Search PubMed⌕ Search

Biomedical subjects

K R Hess

Publications and source records attributed to K R Hess.

At least 55 records · Page 3Linked to original sources
PubMed1998

Allelic deletion analyses of MMAC/PTEN and DMBT1 loci in gliomas: relationship to prognostic significance.

The frequency of loss of heterozygosity (LOH) around MMAC/PTEN and DMBT1 loci and survival analyses based on the LOH status were assessed in 110 patients with different histological groups of gliomas. Twenty-six of the patients had anaplastic oligodendrogliomas, 31 had anaplastic astrocytomas, and 53 had glioblastomas multiforme (GM). At the DMBT1 locus, LOH was observed very frequently in all three histological groups, with no significant difference in the frequency of LOH among the three histological groups. At the MMAC/PTEN locus, patients with GM exhibited a significantly increased frequency of LOH (72%) compared with patients with anaplastic astrocytomas (29%) or anaplastic oligodendrogliomas (31%) (P < 0.0001). Kaplan-Meier survival plots showed that patients with LOH at the MMAC/PTEN locus had a significantly worse prognosis than did patients without LOH at the MMAC/PTEN locus [hazard ratio (LOH versus non-LOH), 2.65; 95% confidence interval (CI), 1.69-4.46; P < 0.0001]. Cox proportional hazards regression analysis, adjusted for age at surgery and histological grades (GM and non-GM), showed that LOH at the MMAC/PTEN locus was a significant predictor of shorter survival [hazard ratio (LOH versus non-LOH), 2.01; 95% CI, 1.1-3.5; P = 0.018). Our analysis failed to indicate a similar association between the frequency of LOH at the DMBT1 locus and patient survival [hazard ratio (LOH versus non-LOH), 2; 95% CI, 0.37-3.13; P = 0.2]. These results suggest that the DMBT1 gene may be involved early in the oncogenesis of gliomas, whereas alterations in the MMAC/PTEN gene may be a late event in the oncogenesis related to progression of gliomas and provide a significant prognostic marker for patient survival.

Agglutinins↗
PubMed1998

Gamma-ray mutagen sensitivity and survival in patients with glioma.

Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic gamma-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness and decreased patient survival. The eligible 76 patients were those with histologically confirmed malignant gliomas, seen at the University of Texas M. D. Anderson Cancer Center between 1994 and 1997, for whom we had sufficient blood for the in vitro gamma-radiation assay. After gamma-irradiation of each subject's lymphocytes, the frank chromatid breaks in 50 metaphases were averaged to calculate breaks/cell. On the basis of our patient series, we established a gamma-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan-Meier and Cox proportional hazards modeling were used for the analysis. The gamma-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence interval, 0.9-2.8; P = 0.15). After adjustment for age, tumor histology, and extent of surgical resection, the hazard rate ratio was 2.4 (95% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that gamma-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.

Adult↗
PubMed1997

Role of surgery in the treatment of brain metastases in patients with breast cancer.

BACKGROUND: Patients whose brain metastases from breast cancer are treated nonsurgically have a median length of survival ranging from 2.5 to 7.5 months, and a median time to recurrence ranging from 2 to 5 months. Patients treated with radiotherapy have a median length of survival ranging from 3 to 4 months. Those treated with chemotherapy have a median length of survival ranging from 5.5 to 7.5 months. METHODS: We conducted a retrospective analysis on 63 patients treated over a 10-year period. Only patients who underwent surgery for nonrecurrent brain metastases were studied. Sixty-one patients (97%) underwent surgery within 2 weeks of diagnosis of the brain metastases. RESULTS: The median length of survival was 16 months (95% confidence interval [CI] 11 to 22 months), and the 5-year survival rate was 17% (CI 9% to 29%). Brain metastases recurred in 27 patients at a median interval of 15 months (CI 12 to 24 months). Eleven patients had local recurrence, 10 had distal recurrence, and seven developed leptomeningeal disease. Significant prognosticators of length of survival were age (p = 0.011), menopause status (p = 0.10), postoperative radiotherapy (p = 0.054), preoperative neurologic status (p = 0.011), and preoperative systemic disease status (p = 0.0003). Systemic disease status had a significant effect on the length of survival but not on the time to recurrence.

Adenocarcinoma↗
PubMed1997

Pelvic exenteration for locally advanced rectal carcinoma: factors predicting improved survival.

BACKGROUND: The purpose of this retrospective review was to determine whether a number of clinicopathologic factors (age, gender, type of exenteration, tumor extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be determined before operation were useful in predicting survival in patients undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992, 40 patients (15 male and 25 female) at our institution underwent pelvic exenteration for rectal adenocarcinoma in which tumor-free pathologic margins were obtained. Twenty-nine patients presented with primary tumors; 11 had recurrent disease. A total exenteration was performed in 20 patients, posterior exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS: By multivariate (Cox proportional hazards regression) analysis, age, preoperative chemoradiation therapy, and an S phase of 10% or greater were found to be significant predictors of survival. Age older than 55 years was associated with a relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect. An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a poor survival. The clinicopathologic factors listed above were used to derive a prognostic index (PI). A PI of less than 1.37 was associated with a 5-year survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These results indicate that adjuvant chemoradiation may significantly improve survival in patients who require pelvic exenteration for resection of locally advanced rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a poor outcome. Use of these factors allowed the generation of a PI that identifies high- and low-risk patients. Consideration of the ability to deliver chemoradiation and the determinates of the tumor S-phase fraction in patients requiring pelvic exenteration for rectal cancer may be helpful in predicting outcome and planning therapy.

Adenocarcinoma↗
PubMed1997

Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period.

Some reports have suggested that influenza virus vaccine is less effective in persons that have received prior annual vaccination(s) than in those receiving it for the first time. This issue was addressed by evaluating the efficacy of annual influenza vaccinations over a 5 year period in healthy adults employing commercially-available, inactivated whole-virus vaccine. Influenza vaccination had minimal effects on overall respiratory illnesses during epidemic periods. However, it reduced influenza virus shedding by an average of 38.8% and conferred protection against influenza virus infection during each epidemic. Some variation in infection rates were noted between vaccine groups given one or more than one annual immunization, and between years, but no consistent pattern of differences was noted in relation to number of successive years of vaccination. These results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of our prophylactic measures against influenza are needed.

Adult↗
PubMed1997

Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma?

PURPOSE: The objectives of this study were to assess clinical outcomes and prognostic factors in unselected, consecutive patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA). PATIENTS AND METHODS: The 1,400 patients analyzed were referred to our unknown-primary tumor (UPT) clinic from January 1, 1987 through July 31, 1994. Clinical data from these patients were entered into a computerized data base for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated using the product-limit method. Multivariate survival analyses were performed using proportional hazards regression and by recursive partitioning. RESULTS: Nine hundred seventy-seven patients were diagnosed with unknown-primary carcinoma (UPC) and 337 of these patients had PDC or PDA. No clinical differences were identified among patients with PDC, PDA, or UPC patients with other carcinoma or adenocarcinoma subtypes. PDC patients enjoyed better survival than PDA patients. Poor cellular differentiation was not an important prognostic variable. Variables predictive of survival included lymph node metastases, sex, number of metastatic sites, histology (PDC v PDA), and age. Although chemotherapy did not appear to influence survival for the entire group of PDC or PDA patients, a subset of patients with good prognostic features experienced median survival durations of up to 40 months. CONCLUSION: The long median survival and chemotherapy responsiveness of UPC patients with PDC and PDA could not be confirmed. However, subpopulations with prolonged median survival durations could be defined, and the value of chemotherapy in this group remains to be determined. Identification and exclusion of treatable or slow-growing malignancies may account for the poor survival of the PDC and PDA patients reported in this study.

Adenocarcinoma↗
PubMed1997

Evaluation of sister chromatid exchange and chromosome breaks in a cohort of untreated Hodgkin's disease patients.

Cytogenetic biomarkers, chromosomal breaks [spontaneous breaks (SB) and bleomycin-induced breaks (BIB)], and sister chromatid exchange (SCE) have been shown to be sensitive cytological assays to defect susceptibility to DNA-damaging effects. However, little information is available on how environmental factors and demographic and clinical characteristics influence variation among individuals. We sought to characterize interindividual variability in a cohort of 105 untreated adult Hodgkin's disease patients. SB, BIB, and SCE data were integrated with epidemiological data by using linear regression analysis. Age, sex, ethnicity, education, histology, history of mononucleosis, and family history of cancer showed no association with any biomarker. In univariate analysis, alcohol intake was significantly associated with high SCEs (P = 0.005) and SBs (P = 0.02). Current smoking was associated only with high frequencies of SCE (P = 0.05). Advanced stage of disease was related with high SBs (P = 0.01). BIBs were not associated with any of the variables studied. In multivariate modeling, current alcohol intake was associated with high SCEs (P = 0.04) and SBs (P = 0.01). Former smokers had higher SBs than nonsmokers did (P = 0.02). A small positive correlation was found among each pair of markers. The higher SCEs and SBs in patients who smoke and consume alcohol indicate the need for evaluating these exposures when interpreting these biomarkers.

Adult↗
PubMed1996

Surgical treatment of metastatic brain tumors.

The most common structural neurologic complication of systemic cancer is brain metastasis. For the most part, treatment is palliative because the majority of patients (> or = 50%) have uncontrollable systemic cancer. However, for patients in whom the only metastasis is to the brain, death is more likely to result from the metastasis than from the systemic disease; hence, treatment of the metastasis is vitally important. Although radiotherapy is generally considered the preferred treatment, surgical removal of the mass, whether single or multiple, may be the most effective palliation, especially for tumors from radio-resistant diseases such as melanoma, kidney and colon cancer. We review the information regarding therapeutic decision-making; advances in surgical procedures, namely computer-assisted stereotactic and/or intraoperative ultrasound and mapping techniques; the efficacy of postoperative WBRT; complications and benefits of surgery; our experience with reoperation for recurrent metastatic brain tumors, the results of which indicate that reoperation for recurrent brain metastasis can prolong survival and improve quality of life for most individuals; our results comparing surgery versus radiosurgery, which show that patients who undergo surgical treatment live longer and have better tumor control than those treated with radiosurgery; and the patient's prognosis. The conclusion is that surgery should remain the treatment of choice whenever possible.

Brain Neoplasms↗
PubMed1996

Cerebrospinal fluid drainage and distal aortic perfusion: reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II.

PURPOSE: This study was conducted to evaluate the role of cerebrospinal fluid (CSF) drainage and distal aortic perfusion (DAP) in the prevention of postoperative neurologic complications for high-risk patients who had undergone type I and type II thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: CSF drainage and DAP were used as an adjunct in the treatment of 94 patients with TAAA (31 type I, 63 type II) between September 1992 and December 1994; 67 were men and 27 were women. The median age was 64 years (range, 28 to 88 years). Aortic dissection occurred in 35 of 94 patients (37%). Thirty-six of 94 patients (38%) had previously undergone proximal aortic surgery. All patients underwent intraoperative DAP and perioperative CSF drainage. Median aortic cross-clamp time was 67 minutes (range, 20 to 131 minutes). RESULTS: The 30-day survival rate was 90% (85 of 94 patients). Early neurologic complications occurred in 5 of 94 patients (5%), and late neurologic complications occurred in 3 of 94 patients (3%). We compared the neurologic complications of our current group of 94 patients with the data from 42 patients (control group) who also underwent repair of TAAA type I and type II with only simple cross-clamp and without CSF drainage or DAP. Both groups were treated by the senior author (HJS) at the same institution. Total neurologic complications for the current group occurred in 8 of 94 patients (9%) versus 8 of 42 patients (19%) for the control group (p=0.090). Neurologic complications for patients with type II TAAA occurred in 8 of 63 patients (13%) versus 17 of 42 patients (41%) (p=0.014). For all patients with aortic clamp times >or=45 minutes, neurologic complications occurred in 7 of 55 (13%) versus 7 of 18 (39%) (p=0.033). CONCLUSION: The period of risk during aortic cross-clamp time is reduced with the adjuncts of CSF drainage and DAP, which significantly lower the incidence of neurologic complications after repair of TAAA types I and II.

Adult↗
PubMed1996

Surgery versus radiosurgery in the treatment of brain metastasis.

Surgery and radiosurgery are effective treatment modalities for brain metastasis. To compare the results of these treatment modalities, the authors followed 13 patients treated by radiosurgery and 62 patients treated by surgery who were retrospectively matched. Patients were matched according to the following criteria: histological characteristics of the primary tumor, extent of systemic disease, preoperative Karnofsky Performance Scale score, time to brain metastasis, number of brain metastases, and patient age and sex. For patients treated by radiosurgery, the median size of the treated lesion was 1.96 cm3 (range 0.41-8.25 cm3) and the median dose was 20 Gy (range 12-22 Gy). The median survival was 7.5 months for patients treated by radiosurgery and 16.4 months for those treated by surgery; this difference was found to be statistically significant using both univariate (p = 0.0018) and multivariate (p = 0.0009) analyses. The difference in survival was due to a higher rate of mortality from brain metastasis in the radiosurgery group than in the surgery group (p < 0.0001) and not due to a difference in the rate of death from systemic disease (p = 0.28). Log-rank analysis showed that the higher mortality rate found in the radiosurgery group was due to a greater progression rate of the radiosurgically treated lesions (p = 0.0001) and not due to the development of new brain metastasis (p = 0.75). On the basis of their data, the authors conclude that surgery is superior to radiosurgery in the treatment of brain metastasis. Patients who undergo surgical treatment survive longer and have a better local control. The data lead the authors to suggest that the indications for radiosurgery should be limited to surgically inaccessible metastatic tumors or patients in poor medical condition. Surgery should remain the treatment of choice whenever possible.

Adult↗
PubMed1996

Phase I clinical and plasma and cellular pharmacological study of topotecan without and with granulocyte colony-stimulating factor.

Topotecan, a semisynthetic water-soluble analogue of camptothecin, inhibits human topoisomerase I (topo I). We performed a Phase I clinical and plasma pharmacological study of topotecan administered by 24-h continuous infusion without and with granulocyte colony-stimulating factor (G-CSF). We also measured topo I-DNA complexes in peripheral blood mononuclear cells (PBMCs) in an attempt to correlate formation of topo I-DNA complexes in patients treated with topotecan with toxicity and/or response. One hundred four courses of topotecan at doses of 2.5-15.0 mg/m2 were administered to 44 patients with solid tumors. The maximum tolerated dose without G-CSF was 10.0 mg/m2; granulocytopenia was the dose-limiting toxic effect. The maximum tolerated dose could not be increased with G-CSF because of severe thrombocytopenia. Plasma pharmacology was obtained in 11 patients treated at 12.5 mg/m2 and 15.0 mg/m2. The topotecan lactone end-infusion plasma levels correlated strongly with the area under the curve. Lactone elimination was biexponential with a mean t1/2alpha of 28 min and a t1/2beta of 3.8 h at 12.5 mg/m2. Topo I-DNA complexes were measured before and after treatment in PBMCs from seven patients. Pretopotecan topo I-DNA complexes were available on two additional patients treated at 15 mg/m2. The mean increase in topo I-DNA complexes at the end of the topotecan infusion was 1.25 times the pretreatment value. There was a statistically significant relationship (P = 0.02) between lack of disease progression and the level of topo I-DNA complexes measured in PBMCs before therapy. For Phase II studies of minimally treated adults with solid tumors, the recommended topotecan starting dose administered by 24-h continuous infusion is 10 mg/m2 without G-CSF.

Adult↗
PubMed1995

Graphical methods for assessing violations of the proportional hazards assumption in Cox regression.

A major assumption of the Cox proportional hazards model is that the effect of a given covariate does not change over time. If this assumption is violated, the simple Cox model is invalid, and more sophisticated analyses are required. This paper describes eight graphical methods for detecting violations of the proportional hazards assumption and demonstrates each on three published datasets with a single binary covariate. I discuss the relative merits of these methods. Smoothed plots of the scaled Schoenfeld residuals are recommended for assessing PH violations because they provide precise usable information about the time dependence of the covariate effects.

Bias↗
PubMed1995

Retrograde cerebral perfusion during profound hypothermia and circulatory arrest in pigs.

The purpose of this study was to evaluate the use of retrograde cerebral perfusion via the superior vena cava during profound hypothermia and circulatory arrest (CA) in pigs. In three groups of 5 pigs each, group A (control) underwent cardiopulmonary bypass and normothermic CA for 1 hour, group B underwent cardiopulmonary bypass, profound hypothermia, and CA (15 degrees C nasopharyngeal) for 1 hour, and group C underwent the same procedure as group B plus retrograde cerebral perfusion. In group A none awoke. In group B, 2 of 5 did not awake and 3 of 5 awoke unable to stand, 2 with perceptive hind limb movement and 1 moving all extremities. In group C all awoke, 4 of 5 able to stand and 1 of 5 unable to stand but moving all limbs. In neurologic evaluation group B had significantly lower Tarlov scores than group C (p = 0.0090). Group B mean wake-up time, plus or minus standard error of the mean, was 124.6 +/- 4.6 minutes versus 29.2 +/- 5.1 in group C (p = 0.0090). In group B late phase CA cerebral blood flow dropped 30.9% +/- 4.8%, but in group C it rose 24.7% +/- 9.3% (p = 0.0007, pooled variance t test, two-tailed). In group B late phase CA brain oxygenation decreased 46.0% +/- 13.9% but it increased 26.1% +/- 5.4% in group C (p = 0.0013). This difference was reduced somewhat during rewarming (B, -21.2% +/- 14.9%; C, 16.4% +/- 4.7%; p = 0.043). Group B rewarming jugular venous O2 saturation was 30.8% +/- 2.5% versus 56.0% +/- 4.4% in group C (p = 0.0011). We conclude that in pigs retrograde cerebral perfusion combined with profound hypothermia during CA significantly reduces neurologic dysfunction, providing superior brain protection.

Animals↗
PubMed1995

Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.

PURPOSE: Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.

Adolescent↗
PubMed1995

Aggressive meningeal tumors: review of a series.

A series of 25 patients with aggressive meningeal tumors was studied to determine the efficacy of various management options. The median age of the patients was 52 years, with a range of 13 to 73 years. A marked male preponderance (64%) was noted. Twenty of 25 patients experienced recurrence during a median follow-up time of 47 months. Survival and freedom from recurrence varied with histological diagnosis. Recurrence was noted sooner in patients who had received partial resections on first presentation of tumor than in those who had received total resections at first presentation. Survival time was also shorter for patients who underwent partial resections at first presentation than for patients who underwent total resections. Patients' prognoses did not improve as a result of either chemotherapy or radiotherapy. Of six patients with extracranial metastases, the median time to metastasis was 102 months, with a 5-year metastasis-free rate of 85%. The most common sites of metastasis in these six patients were lung and bone. In each tumor type, histological features used in diagnosis and radiological features studied from computerized tomography and magnetic resonance imaging were evaluated, compared, and discussed. Of eight patients studied with an in vivo bromodeoxyuridine (BUdR) labeling index (LI), seven showed an LI of 1% or more. The authors support the incorporation of the BUdR LI into the diagnostic process to provide a better estimate of the potential for tumor recurrence.

Adolescent↗
PubMed1995

Reoperation for recurrent metastatic brain tumors.

Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I-IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001). Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001). This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.

Adolescent↗