Biomedical subjects

R K Dodge

Publications and source records attributed to R K Dodge.

At least 19 recordsLinked to original sources

PubMed1996

Radiation plus local hyperthermia versus radiation plus the combination of local and whole-body hyperthermia in canine sarcomas.

PURPOSE: The purpose of this study was to assess the effect of increasing intratumoral temperatures by the combination of local hyperthermia (LH) and whole body hyperthermia (WBH) on the radiation response of canine sarcomas. METHODS AND MATERIALS: Dogs with spontaneous soft tissue sarcomas and no evidence of metastasis were randomized to be treated with radiation combined with either LH alone or LH + WBH. Dogs were accessioned for treatment at two institutions. The radiation dose was 56.25 Gy, given in 25 2.25 Gy daily fractions. Two hyperthermia treatments were given; one during the first and one during the last week of treatment. Dogs were evaluated after treatment for local recurrence, metastasis, and complications. RESULTS: Sixty-four dogs were treated between 1989 and 1993. The use of LH+WBH resulted in statistically significant increases in the low and middle regions of the temperature distributions. The largest increase was in the low temperatures with median CEM 43 T90 values of 4 vs. 49 min for LH vs. LH + WBH, respectively (p<0.001). There was no difference in duration of local tumor control between hyperthermia groups (p = 0.59). The time to metastasis was shorter for dogs receiving LH + WBH (p = 0.02); the hazard ratio for metastatic disease for dogs in the LH + WBH group was 2.4 (95% confidence interval, 1.2-5.4) with respect to dogs in the LH group. Complications were greater in larger tumors and in tumors treated with LH + WBH, CONCLUSION: The combination of LH + WBH with radiation therapy, as described herein, was not associated with an increase in local tumor control in comparison to use of LH with radiation therapy. The combination of LH + WBH also appeared to alter the biology of the metastatic process and was associated with more complications than LH. We identified no rationale for further study of LH + WBH in combination with radiation for treatment of solid tumors.

Animals↗

PubMed1996

In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.

Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug were determined, and minimum fungicidal concentrations of SCH56592 and amphotericin B were measured. MICs of SCH56592 were lower than those of amphotericin B and fluconazole but not those of itraconazole. Minimum fungicidal concentrations of SCH56592 were lower than those of amphotericin B. SCH56592 in the presence of human serum produces an in vitro fungicidal effect for Cryptococcus neoformans. The data indicate that SCH56592 might exert fungicidal as well as inhibitory properties in vivo. On the basis of these results, SCH56592 was evaluated with a rabbit model of experimental cryptococcal meningitis; SCH56592 treatment was compared with treatment with fluconazole. Despite no detectable drug concentrations in the cerebrospinal fluid, the activity of SCH56592 against C. neoformans infection was equivalent to that of fluconazole. SCH56592 has potent in vitro activity against C. neoformans and compares favorably to treatment with fluconazole for a central nervous system infection. SCH56592 should be studied for use in humans with cryptococcal infections.

Amphotericin B↗

PubMed1995

Absence of whole body hyperthermia effect on cisplatin distribution in spontaneous canine tumors.

PURPOSE: This study was conducted to evaluate the effect of whole body hyperthermia (WBH) on cisplatin (CDDP)-derived platinum (Pt) disposition in tumor and normal tissue in dogs with spontaneously arising neoplasia undergoing conventional pretreatment diuresis. METHODS AND MATERIALS: Cisplatin was administered to 12 dogs with terminal stage, metastatic neoplasia. Cisplatin (50 mg/M2 over 1 h) was administered following 4 h of forced fluid diuresis (0.9% saline at 10 ml/kg/h). Six of the 12 dogs underwent a WBH procedure (42 degrees C rectal temperature x 90 min) simultaneously with CDDP infusion. Dogs were euthanized following the CDDP infusion, and samples from critical organs, tumor, and normal tissue adjacent to the tumor were immediately collected. RESULTS: No significant differences existed between groups in serum or normal tissue Pt content. Thirty-eight tumor samples were obtained from 27 tumors in the six dogs included in the normothermic group and 43 tumor samples were obtained from 29 tumors in the six dogs undergoing WBH. Tumor volume varied from 0.08 cm3 to 2270 cm3 and multiple samples were obtained from tumors greater than 3 cm in diameter. Twenty-five paired tissue samples of tumor and adjacent normal tissue were collected from dogs in the normothermic group and 31 paired samples were obtained from the hyperthermic group. No differences were observed between groups in tumor Pt content or in the tumor/normal tissue Pt ratios. CONCLUSION: Pt disposition was unaffected by WBH under conditions reported in this study. A forced diuresis is necessary to clinically administer CDDP at maximally tolerable doses. This maneuver results in increased blood flow to critical normal tissue that seemingly obviates any hyperthermia-induced alterations in drug disposition.

Animals↗

PubMed1995

Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B.

BACKGROUND: Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors. METHODS: We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 micrograms per kilogram of body weight per day intravenously over a period of six hours) in a double-blind manner, beginning the day after the completion of three days of daunorubicin (45 mg per square meter of body-surface area per day) and seven days of cytarabine (200 mg per square meter per day by continuous intravenous infusion). If leukemia cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens. RESULTS: Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to receive placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission. CONCLUSIONS: GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.

Aged↗

PubMed1995

A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811.

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.

Adolescent↗

PubMed1995

Prognostic indicators for neuroblastoma: stage, grade, DNA ploidy, MIB-1-proliferation index, p53, HER-2/neu and EGFr--a survival study.

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similarly, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (P = .002).

Antibodies, Monoclonal↗

PubMed1995

Nitric oxide synthase inhibition irreversibly decreases perfusion in the R3230Ac rat mammary adenocarcinoma.

We examined the microvascular effects of competitive nitric oxide synthase (NOS) inhibition with NG-monomethyl-L-arginine (MeArg), followed by L-arginine, on R3230Ac mammary adenocarcinoma perfusion. In window preparations containing tumours, superfusion of 50 microM MeArg reduced diameters of central tumour venules by 13%, of peripheral tumour venules by 17% and of normal venules near tumours by 16% from baseline. MeArg reduced red blood cell (RBC) velocity in central tumour venules by 25%, and increased intermittent flow and stasis frequency by 20% in central tumour venules. Subsequent superfusion of 200 microM L-arginine did not restore diameters or RBC velocity of any tumour preparation venules, and decreased length density in both central tumour venules and peripheral tumour venules. In contrast, MeArg reduced control preparation venule diameter by 30% and RBC velocity by 66%, but did not decrease length density or increase intermittent flow or stasis frequency. Unlike tumour preparation venules, L-arginine restored control venule diameters and velocities. NOS inhibition reduces both tumour and control venule perfusion, but the effect is blunted in the vicinity of tumours, possibly because of increased NOS levels. Perfusion can be subsequently restored in control, but not tumour, venules with L-arginine. Tumour NOS inhibition, followed by normal tissue rescue with L-arginine, may provide a novel means to achieve the goal of selective tumour hypoxia.

Adenocarcinoma↗

PubMed1995

A pial window model for the intracranial study of human glioma microvascular function.

A new model for human brain tumor uses the intracranial placement of tumor xenografts under transparent glass cranial windows in nude rats, which require no immunosuppression for tumor engraftment. Adult male nude rats underwent implantation of human anaplastic astrocytomas (D-54 MG in 10 rats, D-317 MG in 11 rats). The tumors were placed on the pial surface of the left cerebral hemisphere under a glass cranial window overlying the cranium. Six control animals underwent cranial window placement alone. Tumor volumes were estimated from direct measurements of tumor dimensions, revealing a mean doubling time of 1.58 days for the D-54 MG tumors and 2.62 days for the D-317 MG tumors. When tumor volume estimates reached 35 mm3, photomicrographs revealed tumor vasculature in each tumor cell line that was distinct from both the other xenograft and the normal brain parenchyma. Qualitative differences in vascular appearance were supported by length/density coefficient calculations in each study group, with D-317 MG demonstrating the highest vascular density. Vessel caliber tended to be smaller in D-54 MG tumors than in D-317 MG tumors. Laser-Doppler measurements of local blood flow in tumors and normal parenchyma revealed significantly lower blood flow in both tumor cell lines than in control brain. Evaluation of leukocyte/endothelial cell interactions indicated more leukocyte rolling in D-54 MG tumors than in D-317 MG tumors; no evidence of this cell interaction was found in normal pial vasculature. This model allows direct serial inspection of human brain tumor growth and vascular function in an experimental animal and could be used to study tumor vascular and inflammatory responses to a variety of therapeutic manipulations.

Animals↗

PubMed1994

Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer-specific survival. MATERIALS AND METHODS: Inpatient and clinical medical records were analyzed for age, race, gender, clinical T stage, medical history, and presenting symptoms and signs, and admission laboratory values were correlated with the patient's cancer-specific outcome. Both univariate and multivariate analyses of the various clinical factors were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that clinical T classification, preoperative hemoglobin, tumor grade, irritative voiding symptoms, age, preoperative creatinine, obstructive hydronephrosis on preoperative excretory urography, a history of bladder tumors or nephrouretectomy for transitional cell cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive symptoms were all predictive of poor cancer-specific survival. Multivariate analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4 versus Ta, Tis, T1) (P < 0.001), increasing age (< 65 years versus > or = 65 years) (P < 0.001), the presence of irritative voiding symptoms (P = 0.01), higher tumor grade, lower preoperative hemoglobin level (< or = 12 gm/dl versus > 12 gm/dl) (P < 0.001), higher preoperative creatinine level (> or = 1.5 mg/dl versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all predictive of poor cancer-specific survival. CONCLUSIONS: Although clinical T classification and tumor grade remain the best predictors of survival in patients with transitional cell carcinoma of the bladder or prostate, clinical variables such as age, preoperative creatinine and hemoglobin levels, a history of nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at presentation may provide additional prognostic information independent of tumor grade and stage.

Adult↗

PubMed1994

Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras-positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

Adult↗

PubMed1994

Therapy monitoring in human and canine soft tissue sarcomas using magnetic resonance imaging and spectroscopy.

PURPOSE: The goals of this study were to determine whether magnetic resonance parameters (a) can identify early during therapy those patients most likely to respond to hyperthermia and radiotherapy, (b) can provide prior to or early during therapy information about the temperature distributions which can be obtained in patients receiving hyperthermia, and (c) can provide an understanding of the effects of hyperthermia on tumor metabolic status. METHODS AND MATERIALS: Twenty-one human patients and 10 canine patients with soft tissue sarcomas treated with preoperative hyperthermia and radiation had a series of magnetic resonance imaging and phosphorous spectroscopy studies done. To address the goals for both the human and canine populations, changes in mean T2 relaxation times, pH, and various phosphometabolite ratios from the pretreatment (Study 1) to the post first hyperthermia study (Study 2) were correlated with treatment outcome; pretreatment magnetic resonance parameters and changes in magnetic resonance parameters (Study 2-Study 1) were compared with various cumulative thermal descriptors; and thermal descriptors of the first hyperthermia were compared with changes in magnetic resonance phosphometabolite ratios. RESULTS: A decrease in adenosine triphosphate/phosphomonoester from study 1 to study 2 is associated with a greater chance of > or = 95% necrosis in surgical resected tumors from human patients, but no significant relationships were observed between changes in tumor pH or phosphometabolite ratios and time to local failure in dogs. Pretreatment magnetic resonance parameters correlated with various thermal dose descriptors in canines but not in humans. Change in adenosine triphosphate/inorganic phosphate and phosphomonoester signal to noise ratio correlated with cumulative thermal descriptors in dogs and humans, respectively. In dogs only, increases in thermal dose resulted in decreases in high energy phosphometabolites. CONCLUSION: Changes in magnetic resonance parameters early during therapy may be predictive of treatment outcome. Pretreatment and changes in magnetic resonance parameters appear to predict how well a tumor will be heated during hyperthermia. Magnetic resonance spectroscopy also appears to be a useful tool to study the effects of various thermal doses on tumor metabolic status.

Adenosine Triphosphate↗

PubMed1994

Differential immunoreactivity of transforming growth factor alpha in benign, dysplastic and malignant prostatic tissues.

Immunohistochemical examination of radical prostatectomy specimens from 57 patients was performed to determine the differential expression of transforming growth factor alpha in the human prostate. In addition, epidermal growth factor receptor (EGFr) immunoreactivity was assessed in each case. Stromal versus epithelial staining was determined for each histological subtype: benign prostatic hypertrophy (BPH), prostatic intra-epithelial neoplasia (PIN), and prostatic cancer (CaP) by a single pathologist reviewer. TGFa staining was predominant in stroma while EGFr was localized to the epithelial basal cell layer. Immunoreactivity of both TGFa (P = 0.002) and EGFr (P < 0.001) revealed a significant reduction in CaP compared to BPH or PIN. Autocrine stimulation of EGFr by TGFa or other unrecognized factors may be present in CaP. Conversely, altered stromal influence of CaP via TGFa may be present. These observations could form the basis for future cancer therapeutic strategies using antagonist factors.

Aged↗

PubMed1994

Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder.

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

Adult↗

PubMed1994

Prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms.

The prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms was examined by Kaplan-Meier survival analysis. Using a monoclonal antibody that reacts with both mutant and wild-type p53 protein (PAb 1801), reactivity was assessed immunohistochemically in specimens from the first diagnosis of astrocytic neoplasm in 95 patients: 26 astrocytomas (A), 19 anaplastic astrocytomas (AA), and 50 glioblastomas multiforme (GBM). Overall, 53% of cases exhibited any p53 nuclear immunoreactivity, with approximately the same proportion in each histologic grade. Survival was measured from diagnosis to death or last follow-up and ranged from 3 months to 9 years. Histologic grade was a powerful prognostic variable for this group of patients (p < 0.001), with median survivals of 88, 18, and 9 months for A, AA, and GBM patients, respectively. In contrast, patients with p53-immunoreactive or -nonimmunoreactive neoplasms had median survival times of 18 or 15 months, respectively (p = 0.21). These results indicate that p53 immunoreactivity was not prognostically significant in this group of adult patients with supratentorial fibrillary astrocytic neoplasms, although a small difference in survival cannot be excluded.

Adult↗

PubMed1994

MR imaging and spectroscopy for prognostic evaluation in soft-tissue sarcomas.

PURPOSE: To enable prediction of tumor response to a particular treatment. MATERIALS AND METHODS: The authors studied the value of hydrogen-1 T2 and phosphorus-31 magnetic resonance (MR) spectroscopic metabolic determinations as indicators of prognosis in 20 humans and 10 dogs with soft-tissue sarcomas. All patients underwent combined fractionated radiation therapy and hyperthermia. Surgical resection of the entire tumor in humans allowed comparison of pretherapy T2 and MR spectroscopic parameters with subsequent histologic findings. Long-term clinical follow-up (no surgical intervention) was available with the dogs and allowed comparison of pretherapy pH with the duration of local relapse-free survival. RESULTS: A relationship exists between pretherapy pH and T2 and ultimate tumor necrosis in humans and pretherapy pH and time elapsed until local failure in dogs. CONCLUSION: MR imaging and spectroscopy could be useful in the prognosis of patients with soft-tissue sarcomas before therapy is initiated.

Adult↗

PubMed1994

Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms.

Histological grading of fibrillary astrocytic neoplasms has proved to be a valuable prognostic tool, but potentially could benefit from more objective data, such as estimates of proliferative rate. The authors have investigated the prognostic utility of quantitative Ki-67 immunoreactivity in a prospective survival analysis of 36 adult patients with astrocytoma, anaplastic astrocytoma, or glioblastoma multiforme diagnosed between 1987 and 1992. A digital image analyzer was used to assay proliferation indices (PIs) in surgical biopsy specimens obtained at first diagnosis (32 of 36) or at a second biopsy of histologically unchanged high-grade disease (4 of 36). A Ki-67 PI of > or = 7.5% was associated with higher histological grade and poorer survival, and the Ki-67 PI was more significantly related to survival (P < 0.001) than histological grade as determined by a modified Ringertz grading system (P = 0.002). Survival analysis within histological grades suggested that astrocytoma patients with PI > or = 3% may be at increased risk for shorter survival than those with PI < 3%.

Adult↗

PubMed1994

Detection of MLL gene rearrangements in adult acute lymphoblastic leukemia. A Cancer and Leukemia Group B study.

Specific structural rearrangements involving chromosome band 11q23 occur in a variety of hematologic malignancies, including an estimated 2-7% of patients with acute lymphoblastic leukemia (ALL). Translocations involving chromosome band 11q23 have been associated with a poor prognosis in patients with ALL. Recently, a gene known as MLL has been identified which is involved in acute lymphoid and myeloid leukemias with rearrangements at 11q23. A 0.74-kilobase (kb) cDNA probe from the MLL gene can detect both common and uncommon rearrangements involving MLL on conventional Southern blots. We studied 86 newly diagnosed adults entered on an ALL clinical trial to investigate the incidence of MLL gene rearrangements and to determine clinical, morphologic, immunologic and cytogenetic characteristics of such patients. Two of 86 patients had MLL gene rearrangements detected by Southern blot analysis. One of these 86 patients had an 11q23 translocation by cytogenetic analysis whereas the second patient was unevaluable by standard cytogenetic analysis. Southern blot identification of rearrangements involving MLL, especially in patients with limited material for cytogenetic analysis, can provide critical diagnostic and prognostic information which may be useful in the clinical management of patients with these abnormalities.

Adolescent↗

PubMed1994

The negative prognostic implications of thrombocytosis in women with stage IB cervical cancer.

OBJECTIVE: To determine the association between pretreatment platelet count and survival in women with stage IB cervical cancer. METHODS: Clinical records were reviewed for 219 women with stage IB cervical cancer treated by radical hysterectomy from 1971-1984. Univariate and multivariate analyses were performed to identify clinicopathologic variables associated with poor survival. Survival as a function of the preoperative platelet count was analyzed further and corrected for known prognostic factors. RESULTS: The cumulative 5-year survival of women with a preoperative platelet count greater than 300,000/microL (n = 85) was 65%, as compared to 84% for a count equal to or less than 300,000/microL (n = 134) (P = .004). Univariate Cox regression analysis revealed non-white race, large lesion size (greater than 4 cm), platelet count greater than 300,000/microL, and the presence of nodal metastases to be factors related to poor prognosis. A comparison of patients with platelet counts of 300,000/microL or less and patients with platelet counts greater than 300,000/microL revealed no difference with regard to race, nodal metastases, and median age. However, a larger percentage of women with a platelet count greater than 300,000/microL had large lesion size (29 of 60, versus 32 of 114 with a count of 300,000/microL or less). In a multivariate analysis, after adjusting for age, race, the presence of nodal metastases, and lesion size, high platelet count was still associated with poor prognosis (P = .04). CONCLUSION: An elevated platelet count is an independent prognostic factor for poor survival in patients with early-stage cervical cancer.

Adult↗