S. Datta Gupta

Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.

PurposeMatrix metalloproteinases (MMPs) are known to play an important role in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in preinvasive lesions and early esophageal carcinomas.MethodImmunohistochemical analysis of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal tissues (44 cases) and correlated with clinicopathological parameters.Result Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%) of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched distal normal esophageal tissue sections revealed that 26 comprised of normal epithelium, while 15 tissues showed evidence of dysplasia and three tissues showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched histologically normal esophageal tissues, respectively. Higher MMP-2 immunopositivity was observed in well and moderately differentiated SCCs in comparison with poorly differentiated tumors. The expression of MMP-2 was significantly reduced with the progressive de-differentiation of esophageal SCCs (P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC suggests that these alterations occur in early stages of esophageal tumorigenesis.Conclusion Increased levels of MMP-2 and MMP-9 proteins in ESCCs as compared to normal esophageal tissues suggest their association with esophageal tumorigenesis. Increased levels of these MMPs are observed in majority of dysplasias analyzed herein, indicating that these alterations may be early events in esophageal tumorigenesis. In-depth studies are warranted to determine their role in development and progression of esophageal cancer.

Acute hepatic failure in India: A perspective from the East

Acute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95–100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one‐quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high‐risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non‐pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF.
In our centre, approximately one‐third of AHF patients survive with aggressive conservative therapy, whereas two‐thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and Gram‐negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.

Antituberculosis therapy–induced acute liver failure: Magnitude, profile, prognosis, and predictors of outcome

Antituberculosis therapy (ATT)–associated acute liver failure (ATT‐ALF) is the commonest drug‐induced ALF in South Asia. Prospective studies on ATT‐ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT‐ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT‐ALF patients were younger (32.87 [±15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0‐30) days. The median duration of ATT before ALF was 30 (7‐350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non‐A non‐E–induced ALF, ATT‐ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT‐ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (≥10.8 mg/dL), prothrombin time (PT) prolongation (≥26 seconds), and grade III/IV encephalopathy at presentation. Conclusion: ATT‐ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented. Hepatology 2010

SIGNIFICANCE OF PROMOTER HYPERMETHYLATION OF p16 GENE FOR MARGIN ASSESSMENT IN CARCINOMA TONGUE

Loss of p16 expression by promoter hypermethylation has been reported as an early event in the development of oral cancer. The aim of our study was to explore the prognostic implications of presence of promoter hypermethylation of p16 gene in surgical margins in carcinoma tongue.

Prospective derivation and validation of early dynamic model for predicting outcome in patients with acute liver failure

Objective It is difficult to predict the outcome in patients with acute liver failure (ALF) using existing prognostic models. This study investigated whether early changes in the levels of dynamic variables can predict outcome better than models based on static baseline variables. Design 380 patients with ALF (derivation cohort n=244, validation cohort n=136) participated in a prospective observational study. The derivation cohort was used to identify predictors of mortality. The ALF early dynamic (ALFED) model was constructed based on whether the levels of predictive variables remained persistently high or increased over 3 days above the discriminatory cut-off values identified in this study. The model had four variables: arterial ammonia, serum bilirubin, international normalised ratio and hepatic encephalopathy >grade II. The model was validated in a cohort of 136 patients with ALF. Results The ALFED model demonstrated excellent discrimination with an area under the receiver operator characteristic curve of 0.91 in the derivation cohort and of 0.92 in the validation cohort. The model was well calibrated in both cohorts and showed a similar increase in mortality with increasing risk scores from 0 to 6. The performance of the ALFED model was superior to the Kings College Hospital criteria and the Model for End stage Liver Disease score, even when their 3-day serial values were taken into consideration. An ALFED score of ≥4 had a high positive predictive value (85%) and negative predictive value (87%) in the validation cohort. Conclusion The ALFED model accurately predicted outcome in patients with ALF, which may be useful in clinical decision-making.

Effect of cyclosporine on fertility in male rats

Abstract The effect of cyclosporine (CsA) on fertility has assumed greater importance with the increasing numbers of pediatric transplantations being performed all over the world. Conflicting reports on the effects of CsA on sex hormones are available. This experimental animal study was designed to examine the effect of CsA on testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats. Those rats who received CsA (20 mg/kg per day) showed significant reductions in testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05), STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P < 0.001) in the testis, and fertility (P < 0.001) compared to those receiving CsA 10 mg/kg per day and control rats. These findings will have an important bearing for children receiving cyclosporine for long periods to guide the physician in optimally adjusting long-term treatment.

Primitive Neuroectodermal Kidney Tumor: 2 Case Reports and Review of the Literature

Peripheral neuroectodermal tumors are uncommon cancers arising from outside the central nervous system. The urinary system is rarely involved. The differentiation of these tumors from other small cell cancer and neuroblastoma is based on immunohistochemical differences. We report 2 cases of such tumors arising from the renal parenchyma. Tumor behavior and treatment modalities are discussed.

Evaluation of Expression of Apoptosis-Related Proteins and Their Correlation with HPV, Telomerase Activity, and Apoptotic Index in Cervical Cancer

Objective: The aim of this study was to examine the expression of apoptosis-related proteins in cervical cancer, and investigate their correlation with the apoptotic index (AI), telomerase activity, human papilloma virus (HPV) infection and clinicopathological characteristics. Methods: Fifty cervical cancer samples and 20 normal cervical tissues were assessed for the protein expression of survivin, Bcl-2, Cox-2, p53 and p73 by immunohistochemistry. HPV DNA was detected by PCR, telomerase activity by PCR-ELISA, and AI by TUNEL assay. Results: 46/50 cervical tumors (92%) showed an increased telomerase activity as compared to 3/20 (15%) controls. 45/50 (90%) cervical tumors were positive for HPV, of which 30 were HPV-16 positive and 5 were HPV-18 positive. 24/50 (48%) tumors were positive for survivin, 14 (28%) for Bcl-2, 13 (26%) for Cox-2, 19/45 (42%) for p73, 10/45 (24%) for p53. Telomerase activity was highest in tumors with the poorest grade. A positive correlation was seen between survivin and Bcl-2, survivin and tumor stage, Bcl-2 and Cox-2, p73 and p53 and p73 and the AI. Despite the overexpression of various antiapoptotic proteins, no significant difference was observed in the AI between tumors and controls. Conclusions: Since deregulation of the apoptotic pathway appears to occur in cervical cancer, some apoptosis-related proteins could be assessed as potential markers for progression/prognosis in cervical cancer. Additionally, newer proteins such as p73 may play a compensatory role for the nonfunctional proteins such as p53.

Ectopic pancreas associated with a choledochal cyst and extrahepatic biliary atresia.

Abstract. Two children with incidentally-diagnosed ectopic pancreatic tissue in the jejunum at surgery for extrahepatic biliary atresia (EHBA) and choledochal cyst (CC) are reported. No case has been reported in the literature describing the association of a CC with ectopic pancreas, and only one case of EHBA associated with ectopic pancreas has been reported. We believe that incidentally-detected ectopic pancreatic tissue should be excised, even though the patient is symptom-free, in order to prevent the risk of serious complications due to either the mass effect or the potential for acute pancreatitis, cystic degeneration, or malignant transformation at a later date.

Cellular mesoblastic nephroma in an infant: Report of the cytologic diagnosis of a rare paediatric renal tumor

Congenital mesoblastic nephroma is a rare pediatric tumor with a favorable clinical outcome. Cytological features of this uncommon tumor and diagnostic difficulties with other commoner pediatric renal neoplasms have been inadequately discussed in the available literature. We describe the case of a 1‐year‐old girl who presented with a right renal mass. Fine‐needle aspiration smears consisted of a few cellular clusters of spindle cells with mitotic activity and mild nuclear pleomorphism. No blastema was identified. A cytologic impression of mesoblastic nephroma was rendered, which was confirmed on histopathological examination of the right nephrectomy specimen as a cellular mesoblastic nephroma.