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Critical evaluation of the role of nutritional support with chemotherapy.

Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy-treated populations is not established. In randomized trials, no significant improvement in either response or survival was associated with TPN addition to chemotherapeutic treatment of adult patients with lymphoma, sarcoma, colon cancer, adenocarcinoma and small cell carcinoma of the lung, or testicular carcinoma. In two instances, TPN addition was associated with decreased survival, again raising the concern that caloric support in the absence of effective antitumor therapy might stimulate cancer growth. In any event, the hypothesis that nutritional repletion of a malnourished cancer patient receiving chemotherapy will improve clinical outcome remains to be critically tested, as studies demonstrating sequential improvement in lean body mass have not been reported. Most recently, consideration of potential mechanisms underlying the development of cancer cachexia has led to new strategies for nutritional intervention. For example, hypogonadism or low testosterone levels have been described in male patient populations with advanced cancer and correlated with weight loss and adverse outcome, leading to trial of replacement therapy with nandrolone decanoate. Similarly, the frequent identification of abnormal glucose metabolism in the patients with cancer cachexia has stimulated clinical trials with agents such as hydrazine sulfate and insulin designed to reverse the metabolic abnormality. Whether such efforts designed to alter metabolic abnormalities associated with cancer cachexia will improve clinical outcome will be determined in ongoing clinical trials.

Adult↗

Significance of epithelial membrane antigen in the work-up of problematic serous effusions.

Differentiation of reactive and/or atypical mesothelial cells from malignant epithelial cells in serous effusions remains a frequent diagnostic problem. Since epithelial membrane antigen (EMA) positive malignant cells in serous effusions have been reported in almost all adenocarcinomas and most malignant mesotheliomas, immunoreactivity for EMA is felt to be less useful than other antibodies in the workup of problematic serous effusions. However, immunostaining of reactive and/or atypical benign mesothelial cells for EMA has not been well studied, with only a few series reporting either weak or negative staining for EMA. This study was undertaken to evaluate how often reactive and/or atypical appearing mesothelial cells stain positively for EMA. One hundred eighty serous effusions (115 pleural, 55 peritoneal, and 10 pericardial) from 123 females and 57 males ages 20 to 89 yr were evaluated in which an antibody panel including EMA was performed on cell blocks (141 cases), cytospins (36 cases), or both (3 cases). Of the 100 cytologically positive cases, EMA immunoreactivity was present in 97/100 (97%) cases. One EMA negative case suspicious for a metastatic renal cell carcinoma was lost to follow-up and not included in the analysis. The remaining three negative cases consisted of malignancies not expected to have EMA positive cells (small cell carcinoma, neuroblastoma, and synovial sarcoma). Therefore, EMA was positive in virtually 100% of the remaining malignant cases. In the 78 cytologically negative cases, EMA positivity was present in 3/78 (3.8%) cases. Clinical follow-up of up to 14 mo in these three cases revealed no evidence of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages.

Expression of the candidate metastasis-suppressor gene nm23-H1 has been shown to correlate inversely with metastatic potential in some human tumors, but not in all. Until now, few studies have been carried out on the activity of the homologous nm23-H2 gene in human cancer. No nm23 transcription studies exist for human lung cancer so far. To determine whether the nm23 genes could have a metastasis-suppressor function in non-small-cell lung carcinoma (NSCLC), pulmonary sarcoma and carcinoids, we analysed both nm23-HI and nm23-H2 mRNA levels in 37 tumor samples obtained from patients who underwent potentially curative resection between 1986 and 1990, and in 4 metastatic tumors obtained from autopsy. As compared to corresponding healthy lung parenchyma, both nm23-HI and nm23-H2 transcript levels were elevated in 37 of 41 tumors. The increases in nm23 mRNA expression were stronger in advanced stages of squamous-cell carcinoma, large-cell carcinoma, sarcoma and carcinoids than in early stages of the respective tumor types. Within stages I and II of squamous-cell carcinoma, significantly higher nm23 mRNA levels were found in poorly differentiated tumors than in moderately differentiated ones. Moreover, an inverse correlation between nm23 expression and disease-free survival of the patients was observed. In conclusion, our results indicate that the increased nm23 expression in the analysed tumors is not consistent with the proposed metastasis-suppressor function, but the 2 nm23 genes nevertheless may be implicated in the mechanism of tumor progression.

Adenocarcinoma↗

Pharmacodynamics and long-term toxicity of etoposide.

Etoposide has been used in the treatment of a wide variety of neoplasms, including small-cell lung cancer, Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include the pretreatment leukocyte count, the performance status, the extent of prior erythrocyte transfusions, and the serum albumin level. In the past 7 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region. In addition, secondary acute lymphocytic leukemias (involving 11q23) have also been associated with prior epipodophyllotoxin exposure.

Child↗

Preclinical phase II study of ifosfamide in human tumour xenografts in vivo.

The in vivo effects of the oxazaphosphorine compound ifosfamide (IFO) on human tumour xenografts were assessed in thymus aplastic nude mice. The human origin of the tumours was confirmed by isoenzymatic and immunohistochemical methods. Tumour models were selected from a panel of 180 regularly growing, well-characterized xenografts. The maximum tolerated dose in tumour-bearing nude mice was determined to be 130 mg/kg per day given on days 1-3 and 15-17. After 21 days, lethality was 14% after i.p. and 6% after s.c. administration. A total of 43 human tumours were tested for antineoplastic activity, 15 of which (36%) showed regression: 4/5 breast cancer xenografts, 1/3 colon, 1/1 gastric, 2/7 non-small-cell lung cancers (NSCLC), 3/4 small-cell lung cancers (SCLC), 1/2 sarcomas and 3/3 testicular cancers. Two ovarian, two uterine and six renal cancer xenografts as well as three melanomas and five tumours of various histologies were resistant. In 30 human tumour xenografts, the antineoplastic efficacy of the two oxazaphosphorine derivatives cyclophosphamide and IFO was compared. The maximum tolerated dose of cyclophosphamide was 200 mg/kg per day given i.p. on days 1 and 15; it led to 17% lethality after 21 days. Cyclophosphamide induced tumour regression or remission in 10/30 xenografts (33%) and IFO in 13/30 (43%). In conclusion, the observed efficacy of IFO parallels the clinical situation. Breast, lung and testicular cancer and sarcomas proved to be responsive. The antitumoural activity of IFO shows similarities to that of cyclophosphamide; however, a higher response rate and lower toxicity were noted for the former. Preclinical phase II studies in nude mice seem to offer an effective way of identifying active drugs as well as sensitive tumour types for further clinical development.

Animals↗

Hereditary cancer: two hits revisited.

According to a "two-hit" model, dominantly inherited predisposition to cancer entails a germline mutation, while tumorigenesis requires a second, somatic, mutation. Non-hereditary cancer of the same type requires the same two hits, but both are somatic. The original tumor used in this model, retinoblastoma, involves mutation or loss of both are somatic. The original tumor used in this model, retinoblastoma, involves mutation or loss of both copies of the RB1 tumor-suppressor gene in both hereditary and non-hereditary forms. In fact, most dominantly inherited cancers show this relationship. New dominantly inherited cancers show this relationship. New questions have arisen, however. When a tumor-suppressor gene is ubiquitously expressed, why is there any specificity of tumor predilection? In some instances, it is clear that two hits produce only a benign precursor lesion and that other genetic events are necessary. As the number of necessary events increase, the impact of the germline mutation diminishes. The number of events is least for embryonal tumors, and relatively small for certain sarcomas. Stem-cell proliferation evidently plays a key role early in carcinogenesis. In some tissues it is physiological, as in embryonic development and in certain tissues in adolescence. In adult renewal tissues, the sites of the common carcinomas, mutation may be necessary to impair the control of switching between renewal and replicative cell divisions; the APC gene may be the target of such a mutation.

Humans↗

Results after pancreatic resection for metastatic lesions.

BACKGROUND: Unlike primary pancreatic carcinoma, isolated metastatic lesions to the pancreas are uncommon. Although the value of surgical resection is poorly documented, resection may be deemed appropriate in selected cases. The aim of this study was to review our experience with the operative management of pancreatic metastases. METHODS: Sixteen patients who underwent pancreatic resection for the treatment of metastatic disease were identified from a prospective pancreatic database. The clinical features of and results after resection were examined. RESULTS: Renal cell carcinoma was the most frequent primary histopathology (10 of 16; 62%). In the remaining patients, the primary histopathology was non-small-cell lung cancer (n = 3), sarcoma (n = 1), melanoma (n = 1), or transitional cell carcinoma of the bladder (n = 1). A prolonged disease-free interval (median, 7.5 years) was characteristic of most patients. Operative procedures performed included eight pancreaticoduodenectomies, seven distal pancreatectomies, and one total pancreatectomy. The operative mortality was 6%, and the morbidity was 25%. The overall 2- and 5-year actuarial survival rates were 62% and 25%, respectively. A trend toward improved survival was observed in the renal cell carcinoma patients, but this finding was not statistically significant. CONCLUSIONS: Long-term survival after pancreatic resection for metastatic disease is achievable, and patients with primary renal cell carcinoma seem to have a more favorable prognosis. Surgical resection should thus be offered to selected patients with isolated metastatic disease to the pancreas.

Adult↗

Extraskeletal Ewing's sarcoma mimicking traumatic hematoma.

We describe the clinical course of a 16-year-old baseball player with a history of recurrent hematoma of the thigh. The lesion was aspirated percutaneously several times and curetted under the diagnosis of traumatic hematoma. Microscopical examination revealed massive hemorrhage, necrosis, and a small number of Ewing's sarcoma cells. He died of multiple metastases. With recurrent hematoma in the soft tissue, neoplastic lesions should be ruled out.

Adolescent↗

Radiation-induced prostatic sarcoma: a case report.

A 64-year-old man had a prostatic sarcoma 8 years after transurethral prostatectomy and radical bilateral pelvic lymph node dissection with insertion of 125iodine implants for stage B1N carcinoma of the prostate. Therapy for the sarcoma consisted of isolated pelvic perfusion and then pelvic exenteration with creation of an ileal conduit and colostomy. The pathology report showed well encapsulated grade 2 spindle cell sarcoma of the prostate. Multiple small metallic particles were embedded in the tumor specimen.

Adenocarcinoma↗

Clinical applications of monoclonal antibodies against ovarian cancer-associated antigens.

Monoclonal antibodies (McAbs), reactive with tumour-associated antigens (TAAs) present on tumour cells, appear to offer new possibilities in the diagnosis and treatment of cancer (Table I). In addition to these prospects for clinical application, monoclonal antibodies also serve as useful instruments in basic cancer research. The hybridoma technology initiated by Köhler and Milstein in 1975, underwent a very rapid development and has now shown its potential in the field of oncology. This technique made it possible to produce very large quantities of homogeneous antibodies of a stable quality. These McAbs often recognize only one antigenic determinant, or epitope, of cell surface and other molecules. This high specificity is essential for in vivo applications, especially in therapeutic immunotargeting. A central question is whether the antibodies can reach and identify those antigens on ovarian tumour cells that are not shared with normal tissues. Various antibodies have been described in the field of gynaecological oncology, which are assumed to be capable of recognizing such ovarian tumour-related antigens. These McAbs, single or in combination, are capable of showing, unambiguously, the presence of various tumour-associated antigens on ovarian carcinoma cells either in tissue or, when antigen shedding occurs, in blood. However, these McAbs may also react with tumour-associated antigens present on endometrial, cervical, colorectal, breast or other carcinoma cells. The original immunogens used to generate these McAbs differ as to their origin: ovarian cancer cells, breast cancer cells, human milk-fat preparations, trophoblastic cells, endometrial cancer cells have been used as well as osteogenic sarcoma cells, epidermoid carcinoma cells and small-cell lung cancer, colorectal, pancreatic and laryngeal carcinoma cells. The histological distribution patterns of the antigens recognized by these McAbs vary widely: cross-reactions with normal tissue and with carcinomas different from those used as immunogen are frequently seen.

Antibodies, Monoclonal↗

Malignant rhabdoid tumor in adults--heterogenous tumors with a unique morphological phenotype.

Five cases of malignant rhabdoid tumors in adult patients are described. The tumors were characterized by sheets of poorly cohesive cells with distinctive hyaline cytoplasmic inclusions and eccentrically placed large vesicular nuclei with prominent nucleoli. A variety of lineage differentiation was shown by immunohistochemistry and electron microscopy, the lesions representing leiomyosarcoma, gastric carcinoma, epithelioid sarcoma, Merkel cell carcinoma and desmoplastic small round cell tumor. Previously reported cases of rhabdoid tumors in adults support the contention that such tumors, although of distinctive morphologic phenotype, are of heterogenous lineage differentiation, and do not represent a distinct clinicopathologic entity.

Adult↗

[Pleomorphic carcinoma of the lung in a patient with Mounier-Kuhn syndrome].

Pleomorphic carcinoma of the lung (PLC) is a rare malignant tumour presenting with a poor clinical outcome. It is included in the group of non-small cell lung carcinomas that contain sarcoma or sarcoma-like components (spindle cells/giant cells). Because of its rarity and diagnostic difficulties, the authors report a case of PLC in a 44 year-old patient, smoker, with the initial clinical presentation of a dorsal tumoural mass. As the time of diagnosis the tumour was in stage IV (TNM), the patient was treated only with supportive therapy and died five months later. During clinical evaluation, a Mounier-Kuhn Syndrome was confirmed. Clinical-imagiological aspects of this situation are reported as well as cytological and immunocytochemical features.

Adult↗

New perspectives on the toxicity of etoposide.

Etoposide has been used in the treatment of a wide variety of neoplasms, including small cell lung cancer. Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation, and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include pretreatment leukocyte count, performance status, extent of prior erythrocyte transfusions, and serum albumin level. In the past 5 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies, and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region.

Bone Marrow Diseases↗

[Cytotoxic activity of autologous lymphocytes against lung cancer cells; correlation of prognosis and recurrence pattern].

Cytotoxic activity of lymphocytes cultured in IL-2 against autologous primary lung cancer cells was studied in relation to curativity, prognosis and relapse rate. A total of 51 patients, 44 males and 7 females, consisting of those with adenocarcinoma (n = 27), squamous cell carcinoma (n = 19), large cell carcinoma (n = 2), small cell carcinoma (n = 1), lung sarcoma (n = 1), and carcinoid (n = 1), were evaluated. Pathological stages of the patients were stage I (n = 16), stage II (n = 1), stage III (n = 28), and stage IV (n = 6). Thirteen patients (25.5%) underwent curative surgery, 23 patients (45.1%) received relative curative surgery and 15 patients (29.4%) received non-curative surgery. The mean value of cytotoxic activity in the patients who received curative surgery was 34.7 +/- 15.3%, relative curative surgery 26.5 +/- 18.9%, and non-curative surgery 42.8 +/- 22.3%. Among the patients who underwent curative and relative curative surgery, 23 patients survived more than 2 years and 13 patients died of cancer recurrence. Mean value of cytotoxic activity in the former (36.7 +/- 15.9%) was significantly (p less than 0.01) higher than that in the latter (17.1 +/- 14.7%). Positive rate (percentage of patients whose CA exceeded 15%) of the former (86.9%) was also higher than that of the latter (46.1%). Comparison between the survival curves of the positive cases (CA 15.0%) and negative cases (CA less than 15.0%) revealed a significantly better prognosis for the former (generalized Wilcoxon test: W/square root VarW = 2.198). The mean cytotoxic activity in the cases of local recurrence (25.7 +/- 16.6%, n = 7) was higher (p less than 0.10) than that in the cases with distant metastases (9.3 +/- 6.3%).

Cytotoxicity, Immunologic↗

Gliosarcoma with cranial penetration and extension to the maxillary sinus.

A 70 year old woman underwent an anterior rightsided temporal lobectomy for a mixed glioblastoma-fibrosarcoma. Six months later, she presented with rightsided zygomatic and maxillary swellings, associated with rightsided ptosis, chemosis, and nerve palsies of the III, IV, VI, and VII cranial nerves. A computerized scan (CT) of the head revealed tumor erosion of the skull base of the right middle fossa with extension into the maxillary sinus. This was confirmed at surgery. Pathologic examination revealed a predominantly small cell anaplastic glioblastoma associated with sarcoma elements, similar to the original intracranial tumor. This case documents a rare and atypical behavior of malignant glial tumors.

Aged↗

Esophageal cancer. Radiologic diagnosis.

The vast majority of malignant esophageal tumors are either squamous cell carcinomas or adenocarcinomas arising in Barrett's mucosa. This article reviews the spectrum of findings associated with these tumors on barium studies. Particular emphasis is placed on the role of double-contrast esophagography in detecting early cancers, because these lesions have the best possibility for cure. Other less common malignant tumors, such as spindle cell carcinoma, small cell carcinoma, leiomyosarcoma, Kaposi's sarcoma, and malignant melanoma, are also reviewed.

Esophageal Neoplasms↗

Orbital Ewing's sarcoma of the orbit.

PURPOSE: Ewing's tumor is a primary tumor of bone in childhood that only rarely involves the orbit. Most such cases are metastatic from distant sites. This tumor may be confused with other small round cell malignancies of childhood, and immunohistochemical studies are essential in making the diagnosis. METHODS: We present two cases of Ewing's tumor of the orbit. One was in a 22-year-old boy with an occult primary tumor in the frontal bone that became symptomatic after forehead trauma. The other example was in a 7-year-old boy with a known Ewing's primary of the clavicle. The clinical manifestations and diagnostic criteria are discussed. RESULTS: In most cases with orbital involvement, ophthalmic symptoms consist of proptosis, pain, and occasionally visual loss and motility restriction. The diagnosis is typically unsuspected before histologic evaluation. Electron microscopic and immunohistochemical analyses are essential in making the diagnosis and are necessary for all such small round cell tumors. CONCLUSIONS: Ewing's sarcoma is a rare orbital tumor of bone mainly affecting children. Local treatment relying on surgical extirpation and radiotherapy alone has proven inadequate, with 5-year survival rates of <10%. The addition of chemotherapy has improved survival rates significantly to approximately 50%.

Biopsy↗

Osteosarcoma with small cells simulating Ewing's tumor.

Twenty-four patients who had osseous lesions with histological features of both Ewing's sarcoma and osteosarcoma were studied. Because of their appearance, these lesions have been labeled small-cell osteosarcomas. They appear to represent a definite histological entity and the prognosis may be worse for these lesions than for conventional osteosarcomas. It is most important not to misdiagnose this tumor as Ewing's sarcoma because it appears not to be radiosensitive. Radical surgery and modern adjuvant chemotherapy seem to offer the best chance of cure.

Adolescent↗