Retrospective audit of clinico‑pathologic features and treatment outcomes in a cohort of elderly non‑Hodgkin’s lymphoma patients in a tertiary cancer center.

INTRODUCTION: There is limited data from India regarding elderly non‑Hodgkin’s lymphomas (NHL) patients. Hence, this audit was planned to study the clinic‑pathological features and treatment outcomes in elderly NHL patients. METHODS: Retrospective analysis of all NHL patients above age of 59 years treated at the author’s institute, between December 2010 and December 2013 was done. Case records were reviewed for baseline details, staging details, prognostic factors, treatment delivered, response, toxicity and efficacy. SPSS version 16 (IBM, Newyork) was used for analysis. Descriptive statistics was performed. Kaplan–Meir survival analysis was done for estimation of progression‑free survival (PFS) and overall survival (OS). Univariate analysis was done for identifying factors affecting PFS and OS. RESULTS: Out of 141 NHL patients, 67 patients were identified subjected to the inclusion criteria. The median age was 68 years (60–92). Majority were B‑cell NHL (86.6%). The commonest subtype in B‑cell was diffuse large B‑cell lymphoma (55.2%). Fifty‑four patients took treatment. The treatment intent was curative in 41 patients (61.2%). Among the patients receiving curative treatment, 16 patients couldn’t receive treatment in accordance with NCCN guidelines due to financial issues. Two years PFS was 55%. Two years PFS for B‑cell NHL and T‑cell NHL were 55% and 50% respectively (P = 0.982). Two years PFS for standard Rx and nonstandard Rx were 62% and 50% respectively, but it didn’t reach statistical significance (P = 0.537). Two years OS for the entire cohort was 84%. CONCLUSION: Standard treatment in accordance with guidelines can be delivered in elderly patients irrespective of age. There is a need for creating financial assistance for patients, so that potentially curative treatments are not denied.

Patterns of care in geriatric cancer patients – An audit from a rural based hospital cancer registry in Kerala.

BACKGROUND: There is deficit of data from India on elderly patients with cancer. Comprehensive geriatric assessment may lead to a better decision making capacity in this population. However, routine implementation of such assessment is resource consuming. AIM: The aim of this study was to determine the patterns of care in elderly patients treated at a tertiary rural cancer center in India. MATERIALS AND METHODS: All patients with age 70 or above with solid tumors without any definitive treatment prior to the registration at our center and registered between 01/01/2010 and 31/12/2011 were selected for this study. The baseline demographic pattern and the pattern of care of treatment were analyzed. SPSS version 16 (IBM Inc, Armonk, New York, U.S.) was used for analysis. Descriptive data are provided. RESULTS: A total of 761 patients were evaluable subject to the aforementioned inclusion criteria. The median age of this cohort was 75 years (70‑95 years). The most frequent primary sites of malignancies in 451 males were head neck (32.4%), lung (23.3%) and gastrointestinal (23.3%). In 310 females, the most common sites were head neck (31.6%), gynecological (18.4%) and gastrointestinal (24.5%). 228 (30%) of the patients had localized disease, 376 (49.4%) had loco‑regionally advanced disease and 145 (19.1%) had distant metastases at presentation. 334 (46.32%) of patients were treated with curative intent. On logistic regression analysis the factors that predicted use of curative intent treatment were age <75 years, performance status 0‑1, primary site and clinical extent of disease. CONCLUSION: Routine comprehensive geriatric assessment needs to be implemented in our setting as almost 50% of our geriatric patients undergo curative intent treatment.

An audit of febrile neutropenia cases from a rural cancer center in India.

BACKGROUND: Data of febrile neutropenia (FN) from rural cancer centers is sparse. We did a audit of outcome of patients with FN in the period of March 2013‑August 2013. The aim was to help us to develop rational antibiotic usage policies. MATERIALS AND METHODS: Retrospective analysis of all consecutive patients presenting with FN. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. SPSS (Statistical Product and Service Solutions) 16 was used for analysis. RESULTS: 67 patients had FN and there were 91 episodes. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count was 161.5 and nadir platelet count 1,00,000. The median multinational association for supportive care in cancer (MASCC) Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). CONCLUSION: The importance of developing local guidelines for rational antibiotic usage is highlighted.

A phase I trial of tocoferol monoglucoside in patients undergoing hemi-body radiation.

PURPOSE: To evaluate Tocoferol monoglucoside (TMG), a water soluble vit. E. in a phase I trial, as a radiation protector in those undergoing hemi-body radiation for disseminated disease. MATERIALS AND METHODS: Patients scheduled to receive modified hemi-body radiation were accrued for the study. Patients not only had disseminated skeletal disease but, were heavily pretreated Seven patients were accrued for the study. Patients received 1 and 2 gms of TMG. 30-40 minutes before hemibody radiation. A dose of 600 cGy was delivered on telecobalt equipment at mid plane. Immediate Toxicities were evaluated as well as response to pain. RESULTS: All the seven patients underwent radiation uneventfully. There was no drug related toxicity. Pain relief was adequate. CONCLUSION: Tocoferol monoglucoside an effective antioxidant with no significant acute toxicity, when administered in a dose of 1 or 2 gms per oral route. TMG being water-soluble can have global antioxidant and radio protective effects. This needs further clinical evaluation.

Genetic alterations in cervical cancer.

In the pathogenesis of cervical cancer the role of human papillomavirus (HPV) infection is well established. However, other than HPV infection the genetics of cervical cancer remains poorly understood. In the pathogenesis of cervical cancel three major factors are involved, two of which are related to the presence of HPV and the third is the recurrent genetic alterations not linked to HPV infection. Several chromosomal regions with recurrent loss of heterozygosity (LOH) in cervical cancer have been identified. However; the putative tumor suppressor genes located in these chromosomal locations are yet to be identified. Recurrent amplifications have been mapped to the short arm of chromosome 3 in invasive cancer. Microsatellite instability and mutator phenotype do not play a major role in cervical carcinogenesis. As in other cancers, cervical cancer too requires the accumulation of genetic alterations for carcinogenesis to occur. Identification of these alterations could help to provide a better understanding of the disease and thus improve treatment.

Nuclear matrix bound DNA polymerase-beta in mouse fibrosarcoma: effect of gamma-radiation.

Nuclear matrices isolated from the mouse fibrosarcoma tumour cells contain the eukaryotic replicative enzyme DNA polymerase-alpha and the presumptive repair enzyme DNA polymerase-beta. Exposure of tumors to various doses of gamma-radiation (1.95 to 6.5 Gy) causes a 2-fold increase in the levels of only DNA polymerase-beta in the nuclear matrix. The increase in the levels of this enzyme is not discernible if the matrices are isolated 24 hr after irradiation. The rise in the levels of the repair enzyme DNA polymerase-beta could be indicative of radiation stress response of the tumour cells and their repair ability.

Mitochondrial genome organization and cytoplasmic male sterility in plants.

Plant mitochondrial genomes are much larger and more complex than those of other eukaryotic organisms. They contain a very active recombination system and have a multipartite genome organization with a master circle resolving into two or more subgenomic circles by recombination through repeated sequences. Their protein coding capacity is very low and is comparable to that of animal and fungal systems. Several subunits of mitochondrial functional complexes, a complete set of tRNAs and 26S, 18S and 5S rRNAs are coded by the plant mitochondrial genome. The protein coding genes contain group II introns. The organelle genome contains stretches of DNA sequences homologous to chloroplast DNA. It also contains actively transcribed DNA sequences having open reading frames. Plasmid like DNA molecules are found in mitochondria of some plants Cytoplasmic male sterility in plants, characterized by failure to produce functional pollen grains, is a maternally inherited trait. This phenomenon has been found in many species of plants and is conveniently used for hybrid plant production. The genetic determinants for cytoplasmic male sterility reside in the mitochondrial genome. Some species of plants exhibit more than one type of cytoplasmic male sterility. Several nuclear genes are known to control expression of cytoplasmic male sterility. Different cytoplasmic male sterility types are distinguished by their specific nuclear genes (rfs) which restore pollen fertility. Cytoplasmic male sterility types are also characterized by mitochondrial DNA restriction fragment length polymorphism patterns, variations in mitochondrial RNAs, differences in protein synthetic profiles, differences in sensitivity to fungal toxins and insecticides, presence of plasmid DNAs or RNAs and also presence of certain unique sequences in the genome. Recently nuclear male sterility systems based on (i) over expression of agrobacterial rol C gene and (ii) anther specific expression of an RNase gene have been developed in tobacco and Brassica by genetic engineering methods.

Chemical radiosensitization by misonidazole: production and repair of DNA single-strand breaks in Yoshida ascites tumor cells.

Formation of strand-breaks in DNA and its repair in Yoshida ascites tumor cells exposed to gamma radiation (100-400 Gy) in presence and absence of misonidazole (10 mM) were studied. The methodology involved pre-labelling of cellular DNA by 3H-thymidine during cell proliferation in rats, irradiation of cells in vitro and analysing sedimentation profile of DNA by ultracentrifugation in alkaline sucrose density gradients. Irradiation under euoxic conditions resulted in formation of about 1.5 times greater number of strand breaks as compared to those formed during irradiation under hypoxic conditions. Misonidazole (10 mM) by its presence along with the cells during irradiation under hypoxic conditions caused a 3-fold increase in the number of single strand breaks, but under euoxic conditions of irradiation the presence of misonidazole did not enhance the strand break formation. Incubation of cells irradiated in absence of misonidazole for 1 hr in tissue culture medium at 37 degrees C resulted in repair of substantial fraction of the strand breaks while there was no repair of the DNA strand breaks in cells irradiated in the presence of the chemical.

Dipyrone-induced changes in DNA repair and other cell membrane associated processes in Escherichia coli.

The analgesic, dipyrone (l,phenyl 2,3 dimethyl 5 pyrazolone 4 methyl amino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase a cell membrane associated enzyme.