Gestational Trophoblastic Neoplasia: Experience from a Tertiary Care Center of India.

AIMS: Gestational trophoblastic neoplasia (GTN) comprise a spectrum of interrelated conditions originating from the placenta. With sensitive assays for human chorionic gonadotropin (ß-hCG) and current approaches to chemotherapy, most women with GTN can be cured with preservation of reproductive potential. The purpose of this analysis was to address the outcome of GTN in patients from a tertiary care center of India. MATERIALS AND METHODS: We undertook a retrospective and prospective review of GTN cases treated at our center over a period of 7 years from 2008 to 2014. Patients of GTN were assigned to low-risk or high-risk categories as per the FIGO scoring system. The low-risk group was treated with combination of actinomycin-D and methotrexate and the high-risk group received the Etoposide, Methotrexate, Actinomycin-D/ Cyclophosphamide, Vincristine (EMA/CO) regimen. Salvage therapy was Etoposide, Paclitaxel /Paclitaxel, Cisplatin (EP/TP). Treatment was continued for three cycles after normalization of ß-hCG level, after which the patients were followed up regularly. RESULTS: In total, 41 GTN patients were treated at our institution during the above period; 17 were in the low-risk and 24 were in the high-risk category. The lung was the most common site of metastasis. All low-risk patients achieved complete remission. Among high-risk patients, one patient died while receiving first cycle chemotherapy, one patient relapsed, and 22 patients achieved complete remission. The single relapsed patient also achieved remission with second-line chemotherapy. CONCLUSION: Risk-stratified treatment of GTN was associated with acceptable toxicity and resulted in outcome that was comparable with international standards. The use of two-drug combination in low-risk patients is a better option especially in developing countries.

Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir.

BACKGROUND: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. MATERIALS AND METHODS: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. RESULTS: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). CONCLUSIONS: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

Role of vitamin D receptor (VDR) polymorphisms in susceptibility to multiple myeloma in ethnic Kashmiri population.

BACKGROUND: Vitamin D regulates many biological processes including bone metabolism, innate immune response, and cell proliferation and differentiation by binding to its receptor VDR. Vitamin D receptor (VDR) gene polymorphisms have been associated with many cancers like breast, colorectal, prostate, and skin. The main aim of this study was to determine whether VDR polymorphisms (ApaI, BsmI and FokI) are associated with increased risk of multiple myeloma. METHODS: We designed a case control study where 75 multiple myeloma cases were studied for VDR polymorphisms (ApaI, BsmI and FokI) against 150 controls taken from general population. The polymorphisms of VDR gene were investigated using PCR-RFLP method. RESULTS: We did not find any significant association between ApaI and BsmI polymorphisms and multiple myeloma risk (P>0.05), but FokI polymorphism was significantly associated with increased risk for multiple myeloma. We also found a significant association between the ff variant genotype with creatinine levels, albumin levels, and Durie-Salmon stage III. CONCLUSION: Our findings suggest that the FokI polymorphism is involved in the increased susceptibility to development and progression in multiple myeloma in the ethnic Kashmiri population. Furthermore these results suggest that ff genotype is associated with higher risk for developing multiple myeloma.

Comparative efficacy of 5flourouracil/calcium leucovorine versus 5flourouracil/calcium leucovorine plus oxaliplatin in the adjuvant treatment of colonic carcinoma in Kashmir.

AIM: This prospective, randomized comparative study conducted in Kashmir evaluated the clinical profile of colonic carcinoma and the efficacy, side effects and survival advantage of adjuvant treatment with 5FU/CLV versus FOLFOX7. MATERIALS AND METHODS: Between 2007 and 2009, the clinical profiles of 50 patients enrolled and randomized equally into Arm A receiving 5FU/CLV alone (Mayo Clinic Regimen) and Arm B receiving the FOLFOX7 regimen (including oxaliplatin) were evaluated. RESULTS: Majority of the patients were in the 5(th) and 6(th) decade of life (males 70% versus females 30%), and most were from urban dwellings. Consumption of red meat, obesity and physical inactivity were common risk factors. A family history of colonic carcinoma was reported in 12% of the patients. Event-free and disease-free survival for the two arms were: Arm A - 12.8 ± 5 months and 14.2 ± 6 months; Arm B - 13.0 ± 6.7 months and 13.1 ± 6 months, respectively. Treatment-related morbidity was significant in Arm B whereas general well being and surrogate laboratory markers including a hemogram, favored Arm A. CONCLUSION: The clinical profile, risk factors and familial predisposition of Kashmiri colonic carcinoma patients matches that of colon cancer patients elsewhere. There was no added survival advantage by adding oxaliplatin to 5FU and CLV. Although the interim results showed that the Mayo Clinic Regimen has a better total survival advantage compared with the FOLFOX7 regimen, the results were not statistically significant. The Mayo Clinic Regimen was better than the FOLFOX7 regimen in terms of the toxicity profile. However, this finding needs to be studied further. The main idea of conducting this study was to reveal that there is no added advantage of adding oxaliplatin to 5FU and CLV, thereby (a) reducing the toxicity (b) and lowering cost of therapy.

Melorheostosis with renal arterio-venous malformation: A case report with review of literature.

Melorheostosis, also known as Leri's disease and flowing periosteal hyperostosis, is a rare cause of pain and stiffness in a limb. The appearance is of "candle greasing" down one side of one or several bones of the body. We describe a case referred to tertiary care center with suspicion of renal cell carcinoma with diffuse bone metastasis. After reassessment, the patient was diagnosed melorheostosis with renal AV malformation. He was reassured about the benign nature of the disease and is asymptomatic.