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IntroductionThe term "intracystic papillary ductal carcinoma in situ" has recently changed and is now more appropriately referred to "intracystic papillary carcinoma". Intracystic papillary carcinoma in men is an extremely rare disease with only a few case presentations published in the literature so far.Case presentationWe discuss a case of a 44-year-old Caucasian man with an intracystic papillary carcinoma treated with simple mastectomy, sentinel lymph-node biopsy and contralateral risk-reducing mastectomy. These were followed by adjuvant radiotherapy of the breast.ConclusionTriple assessment (i.e. clinical examination and radiological and histological assessment) with a high level of clinical suspicion is necessary to diagnose intracystic papillary carcinoma in men due to its rarity. Furthermore, genetic testing and risk-reducing mastectomy should also be considered in cases of a strong family history for male breast cancer.

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IntroductionAlpha-1 antitrypsin (AAT) deficiency (AATD) is associated with early onset emphysema. The aim of this study was to investigate whether AAT binding to plasma constituents could regulate their activation, and in AATD, exploit this binding event to better understand the condition and uncover novel biomarkers of therapeutic efficacy.MethodsTo isolate AAT linker proteins, plasma samples were separated by size exclusion chromatography, followed by co-immunoprecipitation. AAT binding proteins were identified by mass spectrometry. Complement turnover and activation was determined by ELISA measurement of C3, C3a and C3d levels in plasma of healthy controls (n=15), AATD (n=51), non-AATD patients with obstructive airway disease (n=10) and AATD patients post AAT augmentation therapy (n=5).ResultsDirect binding of complement C3 to AAT was identified in vivo and in vitro. Compared with healthy controls, a breakdown product of C3, C3d, was increased in AATD (0.04 µg/mL vs 1.96 µg/mL, p=0.0002), with a significant correlation between radiographic pulmonary emphysema and plasma levels of C3d (R2=0.37, p=0.001). In vivo, AAT augmentation therapy significantly reduced plasma levels of C3d in comparison to patients not receiving AAT therapy (0.15 µg/mL vs 2.18 µg/mL, respectively, p=0.001).DiscussionResults highlight the immune-modulatory impact of AAT on the complement system, involving an important potential role for complement activation in disease pathogenesis in AATD. The association between plasma C3d levels and pulmonary disease severity, that decrease in response to AAT augmentation therapy, supports the exploration of C3d as a candidate biomarker of therapeutic efficacy in AATD.

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Individuals with Alpha--1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the

A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced nonsmall-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6 -17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8 -18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response þ partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6 -NR). Median PFS was 2.6 months (95% CI: 1.4 -3.8), and the median survival was 7.0 months (95% CI: 5.8 -9.2). Grades 3 -4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3 -4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, noncumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second-or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs.

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