Gianluca Ansaldo

CD8+CD28− T Regulatory Lymphocytes Inhibiting T Cell Proliferative and Cytotoxic Functions Infiltrate Human Cancers

Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+CD28− T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+CD28− T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+CD25+ T regulatory lymphocytes associate with CD8+CD28− T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer.

A model to prioritize access to elective surgery on the basis of clinical urgency and waiting time

BackgroundPrioritization of waiting lists for elective surgery represents a major issue in public systems in view of the fact that patients often suffer from consequences of long waiting times. In addition, administrative and standardized data on waiting lists are generally lacking in Italy, where no detailed national reports are available. This is true although since 2002 the National Government has defined implicit Urgency-Related Groups (URGs) associated with Maximum Time Before Treatment (MTBT), similar to the Australian classification. The aim of this paper is to propose a model to manage waiting lists and prioritize admissions to elective surgery.MethodsIn 2001, the Italian Ministry of Health funded the Surgical Waiting List Info System (SWALIS) project, with the aim of experimenting solutions for managing elective surgery waiting lists. The project was split into two phases. In the first project phase, ten surgical units in the largest hospital of the Liguria Region were involved in the design of a pre-admission process model. The model was embedded in a Web based software, adopting Italian URGs with minor modifications. The SWALIS pre-admission process was based on the following steps: 1) urgency assessment into URGs; 2) correspondent assignment of a pre-set MTBT; 3) real time prioritization of every referral on the list, according to urgency and waiting time. In the second project phase a prospective descriptive study was performed, when a single general surgery unit was selected as the deployment and test bed, managing all registrations from March 2004 to March 2007 (1809 ordinary and 597 day cases). From August 2005, once the SWALIS model had been modified, waiting lists were monitored and analyzed, measuring the impact of the model by a set of performance indexes (average waiting time, length of the waiting list) and Appropriate Performance Index (API).ResultsThe SWALIS pre-admission model was used for all registrations in the test period, fully covering the case mix of the patients referred to surgery. The software produced real time data and advanced parameters, providing patients and users useful tools to manage waiting lists and to schedule hospital admissions with ease and efficiency. The model protected patients from horizontal and vertical inequities, while positive changes in API were observed in the latest period, meaning that more patients were treated within their MTBT.ConclusionThe SWALIS model achieves the purpose of providing useful data to monitor waiting lists appropriately. It allows homogeneous and standardized prioritization, enhancing transparency, efficiency and equity. Due to its applicability, it might represent a pragmatic approach towards surgical waiting lists, useful in both clinical practice and strategic resource management.

Non‐Antigen‐Specific CD8+ T Suppressor Lymphocytes in Diseases Characterized by Chronic Immune Responses and Inflammation

Abstract: Recent studies on regulatory lymphocytes demonstrate that CD8+ T suppressor (Ts) cells may have great relevance in controlling immune system homeostasis and avoiding development of chronic inflammatory diseases. Among the three subpopulations of CD8+ Ts cells so far recognized in humans, the type 2 (non‐antigen‐specific) cell is characterized by the capacity to inhibit both T cell proliferation and cytotoxic T lymphocyte activity through secretion of soluble factors. Previous work has shown the impairment of in vitro generation of type 2 CD8+ Ts cells from the peripheral blood of relapsed patients with multiple sclerosis, systemic lupus erythematosus, or systemic sclerosis. Here, similar findings are demonstrated for patients with human immunodeficiency virus or chronic hepatitis C virus infection. Furthermore, the presence of type 2 CD8+ Ts cells infiltrating diseased tissues in patients with autoimmune thyroiditis or cancer is shown. Collectively, these findings suggest that type 2 CD8+ Ts cells may be involved in the control of pathologic chronic immune responses, contributing in some cases to the pathogenesis of the disease.

Metastases to the thyroid gland from renal cancer

AIMS AND BACKGROUND Metastases to the thyroid gland from renal cancer pose a challenge to physicians, due in part to the rarity of the phenomenon, the prolonged time interval between removal of the primary renal cancer and the appearance of metastases, the difficulty in diagnosis, and the uncertainty regarding long-term prognosis. We report our experience with diagnosis and management of patients affected by thyroid metastases from renal clear cell carcinoma. STUDY DESIGN We report herein three clinical cases of thyroid metastases from renal clear cell carcinoma. We also present a review of the literature and examine common features of clinical presentation and management recommendations. RESULTS Over the past 17 years, 918 patients underewent surgery for thyroid cancer in our institution. Histological examination demonstrated a thyroid secondary malignancy from kidney cancer in 3 cases. Two patients underwent total thyroidectomy, whereas in the third patient a palliative right lobectomy with homolateral latero-cervical lymphoadenectomy was performed. At a 5-year follow-up, only one patient survived and was disease-free. CONCLUSIONS Thyroid metastases from renal clear cell carcinoma are a rare occurrence but should be taken into consideration in the differential diagnosis of a thyroid nodule. Preoperative diagnosis is often difficult. Nevertheless, an extensive diagnostic workup is recommended because the subsequent therapy must be tailored on the basis of the local extension of metastases. Surgical treatment of solitary thyroid metastases is recommended. However, patients with disseminated disease have a poor prognosis, and palliative care is the indicated recommendation. In these patients and in surgically untreatable patients, prolonged survival may be achieved by adjuvant medical therapy.

Efficiency and priority in planning surgical sessions by using the SWALIS model

Operating room (OR) sessions planning is often critical, due to potential clinical consequences of errors, while access to surgery often follows non transparent prioritization. In previous projects we designed the Surgical Waiting List InfoSystem (SWALIS) model to prioritize elective waiting lists. In the present study we present further modeling work, aiming at building instruments to plan OR session. Two new indexes were identified to measure the efficiency of planning both admissions and OR sessions, on the basis of the SWALIS prioritization. The SWALIS original data underwent simulation on a cohort of 1612 patients, including retrospective and cross sectional calculation and trend analysis. The availability of objective information allowed measuring the demand and the provided service. Furthermore, the new intelligible data on the efficiency and appropriateness of the pre-admission management allowed designing tools to plan OR sessions according to the actual and forecasted demand.