Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune syndrome

A 6-year-old female with polyglandular autoimmune syndrome type I, chronic active hepatitis, and renal failure is described. The renal biopsy demonstrated advanced tubulointerstitial disease with antibodies directed against tubular basement membranes. The patient's serum contained circulating antibodies directed against both renal and hepatic parenchyma. Renal disease culminating in renal failure and anti-tubular basement membrane disease have not been previously reported in association with polyglandular autoimmune disease. We describe for the first time a patient with polyglandular autoimmune syndrome, chronic active hepatitis, circulating antibodies directed against both renal and hepatic parenchyma, and primary tubulointerstitial disease culminating in renal failure.     

Multimodality treatment for gastric carcinoid tumor with liver metastases

Carcinoid tumors are the most common neuroendocrine tumors in the gastrointestinal tract, and between 10% and 30% of these tumors are gastric in origin. Three types of gastric carcinoid tumors are recognized: type I, associated with chronic atrophic gastritis type A; type II, associated with multiple endocrine neoplasia; and type III, sporadic and the most malignant. We present a patient with an aggressive, sporadic-type gastric carcinoid that metastasized to the liver. Her symptomatic treatment included the somatostatin analog octreotide. Octreotide scintigraphy demonstrated that this tumor avidly bound the peptide. The patient's gastric carcinoid (assessed by endoscopy and endoscopic ultrasound) regressed and she underwent hepatic artery embolization for her liver metastases. After initial partial CT resolution the tumor grew, compressing the inferior vena cava. The patient underwent orthotopic liver transplant with excellent recovery, although she was subsequently found to have two small lung metastases. She has responded well to adjuvant Indium-111 octreotide receptor targeted therapy. This case highlights the therapeutic options for metastatic neuroendocrine tumors, including liver transplantation and adjuvant receptor targeted therapy.     

Rectal carcinoid tumor associated with the Peutz-Jeghers syndrome

A 59-year-old female underwent mastectomy for right breast cancer in November 1992. She received tamoxifen and anthracycline-containing chemotherapy as adjuvant therapy. In and after September 1994, she developed loco-regional recurrences five times in total, each of which was treated with surgery and conventional combination chemotherapy. In April 1997, she developed liver metastasis, which was refractory to biochemical modulation therapy (low-dose cisplatin + 5-FU). We, therefore, treated her six times with docetaxel 80 mg, which resulted in partial response of the liver metastasis and brought about a marked decrease in serum CA15-3 levels. Adverse effects of docetaxel were grade 3 alopecia and leucocytopenia. She has been well without re-growth of the liver metastasis for over five months.     

Autoimmune rheumatic diseases associated with HIV infection and its pathogenesis

In autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or initiating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on autoimmune or rheumatic disorders associated with HTLV-I or HIV-I infection as well as new data from the autoimmune rheumatic mouse (MLR/1pr mouse) model might help to answer the questions how and what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in patients with HIV-I infection, apoptosis and molecular mimicry to autoantigens opens new approaches to the study of rheumatic disease pathogenesis.     

Autoimmune hepatitis treated with cyclosporin revealed by acute hepatocellular failure

The kidney bears the brunt of the demands of a tropical climate for water and electrolyte homeostasis. We hypothesised that a tropical climate may cause adaptive changes in the entire organism leading to altered renal function in our subjects. Hence renal function data for residents of a temperate climate may not be applicable to tropical residents. We therefore sought to elucidate renal function in subjects residing in a tropical climate. We used lithium clearance, CLi, a non-invasive tool for assessing proximal tubular function in humans, and endogenous creatinine clearance, CCr, to estimate proximal tubular function and glomerular function, respectively, in our subjects. We did this in order to establish whether or not nephron function in our subjects differs from that for residents of a temperate climate. Nineteen male and 12 female Ghanaian subjects aged between 15 and 48 years were studied. The estimated GCr was 117.3 +/- 6.6 ml/min for male subjects and 97 +/- 6.4 ml/min for female subjects. CLi was 20.3 +/- 1.6 ml/min for male and 19.1 +/- 0.4 ml/min for female subjects, respectively. The estimated absolute reabsorption rate of fluid of proximal tubules was 97.0 +/- 6.0 ml/min for males and 78.1 +/- 6.0 ml/min for females. The percentage proximal fluid reabsorption for male and female subjects was 81.2 +/- 1.4 and 79.5 +/- 1.6, respectively. The differences between male and female values (mean +/- SEM) were not statistically significant. The data suggest that the proximal tubule in residents of a tropical climate may reabsorb more fluid compared to that in residents of a temperate climate. Our values for proximal tubular reabsorption are higher than those reported for residents of a temperature climate. Our estimate of glomerular filtration, however, is similar to published data for Caucasians. The difference in proximal tubular function may reflect possible renal adaptation to a hot, humid climate. We conclude that renal function of tropical residents differs from that of residents of a temperate climate. This difference may be due to renal adaptation to the hot, tropical climate.     

Cardiac failure associated with hypocalcemia

Rapid transfusion of citrated whole blood was associated with acute hypotension and a rising central venous pressure in a patient undergoing pelvic exenteration and hemipelvectomy. Evidence of cardiac failure was accompanied by a precipitous decrease in serum ionized calcium (Ca++) concentration. When the rate of blood transfusion was slowed, arterial blood pressure returned to the control level and serum Ca++ increased.     

Granulation tissue polyposis associated with carcinoid tumours of the small intestine

We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy.     

Fulminant hepatic failure associated with bicalutamide

Bicalutamide is a new, nonsteroidal antiandrogen with a favorable toxicity profile. We report the first case of fulminant hepatic failure associated with its use.     

Helicobacter pylori and non-Helicobacter pylori bacterial flora in gastric mucosal and tumour specimens of patients with primary gastric lymphoma

There is an association between Helicobacter pylori (H. pylori) and gastric mucosa-associated lymphoid tissue (MALT) and MALT lymphoma. Histologically, mainly non-specific stains are used to detect H. pylori, such as haematoxylin-eosin (HE) or modified Giemsa (MG). In this study, both a MG and a specific immunohistochemical stain (IMM) for H. pylori (Dako B471) were performed on sequential slides of resected material containing tumour and non-tumorous gastric mucosa from patients with primary gastric lymphoma (n = 52). Special attention was paid to the presence of non-H. pylori bacterial flora diagnosed by a positive MG (according to form and localization) and a subsequently negative IMM. On all slides, bacterial density was scored semiquantitatively (grades 0, 1, 2, 3). In total, 32 (61.5%) patients were H. pylori positive using IMM and 34 (65.4%) were non-H. pylori positive using MG. In 24 out of the 34 patients, the non-H. pylori flora consisted mainly of cocci in combination with rods in 15 patients, mostly in minor quantities; in another 10 patients, high numbers of both cocci and different types of rods were present. Most non-H. pylori bacteria were localized superficially, although in 22 patients minor quantities of non-H. pylori were also seen in the glandular lumina. After all of the patients had been analysed, no differences in the density of H. pylori and of non-H. pylori flora were found. Only when comparing patients who had a small-cell lymphoma with those who had a large-cell lymphoma was a significantly higher density of H. pylori found in the corpus mucosa of large-cell lymphomas and a higher prevalence of non-H. pylori was found in tumours, in antrum or corpus, of patients with large-cell lymphomas. In conclusion, with joint evaluation using MG and a H. pylori-specific immunohistochemical stains, the proportion of H. pylori-positive gastric lymphoma patients was lower than in most previous studies but other bacteria were found in a relatively high proportion. The role of the non-H. pylori intragastric bacterial flora identified in this study has to be further elucidated in the aetiopathogenesis of primary gastric lymphoma.     

Liver failure associated with mitochondrial DNA depletion

BACKGROUND/AIMS: Liver failure in infancy can result from several disorders of the mitochondrial respiratory chain. In some patients, levels of mitochondrial DNA are markedly reduced, a phenomenon referred to as mitochondrial DNA depletion. To facilitate diagnosis of this condition, we have reviewed the clinical and pathological features in five patients with mitochondrial DNA depletion. METHODS: Cases were identified by preparing Southern blots of DNA from muscle and liver, hybridising with appropriate probes and quantifying mitochondrial DNA relative to nuclear DNA. RESULTS: All our patients with mitochondrial DNA depletion died of liver failure. Other problems included hypotonia, hypoglycaemia, neurological abnormalities (including Leigh syndrome) and cataracts. Liver histology showed geographic areas of fatty change, bile duct proliferation, collapse of liver architecture and fibrosis; some cells showed decreased cytochrome oxidase activity. Muscle from three patients showed mitochondrial proliferation, with loss of cytochrome oxidase activity in some fibres but not in others; in these cases, muscle mitochondrial DNA levels were less than 5% of the median control value. The remaining two patients (from a single pedigree) had normal muscle histology and histochemistry associated with less severe depletion of mitochondrial DNA in muscle. CONCLUSIONS: Liver failure is common in patients with mitochondrial DNA depletion. Associated clinical features often include neuromuscular disease. Liver and muscle histology can be helpful in making the diagnosis. Mitochondrial DNA levels should be measured whenever liver failure is thought to have resulted from respiratory chain disease.     

Horseshoe kidney is associated with an increased relative risk of primary renal carcinoid tumor

PURPOSE: Carcinoid tumor is a rare neoplasm of the kidney with an unknown histogenesis. Of only 31 cases previously reported in the literature 4 arose within horseshoe kidneys. We report a case of primary carcinoid tumor arising within a horseshoe kidney and discuss the unique insight it provided into the pathogenesis of this tumor. MATERIALS AND METHODS: We reviewed in detail all 31 reported cases of renal carcinoid tumor and, using reported incidence rates of horseshoe kidney, we calculated the relative risk of renal carcinoid tumor arising within a horseshoe kidney. Immunohistochemical staining for neuroendocrine related markers was performed on tissue sections from the present carcinoid tumor, the adjacent kidney and 5 control samples of normal renal parenchyma. RESULTS: Of the reported tumors 15.6% occurred in horseshoe kidneys, yielding a calculated relative risk of 62. The present tumor was multifocal, arising from the wall of a cystic lesion and possibly representing a dilated calix within the isthmus. Intestinal epithelium lining the cyst cavity exhibited multifocal neuroendocrine cell hyperplasia with an immunohistochemical profile identical to that of the carcinoid tumor cells. CONCLUSIONS: The relative risk of renal carcinoid tumor developing in a horseshoe kidney is markedly greater than that for Wilms tumor or transitional cell carcinoma. The clinical course of renal carcinoid tumor arising within a horseshoe kidney appears to be more benign than that of the nonhorseshoe variant. Our observations support the hypothesis that renal carcinoid tumors may arise from neuroendocrine cells within foci of metaplastic or teratomatous epithelium within the kidney.     

Infantile Helicobacter pylori associated with thickened gastric folds

This report extends our investigation of double base lesions produced by irradiation of DNA model compounds. Studies of d(CpGpTpA) X-irradiated in oxygenated aqueous solution show that two of the five principal products are oligomers having adjacent bases damaged. In these oligomers guanine is hydroxylated at the 8-position and an adjacent pyrimidine is degraded to a formamido remnant.     

Pulmonary sequestration associated with a gastric duplication cyst

A case of right subdiaphragmatic extralobar pulmonary sequestration (PS) associated with a gastric duplication cyst is reported. To the authors' knowledge such a case has not been reported previously in the English literature. PS was first noted as a defect on a nuclear liver image. The duplication cyst was defined by ultrasonography. A review of the English literature is included.     

Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma

BACKGROUND: Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine-deficient area. METHODS: The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin-embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non-radioactive PCR-based screening method was used for detection of MSI. RESULTS: Twenty-seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (chi2 < 0.01) lower pT stage (pT1, pT2) than cases without thyroiditis. No statistical association was found by comparing multifocality or sclerosing variants with the grade of lymphocytic infiltration. MSI was detected neither in patients with severe inflammation nor in the absence of thyroiditis. CONCLUSIONS: MSI does not seem to play a role in the pathogenesis of thyroid carcinoma. Coexistent thyroiditis is associated with a lower pT stage and thus could be an indicator of a better prognosis.