Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients.

OBJECTIVES: The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. METHODS: g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. RESULTS: 135 g/sBMOC patients were identified (6% sBRCA1/2 mutations). The median number of chemotherapy lines was 2 (1-7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3-7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4-11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. CONCLUSIONS: Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients.

Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs.

BACKGROUND: Multiple NSAID-induced urticaria/angioedema (MNSAID-UA) is an entity well differentiated from aspirin-exacerbated respiratory disease (AERD), although no detailed phenotype analysis has yet been performed. The objective was to evaluate the functional characteristics of MNSAID-UA subjects by analyzing the response to nasal lysine-aspirin challenge and measurement of nasal inflammatory mediator release compared with AERD subjects and controls. METHODS: The study included 85 subjects with confirmed hypersensitivity to NSAIDs (≥3 episodes with >2 different NSAIDs or positive drug provocation) with either cutaneous (MNSAID-UA, n = 25) or respiratory manifestations (AERD, n = 60) and 30 tolerant controls (15 aspirin-tolerant asthmatic patients and 15 healthy controls). Nasal lavages at 0, 15, 60, and 120 min after lysine-aspirin challenge were analyzed for ECP, tryptase, PGE2 , PGD2 , LTD4 , and LTE4 . RESULTS: Lysine nasal challenge was positive in 80% of the AERD cases but positive only in 12% of the MNSAID-UA group. MNSAID-UA subjects showed no changes in nasal ECP, whereas subjects with AERD had increased levels of ECP, with the highest peak at 15 min after challenge (P < 0.05). Tryptase levels were higher in AERD compared with MNSAID-UA and controls with the highest release of tryptase at 60 min (P < 0.05). Significant increases in PGD2 , LTD4 , and LTE4 were observed in AERD (at 60 min for PGD2 , LTD4 , and LTE4 ) but not in MNSAID-UA or control subjects (P < 0.05). CONCLUSIONS: Data support the observation that MNSAID-UA, although sharing a common response with AERD to COX inhibitors, seems to have a distinctive phenotype, based on the response to nasal challenge and the release of inflammatory mediators.

Xanthogranulomatous cholecystitis: a radiological study of 12 cases and a review of the literature.

BACKGROUND: Twelve cases of xanthogranulomatous cholecystitis (XGC) are presented, and their radiologic appearance is described. METHODS: Four men and eight women, aged 31-82 years old, with XGC were reviewed. Abdominal ultrasound (US) was performed in all patients. Computed tomography (CT) was performed in five patients, barium enema examination in two, and percutaneously CT-guided fine-needle aspirative biopsy of the gallbladder in one. RESULTS: Barium enema examination showed an indentation of the hepatic flexure. Cholelithiasis was present in all patients, and sludge was present in six. The gallbladder wall was thickened in all patients, irregular in nine, and could not be properly differentiated from surrounding liver parenchyma or from other adjacent structures in most patients. A curvilinear halo, hypoechoic on US and with low attenuation on CT, within the gallbladder wall was found in three patients and pericholecystic fluid in two others. On CT, the pericholecystic fat had streaky soft tissue densities in three cases. Percutaneously CT-guided fine-needle aspirative biopsy of the gallbladder was nondiagnostic. The diagnosis of gallbladder carcinoma was considered preoperatively in three patients. CONCLUSION: Despite the characteristic histologic appearance of XCG, radiologic findings are nonspecific, varying from signs observed in other forms of cholecystitis to the appearance of a gallbladder neoplasm.

Fine-needle aspiration biopsy of metaplastic carcinoma of the breast: report of a case with abundant myxoid ground substance.

Metaplastic carcinoma (MC) is an uncommon neoplasm of the breast. There are several variants of MC depending on the dominant histologic pattern. The components include over infiltrating ductal carcinoma, extensive squamous differentiation and spindle cell proliferation with or without chondroid or asseous heterologous elements. In FNA smears, only 57% of cases show both ductal carcinoma and metaplastic component. Thus, in almost one half of the cases, the diagnosis is not possible by FNA. Often it is difficult to define the epithelial or sarcomatous character of malignant cells. We describe a case of metaplastic carcinoma of the breast studied by fine-needle aspiration cytology in which myxoid ground substance was the dominant feature in the cytology smears. The rest of the material was composed of scanty isolated atypical cells with large and irregular nuclei. It is important to bear in mind the diagnosis of MC and make a careful search for atypical cells when the cytological smears are mainly composed of myxoid ground substance.

[Ultrasonics in endodontics. 2. Clinical applications]. / Ultrasonidos en endodoncia: II parte. Aplicaciones clinicas.

The present study, second of three dwelling with ultrasonic in endodontic therapy, is a review of the literature about clinical applications of some of the sonic and ultrasonic system.

[Ultrasonics in endodontics: mechanism of action]. / Ultrasonidos en endodoncia: mecanismo de acción.

The present study, first of three dwelling with ultrasonics in endodontic therapy, is a review of the literature about mechanisms involved and appliance of some of the sonic and ultrasonic system.