Development of sentinel node localization and ROLL in breast cancer in Europe

The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the â\u80\u9cprimary glandâ\u80\u9d. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Mortonâ\u80\u99s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects

Contraindications of sentinel lymph node biopsy: Áre there any really?

BACKGROUND: One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient. METHODS: In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery. RESULTS: Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure. CONCLUSION: When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer

The immunobiology of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease