Results of surgical treatment of primary lung cancer with synchronous brain metastases.

INTRODUCTION: The surgical treatment of non-small cell lung cancer (NSCLC) with synchronous brain matastases is more effective than other therapeutic options, but this management is still controversial. THE AIM OF THE STUDY: The aim of the study was to evaluate the survival of patients after pulmonary resection NSCLC preceded by resection of brain metastases. MATERIAL AND METHODS: From 2007 to 2012, 645 patients underwent pulmonary resection for NSCLC at our department. In 25 of them (3.87%) thoracic surgery was preceded by resection of a single brain metastasis of NSCLC and a PET CT scan. No signs of nodal involvement or distant metastases were detected. RESULTS: The group consisted of 18 men (72%) and 7 women (28%). Average age was 57.62 years (46-70). In all cases, whole brain radiotherapy (5 × 4 Gy) was performed. The average interval between excision of brain metastasis and lung resection was 31.4 days (27-41). Pneumonectomy was performed in 1, lobectomy/bilobectomy in 17 and wedge resection in 7 cases. Pathological stage N0 was diagnosed in 17, N1 in 5 and N2 in 3 patients. Average survival was 18.68 months (4-74). Survival at 1, 2 and 5 years was 64%, 28% and 28% respectively. Average disease-free survival was 17.52 months. Histological type (p = 0.57) and G (p = 0.82) have no influence on survival. All the patients with hilar lymph node involvement died within 26 months and with mediastinal one within 12 months. CONCLUSIONS: Surgical treatment of patients with NSCLC with synchronous brain metastases may prove beneficial in selected patients after excluding other distant metastases and lymph node involvement.

Cost-effectiveness analysis of lung cancer screening with low-dose computerised tomography of the chest in Poland.

AIM OF THE STUDY: To determine the cost-effectiveness of lung cancer (LC) screening with low-dose computerised tomography of the chest, as compared to an approach without screening, reimbursed today by the National Health Fund (NHF) in Poland. MATERIAL AND METHODS: In order to analyse the current costs of diagnostic and therapeutic procedures of a model LC patient treated today, a model group consisting of 199 consecutive patients diagnosed and treated in the Oncology Centre in Bydgoszcz, Poland from January 2007 to April 2010 was used. The number and type of performed procedures in this group was obtained from the Polish Register of Neoplasms and the NHF. Only direct medical costs were analysed. To calculate the total costs of screening, diagnostics, and treatment of the hypothetical LC patient who would have cancer diagnosed with screening CT, data from the literature and costs calculated for the model group were used. Prices of procedures were obtained from the price list of the NHF on 30 April 2010 and did not change from that time until June 2014. One-way sensitivity analysis was performed. RESULTS: The average cost per LC patient, diagnosed and treated without screening, is 5567.50 EUR, and median LC-specific survival is one year. In the hypothetical LC patient with cancer diagnosed by screening, the average cost is 13689.35 EUR per LC patient, with a median LC-specific survival of at least seven years. A calculated incremental cost-effectiveness ratio (ICER) is 1353.64 EUR/year of life gained. CONCLUSIONS: Lung cancer screening with low-dose CT would be highly cost-effective in Poland.

The effect of glycogen phosphorolysis on basal glutaminergic transmission.

Astrocytic glycogen metabolism sustains neuronal activity but its impact on basal glutamatergic synaptic transmission is not clear. To address this issue, we have compared the effect of glycogen breakdown inhibition on miniature excitatory postsynaptic currents (mEPSCs) in rat hippocampal pure neuronal culture (PNC) and in astrocyte-neuronal co-cultures (ANCC). Amplitudes of mEPSC in ANCC were nearly twice as large as in PNC with no difference in current kinetics. Inhibition of glycogen phosphorylase reduced mEPSC amplitude by roughly 40% in ANCC being ineffective in PNC. Altogether, these data indicate that astrocyte-neuronal interaction enhances basal mEPSCs in ANCC mainly due to astrocytic glycogen metabolism.

Pneumonectomy due to lung cancer results in a more pronounced activation of coagulation system than lobectomy.

UNLABELLED: Surgical treatment of lung cancer is associated with an elevated risk of thrombo-embolic complications. The question is whether the extent of pulmonary resection influences the concentration of serum coagulation system proteins. OBJECTIVE: This study aims to compare the blood coagulation activation parameters among patients undergoing pneumonectomy and lobectomy due to primary lung cancer. METHODS: A prospective study was carried out in 40 patients. Of whom, 30 underwent lobectomy and 10 treated with pneumonectomy. Serum concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), tissue factor pathway inhibitor-activated factor X complex (TFPI/Xa), thrombin-antithrombin complex (TAT), L-selectin, E-selectin and P-selectin were measured on the first and seventh postoperative days. RESULTS: On the first postoperative day, the results of selected proteins concentrations were similar in both groups. However, on the seventh postoperative day, significantly higher concentrations of TF, TAT complex and E-selectin were found in patients who underwent pneumonectomy (median values: TF: 182.4 pg ml(-1) vs 116.6 pg ml(-1), P=0.031; TAT: 6.2 mg ml(-1) vs 3.9 mg ml(-1), P=0.048; E-selectin 40.24 ng ml(-1) vs 26.54 ng ml(-1), P=0.049). CONCLUSIONS: Pneumonectomy was associated with significantly higher activation of coagulation system on the seventh postoperative day than lobectomy. TAT complex, TF and E-selectin are promising markers of extensive postoperative activation of coagulation and efficacy of antithrombotic prophylaxis.

Influence of clavata3-2 mutation on early flower development in Arabidopsis thaliana: quantitative analysis of changing geometry.

Early development of the flower primordium has been studied in Arabidopsis thaliana clavata3-2 (clv3-2) plants with the aid of sequential in vivo replicas and longitudinal microtome sections. Sequential replicas show that, although there is no regular phyllotaxis in the clv3-2 inflorescence shoot apex, the sites of new primordium formation are, to a large extent, predictable. The primordium always appears in a wedge-like region of the meristem periphery flanked by two older primordia. In general, stages of primordium development in clv3-2 are similar to the wild type, but quantitative geometry analysis shows that the clv3-2 primordium shape is affected even before the CLAVATA/WUSCHEL regulatory network would start to operate in the wild-type primordium. The shape of the youngest primordium in the mutant is more variable than in the wild type. In particular, the shape of the adaxial primordium boundary varies and seems to be related to the shape of the space available for the given primordium formation, suggesting that physical constraints play a significant role in primordium shape determination. The role of physical constraints is also manifested in that the shape of the primordium in the later stages, as well as the number and position of sepals, are adjusted to the available space. Longitudinal sections of clv3-2 apices show that the shape of surface cells of the meristem and young primordium is different from the wild type. Moreover, there is only one tunica layer in both the meristem and in the primordium until it becomes a bulge that is distinctly separated from the meristem. Starting from this stage, the anticlinal divisions predominate in subprotodermal cells, suggesting that the distribution of periclinal and anticlinal cell divisions in the early development of the flower primordium is not directly affected by the clv3-2 mutation.

Systematic mediastinal lymphadenectomy does not increase postoperative immune response after major lung resections.

OBJECTIVE: To assess the influence of mediastinal lymphadenectomy on postoperative concentration of interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1 ra) in serum, sputum, and pleural fluid, in patients operated upon due to lung cancer and benign pulmonary diseases. METHODS: Thirty-three patients undergoing uncomplicated resections, including 23 with lung cancer and 10 with benign diseases, were analyzed. In patients with right lung cancer we performed a systematic lymphadenectomy, while in patients with left lung cancer systematic sampling was performed. Serum IL-6 and IL-1 ra concentration was measured before and after surgery, and on postoperative days 1, 3, and 7, as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1, by ELISA test. RESULTS: In 23 patients with cancer, 19.0+/-11.43 mediastinal lymph nodes were removed (in 11 patients with right lung cancer 27.6+/-7.6 and in 12 patients with left lung cancer 11.1+/-8.1). No differences were found in serum and sputum concentration of IL-6 and IL-1 ra between patients after right and left thoracotomy due to cancer and between patients with cancer and patients with benign diseases. Patients with cancer had a lower concentration of IL-1 ra in pleural fluid (median 16950, range 16050-45470.05 pg/ml) than patients with benign diseases (76665.6 pg/ml (range 53618-89617.9); p=0.0008). In 23 cancer patients a negative correlation between concentration of cytokines in pleural fluid and a number of mediastinal lymph nodes resected was observed (Spearman correlation coefficient for IL-6: r=-0.44, p=0.04; for IL-1 ra: r=-0.57, p=0.01). Such correlation was not observed for a number of positive N2 lymph nodes. CONCLUSIONS: Systematic lymphadenectomy added to major lung resection does not increase postoperative humoral immune response in uncomplicated cases, as measured by levels of IL-6 and IL-1 ra in serum, pleural fluid, and sputum.

Interleukin 6 and interleukin 1 receptor antagonist as early markers of complications after lung cancer surgery.

OBJECTIVE: To assess changes of interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1ra) in serum, sputum, and drained pleural fluid of patients operated on due to lung cancer. METHODS: Twenty-seven patients treated with lobectomy or pneumonectomy, including 14 with complications and 13 without complications, were analyzed. Serum IL-6 and IL-1ra concentration was measured before, at the end of surgery, and on postoperative day 1, 3, and 7, by ELISA test. Additionally, concentration of IL-6 and IL-1ra was measured in sputum at the end of surgery and in pleural fluid on postoperative day 1. RESULTS: In the entire group serum concentrations of IL-6 and IL-1ra were significantly elevated after surgery, in comparison with preoperative values. Serum IL-6 concentration was higher in patients with complications only on day 7 (median 59.0 (range: 41.25-76.65) pg/ml vs 21.5 (9.87-35.0) pg/ml; p=0.012). Patients with complications had higher concentration of IL-6 in pleural fluid (91312 (51812-94872) pg/ml vs 2006 (1926-2108) pg/ml; p=0.00008). Serum IL-1ra concentration was higher in patients with complications on day 1 (1832.4 (1144.7-2362.2) pg/ml vs 1088.4 (817.5-1312.5) pg/ml; p=0.01). Concentration of IL-1ra in drained fluid was higher in patients with complications (68128.8 (48104-108564) pg/ml vs 16470 (15930-16875) pg/ml; p=0.0003). On day 1 after surgery a significant correlation between serum and pleural fluid concentration for IL-6 as well as for IL-1ra were observed (Spearman test for IL-6: r=0.47; p=0.02; for IL-1ra: r=0.48; p=0.02). CONCLUSIONS: Elevated concentrations of IL-6 and IL-1ra in pleural fluid on postoperative day 1 are promising early markers of postoperative complications. Elevated concentrations of IL-6 and IL-1ra in serum are good early markers of severity of surgical injury and may reflect development of postoperative complications.

[Changes in humoral and cellular immunity in patients operated on due to esophageal cancer]. / Zaburzenia odpornosci humoralnej i komórkowej u chorych operowanych z powodu raka przelyku.

The aim of this paper was to analyze changes in immune system in patients operated on due to esophageal carcinoma. A special interest was paid to selected parameters of humoral and cellular immunity in peripheral blood as well as local changes in the immune system. A practical aspect of changes in immune system in the diagnosis of postoperative complications was taken into account. Results of the analyzed studies show that in patients with esophageal carcinoma occur significant changes in humoral and cellular immunity which increase the risk of postoperative complications. A high rate of postoperative complications in patients after esophagectomy due to esophageal carcinoma is caused predominantly by preoperative immunocompromised and malnutrition. The extent of operative stress as well as increased activity of immune cells in the early postoperative period, are other factors which increase the risk of severe, especially respiratory complications. It seems that early diagnosis and correction of compromised immunity (for example with nutrition) can significantly improve the results of the treatment.

Surgical treatment of small cell lung cancer.

Chemoradiotherapy remains a gold standard in the treatment of limited-disease small cell lung cancer. Currently, three indications for the surgical treatment of very limited disease (stage I, II, or highly selected IIIa) small cell lung cancer can be identified: (1) primary surgery in peripheral clinical N0 lesions followed by adjuvant chemotherapy or chemoradiotherapy; (2) primary chemotherapy or chemoradiotherapy followed by surgery +/- radiotherapy in patients with a good response to initial treatment; and (3) salvage operations in patients who recur or persist at the primary site but still have resectable disease. The value of these approaches has been assessed in retrospective analyses and prospective nonrandomized trials. A large prospective randomized trial failed to prove any added value for surgery in the multidisciplinary treatment of limited-disease small cell lung cancer, but very few very-limited-disease patients were included.