One trial has suggested improved survival with preoperative chemotherapy and radiation therapy with acceptable morbidity and mortality. Other studies have not demonstrated apparent improvement in survival, although the protocols are somewhat different. Longer follow-up is needed in these preliminary studies, and well-designed, prospective, multicenter randomized trials are necessary in the future. These studies should compare identical CRT and surgery regimens and identify a group of esophageal patients that might benefit from preoperative chemotherapy or radiation therapy. In order to evaluate the results of future trials without bias and to determine which group of esophageal patients will benefit from preoperative CRT, pretreatment, accurate TNM staging by CT and EUS combined with pathologic LN staging when possible will be crucial in future trimodality therapy trials for esophageal cancer. The investigation of biologic molecular markers to predict chemoradiation sensitivity and prognosis deserves careful exploration. Unfortunately, those patients without a response do not benefit from the preoperative chemotherapy but still may suffer the associated toxicity. These patients may have a much higher risk of postoperative fatal complications including respiratory failure, bone marrow suppression, and sepsis. It has been shown that CR patients in the chemotherapy/surgery group survive longer than nonresponders; it would be helpful to find useful molecular biomarkers to identify chemotherapy-sensitive patients before the preoperative chemotherapy is employed. Several pilot trials are underway using chemotherapy sensitivity testing on the endoscopic biopsy specimen before the chemotherapy is applied.

Chemotherapy, Adjuvant↗

PubMed1999

Technology assessment of multileaf collimation: a North American users survey.

PURPOSE: The American Association of Physicists in Medicine (AAPM) initiated an Assessment of Technology Subcommittee (ATS) to help the radiotherapy community evaluate emerging technologies. The ATS decided to first address multileaf collimation (MLC) by means of a North American users survey. The survey attempted to address issues such as MLC utility, efficacy, cost-effectiveness, and customer satisfaction. METHODS AND MATERIALS: The survey was designed with 38 questions, with cross-tabulation set up to decipher a particular clinic's perception of MLC. The surveys were coded according to MLC types, which were narrowed to four: Elekta, Siemens, Varian 52-leaf, and Varian 80-leaf. A 40% return rate was desired. RESULTS: A 44% (108 of 250) return was achieved. On an MLC machine, 76.5% of photon patients are being treated with MLC. The main reasons for not using MLC were stair stepping, field size limitation, and physician objection. The most common sites in which MLC is being used are lung, pelvis, and prostate. The least used sites are head & neck and mantle fields. Of the facilities, 31% claimed an increase in number of patients being treated since MLC was installed, and 44% claimed an increase in the number of fields. Though the staffing for block cutting has decreased, therapist staffing has not. However, 91% of the facilities claimed a decreased workload for the therapists, despite the increase in daily treated patients and fields. Of the facilities that justified MLC purchase for more daily patients, 63% are actually treating more patients. Only 26% of the facilities that justified an MLC purchase for intensity-modulated radiotherapy (IMRT) are currently using it for that purpose. The satisfaction rating (1 = low to 5 = high) for department groups averaged 4.0. Therapists ranked MLC as 4.6. CONCLUSIONS: Our survey shows that most users have successfully introduced MLC into the clinic as a block replacement. Most have found MLC to be cost-effective and efficient. The use of MLC for IMRT has progressed slower, but users anticipate escalated use.

Consumer Behavior↗

PubMed1999

Internal schisms are bad medicine.

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Attitude of Health Personnel↗

PubMed1999

Changing the norm. Ten suggestions to redress the rural crisis.

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Attitude of Health Personnel↗

PubMed1997

Evaluation of potential genotoxicity of pulsed electric and electromagnetic fields used for bone growth stimulation.

Medical devices emitting pulsed electric and electromagnetic fields have been found to be effective for a number of clinical applications including stimulation of bone and tissue growth. To determine whether pulsed fields of the type used in these clinical applications present a mutagenic hazard, electric and electromagnetic fields at two exposure levels were tested in the Ames test, CHO cell chromosomal aberration assay, BALB/3T3 cell transformation assay and unscheduled DNA synthesis assay in primary rat hepatocytes. For both field types, initial and independent repeat studies were performed for each assay at both clinical and supra clinical doses. In all assays, the results show a lack of cytotoxic, transforming and mutagenic activity. The data suggest that pulsed electric and electromagnetic fields of the type and dose levels used in bone growth stimulation lack mutagenic and transforming activity.

3T3 Cells↗

PubMed1995

Pharmacokinetic interactions of nifedipine and quinidine.

Several clinical investigations have been published regarding the interaction of nifedipine and quinidine. The results of these studies are contradictory. In vitro studies indicate that the 3-hydroxylation and N-oxigenation of quinidine appear to involve the P4503A4 family, a form of cytochrome that predominantly catalyzes the aromatization of nifedipine, too. The aim of our study was to investigate the effect of oral intake of 200 mg quinidine on the kinetics of 20 mg nifedipine as a retarded formulation and vice versa. Twelve healthy male volunteers between 18 and 40 years were treated. Each subject was studied on three occasions each separated by a one week washout period. Drug administration consisted of one oral dose of nifedipine (Adalat retard 20 mg), one oral dose of quinidine (Chinidin sulfuricum "Buchler" 200 mg) or a combination of both (20 mg nifedipine and 200 mg quinidine) in a randomised 3 way crossover. Administration of the test drugs in combination slightly increased the bioavailability of both--nifedipine [N] to 18% and quinidine [Q] to 16%--and decreased the clearance of both drugs. The results were not statistically significant. Based on our data, the combination of nifedipine and quinidine seems to lack a clinically relevant interaction.

Adult↗

PubMed1995

Analysis of amount, expenditures and indications of drug and blood product prescriptions at surgical intensive care units.

Analysis of indication-related drug prescription patterns is of particular interest with regard to rising costs of the health service being also reflected in higher expenditures for drugs at the University Hospital of the Friedrich-Schiller-University Jena. This is especially important at ICU's, since treatments in patients with acute or chronic multiorgan failure are very expensive. Over a period of 4 months in 1994 the indication-related drug consumption of 2 surgical ICU's of the University of Jena has been recorded and analyzed using a notebook-PC. The total costs of these drugs and blood products, which caused 80% of total costs in the last year, came up to 1,144,773 DM for 465 patients. Nearly two thirds of the recorded expenditures were caused in patients with severe trauma or with acute bleeding. The 10 leading substances (antithrombin III, human albumin 20%, prothrombine complex, etc.) represent 67% of total costs including blood products, antibiotics/antimycotics and IgM enriched intravenous immunoglobulines. Therefore, the indications of these drugs in particular have been further investigated. During and after the study the results have been discussed with the treating medical staff leading to new therapy recommendations. Until the end of 1994 a remarkable cost saving could already be achieved for some drugs by more critical and purposeful use providing same high standard of medical treatment. Blood products have to be included into analyses of indication-related drug administration on the meaning of high costs, difficulties of accurate indication, and possibly undesired side-effects. However, medical and ethical aspects, e.g. minimizing of side-effects, have to take priority over pharmacoeconomical considerations especially in intensive care medicine.

Animals↗

PubMed1994

Evaluation and treatment of patients receiving radiation for cancer of the rectum or sigmoid colon in the United States: results of the 1988-1989 Patterns of Care Study process survey.

PURPOSE: For the first time, a Patterns of Care Study (PCS) was conducted in 1989 to determine the national practice standards of radiation oncologists in evaluating and treating adenocarcinoma of the rectum and sigmoid colon. MATERIALS AND METHODS: A national survey of 73 institutions using two-stage cluster sampling was conducted, and specific information on 408 patients from 69 facilities with adenocarcinoma of the rectum and sigmoid colon who received radiation as part of definitive or adjuvant management was collected. RESULTS: Using the modified Astler-Coller (MAC) pathologic staging system, the stage distribution was as follows: A, 0.5%; B1, 4.4%; B2, 23.5%; B3, 5.1%; C1, 8.9%; C2, 30.2%; and C3, 6.6%. Preoperative radiation was used in 29% of patients, but the total dose was greater than 40 Gy in only 20%. Seventy-three percent of patients received postoperative radiation, with approximately 4% receiving combined preoperative and postoperative radiation. Chemotherapy was administered to 44% of patients overall, representing 55% of patients with disease through the bowel wall and/or involving lymph nodes. Only 37% of all patients received chemotherapy concurrent with radiation. An abdominoperineal resection was used in 43%; a low anterior resection was used in 43% as well, while 5% underwent other types of bowel resection. Approximately 8% of patients were treated with a local curative procedure less than bowel resection (eg, local excision, endoscopic resection, fulguration, or contact radiation). At least one third of patients had interruption in their pelvic irradiation of greater than 3 days. There was no statistically significant difference in the frequency of treatment interruptions by dose per fraction or whether chemotherapy was given concurrent with radiation. There was no significant difference in total dose delivered to patients staged B2 and higher treated without chemotherapy compared with concurrent chemotherapy and radiation. Also, there was no significant difference in total dose delivered to patients with B1 and B2, or C1 and C2 versus B3 or C3 cancer. CONCLUSION: This study was conducted on patients treated just before the 1990 National Institutes of Health consensus guidelines issued on the management of colon and rectal cancer. This study indicates that the minority of patients treated with radiation in 1988 and 1989 received concurrent chemoradiation, as currently recommended. Additionally, insofar as present studies are investigating important issues such as the use of sphincter-sparing procedures, preoperative radiation and chemotherapy, and the importance of radiation dose and scheduling with chemotherapy, the information provided by this study will serve as a useful baseline to track future changes in rectal cancer evaluation and management.

Adenocarcinoma↗

PubMed1990

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties.

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

Adult↗

PubMed1990

Early B-lymphocyte precursor cells in mouse bone marrow: subosteal localization of B220+ cells during postirradiation regeneration.

The localization of early B-lymphocyte precursor cells in the bone marrow of young mice has been studied during recovery from sublethal whole body gamma-irradiation (150 rad). Initial studies by double immunofluorescence labeling of the B-lineage-associated cell surface glycoprotein, B220, and of mu heavy chains in bone marrow cell suspensions, demonstrated a sequential wave of regeneration of early B precursor cells, pre-B cells, and B cells. Early B precursor cells expressing B220 but not mu chains were enriched at 1-3 days following irradiation. After in vivo administration of 125I-labeled monoclonal antibody 14.8 to detect B220+ cells in situ, light and electron microscope radioautography of femoral bone marrow sections revealed concentrations of labeled B220+ cells located peripherally near the cortical bone at 1-3 days following irradiation, increasing in numbers in more central areas by 5-7 days. Proliferative B220+ precursor cells were found within layers of bone-lining cells and in a subosteal area characterized by a prominent electron-dense extracellular matrix, often associated with stromal reticular cells. The results demonstrate that the precursor cells that are active in the bone marrow early in the recovery of B lymphopoiesis after gamma-irradiation are located both within and near the endosteum of the surrounding bone. The distinctive extracellular matrix and stromal cell associations noted in this region may contribute to a supportive local microenvironment for early hemopoietic progenitor cells.

Animals↗

PubMed1988

Local excision and irradiation as primary treatment of rectal cancer.

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Adenocarcinoma↗

PubMed1986

A comparative evaluation of rare earth screen-film systems. Free-response operating characteristic analysis and anatomic criteria analysis.

Diagnostic accuracy was evaluated in a signal detection experiment that used low-contrast acute lesions in a living dog model. At the high levels of certainty normally used by radiologists, rare earth screen-film systems provided accuracy comparable to that of a reference calcium tungstate screen-film system. Additionally subjective image quality evaluation for a given imaging task (clinical pediatric anterior-posterior chest films) based on visualization of anatomic landmarks and physical parameters has been conducted for several rare earth and one calcium tungstate screen-film system. The correspondence of subjective physical ranking with physical and psychophysical measurements was investigated. Evaluating the visualization of anatomic parameters can provide a clear and objective distinction among systems with comparable physical and psychophysical properties.

Animals↗

PubMed1985

A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk.

Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the chemotherapy arm was 77%, compared to 49% in the no-chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the chemotherapy arm was 92%, compared to 47% in the no-chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the chemotherapy arm was 82%, compared to 61% in the no-chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with chemotherapy was doxorubicin-induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.

Actuarial Analysis↗

PubMed1985

Results of multimodality therapy of resectable soft-tissue sarcomas of the retroperitoneum.

Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate). A subset of 15 patients were entered into a prospective, randomized study testing the efficacy of adjuvant chemotherapy (eight received chemotherapy; seven did not). Two-year actuarial survival rates were inferior in the chemotherapy arm (100% versus 47%; p = 0.06), but the small number of patients precluded drawing definitive conclusions from this randomized study alone. Among the entire 37 patients (21 received chemotherapy; 16 did not) the actuarial 3-year survival rate was 43% and appeared unaffected by chemotherapy. Two patients suffered doxorubicin infiltration, three sustained cardiac toxicity, two developed cyclophosphamide-induced cystitis, and three withstood transient, severe bone marrow suppression. Eight patients suffered severe radiation enteritis, and one patient died after bowel resection for this problem. Thus the chemotherapy regimen we administered did not appear to improve survival but was associated with major morbidity. Radiotherapy was also associated with major complications, and since all patients received radiotherapy, it remains to be established if this modality is beneficial in improving survival.

Actuarial Analysis↗