Showing papers by "Tata Memorial Hospital published in 1991"

The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.

Abstract: DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.

Osteosarcoma of the craniofacial bones: A Clinico-Pathological study

Abstract: Thirty-four cases of osteosarcoma involving the craniofacial bones over a period of 19 years were reviewed. They formed 6.2% of osteosarcomas occurring in the skeleton during the same period at the Tata Memorial Hospital. Mean age of occurrence was 30.9% years, with a range of 7 to 61 years. Male preponderance was noted in maxillary tumours (M:F = 2.6:1), while the mandibular tumours occurred with equal frequency in both sexes. The mandible was the bone of origin in 56%, maxilla in 32% and other craniofacial bones in 12% of patients. Histological sub-type did not affect the prognosis. Radical surgery with resection of adequate disease-free margins is the most effective mode of treatment. Morbidity and mortality is due to extensive local recurrence of disease, particularly with maxillary tumours. Metastasis to other organs occurs rarely. No statistically significant difference in survival was observed between tumours of the mandible and maxilla, or between patients above and below 20 years of age.

Primary lymphoma of bone: A clinicopathologic study of 25 cases reported over 10 years

Abstract: Twenty-five cases of primary lymphoma of bone (PLB) reported over a 10-year period were reviewed. The presenting symptom was related to involvement of a single bone with or without regional nodal disease. None showed dissemination of lymphoma in the subsequent six months. Patients affected were 7-65 years of age. An equal predilection for the axial and appendicular skeleton was noted. Histologically, the commonest subtype was diffuse histiocytic lymphoma (DHL, 17 cases), whereas four were poorly differentiated lymphocytic (PDL) type and another four were unclassifiable. Follow-up was available in 18 out of 25 patients for periods ranging from 7 months to 8 years. On clinicopathologic correlation we found that 75% of disease-free patients had a DHL whereas 60% of those alive with disease had a PDL. This study reiterates the view that PLB has a good prognosis and the DHL subtype is especially amenable to complete eradication.

Tumors in undescended testis.

Abstract: We herein report our experience in the management of 21 patients with tumors in undescended testis. The primary tumor was in the abdominal testis in six patients and in the inguinal testis in 15 patients. Seventeen patients had unilateral involvement and four had bilateral. Prior orchiopexy was reported in six (30%) patients, unilateral in three and bilateral in the other three, although tumors occurred in one side of three bilateral orchiopexy patients. Clinical staging showed five as stage I, six at stage IIb, two as stage IIc, seven as stage III, and in one no stage was possible. Microscopy showed seminoma, non-seminoma, and mixed tumors in 12, six, and three patients, respectively. As per protocol, stages I and IIb had either radiotherapy or retroperitoneal node dissection, giving three and five year survival of 11/11 (100%) and 7/7 (100%). All nine patients with stage IIc and stage III received induction chemotherapy (VAB-6) first and showed complete response (CR) in four (45%) and partial response (PR) in five (55%). Three and 5 year survival was 45% and 33%, respectively. Overall, 3 and 5 year survival was 70% and 69% respectively in all patients. Early stage disease (stages I, IIb) had excellent survivals, showing the adequacy of treatment, while patients with advanced tumor can still be salvaged with a combination of surgery, chemotherapy, and radiotherapy.

Loss of allelic heterozygosity at the harveyras locus in human oral carcinomas

Abstract: The Harveyras locus was examined for restriction fragment polymorphism and loss of allelic heterozygosity in 62 oral cancer patients. Southern blot analysis onBamHI digests of the tumour tissue DNA, revealed 23 patients with H-ras-1 heterozygosity. The probes used to study the polymorphism were theBamHI 6.6-kb fragment encoding the complete H-ras-1 sequence plus the variable tandem repeat (VTR) region, and the 1-kbMspI fragment encoding the VTR region. The allelic heterozygosity was better resolved byPvuII and further confirmed byTaqI. In addition,TaqI digestion demonstrated a unique VTR rearrangement indicated by 2.1-kb, 0.9-kb and 0.6-kb fragments, implying additionalTaqI sites, in three of the patients. Further analysis of matched tumor tissue and peripheral blood cell DNA from the same patient demonstrated tumor-associated loss of one of the allelic fragments in 7/23 (30%) of the patients with H-ras-1 heterozygosity. However, the loss was not significantly correlated to clinicopathological parameters staging the disease. Thus, our data showing loss of H-ras-1 alleles and VTR rearrangement, with relatively high incidence (9/23; 39%) in the oral cancer patients at various stages of the disease, implies H-ras-1 involvement as an early event in the process of oral carcinogenesis.

Isolated pancreatic metastasis from locally controlled breast cancer: a case report.

Abstract: An unusual isolated metastatic carcinoma to the head of pancreas following modified radical mastectomy for operable breast cancer (T2NOMO) done three years earlier is reported. Patient remains free of disease at 27 months following whipple's pancreaticoduodenectomy.

Dysgerminoma of the ovary: review of 27 cases.

Abstract: Twenty-seven patients with pure dysgerminoma were seen at the Tata Memorial Hospital, Bombay, between January 1980 and December 1984. Of the 10 patients in stage I, 2 patients underwent a unilateral salpingoophorectomy (USO) and were kept under observation without any adjuvant therapy, while the remaining patients received adjuvant treatment following surgery. All of the 6 patients in stage II and 4 of 7 in stage III had total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) followed by postoperative radiotherapy. One patient presented in stage IV and 3 patients presented with recurrence after previous definitive treatment undertaken at other institutions. The disease free, as well as the overall survival, at 108 months, for the 24 cases primarily treated at this institution, is 81% and 88% respectively, and, for patients in stages I and II, 100% (Kaplan-Meier estimation). The need for controlled clinical trials to devise optimal therapy in the early clinical stages and use of chemotherapy for advanced stages of this highly curable entity are stressed.

T-lymphoid blast crisis in chronic myeloid leukemia

Abstract: Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differentiation frequently occurs along B-cell lineage. We report four patients of CML who terminated in T-cell extramedullary BC in lymph nodes after a variable duration of chronic phase. The T-lineage was established by characteristic cytochemical staining and reactivity with a panel of anti-T-cell monoclonal antibodies. All four cases were Philadelphia (Ph) chromosome positive and demonstrated the Ph chromosome and associated anomalies (extra Ph, +19) in the lymph nodes. Our data adds to the growing evidence that CML is a disorder of the common stem cell from which T, B, and myeloid precursors originate.

Sonographic appearance of primary testicular lymphoma

Abstract: A 50-year-old man had an orchiectomy for malignant lymphoma (diffuse histiocytic type) of the right testis. He was referred to our hospital for further treatment. CT and sonographic examination of the abdomen and pelvis did not reveal enlarged nodes. The diagnosis of primary right testicular lymphoma was reached, and he began combination chemotherapy. A month later, nontender swelling of the left testis was noted. Sonograms obtained with a 7.5-MHz transducer with an attached water bath revealed an enlarged testis and a diffusely hypoechoic parenchyma (Fig. 1). In view of the patient’s history, a preliminary diagnosis of malignant lymphoma of the testis was made. A biopsy was done with fine-needle aspiration, and the results were suggestive of lymphoma. An orchiectomy was performed, and final histopathology confirmed the diagnosis of malignant lymphoma (diffuse histiocytic type).

Adenocarcinoma of the bladder : study of 14 cases and review of the literature

Abstract: Summary Fourteen patients with adenocarcinoma of the bladder have been seen over a 14-year period; 6 tumours were of urachal origin and the remaining 8 were primary. All tumours were muscle-infiltrating. The 6 patients with urachal tumours were subjected to surgery; 3 underwent partial cystectomy and 3 radical total cystectomy. All patients who underwent partial cystectomy are alive and free of disease at 60 months, 12 months and 12 months respectively. The other 3 patients who underwent radical cystectomy suffered recurrence and 2 succumbed to their disease within 1 year. All patients with primary adenocarcinoma of the bladder underwent radical cystectomy, 5 of them after planned pre-operative radiotherapy. There were 3 post-operative deaths. One patient died of an unrelated cause 30 months after surgery and 2 died of disseminated disease 8 and 16 months after surgery. One patient developed inguinal lymph node metastases 4 months after surgery and is controlled at 12 months with radiotherapy. Only 1 of the 8 patients with primary adenocarcinoma of the bladder is alive and free of disease at 6 months.

The role of intraluminal radiotherapy and concurrent 5‐fluorouracil infusion in the management of carcinoma esophagus: A pilot study

Abstract: Fifty patients with carcinoma of the esophagus were entered in a randomized pilot study to test the efficacy of intraluminal radiotherapy (ILRT) and concurrent 5-fluorouracil (5-FU) infusion. The median age was 65 years, with 80% having middle third lesions; in 62%, the lesions were longer than 5 cm. After external beam therapy of 50 Gy in 5 weeks, patients were randomized to receive chemotherapy. Significant improvement in dysphagia was recorded in 76% patients with complete response in 47 cases ranging from 6 to 27 months. The overall survival at 2 years was 15% with ILRT alone versus 22% with ILRT plus 5-FU infusion.

Impairment in proliferation, lymphokine production and frequency distribution of mitogen-responsive and interleukin-2-producing cells in Hodgkin's disease

Abstract: In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon γ (IFNγ), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA-responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFNγ in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFNγ. Levels of IL-2 and IFNγ in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regressison (r = 0.79 andr = 0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate (r = +0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111–1/554 and 1/3009–1/6709 respectively) were also less than those of the healthy donors (ranges 1/80–1/181 and 1/761–1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11 214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2-producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease.

Thoracoscopy in the diagnosis of pleural effusion of ambiguous etiology

Abstract: Between 1985 and 1989, 27 patients underwent thoracoscopy for an undiagnosed pleural effusion. Prior thoracocentesis (in all patients) and a needle pleural biopsy (in 15 patients) had been nondiagnostic. The rigid thoracoscope was used in 21 patients, the cystoscope in 4 patients, and the flexible bronchoscope in 2 patients. We had one mortality, and there was no operative morbidity. Thoracoscopy was diagnostic in 24 of the 27 patients (4 benign, 20 malignant). The average duration of stay in the hospital was 48 hr. We conclude that thoracoscopy is an important diagnostic aid in the management of a pleural effusion of ambiguous origin and that it is a relatively safe procedure that can be performed with an acceptable morbidity and mortality.

Expression of the multidrug transporter P-glycoprotein and in vitro chemosensitivity: correlation with in vivo response to chemotherapy in acute myeloid leukemia.

Abstract: Thirty four patients with acute myeloid leukemia (AML) (30 de novo and 4 relapsed) were evaluated for P-glycoprotein (P-gp) expression, and in vitro chemosensitivity. The P-gp expression w...

Rhabdomyosarcoma of the bladder and prostate in children

Abstract: Fifteen children, 14 males and 1 female with a mean age of 4.9 years, were treated for rhabdomyosarcoma of the bladder and the prostate, between 1976 and 1985. In 14 patients, the disease was limited to the pelvis, while one had pulmonary metastases. The lesions were trigonal in 12 patients and involved the prostate in the other three. Eleven patients received vincristine-Adriamycin-cyclophosphamide (VAC) chemotherapy, followed by radiation therapy. Four of these 11 patients required cystoprostatectomy for residual or persistent disease. Of the remaining four patients, two underwent radical cystoprostatectomy, one partial cystectomy and the patient with pulmonary metastases received only chemotherapy. Six patients were alive at 5 years (40% 5-year survival). Six patients died of local relapse within 18 months, one patient died of an unknown cause, while two patients were lost to follow-up free of disease after 2 years.

Non-Hodgkin's lymphoma of prostate: a rare site of primary extranodal presentation (a report of two cases).

Abstract: We report two cases of primary extranodal lymphoma of the prostate, an unusual site for extranodal presentation. The clinical presentation and treatment is discussed.

The severity of late rectal and recto-sigmoid complications related to fraction size in irradiation treatment of carcinoma cervix stage III B.

Abstract: A retrospective analysis of late rectal and recto-sigmoid complications was carried out of the 203 patients with stage III B carcinoma of uterine cervix, treated using radiation therapy alone during January 1979 to December 1983. The patients were treated with a combination of external irradiation and single intracavitary insertion. External irradiation was randomised to one of the four different fractionation regimens having dose per fraction of 2 Gy, 3 Gy, 4 Gy and 5.4 Gy, delivering with five fractions/week, three fractions/week, two fractions/week and one fraction/week, respectively. The total doses in four different regimens were adjusted using the TDF model. There were 39 cases of late radiation induced rectal and recto-sigmoid complications. The complication rate was correlated with the dose per fraction and TDFs delivered in each regimen. The complication rate of 8.2% for 2 Gy per fraction was increased to 33.33% for 5.4 Gy per fraction. It was found that there is strong correlation (P less than 0.05) between size of dose per fraction and the risk of late complications. Present analysis shows that the empirical models as the NSD and TDF do not predict correctly, the late normal tissue damage for different dose fractionations.

Angiolymphoid hyperplasia with eosinophilia (Kimura's disease): report of a large-sized lesion.

Abstract: Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon lesion with a predilection for skin of the head and neck region. It usually presents as one or a few smooth-surfaced nodules which are often asymptomatic. Histologically the nodules reveal two components: abnormal proliferating vessels and a cellular infiltrate consisting of lymphocytes and eosinophils, involving both the dermis and the subcutaneous tissue. A case is presented of an unusually large recurrent lesion on the scalp.

Differences in oestrogen receptor status and histological grade of breast cancer in different religious communities in Bombay.

Abstract: The various religious communities in India viz.Hindu, Muslim, Christian, Parsi have different breast cancer incidence rate. It is not known whether there might also exist differences in biological properties of breast cancer between these communities. To investigate this possibility we have studied the distribution of oestrogen receptor (ER) status and histological grade of tumour in these four communities. Significant differences were observed in the overall distribution of ER positivity and histological grade between the communities P less than for both parameters). Christians had the highest incidence of ER +ve (65.2%) and grade I + II tumours (16.0%), while Muslims had the lowest incidence of ER +ve (35.8%) and Grade I + II tumours (4.7%). In general, we found a significant positive relationship between ER status and age of the patient (p less than 0.0.1). The mean age of the christians was slightly but significantly higher than that of the Hindus and Muslim. The difference ER positivity between the communities might, therefore, be partly (but probably not wholly) explained by difference in age of the patients. However, the difference with respect to grade of tumour cannot be explained as a function of age since no significant association was found between grade of the tumour and age of the patient. Further investigation with respect to difference in the biology of the breast cancer between the communities are warranted.

Amelioration of doxorubicin resistance by pentoxifylline in human chronic myeloid leukemia cells in vitro.

Abstract: Doxorubicin (DOX) is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Pentoxifylline (PTX) is a non-toxic methylxanthine used clinically for the treatment of intermittent claudication. It is an active haemorheological agent, used for the treatment of defective microcirculation. In the present study, we employed PTX as a drug response modulator in combination with DOX to achieve increased cytotoxicity in human chronic myeloid leukemia (CML) cells. Inhibition of H-TdR incorporation was used as a measure of cytotoxicity. PTX at lOOuM concentration significantly (P < 0.001) potentiated DOX-mediated DNA biosynthesis inhibition in CML cells in vitro. Significant synergistic inhibition was seen in 13 out of 22 CML samples. Decreased DOX accumulation is a characteristic feature of DOX resistant tumor cell lines. Drug accumulation studies demonstrated that PTX significantly (P < 0.02) increased the intracellular accumulation of DOX in the CML cells. T...

Fanconi's anemia: a clinico-hematological and cytogenetic study.

Abstract: Eleven patients with typical features of Fanconi's anemia with cytogenetic studies were evaluated. Cytogenetic abnormalities was seen in all but one patient. Two patients had acute non-lymphoblastic leukemia (ANLL) and nine had Fanconi's anemia (FA). All patients with FA responded to oxymetholone and are well with a median follow up of 38.6 months. Both patients with ANLL died. This study stresses the need of an accurate cytogenetic analysis in FA patients along with a clinicohematological correlation.

Perioperative chemotherapy in oral cancer.

Abstract: This is an interim report of a study of perioperative adjuvant chemotherapy following radical surgery for oral cancer, based on the hypothesis of Goldie and Coleman. 135 patients of alveolobuccal carcinoma, clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The test arm received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The control arm was only observed. This analysis at 12 months showed a disease free survival of 71% in the test arm vs. 45% in the control arm, which is statistically highly significant (P less than 0.01). Analysis of recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P less than 0.01). Our study provided further clinical evidence in support of the concepts of Goldie and Coleman that the timing of chemotherapeutic drugs is very critical for a successful end result.

Production of interleukin-1 and tumour necrosis factor in non-Hodgkin's lymphoma patients.

Abstract: Peripheral blood monocytes from non-Hodgkin's lymphoma (NHL) patients were assessed for the monocyte functions with respect to their ability to secrete interleukin-1 and tumour necrosis factor (TNF) and their cytotoxic potential to tumour target WEHI 164 clone 13. Our results indicate comparable levels of interleukin-1 and TNF production by NHL patients. The cytotoxic potential by monocytes was also not depressed in these patients. The data obtained suggest normal monocyte functions in NHL patients.

Malignant mixed tumor of the salivary gland with bone metastasis: a case report and literature review.

Abstract: Malignant mixed salivary tumors are rare, accounting for 2%-10% of all mixed salivary tumors. Rarer still are metastasis from a malignant mixed salivary tumor. A case of malignant mixed salivary tumor occurring in the parotid gland and presenting as a parapharyngeal mass; with asymptomatic multiple bony metastasis is presented with a brief review of literature.

Chronic myeloid leukemia following radioactive iodine (131)I therapy of thyroid cancer.

Abstract: We describe a 51 years old female patient who developed Ph(1) positive chronic myeloid leukemia 7 years following radioactive iodine therapy for follicular carcinoma of thyroid. Until now, only two patients have been reported to have developed CML after this kind of therapy. The underlying mechanisms are discussed and the need to study such patients at cytogenetic, molecular biologic and cell kinetic levels is stressed.