Showing papers by "Tata Memorial Hospital published in 2002"

Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population

Abstract: This study evaluates the influence of genetic polymorphism at GSTM1, GSTM3 and GSTT1 gene loci on oral cancer risk among Indians habituated to the use of, smokeless tobacco, bidi or cigarette. DNA extracted from white blood cells of 297 cancer patients and 450 healthy controls by the proteinase K phenol-chloroform extraction procedure were analyzed by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) analyses. Lifetime tobacco exposure was evaluated as a risk factor in relation to the polymorphism at the GST gene loci using logistic regression analysis. There was no significant difference in the distribution of the GSTM3 and GSTT1 genotypes between oral cancer patients and controls. In contrast, a significant 3-fold increase in risk was seen for patients with the GSTM1 null genotype (age adjusted OR = 3.2, 95% CI 2.4-4.3). The impact of the GSTM1 null genotype on oral cancer risk was also analyzed in separate groups of individuals with different tobacco habits. The odds ratio associated with the GSTM1 null genotype was 3.7 (95% CI 2.0-7.1) in tobacco chewers, 3.7 (5% CI 1.3-7.9) in bidi smokers and 5.7 (95% CI 2.0-16.3) in cigarette smokers. Furthermore, increased lifetime exposure to chewing tobacco appeared to be associated with a 2-fold increase in oral cancer risk in GSTM1 null individuals. The results suggest that the GSTM1 null genotype is a risk factor for development of oral cancer among Indian tobacco habitues.

Poor-prognosis high-grade gliomas: evolving an evidence-based standard of care

Abstract: Patients with high-grade glioma (HGG) can be classified as having a favourable prognosis (younger or with good performance status) or a poor prognosis (older or with poor performance status) with median survival of 12-24 months and 6-9 months, respectively. The standard management for the favourable subgroup is maximum safe resection followed by adjuvant conventionally fractionated radio therapy, with or without chemotherapy. However, most patients with HGG have a poor prognosis and their optimum management has yet to be defined. In the poor-prognosis HGG subgroup, short-course radiotherapy is equivalent to conventional radiotherapy in terms of survival and palliation (level II evidence), but chemotherapy is not recommend ed (level II evidence). The problems with the existing systems of prognosis are discussed and a pragmatic system proposed. Owing to lack of any level I evidence, the need to conduct prospective randomised trials with quality of life and palliative effect as primary endpoints is emphasised. Until such time, maximum safe resection followed by a short course of focal radiotherapy is recommended as the standard of care in poor prognosis HGG.

Palliation of advanced/recurrent esophageal carcinoma with high-dose-rate brachytherapy

Abstract: Purpose: The aim was to assess the improvement in swallowing status, complication rate, and overall survival. Patients and Methods: Fifty-eight patients with advanced/recurrent esophageal carcinoma were treated for palliation with high-dose-rate intraluminal brachytherapy (HDR-ILRT) with a remote afterloading microSelectron unit (192Ir source) with or without external radiation from November 1994 to May 2000 at the Tata Memorial Hospital. The mean age was 64 years. The mid-third of the esophagus was involved in 38 patients (66%). The group was comprised of 37 previously untreated patients (29 with ≤50% Karnofsky performance status and old age, 4 with metastatic disease, and 4 with second primary esophageal lesions) and 21 patients with post-treatment recurrent tumors. Thirty-eight patients (65%) received intraluminal brachytherapy alone, whereas the remaining 20 patients (35%) received a combination of external and intraluminal radiation therapy. All patients received 2 fractions of HDR-ILRT 1 week apart with 600 cGy per fraction at 1 cm off axis. Results: Overall improvement in swallowing status was seen in 22 patients (48%), and 24 (41%) maintained pretreatment swallowing status. Median dysphagia-free survival was 10 months. Overall complication rates were 30%, with stricture seen in 9 patients (15%), ulceration in 6 (10%), and tracheo-esophageal fistula in 3 patients (5%). Complication rates were higher in the post-treatment group (38%) than in the previously untreated group (27%) (p = 0.29). The median overall survival for the entire group was 7 months. Median survival was better, although not significantly, for the previously untreated cohort: 7.8 months vs. 6 months for the post-treatment group (p = 0.77). Conclusion: HDR-ILRT brachytherapy achieves good palliation with acceptable complications in advanced/recurrent esophageal carcinoma.

A case-control study of stomach cancer in Mumbai, India.

Abstract: Stomach cancer incidence rates are much lower in India than elsewhere, but the stomach remains one of the 10 leading sites of cancer in both sexes in most of the metropolitan registries. This is an unmatched case-control study of stomach cancer carried out at Tata Memorial Hospital (TMH), Mumbai. Our purpose was to identify the association of tobacco and alcohol use, occupational hazards, diet, consumption of beverages like tea and coffee, the living environment, cooking media and literacy with stomach cancer. Our study included 170 stomach cancer cases and 2,184 hospital controls interviewed during the period 1988-1992. Tobacco chewing, bidi or cigarette smoking and alcohol drinking did not emerge as high risk factors for stomach cancer. Consumption of dry fish at least once a week compared to never or once a every 2 weeks showed a 12-fold excess risk (OR = 12.4, 95% CI 7.0-22.1, p < 0.0001) for stomach cancer among the nonvegetarian food items considered. A protective effect of tea consumption (OR = 0.4, 95% CI 0.2-0.9, p = 0.03), showing 59% reduction in risk, was identified, which could be of use for possible control and prevention of this cancer.

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer.

Abstract: Purpose:This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response.

Expression of bcl-2 and bax in chewing tobacco-induced oral cancers and oral lesions from India.

Abstract: Deregulation of oncogenes and tumor suppressor genes involved in apoptosis has been associated with tumor development and progression. To investigate the involvement of apoptosis regulating proteins in oral cancer in Indian patients, primarily associated with chewing tobacco habits, immunohistochemical expression of bcl-2 and bax was examined in 63 oral squamous cell carcinomas, and 31 putative premalignant lesions. Our studies revealed overexpression of tumor specific cytoplasmic bcl-2 in 56% and bax in 43% oral cancers. The oral cancers in the Indian patients are preceded by premalignant oral lesions; hence oral lesions were examined for bcl-2 and bax expression. We observed aberrant expression of bcl-2 in 16% oral lesions comprising leukoplakias and SMF and bax in 55% oral lesions. We have already reported, p53 expression in these oral cancers and lesions. It was noteworthy that 30% oral cancers demonstrated a p53+bcl2+ pattern, and 14% samples exhibited p53+bcl2+bax+ pattern. However, none of the oral lesions showed concurrent deregulation of p53 and bcl-2 or all the three genes. Interestingly 45% oral lesions were p53-bax+ as compared to 18% oral cancers; while 39% oral lesions were bcl2-bax+ as compared to 14% oral cancers, indicating overexpression of bax in oral lesions, in the absence of p53 and bcl-2 proteins. Significant correlation was observed between positive nodal status and bcl2+ (p=0.047) and p53+bcl-2+ (p=0.01) in oral cancers. Kaplan Meier survival analysis showed significantly (p=0.059) higher survival in patients with p53-oral tumors than with p53+ tumors. Our studies thus indicate frequent overexpression of apoptosis regulators bcl-2, bax and p53 proteins in oral cancers, and a subset of oral lesions, representing early events in oral carcinogenesis. The aberrant bcl-2 expression and loss of p53 function observed, may play an important role in the tumorigenesis of oral cancers by allowing escape from apoptosis and enabling additional genetic alterations to accrue.

Bcl-2 family of proteins in indolent B-cell non-Hodgkin's lymphoma: study of 116 cases

Abstract: The bcl-2 family of proteins comprises both antagonists and agonists of apoptosis. We have investigated whether subsets of indolent B-cell non-Hodgkin's lymphoma (IB-NHL) differ in the expression of the bcl-2 family members; 116 cases of IB-NHL, composed of chronic lymphocytic leukemia (CLL, n = 48), follicular lymphoma (FL, n = 38), marginal zone B-cell lymphoma (MZBCL, n = 15), and mantle cell lymphoma (MCL, n = 15), were investigated for expression of bcl-2, bcl-X, mcl-1, bax, and bak proteins by immunohistochemistry. Expression of bcl-2 and bcl-X proteins was moderate/high among most IB-NHLs. Expression of mcl-1 was low/absent in most cases of CLL and MCL and low/moderate in most cases of FL and MZBCL. Most MCLs did not express bax protein. Bax expression was absent/low among most cases of CLL and low/moderate among most cases of FL and MZBCL. Expression of bak was moderate/low among most cases of CLL, MZBCL, and MCL but was absent/low among most cases of FL. The different subsets of IB-NHLs differ in their expression of mcl-1, bax, and bak proteins. Am. J. Hematol. 70:278–282, 2002. © 2002 Wiley-Liss, Inc.

Efficacy of intravenous ketoprofen for pre-emptive analgesia.

Abstract: AIM: To determine whether intravenous ketoprofen is effective as pre-emptive analgesia for breast surgery. DESIGN: Randomised, controlled, double blind study. PATIENTS AND METHODS: 50 patients undergoing breast surgery under general anaesthesia randomised to receive either 100 mg intravenous ketoprofen 30 minutes before (Group I), or immediately after surgical incision (Group II). Postoperatively, pain scores (Visual Analogue Scale, VAS) and time to rescue analgesic were recorded by an independent, blinded observer. The study was terminated when rescue analgesic was required (VAS > or =4 or demand for analgesic). STATISTICAL ANALYSIS: Continuous variables were analysed by the unpaired 't' test, discrete variables with the chi square test, and survival curves by the log-rank test. RESULTS: Pain scores were significantly lower in Group I till 10 hours after surgery. The number of patients requiring analgesia at 4, 6, 8 and 10 hours was significantly lower in group I (0% vs. 47% [P <0.0001], 0% vs. 44% [P <0.003], 0% vs. 80% [P <0.0001], 0% vs. 100% [P <0.0001] respectively). The mean time for rescue analgesic was 15.47 -/+ 2.87 hours in group I versus 4.22 -/+ 2.55 hours in group II (P <0.0001). CONCLUSION: Pre-emptive analgesia with Intravenous ketoprofen (100mg) produces better postoperative pain-relief in patients undergoing breast surgery.

Progesterone Receptor as an Indicator of Sperm Function

Abstract: Expression of progesterone receptor (PR) localization on spermatozoa was determined in men with normal and abnormal spermiograms. Studies were also carried out to evaluate the potential of PR as a marker of sperm function. Progesterone receptor expression on spermatozoa from men with normozoospermia (n = 8), oligozoospermia (n = 7), asthenozoospermia (n = 8), oligoasthenozoospermia (n = 7), and teratozoospermia (n = 11) was analyzed using an immunocytochemical method with monoclonal antibodies against PR, and flow cytometry using a cell-impermeable fluorescein-tagged progesterone coupled to BSA complex (P-FITC-BSA). Both methods revealed significantly fewer (P < 0.05) PR-positive spermatozoa in men with oligozoospermia, asthenozoospermia, oligoasthenozoospermia, and teratozoospermia compared with men with normozoospermia, thereby suggesting that down-regulation of PR expression in spermatozoa may be one of the causes of male infertility. Spermatozoa from men with normozoospermia (n = 12), oligozoospermia (n = 12), asthenozoospermia (n = 12), oligoasthenozoospermia (n = 9), and teratozoospermia (n = 10) were exposed to low osmotic conditions in the hypoosmotic swelling (HOS) test and then analyzed for PR expression using P-FITC-BSA complex. A significantly higher percentage (P < 0.05) of spermatozoa with physiologically active plasma membrane (HOS+) lacked PR expression (HOS+PR-) in all categories of men with infertility, thereby suggesting that compared to the HOS test, PR expression is a better indicator of sperm function. Furthermore, PR expression in spermatozoa showed a strong (P < 0.05) positive correlation with their ability to undergo an in vitro acrosome reaction. This was observed in all study groups (i.e., normozoospermia, r = 0.8545; oligozoospermia, r = 0.8711; asthenozoospermia, r = 0.7645; oligoasthenozoospermia, r = 0.9003; and teratozoospermia, r = 0.8676). This suggests a potential role for PR in the events leading to the acrosome reaction in sperm.

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette‐Guérin (Danish 1331 strain)

Abstract: Objective To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guerin (BCG, Danish 1331 strain) after complete transurethral resection Patients and methods Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival Results Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR) Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR Conclusion This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients

Lymphoid neoplasms in HIV-positive individuals in India.

Abstract: The HIV epidemic in the Asian subcontinent has a significant impact on India. Patients with AIDS have an increased risk of developing non-Hodgkin lymphoma (NHL). In this study, we have investigated the pattern of distribution of lymphoid neoplasms and also studied the Epstein-Barr virus (EBV)-association and p53 expression in 35 HIV-positive patients from India. The biopsy samples were studied for histology and for expression of CD20, CD3, CD15, CD30, light chains, CD138, bcl-6, epithelial membrane antigen, EBV-latent membrane protein-1, and p53 protein. In situ hybridization was performed with digoxigenin-labeled anti-sense EBV-encoded nuclear RNA-1 (EBER-1) probe. Polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections for EBV-subtype analysis. The 35 cases included 7 cases of Hodgkin disease (HD), 4 cases of plasmacytoma (PL), and 24 cases of NHL. Among the cases of NHL, 3 were Burkitt lymphoma (BL), 4 were diffuse large B-cell lymphoma (DLBL) of centroblastic type (CBL), 10 were DLBL of immunoblastic type (IBL), 4 were high-grade B-cell lymphoma (unspecified) and the rest were other subtypes. EBV-association was noted in all cases of HD, 2 of 3 BL, and 3 of 10 IBL. PCR analysis of the EBNA-3C gene revealed amplimers corresponding to type A. A p53 protein overexpression was noted in 6 of 10 IBLs, 1 of 3 BLs, 2 of 3 CBLs, and 5 of 7 cases of HD. This is the first reported study of lymphoid malignancies in HIV-positive individuals from India.

The prevalence of high-grade prostatic intraepithelial neoplasia in surgical resection specimens: an Indian experience.

Abstract: BACKGROUND To the authors' knowledge there is a paucity of literature regarding the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in the Indian subcontinent. The objective of the current study was to document the prevalence of HGPIN in a low-risk Indian population. METHODS A total of 110 prostate specimens (61 taken from the test group and 49 taken from the control group) were studied to document the prevalence of HGPIN in a low-risk Indian population. RESULTS None of the benign prostate samples were found to harbor HGPIN, whereas 85.24% of the samples from malignant prostates did so. CONCLUSIONS A strong correlation between HGPIN and invasive carcinoma was observed, a finding that reinforces the view that HGPIN is a strong indicator of concurrent invasive prostate carcinoma. Cancer 2002;94:2350–2. © 2002 American Cancer Society. DOI 10.1002/cncr.10495

Sentinel lymph node detection in canine oncological patients.

Abstract: BACKGROUND: Sentinel lymph node detection was investigated in dogs with spontaneously occurring tumours. MATERIAL AND METHODS: In this pilot study, 24 client-owned spontaneously tumorous dogs presented for sentinel lymph node detection. A multiple method was used with a nuclear medicine technique (injection of 99mTc human serum albumin colloid) with scintigraphy and intraoperative guidance, and blue dye injection. RESULTS: Of the 35 lymph nodes histologically demonstrated to contain metastases, 34 (97%) were found by radioguided surgery, which means that one would have been missed in the intraoperative localisation process; 31 nodes (89%) were clearly visualised in the gamma camera images; only 27 (77%) were blue-stained by vital dye; a mere 8 lymph nodes (23%) were enlarged and therefore easily detectable by palpation. CONCLUSIONS: Data obtained from the harmless application of the sentinel node concept are useful for the radiopharmaceutist. The sentinel lymph node concept is well applicable in the veterinary clinic.

Near‐Total Laryngectomy in Advanced Laryngeal and Pyriform Cancers

Abstract: Objective To demonstrate the oncologic and physiological safety of near-total laryngectomy (NTL), its success in voice conservation, and its versatility for use in extensive resections that necessitate pharyngoplasty, and even in post-radiation recurrences. Study In this study of 137 cases of NTL for cancer of the larynx (45 cases) and pyriform (92 cases), 86.9% were stage T3/T4 and 60.6% were N+. A total of 8.8% had extended pharyngeal resections necessitating patch pharyngoplasty (ENTLP). In 10.9% cases, NTL was used as salvage of post-radiation failures. Concurrent neck dissection was performed in 99 cases. Results A total of 70.1% was alive and disease-free at the last follow-up ranging from 12 months to 104 months (median, 35 mo). A total of 7.3% had local/locoregional recurrences and 11.7% had purely regional recurrences. The local control rate for post-radiation salvage with NTL was 93.3%. A total of 88.6% developed communicable speech, and the speech success rate was 100% in 12 cases of ENTLP. Complications included major wound dehiscence with total shunt breakdown in 2 cases (1.5%), pharyngeal leak requiring surgical intervention in 7 cases (3.6%), significant aspiration through the shunt necessitating completion laryngectomy in 1 case (0.7%), and complete shunt stenosis in 9 cases (6.6%). Conclusion The study shows that NTL is an oncologically safe voice conservation procedure in advanced, lateralized laryngeal and pyriform cancers treated not only per primum, but also in carefully selected post-radiation failures. It has a high success rate of speech development even in those cases requiring extensive pharyngeal resections. Major complications were acceptably low.

Effective rehabilitation after partial glossectomy.

Abstract: Objective The surgical treatment of cancer of tongue results in speech deficits. Speech disorders in the glossectomised patients fall into, categories of impaired articulation, reduced speech intelligibility, altered oral & nasal resonance, impaired voice quality & reductions in global speech proficiency. Since speech is a social tool, its most significant measurements start with the degree to which it can be understood.

Hypofractionated radiotherapy in carcinoma cervix IIIB: Tata Memorial Hospital experience.

Abstract: Purpose of the study To analyze the role of hypofractionated radiotherapy in advanced carcinoma of cervix. Basic procedure Medical records of 62 women with advanced carcinoma cervix III3 treated during 1994-1996 were reviewed. Patients were treated with standard pelvic portals to a total dose of 39Gy in 13 fractions over 17 days followed by intracavitary brachytherapy. Forty-eight patients completed the planned treatment and were considered suitable for analysis of late reactions and survival. Main findings The 5-year disease free survival was 59% and the overall survival was 50% at the mean follow up of 40 months. Twenty-one (44%) patients developed acute gastrointestinal toxicity of which 5 patients had grade III and one patient had grade IV reaction. Ten patients (21%) developed acute genitourinary complications, 13 patients (27%) had late rectal reactions and 10 patients (20%) had late bladder complications. Three patients had grade I, five had grade II and five had grade III late rectal toxicity. Conclusion Survival in patients treated hypofractionated radiotherapy appears comparable to that of standard fractionation. The acute gastrointestinal and skin reactions were mainly grade I or grade II. Hypofractionated radiotherapy can certainly be considered in a select group of patients where the local disease is extensive and is unsuitable for conventional treatment.

The detection of HBV antigens and HBx-transcripts in an Indian fibrolamellar carcinoma patient: a case study.

Abstract: Fibrolamellar carcinoma (FLC) of the liver is a rare variant of hepatocellular carcinoma (HCC). Here we report the case of a 12-year-old Indian male with typical FLC with no apparent hepatitis B virus (HBV) infection and a non-cirrhotic liver. The patient, though seronegative for HBsAg, showed expression of HBcAg in both the liver and tumour tissue. RT-PCR analysis revealed the presence of full-length HBx-transcripts in both liver/tumour tissue, along with truncated HBx-transcripts only in the tumour tissue. The lymphocytes in both peripheral and liver/tumour compartments showed a proliferative response to either/or HBcAg and HBxAg, which could be further augmented on addition of rIL-2. This is the first study to show not only the presence of HBcAg in the liver/tumour tissue but also prior exposure of the FLC patient's lymphocytes to HBV antigens. Also, the presence of the full-length and truncated HBx-transcripts in the tumour tissue, a proposed tumorigenic marker for hepatocarcinogenesis in chronic HBV patients, suggests an oncogenic role of HBV in this rare variant of HCC.

Late splenic metastasis after curative resection for oesophageal carcinoma.

Abstract: The spleen is an unusual site of distant metastasis from solid tumours. While contiguous involvement of the spleen may occur in tumours arising from the stomach, pancreas or colon; the spleen as the seat of distant metastasis is a rare occurrence. We report herewith one such instance of metastatic involvement of the spleen in an operated case of carcinoma oesophagus.

Regional variation in the distribution of subtypes of lymphoid neoplasms in India.

Abstract: Lymphoid malignancies (LM) are a heterogeneous group of tumours. The relative frequencies of the various types of LMs vary across geographic regions. The pattern in India shows significant differences from the rest of the world. As India is a vast country, we set out to investigate whether there are regional differences in the relative frequencies of the various LMs. A total of 562 LMs from three different regions in India--Barshi (western India, 102 cases), Pondicherry (southern India, 156 cases) and Jaipur (northern India, 304 cases) were analysed according to the WHO classification. The non-Hodgkin lymphoma (NHL) to Hodgkin disease (HD) ratio was 6.28 in Barshi, 1.26 in Pondicherry and 2.27 in Jaipur. The frequency of HD's various subtypes did not significantly differ among the three regions. While T-cell NHLs constituted only 12.5% of NHLs at Barshi, they accounted for 31 and 27.5% of all NHLs at Pondicherry and Jaipur, respectively. There were also notable differences in the specific subtypes of NHL between the three different geographic regions in India.

Leydig cell tumor: a case report and review of the literature.

Abstract: We report a case of Leydig cell tumor, which is a rare testicular neoplasm. Most of them are benign. Malignant Leydig cell tumor is associated with a poor prognosis. The clinical features and treatment of Leydig cell tumor are discussed in this case report.