Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

In vitro and in vivo evaluations of oxacillin efficiency against mecA-positive oxacillin-susceptible Staphylococcus aureus.

Community-type Staphylococcus aureus strains that are positive for mecA and PBP2a but appear phenotypically susceptible to oxacillin are increasingly reported worldwide. Four S. aureus clinical isolates carrying the mecA gene with oxacillin MICs of <2 microg/ml were tested for oxacillin efficiency by population analyses and experimental thigh infections. These isolates harbored staphylococcal cassette chromosome mec type IV and belonged to two genotypes. Two of the four isolates were found by population analysis to be truly oxacillin susceptible. All four isolates exhibited significant reductions in the numbers of colonies grown after dicloxacillin treatment of experimental thigh infections, as also did a mecA-negative S. aureus control strain. These observations indicate that some of the phenotypically oxacillin susceptible mecA-positive Staphylococcus aureus isolates may be at least partially responsive to oxacillin.

Relationship between Chlamydia-Ureaplasma-Mycoplasma Genital Detection with Semen Concentration and Motility among Greek Men.

One hundred and seventy two men at the State of Thessaly, Greece, inquiring semen analysis were enrolled in the study in order to investigate the incidence of Chlamydia, Ureaplasma and Mycoplasma (C-U-M) genera in respect to total sperm number (TSN), progressive motility (grades a and b) and total motility (grades a, b and c). Putative relation of C-U-M acquirement with sexual behavior was also investigated. Incidence of C-U-M among non-oligozoospermic and oligozoospermic men was similar. Νο correlation of C-U-M carriage to either oligozoospermia or asthenozoospermia was found. The tested semen parameters were negatively correlated to the age of sexual intercourse initiation and positively correlated to the number of sex partners. Early age of sexual intercourse initiation or high number of sexual partners was not statistical significantly correlated to C-U-M acquirement. Overall, TSN and motility (either progressive or total) were not influenced by the presence of C-U-M genera in a sample of Greek population undergoing semen evaluation. To distinguish the role of C-U-M in male infertility and clarify the so far controversial scarce literature, large control case studies are needed using nucleic acid amplification techniques to detect these pathogens.

Prognostic factors for long term survival in patients with advanced non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. METHODS: We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. RESULTS: The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally, large cell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. CONCLUSIONS: This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors such as weight loss, radio lung and doublet platinum-based. On the other hand, it excludes significant factors such as gender, age and smoking.

Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1.

BACKGROUND: Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets. METHODS: Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data. RESULTS: VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1. CONCLUSION: Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.

Pharmacokinetics of imatinib mesylate in end stage renal disease. A case study.

AIM: To evaluate the pharmacokinetics of imatinib mesylate (Glivec) and its main metabolite (CGP74588) in a patient with end stage renal disease on hemodialysis and compare it with published data from subjects with normal renal function. PATIENTS AND METHODS: Serial blood samples were collected over a 2-weeks period in a patient who was receiving daily 400 mg oral imatinib mesylate for the treatment of a gastrointestinal stromal tumor metastatic to the liver while on hemodialysis. Plasma levels of imatinib and CGP74588 were determined by a liquid chromatography-tandem mass spectrometry assay. RESULTS: The pharmacokinetic values for imatinib and CGP74588, respectively, were: maximum concentration (3,340 and 781 ng/ml), time to maximum concentration (2 h), half-life (18.2 and 34.0 h), area under the curve (53.9 and 14.8 microg.h/ml), and trough concentration (1,540 and 508 ng/ml) for at least 24 h. All obtained values fell within the range of values of imatinib and its metabolite obtained in patients with normal renal function. Dialysis courses were not found to intervene with plasma kinetics of the study drug. CONCLUSIONS: Our results indicate that the pharmacokinetics of imatinib and its metabolite CGP74588 do not change in patients with end stage renal disease on hemodialysis. Thus, the standard dose of imatinib can be safely administered to patients on hemodialysis, and probably with renal failure, at any stage.

Oxaliplatin (Eloxatin) plus irinotecan combination chemotherapy found effective in refractory metastatic insular thyroid carcinoma.

Therapeutic options for metastatic insular thyroid carcinoma (ITC) are very limited. We present the case of a 39-year-old woman with refractory metastatic ITC who responded to oxaliplatin plus irinotecan chemotherapy. She was initially diagnosed with a locally advanced and metastatic to lung ITC and underwent near-total thyroidectomy. After surgery she was treated and failed to respond first to radioiodine and subsequently to liposomal doxorubicin plus paclitaxel combination chemotherapy and was offered palliative external irradiation for metastases to bone and the brain. Eleven months postdiagnosis the patient became severely dyspnoic as a result of progression of lung metastases and elected to be treated with oxaliplatin plus irinotecan as a secondline chemotherapy. She experienced relief of her dyspnea shortly after treatment initiation and an objective response of her lung metastases was documented after the third course of treatment. Treatment continued for six cycles and tumor remission lasted for 5 months. Toxicity was mild. Confirmatory testing of oxaliplatin-irinotecan combination in case series or single cases of metastatic ITC is warranted.

Barotrauma and pneumothorax.

Barotrauma is physical damage to body tissues caused by a difference in pressure between a gas space inside, or in contact with the body, and the surrounding fluid. This situation typically occurs when the organism is exposed to a significant change in ambient pressure, such as when a scuba diver, a free-diver or an airplane passenger ascends or descends, or during uncontrolled decompression of a pressure vessel, but it can also happen by a shock wave. Whales and dolphins are also vulnerable to barotrauma if exposed to rapid and excessive changes in diving pressures. In the current review we will focus on barotraumas from definition to treatment.

Pneumothorax: an up to date "introduction".

The pneumothorax is an abnormal collection of air or gas in the pleural space that separates the lung from the chest wall. Like pleural effusion where a large abnormal concentration of fluid (>100 mL) is liquid buildup in that space, pneumothorax may interfere with normal breathing. A medical term that it is used is the collapsed lung, although that term may also refer to atelectasis. There are two major types of pneumothorax; there is one that occurs without an apparent cause and in the absence of significant lung disease, while the so called; "secondary" pneumothorax occurs in the presence of existing lung pathology. In a minority of cases, the amount of air in the chest increases markedly when a one-way valve is formed by an area of damaged tissue, leading to a third type of pneumothorax, called "tensioned".

Heimlich valve and pneumothorax.

The Heimlich valve is a small one-way valve used for chest drainage that empties into a flexible collection device and prevents return of gases or fluids into the pleural space. The Heimlich valve is less than 13 cm (5 inches) long and facilitates patient ambulation. Currently there are several systems in the market. It can be used in many patients instead of a traditional water seal drainage system. The Heimlich chest drainage valve was developed so that the process of draining the pleural cavity could be accomplished in a safe, relatively simple, and efficient manner. This valve system has replaced the cumbersome underwater drainage bottle system. Moreover; the Heimlich valve system connects to chest tubing and allows fluid and air to pass in one direction only. This system functions in any position, and it does not ever need to be clamped, a regulated suction can be attached to it if necessary. The valve drains into a plastic bag that can be held at any level, allowing the patient undergoing chest drainage to be ambulatory simply by carrying the bag. In the current mini review we will present the Heimlich valve system and method of insertion.

Minimally invasive procedures.

Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small "ports" from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry-meaning only one small incision, like the "uniport" video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional "open" surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

Pneumothorax from diagnosis to treatment, hands on course: Part II.

Pneumothorax is a situation where air is inserted in the pleural space that separates the lung from the chest wall. Pneumothorax can be primary or secondary. There is also a third type called; tensioned. Based on the concentration of air and type of pneumothorax the proper treatment has to be selected. There are cases where the concentration is minimal and observation is enough and more severe cases where surgery is required. Currently there are many techniques used for the biopsy of lung lesions. The bronchoscope (forceps, fine needle aspiration), fine needle aspiration under computed tomography scan and endobronchial ultrasound (EBUS) are commonly used. However, all these techniques have in common a possible side effect; pneumothorax. In our current issue we will focus on the different minimally invasive techniques of pneumothorax management. Moreover, a presentation will be made for several systems that are being used for air or fluid aspiration.

Pacemaker insertion.

A pacemaker (PM) (or artificial PM, so as not to be confused with the heart's natural PM) is a medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The primary purpose of this device is to maintain an adequate heart rate, either because the heart's natural PM is not fast enough, or there is a block in the heart's electrical conduction system. Modern PMs are externally programmable and allow the cardiologist to select the optimum pacing modes for individual patients. Some combine a PM and defibrillator in a single implantable device. PMs can be temporary or permanent. Temporary PMs are used to treat short-term heart problems, such as a slow heartbeat that's caused by a heart attack, heart surgery, or an overdose of medicine. Permanent PMs are used to control long-term heart rhythm problems. A PM can relieve some arrhythmia symptoms, such as fatigue and fainting. A PM also can help a person who has abnormal HRs resume a more active lifestyle. In the current mini review we will focus on the insertion of a PM and the possible pneumothorax that can be caused.

Chest drainage systems in use.

A chest tube is a flexible plastic tube that is inserted through the chest wall and into the pleural space or mediastinum. It is used to remove air in the case of pneumothorax or fluid such as in the case of pleural effusion, blood, chyle, or pus when empyema occurs from the intrathoracic space. It is also known as a Bülau drain or an intercostal catheter. Insertion of chest tubes is widely performed by radiologists, pulmonary physicians and thoracic surgeons. Large catheters or small catheters are used based on each situation that the medical doctor encounters. In the current review we will focus on the chest drain systems that are in use.

Use of proteins as biomarkers and their role in carcinogenesis.

SUMMARY: Improved diagnostic methods and medical therapies are necessary for early detection and treatment and an improved prognosis. It is thus vital to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. It is essential to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. The purpose of this review is twofold. Firstly, it is to evaluate recent data about which proteins can be utilized as biomarkers in carcinogenesis. The proteins reviewed include: CPTP, IL-6, CCN, and S100. Secondly, it is to evaluate the contribution of dietary proteins in cancer activity. Specifically, how whey protein, soy proteins and lectin, a phytochemical could be useful in cancer prevention and treatment. RECENT FINDINGS: Whey protein, present in dairy products, is an excellent source of the sulphur amino acid cysteine, the rate limiting substrate in glutathione synthesis. Notably, this protein survives digestion and has been shown to have anti-carcinogenic properties in animal studies. Lectins are phytochemicals present in plant foods, and have active components which alters cancer initiation, promotion and progression. Lectins have been characterized as a useful tool in biochemistry, cell biology, immunology and in diagnostic and therapeutic purposes in cancer research. Soy proteins contain various compounds, including isoflavones, protease inhibitors and protein kinase inhibitors, which have been proven effective in tumor growth inhibition. They have therefore, been greatly emphasized in cancer prevention and treatment. It has been proved that soy food consumption was associated with decreased risk of death and recurrence of breast cancer. CPTP is a recently discovered protein whose main role is to transport C1P, a pro-inflammatory molecule. The discovery of CPTP may shine a light on the mechanism of inflammatory diseases, and hopefully offer a potential target for therapeutic purposes in cancer research. Interleukin-6 is a multifunctional cytokine that affects the activity of cancer cells. It is involved in tumor growth, and elevated levels is associated with an increased risk of cancer. S100B is a well-established biomarker for malignant melanoma, and useful in assessing tumor load, stage and prognosis for patients with this disease. Other members of this family of proteins include S100A4, which has been associated with several malignancies and S100A2, which has been found to be decreased in some cancers. CCN are a group of regulatory proteins, located in the extracellular matrix (maricellular). They are involved in cellular adhesion, mitogenesis, chemotaxis, cell survival, and wound healing. CCN proteins are also able to modulate the signals of several proteins, which may also influence skeletal development and angiogenesis. Many of the functions of these proteins are thus also related to tumor growth. Furthermore, CCN interacts with estrogen in the development of cancer, and is implicated in some breast and ovarian cancers.

Enhancement of Intratumoral Chemotherapy with Cisplatin with or without Microwave Ablation and Lipiodol. Future Concept for Local Treatment in Lung Cancer.

Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (10(6)) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm(3) the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect.

Could Somatostatin Enhance the Outcomes of Chemotherapeutic Treatment in SCLC?

PURPOSE: Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Furthermore, somatostatin (SST) receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and are overexpressed in tumors. Since, human small-cell lung cancer overexpresses somatostatin receptors (STTR), they could be legitimate targets for treating SCLC.The aim of this study was the evaluation of cytotoxicity of somatostatin in combination with several anticancer drugs in HTB-175 cell line (Small Cell Lung Cancer Cell line that expresses neuron specific enolase). METHODS: Docetaxel, Paclitaxel, Carboplatin, Cisplatin, Etoposide, Gemzar, Navelbine, Fluorouracil, Farmorubicin are the chemotherapeutic drugs that we used for the combination before and after adding somatostatin in SCLC cell culture. HTB-175 cell line was purchased from ATCC LGC Standards.At indicated time-point, 48h after the combination, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. RESULTS: Flow cytometry showed that Docetaxel, Paclitaxel, Gemzar and Cisplatin induced apoptosis more when they were added before somatostatin, whereas etoposide induced apoptosis more after somatostatin treatment. Navelbine alone or in combination with somatostatin showed no differences in apoptosis. Farmorubicin showed equal toxicity in all combinations. Fluorouracil and Carboplatin induced apoptosis more when added alone in HTB-175 cell line. However, increased apoptosis was also observed when Carboplatin was administered before somatostatin in higher concentrations. CONCLUSION: Our results indicated that depending on the drug, somatostatin treatment before or after chemotherapeutic drugs increased apoptosis in small cell lung cancer cells. We suggest that long acting somatostatin analogues could be used as additive and maintenance therapy in combination to antineoplastic agents in SCLC patients.

Thoracocentesis: from bench to bed.

Lung cancer can be diagnosed with minimal interventional procedures such as: bronchoscopy, endobronchial ultrasound (EBUS), fine needle aspiration under CT guidance and esophageal ultrasound. In our current editorial we will provide a definition and current up to date information regarding fine needle aspiration under CT guidance. We will focus on pneumothorax and treatment methods.

Pleura space anatomy.

The pleural cavity is the potential space between the two pleurae (visceral and parietal) of the lungs. The pleurae are serous membranes which fold back onto themselves to form a two-layered membranous structure. The thin space between the two pleural layers is known as the pleural cavity and normally contains a small amount of pleural fluid. There are two layers; the outer pleura (parietal pleura) is attached to the chest wall and the inner pleura (visceral pleura) covers the lungs and adjoining structures, via blood vessels, bronchi and nerves. The parietal pleurae are highly sensitive to pain, while the visceral pleura are not, due to its lack of sensory innervation. In the current review we will present the anatomy of the pleural space.