Randall E. Brand

Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: The familial atypical multiple mole melanoma-pancreatic carcinoma syndrome

Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations.

Gender differences in colorectal polyps and tumors

Abstract OBJECTIVES: To use a national endoscopy database (CORI) to determine 1) whether gender differences are noted in the prevalence and location of polyps and tumors; 2) whether women have a higher rate of right-sided polyps or tumors; and 3) whether age influences these results. METHODS: CORI database from April 1, 1997 to February 19, 1999, captured in a computer-generated report, was analyzed. Polyps for this study were defined as sessile or pedunculated and as >9 mm. Tumors were defined as lesions characteristic of adenocarcinoma (mass, apple-core). Pure right-sided colon (PRS) was defined as cecum, ascending, hepatic flexure; right-sided as PRS plus the transverse colon; and left-sided as the splenic flexure, descending, sigmoid and rectum. RESULTS: Men have a greater risk of polyps [odds ratio (OR), 1.5] and tumors (OR, 1.4) than women. The risk of finding polyps and tumors at colonoscopy increases with age, with the highest risk noted in those >69 yr of age relative to patients 60 yr of age. Women have a greater risk of developing pure right-sided polyps (OR, 1.2), tumors (OR, 1.6) and right-sided tumors (OR, 1.5) than men. CONCLUSIONS: Men have a higher prevalence of colon polyps and tumors than women. A progressive risk of polyp or tumor formation is noted with aging. Women had a greater number of pure right-sided polyps and tumor development. Colonoscopy is needed to correctly diagnose an increasing prevalence of right-sided pathology in the elderly.

Endoluminal delivery of radiofrequency energy to the gastroesophageal junction in uncomplicated GERD: efficacy and potential mechanism of action.

OBJECTIVES: The endoluminal delivery of radiofrequency energy to the gastroesophageal junction has been shown to decrease symptoms of gastroesophageal reflux disease in a multicenter study. In this single-center trial, we sought to further examine its efficacy and physiological effects in patients with uncomplicated gastroesophageal reflux disease. METHODS: Patients with chronic heartburn requiring maintenance antisecretory therapy but without a hiatal hernia >2 cm, severe esophagitis, or complications of gastroesophageal reflux disease were prospectively studied. Radiofrequency energy was delivered to the gastroesophageal junction using a transorally delivered, flexible bougie-tipped catheter and a thermocouple-controlled generator, under sedation and analgesia. The primary outcome measure was effect on reflux symptoms, assessed at baseline and at 1, 3, and 6 months, after treatment. Other outcome measures included effects on antireflux medication use, quality of life, overall patient satisfaction, esophageal motility, esophageal acid exposure, esophageal wall thickness, appearance of the cardioesophageal flap valve, and vagal efferent function. RESULTS: A total of 18 patients underwent successful outpatient treatment without a serious adverse event. A significant improvement in symptom scores (Gastroesophageal Reflux Disease [GERD] Activity Index: 112.5 [range 76.2-140.6] vs 81.0 (74.2-97.6); p < 0.0001) and antacid use (17/wk [range 0-81] vs 0 (0-10); p < 0.0001) was noted at 6-month follow-up. No adverse effect on abdominal vagal function was identified and no significant change in any esophageal motility parameter was seen; however, a trend was noted toward a reduction in the number of transient lower esophageal sphincter relaxations induced by gastric air distension (3.5/h vs 1.0/h, p = 0.13). No detrimental effects on peristalsis or swallow-induced lower esophageal sphincter relaxation pressure were seen. Nonsignificant trends (p = 0.06) were noted regarding a decrease in the Hill score and an increase in esophageal wall thickness after treatment. Finally, although a decrease in all pH parameters in both the upper and lower esophagus was seen, none reached statistical significance. CONCLUSIONS: Radiofrequency energy delivery to the region of the gastroesophageal junction provides effective symptom relief over the short term in patients with uncomplicated gastroesophageal reflux disease. It may achieve its therapeutic effect by reducing the frequency of transient lower esophageal sphincter relaxations triggered by gastric distension.

A Phase I trial of weekly gemcitabine administered as a prolonged infusion in patients with pancreatic cancer and other solid tumors

Purpose: Pharmacological studies of gemcitabine (2′,2′-difluorodeoxycytidine) have shown that increased levels of the active triphosphate metabolite are achieved by prolonging infusion time while holding the dose rate constant. The primary aim of this study was to determine the maximum tolerated dose (MTD) of gemcitabine administered as a fixed rate infusion (10 mg/m2/min) on a weekly schedule in patients with untreated non-hematologic malignancies.Patients and methods: Twenty-seven patients (21 pancreatic adenocarcinoma, 3 hepatoma, 1 neuroendocrine tumor, and 2 adenocarcinoma of unknown primary) were enrolled in this open-label, non-randomized study. Three different entry dose levels (1200 mg/m2, 1500 mg/m2 and 1800 mg/m2) were evaluated for gemcitabine administered on days 1, 8, and 15 of a 28-day cycle.Results: The MTD was defined as 1500 mg/m2 with granulocytopenia and thrombocytopenia being dose-limiting. There were no non-hematological dose limiting toxicities. The maximum WHO grade 3 or 4 toxicities for hemoglobin, leukocytes, neutrophils, and platelets for all doses of gemcitabine administered were 11.5%, 30.8%, 57.7%, and 26.9%, respectively. Non-hematologic toxicities included nausea, vomiting and fever. Four patients were withdrawn from the study for non-hematological toxicities: pneumonitis, ascites, disabling fatigue, and an acute myocardial infarction. Two of these events were severe (pneumonitis and myocardial infarction) but these may not be related to drug administration.Conclusion: Gemcitabine administered at a rate of 10 mg/m2/min was tolerated up to 1500 mg/m2 in patients with previously untreated non-hematologic malignancies. Myelosuppression seen in this study is more severe than anticipated based on previous reports of bolus administration of similar doses of gemcitabine. This supports earlier studies suggesting that prolonged duration of infusion increases the intracellular accumulation of active metabolites of gemcitabine.

The time and financial impact of training fellows in endoscopy

Abstract OBJECTIVE: To use a national endoscopy database (Clinical Outcomes Research Initiative, CORI) to determine 1) if fellow involvement increases procedure time; and 2) the financial impact of fellow participation for academic centers compared to private practice. METHODS: CORI database from 4/1/97 to 4/1/99 was used to compare endoscopists from private practices, academic medical centers, and Veterans Administration hospitals, with or without fellows-in-training. Data were captured in a computer-generated endoscopy report and transmitted to a central database for analysis. Duration of procedure (minutes) was recorded for diagnostic esophagogastroduodenoscopy (EGD), EGD with biopsy, diagnostic colonoscopy, and colonoscopy with biopsy, in ASA 1 patients. Financial outcomes used 1999 Medicare reimbursement rates for respective procedures and were calculated as procedures per hour on a theoretical practice of 4000 procedures. RESULTS: Teaching fellows endoscopy added 2–5 min for EGD, with or without biopsy, and 3–16 min for colonoscopy, with or without biopsy. Calculating the number of procedures/h of endoscopy, the reimbursement loss resulting from using fellows-in-training in a university setting would be half a procedure/h. In Veterans Administration hospitals, training of fellows would lose a full procedure/h. In a model of 1000 procedures each of EGD, EGD with biopsy, colonoscopy, and colonoscopy with biopsy, the reimbursement difference between private practice physicians or academic attending physicians and procedures involving fellows-in-training would be

Hereditary pancreatic adenocarcinoma. A clinical perspective.

500,000 to

Effects of low doses of erythromycin on the 13C Spirulina platensis gastric emptying breath test and electrogastrogram: a controlled study in healthy volunteers

1,000,000/yr. CONCLUSIONS: Fellow involvement prolonged procedure time by 10–37%. Thus, per-hour reimbursement is reduced at teaching institutions, causing financial strain related to these time commitments.

Gastric myoelectrical activity and its relationship to the development of nausea and vomiting after intensive chemotherapy and autologous stem cell transplantation

Although the total number of patients in these various high-risk groups is relatively small, they nevertheless provide excellent models for studying the cause, natural history, pathogenesis, and treatment of pancreatic cancer. These patients would also benefit greatly from procedures capable of detecting cancer at an early stage. This knowledge would be useful for the much commoner sporadic form of pancreatic cancer, in which diagnosis is almost always late and prognosis fatal. With early diagnosis, surgical resection before the cancers extension beyond the organs anatomic confines could be curative. The establishment of a National Familial Pancreatic Cancer Registry is essential and would increase the availability of these invaluable families for medical research.

Gastroparesis as a cause of nausea and vomiting after high-dose chemotherapy and haemopoietic stem-cell transplantation

Effects of low doses of erythromycin on the 13 C Spirulina platensis gastric emptying breath test and electrogastrogram: a controlled study in healthy volunteers

IMAGING TECHNIQUES IN THE EVALUATION OF ADENOCARCINOMA OF THE PANCREAS

Gastric myoelectrical activity and its relationship to the development of nausea and vomiting after intensive chemotherapy and autologous stem cell transplantation