Showing papers by "Tata Memorial Hospital published in 2000"

Primary Ewing's sarcoma of the cranium.

Abstract: OBJECTIVE: We analyzed the data for a series of 14 patients with primary Ewing's sarcomas of the cranium who were treated since 1985. Our aim was to assess the long-term outcomes and the selection of appropriate treatment methods. METHODS: The patients were reviewed with respect to their clinical presentations, treatment, and outcomes. Computed tomographic scanning of the brain was performed for all patients. Skeletal surveys with routine radiographs and technetium-99 bone scans to detect extracranial Ewing's sarcomas were performed for all patients. For all 14 patients, radical tumor excision was achieved surgically. All patients were then subjected to adjuvant multidrug chemotherapy and radiotherapy. The follow-up periods ranged from 8 months to 8 years (mean, 4.25 yr). RESULTS: The predominant presenting features were headaches, increased intracranial pressure, and scalp swelling. Excision was nearly total for nine patients and total for five patients. All patients experienced uneventful postoperative courses. One patient experienced a local recurrence, which was detected 2 years after surgery. This recurrent tumor was completely excised, and additional chemotherapy was administered. Eight of the 14 patients (57.1%) studied have survived 5 years or longer. CONCLUSION: Although primary Ewing's sarcoma of the cranium is a malignant bone tumor, it is associated with a good prognosis when treated with radical surgery, aggressive multidrug chemotherapy, and radiotherapy.

Prognostic factors in head and neck soft tissue sarcomas

Abstract: BACKGROUND Soft tissue sarcomas of head and neck constitute a heterogeneous group of rare malignant tumors occurring at rare sites. The purpose of this retrospective study is to evaluate the pathologic features, treatment modalities, outcome, patterns of failure, survival, and other prognostic factors. METHODS The medical records of 72 patients whose tumors were diagnosed as head and neck sarcomas, treated at Tata Memorial Center between 1981 to 1995 were reviewed. Potential prognostic factors including age, gender, tumor size, histology, grade, and adjuvant treatment were evaluated. RESULTS The overall and disease free survival at 5 years was 60% and 45%, respectively. The median survival and follow-up was 76 and 38 months, respectively. Thirty-two patients (44.4%) developed recurrence of which 13 patients were salvaged. The univariate and multivariate analysis showed tumor size and grade as important prognostic factors for the survival. CONCLUSIONS Tumor size greater than 5 cm and high grade tumors were important prognostic factors for survival. Every effort should be made for early diagnosis and wide surgical excision. For localized recurrent tumors without evidence of distant metastasis, surgery should be attempted whenever possible. High rates of locoregional failure in head and neck area indicate the need for improved treatment strategies. Cancer 2000;89:868–72. © 2000 American Cancer Society.

Is clinical breast examination an acceptable alternative to mammographic screening

Abstract: Breast cancer screening and mammography have almost become synonymous in the public perception, yet this should not necessarily be the case. Ideally, a screening tool for breast cancer would reduce mortality from breast cancer while having a low false alarm rate and being relatively cheap. Screening should not be at the expense of the symptomatic services nor inappropriately divert scarce resources away from equally deserving areas of the NHS that are less politically sensitive.1 An ideal screening test would be simple, inexpensive, and effective. Of the three modalities of breast cancer screening—breast self examination, clinical breast examination, and mammography—breast self examination fulfils the first two criteria, but early results of two randomised trials conducted in Russia and China suggest that it would not be effective in reducing mortality from breast cancer. 2 3 Clinical breast examination is also relatively simple and inexpensive, but its effectiveness in reducing mortality from breast cancer has not been directly tested in a randomised trial. Mammography is complex, expensive, and only partially effective. We believe that there is sufficient circumstantial evidence to suggest that clinical breast examination is as effective as mammography in reducing mortality from breast cancer and that the time has come to compare these two screening methods directly in a randomised trial. #### Summary points The goal of breast screening is to prevent death and not simply to detect cancers by mammography Mammography does detect some cancers “early,” but many of these are not potentially lethal and their detection causes needless anxiety Clinical breast examination is more likely to detect cancers that are potentially lethal Results of the second Canadian national breast screening study suggest that mammographic detection of cancers that are not palpable does not affect mortality New GMC guidelines on informed consent state that women in the NHS breast screening programme should …

Primary carcinoma of the vagina: Tata Memorial Hospital experience

Abstract: Purpose: Carcinoma of the vagina is a rare gynecological malignancy comprising approximately 2% of all the gynecological malignancies. We have analyzed the treatment outcome of the patients treated at the Tata Memorial Hospital from January 1984 to December 1993. Methods and Materials: In this 10-year period, 134 patients of primary vaginal cancers were registered at our hospital. Of these, 75 patients received complete treatment and are analyzed. Results: Disease-free survival (DFS) for the whole group is 50%, and overall survival (OAS) is 60%. Most locoregional recurrences and distant failures are noted in the 2 years following treatment. DFS at 5 years is as follows: Stage I (5 patients), Stage IIA (37 patients), Stage IIB (15 patients), Stage III (14 patients), and Stage IV (4 patients); are 40%, 55%, 60%, 50%, and 25%, respectively. The DFS for patients with complete response (42 patients) to external radiation at 5 years is 68%, with partial response (25 patients) is 35%, and with poor or no response (6 patients) is 18% ( p = 0.0000). We observed that brachytherapy was an important part of the treatment, and patients who received brachytherapy (59 patients), either with a vaginal intracavitary applicator (30 patients) or interstitial implant (29 patients) had a DFS of 53% and 56%, respectively, while 15 patients who received external radiation alone had a DFS of 30%. Patients receiving brachytherapy within 4 weeks of external radiation had a DFS of 60% as compared to 30% when the interval was more than 4 weeks. Conclusion: The factors indicating prognosis are: site and extent of involvement, presence of lymph nodes at presentation, technique of brachytherapy, and interval between external radiation and brachytherapy.

Epidemiology of digestive tract cancers in India. VI. Projected burden in the new millennium and the need for primary prevention.

Abstract: The incidence rates of most digestive cancers in India are moderate or low. The highest rates are recorded in the urban population of Mumbai and the lowest in the rural population of Barshi in Maharashtra state. The rates will rise as the life expectancy of Indians increases along with urbanization and, within the next few decades, may reach those recorded in Indians living abroad. Based on available population data, we estimate that in the year 2001 there will be approximately 145,000 new cases of digestive cancers in India. In men, the esophagus would be the commonest site (n = 24,925), followed by the stomach (23,100), rectum (10,462), liver (8812), colon (8004), pancreas (5757) and gall bladder (3967). In women, the esophagus would be the commonest site (n = 18,608), followed by the stomach (11,890), gall bladder (7360), rectum (6983), colon (6115), liver (4227) and pancreas (3435). The incidence of cancers of the esophagus and stomach is declining spontaneously in India. It may be possible to accelerate this by reducing the use of tobacco and improving the diet. At the same time the incidence of cancers of the colon, pancreas, liver and gall bladder is rising, largely due to urbanization that leads to major changes in the diet and personal habits. A preventive approach is needed by public health education. Indians should be encouraged to retain their traditional protective diets, eat more fruits and vegetables, do more physical activity, and abstain from tobacco. Gastroenterologists can also help in secondary prevention by screening high-risk individuals, e.g., patients with chronic liver disease for liver cancer and relatives of patients with familial bowel cancer.

Radiation therapy in T1-T2 glottic carcinoma: influence of various treatment parameters on local control/complications.

Abstract: Purpose: To evaluate the influence of various treatment parameters on local control as well as complications in T1 and T2 glottic carcinomas. Methods and Materials: Between 1975 and 1989, 676 patients with early glottic carcinoma (460 T1 and 216 T2) received curative radiation with three different treatment regimens, as follows: Regimen 1—50 Gy/15 Fr/3 weeks (3.33 Gy/daily) for 192 patients; Regimen 2—60–62.5 Gy/24–25 Fr/5 weeks (2.5 Gy/daily) for 352 patients; and Regimen 3—55–60 Gy/25–30 Fr/5–6 weeks (2–2.25 Gy/daily) for 132 patients. Results: The local control at 10 years was 82% and 57% for T1 and T2 lesions respectively ( p = 0.0). For the T1N0M0 group, field size had significant impact on local control with both univariate ( p = 0.05) and multivariate ( p = 0.03) analysis. For T2N0M0, group field size ( p = 0.03) as well as registration year ( p = 0.016) were significant in univariate analysis whereas only field size remained significant on multivariate analysis. Persistent radiation edema was noted in 146 (22%) patients and was significantly worse with larger field size ( p = 0.000) but not related to different treatment regimens. Conclusion: The shorter fractionation schedule had comparable local control, without increased complications in comparison to the protracted schedule and is best suited for a busy department.

γδ T cells lyse autologous and allogenic oesophageal tumours: involvement of heat-shock proteins in the tumour cell lysis

Abstract: T cells expressing γδ receptors were isolated from the peripheral blood of oesophageal cancer patients and analysed for their potential to lyse tumour targets. Immunophenotyping by flow cytometry showed that the dominant population of γδ T cells expressed the Vγ9 and the Vδ2 T cell receptor, and a minor population expressed the Vδ1 receptor. Cytotoxicity assays revealed that activated γδ T cells lysed Daudi Burkitt's lymphoma and K562 cells. Lysis of autologous oesophageal tumours was higher than of allogenic tumours. Anti-hsp60 and anti-hsp70 mAb significantly inhibited the cytotoxicity of γδ T cells to both autologous and allogenic oesophageal tumours. Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry. In conclusion, γδ T cells isolated from the peripheral blood of oesophageal cancer patients have the ability of kill oesophageal tumour cells. The lysis of tumour targets by the γδ T cells is brought about via recognition of heat-shock proteins expressed on the surface of tumour cells. γδ T cells isolated from the peripheral blood may have applications in adoptive immunotherapy of oesophageal cancer.

Scrape cell-block technique for fine needle aspiration cytology smears.

Abstract: An inconclusive diagnosis on fine needle aspiration cytology (FNAC) may be due to poor spreading and presence of thick tissue fragments despite aspiration of adequate material. Repeat aspiration may not be possible especially when aspirates of deep seated organs have been obtained by image guided techniques. We have resorted to a 'scrape cell-block' (SCB) technique in such cases. In this technique the cellular material on the slides which had already been fixed and stained, was carefully removed by scraping following destaining and then processed as a cell block. SCB interpretation was then compared with the smear diagnosis and histological diagnosis, wherever available. A total of 27 cases were studied. In 12 cases SCB slides added information to the FNAC smears. In 14 cases SCB did not offer any additional information. SCB was inconclusive in one case. Final histological correlation was available in eight cases and the SCB diagnosis was confirmed in six cases, whereas in two cases SCB failed to identify the tumour. Immunocytochemistry (ICC) was done in one case. SCB is a useful technique to make the best use of the available material when reaspiration is difficult.

Late esophageal toxicity using a combination of external beam radiation, intraluminal brachytherapy and 5-fluorouracil infusion in carcinoma of the esophagus.

Abstract: One hundred patients with potentially curable squamous cell carcinoma of the esophagus were treated using a combination of external beam radiation, medium-dose intraluminal brachytherapy (ILBT), and 5-fluorouracil infusion (as a radiosensitizer) from January 1990 to December 1993 The main objective was to determine late toxicity and optimization of the dose of intraluminal radiation All patients had external radiation of 50 Gy over 5 1/2 weeks, followed by ILBT of 20 Gy for 50 patients (group 1) and 15 Gy for a subsequent 50 patients (group 2), using a dose rate of 315-330 cGy/h with the prescription at 1 cm off axis The 5-fluorouracil infusion was 500 mg/m2 administered 12 h prior to ILBT The treatment-related complications among groups 1 and 2 were strictures 24% vs 8% (p = 0029), ulceration 30% vs 28% (p = 08), and tracheoesophageal fistulae 12% for both groups The overall survival for groups 1 and 2 was 8% and 23% at 5 years The development of life-threatening complications is a major concern and extreme caution is urged before selecting patients for a combination of ILBT and 5-fluorouracil treatment

Cytokeratin expression in human fetal tongue and buccal mucosa.

Abstract: Expression of cytokeratins (CK), a subset of intermediate filament (IF) proteins in epithelia, is developmentally regulated. CK expression may also change after malignant transformation. Our earlier studies on CK expression in human oral tumours and pre-cancerous lesions have shown specific changes in CK expression. We analysed CK expression in human tongue and buccal mucosa (BM) in fetuses in the embryonic age group of 16 to 27 weeks using biochemical and immunohistochemical techniques to find out whether there is any similarity in CK expression in human oral squamous cell carcinomas (SCC) and fetal oral tissues. CK 1, 8 and 18 were detected in a majority of samples using both techniques. Our earlier studies had shown aberrant expression of CK 1 and 18 in many of the oral SCC and leukoplakias. Studies by immunohistochemistry showed that these different CK antigens were expressed in different cell layers. CK 1(2) were present in the stratified epithelial layers whereas CK 8 and 18 were restricted to glandular epithelium. Till 27 weeks of gestation, both tongue and BM expressed CK 1, 8 and 18 along with CK 6 and 16. Thus, fetal tissues showed some similarities in CK pattern with their respective SCC.

Clinical significance of lipid profile in cancer patients.

Abstract: In the present study, we have examined lipid profile in normal healthy age matched control and patients with various malignancies. Analysis of data revealed that total lipids, cholesterol and HDL cholesterol levels are inversely associated with incidence of cancer where as triglycerides levels were significantly elevated in cancer patients. Electrophoretic separation of lipoproteins revealed a significant decrease in the mean values of alpha fraction in patients with malignancy when compared with the corresponding control group. The other fractions beta and pre-beta did not show any change in the mean values in patients with cancer as compared to the normal corresponding control group.

Circulating levels of TNFα and TNF receptor superfamily members in lymphoid neoplasia

Abstract: We have correlated the serum levels of TNFα and soluble TNF receptor superfamily members with clinico-pathologic parameters in patients of Hodgkin's disease (HD, N = 26) and non-Hodgkin's lymphoma (NHLs, N = 35). HD patients had significantly higher levels of TNFα, sTNFRI, and sTNFRII in serum while NHL patients had significantly higher levels of sTNFRI, sTNFRII, sCD27, and sFas as compared to controls. In NHL patients the levels of sCD27 correlated directly and significantly with the high-stage disease, bone marrow involvement, lymph nodal presentation, and serum LDH levels. Similarly in NHL patients, levels of sFas also correlated directly and significantly with the presence of high stage disease. HD patients with B symptoms had significantly higher levels of sTNFRII. Am. J. Hematol. 65:105–110, 2000. © 2000 Wiley-Liss, Inc.

Analysis of BRCA1 involvement in breast cancer in Indian women.

Abstract: The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular pathogenesis of breast cancer and was in accordance with its well-documented tumour suppressive function.

A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study.

Abstract: A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

Embryonal rhabdomyosarcoma of prostate in an adult--a diagnostic dilemma.

Abstract: Embryonal rhabdomyosarcoma of the prostate is a rare. Highly malignant tumour. The median age of occurrence is five years, but sporadic cases have been reported in adults' To the best of our knowledge, till date, fewer than ten cases have been reported of which only two are above the age of sixty years. We report a case of embryonal rhabdomyosarcoma of prostate in a patient more than sixty years of age. If one is not aware of this entity, one can make a mistake in the diagnosis as well as treatment.

Avascular Necrosis of Head of Femur in a Patient with Acute Promyelocytic Leukemia

Abstract: Avascular necrosis (AVN) of head of the femur is associated with various pathological conditions and treatment modalities. We present a case of acute promyelocytic leukemia who was treated with all-transretinoic acid (ATRA), daunomycin, cytarabine and a short course of dexamethasone. He developed AVN of bone after 2 years of treatment. Whether this is related to ATRA is dealt with in the discussion.

T-cell Receptor γ and δ Gene Rearrangements in T-cell Acute Lymphoblastic Leukemia in Indian Patients

Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a clonal lymphoid malignancy and junctional sequences of rearranged T-cell receptor (TCR) represent the best suitable marker to study clonality in these patients. A sensitive, non-radioactive, and rapid approach of PCR coupled with heteroduplex analysis was used to analyse clonality of TCR γ and 8 gene rearrangements in 26 Indian T-ALL patients. Amongst TCR γ gene family, Vγ1-Jγ1.3/2.3 sequences were most utilized (53.9%) while from TCRδ repertoire Vδ1-Jδ1 sequences were preferentially rearranged (23.1%) in these patients. 19.2% of Indian T-ALL patients demonstrated both clonal TCR γ and δ gene rearrangements along with surface expression of TCRγδ. Although the majority of T-ALL patients showed surface expression of TCRα β, the small fraction (19.2%) of TCRγδ+ T-ALL represent a distinct subgroup which needs further evaluation.

Hemangiopericytoma of greater omentum.

Abstract: A 67-year-old man presented with a painless abdominal lump. CT scan revealed a large vascular intraperitoneal mass. At laparotomy, a large, vascular tumor was seen to arise from the greater omentum, which was resected. At histology, this tumor was a benign hemangiopericytoma.

Actin polymerization in response to different chemoattractants is reduced in granulocytes from chronic myeloid leukemia patients.

Abstract: Chronic myeloid leukemia (CML), a hematopoietic stem cell disorder, is characterized by the presence of Philadelphia chromosome (Ph 1 ). Earlier studies have shown that various functions, such as chemotaxis, fluid phase pinocytosis, phagocytosis, and degranulation in response to chemotactic peptide formyl-methionylleucyl-phenylalanine (fMLP), were defective in polymorphonuclear leukocytes (PMNL) from CML patients. These functions depend on actin microfilaments (MF). Further studies showed that fMLP-induced actin polymerization was lower in CML PMNL. To see if this defect is specific to stimulation by fMLP alone or is a global phenomenon involving other chemoattractant receptors, chemotaxis and actin polymerization were studied in response to fMLP, an analog of fMLP, formyl-methionine-1 aminocyclooctane 1 carboxylic acid-phenyalanine-O-methionine (FACC 8 ), platelet-activating factor (PAF), and leukotriene B4 (LTB4). These compounds bind to different chemoattractant receptors. Chemotaxis and actin polymerization in response to all four chemoattractants were significantly lower in CML PMNL compared with PMNL from normal subjects and were differentially affected for the different chemoattractants. These results suggest a global phenomenon involving all four chemoattractant-stimulated pathways. This lower amount of F-actin may be responsible for the defective chemotaxis seen in these cells. Cytometry (Comm. Clin. Cytometry) 42:379 ‐386, 2000. © 2000 Wiley-Liss, Inc.

HLA Antigen Distribution in Gujarathi Speaking Hindu Population from Mumbai, Maharastra, India

Abstract: Abstract Four hundred and fourteen unrelated Gujarathi speaking Hindu people residing in Mumbai, Maharastra (Western India) were studied for HLA A, B, C and DR locus antigen profiles. The phenotypic frequenci es of HLA A1, A2, A9, A11, A24, B5, B35, B40, Cw4, DR2, DR3, DR4, DR5 and DR7 were increased while frequencies of HLA A10, A19, A26, A28, A29, B14, B16, B18, B21, B22, B27, B37, Cwl, DR1, DR6 and DR9 were decreased in the Gujarathi speaking Hindus. The genotype frequencies of HLA A3, A9, B18, B21, B22, B40, DR3 and DR5 were increased while that of A19 A2 8 B7 B13, B15, Cw1, Cw2, Cw8, DR1, DR6 and DR9 were decreased when compared with gene frequ encies of other Indian Hindu popu lations reported. Two Locu s h aplotype an aly sis revealed that A1-B17, A10-B8 and A19-B12 were common Indian Hindu haplotypes where as A3-B18, A9-B5 A24-B5 and A11-B62 were unique for the Gujarathi Hindus. Haplotype A2-B40 observed in Gujarathi Hindus were also observed among South Indian Hindus, while A11-B35 have been observed among immigrant Indian Hindus. Another haplotype A3-B7 reported from both south Indian and north Indian Hindus was not observed in Gujarathi Hindus. Significant negative linkage disequilibrium was observed for haplotype A1-B35 in Gujarathi H indus. Thus the observed antigen frequencies and linkage disequilibrium in Gujarathi Hindus suggest the Influence of genetic drift cau sed by selection, geography and culture. Further the study reveals that the Hindu population of India cannot be considered as single panmictic population with reference to genetic characteristics.

IL-12 and IL-2 potentiate the in vitro tumor-specific activity of peripheral blood cells from cervical cancer patients.

Abstract: We have carried out a detailed analysis of the cellular immune functions of cervical cancer patients in comparison with healthy controls. It has been observed that the freshly isolated peripheral blood mononuclear cells (PBMC) exhibit natural cytotoxicity (NC) against a number of targets including tumor cells, mainly delivered by NK cells, which are non-adoptive and MHC unrestricted. Upon stimulation with cytokines like IL-2, IL-7, IL-12, IL-15 and interferons, PBMC acquire lymphokine activated killer (LAK) activity which enables them to lyse a wide range of targets including fresh tumor cells and virally infected cells. We compared the effect of IL-2 and IL-12 on enhancement of NC of PBMC from cervical cancer patients. IL-12 stimulated cultures (CD3+, CD56+) exhibited significant levels of tumoricidal activity. IL-2 stimulated lytic activity sustained even after 10 days while that of IL-12 stimulated cells declined after 6 days. Activation of PBMC was marked by increase in the expression of activation marker CD45RO and adhesion molecules LFA-1alpha, ICAM-1 and CD44. Addition of IL-12 to IL-2 stimulated cultures further enhanced the degree of lytic activity. Our data, thus, provide an evidence that PBMC from cervical cancer patients can be stimulated in response to cytokines and local or systemic treatment with low doses of cytokines may help to yield a better immune response against virus infected tumor cells in cervical cancer.