Showing papers by "Memorial Sloan Kettering Cancer Center published in 1990"

Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues.

Abstract: We have characterized the normal human tissue distribution and tumor expression of the human multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) by immunohistochemical staining of frozen tissue sections of human normal and tumor tissues, using three mouse monoclonal antibodies (MAb) which recognize at least two different epitopes of Pgp. Pgp expression on normal human tissues was detected in specialized epithelial cells with secretory/excretory functions, trophoblasts in the placenta, and on endothelial cells of capillary blood vessels at blood-tissue barrier sites. There were significant differences in the staining patterns of these MAb. Mouse MAb HYB-241 and HYB-612 each recognize an extracellular epitope of Pgp, whereas mouse MAb C219 detects a carboxy terminal intracellular epitope and has recently been reported to crossreact with the MDR3 gene product. HYB-241 and HYB-612 strongly stain endothelial cells and trophoblasts, whereas C219 is weakly positive or unreactive on these cells. Likewise, C219 strongly stains the biliary pole of hepatocytes, skeletal and heart muscle fibers, whereas HYB-241 and HYB-612 are unreactive on these cells. Immunopathological studies were performed on a wide variety of human tumors. Pgp expression on human tumors was most commonly detected in colon. renal, and adrenal carcinomas; rarely in lung and gastric carcinomas and certain germ cell tumors; and was undetectable in breast and endometrial carcinomas tested. Few sarcomas and none of the melanomas, neuroblastomas, gliomas, and pheochromocytomas had detectable Pgp expression. Intensity and pattern of staining varied among different cases of a given tumor type; although homogeneous immunoreactivity was observed, heterogeneity of expression in a single histological section was more common. The finding of Pgp expression in a variety of normal tissues with diverse physiological functions suggests that the role of Pgp may not be limited to excretion of xenobiotics. Pgp expression in capillaries of the brain and testis may explain the failure of drugs such as vincristine and actinomycin-D to penetrate into these tissues, allowing them to remain as pharmacological sanctuaries for malignant cells. Although Pgp expression can now be detected in a variety of human tumors, further studies are needed to establish the possible significance of this finding.

Breakthrough pain: definition, prevalence and characteristics

Abstract: In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.

Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract

Abstract: A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the orpharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended.

Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers.

Abstract: The F19 antigen is a cell surface glycoprotein (Mr, 95,000) of human sarcomas and proliferating, cultured fibroblasts that is absent from resting fibroblasts in normal adult tissues. Normal and malignant epithelial cells are also F19-. The present immunohistochemical study describes induction of F19 in the reactive mesenchyme of epithelial tumors. F19+ fibroblasts were found in primary and metastatic carcinomas, including colorectal (18 of 18 cases studied), breast (14/14), ovarian (21/21), bladder (9/10), and lung carcinomas (13/13). In contrast, the stroma of benign colorectal adenomas, fibrocystic disease and fibroadenomas of breast, benign prostate hyperplasia, in situ bladder carcinomas, and benign ovarian tumors showed no or only moderate numbers of F19+ fibroblasts. Analysis of dermal incision wounds revealed that F19 is strongly induced during scar formation. Comparison of F19 with the extracellular matrix protein tenascin, a putative marker of tumor mesenchyme, showed a cellular staining pattern for F19 vs. the extracellular matrix pattern for tenascin and widespread expression of tenascin in F19- normal tissues and benign tumors. Our results suggest that the F19+ phenotype correlates with specialized fibroblast functions in wound healing and malignant tumor growth. Because of its abundance in tumor mesenchyme, F19 may serve as a target for antibodies labeled with radioisotopes or toxic agents, or inflammatogenic antibodies, in carcinoma patients.

Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity.

Abstract: To study the effects of localized secretion of cytokines on tumor progression, the gene for human interleukin 2 (IL-2) was introduced via retroviral vectors into CMS-5 cells, a weakly immunogenic mouse fibrosarcoma cell line of BALB/c origin. Secretion of low levels of IL-2 from the tumor cells abrogated their tumorigenicity and induced a long-lasting protective immune response against a challenge with a tumorigenic dose of parental CMS-5 cells. Co-injection of IL-2-producing CMS-5 cells with unmodified tumor cells inhibited tumor formation even when highly tumorigenic doses of CMS-5 cells were used. Cytolytic activity in mice injected with parental CMS-5 cells was transient and was greatly diminished 3 wk after injection, as commonly observed in tumor-bearing animals. However, in mice injected with IL-2-producing cells, tumor-specific cytolytic activity persisted at high levels for the duration of the observation period (at least 75 d). High levels of tumor-specific cytolytic activity could also be detected in parental CMS-5 tumor-bearing animals 18 d after inoculation with tumor cells, if IL-2-producing CMS-5 cells but not unmodified parental tumor cells were used as targets. These studies highlight the potential advantages of localized secretion of cytokines mediated via gene transfer to induce potent anti-tumor immune responses.

Solution structure of the glucocorticoid receptor DNA-binding domain

Abstract: The three-dimensional structure of the DNA-binding domain (DBD) of the glucocorticoid receptor has been determined by nuclear magnetic resonance spectroscopy and distance geometry. The structure of a 71-residue protein fragment containing two "zinc finger" domains is based on a large set of proton-proton distances derived from nuclear Overhauser enhancement spectra, hydrogen bonds in previously identified secondary structure elements, and coordination of two zinc atoms by conserved cysteine residues. The DBD is found to consist of a globular body from which the finger regions extend. A model of the dimeric complex between the DBD and the glucocorticoid response element is proposed. The model is consistent with previous results indicating that specific amino acid residues of the DBD are involved in protein-DNA and protein-protein interactions.

The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions.

Abstract: In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain e.g., neuropathic pains, may be unresponsive to these drugs. This concept has important implications for both clinical practice and basic understanding of opioid mechanisms. We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation. The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone. From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of ‘complete’ or ‘adequate’ analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs. Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects.

Measuring PET scanner sensitivity: relating countrates to image signal-to-noise ratios using noise equivalents counts

Abstract: True coincidence count (TCC) and noise equivalent count (NEC) curves were measured with a standardized 20-cm-diameter nylon cylinder for five different CTI/Siemens PET (positron emission tomography) scanners with several scanner-collimator combinations: (1) 831/08-12 with 1-mm collimator septa; (2) 933/08-12 and 933/08-16 with 3 to 1-mm tapered collimator septa; and (3) 931/08-12 with 3 to 1-mm tapered and a 1-mm collimator septa and the 931/08-16 with 3 to 1-mm tapered collimator septa In addition, TCC and NEC curves on the 933/08-12 were compared with those from an Alderson brain phantom In general, it is found that the TCC curves indicated peak count rates and activity levels that were as much as 50% higher than the corresponding values from NEC curves The primary factor causing this difference is the noise effect of the randoms component It is demonstrated that, compared to the Alderson brain phantom, the standard 20-cm cylinder is a poor predictor of count rate performance for PET brain imaging >

The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity.

Abstract: A retrospective review of the records of 501 previously untreated patients from January 1, 1965 through December 31, 1986 with squamous cell carcinoma of the oral cavity was undertaken to ascertain the prevalence of ipsilateral neck node metastases (NM) by neck level. The 501 patients underwent 516 radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection (ED) in the N0 neck, immediate therapeutic dissection (ITD) in the N+ neck, and subsequent therapeutic dissection (STD) in the neck observed which converted clinically to N+. Pathologically identified NM occurred 34% of the time in ED, 69% in ITD and 90% in STD. The sensitivity, specificity, and overall accuracy of the clinical exam was 70%, 65%, and 68%, respectively. Detailed analysis was performed for each group based on the primary site. This revealed a prevalence of NM in level IV of 3% (five of 167) for ED versus 17% (49/296) for ITD + STD (P less than 0.001). Tongue, retromolar trigone, and cheek did not have NM in level V in any group. The prevalence of NM in level V for floor of mouth or gum primaries was less than 1% (one of 109) in ED versus 6% (ten of 167) in ITD + STD (P less than 0.03). These data support the trend toward selective limited neck dissection in both N0 and N+ patients. Further, they provide the foundation for planning of future prospective trials to assess the efficacy of modifications in the extent of neck dissection.

Protein splicing converts the yeast TFP1 gene product to the 69-kD subunit of the vacuolar H(+)-adenosine triphosphatase.

Abstract: The TFP1 gene of the yeast Saccharomyces cerevisiae encodes two proteins: the 69-kilodalton (kD) catalytic subunit of the vacuolar proton-translocating adenosine triphosphatase (H(+)-ATPase) and a 50-kD protein. The 69-kD subunit is encoded by the 5' and 3' thirds of the TFP1 coding region, whereas the 50-kD protein is encoded by the central third. Evidence is presented that both the 69-kD and 50-kD proteins are obtained from a single translation product that is cleaved to release the 50-kD protein and spliced to form the 69-kD subunit.

Retroviral vector-mediated γ-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity

Abstract: Retroviral vectors were used to introduce the γ-interferon (IFN-γ) gene into CMS-5 cells, a weakly immunogenic tumor of BALB/c origin. After selection in G418-containing medium, colonies were isolated, cloned, and expanded to cell lines. IFN-γ secretion was assessed using a bioassay and enzyme-linked immunosorbent assay, and high (25 units/ml) and low (5 units/ml) IFN-γ producers were isolated. Tumor growth was followed after intradermal injection, and spleen cells were isolated at different time points. IFN-γ secretion by tumor cells abrogated their tumorigenicity and induced a persistent and specific antitumor immunity. In contrast to the normally observed cellular immunosuppression in unmodified CMS-5 tumor-bearing mice, IFN-γ-producing tumors induced a long lasting state of T-cell immunity, as judged by rejection of a CMS-5 tumor challenge and persistence of specific cytotoxic activity in the spleen cell population. High levels of tumor-specific cytotoxic activity could also be detected if IFN-γ-secreting tumor cells, but not unmodified CMS-5 cells, were used as targets at a time point when immunosuppression was usually seen. These studies highlight the potential advantages of localized IFN-γ secretion to induce potent antitumor immune responses.

Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization

Abstract: Chronic myelogeneous leukemia (CML) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9, respectively. In most cases, the fusion involves a reciprocal translocation t(9;22)(q34;q11), which produces the cytogenetically distinctive Philadelphia chromosome (Ph1). Fusion can be detected by Southern (DNA) analysis or by in vitro amplification of the messenger RNA from the fusion gene with polymerase chain reaction (PCR). These techniques are sensitive but cannot be applied to single cells. Two-color fluorescence in situ hybridization (FISH) was used with probes from portions of the bcr and abl genes to detect the bcr-abl fusion in individual blood and bone marrow cells from six patients. The fusion event was detected in all samples analyzed, of which three were cytogenetically Ph1-negative. One of the Ph1-negative samples was also PCR-negative. This approach is fast and sensitive, and provides potential for determining the frequency of the abnormality in different cell lineages.

Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis

Abstract: We established a continuous cell line, NCI-H295, from an invasive primary adrenocortical carcinoma. The cell line was established in a fully defined medium (HITES) and later could be adapted for growth in a simple medium supplemented only with selenium, insulin, and transferrin and devoid of serum, steroids, fibroblast growth factor, and a source of exogenous cholesterol. NCI-H295 cells had a relatively long population doubling time and were tumorigenic when inoculated s.c. into athymic nude mice. The cultured cells had ultrastructural features of steroid-secreting cells and contained complex cytogenetic abnormalities including the presence of multiple marker chromosomes. Steroid analyses (radioimmunoassays and mass spectrometry), performed 7 to 9 years after culture initiation, demonstrated secretion of more than 30 steroids characteristic of adrenocortical cells. Total unconjugated steroid secretion in serum-supplemented medium was 2.83 micrograms/10(6) cells/24 h and about 4-fold less in serum-free medium. The major pathway of pregnenolone metabolism in NCI-H295 cells is androgen synthesis, with formation of dehydroepiandrosterone, androstenedione, testotesterone, and at least three sulfated androgens, as well as estrogens. In addition, formation of cortisol, corticosterone, aldosterone, and 11 beta-hydroxyandrostenidione indicated the presence of 11 beta-hydroxylase. Thus, multiple pathways of steroidogenesis are expressed by NCI-H295 cells, including formation of corticosteroids, mineralocorticoids, androgens, and estrogens. Our findings indicate the presence in NCI-H295 cells of all of the major adrenocortical enzyme systems, including 11 beta-hydroxylase, desmolase, 21 alpha-hydroxylase, 17 alpha-hydroxylase, 18-hydroxylase, lyase, sulfokinase, and aromatase. The NCI-H295 cell line should prove of value in studying the regulation, metabolic pathways, and enzymes involved in steroid formation and secretion. In addition, it may provide insights into the biology and treatment of adrenocortical carcinoma.

Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer—A quantitative western blot analysis

Abstract: We looked for the presence of the anti-Hu antibody in the sera from 50 normal subjects; 44 patients with small cell lung cancer, not associated with paraneoplastic disease; and 25 patients with small cell lung cancer associated with paraneoplastic sensory neuropathy, encephalomyelitis, or both. Using the avidin-biotin immunoperoxidase method and a highly sensitive quantitative Western blot analysis, the anti-Hu antibody was not detected in the 50 normal human sera. Seven of the 44 patients with small cell lung cancer but no paraneoplastic syndrome had detectable levels (average titer, 76 U/ml) of anti-Hu antibody on Western blot. These levels are significantly lower than the average titer of the 25 patients who had small cell lung cancer and paraneoplastic sensory neuropathy or encephalomyelitis (average titer, 4,592 U/ml). In the group with nonparaneoplastic small cell lung cancer (low anti-Hu titer) there was a predominance of women (5 women: 2 men), and all patients had "limited" disease when diagnosed. In the antibody-negative group the sex ratio was 16 women to 21 men and 51% of the patients had "extensive" disease. None of the 7 patients with a low-titer anti-Hu antibody developed a paraneoplastic syndrome by the time of writing. The anti-Hu antibody appears, when present, to be a good marker for small cell lung cancer and, when present at high titer, for small cell lung cancer associated with a paraneoplastic syndrome.

Dihydrofolate reductase as a therapeutic target.

Abstract: The folate antagonists are an important class of therapeutic compounds, as evidenced by their use as antiinfective, antineoplastic, and antiinflammatory drugs. Thus far, all of the clinically useful drugs of this class have been inhibitors of dihydrofolate reductase (DHFR), a key enzyme in the synthesis of thymidylate, and therefore, of DNA. The basis of the antiinfective selectivity of these compounds is clear; the antifolates trimethoprim and pyrimethamine are potent inhibitors of bacterial and protozoal DHFRs, respectively, but are only weak inhibitors of mammalian DHFRs. These species-selective agents apparently exploit the differences in the active site regions of the parasite and host enzymes. Methotrexate is the DHFR inhibitor used most often in a clinical setting as an anticancer drug and as an antiinflammatory and immunosuppressive agent. Considerable progress has been made recently in understanding the biochemical basis for the selectivity of this drug and the biochemical mechanism (or mechanisms) responsible for the development of resistance to treatment with the drug. This understanding has led to a new generation of DHFR inhibitors that are now in clinical trials.

Significance of positive margins in oral cavity squamous carcinoma

Abstract: Three hundred ninety-eight consecutive, previously untreated patients undergoing surgery for epidermoid carcinoma of the oral cavity from 1979 to 1983 were reviewed. One hundred twenty-nine patients were classified as having positive surgical margins. Of these, 83 patients had tumor within 0.5 mm of the surgical margin, 9 had premalignant changes at the margin, 9 had in situ carcinoma at the margin, and 28 had invasive cancer at the margin. The remaining 269 patients had uninvolved margins. The significance of positive margins relating to survival, subsequent clinical course, local recurrence, and patterns of treatment failure was examined, along with the impact of adjuvant postoperative radiotherapy on positive margins. The percentage of patients having positive margins progressively increased with increasing T stage: 21% in T1 versus 55% in T4 primary cancers. The overall 5-year survival for patients with negative margins was 60%. For patients with positive margins, 5-year survival was 52%. This difference was statistically significant. The incidence of local recurrence in patients having positive surgical margins was twice as much as in those with negative margins (36% versus 18%). Metastasis rates in the neck and at distant sites were not significantly influenced by the status of the surgical margin. Of the 129 patients with positive margins, 49 received postoperative radiotherapy. In those patients so treated, a trend toward lower recurrence rates was noted. Differences were not statistically significant. This retrospective review confirms the importance of adequate resection of the primary tumor as well as the relative ineffectiveness of adjuvant postoperative radiotherapy in the improvement of local control in patients with positive surgical margins.

Malignant peripheral nerve sheath tumors of the buttock and lower extremity. A study of 43 cases.

Abstract: Using strict clinical and pathologic criteria for the inclusion of cases, the authors have reviewed the clinicopathologic features of 43 malignant peripheral nerve sheath tumors of the buttock and extremity seen over a 35-year period. Twenty-three (53%) of the patients had neurofibromatosis (VRN), whereas 20 (47%) did not. Fifty-one percent of the patients were women. The mean age at presentation was 36 years for patients with VRN and 44 years for patients without VRN. A nerve of origin was identified for 72% of the cases and an associated neurofibroma for 44% (65% with VRN and 20% without VRN). The mean greatest dimension of the tumors was 12.3 cm, and this did not differ significantly between the two groups. The predominant histologic pattern in 86% of the tumors was that of tightly packed spindle cells in an interlacing and woven pattern; heterologous sarcomatous elements were noticed in 12% of the cases. Surgical resection was the main modality of treatment for all patients; 65% also received adjuvant therapy. Follow-up evaluation was done in every case. An unexpected finding was the absence of a significant difference in survival rates between patients with and without VRN. Overall, 63% of the patients died of tumor: 65% of the patients with VRN and 60% of the patients without VRN. Large tumor size and high mitotic rate (greater than 20 per 10 high-power fields) portended a poor prognosis, as did the need for resection by amputation. Adjuvant radiation therapy and chemotherapy did not affect survival rates.

Bone Marrow–Allograft Rejection by T Lymphocytes Recognizing a Single Amino Acid Difference in HLA-B44

Abstract: BONE marrow from unrelated donors is increasingly being transplanted for the treatment of patients with leukemia, aplastic anemia, and lethal congenital disorders of hematopoiesis and immunologic function. National and international registries of HLA-typed volunteer donors have been developed to optimize HLA matching between unrelated donors and recipients.1 , 2 The fate of marrow grafts depends on many factors, including conditioning regimens, the composition of the cells in the graft, immunosuppression after transplantation, and the degree of histocompatibility between donor and recipient. Clinically serious graft-versus-host disease occurs in 20 to 50 percent of patients receiving marrow grafts from HLA-identical siblings, and some measure . . .

Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length

Abstract: The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction.

Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum.

Abstract: From 1982 to 1987, 114 patients underwent operation at Memorial Sloan-Kettering Cancer Center for soft-tissue sarcoma of the retroperitoneum. A retrospective analysis of these patients defines the biologic behavior, surgical management of primary and recurrent disease, predictive factors for outcome, and impact of multimodality therapy. Complete resection was possible in 65% of primary retroperitoneal sarcomas and strongly predicts outcome (p less than 0.001). The rate of complete resection was not altered by histologic type, size, or grade of tumor. These patients had a median survival of 60 months compared to 24 months for those undergoing partial resection and 12 months for those with unresectable tumors. Forty-nine per cent of completely resected patients have had local recurrence. This is the site of first recurrence in 75% of patients. These patients undergo reoperation when feasible. Complete resection of recurrent disease was performed in 39 of 88 (44%) operations, with a 41-month median survival time after reoperation. Tumor grade was a significant predictor of outcome (p less than 0.001). High-grade tumors (n = 65) were associated with a 20-month median survival time compared to 80 months for low-grade tumors (n = 49). Gender, histologic type, size, previous biopsy, and partial resection versus unresectable tumors did not predict outcome by univariate analysis. Adjuvant radiation therapy and chemotherapy could not be shown to have significant impact on survival. Concerted attempt at complete resection of both primary and recurrent retroperitoneal soft-tissue sarcoma is indicated.

Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias.

Abstract: We reviewed 63 cases of cytologically confirmed leptomeningeal metastases (LM) 31 (49%) had solid tumors 17 (27%) had leukemia and 15 (24%) had lymphoma The most common presenting symptom was pain (76%) with radicular discomfort (58%), headache (32%), neck or back pain (17%) The predominant neurological signs were mental status abnormalities (49%), weakness (47%), seizures (14%) The mode of presentation varied with tumor type Patients with leukemia (18%) and lymphoma (13%) tended to present frequently with LM without systemic involvement, or during periods of apparent remission (leukemia 35%, lymphoma 27%), while patients with solid tumors had established systemic metastases (90%) at time of presentation Laboratory studies did not vary among the groups 71% had positive cytology on the first lumbar puncture (LP) and only 8% required more than 2 LPs The cell count was a poor predictor of positive cytology as 29% of LP's with positive cytology and 36% of all LP's had less than 4 cells/mm We conclude that 1) LM presents with pain and seizures more frequently than has been previously recognized; 2) LM is frequently the mode of presentation in patients with leukemia and lymphoma and; 3) cytology is positive frequently in CSF specimens with normal cell counts and chemistries

Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection.

Abstract: One hundred eighty-five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors (NSGCT) treated with Memorial Hospital front-line cisplatin- or carboplatin-based combination chemotherapy protocols between 1979 and 1988. Clinical, pathologic, and radiologic features were correlated with the pathologic findings at surgery. The size of a residual retroperitoneal mass, the degree of shrinkage that occurred with chemotherapy, and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy. Multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase (LDH) and alphafetoprotein (AFP) levels as the best predictors of finding only necrotic debris. No factors could be found, however, that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum. Of 39 patients with residual retroperitoneal masses measuring less than or equal to 1.5 cm in maximal diameter, three had residual malignancy and five had teratoma resected. No factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery. If serum markers have normalized after chemotherapy for NSGCT, resection of all residual abnormalities on imaging studies of the retroperitoneum, lungs, and mediastinum is recommended. In addition, retroperitoneal lymph node dissection (RPLND) is recommended for all patients with initial bulky metastases (greater than or equal to 3 cm in diameter) in the retroperitoneum, irrespective of the findings of postchemotherapy computed tomography (CT).