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Three-dimensional photon treatment planning for Hodgkin's disease.

A multi-institutional study was undertaken using computerized planning systems to develop three-dimensional (3-D) radiotherapy plans for Hodgkin's disease (H.D.). Two patients, the first afflicted with bulky stage II disease and another one with early stage I H.D., were studied. Three main categories of plan were produced for each patient: a) a traditional plan which modelled a conventional mantle treatment on the 3-D system, b) a 3-D standard plan where anterior and posterior fields were designed to cover 3-D target volumes, and c) a 3-D unconstrained plan where innovational techniques were employed. Three-dimensional planning provides information about the dose distribution throughout the large volume irradiated in patients with H.D. that is not available with conventional mantle planning. The use of 3-D techniques resulted in improved tumor coverage, but by allowing for uncertainties such as motion, the doses to normal tissues tended to be higher. The use of unorthodox beam arrangements introduced added complexities, and further increased the lung doses. The most even dose distributions were obtained by incorporating compensating filters into anterior fields. Clinicians showed wide variations in their assessment of the plans, possible reasons for which are addressed in this paper. In addition, calculated probabilities from models of tumor control and normal tissue damage are also presented.

Hodgkin Disease↗

Resection of hepatic metastases from colorectal cancer. Biologic perspective.

During the past decade the results of slightly fewer than 1000 resections of liver metastases from colorectal carcinoma have been analyzed, retrospectively reanalyzed, and reviewed. The following are confirmed conclusions: major liver resection can be performed safely (less than a 5% operative mortality rate); 20% to 25% of these patients are cured; no other regional therapy options have any curative potential. The following caveats are also obvious: most patients who are operated on are not cured; although predictors have been proposed to select patients most likely to benefit from surgery, none is discriminating in and of itself; most therapy questions in this group of patients have not been addressed in any formal way; surgery for isolated regionally recurrent colon and rectum carcinoma remains an important stopgap only until effective systemic therapy is discovered. This review of our own and other single and multi-institutional prospective and retrospective data will be framed by the following questions. (1) Does resection of liver metastases cure patients or simply select those who would have survived in the long-term without any therapy? (2) In the absence of any formalized, properly designed trial, how can one judge the benefit of resection? (3) Why do metastases recur only in the liver? (4) What new therapies should focus on the predominant secondary failure sites in the majority of patients who do not benefit from hepatic metastasis resection?

Colorectal Neoplasms↗

Multi-institutional privileging: a pilot demonstration project of the United States Navy and the Joint Commission on Accreditation of Healthcare Organizations.

The U.S. Navy and the Joint Commission on Accreditation of Healthcare Organizations have undertaken a 3-year multi-institutional privileging project. The concept involves granting privileges in one Navy facility that are recognized throughout the system during the staff appointment period. It entails: (1) use of specialty-specific standardized privilege lists, (2) designation of one authority at a time to grant the appointment with privileges, (3) use of a single credentials file during the practitioner's career, and (4) medical staff bylaws applicable to the entire system. The concept is potentially useful in other armed services, the Veterans Administration, and some civilian systems.

Hospitals, Military↗

Health care delivery: strength in numbers.

The number and types of multi-institutional arrangements among health care facilities are on the increase, and the days of the completely autonomous, independent hospital are coming to a close. Although by themselves hospital systems are no panacea in dealing with the challenges facing hospitals today, many such arrangements offer more opportunities than problems in coping with the rapid changes currently facing the health care industry. The pros and cons of seven arrangements are discussed in detail.

Area Health Education Centers↗

Hematoporphyrin photodynamic therapy: is there truly a future in head and neck oncology? Reflections on a 5-year experience.

Photodynamic therapy, which consists of the selective destruction of tumors using a combination of a photosensitizer administered systemically (dihematoporphyrin ether) and an argon dye-pumped laser, has provoked profound interest amongst oncologists and has particularly titillated head and neck oncologists with its potential. Unfortunately, no multi-institutional trials for head and neck tumors have been introduced, and the literature is replete with anecdotal reports from individual researchers on the management of advanced cancers for palliation, superficial early cancers, and field cancerization of the mucosa ("condemned mucosa"). A personal 5-year experience with 41 head and neck cancers was reviewed, as was the current literature. An attempt was made to place in perspective the true role and future direction of this technology.

Carcinoma, Squamous Cell↗

Systemic therapy of head and neck cancer: most effective agents, areas of promise.

The management of squamous cell cancer of the head and neck is a challenging problem. However, "induction" chemotherapy administered prior to surgery and radiation therapy in newly diagnosed patients is showing encouraging results for the preservation of organ function and is the focus of multi-institutional trials. Concurrent chemotherapy and radiation therapy is another approach with promise for unresectable disease. Recent studies combining cisplatin with radiation therapy have reported minimal enhancement of mucocutaneous toxicity and promising survival data. Other strategies which are just beginning to receive attention in clinical research trials include adjuvant chemotherapy in the disease-free patient and biologic response modifiers.

Antineoplastic Agents↗

Multi-institutional approach to regionalization of pediatric critical care. Seven year experience.

A multi-institutional, pediatric intensive care program initiated in Jacksonville, Florida, is a systematic approach to critical care which avoids costly duplication and provides efficient clinical services and an academic fellowship program. A total of 6,876 consecutive admissions to the two units over a seven-year period are discussed and compared to national data. A coordinated system may provide a model for other communities; however, the ability to expand services in a market where public and private third party funding is being reduced may become a problem.

Adolescent↗

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. DESIGN: Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. SETTING: Multi-institutional medical and surgical ICUs. PATIENTS: Patients meeting predetermined criteria for severe sepsis syndrome. INTERVENTIONS: Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. CONCLUSIONS: This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

Adolescent↗

The impact of PACS on research and education.

Picture Archiving and Communication Systems (PACS) are rapidly evolving and the total digital radiology department may be a reality within the next decade. PACS can have a major impact on the educational and research responsibilities of a medical institution. The possibility of correlating real patient data with existing radiological teaching files opens up numerous possibilities. Multi-institutional research can be strengthened by employing the PACS as the means to the end. This paper discusses the representative examples of how teaching and research can be enhanced with PACS and the technical requirements to achieve the inter-connectivity.

Education, Medical↗

A model for multidisciplinary data collection for cervical metastasis.

A system for multidisciplinary data collection for metastatic neck disease is discussed. Information from 87 neck dissections and 3218 lymph nodes is reported to illustrate the strength of the model. Clinical (endoscopic) assessment under general anesthesia, surgical assessment during the neck dissection, and radiographic (computed tomographic scan) assessment were compared with the pathological evaluation. All disciplines stratified the necks by region and node size. This model provides an effective stratagem for multi-institutional studies.

Data Collection↗

Chinese medical school exit objectives: a multi-institutional survey of teacher opinion.

This paper describes a collaborative survey of Chinese medical school teacher opinion concerning clinical behaviours and skills that Chinese students should be expected to demonstrate prior to graduation from medical school. Selected teachers from four Chinese medical schools indicated whether each of 77 objectives was: essential for every student to know or demonstrate prior to graduation; useful but not essential; or not applicable to their educational programmes. Results show teachers' expectations regarding some of the behaviours and skills Chinese medical school teachers consider to be important for students to learn. Forty-nine per cent of the exit objectives were regarded as essential by 75% or more of the teachers. The most essential objectives involved performing clinical procedures, collaborating and communicating with health care professionals, conducting organ system examinations, formulating hypotheses and defining problems. Other essential objectives were concerned with communicating with patients and their families, maintaining currency within the discipline, and recognition, evaluation and triage of patients with life-threatening or chronic conditions. Exit objectives related to health promotion and risk assessment were regarded as useful but not essential at the undergraduate level. Implications for Chinese medical education are discussed.

China↗

Graduate medical education into the 1990's. A call for debate.

The authors have reviewed the present system of graduate medical education, including independent, affiliated, and integrated residency training programs. Advantages and disadvantages are considered in light of recent changes in health-care delivery systems. Structure, historical development, present status, and limitations of the programs are discussed. Personnel resources of the residency program are classified as United States citizens and non-citizens, American medical school graduates, United States citizen graduates of foreign medical schools, and alien foreign medical school graduates, and their different educational backgrounds are compared. Financial aspects of these programs are considered, and the need to increase university control over residency programs, especially in multi-institutional affiliated residency training programs is discussed. The authors recommend upgrading the status of residents from that of student to that of full-fledged medical doctor with concomitant authority and responsibility.

Education, Medical, Graduate↗

High Prevalence of Potential Molecular Therapeutic Targets in Poorly Differentiated Thyroid Carcinoma.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid cancer with aggressive clinical course and peculiar clinical/pathological characteristics but lacking effective therapeutic options, when surgery is not curative. We aimed at the molecular characterization of PDTC with a specific focus on the identification of potential therapeutic targets. A series of PDTC cases was selected from a multi-institutional network. Fifty-nine samples underwent wide targeted DNA and RNA next-generation sequencing (NGS) testing and immunohistochemical analysis for mismatch repair (MMR) proteins. Gene fusion analysis was enriched by 25 additional samples. Prevalence of MMR protein loss was 11.9%. The most prevalent mutations were in NRAS (25%) and TP53 (25%), mutually exclusive. TERT promoter (TERTp) mutations were detected in 19.6% of cases (10/51). NRAS-mutated cases were enriched for mutations in genes belonging to the same pathway. TP53-mutated samples lacked TERTp co-mutations, but were associated with mutations in PTEN and in genes related to MMR system and/or loss of MMR proteins. TERTp mutations were the most prevalent alterations (28%, 7/25) in a third group that lacked NRAS or TP53 mutations. Four cases harbored gene fusions, including two cases harboring the TBL1XR1::PIK3CA fusion that has never been reported in thyroid cancer, so far. In conclusion, PDTC may be genomically segregated in subgroups with specific molecular characteristics. Overall, targetable gene fusions have a prevalence of 9% (4/42). Moreover, 47% of cases are potential candidates for individualized target therapies since they harbor mutations in genes coding for potentially targetable molecules and/or have defects in the MMR system.

Humans↗

National Pediatric Trauma Registry.

The National Pediatric Trauma Registry (NPTR) is a multi-institutional database designed to compile information concerning all aspects of pediatric trauma care. The registry is designed and operated in a manner that maximizes data accuracy and provides this information to all participating investigators. The growth of the database has allowed the NPTR to provide the first accurate epidemiologic description of pediatric trauma as a national disease, as well as to develop national norms for pediatric trauma care. The registry presently contains 10,177 patients, and is undergoing revisions (phase II) to allow a more focused evaluation of various aspects of the clinical care and rehabilitation of the pediatric trauma patient.

Child↗

[Immunity of gut-associated lymphoid tissue and the role of the oral immunotherapy in multi-disciplinary treatment of the digestive organ cancer].

In order to augment antitumor immunity of gut-associated lymphoid tissue in digestive organ cancer, oral administration of various biological response modifiers were studied using mice transplanted with cecal tumor. Among them OK-432 was the most effective and clinical application of oral OK-432 was studied. Autoradiogram and immunofluorescence studies showed the absorption of orally administered OK-432 from the gut. In phase I study oral OK-432 was much less toxic than other administration routes. Phase II study showed that oral OK-432 at various doses augmented antitumor immunity of the lymphocytes of peripheral blood and regional lymph node. In a multi-institutional study on postoperative adjuvant immunotherapy, 1011 gastric cancer patients were accumulated and randomized to compare the effects of oral and intradermal OK-432. In patients who underwent curative operation, 1-, 2- and 3-year survival rates (%) were 95, 88 and 82 for oral OK-432 group (n = 255), 88, 83 and 80 for the placebo group (n = 260), and 89, 79 and 73 for intradermal OK-432 group (n = 261). There was significant differences among cumulative survivals of three groups, and this life-prolonging effect of oral OK-432 was remarkable for stage II or III patients. These results demonstrate that oral immunotherapy with OK-432 is useful as an immunotherapy of digestive organ cancers.

Administration, Oral↗

Pulmonary hypertension in connective tissue disease. Clinical analysis of sixty patients in multi-institutional study.

Clinical features and prognosis of sixty patients with connective tissue disease accompanied by pulmonary hypertension (PH) (26 MCTD, 20 SLE, and 14 PSS) reported retrospectively by multi-institutions were compared. Though the obtained data were incomplete and lacking in uniformity, no significant difference in the clinical features among the three diseases were observed except high incidence of pulmonary fibrosis and low % VC in PSS and PH patients. Statistically significant difference, however, was observed between live and dead patients of three diseases gathered in post sternal pain, pulmonary diastolic murmur, right ventricular hypertrophy on ECG and mean pressure of pulmonary artery. Higher incidence of anti-nRNP antibody was observed in SLE with PH and PSS with PH patients than with the general population. A quicker occurrence of PH and shorter survival time were observed in MCTD patients with PH than in SLE and PSS patients with PH.

Adult↗

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.

BACKGROUND: In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question. METHODS: Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS: For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS: As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

Administration, Cutaneous↗

Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.

Humans↗