Presence Of Clinical Metastasis Research Articles

Canadian Urological Association Best Practice Report: Long-term surveillance following resection of pheochromocytoma.

Background Pheochromocytoma is a tumor of the catecholamine-producing cells of the adrenal medulla. The incidence is estimated to be 1–2 cases per 100 000 individuals and they make up approximately 5% of incidental adrenal masses.1 Classical symptoms of pheochromocytomas include headache, episodic perspiration, tachycardia, flushing, nausea, and hypertension, although many tumors can be asymptomatic.1 These tumors can be sporadic or hereditary. 2 Familial cases account for up to 30% of tumors.3 Pheochromocytomas can also occur outside the adrenal gland, known as paragangliomas, in up to 25% of cases.4 About 10% of pheochromocytomas are malignant.5 Although there are several clinical and genetic factors associated with an increased risk of malignancy, at this time, there are no molecular, cellular, or histological criteria that can reliably differentiate benign from malignant disease.5 Therefore, malignancy is defined by the presence of clinical metastases. The most common sites for metastases are lymph nodes, bones, liver, and lungs.6 Evaluation of suspected pheochromocytoma begins with confirming a biochemical disturbance by measuring plasma-free metanephrines or urinary fractionated metanephrines, followed by computed tomography (CT) imaging. Once a pheochromocytoma is confirmed, complete surgical resection of the tumor is advised, preferably via laparoscopic or robot-assisted adrenalectomy. The full details regarding workup and treatment of pheochromocytomas is beyond the scope of this review, but there are recent published guidelines on this topic.7 Following surgery, patients are at risk for tumor persistence and recurrence. Despite an overall good prognosis, the disease can recur in up to 16% of patients within 10 years following surgery.8,9 Recurrences may be local or metastatic and have been reported up to 53 years post-initial resection, making long-term followup essential.10 Extra-adrenal disease, hereditary pheochromocytomas, right-sided tumors, bilateral tumors, and larger tumors are thought to be risk factors for recurrence. Currently, there is no consensus on the proper methodology for followup. There have been no randomized studies addressing optimal followup nor prospective registries to provide higher-quality evidence for this issue. Important clinical questions remain regarding duration of followup and which tests should be used to detect and monitor recurrences.

Standards and Definitions in Neck Dissections of Differentiated Thyroid Cancer.

Papillary and follicular thyroid carcinomas arising from the follicular epithelial cells and forming differentiated thyroid cancer (DTC) consist of >95% of thyroid cancers. Lymph node metastasis to the neck is common in DTC, especially in papillary thyroid cancer. The removal of only the metastatic lymph nodes (berry picking) does not help to achieve a potential positive contribution to the survival and recurrence of lymph node dissection in the DTC. Thus, systematic dissection of the cervical lymph nodes is needed. Today, according to the widely accepted and commonly used definitions and lymph node staging, the deep lymph nodes of the lateral side of the neck are divided into five regions. Based on the fact that some groups have biologically independent regions, Groups I, II, and V are divided into the A and B subgroups. The central region lymph nodes contain VI and VII region lymph nodes, which consist of the prelaryngeal, pretracheal, and right and left paratracheal lymph node groups.Radical neck dissection (RND) is accepted as the standard basic procedure in defining neck dissections. In this method, in addition to all the regions of the Groups I–V lymph nodes at one side, the ipsilateral spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle are removed. Sparing of one or more of the routinely removed non-lymphatic structures in the RND is called modified RND (MRND), whereas the preservation of one or more of the routinely removed lymph node groups in the RND is termed as selective neck dissection (SND). In difference, the procedure with an addition of a lymph node and/or non-lymphatic structures to routinely removed neck structures in RND is called extended RND. Generally, involving one or more regions of SND are applied for DTC.The removal of the paratracheal, prelaryngeal, and pretracheal lymph node groups at one side is termed as ipsilateral central dissection, whereas the removal of the bilateral paratracheal lymph node groups, in other words, the excision of four lymph node groups in the central region (Groups VI and VII), is defined as bilateral central dissection. In conclusion, bilateral central neck dissection (CND) is the SND in which the regions of VI and VII are removed.In the DTC, CND is prophylactically and therapeutically applied, whereas lateral neck dissection is performed only therapeutically in the presence of clinical metastasis (N1b) in the lateral neck region. Debates on the extent of SNDs to be made in the central and lateral neck regions are still ongoing. Central dissection should be made at least unilaterally. In the lateral side of the neck, SNDs can be applied in different combinations in which at least one region from Groups I to V is removed. The main variables that determine the extent of SND in the central and lateral regions in DTC are the complication rates, the effect of the procedure, and its effect on prognosis and recurrence.

MP73-09 RENAL ANGIOMYOLIPOMAS IN CHILDREN AND ADOLESCENTS WITH TUBEROUS SCLEROSIS COMPLEX

were used to test the accuracy of all the available clinical characteristics in predicting LNI. A nomogram predicting the probability of LNI was constructed using the logistic regression-derived coefficients. Log transformation was applied for clinical tumor size after non-linearity analysis. Calibration plot and leave-one-out cross validation (LOOCV) were used for internal validation. RESULTS: Overall, 204 patients (4.1%) had LNI. In multivariable analyses, symptoms at diagnosis (OR: 1.64; p<0.006), clinical tumor size (OR: 1.11; p<0.001), non-organ confined (OR: 2.65; p<0.001), clinical LNI (OR: 15.6; p<0.001) and presence of clinical metastases (OR: 2.4; p<0.001) were each significantly associated with the risk of LNI. The curve depicting the relationship between predicted and observed LNI closely approximates the ideal predictions, which indicates excellent calibration. In LOOCV, the C-index of our model was 92.1%. Using a 5% nomogram cut-off, 4.346 of 4.948 patients (87.8%) would be spared lymph-node dissection (LND) and LNI would be missed in 39 patients (0.9%, 19.1% of all LNI). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 80.9%, 90.8%, and 99.1%, respectively. To minimize the number of LNI patients missed, a 1% nomogram cut-off may be considered, allowing to spare 57% of LND and missing only 7 LNI patients (0.1%, 3% of all LNI cases). CONCLUSIONS: We developed and internally validated a tool capable of highly accurately predicting LNI in RCC patients. This accurate tool could be useful for patient counseling and risk stratification at medical decision-making. Based on our model, patients with a LNI risk < 1% may be safely spared LND. Given the number of LNI cases missed when higher cutoffs were considered, further studies aimed at identifying accurate biomarkers of hidden LNI are urgently needed, especially in low-stage disease.

MP73-07 PREDICTION OF LYMPH NODE INVASION IN PATIENTS WITH RENAL CELL CARCINOMA: RESULTS FROM A LARGE INTERNATIONAL CONSORTIUM

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2016MP73-07 PREDICTION OF LYMPH NODE INVASION IN PATIENTS WITH RENAL CELL CARCINOMA: RESULTS FROM A LARGE INTERNATIONAL CONSORTIUM Paolo Dell'Oglio, Grant Stewart, Tobias Klatte, Alessandro Volpe, Bulent Akdogan, Marco Roscigno, Hans Langenhuijsen, Martin Marszalek, Oscar Rodriguez Faba, Maciej Salagierski, Andrea Minervini, Sabine Brookman-May, and Umberto Capitanio Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Grant StewartGrant Stewart More articles by this author , Tobias KlatteTobias Klatte More articles by this author , Alessandro VolpeAlessandro Volpe More articles by this author , Bulent AkdoganBulent Akdogan More articles by this author , Marco RoscignoMarco Roscigno More articles by this author , Hans LangenhuijsenHans Langenhuijsen More articles by this author , Martin MarszalekMartin Marszalek More articles by this author , Oscar Rodriguez FabaOscar Rodriguez Faba More articles by this author , Maciej SalagierskiMaciej Salagierski More articles by this author , Andrea MinerviniAndrea Minervini More articles by this author , Sabine Brookman-MaySabine Brookman-May More articles by this author , and Umberto CapitanioUmberto Capitanio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1662AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Few models predicting the presence of lymph node invasion (LNI) in patients with renal cell carcinoma (RCC) are available. In this study, we tested the ability of LNI risk estimation relying on clinically attainable variables. METHODS Between 1987 and 2014, 4,948 RCC patients treated with either partial or radical nephrectomy within a multi-institutional cohort were identified. Multivariable logistic regression analyses were used to test the accuracy of all the available clinical characteristics in predicting LNI. A nomogram predicting the probability of LNI was constructed using the logistic regression-derived coefficients. Log transformation was applied for clinical tumor size after non-linearity analysis. Calibration plot and leave-one-out cross validation (LOOCV) were used for internal validation. RESULTS Overall, 204 patients (4.1%) had LNI. In multivariable analyses, symptoms at diagnosis (OR: 1.64; p<0.006), clinical tumor size (OR: 1.11; p<0.001), non-organ confined (OR: 2.65; p<0.001), clinical LNI (OR: 15.6; p<0.001) and presence of clinical metastases (OR: 2.4; p<0.001) were each significantly associated with the risk of LNI. The curve depicting the relationship between predicted and observed LNI closely approximates the ideal predictions, which indicates excellent calibration. In LOOCV, the C-index of our model was 92.1%. Using a 5% nomogram cut-off, 4.346 of 4.948 patients (87.8%) would be spared lymph-node dissection (LND) and LNI would be missed in 39 patients (0.9%, 19.1% of all LNI). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 80.9%, 90.8%, and 99.1%, respectively. To minimize the number of LNI patients missed, a 1% nomogram cut-off may be considered, allowing to spare 57% of LND and missing only 7 LNI patients (0.1%, 3% of all LNI cases). CONCLUSIONS We developed and internally validated a tool capable of highly accurately predicting LNI in RCC patients. This accurate tool could be useful for patient counseling and risk stratification at medical decision-making. Based on our model, patients with a LNI risk < 1% may be safely spared LND. Given the number of LNI cases missed when higher cutoffs were considered, further studies aimed at identifying accurate biomarkers of hidden LNI are urgently needed, especially in low-stage disease. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e962-e963 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Paolo Dell'Oglio More articles by this author Grant Stewart More articles by this author Tobias Klatte More articles by this author Alessandro Volpe More articles by this author Bulent Akdogan More articles by this author Marco Roscigno More articles by this author Hans Langenhuijsen More articles by this author Martin Marszalek More articles by this author Oscar Rodriguez Faba More articles by this author Maciej Salagierski More articles by this author Andrea Minervini More articles by this author Sabine Brookman-May More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Immunohistochemistry Expression of P53, Ki67, CD30, and CD117 and Presence of Clinical Metastasis at Diagnosis of Testicular Seminoma

We evaluated the immunohistochemical expression of p53, Ki67, CD30, and CD117 and correlated it with histological features and presence of clinical metastasis at diagnosis of testicular seminomas. A retrospective study of 62 patients was performed in patients with pure seminoma. The retroperitoneum was staged with computed tomography scan and the thorax with simple x-rays and/or computed tomography scan. Pathologists were unaware of the clinical stage of the patients. Manual microarrays were created from a tissue representative of tumor. The expression of p53, Ki67, CD30, and CD117 was evaluated as negative, any degree of expression, and expression in more than 50% of neoplastic cells. Univariate and multivariate analysis were performed. Sixty-two cases were analyzed: 43 cases were in clinical stage I (69.4%), 17 were in clinical stage II (27.4%), and 2 were in clinical stage III (3.2%). Fifty-six cases expressed CD117 (90%), 42 p53 (68%), 8 CD30 (13%), and all cases Ki67. There were no differences in p53, Ki67, CD30, and CD117 expression between testicular seminoma with and without clinical metastasis at diagnosis, regardless of the magnitude of expression. Neither of them found positive association between these marker expressions and morphologic risk factors such as tumor size greater than 6 cm and rete testis invasion. This study shows that expression of p53, Ki67, and CD30 and loss of CD117 expression fail to predict the presence of clinical metastasis at diagnosis of testicular seminoma and do not correlate with other histopathological risk factors in clinical stage I patients.

Correlation Between Primary Tumor Pathologic Features and Presence of Clinical Metastasis at Diagnosis of Testicular Seminoma

To compare several risk factors in the testicular biopsy of patients with pure seminoma with and without clinical metastasis at diagnosis. We performed a retrospective study of patients with pure seminoma. The retroperitoneum was staged with computed tomography and the thorax with simple radiography and/or computed tomography, taking into account the original reports and clinical stage. The previous reports and original pathology plates were reviewed by pathologists who were unaware of the clinical stage of the patients. Patients with beta-human chorionic gonadotropin greater than 800 mUI/mL were excluded. A total of 86 patients had sufficient data and comprised the study cohort. Of the 86 patients, 62 had clinical Stage I (72%), 20 had Stage II (23%), and 4 had Stage III (5%). On univariate analysis, tumor size greater than 4 cm (P = 0.0135), testicular vascular invasion (P = 0.0042), rete testis invasion (P = 0.0002), tunica albuginea penetration (P = 0.00001), base of the spermatic cord invasion (P = 0.0002), epididymis invasion (P = 0.001), and vascular invasion of the cord (P = 0.024) were predictive of metastasis. On multivariate analysis, tumor size greater than 6 cm (odds ratio 6.9, 95% confidence interval 1.3 to 35, P = 0.02) and rete testis invasion (odds ratio 6.1, confidence interval 1.2 to 30, P = 0.025) remained as important predictors of metastasis (tumor size less than 6 cm was not significant on multivariate analysis). The results of this study have demonstrated that rete testis invasion and tumor size correlate independently with the presence of clinical metastasis at diagnosis of testicular seminoma.

P53 mutations and overexpression in locally advanced breast cancers.

Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer.