About 40 percent of all patients diagnosed with non-small-cell lung cancer (NSCLC) have locally advanced stage IIIA or IIIB disease. Such disease is at the borderline of anatomic resectability and associated with poor survival prospects with any present therapy. The Lung Cancer Study Group, Eastern Cooperative Oncology Group, and Radiation Therapy Oncology Group, among other North American clinical cooperative groups, have integrated radiation and chemotherapy in an attempt to prolong survival and, in some cases, cure patients with unresectable NSCLC. These two modalities have been given sequentially, concurrently, and in an alternating fashion with varying degrees of success. Trials employing cisplatin-containing chemotherapy have produced more positive results than those using other regimens, although this is not invariably so. Clearly, better treatments are needed for local and systemic disease. This paper considers possible mechanisms for combining radiation and chemotherapy, reviews the status of recent and current clinical trials, and outlines some directions for future research.

The Lung Cancer Study Group has performed a number of postoperative adjuvant trials in patients with resectable non-small-cell lung cancer (NSCLC). Adjuvant cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy was compared with immunotherapy in the treatment of 130 patients with stage II or III adenocarcinoma or large cell undifferentiated carcinoma. Careful intraoperative staging was performed in all patients. Disease-free interval was significantly prolonged in the chemotherapy group (p = 0.032). After 7.5 years of follow-up, the difference in time to recurrence and cancer deaths remains statistically significant. Another study compared CAP chemotherapy plus radiotherapy with radiotherapy alone in advanced stages II and III resected NSCLC. Again, the chemotherapy arm had significantly increased disease-free survival. In a third study, patients with high-risk stage I NSCLC were randomized after surgery to CAP chemotherapy or observation. In this study there was no difference in recurrence-free survival or overall survival.

Research on dominant oncogenes and tumor suppressor genes has characterized differences in genetic lesions between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and identified associations with clinical parameters. More than one half of all lung cancers contain a mutation of the p53 tumor suppressor gene. There does not appear to be an association between the presence of this mutation and survival. A ras family oncogene was found to be mutated in approximately 20 percent of tumors and tumor cell lines from patients with NSCLC in contrast to none of 45 tumors and tumor cell lines from patients with SCLC. The presence of a K-ras mutation was determined to be an adverse prognostic factor for survival in retrospective studies of patients with NSCLC. Mutations of K-ras are more common in tumors from smokers than nonsmokers and have not been detected in lung cancers resulting from occupational exposure to radon. Mutations in both the p53 gene and K-ras oncogene are most commonly G to T transversions in lung cancer vs G to A transitions in other cancers. Prospective studies of these mutations in resected tumor specimens taken from patients with accurate follow-up may continue to provide important clues about their potential clinical and biologic significance.

Diagnosis and treatment of lung cancer can significantly affect a patient's quality of life. Survival rates are dismal, but improvements have been made in dealing with common symptoms and side effects. This article reviews the nature of the problem, pertinent risk factors, and symptoms associated with nausea and vomiting, cachexia, hypercalcemia, and pain. Physicians, nurses, and other health care professionals can play a vital role in the identification and management of these complications, and thereby help to improve quality of life.

This brief review attempts to describe the present understanding of the pathogenesis of venous thrombosis in general with special reference to venous thromboembolism in spinal cord injury patients with paralysis. The component parts of Virchow's triad are examined. Most venous thrombi seem to originate in regions of slow blood flow, ie, the large venous sinuses of the calf and thigh or in valve cusp pockets. Decreased blood flow or even stasis due to lack of the pumping action of the large muscle packages in paralyzed patients is undoubtedly one of the major factors. As blood pools, activation products of the coagulation system accumulate locally leading potentially to local hypercoagulability. Activation products of clotting and fibrinolysis can induce endothelial damage which in turn leads to further activation of the hemostasis system. Endothelial damage may also result from distension of the vessel walls by the pooling blood. Blood flow is further decreased by hyperviscosity due to elevated fibrinogen levels and dehydration. Some spinal cord injury patients may sustain direct trauma to the legs; others may encounter vessel wall damage by the immobilized limbs. Shortly after injury, certain changes develop in the clotting system, especially increases in components of the von Willebrand factor macromolecular complex and increased platelet aggregability which could further contribute to hypercoagulability. Recently, an inhibition of the fibrinolytic system was suggested which also could add to a prothrombotic state. All of these interrelated processes clearly explain the high risk of venous thromboembolism in spinal cord injury patients with paralysis which has been clearly demonstrated by many investigators. It is hoped that intense thrombosis prophylaxis will reduce the incidence of this potentially devastating complication.

A 46-year-old man underwent cosmetic facial surgery under general anesthesia. He was ventilated by mask with an oxygen-enriched gas mixture for 4 to 6 h and monitored by pulse oximetry. Despite adequate arterial saturation (SaO2 > 90 percent) throughout the procedure, he remained in a deep coma after termination of anesthesia. Initial arterial blood gas analysis revealed a pH of 6.60 and a PaCO2 of 375 mm Hg. The patient was intubated and placed on mechanical ventilation. As his respiratory acidosis resolved, he regained consciousness quickly and recovered without any neurologic deficits. This case of record extreme hypercapnia and review of the literature demonstrates that survival is possible in acute severe respiratory acidosis as long as tissue anoxia and ischemia are prevented. We discuss the tissue effects of acute hypercapnia and newer aspects of the nature of intracellular pH regulation in critical tissues that afford considerable tolerance to acidosis. The dependence of these mechanisms upon active ion transport underscores the importance of adequate tissue oxygenation and perfusion.

Patients with acute heart failure or cardiogenic shock following myocardial infarction have a high mortality. The first priority is to salvage any remaining viable myocardium, either by thrombolytic agents or, if necessary, by coronary angioplasty. A mechanical cause for the heart failure or shock needs to be excluded. Thereafter, the optimal therapeutic regimen needs to be chosen on the basis of each patient's hemodynamic profile. Patients can be broadly classified into three groups: (1) patients with a high left ventricular filling pressure (> 18 mm Hg) and a cardiac index < 2.2 L/min/m2 but systolic arterial pressure > 100 mm Hg; (2) patients with a systolic arterial pressure < 90 mm Hg, left ventricular filling pressure > 18 mm Hg, and cardiac index < 2.2 L/min/m2; and (3) patients with an elevated right ventricular filling pressure (> 10 mm Hg) and cardiac index < 2.2 L/min/m2 and a systolic arterial pressure < 100 mm Hg. Patients in the first subset usually require the use of vasodilator therapy and/or dobutamine. The choice of inotropic agent in patients in the second hemodynamic subset depends on the degree of systemic hypotension; dopamine is usually preferred initially because it increases arterial pressure in addition to improving cardiac output. Once the systemic blood pressure has been stabilized, dobutamine can be substituted for superior augmentation of cardiac output and its additional beneficial effects on the left ventricular filling pressure. Norepinephrine may be indicated in cases of severe systemic hypotension. Patients in hemodynamic subset 3, ie, right ventricular infarction, are treated with volume expansion and dobutamine. Use of nonpharmacologic means of circulatory support, eg, intra-aortic balloon pump or left ventricular assist device may also be required in any of these subsets.