Showing papers by "Memorial Sloan Kettering Cancer Center published in 1989"
TL;DR: P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.
Abstract: Endothelial cells of human capillary blood vessels at the blood-brain and other blood-tissue barrier sites express P-glycoprotein as detected by mouse monoclonal antibodies against the human multidrug-resistance gene product. This pattern of endothelial cell expression may indicate a physiological role for P-glycoprotein in regulating the entry of certain molecules into the central nervous system and other anatomic compartments, such as the testes. These tissues, which limit the access of systemic drugs, are known pharmacologic sanctuaries for metastatic cancer. P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.
1,716 citations
TL;DR: The fibula was investigated as a donor site for free-flap mandible reconstruction and the aesthetic result of the reconstruction was excellent in most patients, particularly in "bone only" defects.
Abstract: The fibula was investigated as a donor site for free-flap mandible reconstruction. It has the advantages of consistent shape, ample length, distant location to allow a two-team approach, and low donor-site morbidity. It can be raised with a skin island for composite-tissue reconstruction. Twelve segmental mandibular defects (average 13.5 cm) were reconstructed following resection for tumor, most commonly epidermoid carcinoma. Five defects consisted of bone alone, and four others had only a small amount of associated intraoral soft-tissue loss. Eleven patients underwent primary reconstructions. At least two osteotomies were performed on each graft, and miniplates were used for fixation in 11 patients. Six patients received postoperative radiation, and two patients received postoperative chemotherapy. The flaps survived in all patients. All osteotomies healed primarily. The septocutaneous blood supply was generally not adequate to support a skin island for intraoral soft-tissue replacement. The aesthetic result of the reconstruction was excellent in most patients, particularly in "bone only" defects. There was no long-term donor-site morbidity.
1,392 citations
TL;DR: A method has been developed to calculate complication probability factors for non-uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform partial organ irradiation, and the method is shown to obey various boundary conditions.
Abstract: An estimation of normal tissue complication probability factors is important, particularly for evaluating 3-dimensional treatment plans. A method has been developed to calculate complication probability factors for non-uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform partial organ irradiation. In the effective volume method each volume element of the histogram is considered independently and subject to a power law dose volume relationship. Thus, a non-uniform dose volume histogram is reduced to a uniform one with an effective volume, and a dose equal to the maximum dose to the organ. The complication probability is then obtained from known complication probabilities for uniform partial organ irradiation. The effective volume histogram transformation method is shown to obey various boundary conditions, and is illustrated by comparing probability calculations for alternative 3-dimensional treatment plans for the pelvis. In addition, the limitations of this histogram reduction method are discussed and compared to other calculational techniques. The use of probability factor calculations in treatment plan evaluation, and their role in numerical scoring is explored.
874 citations
TL;DR: It is believed that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases.
Abstract: When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.
858 citations
TL;DR: The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.
Abstract: Recurrence patterns of glioblastoma multiforme (25) and anaplastic astrocytoma (9) were studied using CT scans of 34 patients who received all or a portion of their surgical treatment at Memorial Sloan-Kettering Cancer Center from January 1983 through February 1987. Thirty-two patients presented with unifocal tumors and two with multifocal tumors. All patients received radiation therapy following initial surgery. Eighteen patients who underwent re-operation following CT evidence of recurrence had histologic verification of recurrent tumor; sixteen patients had radiographic evidence of recurrence only. Seventy-eight percent (25/32) of unifocal tumors recurred within 2.0 cm of the pre-surgical, initial tumor margin, defined as the enhancing edge of the tumor on CT scan. Fifty-six percent (18/32) of tumors recurred within 1.0 cm of the initial tumor margin. Tumors for which a gross total resection was accomplished tended to recur closer to the initial tumor margin than did subtotally resected tumors (p greater than 0.1). Extensive pre-operative edema was associated with a decreased distance between initial and recurrent tumor margins. Large tumors were generally not more likely to recur further from the initial tumor margin than were smaller tumors. No unifocal tumor recurred as a multifocal tumor. Only one tumor (initially near the midline) recurred in the contralateral hemisphere. The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.
728 citations
TL;DR: Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2‐year and 3‐year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients.
Abstract: Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% +/- 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +/- 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T less than pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3-4M0 patients who achieved CR versus 33% of 100 with N0-+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% greater than or equal to 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.
614 citations
TL;DR: It is demonstrated that the c-kit associated tyrosine-specific protein kinase is functionally impaired in W/WV mast cells, thus providing a molecular basis for understanding the developmental defects that result from mutations at the W locus.
Abstract: The proto-oncogene c-kit, a transmembrane tyrosine protein kinase receptor for an unknown ligand, was shown recently to map to the dominant white spotting locus (W) of the mouse. Mutations at the W locus affect various aspects of hematopoiesis, as well as the proliferation and/or migration of primordial germ cells and melanoblasts during development. Here, we show that c-kit is expressed in tissues known to be affected by W mutations in fetal and adult erythropoietic tissues, mast cells, and neural-crest-derived melanocytes. We demonstrate that the c-kit associated tyrosine-specific protein kinase is functionally impaired in W/WV mast cells, thus providing a molecular basis for understanding the developmental defects that result from these mutations.
526 citations
TL;DR: Treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital agranulocytosis, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased.
Abstract: Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 μg per kilogram of body weight per day to five patients with congenital agranulocytosis. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that ...
444 citations
TL;DR: Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone,BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin).
Abstract: Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.
417 citations
TL;DR: No survival advantage could be demonstrated for patients who received chemo and/or radiotherapy, although numbers are small and staging not uniform, and an evaluation by electron microscopy and immunohistochemistry cannot confirm recent claims that ASPS is a muscle tumor.
Abstract: In the period from 1923 to 1986 our pathologists examined pathologic material from 102 patients with alveolar soft-part sarcoma (ASPS). Followup clinical data is available for 91. Median followup is 7 years (range 1 month to 27 years). Local recurrence was only found if residual disease was left at the time of the original excision. Survival in those patients who presented without metastases was 77% at 2 years, 60% at 5 years, 38% at 10 years and 15% at 20 years (median 6 years). No survival advantage could be demonstrated for patients who received chemo and/or radiotherapy, although numbers are small and staging not uniform. An evaluation by electron microscopy and immunohistochemistry cannot confirm recent claims that ASPS is a muscle tumor. ASPS is an unusual neoplasm; the primary therapeutic option is aggressive surgical excision. Survival even with the development of metastases can be long.
411 citations
TL;DR: Recommendations include a standardized format for documenting the extent of KS on initial and subsequent evaluations, response definitions that include assessments of lesion nodularity and tumor-associated edema in addition to more traditional methods for evaluating tumor response, and a new staging system that includes extent of tumor, immune status, and other AIDS-related disease manifestations.
Abstract: The availability of uniform and precise criteria for disease evaluation, response to treatment, and clinical staging of Kaposi's sarcoma (KS) in individuals with the acquired immune deficiency syndrome (AIDS) would facilitate therapeutic trials in patients with this neoplasm. Recently, a group of oncologists conducting clinical trials in patients with AIDS-associated KS as part of a cooperative group established by the National Institute of Allergy and Infectious Diseases (NIAID) drafted such criteria. The criteria take into account the unique problems associated with the evaluation of patients with a disseminated cutaneous neoplasm in the setting of a systemic virus infection associated with immune deficiency. The recommendations include a standardized format for documenting the extent of KS on initial and subsequent evaluations, response definitions that include assessments of lesion nodularity and tumor-associated edema in addition to more traditional methods for evaluating tumor response, and a new st...
Journal Article•
TL;DR: Results imply that morphine-6 beta-glucuronide elicited its analgesic actions through the same receptor mechanisms as morphine, which strongly suggests that this metabolite plays an important role in morphine's actions.
Abstract: Morphine-6 beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To define more fully the importance of this compound in morphine action, we have compared the analgesic actions of morphine and its 6 beta-glucuronide metabolite after both peripheral and central administration. Given s.c., morphine-6 beta-glucuronide elicited analgesia with an effect approximately twice that of morphine due, in part, to its long duration of action and also inhibited gastrointestinal motility. Both actions were easily reversed by naloxone (s.c.). However, when injected either i.c.v. or intrathecally, morphine-6 beta-glucuronide was approximately 90- and 650-fold more potent an analgesic than morphine, respectively. Whereas morphine in these studies was equipotent at both levels of the neuraxis as an analgesic, the 6 beta-glucuronide was approximately 5-fold more effective at the level of the spinal cord than supraspinally. The mu 1-selective antagonist naloxonazine blocked the analgesic effect of systemic and i.c.v. morphine-6 beta-glucuronide much as it blocked morphine, implying a role for mu1 receptors in these actions. Like morphine, morphine-6 beta-glucuronide analgesia after intrathecal injection was not sensitive to naloxonazine, suggesting a mu2 mechanism within the spinal cord. Together, these results imply that morphine-6 beta-glucuronide elicited its analgesic actions through the same receptor mechanisms as morphine. Mice highly tolerant to morphine after implantation of morphine pellets showed cross-tolerance to morphine-6 beta-glucuronide (s.c.). The high potency of morphine-6 beta-glucuronide strongly suggests that this metabolite plays an important role in morphine's actions.
TL;DR: It is demonstrated that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation and its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.
TL;DR: Investigation of the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma found patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence-free survival as a result of systemic adjuvant treatment.
Abstract: This study was undertaken to investigate the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma. After a median follow-up of 18.2 years, 23% were dead of recurrent breast carcinoma, 3% were alive with recurrent disease, and 74% had not experienced a recurrence. The probability of recurrence was directly related to the initial extent of the disease. Overall, 16% of recurrences and 25% of deaths due to disease occurred in the second decade of follow-up. The proportion of recurrences detected in the second decade was inversely related to the stage of the primary tumor at diagnosis. When stratified by tumor size, T1N0M0 patients with tumors 1.0 cm or less in diameter had a significantly better 20-year recurrence-free survival (86%) than did T1N0M0 patients with tumors 1.1 to 2.0 cm (69%). When observed and expected survival curves were compared by the method of Brinkley and Haybittle, it appeared that 80% of T1N0M0 patients with tumors 1 cm or less might be cured at 20 years, whereas for those in the 1.1- to 2-cm group, the proportion cured was indeterminate, but might be as high as 70%. A potentially cured group could not be identified among T1N1M0 patients, but an estimated 52% of these patients did not have a recurrence within the nearly 20-year follow-up period. These data are important when one considers the proper role of adjuvant therapy for stage I disease. Patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence-free survival as a result of systemic adjuvant treatment, while women in the T1N0M0 group with an especially favorable recurrence-free survival, particularly those with tumors 1 cm in diameter or smaller, might be spared adjuvant therapy.
TL;DR: It is evident that patients with T1 breast carcinoma can be subdivided into differing prognostic groups and this must be taken into account when considering the role of adjuvant chemotherapy for stage I disease.
Abstract: Prognostic factors have been examined in 644 patients with tumor-node-metastasis (TNM) stage T1 breast carcinoma treated by mastectomy and followed for a median of 18.2 years. Overall, 148 patients (23%) died of recurrent breast carcinoma. Eighteen (3%) were alive with recurrent disease and 478 (74%) were alive or died of other causes without recurrence. Unfavorable clinicopathologic features were larger tumor size (1.1 to 2.0 cm v less than or equal to 1 cm), perimenopausal menstrual status, the number of axillary lymph node metastases, poorly differentiated grade, presence of lymphatic tumor emboli (LI) in breast tissue near the primary tumor, blood vessel invasion (BVI), and an intense lymphoplasmacytic reaction around the tumor. Median survival after recurrence for the entire series was 2 years. This was not significantly influenced by tumor size, the number of axillary nodal metastases, the type of treatment for recurrence, or the interval to recurrence. The proportions surviving 5 and 10 years after recurrence were 17% and 5%, respectively. Among T1N0M0 cases, the chance of a local recurrence was 2.8% within 20 years. Median survival of T1N0M0 cases after local recurrence (4.5 years) was significantly longer than after systemic recurrence (1.5 years). A similar trend (3.7 v 2.0 years), not statistically significant, was seen in T1N1M0 patients, who had a 6.5% chance of local recurrence within 20 years. Median survival following systemic recurrence detected 10 or more years after diagnosis in T1N0M0 and in T1N1M0 patients was significantly longer than the median survival for systemic recurrences found in the first decade of follow-up. This difference did not apply following local recurrence in either T1N0M0 or T1N1M0 cases. It is evident that patients with T1 breast carcinoma can be subdivided into differing prognostic groups and this must be taken into account when considering the role of adjuvant chemotherapy for stage I disease. Systemic adjuvant treatment may prove to be beneficial for patients with unfavorable prognostic factors, while women with an especially low risk for recurrence (eg, T1N0M0 tumor 1.0 cm or less) might be spared such treatment.
TL;DR: It is reported here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices.
Abstract: Transforming growth factors beta 1 and beta 2 bind with high affinity to the core protein of a 250-350-kD cell surface proteoglycan. This proteoglycan (formerly referred to as the type III TGF-beta receptor) coexists in many cells with the receptor implicated in TGF-beta signal transduction (type I TGF-beta receptor), but its function is not known. We report here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices. As has been shown for the membrane-bound form, the soluble proteoglycans have a heterogeneous core protein of 100-120 kD that carries chondroitin sulfate and/or heparan sulfate glycosaminoglycan chains and a small amount of N-linked carbohydrate. The membrane-bound form of this proteoglycan is hydrophobic and associates with liposomes, whereas the soluble forms lack a membrane anchor and do not associate with liposomes. Differences in the electrophoretic migration of the soluble and membrane forms of this proteoglycan suggest additional structural differences in their core proteins and glycosaminoglycan chains. These soluble and membrane-bound proteoglycans, for which we propose the name "betaglycans," might play distinct roles in pericellular retention, delivery, or clearance of activated TGF-beta.
TL;DR: In this paper, the authors reviewed the Radiation Therapy Oncology Group's (RTOG) prospectively collected registry of all head and neck patients seen in participating member institutions between February 1977 and April 1980.
Abstract: The development of second malignant tumors (SMTs), in patients who have had their first tumor treated successfully, represents a serious limitation of current therapeutic strategies for head and neck cancers. To improve our understanding of the current magnitude of the problem and the various factors that might influence its importance, we reviewed the Radiation Therapy Oncology Group's (RTOG) prospectively collected registry of all head and neck patients seen in participating member institutions between February 1977 and April 1980. A total of 928 patients were identified who had squamous cell carcinomas of the head and neck region, no prior or coincident history of another malignant tumor, and whose planned treatment consisted of radiation therapy only. A total of 110 second, independent, malignant tumors occurred in these patients. Overall, the estimated risk of developing a second tumor within 3 years of radiotherapy was 10%, within 5 years 15%, and within 8 years 23%. Minor differences in frequency were observed for different primary sites. These SMTs unquestionably influenced subsequent survival adversely. Analysis of the database also revealed that the extent of the primary tumor influenced the risk of a second; most occurred in patients who presented with the smallest primary tumors because of their better survival. Our data indicate that preventive medicine should have its greatest impact in those patients who are treated for an early stage primary tumor.
Journal Article•
TL;DR: Competition studies with both alpha-neoendorphin and dynorphin B together suggest that both compounds label the same site with high affinity, whereas Classical kappa opiates and dynoirin A have high affinity for both subtypes whereas dynorphIn B and alpha-Neo endorphin label kappa 1b over 50-fold more potently than kappa 2a sites.
Abstract: Kappa receptor multiplicity is a complex area. We now present evidence from binding studies suggesting the existence of four kappa receptor subtypes. The guinea pig cerebellum contains high levels of U50,488-sensitive, or kappa 1, receptors. Kappa opiates (U50,488, tifluadom, Mr2034, Mr2266 and Win44,441) compete [3H]ethylketocyclazocine binding to kappa 1 receptors with kappa, values under 10 nM and Hill coefficients of approximately one, as does dynorphin A (kappa 1, 0.27 +/- 0.05 nM; Hill coefficient, 0.83 +/- 0.20, n = 4). However, competition studies with dynorphin B yield a Hill coefficient of 0.46 +/- 0.03 (n = 5) and nonlinear regression analysis of the competition curve is best fit by two sites. alpha-Neoendorphin Neoendorphin competition curves (Hill coefficient, 0.46 +/- 0.07; n = 3) also were best fit with two components. Competition studies with both alpha-neoendorphin and dynorphin B together suggest that both compounds label the same site with high affinity. Similar results were obtained using [3H]U69,593. Dynorphin B and alpha-neoendorphin competed binding with Hill coefficients of 0.45 +/- 0.04 (n = 3) and 0.59 +/- 0.09 (n = 3), respectively. These data suggest two subtypes of kappa 1 receptors in the guinea pig cerebellum: kappa 1a and kappa 1b. Classical kappa opiates and dynorphin A have high affinity for both subtypes whereas dynorphin B and alpha-neoendorphin label kappa 1b over 50-fold more potently than kappa 1a sites. [3H]Naloxone benzoylhydrazone [( 3H]NalBzoH) labels a novel, U50,488-insensitive kappa receptor subtype, kappa 3, in membranes from calf striatum, rat and mouse brain. We now have developed a relatively selective assay in calf striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: It is confirmed that desmoid tumors are malignant soft-tissue neoplasms that warrant aggressive therapy and have independent predictive value for recurrence.
Abstract: The necessity of aggressive therapy for desmoid tumors has not been clearly established. To evaluate the therapeutic value of adequate resection and radiation therapy, we conducted a retrospective study of 138 patients treated from 1965 through 1984. Univariate analysis revealed five factors predictive of local failure: (1) age between 18 and 30 years, (2) presentation with recurrent disease, (3) partial or limited margin excision, (4) tumor at or close to the microscopic margin of resection, and (5) radiation therapy not administered for gross residual disease. Multivariate analysis identified two of these factors as having independent predictive value for recurrence: (1) presentation with recurrent disease and (2) less-than-adequate margins of resection. The five-year survival probability was 92%, but 11 of the 138 patients died as a consequence of locally uncontrolled tumor. These findings confirm that desmoid tumors are malignant soft-tissue neoplasms that warrant aggressive therapy.
TL;DR: There would appear to be justification for reexamining extended nodal dissection for gastric cancer in the US, although patients with both apparent and confirmed direct adjacent organ invasion can be helped by resection of those organs, extended resections of uninvolved pancreas and spleen do not improve rate of survival.
Abstract: Overall results after operations for gastric cancer in Japan are far superior to results obtained in the US and Europe. We have reviewed the Japanese literature in an effort to determine what factors explain this difference. It appears that the survival differences are due mainly to a greater frequency of early gastric cancer in Japan; meticulous histopathologic evaluation of the surgical specimens, resulting in more accurate pathologic staging; and the presumed benefit of extended nodal dissection when it extends outside of the level of node-positive disease. Although patients with both apparent and confirmed direct adjacent organ invasion can be helped by resection of those organs, extended resections of uninvolved pancreas and spleen do not improve rate of survival beyond the benefit of improved nodal dissection. Overall, there would appear to be justification for reexamining extended nodal dissection for gastric cancer in the US. Opportunities for a meaningful national study are significant.
TL;DR: To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis, records of 98 patients who had elective craniotomy between 1978 and 1985 were reviewed.
Abstract: To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis we reviewed the records of 98 patients who had elective craniotomy between 1978 and 1985. Seventy-nine patients received postoperative WBRT (Group A) and 19 patients no radiotherapy (RT) (Group B). Neurological relapse was designated as local (i.e., at the site of the original metastasis) or distant (i.e., elsewhere in the brain). Postoperative WBRT significantly prolonged the time to any neurological relapse (P = 0.034) with a 1-year recurrence rate of 22% in Group A and 46% in Group B patients; however, it did not specifically control either local or distant cerebral recurrence. Recurrence of metastatic brain disease was not affected by location of the original lesion; however, meningeal relapse occurred in 38% of cerebellar lesions, but only in 4.7% of supratentorial metastases (P = 0.003). The total radiation dose or fractionation scheme of RT did not affect survival nor time to neurological relapse. The median survival was 20.6 and 14.4 months for Groups A and B, respectively (not statistically different). Forty-eight percent of Group A and 47% of Group B patients survived for 1 year or longer; however, 11% of patients who had received RT and survived 1 year developed severe radiation-induced dementia. All patients with radiation-related cerebral damage received hypo-fractionated RT with high daily fractions as commonly designed for rapid palliation of macroscopic brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The removal of mature cells from the marrow graft did not affect the rate or degree of recovery of myeloid and lymphoid cells but did affect the regeneration of in vitro T-cell dependent functions.
TL;DR: There is an increased frequency of the Lewis blood-group nonsecretor (Le (a+b-] and recessive (Le(a-b-)] phenotypes among women with recurrent urinary tract infections.
Abstract: Blood-group antigens are found on the surface of urothelial cells and may affect bacterial adherence and thereby the susceptibility to urinary tract infection. We determined the ABO, P, and Lewis blood-group phenotypes in 49 white women with histories of recurrent urinary tract infections and compared them with those found in 49 healthy control women without recurrent urinary tract infections. There was no significant difference between the two groups in the distribution of the ABO or P phenotypes. The distribution of Lewis blood-group phenotypes among control women was similar to that in the general population: secretor phenotype (Le(a-b+)), 74 percent; nonsecretor phenotype (Le(a+b-)), 18 percent; and recessive phenotype (Le(a-b-)), 8 percent. The following distribution was noted among the women with recurrent urinary tract infections: secretor phenotype, 45 percent; nonsecretor phenotype, 29 percent; and recessive phenotype, 26 percent (P = 0.002). When the women with nonsecretor and recessive phenotypes were combined and considered collectively, the odds ratio (an estimate of relative risk of recurrent urinary tract infection) for those without the secretor phenotype was 3.4 (95 percent confidence interval, 1.5 to 7.9). We conclude that there is an increased frequency of the Lewis blood-group nonsecretor (Le(a+b-] and recessive (Le(a-b-] phenotypes among women with recurrent urinary tract infections.
TL;DR: Analysis of prognostic factors identifies a group of patients at high risk for recurrence and decreased survival for whom prospective trials of adjunctive treatment should be considered.
TL;DR: The two-drug combination of oral metoclopramide plus dexamethasone is well tolerated, safe, and more effective than dexamETHasone alone or placebo in controlling delayed vomiting following cisplatin.
Abstract: The majority of patients receiving cisplatin at a dose of 120 mg/m2 experience delayed nausea and vomiting occurring between 24 and 120 hours after chemotherapy administration. Ninety-one patients who were receiving cisplatin (120 mg/m2) as initial chemotherapy were entered into this double-blind trial. All patients received intravenous (IV) metoclopramide, dexamethasone, and lorazepam for the control of acute emesis during the period from 0 to 24 hours after cisplatin. Patients were then randomized to one of three treatment regimens: placebo; oral dexamethasone, 8 mg twice daily for two days, then 4 mg twice daily for two days; or the combination of oral metoclopramide, 0.5 mg/kg four times daily for four days, plus oral dexamethasone administered as above. Forty-eight percent of individuals who received the two-drug combination of metoclopramide plus dexamethasone experienced delayed vomiting as opposed to 65% who were administered dexamethasone alone and 89% who received placebo (P = .006). Scores asse...
TL;DR: Evaluation of patients with superficial bladder carcinoma at 6 months after intravesical bacillus Calmette-Guerin therapy identifies the probability of tumor progression.
TL;DR: In this paper, the authors used MR imaging to investigate normal and abnormal meningeal enhancement, with an emphasis on Meningeal Carcinoma (MCC) and Meningal Infection (MI) associated with pathologic conditions of the meninges.
Abstract: MR imaging was used to investigate normal and abnormal meningeal enhancement, with an emphasis on meningeal carcinomatosis. Three groups of patients were studied on a 1.5-T system. In group 1, the normal meninges were examined in 20 patients and were found to show fine linear enhancement in short segments, especially in a parasagittal distribution. In group 2, all gadolinium-enhanced head scans were reviewed retrospectively. Abnormal meningeal enhancement was detected in 52 patients. In some of these, the enhancement was associated with pathologic conditions of the meninges, including leptomeningeal tumor and meningeal infections and other inflammatory conditions; in others the enhancement was adjacent to subdural hematomas, subacute infarcts, and skull lesions, such as metastases or postoperative defects. In group 3, 30 cases of meningeal carcinomatosis were studied prospectively. Enhancement was seen in approximately two-thirds of cases and usually was quite diffuse and applied to the inner table of the...
TL;DR: The current knowledge about the epidemiology of cancer pain and its syndromes is summarized.
Abstract: Medical practitioners face the challenge of assuring that pain management has a central place in the treatment of patients with cancer. To meet this challenge, they must understand the prevalence of pain in cancer patients, the frequency with which cancer pain goes untreated or is inadequately managed, and the numerous causes and manifestations of cancer pain. With the goal of contributing to this understanding, this article summarizes the current knowledge about the epidemiology of cancer pain and its syndromes.
Journal Article•
TL;DR: The role of ras mutations may be limited to an indirect involvement in the transformation of a subset of melanomas and no ras gene mutations were found in any precursor lesion, specifically normal nevi and dysplastic nevi.
Abstract: This study examined noncultured and cultured melanomas and related precursor specimens for (i) mutated ras genes using polymerase chain reaction (PCR) methodology, (ii) correlation of mutated ras genes with differentiation related phenotypic characteristics, (iii) expression of ras-encoded p21 proteins in tissues by immunoperoxidase analysis, (iv) quantitative expression of mutated and wild-type ras encoded p21 proteins by flow cytometry, and (v) correlation between p21 expression, the occurrence of ras mutations, and cell cycle kinetics. The results of these studies are (1) 24% of cultured malignant melanomas have activated ras genes, with N-ras being activated ten times as frequently as Harvey (Ha)-ras. Each example of an activated ras gene showed a mutation at the 61st codon of the protein, with the exception of one melanoma which showed a mutation at codon 13 of the N-ras gene; (2) all the melanomas displaying an activated ras gene had a similar cell surface phenotype and appear to come from a similar phase of differentiation; (3) 5-6% of noncultured primary and metastatic melanomas have mutated ras genes; (4) no ras gene mutations were found in any precursor lesion, specifically normal nevi and dysplastic nevi; (5) immunoperoxidase analysis of paraffin-embedded specimens indicated no quantitative or qualitative alterations in p21 expression that correlate with tumor progression; (6) there were no observable differences in p21 expression between melanoma cells growing exponentially or in plateau phase, or between melanoma cells with or without ras mutations; nor were any cell kinetic differences found between cells with and without mutated ras genes. These studies suggest that the role of ras mutations may be limited to an indirect involvement in the transformation of a subset of melanomas.
TL;DR: Excerpt Although a significant problem in Latin America, the transmission of Trypanosoma cruziinfection by transfusion has not been unequivocally documented in the United States, and a caseload of cases is reported.
Abstract: Excerpt Although a significant problem in Latin America (1), the transmission ofTrypanosoma cruziinfection by transfusion has not been unequivocally documented in the United States. We report a cas...