Survivin in adrenocortical tumors - pathophysiological implications and therapeutic potential.

Treatment options for adrenocortical carcinoma (ACC) are very limited. In other solid tumors, small vaccination trials targeting the anti-apoptotic molecule survivin suggested immunological and clinical benefit in selected patients. Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC. Survivin mRNA and protein expression was assessed in adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands]. Expression was correlated with clinical outcome using Kaplan-Meier and Cox regression analyses. The anti-apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA. The presence of spontaneous survivin specific T-cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls. Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein expression in 97% of the ACCs. In 83% of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [hazard ratio for death 2.28 (95% CI 0.99-5.28); p=0.053]. Survivin knockdown in SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion, our data suggest that survivin could play an important role in the anti-apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease.

OCIS: 15 years' experience with patient-centered computing.

In the mid-1970s, the medical and administrative staff of the Oncology Center at Johns Hopkins Hospital recognized a need for a computer-based clinical decision-support system that organized patients' information according to the care continuum, rather than as a series of event-specific data. This is especially important in cancer patients, because of the long periods in which they receive complex medical treatment and the enormous amounts of data generated by extremely ill patients with multiple interrelated diseases. During development of the Oncology Clinical Information System (OCIS), it became apparent that administrative services, research systems, ancillary functions (such as drug and blood product ordering), and financial processes should be integrated with the basic patient-oriented database. With the structured approach used in applications development, new modules were added as the need for additional functions arose. The system has since been moved to a modern network environment with the capacity for client-server processing.

Integrated ambulatory care resource scheduling in oncology.

In a modern managed-care environment, the scheduling of ambulatory care activities must be viewed as a series of closely related activities rather than a group of unique and independent events. These activities must be sequenced in a logical manner, and linked with a variety of information on other clinical, operational, and administrative activities. This article focuses on such an integrated scheduling system which supports the ambulatory care services at the Johns Hopkins Oncology Center.

Chemotherapy and treatment scheduling: the Johns Hopkins Oncology Center Outpatient Department.

The Chemotherapy and Treatment Scheduling System provides integrated appointment and facility scheduling for very complex procedures. It is fully integrated with other scheduling systems at The Johns Hopkins Oncology Center and is supported by the Oncology Clinical Information System (OCIS). It provides a combined visual and textual environment for the scheduling of events that have multiple dimensions and dependencies on other scheduled events. It is also fully integrated with other clinical decision support and ancillary systems within OCIS. The system has resulted in better patient flow through the ambulatory care areas of the Center. Implementing the system required changes in behavior among physicians, staff, and patients. This system provides a working example of building a sophisticated rule-based scheduling system using a relatively simple paradigm. It also is an example of what can be achieved when there is total integration between the operational and clinical components of patient care automation.

Integrated ambulatory care services in oncology.

In today's medical care environment of cost containment and restricted reimbursement, it is important to maximize the use of expensive facility and personnel resources. Concurrently, it is important to provide superior and timely patient services in order to remain competitive in an extremely flexible market. There are many areas in today's larger hospital environments where such ideals can be easily achieved. One of the more obvious areas is the automation of appointment and resource scheduling for ambulatory care services. This article focuses on maximizing the use of available physical and personnel resources in the ambulatory care setting of large and specialty hospitals. The Johns Hopkins Oncology Center's integrated outpatient scheduling and resource management systems are used as examples of what can be achieved. It is hoped that the experiences of the Oncology Center in developing these integrated systems will help others in similar efforts.

The Oncology Clinical Information System.

This presentation provides an overview of the functions of the Oncology Clinical Information System (OCIS) focusing on three new applications. The first part of the presentation will describe the structure of OCIS and show the basic clinical decision-support aspects of the system on-line. The second part of the presentation will provide on-line demonstrations of three new applications: a sophisticated blood products ordering systems, a chemotherapy and treatment scheduling system, and a radiation therapy scheduling system.