Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts.

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.

Does postoperative mechanical ventilation predispose to bronchopleural fistula formation in patients undergoing pneumonectomy?

A best evidence topic was written according to a structured protocol. The question addressed was whether postoperative mechanical ventilation has any effect on the incidence of development of bronchopleural fistulas (BPFs) in patients undergoing pneumonectomy. A total of 40 papers were identified using the reported search, of which 8, all retrospective, represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. Of the eight identified papers, six of them reported a statistically significant relationship between postoperative mechanical ventilation and the occurrence of bronchopleural fistula in patients undergoing pneumonectomy (P = 0.027-0.0001). In two of these studies, postoperative mechanical ventilation was identified during multivariate analysis as an independent predictor for the development of BPF after pneumonectomy (odds ratio 15.57 and 33.1), indicating a causal relationship whereas, in the other four reports, statistical significance was the result of univariate analysis. In another study, the difference between these two groups approached but did not reach statistical significance (P = 0.057). Finally, one study reported no association between postoperative mechanical ventilation and the development of post-pneumonectomy BPF (0.16). Apart from mechanical ventilation, pre-existing pleuropulmonary infection was reported by one study as an independent predictor for the development of post-pneumonectomy BPF whereas, in two other studies, its impact approached but did not reach statistical significance. Another study did not find any association between preoperative infection and postoperative BPF occurrence. In conclusion, the majority of the reported studies report a significant relationship between mechanical ventilation after pneumonectomy and the occurrence of BPF. Every effort should be made to achieve extubation at the earliest possible time to withdraw the effects of the continuous barotrauma on the bronchial stump, although its impact cannot be quantified. Performing pneumonectomy in the presence of infectious conditions may contribute to the development of postoperative BPF, but its role is less well defined.

Pleural lavage cytology: where do we stand?

Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non-small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space.

The role of intercostal cryoanalgesia in post-thoracotomy analgesia.

OBJECTIVES: Patients undergoing thoracotomy were studied to compare the effects of cryoanalgesia, combined with intravenous patient-controlled analgesia (IVPCA), against IVPCA alone during the four days following surgery. METHODS: Fifty patients were randomized into two groups: an IVPCA group (n = 25) and an IVPCA-cryo group (n = 25). Subjective pain intensity was assessed on a verbal analogue scale at rest and during coughing. The intensity and the incidence of post-thoracotomy pain, numbness, epigastric distension and/or back pain, the analgesic requirements, as well as the blood gas values and respiratory function tests were evaluated up to the second postoperative (postop) month. Haemodynamic data and episodes of nausea and/or vomiting were recorded over the four postop days. RESULTS: In the cryo group there was a statistically significant improvement in postop pain scores (P = 10(-4)), reduction in consumption of morphine (P = 10(-4)) and other analgesics (P = 10(-4)), optimization (less acidosis) of the pH values of blood gases (P < 0.015 over 72 hours postop and P < 0.03 on the first and second postop months), increase in systolic blood pressure (P < 0.05 over 96 hours postop), reduction in heart rate (P < 0.05 over 96 hours postop), increase in values of FEV1 (P < 0.02) and FVC (P < 0.05) at the first and second postop months, reduction in the incidence of nausea (0.05 < P < 0.1 over 18 hours postop), numbness, epigastric distension and back pain (P < 0.05 at days 5, 6, 7, 14, 30 and 60 following surgery). CONCLUSIONS: We suggest that cryoanalgesia be considered as a simple, safe, inexpensive, long-term form of post-thoracotomy pain relief. Cryoanalgesia effectively restores FEV1 values at the second postop month.

Primitive neuroectodermal tumor of the thoracic wall in a 48-year-old man.

We describe a rare case of primitive neuroectodermal tumor arising from the thoracic wall in a 48-year-old man. He underwent extensive resection of the tumor en bloc with the diaphragm and the thoracic wall, followed by adjuvant chemoradiotherapy. Primitive neuroectodermal tumor may be included in a multidisciplinary protocol incorporating neoadjuvant chemotherapy, surgery, and adjuvant chemoradiotherapy.

The significance of one-station N2 disease in the prognosis of patients with nonsmall-cell lung cancer.

BACKGROUND: A retrospective study was conducted to define the characteristics and the prognosis of N2 disease subgroups according to their patterns of spread. METHODS: From January 1993 to December 2004, 1,329 patients underwent lung resection for bronchogenic carcinoma The records of all patients with positive mediastinal lymph nodes at the surgical specimen (pIIIA/N2) after radical resection were analyzed, and the pattern of mediastinal lymphatic spread was classified according to regional spread, to skip metastasis, and to one or two or more lymph node stations, in relation to primary tumor location. Age, sex, type of resection, right or left lesion, T status, primary tumor location, tumor size, tumor central or peripheral location, histology, and survival were recorded and analyzed. Survival was analyzed according to regional spread or not, number of mediastinal lymph node stations involved, and skip metastasis status. RESULTS: Among 302 cases (22.7%) with positive mediastinal lymph nodes pIIIA/N2, 66 (22%) were skip metastases, 72 (24%) had a nonregional mode of spread, and 199 (66%) included two or more stations of mediastinal lymph node invasion. Cox regression analysis of all cases disclosed malignant invasion in only one mediastinal lymph node station as the only favorable factor of survival (p < 0.001, odds ratio 0.57, 95% confidence interval: 0.42 to 0.78). CONCLUSIONS: The presence of one-station mediastinal lymph node metastasis in patients with nonsmall-cell lung cancer who underwent major lung resection with complete mediastinal lymph node dissection proved to be a good prognostic factor that should be taken into account in the future.

Asymptomatic solitary mediastinal cystic lymphangioma: a rare entity.

Solitary mediastinal cystic lymphangioma is an extremely rare tumor-like abnormality of the lymphatic system, of congenital origin. From 1996 to 2003, 4 cases of solitary mediastinal cystic lymphangioma were managed in our department. The clinicopathologic characteristics were recorded and analyzed. The incidence proved to be 1.2% among all cases of mediastinal masses admitted to our department. All patients were asymptomatic, they shared common radiologic features, and all were managed by radical surgical excision. No recurrence or mortality were noted during follow-up ranging from 2 to 7 years. Complete excision of this benign entity has an excellent prognosis.

Massive hemorrhage caused by major pulmonary vessel-cutaneous fistula in the late postoperative period: report of two cases.

Sudden life-threatening hemorrhage caused by erosion of the wall of a thoracic blood vessel such as the aorta, pulmonary artery, or pulmonary vein, in the late postoperative period is extremely rare and presents a challenging emergency. We report the cases of two patients whose only clinical manifestation was a hemorrhagic cutaneous chest wall fistula. Both patients were treated by emergency surgery. The diagnosis and management of this clinical entity requires a high index of suspicion and innovative therapeutic solutions.

Early use of intrapleural fibrinolytics in the management of postpneumonic empyema. A prospective study.

OBJECTIVE: A prospective randomized study was conducted in order to analyze the role of fibrinolytics in the treatment of complicated parapneumonic effusion. METHODS: From 2001 to 2004, 127 consecutive patients were managed for thoracic empyema. In all cases the cause was bacterial pneumonia. Seventy patients were managed with sole tube thoracostomy (group A) and 57 with combination of tube thoracostomy and streptokinase instillation (group B). Groups were statistically compared for the age, gender, duration of symptoms, quality of pleural fluid, chest imaging, complete drainage, length of hospital stay and mortality. Multivariate analysis was used in order to define the factors that affect outcome. RESULTS: Tube thoracostomy was successful in 47 (67.1%) cases (group A), while fibrinolysis led to a favorable outcome in 50 cases (87.7%) (P<0.05). The length of stay in thoracic surgical department was significantly longer for group A (P<0.001). Mortality rate in group A was significantly higher (P<0.001). Multiple regression analysis disclosed as sole independent favorable factor for pleural drainage, the use of fibrinolysis during the course of chest tube drainage (P=0.006, odds ratio 4.29, 95% CI 1.51-12.14). CONCLUSIONS: Fibrinolytic agents are a useful adjunct in the management of complicated parapneumonic effusions. Intrapleural fibrinolytics, if used early in the fibrinopurulent stage of a parapneumonic effusion, decrease the rate of surgical interventions (VATS or open decortcation) and the length of hospital stay with minor associated morbidity.

A phase I-II study of docetaxel-ifosfamide-cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer.

In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC (stages III-IV), WHO-PS< or =2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80-100 mg/m2 day 1), ifosfamide (4-5 g/m2) and cisplatin (80-100 mg/m2), both divided over days 1 and 2 every 21 days. G-CSF (lenograstin) was administered from days 4-13. Fifty-five patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40-72); PS = 1 (0-2); gender = 48 males, 7 females; stages IIIA = 8, IIIB = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6), brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose-limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 100 mg/m2) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase II testing. Among evaluable patients in phase II, 31/46 (67%; CI = 54-81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2-21+), median time to progression (TTP) 8 months (1-23+) and median overall survival (OS) 13 months (2-23+). The 1-year survival was 57%. Grade (Gr) 3/4 toxicities included neutropenia 39/46 with 27 developing Gr4 (< or =7 days) and 20% FN managed successfully with broad-spectrum antibiotics, thrombocytopenia Gr3 3/46-Gr4 1/46, no Gr3 neuropathy, Gr1-2 CNS toxicity in 12, no renal toxicity, 15 Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I-II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2-drug regimens will be warranted.