Kusum Joshi

A Randomized, Controlled Trial of Steroids and Cyclophosphamide in Adults with Nephrotic Syndrome Caused by Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size, quality, and duration. This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, development of ESRD, and quality of life in a randomized, controlled trial. Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat basis. A total of 93 patients completed the study. Of the 47 patients who received the experimental protocol, 34 achieved remission (15 complete and 19 partial), compared with 16 (five complete, 11 partial) of 46 in the control group (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and the likelihood of survival without death, dialysis, and doubling of serum creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia, hyperlipidemia that required therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and better quality of life on follow-up. The incidence of infections was similar in the two groups. In conclusion, untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function. A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion, arrests progression of renal insufficiency, and improves quality of life.

The high incidence of tuberculosis among renal transplant recipients in India.

Tuberculosis is an important infection encountered after renal transplantation in third-world countries. Over an 8-year period, 36 cases of tuberculosis were encountered in 305 renal transplant recipients (11.8%) with grafts functioning for more than 3 months followed up at our center. The infection was limited to the thoracic cavity in 41.7% and a single extrapulmonary site in 11.1%, and it was disseminated in 27.8% cases. In 19.4% of cases, the disease appeared as pyrexia of unknown etiology and the diagnosis was confirmed by a good therapeutic response to antitubercular therapy. Tuberculosis was diagnosed within 1 year of transplantation in 58.3% of cases. There was no significant difference in the incidence of tuberculosis in patients on different immunosuppressive regimens. The Mantoux test was positive in 33.3% patients. A total of 23 patients were treated with isoniazid and rifampicin, with the addition of a third drug for the first 2 months. Treatment was continued for 9 months in 11 cases with isolated pleuropulmonary disease and for 12-15 months in the other 12 patients. The other 13 were on cyclosporine and were given isoniazid, pyrazinamide, and ethambutol for 18 months. Two patients died of fulminant disease and five more died from unrelated causes. No recurrence of disease has been noted in any of the patients after a mean follow-up of 14.6 months. We conclude that the incidence of tuberculosis in renal allograft recipients in third world countries is much higher than that seen in the western world. Most of the cases are encountered in the first posttransplant year. Tuberculosis must be considered seriously in all patients who have prolonged fever of undetermined etiology. Treatment with isoniazid and rifampicin for 9 months is adequate for patients with localized pleuropulmonary disease. In patients on cyclosporine to whom rifampicin cannot be given because of economic considerations, treatment with isoniazid, pyrazinamide, and ethambutol should be given for 18 months.

Acute Renal Cortical Necrosis—A Study of 113 Patients

Over a 28-year period, 113 out of 2986 (3.8%) patients dialysed for acute renal failure at a referral center in North India were diagnosed to have acute renal cortical necrosis (ACN). Obstetric causes were responsible for ACN in 56.6% patients and nonobstetric causes in 43.4%. Within the obstetric group, ACN developed in association with complications of late pregnancy in 37.1% and following septic abortion in 19.5%. The various nonobstetric causes included viperine snake bite in 14.2%, hemolytic uremic syndrome in 11.5%, renal allograft rejection in 5.3%, acute gastroenteritis in 4.4%, acute pancreatitis in 3.5%, septicemia in 2.7%, and trauma and drug-induced IV hemolysis in 0.9% patients. Total anuria was the commonest presenting feature and was noted in 78.8% of patients. Renal histology showed diffuse cortical necrosis in 62.8% and patchy lesions in 37.2% patients. Computerized tomography (CT scan) of the kidneys revealed characteristic diagnostic findings in all the 5 patients in whom it was done. Dialytic support could be withdrawn as a result of improvement in renal function in 19 patients with patchy cortical necrosis. Dialysis-free survival of as long as 12 years has been recorded. The present study shows that, in contrast to the Western world, ACN continues to be a common cause of acute renal failure in developing countries. CT scan of the kidneys is helpful in establishing an early diagnosis.

Intratumoral FOXP3 expression in infiltrating breast carcinoma: Its association with clinicopathologic parameters and angiogenesis.

The activity of T regulatory cells (Tregs) is known to be closely associated with the expression of forkhead/winged helix transcription factor, FOXP3. To determine, whether accumulation and activation of intratumoral Tregs help in the progression of breast carcinoma, we have analyzed the intratumoral expression of FOXP3 in invasive breast carcinoma and compared it with its level in ductal carcinoma in situ (DCIS) and adjacent normal tissue with the main aim of using this factor as marker of tumor progression. Intratumoral FOXP3 levels were correlated with the levels of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF, an invasogenic and angiogenic growth factor) and intratumoral microvessel density (IMD, a prognostic marker for angiogenesis). We also analyzed whether FOXP3 gene expression correlated with other clinicopathological variables like age, tumor stage, histological grade and lymph node metastasis. Infiltrating cancers had higher FOXP3 transcription (7.43±3.44) than did ductal carcinoma in situ (4.27±1.97, p<0.05) and normal tissues (3.51±1.22, p<0.001). Intratumoral FOXP3 expression was significantly higher in patients with stage III disease (TNM classification) compared to patients who had stage II disease (p=0.037). In infiltrating carcinoma, a significant positive correlation between FOXP3 expression and TGF-β1 expression was noted (p<0.001). Furthermore, a positive correlation between FOXP3 expression with VEGF expression and IMD values was also detected, however, statistically that was non-significant. A linear association of intratumoral FOXP3 expression with invasion, size and vascularity suggests a utility of FOXP3, an indicator of Treg activity as a marker of tumor progression and metastasis in breast carcinoma.

MDCT in the Staging of Gallbladder Carcinoma

OBJECTIVE The purpose of our study was to determine the utility of dual-phase MDCT with 3D reconstruction in the staging and resectability of gallbladder carcinoma. SUBJECTS AND METHODS Twenty-seven consecutive patients with suspected gallbladder carcinoma on clinical examination and routine sonography were prospectively analyzed with dual-phase MDCT. Of these patients, only 20 who underwent a laparotomy for extended cholecystectomy or a palliative surgery were included in the study. Three-dimensional volume-rendered reconstruction was used for evaluation of the vascular invasion and anatomy. The staging and resectability as determined on CT were compared with preoperative findings. RESULTS On the basis of the CT findings, eight tumors were resectable and 12 were unresectable. On surgery, 11 tumors were found to be resectable and the remaining were unresectable. Overstaging by CT occurred in three patients due to overassessment of duodenal infiltration. CT had a sensitivity of 72.7%, a specificity of 100%, and an accuracy of 85% for determining resectability of gallbladder carcinoma. For the diagnosis of hepatic and vascular invasion by the tumor, there was 100% correlation between CT and surgery. Vascular variations were found in six of the 11 patients who underwent radical cholecystectomy. CONCLUSION Dual-phase MDCT with 3D reconstruction is a comprehensive imaging technique for staging gallbladder carcinoma and determining the vascular road map before surgery.

Spectrum of fungal rhinosinusitis; histopathologist's perspective

Aims: Clinical presentation can provide a clue to the subcategories of fungal rhinosinusitis (FRS); however, tissue examination provides accurate classification. The aim was to analyse the incidence and histopathological spectrum of FRS.

The high incidence of BK polyoma virus infection among renal transplant recipients in India.

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.

The Utility of 1‐ and 3‐Month Protocol Biopsies on Renal Allograft Function: A Randomized Controlled Study

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1‐ and 3‐month protocol biopsies findings on 1‐year renal allograft function in a prospective randomized study. Out of 102 living‐donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2‐h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short‐term renal allograft function.

Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver.

Aims : Ductal plate malformation (DPM) is the persistence of excess of embryonic bile duct structures in the portal tracts. Most of the congenital diseases of intrahepatic bile ducts represent examples of DPM at different levels of the biliary tree. The aim of the present study was to evaluate the histopathological spectrum and immunohistochemical properties of DPM in various paediatric liver diseases and compare them with those of the normal embryonic ductal plates of human fetuses.

Cyclooxygenase-2 expression increases with the stage and grade in transitional cell carcinoma of the urinary bladder.

Objectives: Experimental models of carcinogenesis show that non-steroidal anti-inflammatory drugs (NSAIDs) increase apoptosis, inhibit angiogenesis and reduce metastases. A linkage between the activity of prostaglandin synthase enzyme cyclooxygenase-2 (COX-2), a known mediator of inflammation, and cancer angiogenesis is implicated. We investigated the expression of COX-2 in bladder cancer tissue specimens using immunohistochemistry. Methods: The immunohistochemical expression of COX-2 in bladder cancer was evaluated by scoring the intensity of immunoreactivity from 0 to 3. Further, the degree of COX-2 expression was correlated with the tumor grade and depth of invasion (T stage). Result: Fifty eight percent patients (n=22) had superficial bladder tumors, while 42% (n=16) were invasive bladder cancers. Overall, COX-2 immuno-positivity was seen in 84.2% (32/38) patients. COX-2 expression was positive in 76.4% (13/17) cases with pTa tumors, 100% (5/5) of pT1 tumors, 86.6% (13/15) of pT2 tumors and in 100% (1/1) of pT3 tumor. The higher stage tumors stained more intensely; this correlation wassignificant(p=0.01987; χ2=19.6977). With reference to the grade of tumors, a positive expression was seen in 81.25% (13/16) of the low-grade tumors and 89% (17/19) of the high-grade tumors. The differential COX-2 expression relative to the grade of tumor was found to be statistically significant (p=0.05; χ2=15.8612). Conclusion: The degree of COX-2 expression is significantly increased with advancing grade and T stage of disease (p < 0.05).