PubMed Health⌕ Search

Biomedical subjects

G Ganem

Publications and source records attributed to G Ganem.

At least 37 records · Page 2Linked to original sources

Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (interleukin beta, interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans.

Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamo-pituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cytokines induced by ionizing radiation remain to be determined.

Adrenocorticotropic Hormone↗

Further studies of a staggered hybrid zone in Mus musculus domesticus (the house mouse).

In the extreme north-east of Scotland (near the village of John o'Groats) there is a small karyotypic race of house mouse (2n = 32), characterized by four metacentric chromosomes 4.10, 9.12, 6.13 and 11.14. We present new data on the hybrid zone between this form and the standard race (2n = 40) and show an association between race and habitat. In a transect south of John o'Groats we demonstrate that the clines for arm combinations 4.10 and 9.12 are staggered relative to the clines for 6.13 and 11.14, confirming previous data collected along an east-west transect (Searle, 1991). There are populations within the John o'Groats-standard hybrid zone dominated by individuals with 36 chromosomes (homozygous for 4.10 and 9.12), which may represent a novel karyotypic form that has arisen within the zone. Alternatively the type with 36 chromosomes may have been the progenitor of the John o'Groats race. Additional cytogenetic interest is provided by the occurrence of a homogeneous staining region on one or both copies of chromosome 1 in some mice from the zone.

Animals↗

[Esophageal cancer: did combined treatments improve prognosis?].

Prognosis of esophageal cancer is very poor. Five-year survival does not exceed 20% after radical surgery, the best available treatment. Unfortunately, only 40% of the patients are amenable to surgery because of poor general status and/or locoregional extension. Adjuvant treatment did not yield survival improvement. Preoperative radiotherapy (three randomized trials) or postoperative radiotherapy (one randomized trial) showed only a decrease of regional relapses, perhaps only for the nodes negative patients. Neoadjuvant chemotherapy obtains some interesting response rate (20-60%), but there has been no evidence yet for survival improvement. Recently, promising results were presented after combination of radiotherapy and chemotherapy. In this paper, we review the present status of combined treatment for esophageal cancer. Our multicentric group (OSOF) is now completing a phase II trial, that should soon form the basis for a phase III prospective study.

Combined Modality Therapy↗

Conservative treatment for breast cancer: long-term results (15 years).

From 1961 to 1974, 245 patients with unilateral "operable" breast cancer (25% T1, 56% T2, 19% T3) were treated with breast conservation and irradiation at the Gustave Roussy Institute (1961-1969) or at the Henri Mondor Hospital (1970-1974). The minimum follow-up is 15 years. Most patients with T greater than 3 cm underwent radiation therapy with the tumor in place, while the greater part of patients with T less than 3 cm received radiation therapy after tumorectomy. The breast and draining lymph node areas received widefield telecobalt irradiation to 45 Gy. The dose to the tumor site was boosted using iridium-192 implantation. Additional irradiation was given to the internal mammary and lower axillary nodes using an electron beam. The 15 years NED survival rate was 63%, 51% and 26% for T1, T2 and T3 tumors, respectively. The NED survival for T less than or equal to 1 cm was 86%. The local recurrence rate was 8, 12 and 19% for T1, T2 and T3 tumors, respectively. Of the patients with local recurrence, 85% underwent surgical salvage. Complications were rare. Cosmetic results were satisfactory in most patients including the T3 group. The proportion of breasts conserved among patients living NED at 15 years, was 97, 88 and 93% for T1, T2 and T3 tumors, respectively. In 1980, after almost 20 years experience using breast conserving techniques, we modified our treatment policies in close collaboration with our surgical team, hel cbye extending the indications for tumorectomy and associating routine surgical exploration of the lower axilla.

Breast Neoplasms↗

Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission.

This study defines the risk of central nervous system (CNS) relapse in patients undergoing bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission, with no posttransplant prophylactic CNS therapy. Ninety-two consecutive patients in complete remission received BMT for ALL (n = 82) or high-grade non-Hodgkin's lymphoma with poor prognostic factors at diagnosis (n = 10). Sixty-six patients received allogeneic BMT (Allo-BMT) and 26 patients, without an identical sibling, underwent autologous BMT (Auto-BMT). Fifteen patients had CNS involvement at diagnosis and underwent BMT in first remission. Eight patients experienced CNS relapse after BMT, corresponding to a probability of 11% at 3 years. Apart from a history of prior CNS involvement, no patient characteristic evaluated statistically influenced CNS relapse after BMT. The probability of CNS relapse was 5.5% for the 70 patients without history of CNS involvement and 27.5% for the 22 patients with prior CNS involvement. However, subgroup analysis showed that the increased risk of CNS relapse is mainly observed in Auto-BMT patients with history of prior CNS involvement, particularly in patients undergoing BMT in first remission (three of five Auto-BMT versus one of ten Allo-BMT). Taking into account the multiple factors which influence the occurrence and the treatment of CNS leukemia, the results on this retrospective study suggests that (1) for patients without CNS involvement at diagnosis and for whom BMT is performed in first remission, cranial irradiation before BMT and posttransplant prophylactic CNS therapy can be omitted because of the low probability of CNS relapse after BMT (3.4%), when total-body irradiation (TBI) is included in the conditioning regimen; and (2) the difference observed between Allo-BMT and Auto-BMT patients with previous CNS involvement and undergoing BMT in first remission could indicate that graft-versus-host leukemia acts even in the CNS in Allo-BMT patients.

Adolescent↗

[Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

Amylases↗

[Cancer of the breast: intensive treatment with bone marrow autografts].

High dose chemotherapy with autologous bone marrow transplantation has been proposed in metastatic and inflammatory breast cancer. Data in the literature reported an improvement of the quality and of the rate of response. However, the impact on survival remains to be demonstrated. Since 1985, a pilot study in inflammatory and directly metastatic breast cancer has been started in order to determine the impact of high dose chemo-radiotherapy. Patients were treated with an induction regimen consisting of cyclophosphamide 1,200 mg/m2 and 4'epi-adriamycin 75 mg/m2 every 15 days x 4. Mastectomy was performed associated for patients younger than 50 years with bone marrow collection and cryoconservation. In this group, late intensification with cyclophosphamide 2.2 g/m2 day 1 and 2, TBI and autologous bone marrow transplantation was performed. Fourteen patients have been treated: 9 inflammatory breast cancers T4 b N1 M0, 5 metastatic cancers at presentation including 3 with inflammatory breast cancer T4 b N1 M1 and 2 metastatic T2 N1 M1. Relapses had occurred in 7 patients, of them 4 were metastatic. Five patients died from their disease, and one from CMV interstitial pneumonitis. Six patients are alive free of disease but only one was metastatic. On this limited number of patients, survival of metastatic breast cancers does not seem to benefit from this regimen.

Adult↗

Establishment and characterization of three transplantable EBV-containing nasopharyngeal carcinomas.

Three transplantable nasopharyngeal carcinoma (NPC) tumors, designated C15, C17 and C18, have been obtained and characterized. C15, derived from a primary NPC tumor, has been propagated in nude mice for 30 passages. C17 and C18, derived from metastatic NPC tissue, have been passaged 10 times. Desmosomes, present in every case, provided confirmation of the epithelial origin of all 3 tumors. The Epstein-Barr virus (EBV) genome is contained in C15, C18 and C17 tumor cells with 30, 12 and 3 copies, respectively. The Epstein-Barr virus nuclear antigen (EBNA) was stained by the classical anti-complement immunofluorescence (ACIF) technique. Fluorescence intensity was strong in C15, moderate in C18, and hardly detectable in C17 cells. No expression of the EA and VCA antigens was detected. Flow cytometry analysis performed on monocellular suspensions showed the absence of detectable CR2 molecules (the EBV receptor on B lymphocytes) in all 3 tumors, and the constitutive expression of HLA class-II antigens in C15 and C17 cells. IL-1 activity was demonstrated in the supernatant of C15 and C17 cells cultivated in vitro for 3 days. These data confirm that the constitutive synthesis of MHC class-II molecules and the release of IL-1-like activities are frequent features of NPC cells. These characteristics could be of importance in relation with the T-cell infiltrate found in NPC primary tumors.

Adolescent↗

Treatment of inflammatory breast cancer with combination chemotherapy and mastectomy versus breast conservation.

Twenty-six consecutive patients with nonmetastatic inflammatory breast cancer (IBC), were treated in a single institution using the same protocol, and all were followed for at least 48 months. The first phase of treatment consisted of two monthly cycles of combination chemotherapy with Adriamycin (Adria Laboratories, Columbus, OH), vincristine, cyclophosphamide and 5-fluorouracil. Local treatment was then undertaken using in all cases a cobalt 60 beam to deliver 45 Gy to the entire mammary gland and lymph-draining areas. Local treatment was completed either by mastectomy, or by conservation of the breast and interstitial irradiation of the primary tumor site. Chemotherapy was resumed after completion of local treatment for a total of 6 cycles. Metastatic disease occurred in 19 of 26 patients from 8 to 55 months; five patients are alive and free of disease from 48 to 81 months. Failure to control local disease or local recurrences was noted in two of ten patients undergoing mastectomy, and in seven of 13 patients with conservation of the breast. While this difference is not statistically significant we concluded that methods of breast conservation which limit the high dose volume to the tumor site do not assure local control in IBC. The median disease-free survival and overall survival of 12 and 31 months, respectively, are not satisfactory. Better systemic treatment is needed.

Adult↗

Venocclusive disease of the liver after allogeneic bone marrow transplantation in man.

One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a 60 Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a "standard-risk" of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with "higher-risk" of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D. Univariate analysis showed that four characteristics were significantly related to an increased prevalence of V.O.D.: sex (11/62 females vs 6/89 males; p less than 0.05); history of liver disease (7/28 vs 10/117 patients without antecedent; p less than 0.01); ASAT and/or ALAT levels greater than 1.5 upper normal limit (11/49 vs 6/102 patients with levels less than 1.5; p less than 0.01) and intensified conditioning regimen (6/25 vs 11/126 patients with classical regimen; p less than 0.05). The conditioning regimen and history of liver disease were highly correlated to transaminases levels. Only two factors, transaminases levels and female sex, remained significantly associated with V.O.D. after multivariate analysis.

Adolescent↗

Combined external irradiation and interstitial implantation for T1 and T2 epidermoid carcinomas of base of tongue: the Creteil experience (1971-1981).

Forty-eight patients with T1 or T2 epidermoid carcinomas of the base of tongue were treated at the Henri Mondor Hospital between 1971 and 1981. Forty-one patients received moderate dose 60Co external beam irradiation (mean: 48.6 Gy) to the primary tumor and regional nodes, followed by an interstitial iridium 192 implant to the primary tumor (mean: 32 Gy). This completed the treatment for the 30 node negative patients, but those with clinically positive nodes were managed by either an additional electron beam boost to the involved nodes or a neck dissection. Seven tumors were treated exclusively by implantation to the base of tongue (mean: 63 Gy). Five-year crude disease-free survival is 50% with 35% of patients dying of recurrent disease. Definitive local control for T1 lesions is 85% (11/13) and for T2 is 71% (25/35). A dose response effect was observed with local control of 79% (26/33) obtained with a combined dose greater than or equal to 75 Gy, but only 50% (4/8) for less than or equal to 70 Gy. For N0 patients definitive regional control is 97% and for N1-3 is 89%. Minor or moderate soft tissue ulceration was observed in 12 patients, including 3 cases that progressed to osteonecrosis. None required surgical intervention. No correlation exists between necrosis and tumor size or total dose.

Adult↗

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-year results of 70 cases.

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

Adult↗

The indications for total cutaneous electron beam radiation therapy of mycosis fungoides.

From 1977 to 1984, we treated 34 patients with mycosis fungoides and 9 patients with B cutaneous lymphomas. Eighteen patients with mycosis fungoides were treated with total skin electron irradiation (TSEI) and had a minimum follow-up of 15 months (range 15 months to 7 years). The lowest electron energy of the linear accelerator was 8 MeV therefore we placed a plexiglas screen between the patient and the machine; the resulting electron energy was 4 MeV. The total dose was 30 Gy delivered in 12 fractions over 40 days. There were 8 males and 10 females. The median age was 48 years (ranging from 13 to 78 years). All patients were staged as follows: Stage A = superficial lesions covering less than 50% of the body surface; Stage B = superficial lesions covering more than 50% of the body surface; Stage C = tumors involving the skin, lymph nodes and/or visceral organs. Five patients with Stage A (5/5) and 5 patients with Stage B (5/5) had a complete remission, 1 stage A patient relapsed 6 months after completion of treatment. All the Stage B patients recurred between 3 and 15 months. The recurrences were localized to the skin and were well controlled with topical nitrogen mustard or puvatherapy. Among the Stage C patients, 3 did not respond to treatment and died of their disease; the remaining 5 patients achieved complete remission but they all relapsed from 2 to 9 months following completion of treatment. The median follow-up was 32 months and the average time for relapse was 6.5 months. All relapses except one (15 months) occurred within the first year. We feel that total skin electron irradiation is indicated in Stage A and B patients. However, we feel Stage C patients should receive TSEI for palliative purposes only.

Adolescent↗