MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas.

Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6fl/fl;MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6fl/fl;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes (P=5 × 10-11). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a. These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies.

Assessment of short-term survival after liver transplant by the Model for End-Stage Liver Disease.

UNLABELLED: The Model for End-Stage Liver Disease (MELD) score has demonstrated the ability to predict mortality among patients with chronic liver disease on the liver waiting list. The aim of this study was to assess the capability of the MELD score to correctly predict posttransplantation survival in Spain and to determine specific thresholds of MELD above which liver transplantation should be discouraged and the patient removed from the waiting list. METHODS: In this study, we retrospectively applied the MELD score to 168 patients at time of transplantation to estimate 1-month and 3-month posttransplant survivals by stratifying them into four groups: group A, MELD score < 10; group B, MELD score 10-18; group C, MELD score 19-24; group D, MELD score > 24. RESULTS: One-, 2-, and 3-month survivals were 84.3%, 80% and 79.5%, respectively. One-, 2-, and 3-month survivals in group A (18 patients) were identical (77.8%). In group B (80 patients), 1-month survival was 84.8%, and 2- and 3-month survivals were 78.4%. In group C (42 patients) 1-month survival was 90.5% and 2- and 3-month survivals were 88%. One-, 2-, and 3-month survivals in group D (28 patients) were 77.9%, 74%, and 70%, respectively. We defined a new group (group E) formed by patients with MELD score < or =24. When we compared 1-, 2-, and 3-month survival rates in group E (85.6%, 81.25%, and 81.25%, respectively) with survival rates in group D, the difference was not significant (P > .05). CONCLUSIONS: Although overall outcomes of patients whose MELD scores were high at the time of liver transplantation were inferior to those of patients whose MELD scores were lower, there was no significant difference for specific thresholds of MELD above which liver transplantation should be discouraged and the patient removed from the waiting list.

Community health centers and quality of care: a goal to provide effective health care to the community.

The uniqueness of community health centers provides for a sound environment for total quality management (TQM). Structure, process, and outcome are valued equally under TQM. With strong management leadership and a framework for quality of care, community health care specialists (e.g., advanced practice nurses) can easily incorporate the TQM measurement criteria in their daily practice routines. By applying the principles of TQM, the community health center will advance toward its goal of enhancing the effectiveness of health care delivery to a community and its members in partnership with the community.

A heuristic approach to edge detection in on-line portal imaging.

PURPOSE: Portal field edge detection is an essential component of several postprocessing techniques used in on-line portal imaging, including field shape verification, selective contrast enhancement, and treatment setup error detection. Currently edge detection of successive fractions in a multifraction portal image series involves the repetitive application of the same algorithm. As the number of changes in the field is small compared to the total number of fractions, standard edge detection algorithms essentially recalculate the same field shape numerous times. A heuristic approach to portal edge detection has been developed that takes advantage of the relatively few changes in the portal field shape throughout a fractionation series. METHODS AND MATERIALS: The routine applies a standard edge detection routine to calculate an initial field edge and saves the edge information. Subsequent fractions are processed by applying an edge detection operator over a small region about each point of the previously defined contour, to determine any shifts in the field shape in the new image. Failure of this edge check indicates that a significant change in the field edge has occurred, and the original edge detection routine is applied to the image. Otherwise the modified edge contour is used to define the new edge. RESULTS: Two hundred and eighty-one portal images collected from an electronic portal imaging device were processed by the edge detection routine. The algorithm accurately calculated each portal field edge, as well as reducing processing time in subsequent fractions of an individual portal field by a factor of up to 14. CONCLUSIONS: The heuristic edge detection routine is an accurate and fast method for calculating portal field edges and determining field edge setup errors.

Picture archiving and communications systems in radiation oncology (PACSRO): tools for a physician-based digital image review system.

Digital imaging is becoming more and more important in the diagnosis, staging, and treatment of patients in radiation oncology. In order to facilitate the most efficient interface of this technology to physicians and other users of this information, a medical image display system (MID) has been developed at the Fox Chase Cancer Center (FCCC). The system runs on 20 personal computers situated in physicians offices as well as a modified system located in the radiation oncology conference room. Access to CT, MRI, and EPID information is achieved through an Ethernet connection to the hospital picture archiving and communications system (PACS). Over a 1-year period a total of 503 patients and 3845 images have been stored on the system. Physician approval using the MID system (without conventional films) was performed on 106 patients. Of these, 22%, 16%, 11%, 10%, and 9% consisted of breast, prostate, pelvic, lung, and head and neck patients, respectively. Digital images sent from a variety of image sources to the MID system take up to 15 s to process and format while image access and display can take 2-5 s, dependent upon image size and speed of the host computer.

Swallowing function in patients with esophageal cancer treated with concurrent radiation and chemotherapy.

BACKGROUND: Major goals of concurrent radiation and chemotherapy in the treatment of esophageal cancer are the early restoration and long-term maintenance of swallowing function. The purpose of this study was to determine the impact of concurrent radiation and chemotherapy on swallowing function. METHODS: Between September 1980 and September 1990, 120 patients with esophageal cancer were treated at the Fox Chase Cancer Center on the basis of one of three prospective nonrandomized protocols using concurrent chemotherapy and radiation. Swallowing function was retrospectively assessed in these patients by use of a swallowing-function scoring system. In addition, patients who had long-term control of their esophageal cancer underwent a more detailed analysis of swallowing function. RESULTS: Initial improvement in dysphagia occurred in 88% of the 102 assessable patients, with a median time to improvement of 2 weeks. There was no difference in overall percentage of initial improvement for patients with adenocarcinoma versus squamous cell carcinoma. Patients with distal tumors, however, showed both earlier and higher frequency of initial improvement than did patients with tumors in the upper two-thirds of the thoracic esophagus (95% versus 79%). Local relapse-free survival of definitively treated patients at 3 years was 60% and was significantly better for patients with Stage I (76%) versus Stage II cancers (55%) (P < 0.05). All 25 patients treated with curative intent who survived for more than 1 year without evidence of disease were able to eat soft or solid foods and had a benign stricture rate of only 12%. Even in patients with advanced disease who were treated with palliative intent, 91% had an initial improvement in swallowing function and 67% had improvement in swallowing function that lasted until death. CONCLUSIONS: High-dose concurrent radiation and chemotherapy provides rapid improvement in dysphagia, and this improvement results in normal or near-normal swallowing function of long duration.

Digital imaging in the radiation oncology environment: a personal computer local area network solution.

Personal computer (PC) driven digital imaging devices are now becoming available in the market place for use in radiation oncology to produce what are known as real time portal images. These limited contrast images are used to verify the patient anatomy under treatment by megavoltage x-rays and are a vital part of the patient treatment. The current generation of devices can produce both single and movie loop images in real time for physician review and approval. To disseminate these images and other digital images used in the planning and delivery of radiation therapy, a PC-based picture archiving and communications system has been developed that is tailored to the special needs of radiation oncology.

[Obliteration of the juxtarenal abdominal aorta. 90% stenosis of the left renal artery. Thrombosis of the right renal artery and renal atrophy. Treatment with aortic deobliteration, aorto-bifemoral prosthesis, left aorto-renal bypass and right nephrectomy. A case report]. / Obliteración de aorta abdominal yuxtarrenal. Estenosis 90% de arteria renal izquierda. Trombosis arteria renal derecha y atrofia renal. Tratado con desobliteración aórtica, prótesis aorto-bifemoral, by-pass aorto-renal izquierdo y nefrectomía derecha. Presentación de un caso.

A case report of a juxtarenal abdominal aortic obliteration, associated to a annulated right kidney, a 90% left renal arterial stenosis, hypertension and chronic renal failure is presented. An aortic desobliteration was performed, with a termino-terminal aortobifemoral prosthesis, a left aortorenal by pass and a right nephrectomy. The result was successfully and allowed a satisfactory evolution of its renal failure and hypertension.

Human T helper cells specific for antigens of typhus group rickettsiae enhance natural killer cell activity in vitro.

The peripheral blood mononuclear cells (PBMC) from 5 individuals immune to typhus group rickettsiae and from 13 nonimmune individuals were stimulated in vitro for 7 days with typhus group rickettsial antigen (TGRA). At the end of day 7, lysis of the natural killer (NK)-susceptible target K562 by these PBMC was determined. As controls, PBMC from both groups of donors were cultured in vitro for 7 days without antigen or were freshly isolated, and lysis of the K562 target was determined. There was no significant difference between the level of NK activity in freshly isolated PBMC from immune and nonimmune donors. PBMC from immune donors which were stimulated with antigen for 7 days exhibited significantly greater NK activity than did the control population, which was cultured for 7 days without antigen. PBMC from immune donors which were stimulated with TGRA demonstrated significantly higher NK activity than the same PBMC stimulated with antigen derived from an antigenically unrelated rickettsia, Coxiella burnetii. There was no significant difference, however, in the level of NK activity of nonimmune antigen-stimulated PBMC compared with that of the same PBMC population cultured without antigen. Most of the antigen-stimulated NK activity was mediated by Leu-11-positive cells as determined by electronic cell sorting. The ability of TGRA to sustain the NK activity of PBMC from immune donors was abolished when the T4/Leu-3-positive population of lymphocytes was eliminated by positive or negative selection prior to antigen stimulation. The ability of TGRA to sustain the NK activity of PBMC from immune donors was also significantly decreased in the presence of antibodies against human interleukin-2. The results suggest that the activity of human NK cells can be sustained in vitro by antigen-specific T helper cells and that the effect of the T helper cell is mediated, at least in part, by interleukin-2.