K. C. Redmond

The mortality from acute respiratory distress syndrome after pulmonary resection is reducing: a 10-year single institutional experience.

OBJECTIVE Acute respiratory distress syndrome (ARDS) is a major cause of death following lung resection. At this institution we reported an incidence of 3.2% and a mortality of 72.2% in a review of patients who underwent pulmonary resection from 1991 to 1997 [Kutlu C, Williams E, Evans E, Pastorino U, Goldstraw P. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg 2000;69:376-80]. The current study compares our recent experience with this historical data to assess if improved recognition of ARDS and treatment strategies has had an impact on the incidence and mortality. METHODS We identified and studied all patients who developed ARDS following a lung resection of any magnitude between 2000 and 2005 using the 1994 consensus definition: characteristic chest X-ray or CT, PaO2/FiO2 < 200 mmHg, pulmonary capillary wedge pressure < 18 mmHg and clinical acute onset. Overall incidence and mortality were recorded. Univariate analyses (t-test or chi(2), as appropriate) were carried out to identify correlations between pre-, peri- and postoperative variables and outcomes. RESULTS We performed 1376 lung resections during the study period. Of these 705 (51.2%) were for lung cancer and 671 (48.8%) for other diseases. Twenty-two patients fulfilled the criteria for ARDS with 10 deaths in this group. The incidence and mortality from ARDS had fallen significantly over the two study periods (incidence from 3.2% to 1.6%, p=0.01; mortality from 72% to 45%, p=0.05). Although no significant correlations with incidence and mortality were identified, we found a number of significant trends. In keeping with the ARDS network study recommendations, postoperative tidal volumes were maintained at a lower level when a higher number of pulmonary segments were excised (p=0.001). Furthermore, consistent with findings in previous studies, the highest incidence and death from ARDS were in pneumonectomy patients (incidence 11.4%; mortality 50%). Although the incidence and mortality from ARDS following pneumonectomy were not significantly different between the two study periods (p=0.08, p=0.35), we found that fewer pneumonectomies were performed in the later period (pneumonectomy rate of 6.4% vs 17.4%). CONCLUSIONS The incidence and mortality of ARDS have decreased in our institution. We postulate that this is due to more aggressive strategies to avoid pneumonectomy, greater attention to protective ventilation strategies during surgery and to the improved ICU management of ARDS.

The role of COX-2 inhibitors in lung cancer

BACKGROUND Human lung cancer is a major cause of death worldwide with few known effective therapeutic modalities. The isoenzyme cyclooxygenase 2 (COX-2) is an inducible inflammatory enzyme with increased activity evidenced in lung carcinoma. The objective was to determine the effect of a selective COX-2 inhibitor on proliferation and apoptosis rates in the Lewis lung (3LL) tumor cell line in vitro. METHODS First, 1 x 10(4) 3LL cells were plated in a 96-well plate. Cells were incubated for 24 hours with either a control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete Dulbeccos Modified Eagles Medium culture medium. Cell proliferation was measured using BrdU enzyme-linked immunosorbent assay. Next, 1 x 10(6) 3LL cells were similarly treated. Cells were permeabilized, immunostained with propidium iodide and apoptotic rates were measured using flow cytometry. Then, 5 x 10(4) cells were plated on a 24-well plate. Cells were incubated for 24 hours with either control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete culture medium. Supernatant was collected and lactate dehydrogenase was measured for cell necrosis using a cytotoxicity detection kit. RESULTS The selective COX-2 inhibitor rofecoxib resulted in a dose-dependent increase in apoptosis and dose and time-dependent growth inhibition in cell proliferation. However, rofecoxib did not cause cell necrosis. CONCLUSIONS There was a significant decrease in proliferation and increase in apoptosis of 3LL tumor cells when treated with the highly selective COX-2 inhibitor rofecoxib. COX-2 inhibitors may have a potential role to play in the treatment of lung carcinoma.

Coiling of Major Aortopulmonary Collateral Arteries With Agenesis of the Left Pulmonary Artery Prior to Pneumonectomy

The case of a patient with a left upper lobe lung tumor and unilateral agenesis of the left pulmonary artery with multiple aortopulmonary collaterals is discussed. Preoperative angiographic localization with embolization of the dominant multiple aortopulmonary collaterals allowed pneumonectomy to be performed safely with acceptable blood loss.

Bone marrow micrometastases have upregulation of ICAM-1 and αVβ3 integrins: a putative survival mechanism for tumour dissemination?

ConclusionThis study provides a novel insight into the adhesion molecule profile of micrometastatic epithelial cells in women with breast cancer. The upregulation of ICAM-1 and αVβ3 reveals new evidence for the pro-angiogenic nature of micrometastatic cells and may offer further therapeutic options.

Limb Salvage Surgery in the Excision of a Massive Fibromatosis

Fibromatosis is a rare fibroproliferative disorder with a tendency for local infiltrative and destructive growth. Local recurrence is frequent, despite apparent complete resection after radical excision. We present a case of a 22-year-old woman with massive recurrent thoracic fibromatosis extending into the neck and impairing the function of her right upper limb. This required a multidisciplinary approach to surgery to salvage the limb. The case highlights the fact that while every attempt should be made to achieve negative histologic margins, local recurrence is not uncommon. Therefore, if fibromatosis occurs adjacent to or involves vital structures, these should not be sacrificed to achieve negative margins. Function and structure preserving procedures are important as the primary goal, if not even more important.

Nodal status does not predict micrometastatic burden in the bone marrow of patients with breast cancer

ConclusionWhile there are increased HEA positive cells in the bone marrow of women with locally advanced tumours, nodal status does not predict bone marrow positivity in breast cancer. This novel finding offers insights into the differing mechanisms of lymphatic and haematogenous spread in breast cancer.

Vascular endothelial growth factor receptor 1 expression in breast carcinoma is a predictor of sentinel lymph node micrometastatic disease

ConclusionVEGFR1 is related to tumour angiogenesis and potential metastatic spread. Initial data suggests that VEGFR1 analysis may be an important adjunct to both staging and treatment of malignant disease.

A direct anti-tumour effect of the cyclooxygenase-2 inhibitor, rofecoxib, on Lewis Lung 3LL tumour cell line

ConclusionThere was a significant dose-dependent decrease in proliferation and increase in apoptosis of 3LL tumour cells when treated with the highly selective COX-2 inhibitor rofecoxib. COX-2 inhibitors may have a potential role to play in the treatment of lung carcinoma.

Surgery does not affect the number of circulating tumour cells in the bone marrow of patients with breast carcinoma

ConclusionSurgery does not alter the incidence of cytokeratin positive epithelial cells in the peripheral blood or bone marrow of patients undergoing resection of primary breast tumours.

The highly selective cyclo-oxygenase 2 inhibitor rofecoxib demonstrates anti-tumour effects in Lewis lung cancer cell line and anti-angiogenic effects in vitro

ConclusionRofecoxib suppresses growth in 3LL cells in vitro by increasing apoptosis and decreasing cell proliferation in a dose-dependent manner. Similarly it inhibits endothelial cell growth and capillary microtubular formation in vitro. The ability of rofecoxib to block angiogenesis and suppress tumour growth suggests a potential therapeutic role in the treatment and prevention of primary and secondary lung cancer.