Delayed malignant melanoma recurrence simulating primary ovarian cancer: Case report

BACKGROUND: Metastatic involvement of the ovary from malignant melanoma is uncommon and presents a diagnostic challenge. Most cases are associated with disseminated disease and carry a dismal prognosis. Delayed ovarian recurrences from melanoma may mimic primary ovarian cancer and lead to aggressive cytoreductive procedures. CASE PRESENTATION: A case of malignant melanoma in a premenopausal patient is presented with late abdominal and ovarian metastatic spread, where ascitic fluid cytology led to an accurate preoperative diagnosis and the avoidance of unnecessary surgical procedures. CONCLUSION: Secondary ovarian involvement is associated with a poor prognosis and efforts should be made for adequate palliation. Pathologic diagnosis with non-invasive procedures is crucial in order to avoid unnecessary surgery. Surgical interventions may be undertaken only in selected cases of limited metastatic disease, where complete resection is expecte

Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model

<p>Abstract</p> <p>Background</p> <p>The treatment paradigm in advanced renal cell carcinoma (RCC) has changed in the recent years. Sunitinib has been established as a new standard for first-line therapy. We studied the prognostic significance of baseline characteristics and we compared the risk stratification with the established Memorial Sloan Kettering Cancer Center (MSKCC) model.</p> <p>Methods</p> <p>This is a retrospective analysis of patients treated in six Greek Oncology Units of HECOG. Inclusion criteria were: advanced renal cell carcinoma not amenable to surgery and treatment with Sunitinib. Previous cytokine therapy but no targeted agents were allowed. Overall survival (OS) was the major end point. Significance of prognostic factors was evaluated with multivariate cox regression analysis. A model was developed to stratify patients according to risk.</p> <p>Results</p> <p>One hundred and nine patients were included. Median follow up has been 15.8 months and median OS 17.1 months (95% CI: 13.7-20.6). Time from diagnosis to the start of Sunitinib (<= 12 months vs. >12 months, p = 0.001), number of metastatic sites (1 vs. >1, p = 0.003) and performance status (PS) (<= 1 vs >1, p = 0.001) were independently associated with OS. Stratification in two risk groups ("low" risk: 0 or 1 risk factors; "high" risk: 2 or 3 risk factors) resulted in distinctly different OS (median not reached [NR] vs. 10.8 [95% confidence interval (CI): 8.3-13.3], p < 0.001). The application of the MSKCC risk criteria resulted in stratification into 3 groups (low and intermediate and poor risk) with distinctly different prognosis underlying its validity. Nevertheless, MSKCC model did not show an improved prognostic performance over the model developed by this analysis.</p> <p>Conclusions</p> <p>Studies on risk stratification of patients with advanced RCC treated with targeted therapies are warranted. Our results suggest that a simpler than the MSKCC model can be developed. Such models should be further validated.</p

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.</p> <p>Methods</p> <p>We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.</p> <p>Results</p> <p>From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).</p> <p>Conclusions</p> <p>This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.</p

The role of acalabrutinib in adults with chronic lymphocytic leukemia.

The treatment landscape of chronic lymphocytic leukemia (CLL) has significantly changed in the past decade. This paradigm shift is due to the introduction of novel agents to the field. The two major classes of drugs that have contributed to this dramatic evolution include the Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors. Ibrutinib was the first-in-class drug which was initially approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory and later for patients with treatment-naïve CLL. Despite encouraging efficacy outcomes, its use has been associated with cardiovascular and gastrointestinal toxicities likely due to off-target inhibition of ITK, TEC and EGFR family kinases. The next generation of BTK inhibitors was developed to be more selective with less off-target inhibition with the prospect to improve tolerability without compromising efficacy. Acalabrutinib, a selective covalent BTK inhibitor, is a second generation BTK inhibitor. The focus of this review is on two major phase III trials that resulted in the FDA approval of acalabrutinib in 2019. The ELEVATE TN trial investigated acalabrutinib with or without obintuzumab versus chlorambucil-obinutuzumab in older and frail patients with previously untreated CLL. The ASCEND trial explored acalabrutinib versus chemoimmunotherapy in patients with relapsed/refractory CLL. Both trials demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. Unfortunately, the availability of new generation BTK inhibitors has not resulted in mitigating the financial toxicities associated with these potentially life-long treatments

Prognostic molecular biological markers in patients with urinary bladder cancer

Aim: The diagnosis and follow-up of patients with urinary bladder tumors classically become by cystoscopy and urine cytology. In the aim of early diagnosis and/or relapse of disease, and improvement of the overall survival many studies referring to circulating tumor-markers are ongoing. Material-Methods: Patients with histologically confirmed transitional cancer of urinary bladder were eligible. Patients with other histological type (squamous cell, small-cell, etc), or other malignancy, or patients with presence of chronic urinary infection (prostatitis, cystitis, urinary TBC), or with presence of lithiasis were excluded. A total of 142 patients and 33 healthy controls entered this study. Fifty-six patients had local disease (T1-4N0M0, clinical stages I, II, III), and 86 had metastatic disease (TanyN1-3M0-1 or in relapse after previous surgery and/or radiotherapy). The following parameters were studied: Serum levels of metalloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalolproteinase (TIMP)-2, MMP-2/TIMP-2 ratio, CYFRA 21-1, CEA, Ca 125, Ca 19-9, β-HCG, AFP, and urine levels of NMP-22 and EGF. Serum or urine values of the above parameters were correlated with tumor size, tumor differentiation, clinical stage, and overall survival. In the group of patients with metastatic disease who were included for chemotherapy treatment, the correlation of the above parameters with treatment response was estimated. Results: In the group of patients with local disease, the cystoscopy and the urine cytology were found positive for 87.5% and 80.4% of patients respectively. Positive correlation between abnormal NMP-22 values and bladder tumor presence was found; on the contrary no correlation was established between abnormal EGF values and local disease. Patients with metastatic disease compared with those with local disease showed a statistical increase of all serum markers. Serum levels of MMP-2, MMP-9, TIMP-2, MMP2/TIMP2 ratio and CYFRA 21-1 had statistically significant difference among groups of local disease, metastatic disease and healthy controls. Specifically, in the group of patients with metastatic disease MMP-2 and CYFRA 21-1 showed significant differences between patients with lymphnode and soft tissue metastases. During chemotherapy period, MMP-2, MMP-9, MMP2/TIMP2 ratio, CYFRA 21-1 and βHCG were proved sensitive markers of treatment response. No correlation was established between value of the above serum parameters and tumor differentiation. Patients with local disease and high levels of serum MMP-9 showed poor survival; in the goup of metastatic disease, normal values of CYFRA 21-1 and βHCG were accompanied with statistically improved survival. Conclusions: Serum MMP-2, MMP-9, MMP-2/TIMP-2 ratio, CYFRA 21-1, and bHCG were found to be reliable markers of staging and follow-up of patients with bladder cancer. NMP-22 compared with EGF showed better correlation with presence of bladder tumor ³T 1.Σκοπός: Η διάγνωση και παρακολούθηση των νεοπλασιών της ουροδόχου κύστης γίνεται κλασσικώς με την κυστεοσκόπηση και την κυτταρολογική εξέταση των ούρων. Πλήθος μελετών υλοποιούνται διεθνώς για την ανεύρεση ειδικών δεικτών στον ορό ή/και τα ούρα, ώστε να βελτιωθούν τα ποσοστά έγκαιρης διάγνωσης ή/και υποτροπής της νόσου, γεγονός που θεωρητικώς συμβάλλει στην μακρύτερη και ποιοτικώς καλύτερη επιβίωση των ασθενών. Υλικό-Μέθοδοι: Στην μελέτη εντάχθηκαν ασθενείς με ιστολογικώς τεκμηριωμένο καρκίνο ουροδόχου κύστης από μεταβατικό επιθήλιο. Αποκλείστηκαν ασθενείς με άλλη ιστολογική ταξινόμηση (πλακώδες, μικροκυτταρικό, κ.ά.), ασθενείς με άλλη κακοήθεια (σύγχρονη ή ετερόχρονη), ασθενείς με παρουσία χρονίας λοίμωξης του ουροποιητικού (προστατίτιδα, κυστίτιδα, TBC ουροποιητικού, κοκ), ασθενείς με παρουσία λιθίασης του ουροποιητικού. Στην μελέτη εντάχθηκαν συνολικώς 142 ασθενείς και 33 φυσιολογικοί μάρτυρες. Tοπική (εντοπισμένη στην ουροδόχο κύστη) νόσο (Τ1-4Ν0Μ0, κλινικά στάδια Ι, ΙΙ, ΙΙΙ) είχαν 56 ασθενείς και μεταστατική νόσο (TanyN1-3M0-1 ή σε υποτροπή μετά από προηγούμενη επέμβαση ή/και ακτινοθεραπεία) 86 ασθενείς. Μελετήθηκαν τα επίπεδα των ακολούθων παραμέτρων α) Mealloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-2, πηλίκον MMP-2/TIMP-2, CYFRA 21-1, CEA, Ca 125, Ca 19-9, β-HCG, AFP ορού, β) NMP-22 και EGF ούρων. Έγινε προσπάθεια συσχέτισης των ανωτέρω παραμέτρων με το μέγεθος του πρωτοπαθούς όγκου, το κλινικό στάδιο της νόσου, τη διαφοροποίηση του όγκου και υπολογίστηκε η επίπτωσή τους στην ολική επιβίωση. Στους ασθενείς με μεταστατική νόσο, οι οποίοι εντάχθηκαν σε πρωτόκολλο χημειοθεραπείας, έγινε παρακολούθηση των ανωτέρω παραμέτρων και συσχετισμός τους με την απάντηση στην θεραπεία. Αποτελέσματα: Στους ασθενείς με τοπική νόσο η κυστεοσκόπηση ανευρέθη θετική στο 87,5% και η κυτταρολογική των ούρων στο 80,4% των ασθενών. Παθολογικές τιμές της ΝΜΡ-22 σε συσχετισμό με την θετική κυτταρολογική εξέταση και την θετική κυστεοσκόπηση έδειξαν μεγάλη αξιοπιστία, εν αντιθέσει με τον EGF των ούρων, ο οποίος αποδείχτηκε μη αξιόπιστη μέθοδος εκτίμησης της παρουσίας ενδοκυστικής νόσου. Όλες οι παράμετροι του ορού έδειξαν σημαντική αύξηση στην ομάδα των ασθενών με μεταστατική νόσο συγκριτικώς με τοπική νόσο. Τα επίπεδα των ΜΜΡ-2, ΜΜΡ-9, ΤΙΜΡ-2, πηλίκο ΜΜΡ-2/ΤΙΜΡ-9 και CYFRA 21-1 είχαν στατιστικώς σημαντική διαφορά ανάμεσα σε ασθενείς με νόσο τοπική στην κύστη, με μεταστατική νόσο και σε φυσιολογικούς μάρτυρες. Ειδικώς για τους ασθενείς με μεταστατική νόσο φάνηκε ότι οι ΜΜΡ-2 και CYFRA 21-1 έχουν σημαντικές διαφορές ανάμεσα σε ασθενείς με λεμφαδενικές και σπλαγχνικές μεταστάσεις. Στην διάρκεια των χημειοθεραπειών οι πλέον ευαίσθητες στην απάντηση στην χημειοθεραπεία παράμετροι αποδείχτηκαν οι ΜΜΡ-2, ΜΜΡ-9, πηλίκο ΜΜΡ-2/ΤΙΜΡ-9, CYFRA 21-1 και η βHCG. Κανείς από τους δείκτες δεν έδειξε συσχέτιση με την διαφοροποίηση του όγκου. Σε αναλύσεις των επιβιώσεων, σε ασθενείς με τοπική νόσο δυσμενής της επιβιώσεως απεδείχθησαν αυξημένες τιμές ΜΜΡ-9. Σε ασθενείς με μεταστατική νόσο φυσιολογικές τιμές CYFRA 21-1 και βHCG συνοδεύτηκαν με στατιστικώς πιο βελτιωμένη επιβίωση. Συμπεράσματα: Οι παράμετροι MMP-2, MMP-9, πηλίκον MMP-2/TIMP-2, CYFRA 21-1, και β-HCG ορού αποδείχθηκαν αξιόπιστοι δείκτες στην σταδιοποίηση και παρακολούθηση των ασθενών με καρκίνο της ουροδόχου κύστης. Από τις παραμέτρους των ούρων η ΝΜΡ-22 συγκριτικώς με τον EGF έδειξε καλύτερο συσχετισμό με την παρουσία ενδοκυστικού όγκου ³Τ1

The role of acalabrutinib in adults with chronic lymphocytic leukemia.

The treatment landscape of chronic lymphocytic leukemia (CLL) has significantly changed in the past decade. This paradigm shift is due to the introduction of novel agents to the field. The two major classes of drugs that have contributed to this dramatic evolution include the Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors. Ibrutinib was the first-in-class drug which was initially approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory and later for patients with treatment-naïve CLL. Despite encouraging efficacy outcomes, its use has been associated with cardiovascular and gastrointestinal toxicities likely due to off-target inhibition of ITK, TEC and EGFR family kinases. The next generation of BTK inhibitors was developed to be more selective with less off-target inhibition with the prospect to improve tolerability without compromising efficacy. Acalabrutinib, a selective covalent BTK inhibitor, is a second generation BTK inhibitor. The focus of this review is on two major phase III trials that resulted in the FDA approval of acalabrutinib in 2019. The ELEVATE TN trial investigated acalabrutinib with or without obintuzumab versus chlorambucil-obinutuzumab in older and frail patients with previously untreated CLL. The ASCEND trial explored acalabrutinib versus chemoimmunotherapy in patients with relapsed/refractory CLL. Both trials demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. Unfortunately, the availability of new generation BTK inhibitors has not resulted in mitigating the financial toxicities associated with these potentially life-long treatments

Inferior vena cava filter thrombosis.

Patients with inferior vena cava (IVC) filters - particularly permanent filters - are at increased risk for recurrent deep venous thrombosis (DVT). Judicious use of IVC filters, as well as the prompt retrieval of temporary IVC filters, substantially reduces the risk of IVC thrombosis