Primary choriocarcinoma of the renal pelvis presenting as intracerebral hemorrhage: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>A choriocarcinoma is a malignant neoplasm normally arising in the gestational trophoblast, gonads and, less frequently, the retroperitoneum, mediastinum and pineal gland. Primary choriocarcinomas of the renal pelvis are extremely rare.</p> <p>Case presentation</p> <p>We report a case of primary choriocarcinoma of the renal pelvis in a 38-year-old Greek woman of reproductive age, presenting with a sudden development of intracerebral hemorrhage due to metastatic lesions. The diagnosis was established with a renal biopsy, along with an elevated serum level of beta-human chorionic gonadotropin. An extensive diagnostic work up confirmed the origin of the choriocarcinoma to be the renal pelvis.</p> <p>Conclusion</p> <p>Extragonadal choriocarcinomas are rare neoplasms that require extensive laboratory and imaging studies to exclude a gonadal origin. Moreover, this is the first case of severe intracerebral hemorrhage as the initial presentation of primary choriocarcinoma of the renal pelvis. Nonetheless, choriocarcinomas should be considered in the differential diagnosis of women of reproductive age.</p

Study of the expression of the COX - 2 factor in patients with muscle-invasive urothelial cancer that had received adjuvant chemohterapy with paclitaxel / carboplatin: correlation with apoptosis, cell proliferation, angiogenesis and prognostic significanse

Urothelial cancer is a common malignancy. The treatment of choice for muscle- invasive urothelial cancer is radical cystectomy and the prognosis is related to the pathological stage of the disease. Systemic neoadjuvant and adjuvant chemotherapy has been used in order to improve prognosis. Biological factors may be adoperated to define groups of patients with different prognosis that may benefit from different therapeutic approaches. Cycloxygenase-2 (COX-2) is an isoenzyme implicated in the production of prostaglandins and related to apoptosis, cellular proliferation and angiogenesis. Prognostic significance of COX-2 was studied in patients with muscle- invasive urothelial cancer and high risk for relapse (pT3a, pT3b or pT4a or lymph node metastases, but not distal metastases), that had undergone surgery followed by adjuvant chemotherapy with paclitaxel/ carboplatin. The methods used were immunohistochemistry and reverse transcription- polymerase chain reaction (RT-PCR). Immunohistochemical expression of COX-2 in 59 patients, of p53 in 52 patients, of ki-67 in 57 patients and of microvessel density (MVD) in 50 patients were studied. On the other hand, COX-2 RNA and VEGF RNA were studied in 43 patients. Correlations with age, sex, pathological T stage, tumor location, lymph node metastases and vascular invasion, as well as overall survival and disease free survival were done. Immunohistochemical expression of COX-2 was positive in 64% of the patients, but no correlation was found with overall survival and disease free survival. Expression of COX-2 RNA was found positive only in 20,9% of the the patients and, in this case also, there was no correlation with overall survival and disease free survival. Interestingly, VEGF RNA expression was observed almost exclusively in those patients that were immunohistochemically positive for COX-2. As far as microvessel density was concerned, levels of MVD ?47 were associated with longer disease free survival that was statistically significant. These results could be attributed to the small number of patients that were included in the analysis, as well as to the difficulties encountered in extracting RNA from the material used for the study. Of all the factors studied, microvessel density (MVD) could serve as a useful indicator of relapse in patients with muscle- invasive urothelial cancer treated with adjuvant chemotherapy.Ο καρκίνος ουροθηλίου αποτελεί συχνό κακόηθες νεοπλασματικό νόσημα. Θεραπεία εκλογής του διηθητικού ουροθηλιακού καρκινώματος είναι η ριζική κυστεκτομή, οπότε η πρόγνωση σχετίζεται με το παθολοανατομικό στάδιο της νόσου. Η χρησιμοποίηση προ ή μετεγχειρητικής χημειοθεραπείας έχει στόχο τη βελτίωση της πρόγνωσης αυτών των ασθενών. Η έκφραση βιολογικών δεικτών μπορεί να χρησιμοποιηθεί για την ανεύρεση ομάδων ασθενών με διαφορετική πρόγνωση που θα μπορούσαν να ωφεληθούν από διαφορετική θεραπευτική αντιμετώπιση. Η κυκλοοξυγονάση-2 (COX-2) είναι ισοένζυμο, που ενέχεται στην παραγωγή των προσταγλανδινών και σχετίζεται με απόπτωση, κυτταρικό πολλαπλασιασμό και αγγειογένεση. Μελετήθηκε η προγνωστική σημασία της COX-2 σε ασθενείς με διηθητικό καρκίνο ουροθηλίου και υψηλό κίνδυνο υποτροπής της νόσου (παθολογοανατομικού σταδίου pT3a, pT3b ή pT4a ή με διήθηση των επιχώριων λεμφαδένων, αλλά χωρίς απομακρυσμένες μεταστάσεις), που είχαν λάβει μετεγχειρητική χημειοθεραπεία με paclitaxel/ carboplatin. Οι μέθοδοι, που χρησιμοποιήθηκαν ήταν η ανοσοϊστοχημεία και η ανάστροφη μεταγραφή- αλυσιδωτή αντίδραση πολυμεράσης (RT-PCR). Μελετήθηκε η ανοσοϊστοχημική έκφραση της COX-2 σε 59 ασθενείς, του p53 σε 52 ασθενείς, του ki-67 σε 57 ασθενείς και της μικροαγγειακής πυκνότητας (MVD) σε 50 ασθενείς. Επίσης, μελετήθηκε το COX-2 RNA και το VEGF RNA σε 43 ασθενείς. Έγιναν συσχετίσεις με την ηλικία, το φύλο, το παθολογοανατομικό στάδιο Τ, τη θέση του όγκου, τη λεμφαδενική διήθηση και την αγγειακή διήθηση, καθώς και με τη συνολική επιβίωση και την ελεύθερη νόσου επιβίωση. Η ανοσοϊστοχημική έκφραση της COX-2 βρέθηκε θετική στο 64% των ασθενών, αλλά δε διαπιστώθηκε συσχέτισή της με τη συνολική επιβίωση και την ελεύθερη νόσου επιβίωση. Το COX-2 RNA βρέθηκε θετικό μόνο στο 20,9% των ασθενών, αλλά και σε αυτή την περίπτωση δε διαπιστώθηκε συσχέτισή του με τη συνολική επιβίωση και την ελεύθερη νόσου επιβίωση. Επίσης, διαπιστώθηκε αποκλειστική έκφραση VEGF RNA στα περιστατικά που ήταν θετικά για COX-2 με ανοσοϊστοχημικές μεθόδους. Όσον αφορά στη μικροαγγειακή πυκνότητα, για επίπεδα MVD ?47 διαπιστώθηκε παρατεταμένη ελεύθερη νόσου επιβίωση, που ήταν στατιστικά σημαντική. Τα αποτελέσματα αυτά θα μπορούσαν να αποδωθούν στο μικρό αριθμό των ασθενών που περιλήφθηκαν στην ανάλυση, καθώς και στις δυσκολίες που παρουσιάζει η απομόνωση του RNA από το υλικό της μελέτης. Και οι δύο περιορισμοί φαίνεται να συνδέονται με το γεγονός ότι πρόκειται για αναδρομική μελέτη. Από τους παράγοντες, που μελετήθηκαν, η μικροαγγειακή πυκνότητα (MVD) θα μπορούσε να αποτελέσει χρήσιμο δείκτη υποτροπής της νόσου σε ασθενείς με διηθητικό καρκίνο ουροθηλίου και υψηλό κίνδυνο υποτροπής, που λαμβάνουν μετεγχειρητική χημειοθεραπεία

Pneumocystis Jirovecii Pneumonia after Initiation of Tofacitinib Therapy in Rheumatoid Arthritis: Case-Based Review.

The use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in rheumatic diseases is constantly increasing during the last decade. Tofacitinib is a new oral Janus Kinase (JAK) inhibitor, approved for rheumatoid arthritis (RA), psoriatic arthritis and ulcerative colitis. Safety data of tofacitinib derived from randomized controlled trials and long-term extension studies has demonstrated a moderate increase in the risk for common serious infections. We describe a case of Pneumocystis jirovecii pneumonia (PJP) in a woman on tofacitinib therapy for RA. Although tofacitinib use has been associated with the development of opportunistic infections, PJP has been rarely reported. PJP should be included in the differential diagnosis of patients with autoimmune disorders under newer oral JAK inhibitors therapy who present with fever, hypoxia and pulmonary infiltrates

Somatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: Evidence for Wnt pathway implication

Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p = 0.043) and more frequent lymph node involvement (75% vs. 38%, p = 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p = 0.07), whereas in multivariate analysis they had shorter disease- specific survival (60.5 vs. 20.6 months, p = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. © 2008 Wiley-Liss, Inc

Topical prebiotics/postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients

Aim: To investigate the efficacy and tolerability of a cream (Rilastil Xerolact PB) containing a mixture of prebiotics and postbiotics, and to validate the PRURISCORE itch scale in the management of atopic dermatitis. Methods: The study is based on 396 subjects of both sexes in three age groups (i.e., infants, children, adults) suffering from mild/moderate Atopic Dermatitis, recruited from 8 European countries and followed for 3 months. Results: The product demonstrated good efficacy combined with good/very good tolerability in all age groups. In particular, SCORAD, PRURISCORE and IGA scores decreased significantly over the course of the study. The PRURISCORE was preferred to VAS by the vast majority of patients. Conclusion: Even though the role of prebiotics and postbiotics was not formally demonstrated since these substances were part of a complex formulation, it can be reasonably stated that prebiotics and postbiotics have safety and standardization features that probiotics do not have. In addition they are authorized by regulatory authorities, whereas topical probiotics are not