Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer.

OBJECTIVE: Sleeve lobectomy is a widely accepted procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study is to assess operative mortality, morbidity, and long-term results of sleeve lobectomies performed for non-small cell lung carcinoma (NSCLC). METHODS: A retrospective review of 218 patients who underwent sleeve lobectomy for NSCLC between 1981 and 2005 was undertaken. There were 186 (85%) men and 32 women with a mean age of 61.9 years (range, 19-82 years). Eighty patients (36.6%) had a preoperative contraindication to pneumonectomy. Right upper lobectomy was the most common operation (45.4%). Vascular sleeve resection was performed in 28 patients (12.8%) and was commonly associated with left upper lobectomy (n=20; 9.1%; p=0.0001). The histologic type was predominantly squamous cell carcinoma (n=164; 75%), followed by adenocarcinoma (n=46; 21%). Resection was incomplete in nine (4.1%) patients. RESULTS: There were nine operative deaths; the operative mortality and the morbidity rates were 4.1% and 22.9%, respectively. A total of 14 (6.4%) patients presented with bronchial anastomotic complications: two were fatal postoperatively, seven patients required reoperation, three required a stent insertion, and two were managed conservatively. Multivariate analysis showed that compromised patients (p=0.001), current smoking (p=0.01), right sided resections (p=0.003), bilobectomy (p=0.03), squamous cell carcinoma (p=0.03), and presence of N1 or N2 disease (p=0.01) were risk factors for mortality and morbidity. Follow-up was complete in 208 patients (95.4%). Overall 5-year and 10-year survival rates were 53% and 28.6%, respectively. After complete resection, recurrence was local in 10 patients, mediastinal in 20, and distant in 25. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0-N1 vs N2; p=0.01) and the stage of the lung cancer (stage I-II vs III, p=0.02). CONCLUSIONS: For patients with NSCLC, sleeve lobectomy achieves local tumor control, even in patients with preoperative contraindication to pneumonectomy and is associated with low mortality and bronchial anastomotic complication rates. Postoperative complications are higher in compromised patients, smokers, N disease, right sided resections, bilobectomies, and squamous cell cancers. The presence of N2 disease and stage III significantly worsen the prognosis.     

The temporal dynamics of postanoxic burst-suppression EEG.

Burst-suppression EEG (BS-EEG) after cardiopulmonary resuscitation implies a bad prognosis, but little is known of the temporal dynamics of postanoxic BS-EEG. The authors studied 24 consecutive patients who developed BS-EEG within 24 hours after cardiopulmonary resuscitation, and followed 20 of these patients with serial EEGs. Except for one patient, BS-EEG was followed by another EEG pattern within 1 day, mainly areactive alpha EEG (n = 6), isoelectric EEG (n = 5), generalized continuous epileptiform discharges (n = 4), or theta; EEG (n = 3). The coexistence of different EEG patterns in the same recording was seen in 10 patients. Serial recordings disclosed a variety of EEG sequences with (often subtle) transitions between the different EEG patterns, including reappearance of BS-EEG. Postanoxic BS-EEG is followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavorable sign in and of itself. The coexistence of different unfavorable EEG patterns in the same recording, and transitions between these EEG patterns in subsequent recordings, are common in patients with postanoxic BS-EEG. It seems reasonable to speculate that BS-EEG and subsequently evolving EEG patterns in anoxic encephalopathy reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process, leading ultimately to severe neuronal loss.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.

PURPOSE: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome. RESULTS: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung. CONCLUSIONS: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.     

IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients

Purpose

High mammographic breast density (BD) is a strong risk factor of breast cancer; however, little is known in women under 40 years of age. Recently, dual-energy X-ray Absorptiometry (DXA) has been developed as a low-dose method to measure BD in young populations. Thus, our aims were to describe BD in relation to risk factors in Chilean women under 40 years old and to explore the equivalence of DXA to mammography for the measurement of BD.

Methods

We selected 192 premenopausal Chilean female participants of the DERCAM study for whom we have anthropometric, sociodemographic, and gyneco-obstetric data. The subjects received both digital mammograms (Hologic) and breast DXA scans (GE iDXA). Mammographic BD was estimated using a fully automated commercial method (VOLPARA^®) and BI-RADS. Breast DXA scans were performed using a standardized protocol and the % fibroglandular volume (%FGV) was estimated considering a two-compartment model of adipose and fibroglandular tissue.

Results

The mean age was 37 years (SD = 6.5) and 31.6% of the subjects were obese. The median %FGV and absolute FGV (AFGV) measured by DXA were 9% and 198.1 cm³ and for VOLPARA^®, 8.6% and 58.0 cm³, respectively. The precision for %FGV after reposition was 2.8%. The correlation coefficients for %FGV, AFGV, and breast volume between DXA and mammography were over 0.7. Age and body mass index (BMI) were inversely associated with %FGV, and BMI was positively related to AFGV as estimated with DXA or mammography. We did not observe an association with gyneco-obstetric characteristics, education, and %FGV and AFGV; smoking was only associated with AFGV as measured by VOLPARA^®.

Conclusions

DXA is an alternative method to measure volumetric BD; thus, it could be used to continuously monitor BD in adult women in follow-up studies or to assess BD in young women.

     

Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non–Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial

Background

Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non–small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.

The stem cell gene “inhibitor of differentiation 1” (ID1) is frequently expressed in non-small cell lung cancer

Aims

Inhibitor of differentiation 1 (ID1) plays a role in cellular differentiation, proliferation, angiogenesis and tumor invasion. As shown recently, ID1 is positively regulated by the tyrosine kinase SRC in lung carcinoma cell lines and with that appears as a potential new therapeutic target in non-small cell carcinoma (NSCLC). To substantiate this hypothesis we examined ID1, SRC and matrix metalloproteinase-9 (MMP-9) immunohistochemically in human NSCLC specimens.

Methods

From 61 consecutive patient tissue samples of a tumor tissue bank a one core tissue microarray (TMA) was produced and whole slide tissue samples of preinvasive lesions used. The staining of commercial antibodies was assessed by the H-score. Statistical analyses based on Spearman's rank correlation coefficient.

Results

ID1 was expressed in the nucleus in 70% of squamous cell carcinomas and 50% of non-squamous cell carcinomas and in vascular endothelium of non-tumor tissue. Cytoplasmic staining was found in all samples for SRC and in 93% for MMP-9. ID1-positive tissue samples co-expressed SRC and MMP-9 in 94%. In non-squamous cell carcinomas, H-scores of ID1 and SRC correlated with each other (p = 0.04). H-score of MMP-9 correlated with tumor grade (p = 0.04). The carcinoma findings were reflected in preinvasive lesions.

Conclusions

We describe for the first time the immunohistochemical expression of ID1 in the majority of NSCLC samples. The almost general co-expression of ID1, SRC and MMP-9 supports their cooperation in vivo and warrants further investigation of ID1 as a therapeutic target.