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G Altshuler

Publications and source records attributed to G Altshuler.

At least 19 recordsLinked to original sources
PubMed1992

Recommendations for modification of terminology of neuroblastic tumors and prognostic significance of Shimada classification. A clinicopathologic study of 213 cases from the Pediatric Oncology Group.

To develop consistency in terminology and pathologic criteria, the authors reviewed the literature and 213 cases of neuroblastic tumors (NT) registered with Pediatric Oncology Group (POG) protocols 8104 and 8441. The patients were given standardized therapy stratified according to POG stage and patient age, and four or more histologic sections of primary tumor resected before therapy were available in each of these 213 cases. All stages were represented. The recommended nomenclature combines conventional terms and criteria with those used by Bove and McAdams and Shimada et al. The main features of the recommended nomenclature are as follows: (1) the terms neuroblastoma (NB) and ganglioneuroblastoma (GNB) are retained instead of stroma-poor NB and stroma-rich NB, recommended by Shimada et al.; (2) undifferentiated NB is considered a subtype separate from poorly differentiated NB; and (3) the term GNB is used only when there is a predominant ganglioneuromatous component admixed with the minor neuroblastomatous component. With the use of these criteria and terms, the Shimada classification was determined in the 213 cases. The results showed that, even after stratification for age, POG stage, and primary site, there is a statistically significant difference in survival rate between favorable histologic and unfavorable histologic prognostic subgroups. The authors recommend that definitive prognostic categorization of an NT according to Shimada classification should be done only when adequate histologic material is available from a primary tumor resected before any other therapy. Categorization done on histologic material from small biopsy specimens, previously treated primary tumors, or metastatic sites should be considered tentative.

Child, Preschool↗
PubMed1992

Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the Pediatric Oncology Group.

Histologic sections (minimum of four sections per patient) from 211 patients with neuroblastoma were reviewed. The tumors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (less than or equal to ten per ten high-power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log-rank tests (P less than 0.0001 and P = 0.0065, respectively). Histologic Grades 1, 2, and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had absence of low MR, i.e., these tumors had high MR [greater than ten per ten high-power fields]). Statistically significant differences in survival were observed in the grades after adjusting for age and stage (P less than 0.001). The degree of differentiation, although significant by itself, was no longer significant after adjusting for the grades. Age groups (less than or equal to 1 versus greater than 1 year of age), which also emerged as an independent prognostic feature (P less than 0.001), were linked with the grades to define two risk groups as follows: (1) a low-risk (LR) group consisting of patients in both age groups with Grade 1 tumors and patients 1 year of age or younger with Grade 2 tumors and (2) a high-risk (HR) group consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statistically significant (P less than 0.001). Concordance between these LR and HR groups and the Shimada classification was observed in 84% of cases. The new histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested on a new data set with an appropriate histologic sample of similar size to confirm these results.

Age Factors↗
PubMed1992

Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study.

On the basis of an extensive recursive partitioning analysis of 668 patients with newly diagnosed neuroblastoma registered on Pediatric Oncology Group (POG) studies between October 1981 and May 1987, four major subsets of patients were created. Important prognostic factors included the patient's stage of disease, age, and level of serum lactate dehydrogenase (LDH). After adjusting for these factors, no other clinical prognostic factors were significant. The implications for protocol design are that (a) fine tuning of current therapy should be sought for the two favorable disease patient subsets, while (b) novel aggressive therapies are needed for the two unfavorable disease patient subsets where the overwhelming majority are dying. This article may serve as a model for others investigating prognostic factors. The data were divided into two subsets: one was used for an exploratory analysis; the other was used to confirm the exploratory findings. Despite spite the large number of statistical tests performed, the likelihood that the findings can be attributed to chance can be dismissed as virtually zero.

Adolescent↗
PubMed1992

Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group study.

PURPOSE: Infants less than or equal to 1 year of age with neuroblastoma (NB) have a favorable outlook with minimal to moderate therapy. Patients with complete or partial removal of the primary tumor but positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) have a higher risk for recurrent disease. To determine the importance of distinguishing infants with POG stage C NB from those with POG stage B disease and to assess the efficacy and toxicity of treating POG stage C infants with limited, postoperative chemotherapy, a study was conducted by the POG. PATIENTS AND METHODS: Forty-four eligible POG stage C infants received cyclophosphamide 150 mg/m2 orally on days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR), every 3 weeks for five courses followed by second-look surgery. No continuation therapy was given if surgical and pathologic complete response (CR) was achieved. Secondary therapy with five courses of cisplatin 90 mg/m2 on day 1 followed by teniposide (VM-26) 100 mg/m2 on day 3 (CDP/VM) was given to infants with gross residual tumor after CYC/ADR and second-look surgery. RESULTS: Thirty-four infants achieved CR after CYC/ADR alone, three after CYC/ADR and second-look surgery, two after CYC/ADR, surgery, and maintenance therapy, and two after alternative treatment with CDP/VM (total CR rate, 42 of 44). The 3-year survival and disease-free survival are both 93%. Toxicity was nominal. CONCLUSIONS: Infants with POG stage C NB have a favorable outlook, which is similar to infants with POG stage B NB; the surgical staging procedure for distinguishing these infant subsets may not be necessary. Future studies should focus on the reduction of treatment toxicity and efficacy maintenance, and address methods to identify infants at risk for failure.

Actuarial Analysis↗
PubMed1992

Meconium-induced umbilical cord vascular necrosis and ulceration: a potential link between the placenta and poor pregnancy outcome.

The literature lacks epidemiologic study of pregnancy outcome with light-microscopic meconium-related lesions. We recently described previously unreported meconium-induced necrosis of placental and umbilical cord vessels and hypothesized that the lesions represent preceding vasocontraction and fetal hypoperfusion. Preliminary experiments then confirmed that meconium produces vasocontraction in isolated umbilical venous tissue. In the present study, we examined whether clinically meaningful abnormalities occur with these vascular signs of remote fetal meconium discharge. In a light-microscopic review of 1100 meconium-stained placentas, we found ten with meconium-induced vascular necrosis. In six of these ten cases, fetal distress necessitated cesarean delivery. Seven newborns had Apgar scores of 3 or less at 1 minute, and each of the seven cases tested had umbilical arterial pH less than 7.19. Because seven of the ten infants were born after December 1, 1989, clinical follow-up was limited. One died, another has neurodevelopmental deficiency, and a third has experienced enlargement of head circumference from the 50th percentile at birth to the 95th percentile at 10 months of age. Two placentas had umbilical cord ulceration, a lesion that has rarely been reported in the literature. We conclude that meconium-induced vascular necrosis seems to be a meaningful, detrimental lesion.

Amniotic Fluid↗
PubMed1991

Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma.

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.

Adolescent↗
PubMed1991

Postoperative treatment of nonmetastatic visible residual neuroblastoma: a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) evaluated in a prospective study the hypothesis that patients who had localized, visible residual neuroblastoma without regional lymph node involvement after surgery (POG stage B) have a favorable prognosis when treated with moderate intensive chemotherapy. Eligible patients were initially treated with five courses of Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co., Evansville, IN) and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) followed by surgery (CY/AD +/- surgery). Those patients not achieving a complete remission (CR) crossed over to five courses of cisplatin and teniposide (PL/VM) +/- surgery. Radiation therapy (XRT) was given to selected patients who still were not in CR after the crossover therapy. Of the 61 eligible patients, 38 (62%) patients achieved CR after CY/AD proven by clinical (31) or surgical (seven) evaluation. One (2%) patient in clinical partial remission (PR-C) entered CR without further therapy. Nineteen (31%) patients achieved CR with the following salvage therapies: surgery (five), PL/VM +/- surgery (five) followed by XRT (three) or autologous bone marrow transplant (ABMT) (one) and further courses of CY/AD +/- PL/VM instead of courses of PL/VM (five). The overall CR rate was 95% (58 of 61). Four patients had recurrence of the disease. The probability of being disease-free at 3 years after initial or salvage therapy was estimated at 84% (SE, 5%). The overall prognosis of children older than 1 year and younger than 1 year was similar (P = .26). If, however, the three remission deaths (all younger than 1 year) were censored, there was only one other failure in 32 children younger than one versus seven of 29 children older than 1 year (P = .018). These results confirm the excellent prognosis for patients with POG stage B neuroblastoma and indicate that most patients are curable with CY/AD +/- surgery, and those not achieving CR with this therapy are curable with alternate therapy.

Abdominal Neoplasms↗
PubMed1991

Solitary fibromatosis of bone. A rare variant of congenital generalized fibromatosis.

Congenital generalized fibromatosis is part of the spectrum of the fibromatoses of infancy and childhood. The lesions are usually multiple and fibrous in nature. They may appear in virtually every organ outside the central nervous system. Congenital generalized fibromatosis can be limited to the skeleton and rarely manifests itself as a solitary bone lesion. Solitary osseous lesions often behave differently than multiple osseous lesions. Solitary lesions often do not regress without treatment and can have a high incidence of recurrence with less than marginal excision. Multiple osseous lesions often regress without treatment.

Bone Neoplasms↗
PubMed1991

Placenta within the medicolegal imperative.

Bad pregnancy outcome includes abortion, stillbirth, neonatal death, morbidity, malformation, cerebral palsy, and mental retardation. These afflictions cause devastating personal impact. In the United States, almost 10% of all school-aged children are handicapped. Neurologic and communicative disorders affect 42 million people and cost $114 billion each year. The cause of cerebral palsy is known in less than 10% of these cases. Enormous litigations have threatened clinicians, paramedical personnel, hospitals, and insurance carriers. The placenta is an important potential means of establishing that fetal damage causes bad pregnancy outcome independently of clinical care. All pathologists serve an important role in the documentation of gross placental features and in the procurement of appropriate light microscopic slides. Pathologic placentas are common. Only an expert can determine whether an abnormal placenta represents the probable cause of bad pregnancy outcome.

Chorioamnionitis↗
PubMed1989

A model of bacterially induced umbilical vein spasm, relevant to fetal hypoperfusion.

From experience with placental pathology and autopsies, we hypothesize that infected amniotic fluid may produce umbilical cord and placental surface vasospasm, reduced fetal perfusion, and perinatal asphyxia, morbidity, and mortality. We tested the hypothesis by a preliminary investigation with group B beta-hemolytic streptococcus, a common cause of perinatal morbidity and mortality. Our methods included suspension of isolated human umbilical vein segments in a 30-mL organ bath with modified Krebs solution, pH 7.3-7.4, under continuous aeration by 95% O2 and 5% CO2 at 37C. The vessels were attached to an isometric transducer which was connected to a polygraph. We tested Krebs solution, sterile culture medium, group B streptococcus spent medium, and washed whole group B streptococcus bacteria. Contractility was compared with results produced by 10(-5) M serotonin. The average contraction produced by 30 microL/mL group B streptococcus spent medium was 40.8% of that produced by serotonin. Whole washed bacteria produced 8.6% of the serotonin contraction. Krebs solution and sterile culture medium did not stimulate vascular contraction. Intraperitoneal injection of group B streptococcus spent medium in mice at four times the maximal experimental dose had little effect. Boiling group B streptococcus spent medium failed to affect its vasoactive stimulatory properties. We conclude that in vitro, group B streptococcus synthesizes a heat-stable, non-protein exotoxin that causes human umbilical vein contraction.

Animals↗
PubMed1989

Meconium-induced vasocontraction: a potential cause of cerebral and other fetal hypoperfusion and of poor pregnancy outcome.

Chronically meconium-stained fetuses may ultimately suffer cerebral palsy and other devastation. The mechanism is unknown. Innocuous pregnancy complications may cause some fetuses to discharge meconium, which may become hazardous, independently of aspiration. We herein report previously undescribed, meconium-induced umbilical and placental vascular necrosis. To investigate whether meconium causes vasocontraction, we tested umbilical vein tissue with an isometric transducer connected to a polygraph. The specimens were suspended in a 30-mL organ bath with Krebs solution (pH, 7.4; temperature, 37 degrees C; under aeration with 95% O2 and 5% CO2). We exposed the tissue to meconium and compared meconium-induced vasocontraction with that induced by Krebs solution and 10(-5) molar serotonin. Meconium maximally produced 62.9% of serotonin-induced vasocontraction. Krebs solution and boiled meconium did not produce vasocontraction. We hypothesize that meconium may cause placental and umbilical cord vasocontraction, cerebral and other fetal hypoperfusion, and major poor outcome.

Asphyxia Neonatorum↗
PubMed1988

Clinicopathologic considerations of fusobacteria chorioamnionitis.

When sought by light microscopy in formalin-fixed tissue, fusobacteria are apparent in 7-18% of chorioamnionitis cases. Brown and Hopps bacterial staining characteristically visualizes their long, slender and filamentous forms. Fusobacteria-like organisms in placentae have previously been associated with prematurity. Our findings indicate that perinatal infection with fusobacteria may cause neonatal death from prematurity, rather than from sepsis. In a study of 586 placentae, 14 specimens with chorioamnionitis and fusobacteria-like organisms were found. On the five occasions when microbiologic tests were made, fusobacteria were isolated. Prematurity of the newborns was associated with twelve of those placentae. Immunofluorescent labelling of the organisms is a helpful but incomplete means of diagnosis. Because fusobacteria antibodies are highly specific, they do not cross-react with other members of the genus Fusobacterium. A typical case is reported, in detail.

Adult↗
PubMed1979

Premature onset of labor, neonatal patent ductus arteriosus, and prostaglandin synthetase antagonists--a rat model of a human problem.

Premature labor and patent ductus arteriosus are two potentially fatal hazards of the human newborn infant. Prostaglandin synthetase antagonists have thus been used to suppress early labor and to close the ductus of the neonate. Indomethacin has been most effective but not free of significant complications. Neuronal necrosis may result from numerous systemic aberrations. A controlled rat model study was therefore devised to investigate fetal neuronal necrosis in relation to maternal indomethacin dose. Dams were given various treatments of 2 mg/kg of 4 mg/kg indomethacin within the last 3 days of gestation. Liquid chromatography was used to assess serum maternal and fetal drug levels. From light microscopy of more than 200 brains it was apparent that fetal neuronal necrosis correlates with maternal dose.

Animals↗
PubMed1978

Placental coccidioidomycosis without fetal disease.

We encountered two cases of maternal coccidioidomycosis with placental involvement. Altered cell-mediated immunity during pregnancy makes the diagnosis of desseminated coccidioidomycosis difficult by the routine serologic tests; placental examination provides specific information. A high index of suspicion regarding this disease and prompt institution of appropriate therapy are necessary in order to decrease maternal and neonatal mortality.

Adult↗