With the discovery of radium by Curie in 1898, researchers recognized that this unique radionuclide had specific biologic properties that were applicable to treating patients with cancer. In the ...beginning, the radium sources were placed within cavities as independent sources and, when needles were available, implanted into tissues. The first combination of brachytherapy technologies with external‐beam radiation therapy was reported by Wright at the Memorial Sloan‐Kettering Cancer Center in New York in 1914 in the treatment of a patient with cervical cancer. Next, there was a rapid implementation of brachytherapy in the treatment of cancer by intracavitary placement of radionuclides, interstitial implantation technologies, and systemic administrations. With the development of new radionuclides, including cesium‐137, cobalt‐60, iridium‐192, iodine‐125, palladium‐103, ruthenium‐109, strontium‐90, iodine‐131, and californium‐225, which had varying types of radiation emissions appropriate when properly selected in treatment of cancer, there was a rapid development of innovative technologies to treat all malignancies, especially gynecologic cancer. The evolution of events brought forth new applicators and techniques that allowed for better distribution of the radiation dosage within the tumor being treated, safer use of radionuclides, and the development of computer programs allowing for varying source applications and dose distributions within the volume implanted. Cancer 1995; 76:2143–51.
This work investigated the suitability of microporous β-tricalcium phosphate (TCP) scaffolds pre-seeded with autologous chondrocytes for treatment of osteochondral defects in a large animal model. ...Microporous β-TCP cylinders (Ø 7mm; length 25mm) were seeded with autologous chondrocytes and cultured for 4weeks in vitro. Only the upper end of the cylinder was seeded with chondrocytes. Chondrocytes formed a multilayer on the top. The implants were then implanted in defects (diameter 7mm) created in the left medial femoral condyle of ovine knees. The implants were covered with synovial membrane from the superior recess of the same joint. For the right knees, an empty defect with the same dimensions served as control. Twenty-eight sheep were split into 6-, 12-, 26- and 52week groups of seven animals. Indentation tests with a spherical (Ø 3mm) indenter were used to determine the biomechanical properties of regenerated tissue. A software-based limit switch was implemented to ensure a maximal penetration depth of 200μm and maximal load of 1.5N. The achieved load, the absorbed energy and the contact stiffness were measured. Newly formed cartilage was assessed with the International Cartilage Repair Society Visual Assessment Scale (ICRS score) and histomorphometric analysis. Results were analysed statistically using the t-test, Mann–Whitney U-test and Wilcoxon test. Statistical significance was set at p<0.05. After 6weeks of implantation, the transplanted area tolerated an indentation load of 0.05±0.20N. This value increased to 0.10±0.06N after 12weeks, to 0.27±0.18N after 26weeks, and 0.27±0.11N after 52weeks. The increase in the tolerated load was highly significant (p<0.0001), but the final value was not significantly different from that of intact cartilage (0.30±0.12N). Similarly, the increase in contact stiffness from 0.87±0.29Nmm−1 after 6weeks to 3.14±0.86Nmm−1 after 52weeks was highly significant (p<0.0001). The absorbed energy increased significantly (p=0.02) from 0.74×10−6±0.38×10−6Nm after 6weeks to 2.83×10−6±1.35×10−6Nm after 52weeks. At 52weeks, the International Cartilage Repair Society (ICRS) scores for the central area of the transplanted area and untreated defects were comparable. In contrast, the score for the area from the edge to the centre of the transplanted area was significantly higher (p=0.001) than the score for the unfilled defects. A biomechanically stable cartilage was built outside the centre of defect. After 52weeks, all but one empty control defect were covered by bone and a very thin layer of cartilage (ICRS 7 points). The empty hole could still be demonstrated beneath the bone. The histomorphometric evaluation revealed that 81.0±10.6% of TCP was resorbed after 52weeks. The increase in TCP resorption and replacement by spongy bone during the observation period was highly significant (p<0.0001). In this sheep trial, the mechanical properties of microporous TCP scaffolds seeded with transplanted autologous chondrocytes were similar to those of natural cartilage after 52weeks of implantation. However, the central area of the implants had a lower ICRS score than healthy cartilage. Microporous TCP was almost fully resorbed at 52weeks and replaced by bone.
Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated ...the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.
Die zeitliche Integration von Operation, Chemotherapie und Strahlentherapie bei der brusterhaltenden Behandlung des Mammakarzinoms ist in den letzten Jahren zunehmend in den Blickpunkt des Interesses ...gerückt. Die Grundlage dieser Studie bilden 74 Patientinnen, die im Zeitraum 1985 bis 1992 an unserem Institut eine postoperative Strahlentherapie erhielten. Die mediane Nachbeobachtungszeit betrug fünf Jahre. In 73% der Fälle waren die Patientinnen prä- oder perimenopausal. Fast alle Patientinnen (91%) befanden sich im UICC-Stadium II. Axilläre Lymphknoten waren dabei in 95% befallen. Eine makroskopisch vollständige Tumorresektion wurde bei allen Patientinnen erreicht, und in 65% der Fälle waren die Resektionsränder frei von invasivem oder intraduktalem Karzinom. Postoperativ wurden in 70% der Fälle sechs Zyklen Polychemotherapie (hauptsächlich CMF) vor Bestrahlungsbeginn appliziert. Die Strahlendosis betrug fast ausschließlich 60 Gy inklusive 10 Gy Boost. Fünf Jahre nach Behandlungsbeginn betrug die Überlebensrate 86% (95%-Vertrauensbereich 76 bis 93%), die krankheitsfreie Überlebensrate 73% (61 bis 83%) und die Lokalrezidivrate 8% (3 bis 16%). Der einzige signifikante prognostische Faktor für das krankheitsfreie Überleben war die Anzahl befallener Lymphknoten: 0 bis 3=86%, ≥4=40% (p<0,0001). Das Intervall zwischen Operation und Bestrahlungsbeginn (≤ oder >20 Wochen) hatte keinen signifikanten Einfluß auf das krankheitsfreie Überleben oder die lokale Tumorkontrolle. Dagegen fand sich ein Hinweis auf eine vermehrte lymphogene und hämatogene Metastasierung bei Verkürzung des Intervalls, bedingt durch die Applizierung von weniger als sechs Zyklen Chemotherapie vor Beginn der Strahlentherapie. In unserer Erfahrung hat die Verzögerung der Strahlentherapie, um die volle Anzahl von Chemotherapiezyklen vor Bestrahlungsbeginn applizieren zu können, keinen negativen Einfluß auf die lokale Tumorkontrolle. Dabei muß allerdings die niedrige statistische Power dieser Auswertung aufgrund der kleinen Patientenzahl beachtet werden. Es erscheint möglich, daß eine weniger intensive Chemotherapie vor Beginn der Bestrahlung mit einer Erhöhung der Fernmetastasierungsrate und einer entsprechenden Verschlechterung der krankheitsfreien Überlebensrate korreliert. Für Patientinnen mit erhöhtem Metastasierungsrisiko befürworten wir daher sechs Zyklen Polychemotherapie vor der Strahlenbehandlung. The timing of breast conserving surgery, chemotherapy, and radiotherapy in breast cancer treatment has become the subject of increasing interest over the last years. Seventy-four patients who underwent postoperative radiotherapy at our institution between 1985 and 1992 form the basis of this study. Median follow-up time was 5 years. Seventy-three percent of patients were pre- or perimenopausal. Almost all patients (91%) were UICC-stage II. Axillary lymph nodes were positive in 95% of cases. Complete gross tumor resection was achieved in all patients, and in 65% final pathological margins were free of invasive or intraductal carcinoma. Postoperatively, 70% of patients received 6 cycles of polychemotherapy (predominantly CMF) before onset of irradiation. The radiation dose was in almost all cases 60 Gy including 10 Gy boost. Five years after start of treatment overall survival, disease-free survival, and local recurrence rates were 86% (95%-confidence limits, 76 to 93%), 73% (61 to 83%), and 8% (3 to 16%), respectively. For disease-free survival, the only significant prognostic factor was the number of involved lymph nodes: 0 to 3=86%, ≥4=40% (p<0,0001). The interval between surgery and radiation (≤versus >20 weeks) had no significant influence on disease-free survival or local tumor control. In contrast, there was a trend of increased regional and distant failure with shortening of the interval due to the delivery of less than 6 cycles chemotherapy before the onset of radiotherapy. In our experience, there was no negative impact of a delay of radiotherapy in order to deliver full course chemotherapy before initiation of radiotherapy. However, the low statistical power of this analysis due to the small number of patients must be considered. It appears possible that a less intense chemotherapy before starting radiation treatment correlates with enhanced distant failure and subsequently decreased disease-free survival rates. Therefore, for patients at increased risk for distant metastasis, we prefer to give 6 cycles polychemotherapy before irradiation.PUBLICATION ABSTRACT
Abstract Background Surgical site infection and nosocomial infections in general have appropriately undergone increased scrutiny over the last decade. Numerous studies have documented pathogenic ...bacterial contamination of personal items such as cell phones, pagers, ties and pens in the hospital setting. It is our understanding that JCAHO requires all personnel to wear an identification badge at all times which includes the operating room environment. Methods Badges, lanyards and pagers from operating room personnel were swabbed and cultured using the same protocol used for surgical specimens in the operating rooms. Personnel included orthopaedic attendings (14), orthopaedic residents (20), nurses (19) and anesthesia personnel (11). Results A total of 64 badges were sampled, with no MSSA or MRSA cultured on any of the badges. Two of 64 had enterococcus (3%), and 1 of those was vancomycin resistant. Pagers had similar results, with only 1/42 growing MSSA or enterococcus (2.4%), and no MRSA. Lanyards showed higher rates of contamination. There were 11% with MSSA or MRSA out of 27 sampled. Highest contamination rates were with orthopaedic staff and resident lanyards, with 3/22 (13.6%) growing MSSA or MRSA. No lanyards grew enterococcus. When comparing rates of MSSA/MRSA between groups, lanyards had a statistically significant higher rate (p < 0.05). Conclusion At a minimum, operating room personnel should probably not use lanyards to display their ID badges.
Management of carcinoma of the bladder Petrovich, Z; Baert, L; Boyd, S D ...
American journal of clinical oncology,
06/1998, Volume:
21, Issue:
3
Journal Article
Peer reviewed
Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In the United States in 1997, CaB was second in frequency of occurrence and third in mortality among genitourinary tumors. ...This tumor has a well-documented history of environmental and industrial causative factors. The strongest etiologic risk factors include the use of tobacco, which is thought to be responsible for half of the CaB diagnosed in men in the United States, and some arylamines. In the past 30 years, there has been major improvement in the survival of patients with this disease. Multiple factors were responsible for this accomplishment and they include: 1) better understanding of the natural history of CaB, 2) development of immunohistochemical analysis helpful in defining prognostic factors, 3) improved imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis and better defining the true anatomical extent of the tumor, 4) development of more effective therapy for carcinoma in situ, 5) major improvement in surgical techniques resulting in better treatment outcomes, and 6) the wide use of adjuvant chemotherapy. Major stress has been placed on the quality of life of patients treated for CaB. Quality of life was improved by optimizing surgical, radiation, and medical treatment techniques. The two most important factors producing this quality-of-life improvement include: 1) the use of organ-preserving therapy in properly selected patients that involves the use of a multimodality therapeutic approach with transurethral resection, radiation therapy, and chemotherapy; and 2) the ability to treat selected men and women with radical cystectomy followed by orthotopic reconstruction that allows patients nearly physiologic voiding. Current research efforts are directed toward better patient selection for appropriate therapy which is expected to increase patient survival and improve quality of life. Of particular importance in the selection of this optimal therapy in patients with CaB is a wide application in the clinical practice of important recent advances in molecular genetics.
Patients with malignant gliomas have a limited survival prognosis. We retrospectively analyzed data of malignant glioma patients with the aim of defining prognostic factors on which individualized ...treatment strategies might be built on.
Seventy-six patients with primary malignant glioma (51 glioblastoma multiforme, 20 anaplastic astrocytoma, 4 anaplastic oligo-astrocytoma, 1 anaplastic glioma) were postoperatively irradiated with 5 and 8 Me V photons, 2 Gy per fraction to a median total dose of 60 Gy (range 50 to 70 Gy).
The youngest quartile of patients (up to 45 years) had the highest 3-year survival rates (mean +/- SE: 15 +/- 8%) and median survival time (17.9 months, 95% confidence interval: 9.2, 24.2 months) as compared to the oldest quartile (> 61 years) with no 3-year survivor and a median survival time of 9.7 months (7.2, 12.3 months). The middle quartiles (46 to 61 years) showed intermediate results. The difference between the youngest and oldest quartile (p = 0.01) and the middle quartile versus the oldest quartile (p = 0.04) was significant. In univariate analysis, tumor size (p = 0.04 for -30 mm vs > 50 mm) was of importance. In multivariate analysis only age of the patient reached statistical significance (p = 0.03). As compared to the youngest quartile of patients, the oldest quartile had a relative risk of 2.1 (95% confidence interval: 0.9, 5.1) of dying from the disease; the age group of 46 to 61 years had a relative risk of 2.0 (0.9, 4.3).
Age of the patient is the most important factor for survival prognosis favouring younger age (< or = 45 years). The possible implications for radiation therapy are discussed.
This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with ...jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.
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