Biomedical subjects

C S Ha

Publications and source records attributed to C S Ha.

At least 55 records · Page 3Linked to original sources

PubMed1998

Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma.

To evaluate the incidence, risk factors, and outcome of central nervous system (CNS) recurrence in adult patients with non-Hodgkin's lymphoma, we evaluated 605 newly diagnosed patients with large-cell and immunoblastic lymphoma who participated in prospective chemotherapy studies. The Kaplan-Meier estimate of probability of CNS recurrence at 1 year after diagnosis was 4.5% (95% confidence interval [CI], 4.4 to 4.6). Twenty-four patients developed CNS recurrence after a median of 6 months from diagnosis (range, 0 to 44 months). In univariate analysis, an increased risk for CNS recurrence was associated with an advanced disease stage (P = .0014), an increased LDH (P = .0000), the presence of B-symptoms (P = . 0037), involvement of more than one extranodal site (P = .0000), poor performance status (P = .0005), and B-cell phenotype (P = .008). Bone marrow involvement (P = .005), involvement of parenchymal organs (P = .03), and involvement of skin, subcutaneous tissue, and muscle (P = .002) were also associated with an increased risk for CNS disease. Multivariate logistic regression analysis identified only involvement of more than one extranodal site (P = .0005) and an increased LDH (P = .0008) as independent predictors of CNS recurrence. Established CNS recurrence had a poor prognosis. Only 1 of 24 patients remains alive and the Kaplan-Meier estimate of probability of survival at 1 year after the diagnosis of CNS recurrence is only 25.3% (95% CI, 6.9 to 43.7). Intrathecal treatment provided symptomatic benefit in only 1 of 6 patients. Radiation treatment provided symptomatic improvement in 6 of 9 patients treated. However, remissions were short and followed by systemic or CNS recurrence. Serum LDH and involvement of more than one extranodal site are independent risk factors for CNS recurrence in patients with large-cell lymphoma. The presence of both risk factors identifies a patient group at high risk for CNS recurrence. Established CNS recurrence can be rapidly fatal. Transient responses occur after radiation treatment.

Adult↗

PubMed1998

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

Abdomen↗

PubMed1998

Utilization of thermoluminescent dosimetry in total skin electron beam radiotherapy of mycosis fungoides.

PURPOSE: The purpose of this report is to discuss the utilization of thermoluminescent dosimetry (TLD) in total skin electron beam (TSEB) radiotherapy to: (a) compare patient dose distributions for similar techniques on different machines, (b) confirm beam calibration and monitor unit calculations, (c) provide data for making clinical decisions, and (d) study reasons for variations in individual dose readings. METHODS AND MATERIALS: We report dosimetric results for 72 cases of mycosis fungoides, using similar irradiation techniques on two different linear accelerators. All patients were treated using a modified Stanford 6-field technique. In vivo TLD was done on all patients, and the data for all patients treated on both machines was collected into a database for analysis. Means and standard deviations (SDs) were computed for all locations. Scatter plots of doses vs. height, weight, and obesity index were generated, and correlation coefficients with these variables were computed. RESULTS: The TLD results show that our current TSEB implementation is dosimetrically equivalent to the previous implementation, and that our beam calibration technique and monitor unit calculation is accurate. Correlations with obesity index were significant at several sites. Individual TLD results allow us to customize the boost treatment for each patient, in addition to revealing patient positioning problems and/or systematic variations in dose caused by patient variability. The data agree well with previously published TLD results for similar TSEB techniques. CONCLUSION: TLD is an important part of the treatment planning and quality assurance programs for TSEB, and routine use of TLD measurements for TSEB is recommended.

Electrons↗

PubMed1998

Localized primary non-Hodgkin lymphoma of the breast.

A single institution's experience with the treatment of localized primary lymphoma of the breast (PLB) was analyzed to understand the natural history of this disease and to identify major prognostic factors and optimal treatment. A retrospective analysis of 23 previously untreated patients who met the strict criteria of PLB from 1972 through 1994 was undertaken. All pathologic materials were reviewed and classified by the Working Formulation. The Ann Arbor stages (AASs) were: IE, 17 patients; IIE, five patients; IV, one patients (bilateral breast involvement without distant metastasis). Pathologic findings were: low grade, two patients; intermediate grade, 18 patients (17 with diffuse large-cell lymphoma (DLCL)); high grade, two patients; and unclassifiable, one patient. The treatments after biopsy or mastectomy were: radiation alone, two patients; chemotherapy alone, six patients; and combined-modality therapy, 13 patients. Two patients had mastectomy alone. Overall survival (OS) and relapse-free survival (RFS) were calculated actuarially. Univariate analyses were performed with patient age, treatment modality, AAS, size of the primary tumor (T stage), and International Prognostic Index (IPI) for the 17 patients with DLCL to define prognostic factors. The median follow-up for the surviving patients was 78 months (range, 45-220 months). The 5-year OS and RFS were 74% and 73%, respectively for all 23 patients, and 65% and 70%, respectively, for the 17 patients with DLCL. Statistically significant factors for OS for DLCL were AAS and IPI. Statistically significant factors for RFS were AAS and T stage. With modern staging evaluation and multiagent combination chemotherapy, localized primary non-Hodgkin lymphoma of the breast, especially diffuse large-cell type, has a prognosis as favorable as that of other DLCL. Ann Arbor stage was a significant factor for both OS and RFS.

Adolescent↗

PubMed1998

Stage I Hodgkin disease: radiation therapy and chemotherapy at the University of Texas M. D. Anderson Cancer Center, 1996-1997.

PURPOSE: To summarize 30 years of experience in treatment of and prognosis for stage I Hodgkin disease. MATERIALS AND METHODS: The authors reviewed retrospectively the cases of 196 patients seen and followed up at one institution from 1967 to 1997. All patients were treated with radiation therapy, and 46 also received combination chemotherapy as part of their initial treatment. Radiation therapy techniques included involved or regional-field irradiation in 83 patients, extended field irradiation (mantle or inverted Y) in 74, and subtotal nodal irradiation in 39 (median radiation doses for subclinical and clinical disease were 30 and 40 Gy, respectively, at 1.5-2.0 Gy per fraction). Of 46 patients treated with combination and radiation therapy, 26 received subtotal nodal irradiation; in the remaining 20, chemotherapy was combined with more limited-field radiation therapy. Follow-up ranged from 3 to 356 months (median, 144 months). RESULTS: The actuarial overall survival, disease-specific survival, and freedom from progression at 10 and 20 years were 82% and 66%, 94% and 91%, and 77% and 70%, respectively. In multivariate analysis, age adversely influenced overall survival, and female sex favorably affected freedom from progression. Mixed cellularity histology and mantle field technique adversely influenced disease-specific survival. Laparotomy significantly influenced disease-specific survival but not overall survival. CONCLUSION: Radiation therapy results in an excellent outcome in patients with favorable stage I Hodgkin disease. Pathologic staging is no longer necessary.

Adolescent↗

PubMed1997

Long-term outcome of treatment for Ann Arbor stage 1 Hodgkin's disease: patterns of failure, late toxicity and second malignancies.

PURPOSE: Radiation therapy results in excellent short-term survival in patients with early-stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves the highest disease-free survival with the minimum long-term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question. METHODS AND MATERIALS: A retrospective study was conducted of 145 patients with Stage I Hodgkin's disease treated at M. D. Anderson Cancer Center from 1967 through 1987. Follow-up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and, and 16 received combination MOPP-based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (49%), extended in 62 (43%), and subtotal nodal irradiation in 12 patients. The median total dose was 40 Gy. RESULTS: The actuarial freedom from progression at 10 and 20 years was 76% and 69%, respectively. Forty of 145 patients relapsed (27.6%). The site of primary disease was cervical adenopathy in 30 (75%), axillary in 7 (17.5%), mediastinal in 2 patients and subdiaphragmatic in one patient. Twenty-two patients were treated with involved/regional technique (55%), 17 with extended (42.5%), and 1 with subtotal nodal irradiation technique. There were three in field and four marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 17 in non-irradiated transdiaphragmatic lymph nodes (57.5%). Nine patients (22.5%) relapsed with visceral disease. Nineteen patients (47.5%) relapsed within the first 2 years, 15 (37.5%) 3 to 10 years after diagnosis and the remaining 6 (15%) after 10 years. Eleven of 40 patients died of disease after the first or subsequent relapses (27.5%). Three of six patients with late relapses had progression in viscera but only two died with disease. Thirty-eight of 145 patients developed late toxicity from the treatment (26.2%). Twenty-three patients experienced ischemic heart disease (15.9%), only 13 of whom received mediastinal irradiation (9%). Fifteen patients developed secondary malignant solid tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two additional patients, one of whom received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non-Hodgkin's lymphoma and lung cancer were the most common second malignancies. CONCLUSIONS: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation can prevent some relapses and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early-stage Hodgkin's disease. Careful long-term surveillance may permit early detection and management of late relapses and treatment complications.

Adolescent↗

PubMed1997

Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy.

BACKGROUND: Lymphoma of the nasal cavity and paranasal sinuses is a rare presentation of extranodal lymphoma with a natural history that is not well characterized in this era of combination chemotherapy. The goals of this retrospective study were 1) to define the natural history of sinonasal lymphomas; 2) to compare the results of radiation therapy (XRT) alone with those of combined modality therapy (CMT) in the treatment of patients with lymphoma of the nasal cavity and paranasal sinuses; and 3) to define prognostic factors for each treatment. METHODS: Between 1947 and 1993, 70 patients with newly diagnosed lymphoma of the nasal cavity and paranasal sinuses were treated. The Ann Arbor stages were: Stage IE: 42 patients; Stage IIE: 14 patients; Stage IIIE: 2 patients; and Stage IV: 12 patients. The distribution of T classifications of the primary tumors was as follows: T1: 2 patients; T2: 16; T3: 18; and T4: 34. Greater than 90% of the patients had intermediate grade lymphoma (Working Formulation), and none had follicular lymphoma. Twenty-eight patients received XRT alone, and 42 received CMT. RESULTS: The actuarial 5-year freedom from progression (FFP) and overall survival (OS) rates for the entire group were 57% and 52%, respectively. For patients with localized disease (Stages IE and IIE) receiving CMT, the actuarial 5-year FFP and OS were 83% and 67%, respectively. In multivariate analysis, treatment with CMT (P = 0.0005) and stage (IE vs. IIIE-IV) (P = 0.0001) were associated with improved FFP. In the group of patients receiving XRT, extent of disease (Stage IE, T1-3 vs. Stage IE, T4 vs. Stage IIE-IV) (P = 0.0001) was the only clinical characteristic associated with improved FFP in multivariate analysis. For patients receiving CMT, International Index (0 vs. 1-3 vs. 4, 5) (P = 0.0001) was the only significant factor predictive of improved FFP in multivariate analysis. One patient failed in the central nervous system (CNS) after initial therapy as a result of a radiation therapy marginal miss. CONCLUSIONS: In a Western population, patients with localized lymphoma of the nasal cavity and paranasal sinuses have a favorable prognosis when treated with CMT. FFP is significantly improved by treatment with CMT. For patients treated with XRT, extent of disease is the strongest predictor of outcome. International Index is the most significant prognostic factor for patients receiving CMT. Failure in the CNS is rare after initial therapy and is associated with local failure.

Adolescent↗

PubMed1997

Localized primary malignant lymphoma of bone.

PURPOSE: A single institution's experience with the treatment of localized primary malignant lymphoma of bone (PLB) was analyzed to identify major prognostic factors, toxicity, and optimal treatment for this rare malignancy. METHODS AND MATERIALS: A retrospective analysis of 45 previously untreated patients with Ann Arbor stage IE and IIE PLB from 1967 to 1992 was undertaken. All histopathologic material was reviewed. Irradiated patients received at least 40 Gy. Systemic chemotherapy was generally doxorubicin based. Overall survival (OS), progression free survival (PFS), and disease-specific survival (DSS) were calculated actuarially. RESULTS: Histologically, there were 41 diffuse large cell, 2 diffuse mixed cell, 1 lymphocytic, and 1 lymphoblastic lymphomas. International Index scores were assessed on 43 patients. Thirty-six patients were treated with chemotherapy and radiation (CMT), five patients were treated with radiation only, and four patients were treated with chemotherapy only. Univariate analysis revealed significantly improved 5-year OS for those patients who had International Index scores of 0 vs. scores of 1 or 2 (85 vs. 53%, respectively, p = 0.004). Analysis failed to demonstrate a difference in OS, PFS, or DSS when comparing radiotherapy alone versus CMT, stage IE vs. stage IIE, or axial skeleton involvement vs. extremities. CONCLUSION: The outcome of patients with PLB is relatively favorable in the era of CMT. Doses of radiation in the range of 46 Gy provide optimal local control with an acceptable rate of complications. The International Index is a valid prognostic tool for PLB.

Adolescent↗

PubMed1997

Enhancing effects of captafol on the development of GST-P-positive liver cell foci in a medium-term bioassay, and protection by L-cysteine of the enhancement in rats.

The modifying effects of captafol and protective effects of L-cysteine on the development of glutathione S-transferase placental form-positive (GST-P +) foci of the liver and expression of proliferating cell nuclear antigen (PCNA) in the kidney were investigated in a medium-term bioassay using D-galactosamine (DGA) in rats. Male 6-week-old F344 rats were initially given a single i.p. injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two i.p. injections of DGA (300 mg/kg) at the ends of weeks 2 and 5, and were fed a diet supplemented with test chemicals for weeks 3-8. Animals in group 1 were given 1500 ppm captafol in the diet, while group 2 received 1500 ppm captafol in diet as well as 1500 ppm L-cysteine in drinking water, animals in control group being given basal diet alone. Positive results regarding increased numbers and areas of GST-P + liver cell foci were obtained in rats treated with captafol alone. On the other hand, significant reduction by L-cysteine in the areas of GST-P + liver cell foci initiated by DEN and promoted by captafol was observed. In addition, the PCNA-labelling indices of renal tubule cells were elevated in rats treated with captafol alone and significantly reduced in rats treated simultaneously with L-cysteine. The protocol used in the present study therefore allowed the in vivo determination of promoting effects of captafol and inhibitory influence of L-cysteine by analyzing GST-P + foci in the livers as marker lesions, within a relatively short period of 8 weeks. Thus, this bioassay protocol could have applicability as a new in vivo assay system for the screening of hepatic carcinogenic or anti-carcinogenic agents.

Animals↗

PubMed1997

Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats.

The protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity were investigated in male Sprague Dawley rats. The total saponins of red ginseng standardized on ginsenosides-Rb1, -Rb2, -Rc, -Rd, -Re, and -Rg1 were used in the present study. The rats were administered the standardized saponins of red ginseng orally at 50, 100, and 200 mg/kg for 7 consecutive days, followed by an administration of carbon tetrachloride at 0.4 ml/kg in corn oil intraperitoneally for 24 h. The administration of saponin changed neither body and organ weights nor hematological and serum clinical parameters. The elevation of SGPT and SGOT activities induced by carbon tetrachloride was partially recovered by the administration of the saponin. The liver vacuolization and lymphoid cell aggregation by carbon tetrachloride were clearly recovered by the red ginseng saponins as examined histologically. The present results indicated that the standardized saponins of red ginseng used in these studies may partially recover the hepatotoxicity induced by carbon tetrachloride in male Sprague Dawley rats.

Animals↗

PubMed1997

Primary non-Hodgkin lymphoma of the large bowel.

PURPOSE: To characterize the natural history of primary non-Hodgkin lymphoma of the large bowel and identify prognostic factors. MATERIALS AND METHODS: Twenty-three patients with primary non-Hodgkin lymphoma according to strict criteria were identified. Seventeen patients underwent resection, and six patients underwent biopsy. Among 19 patients with intermediate- or high-grade lymphoma, 13 had diffuse large cell lymphoma. Ann Arbor stage was I in 15 cases, II in seven cases, and IV in one case. In 15 patients, the International Prognostic Index was available: 0, eight patients; 1, six patients; and 3, one patient. Postoperatively, six patients received combined chemotherapy and radiation therapy, eight patients received chemotherapy, and six patients received radiation therapy. Overall and relapse-free survival were calculated actuarially, and univariate analysis was performed with regard to stage, treatment, extent of surgery, and the International Prognostic Index. RESULTS: Median follow-up was 144 months. Two patients' disease recurred. Overall and relapse-free survival at 10 years were 61% and 82%, respectively. The International Prognostic Index was the only significant prognostic factor for overall survival (P = .03, log-rank test). CONCLUSION: The prognosis of primary non-Hodgkin lymphoma appears to be as good as that of low- or intermediate-grade lymphoma. The only significant prognostic factor for overall survival is the International Prognostic Index.

Adolescent↗

PubMed1997

Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.

PURPOSE: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS: Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS: Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION: NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

Adult↗

PubMed1997

Primary parotid lymphoma: the effect of International Prognostic Index on outcome.

Since the reported survival and failure-free survival (FFS) of adults with primary parotid non-Hodgkin's lymphoma (NHL) is variable, we reviewed our experience of untreated adults with primary parotid NHL. Patients were eligible if they presented to the University of Texas M. D. Anderson Cancer Center Cancer between 1980 and 1995 with parotid enlargement and if the diagnosis of lymphoma was verified according the Working Formulation. Medical records were reviewed to determine Ann Arbor Stage (AAS), the International Prognostic Index (IPI) score, response to therapy, relapse, FFS, and survival. We identified 39 untreated adults with primary parotid NHL representing 1% of all lymphomas and 8.6% of all untreated parotid neoplasms. Three patients were excluded because of suboptimal therapy, leaving 36 patients eligible for outcome analysis. Of the 18 patients with low-grade NHL, two were treated with radiotherapy, eight with chemotherapy and radiotherapy, seven with chemotherapy only, and one with antibiotics. The complete remission (CR) rate was 94%, and with a median follow-up of 36 months for surviving patients the survival and failure-free survival (FFS) at 5 years were 94% and 78%, respectively. The 5-year FFS were not statistically different between patients with early (I or II) or advanced (III or IV) AAS (83% and 74%, respectively; p > 0.05) and favorable (0 or 1) or unfavorable (> 1) IPI scores (73% and 100%, respectively; p > 0.05). All 18 patients with intermediate-grade NHL were treated with doxorubicin-based chemotherapy which was followed by radiotherapy in six. The CR rate was 89%, and with a median follow-up of 51 months for surviving patients the survival and FFS at 10 years were 80% and 72%, respectively. In this group 10-year FFS was better in early than in advanced AAS (100% vs 0%, respectively; p = 0.01) and in favorable (0 or 1) than in unfavorable (> 1) IPI scores (86% vs 20%, respectively; p < 0.01). We conclude the the FFS of patients with low-grade NHL is 78% and not affected by AAS or IPI score. The FFS of patients with intermediate-grade NHL appears comparable with that of NHLs of other primary sites, being 86% for those with IPI < or = 1 and 20% for those with IPI 1. Patients with IPI > 1 should be entered on investigational protocols aiming to increase FFS.

Adult↗

PubMed1997

Serial determination of the bcl-2 gene in the bone marrow and peripheral blood after central lymphatic irradiation for stages I-III follicular lymphoma: a preliminary report.

Two-thirds of patients with follicular lymphoma have rearrangement of bcl-2 major breakpoint region (MBR) through t(14;18) (q32;q21). This rearrangement can serve as a sensitive marker for follicular lymphoma cells. This study was undertaken to assess the molecular complete response rate of stages I-III follicular lymphoma to central lymphatic irradiation (CLI) by detection of PCR-amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. Twenty patients with stages I-III follicular lymphoma were treated with CLI. Twelve of them were part of a prospective randomization trial comparing CLI with multi-agent chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients before the initiation of treatment. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. In PCR-positive patients, bone marrow and blood samples were followed at regular intervals during and after CLI. The results of the PCR amplification were correlated with clinical findings. All 20 patients achieved clinical complete response after CLI. Median follow-up was 22 months (range, 12-37 months), and no patient has relapsed. Pretreatment PCR results were available in all patients (19 patients for peripheral blood samples and 16 patients for bone marrow samples). Nine of 19 peripheral blood samples and 9 of 16 bone marrow samples were PCR-positive for bcl-2 MBR rearrangement. Eight PCR-positive patients converted to negative (8 of 9 blood samples and 2 of 3 bone marrow samples) 2-20 months from the first day of CLI. Bone marrow and peripheral blood with PCR-amplifiable bcl-2 MBR rearrangement can be converted from positive to negative after chemotherapy in patients with follicular lymphoma. Early results from our study show for the first time that peripheral blood and bone marrow can be converted from positive to negative after CLI. The prognostic significance of the observed conversions requires longer follow-up.

Adult↗

PubMed1996

Reappraisal of eight representative carcinogenic and non-carcinogenic compounds in a new medium-term rat liver bioassay using D-galactosamine.

The carcinogenic potential of eight different compounds was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a non-surgical method to induce regeneration in place of partial hepatectomy (PH). Male rats were initially given a single i.p. injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two i.p. injections of DGA (300 mg/kg) at the end of weeks 2 and 5. They were treated with one of the test compounds aflatoxin B1, benzo[a]pyrene, diethylstilbestrol, urethane, sodium saccharin, bucetin, D-mannitol and sodium chloride in the diet or basal diet alone for weeks 3-8. Carcinogenic potential was assessed by comparing the numbers and areas per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for the hepatocarcinogens aflatoxin B1, diethylstilbestrol or urethane, and for the non-liver carcinogen benzo[a]pyrene. Negative values were shown in rats treated with the non-carcinogens, D-mannitol and sodium chloride. The two other non-liver carcinogens sodium saccharin and bucetin, also did not exert positive effects in the system. The present data are consistent with findings in previous medium-term bioassays using PH. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive non-invasive method to screen large numbers of environmental carcinogens.

Animals↗

PubMed1995

Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice.

A possible role of metabolism by cytochrome P450 (P450) in ethyl carbamate-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes (SRBCs), was investigated in female Balb/C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibody response was significantly suppressed from 200 mg/kg. These doses also caused a decrease in thymus weight. An acute dosing of ethyl carbamate at 1 g/kg also caused not only a significant suppression of the antibody response, but also a decrease in thymus weight. The antibody response was most likely to be the IgM antibody response, which was demonstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecutive days, the antibody response was more suppressed than in saline-pretreated controls. Moreover, a study using aminoacetonitrile, a P450 inhibitor, showed that the antibody response suppressed by ethyl carbamate was completely recovered by the inhibitor. The present results suggest that metabolism of ethyl carbamate by P450 may be the critical pathway to produce metabolites capable of suppressing the antibody response.

Animals↗

PubMed1995

PET and SPECT imaging for stereotactic localization.

Stereotactic localization using PET and SPECT has been used together with the Leksell stereotactic frame and the other imaging tools routinely provided to Gamma Knife radiosurgery sites. The accuracy of the measurements has been confirmed with CT and MR using a Radiation Analog Dosimetry phantom. The activity of the radionuclide solution placed in the tubes of Elekta Radiosurgery's MR imaging box is somewhat critical because the window levels chosen for the scan will affect the apparent size of the lesion. A technique is presented to resolve areas of activity more than about 12-14 mm apart, and it may prove useful in targeting epileptogenic sites in patients with medically intractable epilepsy.

Humans↗

PubMed1994

Postoperative radiotherapy for cutaneous melanoma of the head and neck region.

PURPOSE: To assess the efficacy and toxicity of elective-adjunctive radiotherapy given in five 6-Gy fractions to patients with cutaneous melanoma of the head and neck at high risk for local-regional relapse. METHODS AND MATERIALS: From 1983 to August 1992, 174 patients (132 men and 42 women) were enrolled. The ages ranged from 16 to 89 years (median: 54 years). One group (n = 79) received elective irradiation after wide local excision of lesions > or = 1.5 mm thick, or Clark's level IV-V, a second group (n = 32) received adjunctive irradiation after excision of primary lesions plus limited neck dissection, and a third group (n = 63) received irradiation after neck dissection for nodal relapse. Each group had a projected local-regional recurrence rate of approximately 50%. The radiotherapy consisted of five fractions of 6 Gy each, specified at Dmax, delivered twice a week, to a total dose of 30 Gy in 2.5 weeks. Electron beams of appropriate energies were used whenever possible. Junction lines between adjoining fields were moved twice to minimize dose heterogeneity. Patients were seen at regular intervals to assess disease status and therapy-related complications. Patients who relapsed were treated as indicated by the clinical status. RESULTS: With a median follow-up of 35 months, 111 of 174 patients were alive. The disease recurred above the clavicles only in six patients, at distant sites in 58 patients, and both local-regionally and at distant sites in nine patients. The actuarial 5-year local-regional control (LRC) and survival rates for the whole group were 88% and 47%, respectively. The thickness of the primary lesion, presence of more than three positive nodes, and extracapsular extension did not influence the LRC rate after radiotherapy (range: 85-92%). However, lesion thickness strongly affected the 5-year survival rate of group 1 patients (i.e., 100% for < or = 1.5 mm thick, but Clark's level IV, 72% for > 1.5-4 mm, and 30% for > 4 mm). In groups 2 and 3, the 5-year survival rate of patients with > three involved nodes was lower than that of patients with one to three positive nodes (23% vs. 39%). The acute tolerance to adjunctive radiotherapy was excellent. Late radiation complications were observed in only three patients. These were moderate neck fibrosis, mild ipsilateral hearing impairment, and transient exposure of external auditory canal cartilage. CONCLUSION: The safety of this hypofractionated radiotherapy regimen in the management of cutaneous melanoma was established in this study. The overall 5-year actuarial LRC rate of 88% was much higher than that of our historical group and that reported in the literature (50%). The survival rate of patients with lesion of 1.5-4 mm thickness was also higher than that observed in other series. Based on these results a prospective randomized study to further define the role of adjunctive postoperative radiotherapy is planned.

Adolescent↗