Prospective detection of preclinical lung cancer: results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression.

The United States lung cancer epidemic has not yet been controlled by present prevention and treatment strategies. Overexpression of a Mr 31,000 protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, had shown promise as a marker of lung cancer. In a pilot study of archived preneoplastic sputum specimens, hnRNP A2/B1 overexpression more accurately detected preclinical lung cancer than standard cytomorphology.

Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants. NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy.

Background: High grade astrocytomas remain uniformly fatal despite aggressive surgery and radiotherapy. As existing chemotherapeutic agents are of limited benefit, clinical trials are underway to screen new drugs, such as 9-aminocamptothecin (9-AC), for activity in high grade astrocytomas.

Purpose: This study was designed to estimate the efficacy of 9-AC in patients with newly diagnosed glioblastoma multiforme and recurrent high grade astrocytomas.

Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid.

Follicular and Hürthle cell carcinomas of the thyroid cannot be differentiated from adenomas by either preoperative fine needle aspiration or intraoperative frozen section examination, and yet there exist potentially significant differences in the recommended surgical management. We examined, by PCR-based microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22 follicular adenomas, 29 follicular carcinomas, 20 Hürthle cell adenomas (HA), and 12 Hürthle cell carcinomas (HC)] to determine whether a pattern of allelic alteration exists that could help distinguish benign from malignant lesions. Alterations were found in only 7.

A randomized controlled trial comparing the cuffed oropharyngeal airway and the laryngeal mask airway in spontaneously breathing anesthetized adults.

Background: The cuffed oropharyngeal airway (COPA), a modified Guedel airway, was compared with the laryngeal mask airway (LMA) during spontaneous breathing anesthesia. Specifically examined were ease of use, physiologic tolerance, and the frequency of problems.

Methods: Adult patients consented to random (2:1) assignment to either COPA (n = 302) or LMA (n = 151) for airway management during anesthesia with propofol, nitrous oxide, and oxygen.

Practical implementation of a modified continual reassessment method for dose-finding trials.

Purpose: We describe a practical, reliable, efficient dose-finding design for cytotoxic drugs applied in a multi-institutional setting.

Methods: The continual reassessment method (CRM) was modified for use in phase I trials conducted through the New Approaches to Brain Tumor Therapy (NABTT) Consortium. Our implementation of the CRM uses (1) a simple dose-toxicity model to guide data interpolation, (2) groups of three patients to minimize calculations and stabilize estimates, (3) investigators' clinical knowledge or opinion in the form of data to make the process easier to understand, and (4) a flexible computer program and interface to facilitate calculations.

DNA content and other factors associated with ten-year survival after resection of pancreatic carcinoma.

Background And Objectives: The 5-year survival rates after resection of pancreatic carcinoma have recently increased and are predicted by tumor size, DNA content, and lymph node metastases at the time of resection. However, whether the 10-year survival rates have also increased and are similarly predicted by these factors is not known.

Methods: The influence of preoperative imaging tests, alcohol consumption, cigarette smoking, K-ras mutations, anatomic location, details of surgical resection, pathologic findings, and tumor DNA content on survival was tested for 96 patients after a successful resection of a pancreatic carcinoma with 17 patients being followed for more than 5 years.

Immunomodulatory properties of antineoplastic drugs administered in conjunction with GM-CSF-secreting cancer cell vaccines.

Cancer cells genetically modified to secrete immunoregulatory cytokines offer great promise for human cancer treatment as tumor vaccines. However, in preclinical animal studies, large established cancer burdens have appeared difficult to eradicate with such vaccines. For example, lethally-irradiated GM-CSF-secreting CT26 colon carcinoma cell vaccine therapy tends to cure only animals bearing 1 x 10(5) wild-type CT26 cells or less.

Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium.

Purpose: The purpose of this study was to determine the response rate of paclitaxel administered at maximal tolerated doses (MTD) in patients with newly diagnosed glioblastoma multiform.

Patients And Methods: All patients in this multicenter study were 45 years or older and had measurable residual tumor on postoperative MRI scans. Up to 3 cycles of paclitaxel were administered as a continuous 96-hour intravenous infusion prior to radiation, provided that the tumor did not enlarge on serial MRIs.

A new subarachnoid hemorrhage grading system based on the Glasgow Coma Scale: a comparison with the Hunt and Hess and World Federation of Neurological Surgeons Scales in a clinical series.

Objective: Although the Hunt and Hess Scale (HHS) and World Federation of Neurological Surgeons Scale (WFNSS) are the most widely used subarachnoid hemorrhage (SAH) grading systems, neither system has achieved universal acceptance. We propose a simplified grading system based entirely on the Glasgow Coma Scale (GCS), which compresses the 15-point GCS into five grades that are comparable with those of the HHS and WFNSS. We refer to this system as the GCS grading system and present a direct comparison with the HHS and WFNSS for predictive value regarding patient outcome and interrater reliability.

Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed high-grade astrocytoma.

Purpose: To evaluate the activity and toxicity of carmustine (BCNU) and cisplatin administered as a 72-hour continuous intravenous infusion before radiation in adults with newly diagnosed high-grade astrocytomas.

Patients And Methods: Fifty-two patients with a Karnofsky performance status greater than 60 and no prior antineoplastic therapy entered this protocol. The median age of the patients was 55 years.

Correlation of prostate needle biopsy and radical prostatectomy Gleason grade in academic and community settings.

Prior studies have not analyzed grading patterns and accuracy in nonacademic sites and have not analyzed reasons for discrepant grades. We analyzed 499 radical prostatectomy (RP) specimens at The Johns Hopkins Hospital (JHH) from 1994 and compared them with the corresponding JHH needle biopsy Gleason grade and, when available (n = 390), to the outside institution (non-JHH) Gleason biopsy grade. For JHH, there was exact agreement between biopsy and RP in 58% and agreement to within one digit in 93% of cases, compared with 34% and 67%, respectively, for non-JHH.

Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer.

APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis.

Background: Familial adenomatous polyposis (FAP) is caused by germline mutation of the adenomatous polyposis coli (APC) gene on chromosome 5q.

Aims: This study assessed genotype-phenotype correlations for extraintestinal lesions in FAP.

Methods: Mutations of the APC gene were compared with the occurrence of seven extraintestinal manifestations in 475 FAP patients from 51 families.

Artificial neural networks: application to electrical stimulation of the human nervous system.

Artificial neural networks are used increasingly in applications such as graphic pattern recognition, which are difficult to address with conventional statistical methods. In the management of chronic pain, graphic methods are used routinely; patients describe their patterns of pain using "pain drawings." The authors have previously reported an automated, computerized pain drawing methodology, which has been used by patients with implanted spinal cord stimulators to represent a technical goal of the procedure, the overlap of pain by stimulation paresthesias.

Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors.

Two approaches for improving the interstitial administration of carmustine (BCNU) using 3.8% loaded poly(carboxyphenoxypropane-sebacic acid), an implantable biodegradable anhydride which significantly prolongs survival in patients with recurrent malignant gliomas, were evaluated. First, increasing the ratio of carboxyphenoxypropane (CPP) to sebacic acid (SA) in the polymer increases its hydrolytic stability, thus prolonging its half-life in vivo, and extending the period of drug release.

Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors.

Objective: The objective of this article is to introduce a simple method for classifying cholangiocarcinomas and to apply this system to analyze a large number of patients from a single institution.

Summary Background Data: For the past 2 decades, most western reports on cholangiocarcinoma have separated intrahepatic from extrahepatic tumors and have subclassified this latter group into proximal, middle, and distal subgroups. However, "middle" lesions are uncommon and are managed most often either with hilar resection or with pancreatoduodenectomy.

Improved designs for dose escalation studies using pharmacokinetic measurements.

We describe a method for incorporating pharmacokinetic (PK) data into dose escalation clinical trial designs. Doing so can improve the efficiency and accuracy of these studies. The method proposed uses a parametric dose response function that models the probability of response in each person with two effects: the dose of drug administered and an ancillary pharmacokinetic measurements.

An uncertain role for p53 gene alterations in human prostate cancers.

Inactivation of the p53 gene has been implicated in prostate cancer progression. To determine the role of p53 inactivation in the progression of clinical prostatic carcinomas, we assessed 67 tumors derived from patients with clinically localized disease for chromosome 17p and p53 gene allelic loss, p53 gene mutations using single-strand conformational polymorphism and direct sequencing, and p53 protein expression using immunohistochemical staining. Of 55 informative tumors, 10 demonstrated loss of 17p or the p53 gene; however, only a single tumor had a mutation in its remaining p53 allele.

Genetic progression model for head and neck cancer: implications for field cancerization.

A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained obscure. Eighty-seven lesions of the head and neck, including preinvasive lesions and benign lesions associated with carcinogen exposure, were tested using microsatellite analysis for allelic loss at 10 major chromosomal loci which have been defined previously. The spectrum of chromosomal loss progressively increased at each histopathological step from benign hyperplasia to dysplasia to carcinoma in situ to invasive cancer.

Specificity of diagnostic nerve blocks: a prospective, randomized study of sciatica due to lumbosacral spine disease.

Temporary nerve blocks using local anesthetic are employed extensively in the evaluation of pain problems, particularly lumbosacral spine disease. Their specificity and sensitivity in localizing anatomic sources of pain have never been studied formally, however, and so their diagnostic and prognostic value is questionable. There have been anecdotal reports of relief of pain by temporary blocks directed to areas of pain referral, as opposed to areas of documented underlying pathology; but there has been no study to define the frequency or magnitude of this effect.

Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant.

Purpose: We examined the impact of age on outcomes in patients with cancer undergoing autologous bone marrow transplantation (ABMT).

Patients And Methods: All 506 adult patients who underwent ABMT at the Johns Hopkins Oncology Center between January 1987 and January 1994 were studied. A total of 405 patients were aged 18 to 49 years and 101 were aged > or = 50.

Clearance rate of serum-free and total PSA following radical retropubic prostatectomy.

Background: Our objective was to determine the clearance rate of free and total serum PSA following radical retropubic prostatectomy.

Methods: Sera were obtained from 10 men with localized prostate cancer prior to and 1, 4, 8, 24, 48, and 72 hr after radical prostatectomy. No patient received any postoperative blood transfusion.

The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial.

The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) impregnated polymer as the initial therapy for malignant brain tumors are reported. This is the first study of locally delivered BCNU and standard external beam radiation therapy (XRT) given concurrently. Twenty-two patients were treated at three hospitals.

The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis.

Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death).

Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate.

Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases.