Medullary thyroid cancer: clinico-pathological profile and outcome in a tertiary care center in North India.

BACKGROUND: Recent advances in genetic screening have ushered in a new era in diagnosis and management of medullary thyroid cancer (MTC). However, the same is not true for a resource-poor country, where clinicians are still struggling to diagnose and adequately manage this relatively uncommon thyroid malignancy. We hereby present our experience of managing MTC at a tertiary care referral center in North India. METHODS: This was a retrospective study conducted between January 1990 and July 2009. Demographics, clinical profiles, details of surgical procedures, and follow-up records were reviewed. RESULTS: A total of 71 patients with MTC were identified. Mean age of this group was 39.9±14.1 years, and men outnumbered women 1.7:1. Some 84.5% of patients had seemingly sporadic MTC, and 15.5% had familial MTC (MEN2a=14.1%, MEN 2b=1.4%). All patients had a thyroid nodule at the time of presentation. Mean tumor diameter was 4.9 cm. Cervical lymphadenopathy, mediastinal lymphadenopathy, extrathyroidal invasion, and distant metastases were present in 59%, 7.2%, 10%, and 4.2% of patients, respectively. Staging showed that 4.8% of patients were stage I, 17.5% stage II, 14.3% stage III, and 63.6% stage IV. Treatment was as follows: 92.6% of patients had total thyroidectomy (primary or secondary); 67.6% central compartment lymph node dissection, 62.3% lateral cervical lymph node dissection, and 7.2% trans-sternal mediastinal lymph node dissection performed. Some 66.7% of patients suffered from persistent hypercalcitoninemia, and 11.4% of those underwent reoperation. The 5-year and 10-year overall survival (OS) was 74.6% and 58%, respectively. CONCLUSIONS: The majority of the patients with MTC presented at stage IVa, contributing to the high rate of persistent hypercalcitoninemia. Despite a policy of observation and intervening only in overtly symptomatic patients with persistent hypercalcitoninemia, overall survival (OS) in our study was comparable to other series, reinforcing the belief that persistent hypercalcitoninemia has an indolent course in most patients.

Glutathione S-transferase M1 and T1 polymorphism and response to neoadjuvant chemotherapy (CAF) in breast cancer patients.

PURPOSE: Response to neoadjuvant chemotherapy (NACT) for breast cancer patients cannot be predicted; however, polymorphism of the glutathione S-transferase genes GSTM1 and GSTT1 can modify the response to chemotherapy. The aim of this study was to establish whether there is an association between the polymorphism of GSTM1 and GSTT1 and response to NACT. METHODS: The subjects of this study were 45 patients with locally advanced breast cancer (LABC), who received the cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) regimen as NACT. We analyzed the relationship between the genotypes and responses to chemotherapy. RESULTS: The response rates to chemotherapy were better, although not significantly so, in patients with the GSTM1 and GSTT1 null genotypes (odds ratio [OR] 2.06 and 1.45). Similar findings were noted in patients with either or both of the null genotypes (OR 2.67 and 1.16). Among the responders, patients with the GSTM1 and GSTT1 null genotypes had higher rates of complete response following chemotherapy than those with one or more active allele (OR 1.8 and 1.3), although the difference was not significant. CONCLUSIONS: There was an association between the polymorphism of glutathione S-transferases and responses to chemotherapy, but the differences were not significant. However, larger studies are needed to investigate the role and efficiency of GST polymorphism in predicting response to chemotherapy.

Placental lead-induced oxidative stress and preterm delivery.

It has been reported that impaired oxidant/antioxidant status is involved in a variety of pregnancy complications. To elucidate the possible free radical mediated mechanism of preterm delivery due to lead exposure by determining the placental lead level and oxidant/antioxidant status in women with the preterm and full-term deliveries. Twenty-nine women with preterm deliveries (gestational age 28-37 weeks) and 31 women with full-term deliveries (gestational age >37 weeks) attending a local hospital of Lucknow, India were recruited. Placental lead level, thiobarbituric acid reactive species (TBARS) level, as an end product of lipid peroxidation, antioxidant molecule glutathione (GSH) level, and activity of antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) were measured in the placental tissue. In the group with preterm delivery, significantly higher placental lead levels were recorded than in those of full-term (0.39µg/g vs. 0.27µg/g; p<0.05). TBARS was significantly higher while GSH was significantly lower in the placenta of women with the preterm deliveries as compared to the full-term deliveries (p<0.05 for each). Activity of antioxidant enzymes; SOD, CAT, GPx, and GR were significantly higher in the placenta of women having preterm deliveries than those of the full-term (p<0.05 for each). Furthermore, placental lead has significant positive correlations with TBARS (r=0.34, p<0.05), SOD (r=0.30, p<0.05) and CAT (r=0.41, p<0.05), and negative correlation with GSH (r=-0.31, p<0.05). There may be a number of plausible reasons for increased oxidative stress in preterm delivery. However, results of this pilot study suggest that lead-induced oxidative stress may be one of the underlying mechanism(s) of preterm delivery and emphasizes the importance of evaluating the impact of persistent environmental pollutants on adverse pregnancy outcome.

Pediatric and adolescent pheochromocytoma: clinical presentation and outcome of surgery.

OBJECTIVES: To describe the clinical presentation and outcome of surgery in children with pheochromocytoma in a tertiary care hospital in India. METHODS: Clinical records of 24 children who were operated between January 1990 and January 2011 were reviewed. The diagnosis of familial disease was established based on clinical examination and follow-up events. RESULTS: Familial, bilateral, extra-adrenal and malignant pheochromocytoma were observed in 20.8%, 20.8%, 12.5% and 4.2% children, respectively. Median follow-up duration was 36 months. Persistent hypertension was noted in 12.5% patients and similar proportion died in follow-up. CONCLUSIONS: In the absence of routine genetic screening, good history and long- term follow up are essential to rule out familial pheochromocytoma.