George Lazaridis

Liver metastases from cancer of unknown primary (CUPL): A retrospective analysis of presentation, management and prognosis in 49 patients and systematic review of the literature

AIM Patients with liver metastases from cancer of unknown primary (CUPL) have a dismal prognosis. We retrospectively analysed their management and outcome and performed a systematic review of CUPL series published in the literature. PATIENTS AND METHODS Electronic data from 49 CUPL patients referred to Hellenic Cooperative Oncology Group (HeCOG) centers were retrospectively studied for characteristics of clinical presentation, diagnostic workup, management, outcome and prognostic factors. A systematic literature review was undertaken in PubMed and EmBase databases. RESULTS All our patients (males: 31, females: 18; median age: 65) underwent a computed tomography scan (CT) of the abdomen, 71% a thoracic CT, 53% gastroscopy and 47% colonoscopy. The commonest histologic subtypes encountered were adenocarcinoma (N=34) or undifferentiated carcinoma (N=12). The liver was the only metastatic site in 38% of patients, while it was accompanied with other metastatic sites in 62% (the commonest: lung, bone and lymph nodes). Forty-seven patients received first-line chemotherapy (42 platinum based) and 16 second-line. An objective response was observed in six patients (12%), median survival being 10 months (95% CI, 7-13). In univariate analysis, good performance status and normal baseline serum CEA levels were correlated with superior survival, while in multivariate analysis only age<55 (HR 0.16, p=0.02) and the absence of extrahepatic disease (HR 0.21, p=0.007) predicted for a better outcome. Published data from four relevant series (total patients=662) parallel our findings. CONCLUSIONS Patients with liver metastases from CUP are resistant to conventional types of treatment and carry a poor prognosis. Understanding the molecular biology of CUP is essential for the development of new, targeted effective therapies.

Interleukin-7 and Interleukin-15 for Cancer

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.

Pneumothorax in Cystic Fibrosis

Pneumothorax is recognized as a common and life-threatening complication in cystic fibrosis (CF) patients, especially in those who are infected with P. aeruginosa, B. cepacia or Aspergillus, need enteral feeding, are diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA), developed massive hemoptysis, and their respiratory function is seriously compromised. Structural impairment and altered airflow dynamics in the lungs of CF patients are considered as the main predisposing factors, but also inhaled medications and non-invasive positive pressure ventilation (NIPPV) could increase the risk of pneumothorax. Clinical presentation could range from dramatic to very mild. Management of spontaneous pneumothorax occurring to patients with CF is essentially similar to that for non-CF patients. Therapeutic options include intercostal tube drainage, video-assisted thoracoscopic surgery (VATS), and medical or surgical pleurodesis. Pneumothorax increases both short- and long-term morbidity and mortality in CF patients and causes significant deterioration of their quality of life.

Postoperative pain management

Postoperative pain is a very important issue for several patients. Indifferent of the surgery type or method, pain management is very necessary. The relief from suffering leads to early mobilization, less hospital stay, reduced hospital costs, and increased patient satisfaction. An individual approach should be applied for pain control, rather than a fix dose or drugs. Additionally, medical, psychological, and physical condition, age, level of fear or anxiety, surgical procedure, personal preference, and response to agents given should be taken into account. The major goal in the management of postoperative pain is minimizing the dose of medications to lessen side effects while still providing adequate analgesia. Again a multidisciplinary team approach should be pursued planning and formulating a plan for pain relief, particularly in complicated patients, such as those who have medical comorbidities. These patients might appear increase for analgesia-related complications or side effects.

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 TKIs 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.

Physiology of the pleural space

The pleural cavity is created between the 4(th) and 7(th) week of embryologic development. These embryonic components of visceral and parietal pleurae develop different anatomic characteristics with regard to vascular, lymphatic, and nervous supply. There are two layers: a superficial mesothelial cell layer facing the pleural space and an underlying connective tissue layer. The pleura might present inflammatory response and maintenance of the pleural fluid is observed. The latter function is especially important in the mechanical coupling of the lung and chest wall. Fluid is filtered into the pleural space according to the net hydrostatic oncotic pressure gradient. It flows downward along a vertical pressure gradient, presumably determined by hydrostatic pressure and resistance to viscous flow. There also may be a net movement of fluid from the costal pleura to the mediastinal and interlobar regions. In these areas, pleural fluid is resorbed primarily through lymphatic stomata on the parietal pleural surface. In the current review we will present the physiology of the pleural space in a step by step manner.

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.

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.

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.

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.