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Results of treatment of stage IA and IIA Hodgkin's disease.

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70%-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.

Adolescent↗

Sarcomas of the head and neck.

With the exception of pediatric RMS, soft tissue sarcomas only rarely arise in the head and neck region. Soft tissue sarcomas include a diverse array of histologic types because of the variety of mesenchymal tissues from which they originate. The combination of infrequent occurrence, varied pathologic features, and the many potential sites of presentation makes these tumors a challenge for the head and neck oncologist and underscore the need for review by a pathologist experienced with soft tissue tumors. Classification schemes that group sarcomas according to grade have been helpful in providing prognostic information. Although local control of the primary tumor is critical to successful treatment of both high- and low-grade lesions, the high rate of distant metastases in high-grade tumors supports the role of combined modality therapy. Compared with other types of head and neck neoplasms, such as squamous cell carcinoma, soft tissue sarcomas have low rates of regional metastases. Surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumors arising in sites not amenable to resection. Exceptions to this principle include RMSs of the orbit, paranasal sinuses, and masticator space in children; these are usually treated with radiotherapy and combined multiagent chemotherapy, thereby avoiding the functional and cosmetic impact of surgery. Also, extensive angiosarcomas of the scalp should be treated with multimodality therapy combining surgery and wide-field radiation therapy in an attempt to achieve local control. Adjuvant radiotherapy is generally recommended for high-grade sarcomas, large tumors, close or positive surgical margins, and certain histologic variants. Systemic chemotherapy is recommended for those tumors with a significant risk of distant metastases. Increasingly, neoadjuvant chemotherapy is being used to determine responsiveness to chemotherapy, which can help physicians select patients who may benefit from systemic postoperative therapy. Traditional predictors of treatment failure for soft tissue sarcomas include larger tumor size, high-grade histology, and positive surgical margins. The advent of more advanced reconstructive techniques, including free tissue transfer, has made more aggressive surgical resection of these tumors possible. Nevertheless, a considerable number of ancillary support staff are critical to the patient's postoperative rehabilitation and eventual return to a satisfactory level of function and quality of life. In the future, the discovery of the molecular pathogenesis of specific tumor types, such as the cytogenetic findings in synovial sarcoma, will improve physicians' prognostic abilities and selection of patients who are most likely to benefit from emerging adjuvant therapies.

Clinical Trials as Topic↗

Therapy for stage I aggressive non-Hodgkin's lymphoma.

Although radiotherapy was considered sufficient for stage I and limited stage II aggressive non-Hodgkin s lymphoma in the past, new data from randomized studies have shown that intensified chemotherapy or combined modality therapy (multiagent chemotherapy followed by involved field radiotherapy) can result in complete remission in 75-90% of the cases, with 5-year overall survival ranging between 82% and 89%. However, not all patients benefit from this management. Patients above 60 years of age, with high lactate dehydrogenase concentration, poor performance, or extranodal disease localized in the testis or central nervous system have a much worse outcome. Therefore, typical extranodal character of this disease (40-57% of the patients show a primary extranodal localization) needs to be recognized and therapy adapted to these subcategories.

Combined Modality Therapy↗

Changes in monocyte phagocyting activity after multi-agent chemotherapy in non-small cell lung cancer.

Changes in monocyte functions have been described in several human malignancies. The monocyte/macrophage system is known to play a crucial role in the rejection of tumor cells and phagocytosis represents an important defense mechanism used by these cells. This paper reports the adherence power and phagocyting ability (latex beads) of circulating monocytes in 20 patients with unresectable non-small cell lung cancer (NSCLC), stage IIIB or stage IV, before and after multiagent chemotherapy (carboplatin + etoposide + ifosfamide or cisplatinum + etoposide). We demonstrated that both monocyte adherence and phagocytosis were not affected in lung cancer patients before chemotherapy in comparison with healthy controls. After chemotherapy, a statistically significant decrease in monocyte count on day 4 (p < 0.05) and in their phagocyting ability on day 4 and 15 (p < 0.001 and p < 0.05 respectively) was showed. In addition, a statistically reduced monocyte adherence was found on day 4 (p < 0.05). The described impairment was prolonged but reversible. These changes in monocyte functions after chemotherapy could be due to a direct effect of the chemotherapy on these cells or to functionally immature cells circulating after myelodepression. The in vitro assessment of monocyte functions may be useful to better clarify mechanisms by which anti-neoplastic agents may act on immune functions and prevent adverse side effects.

Adult↗

Primary gastrointestinal non-Hodgkin's lymphomas. A retrospective clinicopathologic study of 150 cases.

The records of 150 primary gastrointestinal (GI) lymphomas in adults collected from 1974 to 1982 at the Department of Pathology, University of Vienna, were reviewed. One hundred thirty-three cases of malignant lymphomas (ML) were analyzed with respect to histologic type, presenting tumor stage, and clinical course, as well as for factors influencing prognosis. The histologic type of ML as assessed by the Working Formulation and the Kiel, the Lukes and Collins, and the Rappaport classifications showed only a minor influence on prognosis. MLs of follicular center cell origin prevailed in the stomach and large cell, immunoblastic MLs prevailed in the bowel. Immunoperoxidase studies indicated a B-cell nature of GI MLs and demonstrated intracytoplasmic IgM kappa or lambda in most of the MLs of the small lymphocytic, plasmacytoid, and immunoblastic type, respectively. The 105 cases of gastric MLs represented 3.6% of all malignancies of the stomach collected during the study period. Clinical symptoms preceded the diagnosis by 4.4 months on average, and endoscopic biopsy specimens indicated malignancy in 78%. Presenting tumor stages of gastric MLs according to the Ann Arbor staging system were Stage I in 20%, Stage II in 76.2%, and Stage IV in 3.8%. The 28 cases of intestinal ML localized in the small and large bowel without any site prevalence presented with Stage I in 14%, Stage II in 82%, and Stage III in 4%. Tumor resection was performed in 90% of all cases and was followed by multiagent therapy in 53%. Radical tumor resection was obtained in 58% of the gastric MLs and only 28.6% of the intestinal MLs and was closely related to tumor stage. Statistical analysis demonstrated a significant influence of the presenting tumor stage on prognosis as expressed by the overall 2-year survival rate of 70% for Stage I versus 39% for Stage II ML. In addition, Stage II1 according to Musshoff et al. run a better course than II2 as shown by the disease-free 2-year survival rate of 49% versus 15%, respectively. Radical tumor resection was a major determinant of survival and cure of disease as exhibited by the disease-free 2-year survival rate of 57% after radical resection versus 8% after nonradical resection of ML. Finally, diffuse tumor growth and tumor penetration of the gastric wall beyond serosa decreased the survival rates.

Adult↗

AIDS-associated malignant lymphoma.

Lymphoma has been well described in various states of congenital, acquired, and iatrogenic immune dysfunction, and the clinical and pathologic characteristics in these settings are similar to those seen in patients with HIV-induced immunodeficiency. High grade B cell lymphomas are expected, with widespread extranodal disease at the time of initial presentation. Unusual sites of disease may be seen, such as the CNS. Factors predictive of short survival include low performance status, history of AIDS prior to the diagnosis of lymphoma, stage IV or bone marrow involvement, and low CD4 cells. Use of intensive multiagent chemotherapy may be associated with demise from opportunistic infections. Less intensive regimens may be indicated in patients with poor prognostic indicators, whereas patients lacking these factors may be able to tolerate greater dose intensity.

Central Nervous System Neoplasms↗

Progressive epidermotropic CD8+/CD4- primary cutaneous CD30+ lymphoproliferative disorder in a patient with sarcoidosis.

We describe a patient with a CD8+/CD4- primary cutaneous CD30(+) lymphoproliferative disorder with striking epidermotropic histology and coincident cutaneous and systemic sarcoidosis. This patient illustrates the spectrum of clinical and histologic features of CD30+ lymphoproliferative disorders and the need for adequate staging in such cases. This patient's CD30/CD8 coexpression is rare and has clinical and prognostic implications, including mucosally and acrally accentuated lesions and a potentially more aggressive course. Primary cutaneous CD30+ lymphoproliferative disorders have an excellent prognosis; therefore multiagent chemotherapy modalities are generally not indicated. The combination of T-cell lymphoma and sarcoidosis is also rare and may limit treatment options.

Adult↗

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗

Adult Burkitt's lymphoma.

Burkitt's lymphoma is a mature B-cell lymphoma that is characterized by a rapid proliferative rate and propensity for extranodal sites of involvement such as the gastrointestinal tract and central nervous system. This subtype of non-Hodgkin's lymphoma is associated with unique cytogenetic translocations involving the c-MYC oncogene on chromosome 8, which appears to be involved in the pathogenesis of this disease. Although current literature is limited by a lack of randomized trials, Burkitt's lymphoma appears to be curable in a high proportion of cases if treated with aggressive multiagent chemotherapy regimens. The use of autologous stem cell transplantation appears to benefit patients who have had chemotherapy-sensitive relapses. The role of allogeneic stem cell transplantation for this disease remains uncertain. Patients with HIV-associated Burkitt's lymphoma appear to have a better prognosis today, which is likely a result of more effective antiretroviral therapy and the ability to treat selected patients with more aggressive chemotherapeutic regimens than before. This article will review the epidemiologic, biologic, diagnostic, and therapeutic aspects of Burkitt's lymphoma in adults.

Adult↗

Update on central function relevant to sex: remodeling the basis of drug treatments for sex and the brain.

Sexual function draws on a complex network of peripheral and central neural pathways. The standard focus on erectile difficulties and peripheral therapies has been highly successful clinically but there are many unresolved issues in men and newly discussed issues in women that will likely benefit from improved understanding of the central nervous system and sexual function. The spectrum of future therapies, based on evolving central neurophysiological understanding, will include the management of problems related to orgasm, ejaculation, desire, motivation, anxiety, and pleasure. This new range of therapies will employ old and new neurochemicals and pathways singly or in combination. The capability of hormones to modulate many of the sexual pathways will also contribute to the rise of multiagent therapy. The expanded understanding, in combination with enhanced imaging technologies, will renew the role of diagnosis and cause-specific treatment.

Animals↗

Primary lymphoma of the central nervous system: Manitoba experience and literature review.

We describe eight cases of primary cerebral lymphoma seen in Manitoba from 1980 to 1985. The clinical presentation is similar to other primary brain tumors. The diagnosis should be considered when single or multiple, often deep lesions, show dense enhancement on computerized tomographic (CT) scan, but are avascular at angiography. These tumors are histologically indistinguishable from non-Hodgkins lymphomas arising outside the CNS. The prognosis is poor. However, radiotherapy with or without surgery may offer significant palliation. Although there is no consensus on the value of chemotherapy, corticosteroids alone or multiagent chemotherapy have shown promise in a few cases. For these reasons, histologic diagnosis should be sought in all cases and surgery, radiotherapy, and chemotherapy should be considered, as prolonged survival is possible.

Aged↗

Acute hypotension related to sepsis in the obstetric patient.

While infections are a common complication of pregnancy, bacteremia and septic shock are relatively rare. Efforts to prevent serious bacterial infections are the most effective means of minimizing maternal and fetal morbidity. Screening for first trimester asymptomatic bacteriuria, prompt and thorough evaluation of suspected bacterial infections, and conscientious intrapartum assessment can have a significant impact in decreasing localized bacterial infections. The prompt recognition and institution of antimicrobial therapy in women suspected of having systemic infections is of paramount importance in reducing the incidence of serious maternal morbidity and mortality. Initial efforts in the treatment of sepsis should be directed at intravascular volume expansion in an effort to improve myocardial performance and tissue oxygenation. Inotropic agents occasionally may be necessary; however, they should be used with caution and only after adequate volume expansion has been provided. Adequate antimicrobial therapy requires treatment with multiagent therapy, providing coverage for the wide variety of genital tract pathogens.

Acute Disease↗

Brain metastases in children with solid tumors.

BACKGROUND: Brain metastases are uncommon among children with solid tumors. However, improvements in survival have increased the period of time during which children are at risk for developing these metastases. The authors reviewed brain metastases in children with solid tumors treated at the Centre Léon Bérard during the 9 years between 1987 and 1995. METHODS: Among 486 patients with solid tumors, 162 eventually developed distant metastases in their disease process, including 12 brain metastases detected by imaging. The tumor type, clinical setting, imaging characteristics, treatment modalities, and outcome were assessed for each patient. RESULTS: The most common tumors causing brain metastases were Ewing's sarcoma (in three patients), neuroblastoma (in three patients), and osteogenic sarcoma (in three patients). At the time of initial diagnosis, 9 of the 12 patients had metastatic disease. All but one patient initially received intensive multiagent chemotherapy, including high dose chemotherapy with bone marrow rescue in six patients. The median time from initial diagnosis to the detection of brain metastases was 15 months. These metastases were clinically detectable in 10 patients and subclinical in 2 patients. Brain metastases were present at the time of first relapse in five patients. In two patients, the brain was the only site of relapse. All other patients had extensive systemic disease. Seven patients had multiple brain metastases. Two children underwent surgical resection of solitary metastases, and eight were irradiated. One child achieved complete remission following chemotherapy and irradiation. All other children died, mostly of their systemic disease, within a median period of 3 months. CONCLUSIONS: The introduction of effective systemic chemotherapy has changed the patterns of brain metastases in children. The increasing incidence of these metastases in patients with sarcoma and neuroblastoma suggests that the brain is a pharmacologically protected site in patients initially diagnosed with metastatic disease.

Adolescent↗

Bone marrow transplantation in lymphomatoid granulomatosis. Report of a case.

Lymphomatoid granulomatosis is an unusual disorder histologically characterized by an angiocentric, angiodestructive mixed cellular infiltrate. The most frequent clinical manifestations are seen in the lungs, the skin, and the central nervous system. Progression to lymphoma may occur, particularly in patients who are anergic. The authors report the case of a boy who had had a splenectomy at 2 years of age for presumed Evan's syndrome, and two episodes of pneumococcal meningitis at 5 and 10 years of age. At 14 years, he had severe respiratory compromise, and a lung biopsy specimen showed lymphomatoid granulomatosis. The liver and bone marrow also were affected. Improvement occurred with multiagent chemotherapy, but he had multiple relapses. A bone marrow transplant was performed using a human leukocyte antigen (HLA) identical mixed lymphocyte culture (MLC) nonreactive brother as the donor. He remains in remission more than 3 years post-transplant. In addition, his abnormal immune function has improved.

Adult↗

Immediate breast reconstruction for stage III breast cancer using transverse rectus abdominis musculocutaneous (TRAM) flap.

BACKGROUND: The management of state III breast cancer is challenging; it often includes multimodal treatment with systemic therapy and/or radiation therapy and surgery. Immediate breast reconstruction has not traditionally been performed in these patients. We review the results of immediate transverse rectus abdominis musculocutaneous (TRAM) flap in 21 patients treated for stage III breast cancer. METHODS: Data have been collected retrospectively on 21 patients diagnosed with stage III breast cancer between 1987 and 1994. All patients had mastectomy and immediate TRAM reconstruction. Thirteen patients received primary systemic therapy, 10 patients received postoperative consolidation radiotherapy to the operative site, and 3 patients received preoperative radiation. RESULTS: Mean follow-up for the group was 26 months. Two patients died with disseminated disease: neither of them developed local disease recurrence in the operative site; 82% of the patients followed for at least two years are free of disease. Sixty-two percent of the patients received preoperative chemotherapy, the remaining patients received postoperative multiagent chemotherapy and/or radiation therapy. Two of the patients received autologous bone marrow transplants after their adjuvant therapy. Ten patients had postoperative radiotherapy for consolidation; three patients received preoperative radiation. CONCLUSIONS: Immediate TRAM reconstruction for stage III breast cancer is not associated with a delay in adjuvant therapy or an increased risk of local relapse. It facilitates wide resection of involved skin without skin grafting. Radiation therapy can be delivered to the reconstructed breast when indicated without difficulty. Breast reconstruction facilitates surgical resection of stage III breast cancer with primary closure and should be considered if the patient desires immediate breast reconstruction.

Breast Neoplasms↗

Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Société Française d'Oncologie Pédiatrique.

The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Sociéte Française d'Oncologie Pédiatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died).

Bone Marrow↗

Hospital disaster preparedness in Los Angeles County.

BACKGROUND: There are no standardized measures of hospital disaster preparedness or hospital "surge capacity." OBJECTIVES: To characterize disaster preparedness among a cohort of hospitals in Los Angeles County, focusing on practice variation, plan characteristics, and surge capacity. METHODS: This was a descriptive, cross-sectional survey study, followed by on-site verification. Forty-five 9-1-1 receiving hospitals in Los Angeles County, CA, participated. Evaluations of hospital disaster plan structure, vendor agreements, modes of communication, medical and surgical supplies, involvement of law enforcement, mutual aid agreements with other facilities, drills and training, surge capacity (assessed by monthly emergency department diversion status, available beds, ventilators, and isolation rooms), decontamination capability, and pharmaceutical stockpiles were assessed by survey. RESULTS: Forty-three of 45 hospital plans (96%) were based on the Hospital Emergency Incident Command System, and the majority had protocols for hospital lockdown (100%), canceling elective surgeries (93%), early discharge (98%), day care for children of staff (88%), designating victim overflow areas (96%), and predisaster "preferred" vendor agreements (96%). All had emergency medical services-compatible radios and more than three days' worth of supplies. Fewer hospitals involved law enforcement (56%) or had mutual aid agreements with other hospitals (20%) or long-term care facilities (7%). Although the vast majority (96%) conducted multiagency drills, only 16% actually involved other agencies in their disaster training. Only 13 of 45 hospitals (29%) had a surge capacity of greater than 20 beds. Less than half (42%) had ten or more isolation rooms, and 27 hospitals (60%) were on diversion greater than 20% of the time. Thirteen hospitals (29%) had immediate access to six or more ventilators. Less than half had warm-water decontamination (42%), while approximately one half (51%) had a chemical antidote stockpile and 42% had an antibiotic stockpile. CONCLUSIONS: Among hospitals in Los Angeles County, disaster preparedness and surge capacity appear to be limited by a failure to fully integrate interagency training and planning and a severely limited surge capacity, although there is a generally high level of availability of equipment and supplies.

Cross-Sectional Studies↗

Locally recurrent non-small-cell lung cancer after complete surgical resection.

Between Jan. 1, 1976, and Dec. 31, 1985, at our institution, 37 patients who had undergone prior complete surgical resection of non-small-cell lung cancer received definitive thoracic radiation therapy (TRT) for locally recurrent disease. Of the 37 recurrences, 33 were in the pulmonary parenchyma or the hilar, mediastinal, or supraclavicular lymph nodes; the other 4 were in the chest wall. The initial stage of disease was I in 43%, II in 35%, and IIIA in 19%, whereas at the time of local recurrence, the stage was I in 8%, II in 11%, IIIA in 57%, IIIB in 22%, and IV in 3% (this patient had multiple pulmonary nodules encompassible within a single TRT field). The locally recurrent lesions were squamous cell carcinoma in 30%, adenocarcinoma or large-cell carcinoma in 46%, mixed types in 5%, and unknown type in 19%. All patients received megavoltage TRT, most often 4,000 cGy in 10 fractions administered in a split-course schedule. In addition, 15 patients received multiagent chemotherapy, usually a combination of cyclophosphamide, doxorubicin hydrochloride, and cisplatin or a regimen that included these drugs. The 2-year and 5-year survivals were 30% and 4%, respectively, and the median duration of survival was 13.7 months. Survival was not improved by the addition of chemotherapy. Approximately half of the patients had radiographic and symptomatic responses after TRT. Of 33 patients assessable for post-TRT patterns of failure, 46% had local failure only, 18% had local plus systemic failure, and 32% had systemic failure only. Two-thirds of the patients died as a direct consequence of progressive chest disease, despite receiving TRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗