these criteria are too stringent, and most patients carrying a deleterious germ-line mutation of an MMR gene will not be identified. At present, the recommendation is to try to determine the MSI phenotype after selection with these criteria and to test patients who show an MSI phenotype on polymerase chain reaction products for mutations . An alternative is to test all colorectal cancers with immunohistochemical staining with anti-MLH1 and anti-MSH2 antibodies . The loss of expression of one of these proteins as determined by immunohistochemistry correlates with the MSI phenotype. All patients presenting with a cancer deficient for one of these proteins should therefore be counseled about the search for a mutation on the gene of the deficient protein. Moreover, if several mechanisms can explain the MLH1 deficiency, most patients presenting with an MSH2-deficient cancer will have a germ-line mutation of this gene.
Clinical guidelines for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)
Amsterdam I criteria
Three relatives with colorectal cancer, one being a first-degree relative of the other two
Cases that span at least two generations
At least one colorectal cancer case diagnosed before age 50
Amsterdam II criteria
Three relatives with an HNPCC-associated cancer (colorectal, endometrial, small bowel, ureter, or renal pelvis), one being a first-degree relative of the other two
Cases that span at least two generations
At least one cancer case diagnosed before age 50
Bethesda criteria (revised in 2004)
Colorectal cancer before age 50
Synchronous or metachronous colorectal cancer or other HNPCC-related cancer (endometrial, ovarian, gastric, small bowel, urinary tract, biliary tract, pancreas, brain, or sebaceous gland), regardless of age
Colorectal cancer with MSI-H morphology (characterized by the presence of tumor-infiltrating lymphocytes, mucinous differentiation/signet-ring-cell carcinoma, peritumoral Crohn’s-like lymphocytic reaction, medullary growth pattern) before age 60
Colorectal cancer with one or more first-degree relatives with colorectal cancer or another HNPCC-related cancer, with one of the cancers diagnosed before age 50
Colorectal cancer with two or more relatives with colorectal cancer or another HNPCC-related cancer, regardless of age
24.3.2 Screening Guidelines
HNPCC is more complex than FAP because more genes are involved, penetrance is less complete, and expression is more varied. Furthermore, patients may be diagnosed with HNPCC clinically or biologically. These two subgroups are not identical, especially with regard to the risk of colorectal cancer among their relatives. Therefore, there are no clear recommendations for surveillance.
However, once a diagnosis of HNPCC has been established by either clinical or molecular criteria, an aggressive cancer screening program should be initiated.
Colonoscopy should begin between age 20 and 25 and then repeated every 1–2 years.
Gynecologic examination, annual transvaginal ultrasound, and endometrial aspiration biopsy are recommended because of the high risk of endometrial cancer after age 35.
Even if some deaths are not linked to colorectal or endometrial cancer, there are no standardized guidelines for screening for other tumors; this is usually based on the specific family history.
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