Carcinoembryonic antigen and carbohydrate antigen 19-9 serum levels in non-small cell lung cancer.

PURPOSE: Τo investigate the potential diagnostic and prognostic role of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) serum levels in non-small cell lung cancer (NSCLC). METHODS: One hundred consecutive patients with newly diagnosed primary NSCLC were included in this study (88 men and 12 women). Blood was drawn before any kind of treatment and the collected serum was processed using chemiluminescence in order CEA and CA 19-9 levels to be measured. RESULTS: No significant associations between CEA or CA 19-9 levels and any tested clinical and pathological parameter were detected. Moreover, CEA levels did not seem to affect survival. On the other hand, patients with high CA 19-9 values (≥37 IU/ml) (median survival: 8 months) had a shorter overall survival than patients with low CA 19-9 values (<37 IU/ml) (median survival: 13 months) (p=0.026). However, CA 19-9 levels did not remain an independent prognostic factor in the multivariate survival analysis (p=0.114). CONCLUSION: CEA and CA 19-9 serum levels do not seem to have any diagnostic role in NSCLC. With regard to their prognostic role, CEA values do not seem to affect the prognosis in NSCLC. However, high CA 19-9 values are associated with worse prognosis.

Exploring the time-dependent regulatory potential of microRNAs in breast cancer cells treated with proteasome inhibitors.

PURPOSE: Breast cancer (BrCa) is a predominant type of cancer with a disparate molecular nature. MicroRNAs (miRNAs) have emerged as promising key players in the regulation of pathological processes in BrCa. Proteasome inhibitors (PIs) emerged as promising anticancer agents for several human malignancies, including BrCa, inhibiting the function of the proteasome. Aiming to shed light on the miRNA regulatory effect in BrCa after treatment with PIs, we used two PIs, namely bortezomib and carfilzomib. MATERIALS AND METHODS: Four BrCa cell lines of distinct molecular subtypes were treated with these PIs. Cell viability and IC50 concentrations were determined. Total RNA was extracted, polyadenylated, and reversely transcribed. Next, the levels of specific miRNAs with a significant role in BrCa were determined using relative quantification, and their regulatory effect was assessed. RESULTS: High heterogeneity was discovered in the levels of miRNAs in the four cell lines, after treatment. The miRNA levels fluctuate with distinct patterns, in 24, 48, or 72 hours. Interestingly, miR-1-3p, miR-421-3p, and miR-765-3p appear as key molecules, as they were found deregulated, in almost all combinations of cell lines and PIs. In the SK-BR-3 cell line, the majority of the miRNAs were significantly downregulated in treated compared to untreated cells, with miR-21-5p being the only one upregulated. Finally, various significant biological processes, molecular functions, and pathways were predicted to be affected. CONCLUSIONS: The diversity of pathways predicted to be affected by the diversity in miRNA expression after treatment with PIs paves the way for the recognition of new regulatory axes in BrCa.

Primary extrarenal papillary type II renal cell carcinoma presenting as a pelvic mass: a case report and review of the literature.

We report a case of a 57 years old woman with a solitary mass located in the pelvis diagnosed as an extrarenal papillary renal cell carcinoma, in the absence of a primary renal cancer. The diagnosis was based on cytomorphological features and further confirmed by immunochemistry findings following surgical excision. The hypothesis of a tumor developing in a supernumerary or ectopic kidney was excluded, since no normal renal tissue could be identified in the specimen and in the preoperative computed tomography and MRI images.

A Real-world Study of Everolimus Plus Aromatase Inhibitor in Hormone Receptor-positive, HER2-negative Advanced Breast Cancer.

BACKGROUND/AIM: Everolimus in combination with exemestane was shown to offer benefit versus exemestane monotherapy in hormone receptor (HR)-positive, HER2-negative advanced breast cancer patients who progressed after aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: The medical records of metastatic breast cancer patients, treated with everolimus, were retrospectively reviewed to generate real life safety and efficacy data. RESULTS: Sixty-eight percent of the patients had received chemotherapy (for early or metastatic disease) and 26% had received chemotherapy for metastatic disease. Among the 25 included patients, the most common adverse events were fatigue, neutropenia, epistaxis, stomatitis, and pneumonitis. Toxicity led to treatment discontinuation in 3 patients (12%). The median progression-free survival (PFS) was 7 months (95%CI=3.5-10.5). With a median follow-up of 73.3 months, the median overall survival was not reached. Twenty-five percent of the patients had received prior therapy with CDK4/6 inhibitors. Median PFS was significantly shorter in this subgroup (p=0.025). There was also a trend towards a longer PFS in patients with grade 3 breast cancer (p=0.085) and in patients receiving everolimus as first-line treatment (p=0.081). Some long responses were noted, with four patients exhibiting a PFS >5 years. CONCLUSION: These real-life data show that everolimus in combination with AI in patients with HER2-negative, HR-positive advanced breast cancer is an effective treatment with an acceptable toxicity profile.

Characteristics and outcomes of cancer patients who develop pulmonary embolism: A cross-sectional study.

Pulmonary embolism (PE), along with deep vein thrombosis, are collectively known as venous thromboembolism (VTE). Predisposing factors for PE include post-operative conditions, pregnancy, cancer and an advanced age; of note, a number of genetic mutations have been found to be associated with an increased risk of PE. The association between cancer and VTE is well-established, and cancer patients present a higher risk of a thrombotic event compared to the general population. In addition, PE is a significant cause of morbidity and mortality among cancer patients. The aim of the present study was to illustrate the clinical characteristics, laboratory findings, radiology features and outcomes of cancer patients who developed PE, collected from an anticancer hospital. For this purpose, adult cancer patients diagnosed with PE by imaging with computed tomography pulmonary angiography were enrolled. The following data were recorded: Demographics, comorbidities, type of cancer, time interval between cancer diagnosis and PE occurrence, the type of therapy received and the presence of metastases, clinical signs and symptoms, predisposing factors for PE development, laboratory data, radiological findings, electrocardiography findings, and the type of therapy received for PE and outcomes in a follow-up period of 6 months. In total, 60 cancer patients were enrolled. The majority of the cancer patients were males. The most common type of cancer observed was lung cancer. The majority of cases of PE occurred within the first year from the time of cancer diagnosis, while the majority of patients had already developed metastases. In addition, the majority of cancer patients had received chemotherapy over the past month, while they were not receiving anticoagulants and had central obstruction. A large proportion of patients had asymptomatic PE. The in-hospital mortality rate was 13.3% and no relapse or mortality were observed during the follow-up period. The present study demonstrates that elevated levels of lactic acid and an increased platelet count, as well as low serum levels of carcinoembryonic antigen, albumin and D-dimer, may be potential biomarkers for asymptomatic PE among cancer patients.

Nivolumab in patients with rare head and neck carcinomas: A single center's experience.

Immunotherapy (IO) with anti-PD1 inhibitors is available for the treatment of recurrent/metastatic squamous cell carcinomas of the head and neck (SCCHD) since 2016. Both nivolumab and pembrolizumab were tested in phase 3 randomized trials in adults progressing on or after platinum-based therapy and were found to confer an overall survival benefit compared to investigator's choice. However, very limited data exist concerning IO use in rare subtypes of head and neck carcinoma, like salivary gland carcinoma. We retrospectively collected clinical data of all patients diagnosed with rare subtypes of head and neck carcinoma, who were treated with immune checkpoint inhibitors in our department during the last 5 years. We analyzed safety and efficacy of these therapies. We identified six patients who received nivolumab for recurrent or metastatic head and neck carcinomas, between 31 and 57 years old. All patients had received at least one line of platinum-chemotherapy, as well as radiation therapy. Treatment was administered every 2 weeks, at a dose of 3 mg per kilogram of body weight. Number of nivolumab cycles varied between 2 and 18. Progression-free survival varied from 1 to 12 months and overall survival from 4 to 24 months. Tolerance was very good, except for one case of diabetes and hypothyroidism requiring medication. There is currently insufficient evidence regarding the optimal treatment of the rare non-squamous cell carcinoma of the head and neck. Our case series supports a role for immunotherapy in these patients. However, larger collaborative studies are needed to evaluate this treatment.

Cerebral metastasis from osteosarcoma: "Bone" in the brain.

Although brain metastases from bone and soft tissue sarcoma are uncommon, advances in sarcoma treatment have led to an increasing incidence of them. We present a 23-year-old male with a history of metastatic femoral osteosarcoma, who presented with headache and unsteady gait and was diagnosed with a cerebellar metastasis. CT scan revealed a mass in the left cerebellar parenchyma with large intralesional central calcification and perilesional edema. Corticosteroid treatment led to neurological symptoms resolution, with a rapid tapering. The patient had also lung metastases and we opted to administer systemic treatment with the tyrosine kinase inhibitor cabozantinib. Given the relative radioresistance of osteosarcomas, the patient did not receive radiation therapy.

Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated?

Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (r = -0.17, P = 0.15), FT4 (r = -0.13, P = 0.25), or TSH (r = -0.10, P = 0.39) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 (r = -0.60 and P = 0.004) but not between Ki67 and FT4 (r = 0.04 and P = 0.85) or TSH (r = -0.23 and P = 0.30). In HER2(-) patients, there was no significant correlation between Ki67 and FT3 (r = -0.06, P = 0.67), FT4 (r = -0.15, P = 0.26), or TSH (r = -0.09, P = 0.49). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(-) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling.

BCL2L12: a promising molecular prognostic biomarker in breast cancer.

OBJECTIVES: BCL2-like 12 (BCL2L12) is a new member of the BCL2 gene family that was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC). DESIGN AND METHODS: BCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N=108) and adjacent non-cancerous (N=71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative C(T) (2(-ΔΔC)(T)) method, whereas the association between BCL2L12 expression and clinopathological data, disease-free survival (DFS) and overall survival (OS) were estimated by statistical analysis. RESULTS: BCL2L12 mRNA expression was decreased in malignant samples compared to the histologically normal counterparts (p=0.012). Significant relationships between BCL2L12 expression and TNM stages (p=0.009), metastatic potential (p=0.012), tumor size (p=0.04) and age (p=0.024) were observed. Moreover, Kaplan-Meier and Cox univariate analyses indicated that BCL2L12 expression is associated with longer DFS, whereas multivariate analysis pointed out the independent favorable prognostic value of BCL2L12. CONCLUSIONS: According to our results, BCL2L12 mRNA expression is a favorable prognostic marker of DFS for BC patients, suggesting its possible application as a novel prognostic indicator of this malignancy.

The expression of the CEACAM19 gene, a novel member of the CEA family, is associated with breast cancer progression.

Breast cancer (BC) continues to affect the lives of millions of women worldwide. Several members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) subfamily are involved in tumor progression. Notably, the CEACAM subfamily harbors the already established cancer biomarker CEA, as well as other potential molecular markers. CEACAM19, a recently identified gene belonging to CEACAM subfamily, was discovered and cloned by members of our research group. The present study analyzes, quantitatively, the expression of CEACAM19 and evaluates its clinical relevance in BC. Total RNA was extracted from 143 cancerous and 89 normal adjacent breast tissue specimens. Following reverse transcription, quantitative analysis of CEACAM19 mRNA expression levels was performed via real-time PCR and the comparative Ct (2-∆∆Ct) method. CEACAM19 expression and detailed clinicopathological data were used for extensive biostatistical analyses. CEACAM19 was found to be overexpressed in breast cancer tissue specimens compared to normal tissue counterparts (p=0.013). CEACAM19 mRNA expression status was also associated with clinicopathological features indicative of aggressive behavior and poor prognosis in BC, such as high tumor grade (p=0.031) and high Ki67 proliferative index (p=0.038). A significant negative association was documented between CEACAM19 expression and tumor ER status (p=0.018) as well as patients' menopausal state (p=0.016). Our results suggest that CEACAM19 mRNA expression represents a promising, novel and clinically useful tissue biomarker for breast cancer management.

Effective panitumumab treatment in patients with heavily pre-treated metastatic colorectal cancer: a case series.

In heavily pre-treated patients with metastatic colorectal cancer (mCRC), further chemotherapy has not demonstrated efficacy. Panitumumab is indicated as monotherapy treatment of epidermal growth factor receptor (EGFR)-expressing, Kirsten (K)-RAS wild-type metastatic colorectal cancer after failure of fluoropyrimidine-, oxaliplatin- and irinotecan-containing regimens. However, panitumumab has not been specifically evaluated in patients following failure of a bevacizumab-containing regimen. One female and two male patients with mCRC presented with tumour recurrence in the para-aortic lymph nodes, the liver and the local presacral lymph nodes, respectively. The patients were confirmed to have K-RAS wild-type-expressing tumours. Following the failure of bevacizumab-containing chemotherapy regimens, all three patients received panitumumab monotherapy. Panitumumab was well-tolerated. All the patients responded to panitumumab monotherapy in this late-stage setting. This patient series suggests that panitumumab can improve patient outcomes and may be an alternative treatment option in patients with mCRC who have received prior treatment with bevacizumab plus chemotherapy.

A giant mesenteric lipoblastoma in an 18-month old infant: a case report and review of the literature.

Infantile lipoma (or lipoblastoma) of the mesentery is an extremely rare benign tumor of embryonal fat, with 15 cases reported in the English literature until today and only three of them arise from the ileum mesentery. We report an 18-month old boy presenting with a palpable intraabdominal mass arising from the ileum mesentery. Histopathologic and cytogenetic studies confirmed the diagnosis of mesenteric lipoblastoma (or infantile lipoma). Complete excision of the mass was performed. A follow-up examination consisting of physical examination and an abdominal ultrasound at 30 months postoperatively revealed no recurrence. We also present a review of the English literature regarding the presentation and management of mesenteric lipoblastomas in children.

Increased fluorodeoxyglucose uptake following endovascular abdominal aortic aneurysm repair: a predictor of endoleak?

The main criterion for abdominal aortic aneurysm (AAA) repair is an AAA diameter >/=5.5 cm. However, some AAAs rupture when they are smaller. Size alone may therefore not be a sufficient criterion to determine rupture risk. Fluorodeoxyglucose (FDG) uptake is increased in the presence of inflammation and it was suggested that this may be a better predictor of rupture risk than AAA size. Furthermore, increased FDG uptake following endovascular AAA repair may be an indirect predictor of continuous AAA sac enlargement due to the presence of an endoleak (even if this is not detected by imaging modalities) and/or increased AAA rupture risk. The role of FDG uptake needs to be explored further in the management of AAAs.

Bevacizumab combined with two-weekly paclitaxel as first-line therapy for metastatic breast cancer.

BACKGROUND: Metastatic breast cancer remains a major clinical issue despite progress achieved in recent years. Three randomised trials have demonstrated the benefit of combining bevacizumab with various taxane schedules. Herein, this study sought to investigate an alternative bevacizumab-taxane regimen as first-line treatment for metastatic breast cancer. PATIENTS AND METHODS: Patients with metastatic breast cancer and who received first-line bevacizumab 10 mg/kg with paclitaxel 135 mg/m(2) every 2 weeks were studied. RESULTS: All 43 enrolled patients were evaluable for efficacy and safety. The response rate was 58%; a further 40% achieved stable disease. After a median follow-up of 16 months, disease had progressed in 9 patients (21%). Treatment was well tolerated: grade 4 toxicities were absent; grade 3 adverse events comprised neutropenia (5%; no febrile neutropenia), hypertension (2%) and neuropathy (2%). CONCLUSION: This regimen may provide improved patient acceptability, quality of life and pharmacoeconomic benefits over a weekly paclitaxel schedule, and deserves further evaluation.

Cardiovascular events in chronic dialysis patients: emphasizing the importance of vascular disease prevention.

Cardiovascular disease is the leading cause of death in both chronic kidney disease and peritoneal dialysis/hemodialysis patients. Vascular disease prevention in these patients is therefore important to reduce the incidence of cardiovascular events and the high morbidity and mortality. This Editorial discusses the traditional, (1) smoking, (2) dyslipidemia, (3) body mass index, (4) glycemic control and (5) blood pressure, and non-traditional, (1) anemia, (2) vitamin D/hyperparathyroidism, (3) calcium/phosphorus metabolism and (4) magnesium, risk factors in renal patients. Current evidence does not support routine statin use and antiplatelet medication to dialysis patients. Patient compliance and adherence to proposed measures could be essential to reduce cardiovascular events and mortality rates in this high-risk population.

Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer remains a disease of high mortality and one of the most frustrating, resistant solid neoplasms to treat. The aim of this study was to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with advanced (stage III-IV) pancreatic cancer in terms of overall survival and time to progression of the disease. The secondary aim was to record treatment related toxicities. PATIENTS AND METHODS: Twenty-seven patients with metastatic non-operable pancreatic adenocarcinoma, stage III-IV, consented to receive chemotherapy with gemcitabine and erlotinib. Patients received first-line treatment with gemcitabine (2 g/m(2) via 90 min i.v. infusion every two weeks) and 100 mg erlotinib per os every day, for at least 12 consecutive courses (6 cycles). Treatment was discontinued at disease progression and/or serious toxicity. RESULTS: The objective response rate was 25.9% (95% confidence interval [CI]: 11.1-46.3%) and the stable disease rate was 59.3% (95% CI: 38.8-77.6%). The one-year overall survival was 20%. The median overall survival and time to progression at the time of assessment was 7.5 months (95% CI: 3.6-42 months) and 5.5 months (95% CI: 1.5-10 months), respectively. Overall survival and time to progression were related to response (p<0.001), while time to progression was further related to disease stage (p=0.011). No grade 4 haematological or non-haematological toxicities were observed. CONCLUSION: The biweekly regimen of gemcitabine plus erlotinib has similar toxicity and efficacy to weekly administration, presenting both patients and hospital resource departments with a clearly more convenient therapy alternative.

Emerging indications for statins: a pluripotent family of agents with several potential applications.

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.