Sentinel node in melanoma patients: triple negativity with routine techniques and PCR as positive prognostic factor for survival.
ABSTRACT Lymph node mapping and sentinel lymph node biopsy are currently used to stage patients with cutaneous malignant melanoma. Immunohistochemical stains contribute to the detection of micrometastases; however, molecular biology techniques are associated with better diagnostic sensitivity. Sixty sentinel lymph nodes were included in this study. The primary lesions were malignant melanoma stage I or II, with a follow-up of longer than 2 years. Sentinel lymph nodes were studied with hematoxylin-eosin, immunohistochemistry for S-100 and HMB-45, and molecular biology techniques (reverse transcription (RT)-PCR) for the detection of tyrosinase messenger RNA. In 15 of 60 cases (25%), tyrosinase was detected by RT-PCR; three of these cases were also positive by immunohistochemistry. The population was divided into three groups: (i) hematoxylin-eosin-/immunohistochemistry+/molecular biology techniques+ (3 cases); (ii) hematoxylin-eosin-/immunohistochemistry-/molecular biology techniques+ (12 cases); (iii) hematoxylin-eosin-/immunohistochemistry-/molecular biology techniques- (45 cases). Correlation of the groups with overall survival showed the following: (i) 2 of 3 patients died (67%); (ii) 5 of 12 died (42%), and (iii) all 45 patients are alive, with no lymphadenectomy and a median follow-up of 84 months. The inclusion of molecular biology techniques appears to be of great value for the detection of sentinel lymph node micrometastases in patients with cutaneous malignant melanoma. In our series, those patients who showed negativity with all the three methods had a null recurrence rate. Therefore, this triple negativity could be a positive prognostic factor for overall survival. Our findings suggest the possibility of molecular oncological staging, which would allow the selection of patients with submicroscopic metastases for a complete treatment.
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ABSTRACT: Despite their relevance in clinical medicine, the extension and activity of the bone marrow (BM) cannot be directly evaluated in vivo. We propose a new method to estimate these variables by combining structural and functional maps provided by CT and PET. BM extension and glucose uptake were estimated in 102 patients undergoing whole-body PET/CT because of a history of nonmetastatic melanoma. Image analysis assumed that the BM is surrounded by compact bone. An iterative optimization scheme was applied to each CT slice to identify the external border of the bone. To identify compact bone, the algorithm measured the average Hounsfield coefficient within a two-pixel ring located just inside the bone contour. All intraosseous pixels with an attenuation coefficient lower than this cut-off were flagged as 1, while the remaining pixels were set at 0. Binary masks created from all CT slices were thus applied to the PET data to determine the metabolic activity of the intraosseous volume (IBV). Estimated whole-body IBV was 1,632 ± 587 cm(3) and was higher in men than in women (2,004 ± 498 cm(3) vs. 1,203 ± 354 cm(3), P < 0.001). Overall, it was strictly correlated with ideal body weight (r = 0.81, P = 0.001) but only loosely with measured body weight (r = 0.43, P = 0.01). The average FDG standardized uptake value (SUV) in the thoracic and lumbar vertebrae was 2.01 ± 0.36, Accordingly, intraosseous voxels with SUV ≥ 1.11 (mean spine SUV - 2.5 × SD) were considered as active "red" BM and those with SUV <1.11 as "yellow" BM. Estimated red BM volume was 541 ± 195 ml, with a higher prevalence in the axial than in the appendicular skeleton (87 ± 8 % vs. 10 ± 8 %, P < 0.001). Again, red BM volume was higher in men than in women (7.8 ± 2.2 vs. 6.7 ± 2.1 ml/kg body weight, P < 0.05), but in women it occupied a greater fraction of the IBV (32 ± 7 % vs. 36 ± 10 %, P < 0.05). Patient age modestly predicted red BM SUV, while it was robustly and inversely correlated with red BM volume. Our computational analysis of PET/CT images provides a first estimation of the extension and metabolism of the BM in a population of adult patients without haematooncological disorders. This information might represent a new window to explore pathophysiology the BM and the response of BM diseases to chemotherapy.European Journal of Nuclear Medicine 05/2012; 39(8):1326-38. · 4.53 Impact Factor
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ABSTRACT: BACKGROUND: To determine the anatomic extent of pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients at the time of radical prostatectomy (RP), knowledge about the topography of lymph node (LN) metastases is required. OBJECTIVE: Because small-volume LN metastases may be missed by standard histopathologic examination, we performed an anatomic mapping study combining molecular and histopathologic LN examination in PCa patients treated with RP and extended PLND (ePLND). DESIGN, SETTING, AND PARTICIPANTS: A total of 52 patients with intermediate- (n=15) and high-risk (n=37) PCa underwent RP and ePLND without neoadjuvant treatment. ePLND included dissection of the obturator fossa and the external, internal, and common iliac vessels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: LNs ≥3mm in diameter were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for prostate-specific antigen (PSA) expression and by standard histopathology. Topography of positive LNs was determined descriptively. RESULTS AND LIMITATIONS: Of 1469 dissected LNs (median: 27 LNs per patient), 1186 LNs were ≥3mm. Molecular LN analysis was positive in 127 LNs of 27 patients (52%) including 32 LNs of 12 patients (23%) with histopathologic positive LNs. Molecular examination was negative in 3 of 35 histopathologic positive LNs (9%). Combining both molecular and histopathologic findings, positive LNs were located in the standard PLND field defined by obturator fossa and external iliac vessels in 71%, along the internal iliac vessels in 16%, and along the common iliac vessels in 13%. Of LN-positive patients, 63% had LN metastases outside the standard PLND field. The internal iliac field was involved in 48% and the common iliac field in 37% of node-positive patients. Notably, internal and common iliac vessels were the only positive regions in 7% and 11% of node-positive patients, respectively. A limitation is the small number of patients included. CONCLUSIONS: These findings underline the enhanced sensitivity of qRT-PCR in comparison with standard histopathology for detection of small-volume LN metastases in PCa patients. Our results support an ePLND including the common iliac vessels, at least up to the ureteral crossing, to optimise nodal staging and to remove LNs potentially harbouring metastases.European Urology 02/2013; · 10.48 Impact Factor
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ABSTRACT: A positive lymph node status is a major prognostic factor for tumor recurrence and mortality following radical prostatectomy in prostate cancer patients or radical cystectomy in bladder cancer patients. However, despite having histopathologic negative lymph nodes, a substantial proportion of patient suffers from tumor recurrence within a few years after the operation. Tumor recurrence in node-negative patients may result from hematogeneous or lymphatic metastatic spread which remains undetected by standard clinical or histopathologic examinations. Molecular lymph node analysis is a potential method for detection of lymph node metastases with higher sensitivity and for prognostic risk stratification of patients with histopathologic negative lymph nodes.Der Urologe 03/2014; · 0.46 Impact Factor