Renal sarcoidosis with normal serum vitamin D and refractory hypercalcemia

Introduction

Sarcoidosis is a multi-system disorder characterized by non-caseating epithelioid granulomas in multiple organs. Renal involvement may usually occur as granulomatous interstitial nephritis, but renal failure is uncommon. We report a case of renal-limited sarcoidosis diagnosed by renal biopsy, associated with abnormal calcium metabolism.

Case presentation

A 30-year-old Caucasian male presented with unexplained renal function impairment and hypercalcemia. The patient did not have any history of kidney disease, cough, skin rash, dysuria, hematuria or any other symptoms. Physical examination was unremarkable. Serum creatinine was 2.2 mg/dl and serum calcium was 11.5 mg/dl. Serum intact parathyroid hormone level (12 pg/mL) was decreased. Serum angiotensin-converting enzyme (ACE), 1,25-dihydroxyvitamin D (1,alpha-25 vit D) and pre-proparathyroid hormone (PTHrP) levels and urinary calcium excretion were all in normal range. The renal biopsy showed severe interstitial nephritis with non-caseating granuloma. The patient was treated with prednisone with starting dose of 1 mg/kg. After 2 months of prednisone therapy, serum creatinine decreased. However, because of continued of hypercalcemia unresponsive to low calcium diet and prednisone, chloroquine was prescribed. Six months after the onset, the patient's serum creatinine is stable at 1.30 mg/dl, serum calcium is 10.8 mg/dl, and serum ACE and 1,alpha-25 vit D levels are in normal range. He does not have any signs of extra-renal relapse.

Conclusion

The mechanisms of abnormal calcium metabolism in this patient with renal-limited sarcoidosis are unclear.     

Diagnostic usefulness of carbohydrate antigen-125 in cancerous and noncancerous peritoneal effusions

Carbohydrate antigen-125 (CA-125) is a tumor marker that has been used for differential diagnosis of peritoneal malignancies. The aim of the present study was to evaluate the diagnostic usefulness of simultaneous quantification of CA-125 in peritoneal fluid and serum for abdominal cancer cases and noncancer diseases. Noncancer disease group included cirrhotic patients (n=28) and spontaneous bacterial peritonitis (SBP) patients (n=11). Abdominal cancer group was composed of histologically diagnosed various malignancies (n=10), such as gastric cancer. CA-125 levels were quantified by chemiluminescent enzyme immuno-assay. Diagnostic usefulness tests and receiver operating characteristics (ROC) curve analysis were performed for the levels of peritoneal fluid CA-125 (pCA-125) and serum CA-125 (sCA-125), and the ratio of pCA-125 to sCA-125 (p/sCA-125). The sCA-125 levels were significantly higher in noncancer patients than those in the cancer patients, while the pCA-125 levels showed no significant difference between the two groups. Notably, the p/sCA-125 ratio was significantly lower in the noncancer patients than that in the cancer patients. Area under the ROC curve was 0.267 for sCA-125, 0.542 for pCA-125 and 0.831 for p/sCA-125. The accepted cutoff values were the combination of values that gave the greatest diagnostic sensitivity plus specificity. Either sCA-125 or pCA-125 value gave lower diagnostic accuracy, whereas p/sCA-125 value demonstrated a significantly higher diagnostic accuracy (sensitivity-specificity pairs: 0.40-0.33 for sCA-125, 0.60-0.54 for pCA-125, and 0.80-0.72 for p/sCA-125, respectively). Hence, determination of p/sCA-125 improves the biochemical discrimination of abdominal cancerous cases from noncancerous diseases.     

Thrombotic thrombocytopenic purpura in southern Turkey: a single-center experience of 29 cases

In this retrospective, nonrandomized study, we describe our experience in the management of 29 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids at a single center. We compared the effectiveness of high-dose steroids (20-25 mg/kg methyl prednisolone) as first-line treatment in combination with PE therapy with the combination of standard-dose steroids (1 mg/kg methyl prednisolone) and PE in adult patients with TTP. Clinical, laboratory data and treatment outcomes such as response rate, median time to recovery and survival were evaluated retrospectively. Overall (OR) and complete (CR) response rates were 69 and 52% respectively. Similar response rates were found in patients treated with pulse or conventional dose steroids; however, the median time to response was delayed in the high-dose methyl prednisolone (HDP) group. The median time from the initiation of symptoms to initiation of treatment was approximately 15 days (range: 0-30). Delayed treatment in our patients because of delayed referral to our center resulted in poor response to treatment. In all, four of 14 (27%) complete responders experienced relapses. The predicted relapse rate was 48% at a median of 30 months. All the relapses presented with a combination of thrombocytopenia and microangiopathic hemolytic anemia. This analysis showed that high-dose steroid treatment did not prove to be beneficial for TTP patients as firstline therapy combined with PE. Moreover, pulse steroid interventions might have resulted in delayed responses and our data suggest that initiation of treatment with PE should not be delayed.     

Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma

OBJECTIVES: Tumor growth and metastasis are angiogenesis-dependent events, and several prognostic factors have been determined in malignant mesothelioma. In this study, we investigated the prognostic significance of vascular endothelial growth factor (VEGF), tumor necrosis (TN), and mitotic activity index (MAI) in malignant mesothelioma. For the first time (to our knowledge), we also demonstrated the association between VEGF staining, TN, and MAI in malignant mesothelioma. METHODS: Decortication and VATS materials of 40 patients were investigated. The routinely processed formalin-fixed, paraffin-embedded, hematoxylin-eosin-stained tumor sections that had been used for the original diagnostic purposes were retrieved. Hematoxylin-eosin sections were selected for VEGF immunostaining, TN, and mitotic count. Clinicopathologic data, stage of disease, and survival of patients were all determined. The correlations between variables were evaluated by Spearman rank correlation test. Both univariate analysis using the log-rank test and multivariate analysis using Cox regression model were performed for survival analysis. RESULTS: There was a significant correlation between VEGF staining and TN (r = 0.42, p = 0.006). In univariate analysis, both VEGF staining (p = 0.0002) and TN (p = 0.0055) showed significant correlation with short survival. Also, there was a positive correlation between VEGF and tumor stage (p = 0.046). In multivariate analysis, only VEGF was determined as an independent prognostic factor in malignant mesothelioma (p = 0.001). There was no association between MAI and survival (p = 0.504). CONCLUSIONS: VEGF, known as an important angiogenic peptide, is an independent prognostic factor in malignant pleural mesothelioma. TN stimulates angiogenesis, and we observed a significant correlation between VEGF and TN. However, further studies are needed to evaluate the prognostic significance of angiogenic properties in malignant mesothelioma.     

Nonsense β-thalassemia mutation at codon 37 (TGG>TGA), detected for the first time in three Turkish cases

Thalassemias are genetically heterogeneous group of disorders with reduced or absent production of globin. β-Thalassemia major can be caused by homozygosity or compound heterozygosity for β-globin gene mutation. Here we report, for the first time in Turkey, three cases who carry the nonsense β-thalassemia (β-thal) mutation at codon 37 (TGG>TGA; Trp→Stop) causing premature stop codon.     

Hepatitis C virus positive patient diagnosed after detection of atypical cryoglobulin

A 60-year-old male patient presented with jaundice and dark urine for three days, icteric sclerae and skin rash on his legs for six months. Laboratory investigations revealed an atypical cryoglobulinemia with high hepatitis C virus (HCV)-RNA levels. Imaging studies showed cholestasis was accompanying HCV. Capillary zone electrophoresis using immunosubtraction method revealed a polyclonal immunoglobulin G and immunoglobulin A (IgA) monoclonal cryoglobulin and that IgA lambda was absent in immunofixation electrophoresis. After a liver biopsy, chronic hepatitis C, HCV related mixed cryoglobulinemia and cryoglobulinemic vasculitis were diagnosed and antiviral therapy was initiated. Our HCV patient presented with cryoglobulinemic symptoms with an atypical cryoglobulinemia that was detected by an alternative method: Immunosubtraction by capillary electrophoresis. Different types of cryoglobulins may therefore have a correlation with clinical symptoms and prognosis. Therefore, the accurate immunotyping of cryoglobulins with alternative methods may provide more information about cryoglobulin-generated pathology.