Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States.

BACKGROUND: Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients. AIM: To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres. METHODS: Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians. RESULTS: Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB - 5%, octreotide - 7%) with efficacy generally <50%. CONCLUSIONS: Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.

Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins.

BACKGROUND: Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. AIM: Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. METHODS: Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. RESULTS: Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS: Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition.

Acid steatocrit: a simple, rapid gravimetric method to determine steatorrhea.

OBJECTIVES: The detection and evaluation of steatorrhea in a rapid, quantitative fashion are clinically needed in patients with suspected steatorrhea. Our aim was to evaluate the acid steatocrit method, on random spot stools in adults with and without steatorrhea, relative to the qualitative (microscopic) and quantitative assessments for fecal fat. METHODS: Stool samples were collected 72 h after a diet of 100 g of fat per day and randomly from 15 healthy controls, 14 patients with chronic pancreatitis, and seven patients with small bowel disease. All stools had quantitative, qualitative, and acid steatocrit analyses performed for fecal fat. RESULTS: The sensitivity and specificity for the detection of steatorrhea by the spot stool qualitative fecal fat were 78 and 70%, respectively. The spot stool acid steatocrit correlated linearly with the 72-h stool quantitative fecal fat (g/24 h), r = 0.761 and p < 0.001. The acid steatocrit on random spot stools, compared with the 72-h stool quantitative fecal fat, revealed a sensitivity of 100%, a specificity of 95%, and a positive predictive value of 90% for the detection of steatorrhea. It also estimated the quantitative fecal fat. CONCLUSIONS: The acid steatocrit can be performed accurately on random spot stools and can be used to detect the presence of steatorrhea and estimate the quantitative fecal fat. This assay can be done with readily available equipment for rapid evaluation. Use of a spot stool sample simplifies the acid steatocrit, further improving on the practicality of this test. This study also confirms the clinical usefulness of this simplified method to detect steatorrhea.

Chronic diarrhea associated with thymoma and hypogammaglobulinemia (Good's syndrome).

We report the case of a patient with severe diarrhea and malabsorption who was subsequently found to have hypogammaglobulinemia and thymoma (Good's syndrome). The mechanism by which hypogammaglobulinemia and/or thymoma causes diarrhea is unclear. It may be related to malabsorption caused by a mucosal lesion resembling villous atrophy, which may resolve with restoration of immunologic status. Diarrhea in some patients may respond to commercial gamma globulin injections, fresh frozen plasma, or cholestyramine therapy. The etiologic relationship between thymoma and acquired hypogammaglobulinemia remains unclear. Thymectomy is generally ineffective in improving immunologic deficiencies and coexisting conditions in patients with acquired hypogammaglobulinemia. In our patient's case, severe diarrhea resolved after resection of the thymoma.

Fecal pancreatic elastase 1 is inaccurate in the diagnosis of chronic pancreatitis.

Many tests are available to assess pancreatic function. The ideal test would be simple and have adequate sensitivity in mild to moderate chronic pancreatitis (MCP) and severe CP (SCP). Fecal pancreatic elastase 1 (FPE1) assay (ScheBo Tech) has been proposed as a reliable test to evaluate pancreatic exocrine function, with sensitivities of up to 100% in diagnosing CP. Cutoff values (microgram/g stool) of < 100 have been suggested as SCP, 100-200 as MCP, and > 200 as normal. The test's ability to detect MCP distinguished by the absence of steatorrhea, and its specificity among various etiologies of malabsorption, has not been fully evaluated. The aim of this study was to evaluate this assay in subjects including patients with SCP with steatorrhea, patients with MCP with no steatorrhea, healthy controls, and diseased controls with nonpancreatic malabsorption. Thirty-six subjects [15 healthy controls, 7 malabsorption controls, and 14 subjects with CP (7 MCP, 7 SCP)] had FPE1 assays. One hundred fifty-four assays for FPE1 were run for analysis. The intraassay and interassay intraclass correlation coefficients were 0.93 and 0.90, respectively. All SCP had values of < 100 micrograms/g but more than half of the MCP subjects had FPE1 levels within the normal range. The subjects with nonpancreatic malabsorption had FPE1 values ranging from 55 to > 500 micrograms/g of stool. Although the assay detected SCP with steatorrhea, it did not consistently separate the MCP patients from normals. The majority of those with nonpancreatic malabsorption had false-positive values. These results may differ from previously described data because of the purposeful inclusion of MCP subjects, documented by the lack of steatorrhea, and the inclusion of disease controls with nonpancreatic malabsorption. Although PE1 concentrates in the stool and is not significantly degraded, subtle changes in this enzyme, as in MCP, do not seem to be detectable by this assay. This group continues to be the most difficult group to diagnose clinically.

Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Stevens-Johnson syndrome resulting from whole-brain radiation and phenytoin.

Phenytoin, one of the most widely prescribed anticonvulsants, and steroids are routinely utilized for seizure prophylaxis in patients with various intracranial tumors. We report a case of severe Stevens-Johnson syndrome (SJS), documented by biopsy, which occurred in a patient, with metastatic squamous cell carcinoma receiving phenytoin, whole-brain radiation therapy (WBRT), and a tapering steroid dose. The pathogenesis and implications are then briefly discussed.

Severe diarrhea and Cushing's syndrome from an atypical bronchial carcinoid.

Bronchial carcinoids are uncommon pulmonary tumors, considered neuroendocrine in origin and all types may produce various hormones. We describe a young woman with a 2-year history of radiographically stable atypical bronchial carcinoid, ectopic ACTH production, and a markedly elevated calcitonin level. The Cushing's syndrome and diarrheal illness were due to the ectopic hormones.

Herpes simplex infection associated with short-term use of a fetal scalp electrode. A case report.

A case of localized neonatal herpes simplex virus (HSV) infection involved a prior fetal scalp electrode site. Rupture of the fetal membranes, placement of the fetal scalp electrode and delivery occurred within 30 minutes. The mother had no previous history of genital lesions, and no herpetic lesions were noted at delivery.