Germline testing and genetic counseling in biliary tract cancer: an operative proposal to improve the state of art.

INTRODUCTION: A genetic predisposition seems to be involved in biliary tract cancer, but the prevalence of germline mutations in BTC remains unclear, and the therapeutic role of the germline pathologic variants is still unknown. AREA COVERED: The aim of the present work is to systematically review the data available on the hereditary predisposition of biliary tract cancer by a specific research on PubMed, in order to highlight the most important critical points and to define the current possible role of germinal testing and genetic counseling in this setting of patients. EXPERT OPINION: Basing on data already available, we decided to start in our institution a specific genetic protocol focused on biliary tract cancer patients, which includes genetic counseling and, if indicated, germline test. The inclusion criteria are: 1) Patient with personal history of oncologic disease other than BTC, 2) Patient with familiar history of oncologic disease (considering relatives of first and second grade), 3) Patient with ≤ 50 years old, 4) Patient presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair. The aim of the presented protocol is to identify germline pathogenic variants with prophylactic and therapeutic impact, and to collect and integrate a significant amount of clinical, familial, somatic, and genetic data.

Usefulness of polymerase chain reaction analysis in a case of clinically and histologically atypical nodular granulomatous secondary syphilis.

We report a case of a nodular granulomatous secondary syphilis histologically resembling tuberculids in a patient with positive quantiferon test and serology for syphilis. Polymerase chain reaction (PCR) analysis led to the diagnosis. We underline the usefulness of PCR in clinically and histologically doubtful cases in order to avoid misdiagnosis and delay treatment.

Super-High Magnification Dermoscopy Can Help for the Diagnosis of Lentigo Maligna: a Pilot Study on 61 Cases.

INTRODUCTION: Facial lentigo maligna/lentigo maligna melanoma (LM/LMM) is a significant diagnostic clinical challenge and dermoscopy can help its diagnosis. OBJECTIVES: The following study aimed to evaluate if super-high magnification dermoscopy at 400x can add further details for the diagnosis of the LM/LMM. METHODS: This is a retrospective observational, multicentric study enrolling patients who received a 20x and 400x (D400) magnification dermoscopic examination of facial skin lesions in clinical differential diagnosis with LM/LMM. Dermoscopic images were retrospectively evaluated by four observers for the presence/absence of nine 20x and ten 400x dermoscopic features. Univariate and multivariate analyses were carried out to find predictors of LM/LMM. RESULTS: We enrolled 61 patients with a single atypical skin lesion of the face, including 23 LMs and 3 LMMs. The presence of roundish and/or dendritic melanocytes (P < 0.001), irregular arrangement of melanocytes (P <0.001), irregular in shape and size melanocytes (P = 0.002), and folliculotropism of melanocytes (P <0.001) at D400 were more frequent in LM/LMM than other facial lesions. According to the multivariate analysis, roundish melanocytes at 400x dermoscopy were more indicative of LM/ LMM (Odds Ratio-OR 49.25, 95% CI 8.75-513.2, P < 0.001), and sharply demarcated borders at 20x dermoscopy were more indicative of not-LM/LMM (OR 0.1, 95% CI 0.01-0.79, P = 0.038). CONCLUSIONS: D400 can identify atypical melanocyte proliferation and folliculotropism that can help to identify LM/LMM together with conventional dermoscopy data. Our preliminary observations should be confirmed by larger studies.

Not only monkeypox infection: Keratoderma blenorrhagicum.

We report the case of a 18-year-old boy affected by keratoderma blenorrhagicum mimicking monkeypox infection. PCR test in urine and urethral swab positive for chlamydia trachomatis and a biopsy performed on a lesion of the palm of the hand led to the correct diagnosis. The current monkeypox outbreak is an evolving situation, thus a better understanding of morphological, clinical and temporal features could help in prompt diagnosis of this infection.

Risk of recurrent cerebrovascular events in patients with cryptogenic stroke or transient ischemic attack and patent foramen ovale: the FORI (Foramen Ovale Registro Italiano) study.

BACKGROUND: The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale (PFO) at diagnostic workup remains unclear. The aims of this observational multicenter study were to evaluate: (1) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack (TIA) and PFO who either underwent percutaneous PFO closure or received only medical treatment, and (2) the risk factors associated with recurrent events. METHODS: Consecutive patients (aged 55 years or less) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years. RESULTS: 238 patients were included in the study (mean age 42.2 ± 10.0 years; 118 males); 117 patients (49.2%) received only antithrombotic therapy while 121 patients underwent percutaneous PFO closure (50.8%). Stroke as the qualifying event was more common in the medical treatment group (p = 0.01). The presence of atrial septal aneurysm and evidence of 20 bubbles or more on transcranial Doppler were more common in the PFO closure group (p = 0.002 and 0.02). Eight patients (6.6%) experienced a nonfatal complication during PFO closure. At the 2-year follow-up, 17 recurrent events (TIA or stroke; 3.6% per year) were observed; 7 of these events (2.9% per year) occurred in the percutaneous PFO closure group and 10 events (4.2% per year) in the medical treatment group. The rate of recurrent stroke was 0.4% per year in patients who underwent percutaneous closure (1 event) and 3.4% per year in patients who received medical treatment (8 events). On multivariate analysis, percutaneous closure was not protective in preventing recurrent TIA or stroke (OR = 0.1, 95% CI = 0.02-1.5, p = 0.1), while it was barely protective in preventing recurrent stroke (OR = 0.1, 95% CI = 0.0-1.0, p = 0.053). CONCLUSIONS: The results of this observational, nonrandomized study suggest that PFO closure might be superior to medical therapy for the prevention of recurrent stroke. Periprocedural complications were the trade-off for this clinical benefit. Controlled randomized clinical trials comparing percutaneous closure with medical management are required.

Endothelial dysfunction in patients with kidney failure and vascular risk factors: acute effects of hemodialysis.

BACKGROUND: Patients with kidney failure present endothelial dysfunction, which was shown to be partly corrected by hemodialysis. No data exist on the effects of hemodialysis on endothelial dysfunction in kidney failure patients with associated vascular risk factors. The aim of this study was to evaluate the acute effects of hemodialysis on endothelial dysfunction in patients with kidney failure and associated vascular risk factors and to assess the role of endothelium-toxic substances. METHODS: We assessed endothelial dysfunction in 13 patients with chronic renal failure and other vascular risk factors before and after hemodialysis and in 13 healthy controls and simultaneously measured nitric oxide (NO) synthesis and activity. Endothelial dysfunction was studied using an echographic method as flow-mediated dilation (FMD) of the brachial artery; plasma NO2- and NO3-, cyclic guanosine-5-monophosphate (cGMP), plasma homocysteine levels and low molecular mass-advanced glycation end-products (LMM-AGEs) were simultaneously measured. RESULTS: As compared with healthy controls, patients with renal failure showed a reduced FMD (2.89 +/- 1.43 vs. 7.81 +/- 1.54%, p < 0.01) which was not corrected by dialysis (after dialysis 2.40 +/- 1.65%, p = NS vs. pre). Plasma NO2- and NO3- were normal or slightly increased and remained unchanged after dialysis. Plasma cGMP levels were reduced and remained unchanged after dialysis. Homocysteine and LMM-AGE plasma levels were raised and, although significantly reduced by dialysis, remained higher than in controls. CONCLUSIONS: Patients with kidney failure and associated vascular risk factors show an endothelial dysfunction related to defective NO activity, which is not corrected by hemodialysis despite the reduction, though not to normal, in homocysteine and LMM-AGE levels. Endothelial dysfunction may contribute to the progression of atherosclerosis in patients with kidney failure and vascular risk factors.