Lung cancer and cyclooxygenase-2

Lung cancer is by far the leading cause of cancer-related death. Overall survival is poor and has not improved substantially over the last half century. It is clear that new approaches are needed and these should include prevention, screening for early detection, and novel treatments based on our understanding of the molecular biology of this disease. Recently attention has been drawn to the role of the cyclooxygenase (COX) enzyme and its involvement in tumorigenesis. Investigations have documented two isoforms, COX-1 and COX-2, encoded by different genes. COX-1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions, such as the maintenance of gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is normally undetectable in most tissues, and is induced by cytokines, growth factors, oncogenes, and tumor promoters. A growing body of evidence indicates COX-2 plays a key role in lung cancer, and can serve as a potential marker of prognosis in this disease. Furthermore, the recent availability of COX-2 inhibitor medications offers a unique opportunity to interfere with the development of lung cancer and the progression of metastasis. Because COX-2 inhibitors have been demonstrated to interfere with tumorigenesis, the COX-2 enzyme may be an attractive target for therapeutic and chemoprotective strategies in lung cancer patients.     

Distribution of skeletal metastases in prostatic and lung cancer. Mechanisms of skeletal metastases

The distribution of skeletal metastases in prostatic and lung cancer was examined to test the hypothesis that prostatic carcinoma spreads by a unique hematogenous route. Abnormal technetium-99m methylene diphosphonate bone scans were retrospectively reviewed in 71 patients with prostatic carcinoma and 41 patients with lung cancer comparing patterns of osseous involvement. Differences in the distribution of lesions were not significant. It is concluded that prostatic carcinoma does not metastasize to specific skeletal sites by a singular hematogenous pathway.     

Surgery for skeletal metastases in lung cancer

Background and purpose

Most lung cancer patients with skeletal metastases have a short survival and it is difficult to identify those patients who will benefit from palliative surgery. We report complication and survival rates in a consecutive series of lung cancer patients who were operated for symptomatic skeletal metastases.

Methods

This study was based on data recorded in the Karolinska Skeletal Metastasis Register. The study period was 1987–2006. We identified 98 lung cancer patients (52 females). The median age at surgery was 62 (34–88) years. 78 lesions were located in the femur or spine.

Results

The median survival time after surgery was 3 (0–127) months. The cumulative 12-month survival after surgery was 13% (95% CI: 6–20). There was a difference between the survival after spinal surgery (2 months) and after extremity surgery (4 months) (p = 0.03). Complete pathological fracture in non-spinal metastases (50 patients) was an independent negative predictor of survival (hazard ratio (HR) = 1.8, 95% CI: 1–3). 16 of 31 patients with spinal metastases experienced a considerable improvement in their neurological function after surgery. The overall complication rate was 20%, including a reoperation rate of 15%.

Interpretation

Bone metastases and their subsequent surgical treatment in lung cancer patients are associated with high morbidity and mortality. Our findings will help to set appropriate expectations for these patients, their families, and surgeons.Lung cancer has become one of the most common cancers worldwide and is the predominant cause of death among cancer patients. The American Cancer Society estimated that almost 160,000 patients would die from lung and bronchus cancer in the USA in 2009 (Jemal et al. 2009). Some authors have stated that lung cancer is one of the most important challenges in oncology at the present time (Boyle and Dresler 2005).Historically, about one third of all lung cancer patients are found to have bone metastases during the course of the disease. Symptoms and events of skeletal origin such as pain, pathological fractures, spinal cord compression with paraparesis, and hypercalcemia are common complications. The decline in quality of life and eventual death of these patients can be explained to some extent by skeletal complications and their treatment (Coleman 1997).Lung cancer patients with skeletal events have a short expected survival; however, some case reports have involved patients who survived several years after pathological fractures (Agarwala and Hanna 2005, Hirano et al. 2005). A major problem in selecting patients for surgery is to avoid operating on those who are likely to die very soon after surgery. Although several features help to identify patients with long survival (Bauer and Wedin 1995, Tomita et al. 2001), it is still difficult to identify those who will die early.We analyzed a consecutive series of lung cancer patients who were operated on for skeletal metastases at our department, to determine the complications and reoperation rates after surgery and to identify risk factors for early death.     

Surgery for skeletal metastases in lung cancer

Background and purpose Most lung cancer patients with skeletal metastases have a short survival and it is difficult to identify those patients who will benefit from palliative surgery. We report complication and survival rates in a consecutive series of lung cancer patients who were operated for symptomatic skeletal metastases.

Methods This study was based on data recorded in the Karolinska Skeletal Metastasis Register. The study period was 1987–2006. We identified 98 lung cancer patients (52 females). The median age at surgery was 62 (34–88) years. 78 lesions were located in the femur or spine.

Results The median survival time after surgery was 3 (0–127) months. The cumulative 12-month survival after surgery was 13% (95% CI: 6–20). There was a difference between the survival after spinal surgery (2 months) and after extremity surgery (4 months) (p = 0.03). Complete pathological fracture in non-spinal metastases (50 patients) was an independent negative predictor of survival (hazard ratio (HR) = 1.8, 95% CI: 1–3). 16 of 31 patients with spinal metastases experienced a considerable improvement in their neurological function after surgery. The overall complication rate was 20%, including a reoperation rate of 15%.

Interpretation Bone metastases and their subsequent surgical treatment in lung cancer patients are associated with high morbidity and mortality. Our findings will help to set appropriate expectations for these patients, their families, and surgeons.     

Peripheral intrapulmonary lymph node metastases of non-small-cell lung cancer

Since the development and progress of computed tomographic imaging, peripheral intrapulmonary lymph nodes (IPLNs) have become increasingly described and well-known entities. Intrapulmonary lymph nodes may appear as a solitary pulmonary nodular shadow mimicking a non-small-cell lung cancer (NSCLC) or as multiple nodules masquerading as carcinoma metastases. We describe a case in which IPLNs presented as a clinical "nodular" T4 N0 NSCLC that finally proved to be a pathologic T2 N1 NSCLC, thus raising new questions on this entity.     

Lung cancer after heart transplantation: a 17-year experience

Background

The effects of heart transplantation on lung cancer incidence in heart transplant recipients are unclear.

Methods

In an observational study, we retrospectively reviewed the charts of all patients undergoing heart transplantation at our institution from July 1982 to July 1999. Data on lung cancer incidence, risk factors, treatment, and outcome were collected.

Results

Five hundred seventy-two patients (mean age, 50 ± 11 years; range, 18 to 73) were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20 pack-year history of smoking before transplantation. Lung cancer developed in 2 patients 1 year or less after transplantation and in 8 patients more than 1 year after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up). Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8 months (range, 2 to 37.5). Routine annual chest radiographs after transplantation enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2 to 10.8]; p = 0.0002).

Conclusions

The incidence of lung cancer in our population of heart transplant recipients appears to be no higher than in nontransplant populations with similar risk factors (ie, smoking and age). Routine radiographic imaging of transplant recipients may allow earlier detection of lung cancer and thus offer a survival benefit.     

Brain metastases secondary to tumor emboli from primary lung cancer during lobectomy

It is assumed that dissemination of tumor cells during pulmonary resection may be followed by metastases. A 70-year-old man with pleomorphic carcinoma of the lung had brain metastases develop secondary to brain infarction caused by tumor emboli during lobectomy. This is a rare case that clearly showed brain metastases as a consequence of tumor emboli during pulmonary resection.     

Lung cancer resection combined with lung volume reduction in patients with severe emphysema

OBJECTIVE: Certain patients with resectable lung cancer and severe respiratory limitation due to emphysema may have a suitable operative risk by combining cancer resection with lung volume reduction surgery. The purpose of this study is to review our experience with such patients. METHODS: A review was conducted on 21 patients with lung cancer in the setting of severe emphysema who underwent an operation designed to provide complete cancer resection and volume reduction effect. RESULTS: In the 21 patients, the mean preoperative forced expiratory volume in 1 second was 0.7 +/- 0.2 L (29% predicted), residual volume was 5.5 +/- 1.0 L (271%), and diffusing capacity for carbon monoxide was 8.0 +/- 2.2 mL/min/mm Hg (34% predicted). In 9 patients, the cancer was located in a severely emphysematous lobe and the lung volume reduction surgery component of the procedure was accomplished with lobectomy alone. In the remaining 12 patients, the cancer resection lobectomy (n = 9) and wedge resection (n = 3) were supplemented with lung volume reduction surgery. Final pathologic staging was stage I in 16 patients, stage II in 2 patients, and stage III in 2 patients. One patient was found to have stage IV disease due to multifocal tumors in separate lobes. There were no hospital deaths. Postoperative complications included prolonged air leak in 11 patients, atrial fibrillation in 6 patients, and reintubation for ventilatory assistance in 2 patients. All patients showed improved lung function postoperatively. Survival was 100% and 62.7% at 1 and 5 years, respectively. CONCLUSIONS: Patients with severe emphysema and resectable lung cancer who have a favorable anatomy for lung volume reduction surgery may undergo a combined cancer resection and lung volume reduction surgery with an acceptable risk and good long-term survival.     

Surgery of skeletal metastases in 306 patients with prostate cancer

Purpose

Skeletal metastases are common in patients with prostate cancer, and they can be a source of considerable morbidity. We analyzed patient survival after surgery for skeletal metastases and identified risk factors for reoperation and complications.

Patients and methods

This study included 306 patients with prostate cancer operated for skeletal metastases during 1989–2010. Kaplan-Meier analysis was used to calculate survival. Cox multiple regression analysis was performed to study risk factors, and results were expressed as hazard ratios (HRs).

Results

The median age at surgery was 72 (49–94) years. The median survival after surgery was 0.5 (0–16) years. The cumulative 1-, 2-, and 3-year survival after surgery was 29% (95% CI: 24–34), 14% (10–18), and 8% (5–11). Age over 70 years (HR 1.4), generalized metastases (HR 2.4), and multiple skeletal metastases (HR 2.3) resulted in an increased risk of death after surgery. Patients with lesions in the humerus (HR 0.6) had a lower death rate. The reoperation rate was 9% (n = 31). The reasons for reoperation were deep wound infection (n = 10), hematoma (n = 7), material (implant) failure (n = 3), wound dehiscence (n = 3), increasing neurological symptoms (n = 2), prosthetic dislocation (n = 2), and others (n = 4).

Interpretation

This study involves the largest reported cohort of patients operated for skeletal lesions from prostate cancer. Our survival data and analysis of predictors for survival help to set appropriate expectations for the patients, families, and medical staff.Advances in the treatment of prostate cancer have extended life expectancy (Berruti et al. 2000, Carlin and Andriole 2000, Saad et al. 2006). Approximately 70% of the patients with advanced disease can be expected to develop skeletal metastases (Coleman 2001).The role of orthopedic surgery in patients with skeletal metastases is to treat spinal cord compression and existing or impending pathological fractures in an effort to relieve pain and restore function. Information on outcomes following surgery for skeletal metastases is important for the patients involved, for their families, and for treating physicians (Wedin et al. 2005, Forsberg et al. 2011).Skeletal metastases from other malignancies are most often osteolytic whereas skeletal metastases from prostate cancer are most often osteoblastic, which may mean unique treatment considerations. However, little attention has been paid to survival and postoperative complications in patients with metastatic prostate lesions.We have determined patient survival following surgery for symptomatic skeletal metastases in a large cohort of prostate cancer patients. A secondary aim was to identify patient-related and procedure-related risk factors for complications and reoperation.     

Surgical removal of bone and muscle metastases of renal cancer

Fifteen men and six women with renal cancer underwent surgical removal of metastatic lesions in bone (19 patients) or muscle (two patients). The operation was carried out 2 years before nephrectomy/renal resection in two patients, on the same occasion in four, and 1-196 months after in 15. Surgical interventions of various kinds were undertaken, resulting in the loss of a lower limb in seven patients and an upper limb in one.

The observed 5-year survival was 4 out of 10. Six patients were alive at follow-up, five of them without evidence of disease. Eight of the remaining 15 patients died of an unrelated disease (five without evidence of tumor); the other seven patients died of metastatic tumor disease. Local recurrence was diagnosed, and removed, in two patients. The results compare favourably with reports on surgically removed pulmonary metastases of renal cancer and seem to justify an aggressive attitude towards solitary bone and muscle metastases of renal cancer.     

Surgical removal of bone and muscle metastases of renal cancer

Fifteen men and six women with renal cancer underwent surgical removal of metastatic lesions in bone (19 patients) or muscle (two patients). The operation was carried out 2 years before nephrectomy/renal resection in two patients, on the same occasion in four, and 1-196 months after in 15. Surgical interventions of various kinds were undertaken, resulting in the loss of a lower limb in seven patients and an upper limb in one. The observed 5-year survival was 4 out of 10. Six patients were alive at follow-up, five of them without evidence of disease. Eight of the remaining 15 patients died of an unrelated disease (five without evidence of tumor); the other seven patients died of metastatic tumor disease. Local recurrence was diagnosed, and removed, in two patients. The results compare favourably with reports on surgically removed pulmonary metastases of renal cancer and seem to justify an aggressive attitude towards solitary bone and muscle metastases of renal cancer.