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Registry to look for hereditary pancreatic cancer. (The Aim is Earlier Detection).

NEW YORK--A new cancer registry has been established at Memorial Sloan-Kettering Cancer Center in an effort to detect cases of familial pancreatic cancer in early, potentially curable stages.

Despite the recognition that heredity plays a significant role in pancreatic cancer, most cases--even among family members--are not identified until late in the disease. At that point, the 5-year survival rate is dismal, Dr. Robert C. Kurtz said at the annual meeting of the New York Society for Gastrointestinal Endoscopy.

The 5-year survival rate is 40% in the few patients who are diagnosed with the condition when the primary lesion is less than 3 cm, surgical margins are clear, and there is no spread to regional lymph nodes. In contrast, the 5-year survival rate is 5% in patients with larger lesions.

"We want to know if we can diagnose the disease earlier in high-risk groups, and if that will improve the 5-year survival," said Dr. Kurtz, chief of gastroenterology and nutrition, Memorial Sloan-Kettering Cancer Center, New York.

The investigators also will attempt to identify the precise molecular genetic events that lead to disease development.

Patients with pancreatic cancer are being recruited for the study if they are younger than age 50 years and have one or more first-degree relatives with pancreatic cancer, or two or more second-degree relatives with the disease, he said.

Related individuals without pancreatic cancer also are being enrolled if they have one or more first-degree relatives who were diagnosed with the disease before age 50. These subjects also are eligible if they have two or more affected relatives, one of whom is a first-degree relative.

Related individuals also will be included if they have three or more second-degree relatives with pancreatic cancer. Spouses, partners, and in-laws will serve as controls in the study.

Study enrollees will be evaluated with endoscopic ultrasound and magnetic resonance cholangiopancreatography. The investigators also plan to look for possible tumor markers, including telomerase activity in pancreatic fluid, Dr. Kurtz said.

Familial pancreatic cancer, which is estimated to account for about 10% of cases of the disease, occurs earlier than do nonfamilial forms of the disease. It also occurs progressively younger in each generation, a phenomenon known as anticipation, he said.

"In our surveillance study, testing of well family members will begin 10 years before the earliest age at which pancreatic cancer was diagnosed in that family," Dr. Kurtz said.

The progression from normal pancreatic duct epithelium to ductal dysplasia, carcinoma in situ, and infiltrating carcinoma is als have shown no greater long-term weight loss with very low-calorie diets than with less restrictive regimens.

Weight loss seems to be faster with diets that derive about half of their calories from fat rather than carbohydrate, but that may be due to greater losses of water and salt. However, patients may find the higher-fat diet easier to follow.

Drug treatment may help patients who already are motivated to make lifestyle changes, Dr. Baron said. He cited National Institutes of Health recommendations that drug treatment be reserved for obese patients (those with a body mass index of at least 30 kg/[m.sup.2]), or patients with a body mass index of 27 kg/[m.sup.2] and other comorbidities.

Dr. Baron has found that the results after 1 month of drug treatment are a good predictor of a patient's long-term success, so if a patient's experience isn't satisfactory by then, he discontinues the prescription.

Patients with a body mass index of 40 kg/[m.sup.2] or 35 kg/[m.sup.2] plus other comorbidities may be candidates for gastric bypass surgery. They'll lose as much as 50% of their body weight, but there's also a 30%-50% incidence of adverse effects such as diarrhea, emesis, ulcers, and gallstones. Still, most insurers view the procedure as cost effective and will approve it for selected patients.

Before surgery, Dr. Baron has patients lose about 10% of their body weight by eating 1,000-1,200 calories a day because that's all they'll be able to consume after the operation. He also warns women of childbearing age that it could complicate pregnancy.

When it comes to weight maintenance, exercise is once again the key Dr. Baron said. In a survey of people who had lost weight and kept it off, men and women alike engaged in an hour of moderate physical activity every day.

They also consumed approximately five small high-carbohydrate, low-fat meals or snacks, regularly monitored their weight, and virtually never ate fast food (Annu. Rev. Nutr. 21:323-41, 2001). The Institute of Medicine's Food and Nutrition Board has based its new recommendations for weight maintenance on these findings. (See box.)

Always screen a patient for depression or other psychiatric disorders before starting her on any type of weight loss regimen, Dr. Baron advised. "Don't even touch the obesity" before any emotional or psychiatric problems are addressed.
Recommendations for Healthy Weight Maintenance

Nutrient                         % of Total Daily Calories

Carbohydrate *                             45-65
Fat **                                     20-35
Protein                                    10-35

Fiber                                  Grams per Day

For people under 50 years old   38 (for men) 25 (for women)
For people over 50 years old    30 (for men) 21 (for women)

Exercise                                  Amount

Moderate (e.g., walking 4 mph)           1 hr/day
Intense (e.g., jogging)          20-30 minutes 4-7 days/wk

* Refined sugars should make up less than 25% of total calories.

** As little saturated fat, trans fat, or cholesterol as possible.

Source: Food and Nutrition Board, Institute of Medicine
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Author:Walsh, Nancy
Publication:Family Practice News
Geographic Code:1USA
Date:Feb 1, 2003
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