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Biomedical subjects

G M Mead

Publications and source records attributed to G M Mead.

At least 55 records · Page 3Linked to original sources
PubMed1998

Intratubular germ cell neoplasia of the contralateral testis in testicular cancer: defining a high risk group.

PURPOSE: We define a group of testis cancer patients who are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. MATERIALS AND METHODS: The histology was reviewed in 186 testis cancer patients who underwent contralateral testicular biopsy either because of a history of testicular maldescent or an atrophic contralateral testis (defined as a volume of 12 ml. or less). Testicular volume, semen analysis, serum gonadotropin levels, serum testosterone and estradiol levels were assessed in the majority of patients. RESULTS: Univariate analyses identified contralateral testicular atrophy, low sperm density, young age at presentation and low Johnsen score as factors associated with increased risk of a positive biopsy. A history of maldescent in the absence of atrophy was associated with carcinoma in situ prevalence of only 4%. Multivariate analysis identified only testicular atrophy and age at presentation as independent determinants of a positive biopsy. Testis cancer patients with a small contralateral testis had a 20% and those presenting at age 30 years or younger had a 34% prevalence, respectively, of carcinoma in situ on contralateral testis biopsy (95% confidence interval 20 and 46%, respectively). CONCLUSIONS: Testis cancer patients with an atrophic contralateral testis who present before the age of 31 years are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. It is estimated that this group comprises 6% of all testis cancer patients. We predict that a policy of performing contralateral testicular biopsy will produce positive results for carcinoma in situ in a third of these patients and will detect contralateral carcinoma in situ in approximately 40% of all testis cancer patients.

Adult↗
PubMed1997

The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review.

BACKGROUND: The growing teratoma syndrome is a recognized complication of metastatic nonseminomatous germ cell tumors of the testis and is managed surgically. It may also occur in intracranial nongerminomatous germ cell tumors. METHODS: The authors performed an English language computer search using the EMBASE data base (from January 1980 to December 1996) for pineal tumors, read all abstracts, and then selected all articles pertaining to germ cell tumors at this site. RESULTS: The case history of a 19-year-old male who presented with a pineal nongerminomatous germ cell tumor, which was treated with chemotherapy, is reported. Despite normalization of raised tumor marker levels, the pineal mass enlarged during chemotherapy. This was excised and proved to be a mature teratoma. A review of the literature regarding this complication of intracranial germ cell tumors is also presented. CONCLUSIONS: The authors believe this to be the first reported case of growing teratoma syndrome in the pineal gland of an adult patient, two previously reported cases occurred in children. The authors conclude that the pineal gland is an unusual but important site in which to recognize the growing teratoma syndrome.

Adult↗
PubMed1997

Prognostic factors for patients with advanced seminoma treated with platinum-based chemotherapy.

Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity.

Adult↗
PubMed1997

Germ cell cancers in adult males are associated with a history of infantile pyloric stenosis.

Germ cell cancers (GCT) are the most common cancers of young men and are curable in at least 90% of cases. A number of aetiological factors have been identified which predispose to the development of these cancers, such as cryptorchidism and hernia. We report the association of GCT with infantile pyloric stenosis (IPS). The case records from 542 adult males with germ cell cancer arising from any site were screened for a history of pyloric stenosis requiring surgical treatment. Nine cases were observed (expected number = 2.168; chi squared = 21.5 (P < 0.001), standardised ratio = 4.15; 95% confidence interval 1.9-7.88). The recognition of rare associations of germ cell tumours may lead to the identification of genetic and environmental factors involved in their aetiology.

Adolescent↗
PubMed1997

Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party.

In a retrospective study, data from 302 patients with metastatic testicular seminoma treated with chemotherapy between 1978 and 1990 in 10 European centres were analysed to evaluate the role, if any, of postchemotherapy treatment with irradiation. The primary endpoint of this study was the progression-free survival rate after chemotherapy with or without additional radiotherapy. This was related to the type of primary chemotherapy, sites and sizes of pre- and postchemotherapy masses, the extent of surgical resection after chemotherapy and the use of radiotherapy. 174 patients had residual disease at the end of chemotherapy. The most important prognostic factors for progression were the presence of any visceral metastases or raised LDH prechemotherapy, and the presence of residual disease at visceral sites after chemotherapy. Approximately half the patients with residual masses underwent postchemotherapy radiotherapy, with selection based predominantly on institutional practice. In patients receiving platinum-based chemotherapy, no significant difference was detected in progression-free survival whether or not radiotherapy was employed. Patients receiving BEP (bleomycin, etoposide and cisplatin) had a progression-free survival rate of 88% (95% CI, 80-96%) uninfluenced by postchemotherapy radiotherapy. In patients with residual masses confined to the abdomen after platinum-based chemotherapy, the absolute benefit to radiotherapy was estimated to be 2.3%. The potential benefit of postchemotherapy radiotherapy is minimal, and so it is concluded that the use of adjuvant radiotherapy to residual masses after platinum-based chemotherapy for metastatic seminoma is unnecessary.

Abdominal Neoplasms↗
PubMed1997

Lymphadenopathy due to amyloid deposition in non-Hodgkin's lymphoma.

BACKGROUND: Amyloidosis is a rare complication of non-Hodgkin's lymphoma. Most of the reported patients have had systemic amyloidosis and have died as a result of complications of this disease. MATERIALS AND METHODS: The clinical cases of two patients with lymphoplasmacytic non-Hodgkin's lymphoma who presented with lymphadenopathy due to localised amyloid deposition are reviewed. Immunohistochemical studies were performed on the amyloid deposits and adjacent lymphoma. RESULTS: The amyloid deposits in both patients were derived from monoclonal light chains of the same isotype as those expressed by the lymphoma cells and were localised to areas adjacent to the lymphoma despite the presence of circulating light chains. Both patients had an indolent clinical course and treatment appeared to have little influence on the amyloid deposition. CONCLUSIONS: Non-Hodgkin's lymphoma may be associated with localised amyloidosis secondary to local production and deposition of amyloid from monoclonal light chains synthesised by the lymphoma cells. This is a rare cause of lymphadenopathy which does not respond to treatment of the underlying lymphoma.

Amyloid↗
PubMed1997

PACE BOM chemotherapy: a 12-week regimen for advanced Hodgkin's disease.

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of a 12-week alternating weekly chemotherapy regimen for advanced Hodgkin's disease. Consolidative irradiation of residual masses was used in selected cases. PATIENTS AND METHODS: Eighty-three patients with newly diagnosed advanced Hodgkin's disease (bulky stage IIA, stage IIB-IVB) or with progressive disease after extended field radiotherapy for early stage disease were included in this study. The patients were treated for 12 weeks with PACE BOM comprising oral prednisolone together with intravenous doxorubicin, cyclophosphamide and etoposide alternating weekly with intravenous bleomycin, vincristine and methotrexate. Limited field adjuvant radiotherapy was also given to 21 patients with localised persistent radiological abnormalities visible on chest X-ray after chemotherapy. The study end points were overall survival, failure free survival (FFS) and toxicity, particularly with respect to reproductive function. RESULTS: With a median post treatment follow up of 52 months the actuarial 5-year overall survival is 90% (confidence interval 81%-95%) and FFS is 64% (52%-74%). This treatment was well tolerated and fertility was maintained in a high proportion of young adults. CONCLUSIONS: The brief duration PACE BOM regimen with or without radiotherapy appears to be comparable in efficacy to other doxorubicin containing regimens, with a favourable toxicity profile. Randomised clinical trials are now needed to evaluate the role of this and comparable initial treatment approaches to advanced Hodgkin's disease.

Adolescent↗
PubMed1997

Testicular carcinoma.

Testicular cancer is the commonest malignancy in young males and its incidence has more than doubled in the last 25 years. For clinical purposes, two tumour types are identified, seminoma and non-seminoma germ cell tumours (loosely known as teratomas). Stage I disease is confined to the testes and is managed surgically, with adjuvant chemotherapy or radiotherapy as appropriate. Cisplatin-based chemotherapy is the cornerstone of treatment for metastatic disease, with cure rates exceeding 80%. Early diagnosis and cure should be the aim in all patients. To this end, those with testicular symptoms should be evaluated promptly by ultrasound, and in young male patients presenting with the clinical picture of metastatic disease, germ cell tumour should top the list of differential diagnoses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.

PURPOSE: This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Adult↗
PubMed1996

Primary pure teratoma of the testis.

PURPOSE: Despite its histologically benign appearance, primary pure teratoma of the testis is believed to have metastatic potential and behave similarly to other nonseminomatous germ cell tumors. We present our experience with the natural history and management of pure teratoma. MATERIALS AND METHODS: We reviewed the histological findings and clinical history of 15 patients with primary pure teratoma who were treated during a 15-year period, accounting for 4.2% of all nonseminomatous germ cell tumors treated during the same period. Fourteen patients were available for followup and are included in this report. RESULTS: In 8 patients the tumor was composed entirely of mature teratoma and in 6 immature elements were also present, although this finding was not associated with an increased frequency of metastatic disease. Carcinoma in situ was found adjacent to the tumor in 12 cases. Of 10 patients with stage I disease at presentation who were entered on a surveillance program only 2 have had relapse. The remaining 4 patients had metastatic disease at presentation and, thus, metastatic disease occurred in a total of 6 of the 14 patients (43%) with a median followup of 46 months (range 5 to 197). Metastatic disease was confined to the retroperitoneum in all 6 patients and only 2 patients had elevated serum marker levels. Five patients were treated with primary chemotherapy followed by resection of a residual mass and in all cases teratoma was identified in the resected mass. One patient underwent surgical excision of a retroperitoneal mass, which contained teratoma and yolk sac tumor, followed by chemotherapy. All patients are alive without evidence of progressive disease. CONCLUSIONS: In patients with primary pure teratoma of the testis metastatic disease may develop and the metastases may contain other subtypes of nonseminomatous germ cell tumors in addition to teratoma. There is probably a reduced frequency of relapse, which should be considered when advising patients with stage I disease, but otherwise management should be the same as for other testicular nonseminomatous germ cell tumors and the prognosis should be excellent.

Adolescent↗
PubMed1995

Orchiectomy after chemotherapy in patients with metastatic testicular cancer. Is it indicated?

BACKGROUND: A small proportion of patients with testicular germ cell tumors present with widely metastatic disease and are treated initially with chemotherapy. Little is known about the efficacy of systemic chemotherapy in eradicating the primary testicular germ cell cancer; however, there is concern that the testis may act as a sanctuary site for germ cell cancer in these patients, and orchiectomy, is, therefore, recommended after chemotherapy. METHODS: The results from a clinical and pathologic review of 24 patients who underwent delayed orchiectomy after chemotherapy are presented. The testicular pathologic findings are correlated with those in extragonadal masses and also with a blinded review of postchemotherapy testicular ultrasound scans. RESULTS: The most common testicular pathological finding was a dense fibrous scar that was found in all patients. Three patients had persistent testicular germ cell cancer, six had mature teratoma, and one had carcinoma in situ. There was a strong concordance between the major testicular pathologic findings and those in the resected extragonadal masses. All three patients with persistent testicular germ cell cancer subsequently had disease progression in the extragonadal sites. Testicular ultrasound examination did not distinguish accurately between residual tumor or scar in the testis. CONCLUSION: Persistence of the primary testicular germ cell cancer is most likely due to the same heterogeneous response to chemotherapy observed in different metastatic sites. Because current imaging techniques cannot identify accurately those patients with residual testicular germ cell cancer or related testicular abnormalities that may predispose to subsequent relapse, orchiectomy after chemotherapy remains appropriate.

Adult↗
PubMed1995

A complicated case of metastatic teratoma. Growing teratoma syndrome and cerebral metastasis.

All patients presenting with metastatic teratoma should be regarded as potentially curable and this case demonstrates the multiple treatment modalities which are often needed in the management of such patients. Increasing experience with cisplatin based combination chemotherapy has led to the development of prognostic factors which are used to determine the intensity of treatment given to individual patients. Surgical intervention plays a very important role in the management of residual disease at the completion of chemotherapy. Recognition of the growing teratoma syndrome and the importance of early surgical excision is illustrated by this case. Isolated CNS relapse may occur because the CNS may act as a sanctuary site in patients receiving systemic chemotherapy, but does not preclude long term disease free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Mechanisms in removal of tumor by antibody.

We report two preliminary trials of antibody treatment of B-cell lymphoma. Advanced lymphoma was treated with chimeric FabFc2, in which mouse Fab' gamma is linked to two human Fc gamma 1 fragments so as to recruit natural effectors to tumor targets. Terminal lymphoma was treated with bispecific antibody (BsAb) which recruits the ribosome-inactivating protein saporin. These different mechanisms led to interesting differences in patterns of tumor clearance. Eight patients were treated with chimeric antibody of two specificities, each at 12 mg/kg: anti-CD37, plus either anti-CD38 or anti-CD19 according to tumor phenotype. On completion of the 3-wk treatment, residual plasma antibody had a half-life exceeding 10 d. Tumor cells in blood disappeared rapidly. However significant reductions in solid masses occurred in only three patients, becoming apparent 3-4 wk after beginning treatment and then continuing slowly. Five patients were treated with preformed immune complexes of saporin and F(ab' gamma)2 BsAb. Although doses of saporin reached 10 mg weekly, contact with the tumor can only have been fleeting: plasma antibody was undetectable (< 0.5 micrograms/mL) 48 h after infusion, whereas the saporin disappeared even faster and was undetectable (< 4 ng/mL) at 24 h. Tumor cells disappeared from the blood more slowly than occurred with chimeric antibody. In contrast shrinkage of extravascular tumor was more rapid, and occurred in all patients, but proved less durable.

Antibody Specificity↗