Somatostatinoma: collision with neurofibroma and ultrastructural features.

The clinical presentation, histopathology and immunoelectron microscopic features of two cases of duodenal somatostatinoma are described, one of which is a hitherto unreported example of a collision tumour with a neurofibroma. Ultrastructural morphometric immunoelectron microscopy studies revealed the presence of four types of cells in both tumours, but there was no difference in the proportions of these cells between the collision tumour and the non-collision tumour. Neurosecretory granules ranging in size from 255-815 nm were generally larger than those previously reported for somatostatinomas and somatostatin was identified in granules of all sizes across this range. Neither tumour was associated with the somatostatinoma syndrome comprising associated diabetes mellitis, steatorrhoea and cholelithiasis.

Esophageal atresia and achalasialike esophageal dysmotility.

A 14-year-old boy presented with regurgitation, malnutrition, and chronic lung insufficiency with a history of successful repair of esophageal atresia and tracheoesophageal fistula in the newborn period. Barium swallow and manometry results showed achalasia. Hellar operation with antireflux procedure resulted in complete symptomatic relief. Histology and immunohistochemistry including PGP9.5, MAP5, cKit, and nNOS of myotomy specimen showed intact innervation. Although esophageal dysmotility after esophageal atresia repair usually is caused by gastroesophageal reflux and incoordination of peristalsis, the possibility of achalasia should also be considered, because a casual relationship between esophageal atresia and achalasia may exist.

Myocardial vasoactive intestinal peptide and fibrosis induced by nitric oxide synthase inhibition in the rat.

AIMS: In both normotensive and hypertensive rats, the degree of myocardial fibrosis is inversely correlated with the concentration of vasoactive intestinal peptide (VIP) in the myocardium. Treatment with nitric oxide (NO) synthase inhibitors also causes myocardial fibrosis. In this study, we sought to determine whether the myocardial fibrosis induced by treatment with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) was also associated with depletion of VIP in the myocardium. METHODS: Male Wistar Kyoto (WKY) and spontaneous hypertensive rats (SHR) rats treated with l-NAME were randomized to low, intermediate or high salt content diets. After 4 weeks, the hearts were harvested, the degree of fibrosis quantified and VIP concentration measured. RESULTS: In WKY, systolic blood pressure increased with increasing dietary sodium (P < 0.05). Myocardial fibrosis also increased with increasing dietary sodium (P < 0.005). Myocardial VIP concentration decreased with increasing dietary sodium (P < 0.025). In contrast, in the SHR treated with l-NAME, systolic blood pressure increased but the increase was not affected by sodium intake. Further, myocardial fibrosis and myocardial VIP were unchanged by increased dietary sodium. Higher doses of l-NAME in the SHR did not increase the systolic blood pressure, increase the degree of myocardial fibrosis or decrease the myocardial concentration of VIP. These differences in myocardial VIP concentration may reflect differing effects of l-NAME on VIP metabolism, as l-NAME increased VIP metabolism in the WKY (P < 0.05) but did not change VIP metabolism in the SHR. CONCLUSIONS: We conclude that depletion of VIP in the myocardium is associated with increasing myocardial fibrosis in l-NAME treated WKY. As VIP depletion occurs in other models of myocardial fibrosis, it appears to be a common mechanism. Myocardial VIP depletion may therefore be a new and important factor in the pathogenesis of cardiac fibrosis.

Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC), but the long-term survival benefit remains unclear. METHODS: Pretreatment variables were analysed for factors predictive of actual 5-year survival from a prospective database of patients with inoperable HCC treated by TACE between 1989 and 1996. RESULTS: Complete 5-year follow-up (median 91 months) was obtained for 320 patients who underwent a median of 4 (range 1-41) TACEs. Median tumour size was 9 (range 1-28) cm. There were 25 5-year survivors (8 per cent), including eight with tumours larger than 10 cm in diameter and three with portal vein branch involvement. On univariate analysis, female gender (P = 0.037), absence of ascites (P = 0.028), platelet count below 150 x10(9) per litre (P = 0.011), albumin concentration greater than 35 g/l (P = 0.04), alpha-fetoprotein level below 1000 ng/ml (P = 0.007), unilobar tumour (P = 0.027), fewer than three tumours (P = 0.015), absence of venous invasion (P = 0.011), and tumour diameter less than 8 cm (P = 0.021) were significant predictors of 5-year survival. Albumin concentration greater than 35 g/l (P = 0.011), unilobar tumour (P = 0.012) and alpha-fetoprotein level below 1000 ng/ml (P = 0.014) were independent prognostic factors on multivariate analysis. CONCLUSION: Five-year survival is possible with TACE for inoperable HCC, even in some patients with advanced tumours. Unilobar tumours, alpha-fetoprotein level below 1000 ng/ml and albumin concentration greater than 35 g/l were factors predictive of 5-year survival.

Placental site nodules and plaques: a clinicopathological and immunohistochemical study of 25 cases with ultrastructural findings.

Placental site nodules or plaques (PSN-Ps) are nodular benign lesions of the intermediate trophoblast (IT) cells in the endometrium, endocervix, superficial myometrium or fallopian tube, occurring after a remote intrauterine pregnancy. We present a study of 25 cases of PSN-Ps These lesions occurred in patients aged 18 to 44 years. Most were discovered incidentally in endometrial curettage specimens. The specimens were received as part of clinical investigations for menorrhagia, per vaginal bleeding or pelvic pain. None of the PSN-Ps was visible grossly. Microscopically, they were mostly multiple, well-circumscribed, oval or plaque-like cellular nodules. The IT cells typically had abundant vacuolated or eosinophilic cytoplasm. The nuclei were irregular, large, hyperchromatic, often degenerate-looking and either mononucleated, multinucleated or multiclefted. Hyalinization surrounding individual or groups of IT cells, or located in the centre of the nodules, was a constant feature in all cases. The lesional cells were strongly immunoreactive to CAM 5.2, 34 beta E12, AE1/AE3, EMA and vimentin. Some cases showed focal positivity to HCG and HPL. PLAP staining was consistently negative. Ultrastructurally, the IT cells showed prominent nuclear variation in size and shape. The abundant, vacuolated cytoplasm contained some rough endoplasmic reticulum and loosely arranged filaments. This study describes the clinicopathological and immunophenotypic features of 25 cases of PSN-Ps including the ultrastructural findings of one case.

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length.

UNLABELLED: The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.

Calcification of the aortic valve: its progression and grading.

Three hundred and seventy four aortic valves which had been surgically removed over the past five years were studied by routine histology. Most patients were male and over the age of 60 years. There were 3.7% bicuspid valves, 16% valves with evidence of past rheumatic fever and 2.1% with endocarditis. A range of pathological lesions was seen including calcification, chondroid and osseous metaplasia, neovascularization, inflammation and cholesterol deposition. A common lesion was a progressive dystrophic calcification of the valve cusps. This was studied and graded in relationship to the concomitant structural damage. There has been no previously published grading system for this type of pathological change in the aortic valve. Our criteria for the four grades of aortic valve lesion are described. Most patients were found to have lesions of Grades 3 and 4.

The scanning electron microscopy of scolices in a case of hydatid cyst from human liver.

The scanning electron microscopic (SEM) features of hydatid scolices from a case of hydatid disease of the liver are described. The scolex when fully everted has a double circle of hooklets which occupy a large area of the parasite. The hooklets are inserted into the rostellum with one row of hooklets overlapping the other. Each hooklet is about 20 to 40 um long, has a basic round structure sharp at the distal end and broadens as it curves towards the point of insertion at the rostellum, where 2 blunt projections correspond to the 2 annular bundles of muscle fibres at the orifice of the scolex. The function of the hooklets is not fully understood but they are possibly used for anchorage and/or for the purpose of propulsion in a fluid medium by the act of invagination and evagination of the hooklets.

Progression from Goodpasture's disease to membranous glomerulonephritis.

An unusual case of a patient with Goodpasture's disease presenting with hemoptysis, severe iron deficiency anemia and microscopic hematuria and proteinuria is described. Both circulating and tissue anti-glomerular basement membrane (GBM) antibodies were present, and renal function remained normal throughout. Immunosuppressive therapy was given for subclinical pulmonary hemorrhage with successful resolution of anemia and disappearance of the circulating anti-GBM antibody. Nine months after presentation he developed nephrotic range proteinuria and a repeat renal biopsy revealed membranous glomerulonephritis with no evidence of his original disease. Both the Goodpasture's associated HLA-DR2 and the membranous associated HLA-DR3 class II antigens were present. The association of antibody mediated and immune complex glomerulonephritis is discussed. The simultaneous presence of HLA-DR2 and HLA-DR3 may predispose to this association.

A practical approach to the diagnosis of renal disease by biopsy.

The pathologist has an important role in the diagnosis and monitoring of renal disease. However, for optimal useful information to be derived from renal biopsy specimens, certain guidelines must be adhered to and these are enunciated here. The 3 avenues of observation of renal biopsies viz. light microscopy, immunofluorescence and electron microscopy, all have important roles to play and give differing data which informs the diagnosis for the renal biopsy report. The relative emphasis on each of these modalities of investigation will vary depending upon the situation in which the renal biopsy is performed. The methods used here have been shown to be effective in practice over a period of 20 yrs. Although there may be variations in methodology from centre to centre, the general background aims and principles remain the same. The emphasis in this paper has been on common practical aspects of renal biopsies. Much of the practical information concerning renal biopsies, which is brought together here, is otherwise scattered and not readily available. The aim of this article is to allow the reader to understand the rationale for the steps that are involved in renal biopsy diagnosis.

Neurocysticercosis: a report of four cases.

Cysticercosis is an uncommon disease in Australia. Only 4 cases of neurocysticercosis were found in our hospital with an active neurosurgical service over a 10 yr period. All 4 cases were migrants, 3 from South America and one from Cyprus. Epilepsy, aseptic meningitis and raised intracranial pressure were the common symptoms. Although the cerebral lesions were seen on CT scans, misinterpretation of the X-ray appearances readily occurs and the diagnosis can only be confirmed by histopathological examination of tissues. The pathological features are described including electron microscopy of one case. The cysticercus has a unique ultrastructure which is most helpful in establishing the diagnosis in cases were tissue sample is small and light microscopy is difficult. Neurocysticercosis can masquerade as a glioma or other space occupying lesion or aseptic meningitis. This condition should be considered in obscure neurological syndromes in migrants from affected regions of the world.

A study of parathyroid hyperplasia in chronic renal failure.

Specimens removed at parathyroidectomy from 41 patients with chronic renal failure, 12 patients with parathyroid adenomas and parathyroid glands from 24 autopsies were studied by light microscopy, immunohistochemistry and electron microscopy. The morphological abnormalities were correlated with clinical data obtained from patients' medical records. Glandular enlargement in chronic renal failure, primarily due to parenchymal cell hyperplasia, was as much as 20 times the normal in contrast to 40 times the normal cases of adenomas. Glandular hyperplasia was mostly due to an increase in the number of chief cells and to a lesser extent increase in the number of oxyphil cells, transitional oxyphil cells and water-clear cells. There was a corresponding reduction in fat and intracellular lipid content. There were differences in the overall morphology of normal, hyperplastic and adenomatous glands. The clear histological distinction between hyperplastic and adenomatous glands was at times difficult. There was no correlation between the extent of hyperplasia, the cause of renal failure, duration of chronic renal failure, levels of serum calcium, phosphate or parathyroid hormone. Immunohistochemical studies showed that all 3 types of cells contained parathyroid hormone but in hyperplastic and adenomatous glands there was a reduction in parathyroid hormone and chromogranin A staining. There were no specific ultrastructural abnormalities which would distinguish between hyperplastic and adenomatous glands.

Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats.

Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.

Analgesic nephropathy in Fischer 344 rats: comparative effects of chronic treatment with either aspirin or paracetamol.

This study has compared the relative nephrotoxicity of chronic treatment with aspirin or paracetamol in an animal model. Changes in renal structure and urinary concentrating ability were examined in female Fischer 344 rats after continuous treatment with either aspirin (120-230 mg/kg body wt/day), or paracetamol (140-210 mg/kg body wt/day), and were compared with age-matched untreated control rats. Renal morphological changes were examined after 40-83 weeks of analgesic treatment, using light and electron microscopy. Aspirin caused renal papillary necrosis and a decrease in urinary concentrating ability, whereas paracetamol alone did not cause significant renal damage. Aspirin produced damage to the interstitial cells and matrix, particularly in the mid-papillary region, followed by changes to the thin limbs of the loop of Henle and medullary capillary endothelium. These structural changes were similar to those described previously, when continuous treatment with combined aspirin and paracetamol was studied in the same animal model.

Experimental analgesic nephropathy: changes in renal structure and urinary concentrating ability in Fischer 344 rats given continuous low doses of aspirin and paracetamol.

Long-term treatment with aspirin and paracetamol produced renal papillary necrosis in female Fischer 344 rats. Aspirin (230 mg/kg body weight/day) and paracetamol (380 mg/kg body weight/day) were dissolved in drinking water and given continuously for up to 65 weeks. Renal morphological changes were examined between 21 weeks and 65 weeks of commencement of analgesic treatment using light and electron microscopy, and were compared with age-matched controls. Structural damage initially occurred in the mid-papillary region, and specifically involved the interstitial cells and interstitial matrix. Necrosis of the epithelium of the thin limbs of the loop of Henle was present only after interstitial changes were well established. Cortical interstitial fibrosis and tubular atrophy occurred after renal papillary changes were observed. There was no evidence of significant vascular damage. Urinary concentrating ability was measured sequentially during the period of analgesic treatment. A decrease in urine concentrating ability was present when early changes to the interstitial cells and matrix were observed, and concentrating ability continued to decrease in parallel with increasing morphological damage. This study describes an animal model of analgesic-induced nephropathy, enabling early morphological changes to be studied and correlated with renal functional changes.