Hypercalcemia and pancreatic endocrine neoplasia with elevated PTH-rP: Report of two new cases and subject review

Humoral hypercalcemia of malignancy is widely associated with tumor production of parathyroid hormone related protein (PTH-rP). This peptide functions in endocrine, autocrine and paracrine mechanisms in a manner similar to PTH; increasing renal uptake of calcium, decreasing retention of phosphorous, and stimulating adenylate cyclase and phospholipase C. Although PTH-rP production has been well documented in neoplasms of the exocrine pancreas, we present here two cases of endocrine pancreatic neoplasms elaborating PTH-rP. We then review the literature of previous cases and delve into the pathophysiology of this peptide.     

Oligoastrocytoma presenting with intractable epilepsy.

OBJECTIVE: Oligoastrocytomas (OA) are mixed gliomas with distinct oligodendroglial and astrocytic neoplastic components. Very little about OA has been reported in the intractable epilepsy population. METHODS: We undertook a retrospective review of 923 patients who underwent resective surgery for intractable epilepsy between 1996 and 2004. RESULTS: 6/923 (0.7%) patients were diagnosed with OA. Five patients were female, one was male. Median age at diagnosis was 25 years (range 19-44 years). Tumors arose from the left side in all patients and from the temporal lobe in five patients. Three patients had complex partial seizures. Median length of refractory epilepsy prior to surgery was 10.5 years (range 1-28 years), and the median number of antiepileptic drugs used was 2 (range 1-10). Preoperative WADA testing for language and memory localization was done for three patients; preoperative stereotactical localization was done for three patients. Surgical pathology revealed low-grade OA (WHO II) in five patients, and anaplastic OA in one. There were no surgical complications, clinical or radiographic tumor recurrence at a mean follow up period of 3.2 years (range 2-8). Excellent seizure freedom was achieved in 5/6 patients. CONCLUSION: As a result of our small sample size, general conclusions may be imprecise, but this review suggests that OA behave similar to other tumors related to intractable epilepsy: they usually have a preoperative seizure course of many years, an excellent rate of seizure-freedom following surgery, and are in general, low-grade tumors with an indolent course for which serial imaging is sufficient follow-up.     

Effects of gastric bypass procedures on bone mineral density,calcium, parathyroid hormone,and vitamin d

Weight loss after gastric bypass procedures has been well studied, but the long-term metabolic sequelae are not known. Data on bone mineral density (BMD), calcium, parathyroid hormone, and vitamin D were collected preoperatively and at yearly intervals after gastric bypass procedures. A total of 230 patients underwent preoperative BMD scans. Fifteen patients were osteopenic preoperatively, and three patients subsequently developed osteopenia postoperatively within the first year. No patient had or developed osteoporosis. At 1 year, total forearm BMD decreased by 0.55% (n = 91; P = .03) and radius BMD had increased overall by 1.85% (n = 23; P = .008); both total hip and lumbar spine BMD decreased by 9.27% (n = 22; P < .001) and 4.53% (n = 31; P < .001), respectively. By the second postoperative year, BMD in the total forearm had decreased an additional 3.62% (n = 14; P<.001), whereas radius BMD remained unchanged. Although total hip and lumbar spine BMD significantly decreased at 1 year, by year 2 both total hip and lumbar spine BMD only slightly decreased and were not significantly different from before the operation. Serum calcium decreased from 9.8 mg/dL to 9.2 during the first year (not significant [NS]) and then to 8.8 (NS) by the second year. Parathyroid hormone increased from 59.7 pg/mL (nl 10-65 pg/mL) preoperatively to 63.1 during year 1 (NS) and continued to increase to 64.7 by year 2 (NS). No difference was noted among levels of 25-hydroxy vitamin D preoperatively (25.2 ng/mL; nl 10-65 ng/mL), at 1 year (34.4), and at 2 years (35.4). Our data indicate that bone loss is highest in the first year after gastric bypass with stabilization, and that, in some cases, there is an increase in bone density after the first year. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

Regional Variations in Peer Reviewed Liver Allocation Under the MELD System

The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non-RED's). Our aim was to compare regional practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non-RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29,510 listings were available. 26,947 had complete diagnosis information. There were 827 non-RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28-75%, p<0.0001). The most common non-RED's were complications of portal hypertension (48%). The percentage of patients listed with non-RED's varied significantly among regions (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non-RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting non-REDs.Widespread regional variations exist in the handling of requests for non-REDs. These variations point to the need for reform to standard exception criteria.     

Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy

BACKGROUND. Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy. METHODS. Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA). RESULTS. After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01). CONCLUSION. These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.