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

Will early detection of non-axillary sentinel nodes affect treatment decisions?

Axillary lymph node involvement is the best prognostic factor for breast cancer survival. Staging breast cancers by axillary dissection remains standard management and is part of the UK national guidelines for breast cancer treatment. In the presence of involved axillary lymph nodes best treatment has been shown to be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose nodes are uninvolved avoidance of morbidity is optimal and this will be achieved by minimal dissection of the axilla. Thus, for node-negative women the introduction of the sentinel node biopsy technique may revolutionise the approach to the axilla. These will be women with mammographic screen detected small well and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact of sentinel node biopsy in women who have symptomatic large tumours is unproven, and around half of these women will require a second procedure to clear their axilla or radiotherapy as treatment. Even for those women found to have involved sentinel lymph nodes the ability to use early systemic chemotherapy followed by axillary clearance or radiotherapy may provide long-term survival gains. Sentinel node biopsy should not, however, become routine practice until randomised controlled trials have proven its benefit and safety in reducing morbidity. Several randomised controlled trials (including ALMANAC) are currently underway

Limitations of Tc99m-MIBI-SPECT Imaging Scans in Persistent Primary Hyperparathyroidism

In primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83-100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands. We retrospectively evaluated the localizing accuracy of Tc99m-MIBI-SPECT scans in 19 consecutive patients with persistent PHPT who had a scan before reoperative parathyroidectomy. We used as controls 23 patients with sporadic PHPT who had a scan before initial surgery. In patients with persistent PHPT, Tc99m-MIBI-SPECT accurately localized a pathological parathyroid gland in 33% of cases before reoperative parathyroidectomy, compared to 61% before first PTx for sporadic PHPT. The Tc99m-MIBI-SPECT scan accurately localized intra-thyroidal glands in 2 of 7 cases and a mediastinal gland in 1 of 3 cases either before initial or reoperative parathyroidectomy. Our data suggest that the accuracy of Tc99m-MIBI-SPECT in localizing residual hyperactive glands is significantly lower before reoperative parathyroidectomy for persistent PHPT than before initial surgery for sporadic PHPT. These findings should be taken in consideration in the preoperative workup of patients with persistent primary hyperparathyroidis

Genetic Diversity and Population History of a Critically Endangered Primate, the Northern Muriqui (Brachyteles hypoxanthus)

Social, ecological, and historical processes affect the genetic structure of primate populations, and therefore have key implications for the conservation of endangered species. The northern muriqui (Brachyteles hypoxanthus) is a critically endangered New World monkey and a flagship species for the conservation of the Atlantic Forest hotspot. Yet, like other neotropical primates, little is known about its population history and the genetic structure of remnant populations. We analyzed the mitochondrial DNA control region of 152 northern muriquis, or 17.6% of the 864 northern muriquis from 8 of the 12 known extant populations and found no evidence of phylogeographic partitions or past population shrinkage/expansion. Bayesian and classic analyses show that this finding may be attributed to the joint contribution of female-biased dispersal, demographic stability, and a relatively large historic population size. Past population stability is consistent with a central Atlantic Forest Pleistocene refuge. In addition, the best scenario supported by an Approximate Bayesian Computation analysis, significant fixation indices (ΦST = 0.49, ΦCT = 0.24), and population-specific haplotypes, coupled with the extirpation of intermediate populations, are indicative of a recent geographic structuring of genetic diversity during the Holocene. Genetic diversity is higher in populations living in larger areas (>2,000 hectares), but it is remarkably low in the species overall (θ = 0.018). Three populations occurring in protected reserves and one fragmented population inhabiting private lands harbor 22 out of 23 haplotypes, most of which are population-exclusive, and therefore represent patchy repositories of the species' genetic diversity. We suggest that these populations be treated as discrete units for conservation management purposes

Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma

Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR55.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR52.92, 95% CI 1.33-6.44, P=50.008) and multifocality (OR51.96, 95% CI 1.06-3.62, P=50.031). In disease-free survival analysis, low VHL expression had marginal significance (P=50.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated

Abstract P2-18-12: Surgical management of breast cancer: Breast conserving surgery or mastectomy in the 2010 SEER registries by hormone receptor and HER2 status

Abstract Background Breast conserving therapy and mastectomy have been shown to have similar overall survival outcomes in large trials. After many years of decline, mastectomy rates are on the rise for a variety of reasons. In this context, there is increasing discussion that the risk of loco-regional recurrence is complex and varies by breast cancer subtype. Several, pre-trastuzumab-era, reports have shown that loco-regional recurrence is higher for HER2+ and triple negative breast cancer (TNBC) patients who undergo breast conserving therapy (BCS) compared with women with hormone receptor positive (HR+) disease. Other literature has suggested that some breast cancer subtypes have better outcomes with BCS. To provide the most recent data on surgical choice by breast cancer subtype, we report BCS and mastectomy rates from 2010 SEER data. Surgical choice is presented for ductal carcinoma in situ (DCIS) and invasive breast cancer. For women with invasive disease the subcategories of HR+, HER2+ and TNBC are reported. Methods SEER data were used to identify incident breast cancer patients diagnosed in 2010. Only pathologically confirmed cases were included. In addition, individuals were excluded if they were diagnosed at autopsy or by death certificate, did not receive surgery or if the type of surgery was unknown. Patients were categorized as having received BCS or mastectomy and, for invasive disease, by receptor subtype (HR+, HER2+ and TNBC). For invasive cancers, patients with unknown receptor subtypes were excluded. Results SEER data for 2010 included 65,598 women, 13,849 (21.1%) women had DCIS and 51,749 (78.9%) had invasive disease (Table 1). For invasive cancers after excluding 5,062 patients with unknown receptor status, 12.1% were TNBC, 14.4% were HER2+, and 83.5% were HR+. Overall, 43.5% of women underwent mastectomy (33.2% for DCIS). Mastectomy rate increased by stage at diagnosis: 33.5% for Stage I, 53.9% for Stage II disease and 77.8% for Stage III (OR = 0.49, p&amp;lt;0.001 for Stage 1 compared to other stages). By age, mastectomy rates were 69.0% for &amp;lt;30, 53.4% for 30-49, 43.3% for 50-59, 39.0% for 60-69, 39.4% for 70-79 and 41.1% for 80+ (OR = 2.90, p&amp;lt;0.001 for women under 30 compared to older women). Conclusions In this large, recent series, 43.5% of women underwent mastectomy. This rate is among the highest reported from population-based registries and suggests a continued trend of increasing mastectomy rates. Women with HER2+ and TNBC were younger and significantly more likely to have mastectomy than their HR+ counterparts. Women with HER2+ breast cancer, in this trastuzumab-era cohort, were the subtype most likely to choose to undergo mastectomy. Monitoring for relapse events could contribute to a better understanding of how loco-regional recurrence risk might vary by subtype and surgical choice. Table 1: Percent receiving BCS and mastectomy by subtype for invasive cancersReceptor StatusNMean AgeBCS (%)Mastectomy (%)Odds Ratio*p valueFull cohort51,74961.354.145.9  HR+38,98161.855.744.30.68&amp;lt;0.001HER2+6,73858.143.056.01.61&amp;lt;0.001TNBC5,65858.849.150.91.26&amp;lt;0.001* Odds Ratio of undergoing mastectomy versus lumpectomy for this subtype compared to those not of this subtype. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-12.</jats:p