37 research outputs found
Unexpected Long Survival in Primary Malignant Melanoma of the Male Urethra
A case of primary malignant melanoma of the urethra in a 60-year-old male is presented. Despite multiple adverse prognostic factors and against expectations, after a follow-up of 5.5 years he is still alive
The Role of 11C-Choline-PET/CT-Guided Secondary Lymphadenectomy in Patients with PSA Failure after Radical Prostatectomy: Lessons Learned from Eight Cases
Introduction. 11C-choline-PET/CT is a promising technique for detection/restaging of patients with biochemical failure (BF) after curative therapy for prostate cancer (PCA). The aim of this paper was to evaluate the PSA response in patients with BF after radical prostatectomy (RP) who underwent secondary lymphadenectomy (LAD) due to 11C-choline-PET/CT findings. Material and Methods. Eight patients with BF and positive lymph nodes in 11C-choline-PET/CT after RP were retrospectively included in the study. Extended LAD until the common iliac arteries was performed in all patients. Results. Six of 8 patients had histologically proven lymph node metastases. Four patients showed an initial PSA reduction after LAD, and in 4 patients the PSA increased. Two of the latter had no histological lymph node metastases. Conclusions. Because 50% of our patients showed an initial PSA response, our data suggest that positive 11C-choline-PET/CT after RP and BF could help to select patients that could benefit from secondary LAD
Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature
Introduction: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.
Materials and methods: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.
Results: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.
Conclusions: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence
Comparison of complications from radical cystectomy between old-old versus oldest-old patients
Introduction: The purpose of this study was to evaluate and compare complications after radical cystectomy in patients aged ≥75 years.
Materials and Methods: 251 patients aged 75-95 years (median 79) underwent radical cystectomy between 2000 and 2012 at four institutions. The patients were divided into two groups: ≥75-84 years of age (group 1) versus ≥85 years of age (group 2). Comorbidities, body mass index, and complications were obtained retrospectively, except at the Central Hospital of Bolzano and Weill Cornell Medical Center, which collected data prospectively. Cancer-specific survival, overall mortality, hospital stay, clinical outcome and complications were assessed. Complications were categorized using the Clavien-Dindo classification reporting system. The mean follow-up was 21 months.
Results: The median hospital stay was 17 (2-91) days. Perioperative Clavien-Dindo grade ≥III complications were seen in 24.1% (48/199) of group 1 patients and 19.2% (10/52) of group 2 patients (p = 0.045). 30- and 90-day mortality was 4.5 and 13.5% in group 1 and 6.5 and 32.3% in group 2, respectively. Only the 90-day mortality rate was statistically significant (p < 0.05) between the two groups. The 3-year overall survival was 40% in group 1 and 34% in group 2. The 3-year cancer-specific survival was 52% in group 1 and 50% in group 2.
Conclusions: We evaluated a large series of elderly (≥75 years) patients undergoing radical cystectomy at four institutions. Comparing patients aged ≥75-84 and ≥85 years revealed no significant difference in complications, 30-day mortality, overall and cancer-specific survival rates. Only 90-day mortality rates were significantly higher in the ≥85-year-old patients
Comparison of Radical Cystectomy with Conservative Treatment in Geriatric ( 80) Patients with Muscle-Invasive Bladder Cancer
Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study
Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age
Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations
: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice
Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia
: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress
Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)
BACKGROUND AND AIMS:
Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network).
METHODS:
Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers.
RESULTS AND CONCLUSIONS:
From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 656. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy