Real-world treatment practice in patients with advanced melanoma.

INTRODUCTION: The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. MATERIAL AND METHODS: A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. RESULTS: mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. CONCLUSIONS: The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.

Endothelial dysfunction in patients with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (ß = - 0.3 [95% confidence interval (CI) - 0.5 to - 0.1]), serum level of IL-6 (ß = - 0.36 [95% CI - 0.62 to - 0.1]), and thrombomodulin (ß = - 0.34 [95% CI - 0.6 to - 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.

Acquired Haemophilia A Associated with Subsequent Hepatocellular Carcinoma.

Acquired haemophilia A (AHA) is a rare autoimmune disease caused by antibodies directed against clotting factor VIII. About half of cases are idiopathic, but AHA may also be secondary to autoimmune, dermatologic, or oncologic diseases. In approximately 10% of non-idiopathic cases, the disease occurs after or with the diagnosis of cancer as an extremely rare paraneoplastic syndrome. We describe the case of a 73-year-old male patient diagnosed with AHA and successfully treated with recombinant human activated factor VIIa and immunosuppression. Two and a half years later, however, the disease relapsed and a routine ultrasound revealed a liver tumour that was then diagnosed as hepatocellular carcinoma. We present this case to increase awareness that this life-threatening condition may develop years prior to the diagnosis of cancer.

Endothelial dysfunction in patients with granulomatosis with polyangiitis: a case-control study.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors. OBJECTIVE: To evaluate endothelial dysfunction in GPA patients. METHODS: 44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant's serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography. RESULTS: Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (p = 0.01), 66% of IL-6 (p < 0.001) and 50.9% of thrombomodulin (p < 0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (p < 0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (ß = - 0.18 [95% CI: - 0.32 to - 0.04]), C-reactive protein (ß = - 0.17 [95% CI: - 0.27 to - 0.07]), IL-6 (ß = - 0.29 [95% CI: - 0.39 to - 0.19]), blood creatinine level (ß = - 0.2 [95% CI: - 0.3 to - 0.1]), and IMT (ß = - 0.14 (- 0.24 to - 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%. CONCLUSION: GPA is characterized by endothelial dysfunction. FMD is a useful tool for the detection of endothelial injury.

Associations of anthropometric measures on breast cancer risk in pre- and postmenopausal women--a case-control study.

BACKGROUND: The type of silhouette and quantity of fat tissue are correlated with hormonal imbalance which plays a substantial role in breast carcinogenesis. The goal of the study was to investigate the association between various anthropometric characteristics and breast cancer risk. METHODS: Detailed anthropometric assessment was conducted on 487 women of whom 193 had diagnosed breast cancer and were consecutive patients in the Oncology Center, Cracow, Poland between 2002 and 2004. Measurements were divided into four categories: overall body size (body mass index [BMI], waist circumference [WC], waist-hip ratio [WHR]), regional body sizes (skinfold thicknesses, circumferences), thickness of the skeleton (widths, chest diameters), and body proportions. Additionally, results were analyzed in regard to menopausal status. Differences between groups were assessed using Student's t test and Mann-Whitney's test. Models of logistic regression for selected data were built to estimate the odds ratio. Results were considered statistically significant when the P value was less than 0.05. RESULTS: The BMI in both groups was negatively associated with the risk of cancer. Among premenopausal women, WHR increased the risk of breast cancer (WHR > 0.83, OR, 2.72; 95% CI, 1.01-7.27). Anthropometric indices of hip-to-shoulder ratio in postmenopausal (≥84.2 mm, OR, 0.02; 95% CI, 0.01-0.11) and trunk-to-height ratio in both premenopausal women (≥32.76, OR, 0.09; 95% CI, 0.03-0.28) and postmenopausal women (≥32.76, OR, 0.13; 95% CI, 0.05-0.33) were strongly related to a decreased risk of breast cancer. Thicknesses of the triceps and subscapular skinfolds increased the risk of breast cancer. CONCLUSIONS: Women with breast cancer present with an obese type of silhouette with a specific concentration of fat tissue in the central and upper parts of the body.

Multiple variations of the arterial pattern in upper extremities: a case report and embryological pathogenesis.

During a routine dissection at the Department of Anatomy, Collegium Medicum, Jagiellonian University, one cadaver was found to have multiple variations of the arteries of the upper limbs. The variations pertained to the course of the brachial artery as well as to its distribution. An unusual formation of the superficial palmar arch was observed in both upper limbs. The anatomical peculiarities encountered included: in the left upper limb-the brachioradial artery, which formed the superficial palmar arch by turning to the palmar side of the hand and connecting with the ulnar artery and in the right upper limb-a subscapular-circumflex humeral-deep brachial trunk that correlated with a high division of the brachial artery (in the upper third of the biceps brachii muscle), a large anastomosis between the radial and the ulnar artery, the presence of a persistent median artery, and the unusual formation of the superficial palmar arch, which was created by the median, ulnar, and radial arteries. In this report, we will trace the path of the axillary artery and its branches in detail and emphasize its embryological significance.

Absence of the musculocutaneous nerve associated with a supernumerary head of biceps brachii: a case report.

Unusual neural and muscular variations in the right upper limb were noted during anatomical dissection of a 54-year-old male cadaver. The absence of the musculocutaneous nerve was correlated with a three-headed biceps brachii muscle. The distribution of muscular branches innervating the anterior compartment of the muscles of the arm was different to the cases described in literature hitherto. This report contains a comparison of various instances where the musculocutaneous nerve is absent. We discuss the embryological explanation for this anomaly and its clinical results. It is important to be aware of such possible anatomical variations during clinical practice.