Neo-adjuvant chemo/immunotherapy in the treatment of stage III (N2) non-small cell lung cancer: a phase I/II pilot study.

In a previous randomized study, we showed that adjuvant immunotherapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 (rIL-2) significantly improved survival in resected N2-non small cell lung cancer (NSCLC) patients. The present study assesses feasibility, safety and potential efficacy of combined neo-adjuvant chemotherapy and immunotherapy with peripheral blood mononuclear cells (PBMC) and rIL-2 in resectable N2-NSCLC patients. Eighty-two consecutive N2-NSCLC patients underwent neo-adjuvant chemotherapy with cisplatin and gemcitabine. Out of the 82 patients, 23 were also subjected to leukapheresis prior to neo-adjuvant chemotherapy while the remaining 59 did not. Collected PBMC were analyzed for viability and phenotype and then stored frozen in liquid nitrogen. Thawed PBMC were infused intravenously, 5 days before surgery. After the infusion, rIL-2 was administered subcutaneously until surgery. Only patients with a partial or complete response to neoadjuvant chemotherapy underwent surgery: 13 patients in the experimental immunotherapy group (A) and 32 in the reference group (B). The two groups were homogeneous for all major prognostic factors. Median leukapheresis yield was 10 billion PBMC, (range 3-24 billions). Two to six billion PBMC were infused. The phenotypic analysis showed that similar proportions of CD4 and CD8 cells were present in leukapheresis products, and thawed PBMC, as well as in T lymphocytes isolated from the removed tumours. No severe adverse effects were observed following immunotherapy. No significant differences in overall survival (OS) and event-free survival (EFS) were seen between the two groups. However, the 5-year OS in group A was almost twice as much compared to group B (59 percent vs 32 percent). After adjustment for major prognostic factors, a statistically significant 66 percent reduction in the hazard of death was seen in patients receiving immunotherapy. The OS benefit was more evident in patients with adenocarcinoma than in those with squamous cell carcinoma. This study supports the favorable toxicity profile and potential efficacy of combining neo-adjuvant chemotherapy and immunotherapy with PBMC and rIL-2 in the treatment of N2-NSCLC patients.

Postoperative bleeding after coronary revascularization. Comparison between tranexamic acid and epsilon-aminocaproic acid.

BACKGROUND: Microvascular bleeding after Cardiopulmonary bypass (CPB) is mainly due to consumption of clotting factors, platelets damage, and hyperfibrinolysis. Aprotinin, the only antifibrinolytic drug effective in preserving platelets, is no longer available; an alternative regimen based on pure antifibrinolytic drugs has been proposed, since hyperfibrinolysis is known to contribute both to clot lysis and platelet dysfunction. In this study the efficacy of two antifibrinolytic drugs, Tranexamic acid (TA) and epsilon-aminocaproic acid (EACA), was tested in patients undergoing cardiopulmonary bypass (CPB), for primary myocardial revascularization. METHODS: Forty-eight consecutive patients were randomized to receive prophylactically equipotent doses of EACA (group A) or TA (Group B). Platelet count, prothrombin time, fibrin digestion products, blood loss and transfusion requirements recorded after 6 and 24 hours from the end of surgery were compared. RESULTS: The two groups were comparable for length of CPB and numbers of grafts; no significant difference was observed in the coagulation parameters considered. Blood losses were less in group B (TA) than in group A (EACA), both at 6 and 24 hours after surgery; homologous blood transfused was also less in group B, but no difference was statistically significant. No adverse effect was observed. CONCLUSIONS: In coronary patients, TA and EACA exhibit the same effects on blood loss and requirements after CPB; either drug can be safely used in cardiac surgery.

[Septic pancreatic necrosis in intensive care]. / La necrosi pancreatica infetta in terapia intensiva.

BACKGROUND: Infected necrotizing pancreatitis is the most fulminant variety of this disease. The reported mortality is up to 50%. The haemodynamic features of cardiovascular instability has many similarities to sepsis syndrome, septic shock and multiple organ dysfunction syndrome (MODS). The purpose of this study is to review personal experience in the ICU (hospital of Varese) to determine etiology, treatment and complications. METHODS: Twenty patients treated since 1988 with infected necrotizing pancreatitis required surgical treatment and mechanical ventilation. RESULTS: The mortality rate was 60% and ICU-stay was 26.5 +/- 12.3 days, the median age was 54 +/- 13. Ranson's criteria at admission to the ICU was 6.6 +/- 1.2, Glasgow point was 4.6 +/- 1.2 (5.5 +/- 0.87 died, 3.2 +/- 0.8 survived p < 0.01), Baltazar score 6.2 +/- 2.1 (7.4 +/- 2.1 died, 5.5 +/- 0.9 survived p < 0.05) and SAPS II score 43.4 +/- 12.1 (50.1 +/- 7.8 died, 34 +/- 5.5 survived p < 0.01). The etiology was: gallstones (45%), alcoholism (15%), ERCP (15%) and idiopathic in 25%. Serum pancreatic amylase was 342 +/- 113.9 U/l (550 +/- 100 died, 155 +/- 60 survived p < 0.01), lipase was 334 +/- 176 U/l and transaminases GOT was 123 +/- 46 u/l (156 +/- 90 died, 29 +/- 7 survived p < 0.05). High initial amylase and GOT levels were frequently found in non survived patients. MODS occurred in 17 cases (85%), ARDS in 2 patients (10%), abdominal bleeding in 6 (30%) and septic syndrome in 8 (40%). CONCLUSIONS: It is thus possible that a target-oriented approach including fluid replacement, rapid correction of intestinal underperfusion, inotropic and antibiotic therapy, supply of specific nutrients and other therapeutic strategies as open laparostomy must be employed to prevent MODS or septic syndrome in pancreatic infection after acute necrotizing pancreatitis.