Pancreatic enzyme therapy and clinical outcomes in patients with cystic fibrosis

OBJECTIVE: To assess the relationship between pancreatic enzyme therapy (PET) and the clinical outcomes of growth, abdominal pain, constipation, gassiness, and number of stools in cystic fibrosis (CF). STUDY DESIGN: Patients (n = 1215) >4 weeks of age from 33 Cystic Fibrosis Foundation accredited sites who had a sweat chloride >60 mmol/L or two CF-causing mutations were enrolled using a proportionate sampling strategy in a nonblinded study. Patients submitted a stool sample and completed a questionnaire. The study coordinator also completed a questionnaire for each patient. Enzyme dosing and growth, abdominal pain, gassiness, constipation, and number of stools were compared. RESULTS: Of the 1215 enrolled patients, 1131 (93.1%) were prescribed PET. Only 14.9% had pancreatic function assessed before enrolling in this study. Stool elastase-1 analysis identified 1074 (89%) patients as pancreatic insufficient (PI). There was no association between PET and the outcomes: growth, abdominal pain, gassiness, constipation, and number of stools. CONCLUSION: PET dose is not correlated with growth or gastrointestinal symptoms. More sensitive outcome measures of the effectiveness of PET in patients with CF are needed to guide treatment of PI.     

Predictors of operative death after oesophagectomy for carcinoma

BACKGROUND: Oesophagectomy for carcinoma provides a chance of cure but carries significant risk. This study defined risk factors for death after oesophageal resection for malignant disease. METHODS: Between 1990 and 2003, 773 oesophagectomies for oesophageal cancer were performed. Continuous variables were categorized into quartiles for analysis. Predictors of operative mortality were identified by univariate and multiple logistic regression analysis. RESULTS: The operative mortality rate was 4.8 per cent (37 of 773). In univariate analysis, advanced age, reduced forced expiratory volume in 1 s (FEV1), reduced forced vital capacity, presence of diabetes and tumour located in the upper third of the oesophagus were associated with a higher mortality rate. Multivariate analysis identified age (highest relative to lowest quartile, odds ratio (OR) 4.87 (95 per cent confidence interval (c.i.) 1.35 to 17.55); P = 0.009), tumour position (upper third relative to other locations, OR 4.23 (95 per cent c.i. 1.06 to 16.86); P = 0.041) and FEV1 (lowest relative to highest quartile, OR 4.72 (95 per cent c.i. 1.01 to 21.99); P = 0.018) as independent predictors of death. CONCLUSION: Advanced age, impaired preoperative respiratory function and a tumour high in the oesophagus are associated with a significantly increased risk of death after oesophagectomy for carcinoma.     

Socioeconomic effects on breast cancer survival: proportion attributable to stage and morphology

Breast cancer patients of lower socioeconomic status tend to have poorer survival. Among 10 865 cases of breast cancer from the East Anglian Cancer Registry diagnosed between 1982 and 1993, we estimated the extent to which the differences in survival by socioeconomic status, measured by both occupational and area-based methods, can be explained by differences between socioeconomic groups in stage and morphological type of tumour. In univariate survival analyses, lower social class (manual occupation) was associated with a relative hazard of 1.32 (95% CI 1.12-1.55) for death from breast cancer as underlying cause. Women resident in the most deprived area had a relative hazard of 1.21 (0.95-1.54) for death from breast cancer as underlying cause. Stage of disease accounted for 28% of the effect of social class on survival but for none of the effect of deprivation category. Morphological type accounted for 3% of the effect of social class and none of the effect of deprivation category. Thus, stage at presentation explains some but not all of the socioeconomic differences in breast cancer survival. Future research on histological grade and socioeconomic status is indicated.     

Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections

HYPOTHESIS: After resection of an adenocarcinoma of the ampulla of Vater, certain clinical and pathologic characteristics influence long-term survival. DESIGN: Retrospective case series. SETTING: Major academic medical and pancreatic surgical center. PATIENTS: Fifty-five consecutive patients who underwent Whipple resection for ampullary adenocarcinoma from 1988 through 2001. INTERVENTIONS: Pylorus-preserving Whipple resection in 32 patients and standard Whipple resection in 23 patients. MAIN OUTCOME MEASURES: Postoperative survival. A multivariate Cox proportional hazards model was used to determine the effects of various factors on long-term survival after resection. RESULTS: There were no operative deaths, and all patients left the hospital. After a mean follow-up of 46.9 months, the overall 5-year Kaplan-Meier survival estimate was 67.7%. The median survival of the entire group has not yet been reached. Five-year postoperative survival estimates for node-negative (n = 32) and node-positive patients (n = 23) were 76.5% and 53.4%, respectively (P =.26). Patients whose tumors demonstrated perineural invasion (n = 12) had a 5-year survival estimate of 29.2% vs 78.8% for those whose did not (P<.001). On multivariate analysis, the absence of perineural invasion (P<.001) was an independent predictor of significantly improved postoperative survival. CONCLUSIONS: Compared with previous reports from our own and other centers, this series demonstrates improved postoperative survival by 10% to 20% in patients undergoing Whipple resection for adenocarcinoma of the ampulla of Vater. The reasons for this improved outcome are unclear, and the effect of adjuvant treatment cannot be determined from this analysis. The major factor associated with prolonged survival was the absence of perineural invasion in the resected tumor specimen.     

Age-related differences in the sensitivity of the fish immune response to a coplanar PCB

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants. Because of their persistence and bioaccumulation in aquatic organisms (among other factors), the biological impact of PCB exposure on resident fish populations is of particular concern. To assess the effect(s) of an environmentally relevant coplanar PCB congener on the fish immune response, juvenile and aged Japanese medaka (Oryzias latipes) were injected i.p. with either vehicle or PCB 126 (at 0.01 or 1.0 µg/g BW) and examined after 3 and 14 days. CYP1A protein levels, examined as an indicator of PCB exposure, were significantly increased (compared to controls) in all fish treated with the highest PCB dose. Kidney phagocyte superoxide (O₂ ^·–) production was examined to indicate effects upon innate immune function. After 14 days, unstimulated O₂ ^·– production by kidney phagocytes from juvenile and aged medaka treated with the highest PCB dose was significantly increased compared to controls. Stimulated O₂ ^·– production by aged PCB-treated fish was unaffected (compared to controls) at both post-exposure timepoints. However, phagocytes from PCB-treated juvenile medaka demonstrated reduced O₂ ^·– production at 3 days post-exposure and increased levels after 14 days (compared to controls). These results demonstrate the sensitivity of medaka phagocyte function for examining PCB-induced immunotoxicity.     

Enterocystoplasty in childhood: a second look at the effect on growth

OBJECTIVE: To re-evaluate the assumption that enterocystoplasty in children has a detrimental effect on linear growth (which is almost exclusively based upon a chance finding in a retrospective study 10 years ago) in a larger cohort and with a longer follow-up. PATIENTS AND METHODS: The original 12 children who had impaired linear growth in a previous study 10 years earlier were re-measured. A larger cohort was identified from the 242 children and adolescents who had undergone enterocystoplasty between 1982 and 1997. Patients with conditions involving organ systems apart from the urinary tract, and those with myelomeningocele, malignant diseases, reduced glomerular filtration rate and incomplete notes were excluded. In the definitive study cohort (123; mean age at operation 8.6 years; mean age at investigation 16.8 years) enterocystoplasty had been undertaken using colon in 70, ileum in 37, a combination of both in 11, ileocaecal segments in three and stomach in two patients. RESULTS: Of the original 12 patients, six had regained or surpassed their preoperative position on their growth charts. In all patients with a known target centile range the final height was within their genetic growth potential. In the cohort of 123 patients, 1215 height and weight measurements had been recorded. The distribution of percentile positions before and after enterocystoplasty showed a normal configuration, with 83% and 80% of patients growing within two standard deviations of the 50th percentile. After surgery, 85% either remained on the same or reached a higher centile. Nineteen (15.5%) were in a lower position, with a similar tendency in the weight centile. A clinically relevant growth disorder was recognized in four patients with a complete endocrinological evaluation; in none of these was enterocystoplasty thought to be a causal factor. CONCLUSIONS: It is very unlikely that the loss of the preoperative percentile position on the growth curve in 15% of children after enterocystoplasty is a consequence of the surgery. Rather it is a non-specific phenomenon that has to be considered in any clinical population of the same size and age distribution after the same length of time.     

Distribution of non-phosphorylated neurofilament in squirrel monkey V1 is complementary to the pattern of cytochrome-oxidase blobs

The geniculo-recipient zones of the primate primary visual cortex (V1) stain more strongly for cytochrome oxidase (CO) than other regions. Labeling V1 with an antibody (SMI-32) against neurofilament protein produces a laminar pattern that is largely complementary to that of CO: the layers that receive the strongest geniculate input react weakly for SMI-32. We evaluated whether the complementary laminar relationship extends throughout the superficial layers where there are regularly spaced blobs of dark CO staining that are known to receive geniculate input. In all hemispheres, neurofilament labeling in the superficial layers was indeed complementary to the CO pattern. The density of SMI-32 labeled neurons was quantified and found to be greater within the CO interblobs than in the blobs. These results demonstrate that blobs and interblobs can be distinguished by examining the pattern of neurofilament expression in V1. That neurofilament expression is highest within interblobs raises the possibility that the distribution of cell types may be non-uniform across blobs and interblobs.