Prophylactic total gastrectomy (PTG) for hereditary diffuse gastric cancer (HDGC): the Newfoundland experience with 23 patients.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) results from truncating mutations of the CDH1 (E-cadherin) gene. It is an autosomal dominant cancer susceptibility syndrome with a lifetime risk of diffuse gastric cancer (DGC) of 60-80%, with a mean age of onset of 37 years. There exists no adequate screening test for DGC. Early intramucosal diffuse/signet-ring cell carcinomas have been found in prophylactic total gastrectomy (PTG) specimens following normal preoperative endoscopy. Total gastrectomy has been advocated on a prophylactic basis. The aim of this study was to report our experience with PTG in 23 patients from the Canadian province of Newfoundland and Labrador. This is the largest series worldwide. METHODS: A retrospective study of consecutive patients undergoing PTG for HDGC was performed. All patients were confirmed to have a truncating mutation of the CDH1 gene. RESULTS: Twenty-three patients underwent PTG between February 2006 and November 2008. Major complications were found in 4/23 patients (17%), with no mortality. Two of 23 patients (9%) had positive mucosal biopsies on preoperative EGD. Twenty-two of 23 patients (96%) had evidence of diffuse/signet-ring carcinoma on final standardized pathological evaluation. Therefore, 21/23 (91%) were not picked up by preoperative EGD screening. CONCLUSIONS: PTG can be performed in patients with HDGC with a low rate of serious complications. Methods of reconstruction incorporating a pouch reservoir and preservation of the postgastric branches of the vagus nerves need to be explored. More refined penetrance estimates, effective screening protocols, and long-term psychological and functional outcomes following PTG require organized multicenter collaborative efforts.

Cost analysis of a provincial drug program to guide the treatment of upper gastrointestinal disorders.

BACKGROUND: Concerned with the rising costs of its drug programs for seniors and social-assistance recipients, the government of Newfoundland and Labrador requested physicians and pharmacists at the Memorial University of Newfoundland, and members of the Newfoundland and Labrador Medical Association and the Newfoundland Pharmaceutical Association to provide guidance to the health care community for the use of drugs to treat upper gastrointestinal disorders. METHODS: Algorithms for the management of dyspepsia and gastrointestinal reflux disease were created and distributed to all physicians and pharmacists in the province in June 1996. On July 1, 1996, the provincial government implemented a program to restrict payment for proton-pump inhibitors through its drug programs to situations defined by the algorithms. Restrictions were not applied to the prescribing of cimetidine, ranitidine and prokinetic agents. The status of famotidine and nizatidine was changed from "open benefit" to "special consideration," which requires prescribers to request authorization of their use on a case-by-case basis. RESULTS: Between July 1 and Dec. 31, 1996, 973 of 1078 requests for a proton-pump inhibitor were approved (679 for gastroesophageal reflux, 186 for Helicobacter pylori eradication, 55 for ulcer treatment and 53 for other reasons). The program resulted in a sustained reduction in drug expenditures. Total drug expenditures, which had risen from $39.0 million in 1992/93 to $50.8 million in 1995/96, fell after implementation of the program to $46.4 million in 1996/97 because of a decrease of more than 80% in the use of proton-pump inhibitors. Expenditures on proton-pump inhibitors, which had increased from $0.7 million for the 6 months ending March 1993 to $1.6 million for the 6 months ending March 1996, decreased to $0.3 million for the 6 months ending March 1997. The use of H2-antagonists, but not prokinetic agents, increased concomitantly with the decline in proton-pump inhibitor use. Compared with the year preceding implementation of the program, annual combined expenditures in the subsequent 3 years for H2-antagonists, prokinetic drugs and proton-pump inhibitors were reduced by $1.6 million, $1.7 million and $1.0 million, respectively. Feedback from physicians and pharmacists was supportive for the clinical information and prescribing guidelines. Concerns were mostly limited to process issues. INTERPRETATION: The program, designed by health care professionals, approved by health care associations and implemented by the province of Newfoundland and Labrador to guide the treatment of upper gastrointestinal disorders, has achieved a substantial reduction in drug expenditures.

Compliance with drug therapy by epileptic patients.

Fifty patients with epilepsy were randomly divided into three groups and given, respectively, oral information about the nature, purpose, appearances, functions, and unwanted effects of their medications at an initial interview; the same information supplemented by its presentation in written form for the patient to take home; and the same information by telephone contact only. Compliance with anticonvulsant therapy was assessed by interview and by drug levels. The amount of knowledge retained and the drug levels were measured again 4 weeks later. While no increase in serum levels could be detected over the mean values in the first interview, no reduction in levels could be documented either, although the drug information sheets had listed both the minor and the more serious unwanted effects of the drugs. The patients' information scores improved significantly in all three groups, but the combination of data presented at interview both orally and in written form was markedly superior to the other methods.

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia Working Group.

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient's dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.