Phase II study of all-trans-retinoic acid and alpha-interferon in patients with advanced non-small cell lung cancer.

Between April 1993 and June 1994, 29 patients (pts) with unresectable, locally advanced, or metastatic non-small cell lung cancer were treated with a combination of p.o. trans-retinoic acid (TRA), 150 mg/m2/day, in three divided doses and s.c. IFN-alpha, 3 x 10(6) units/day. The age range was 41-80 years (median, 63 years). The Eastern Cooperative Oncology Group performance status was 0-1 (24 pts) and 2 (5 pts). Pts had advanced disease, refractory to conventional therapy (5 stage IIIB and 24 stage IV). Twenty-one pts had adenocarcinoma, six had squamous cell carcinoma, and two had large cell carcinoma. Only 3 pts completed 8 weeks of treatment, requiring neither interruption nor dose modification. Fatigue occurred in 88% of pts. A syndrome complex consisting of dry oral and nasal mucosa, recurrent sinus infections, and epistaxis occurred in 64% of pts. Grade II/III dermatitis was seen in 52%. Severe scrotal dermatitis was seen in 7 pts (47% of 15 males). Hypertriglyceridemia was moderate/severe in 11 pts, and 3 pts required gemfibrozil for levels up to 1660 mg/dl. Hematological toxicity was not encountered, and none of the pts had leukocytosis. One pt died with complications of myocardial infarction while on TRA/IFN-alpha. Twenty-five pts had more than 2 weeks of treatment and are evaluable for response; two pts died early with complications of cancer, and two pts declined to continue after only 3 and 5 days of treatment. Final assessment of response was by accepted clinical and radiological criteria at 8 weeks. There have been four objective responses: complete response, 2 (18+ and 17 months) and partial response, 2 (7 and 14 months). Responses were observed in all histologies. Combined differentiation treatment with TRA/IFN-alpha has modest but objective activity in non-small cell lung cancer. Toxicity is considerable. Additional studies to elucidate the biological basis of TRA/IFN-alpha and to define prognostic parameters predicting response are needed.

The effect of renin-angiotensin system blockade on visceral blood flow during and after thoracic aortic cross-clamping.

Surgical procedures necessitating clamping of the thoracic aorta are associated with a high incidence of postoperative renal dysfunction. Plasma renin activity is elevated during and after thoracic aortic occlusion in animals. The pathophysiology of the renal dysfunction may involve the renin-angiotensin system. Blockade of the renin-angiotensin system was studied in a canine model during occlusion of the thoracic aorta. Saralasin, a competitive blocker of angiotensin II, and the converting enzyme inhibitor MK422 were studied. Sixteen animals were separated into three treatment groups: control (five animals), saralasin (five), and MK422 (six). All dogs underwent clamping of the thoracic aorta for 60 minutes. In control animals, plasma renin activity increased from 0.16 +/- 0.04 to 6.41 +/- 1.57 ng/ml/hr at 30 minutes after thoracic aortic occlusion (p less than 0.05). Thirty minutes after cross-clamp release, plasma renin activity remained 10 times greater than baseline, 1.47 +/- 0.20 ng/ml/hr (p less than 0.05). Renal blood flow was measured with 15 micron microspheres before, during, and after thoracic clamping. In control animals, renal cortical blood flow decreased during cross-clamping and remained below baseline after clamp release: baseline, 7.05 +/- 0.98 ml/gm/min (standard error of the mean); 30 min after clamp release, 3.77 +/- 0.43 ml/gm/min (standard error of the mean) (p less than 0.05). In the MK422 group, renal cortical blood flows returned to baseline after cross-clamp release: baseline, 6.38 +/- 0.49 ml/gm/min; 30 minutes after clamp release, 7.30 +/- 1.6 ml/gm/min. Infusion of MK422 after placement of the thoracic aortic cross-clamp resulted in normal renal blood flow after clamp release. This protective effect was not seen with saralasin. The resumption of normal renal cortical blood flow after the administration of the converting enzyme inhibitor MK422 suggests that elevated plasma renin activity may contribute to renal dysfunction after thoracic aortic occlusion.

Recombinant aprotinin in coronary artery bypass graft operations.

OBJECTIVE: To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery. DESIGN: An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin. SETTING: Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill., and the Scott & White Memorial Hospital, Temple, Texas). PATIENTS: Patients undergoing primary and reoperation coronary artery bypass grafting were assigned to groups by means of a computer-generated table of random numbers. Treated (n = 48) and control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level. INTERVENTIONS: Recombinant aprotinin was given at two dosages. Dosage level 1 consisted of a bolus of 2 mg/kg intravenously immediately after the induction of anesthesia, 1 mg/kg added to each liter of the oxygenator prime, and 0.5 mg.kg-1.hr-1 infused continuously during operation. At dosage level 2, doses were doubled. Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results. MAIN OUTCOME MEASURES: Preoperative and postoperative hemoglobin levels, amounts of autotransfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells. Adverse clinical events (alterations in renal function, graft thrombosis, myocardial infarction, and death) were recorded. RESULTS: Additional heparin was given to 48% patients in the aprotinin group and to 44% of control patients. Overall red blood cell loss (in milliliters, mean +/- standard deviation [SD]) was decreased with aprotinin at dosage level 1 for reoperations (1040 +/- 162 vs 1544 +/- 198, p < 0.01), and at dosage level 2 for all operations (primary operations, 886 +/- 362 vs 1333 +/- 618, p = 0.02; reoperations, 1191 +/- 560 vs 1815 +/- 1116, p = 0.2). Fewer patients in the aprotinin than in the control group had transfusions of donated blood (6/48 vs 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 vs 20/36, p < 0.01). Among patients receiving dosage level 1, there were no myocardial infarctions or deaths. At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures. Two control patients had hypotension after bypass necessitating intraaortic balloon pumps, and one of these patients died. Postoperative increases in blood urea nitrogen and creatinine levels were small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred. CONCLUSION: We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample.

A decade of experience with the Model 103 and 104 Beall valve prostheses.

Mitral or tricuspid valve replacement with the Beall Model 103 or 104 prosthesis has been associated with a high incidence of late prosthetic malfunction which has necessitated reoperation. Between 1972 and 1975, 57 patients underwent single valve replacement (55 mitral and two tricuspid) with Beall Model 103 or 104 valvular prostheses and survived at least 2 years. The mean follow-up time was 73.7 months (range 24 to 119 months). Of these patients, 22 required explantation of the prosthesis; there was an operative mortality of 27%. Major prosthetic malfunction occurred in four patients: Two occluders were embolized and two occluders were fixed in the open position. All four patients required urgent operation, and two of them died. The development of symptoms of congestive heart failure, systolic murmur, or hemolysis were the reasons for cardiac catheterizations and possible reoperation. Nineteen patients had cardiac catheterization. Fifteen of these subsequently underwent reoperation, with a mortality of 26%. Three patients were considered inoperable. Cardiac catheterization data revealed significant prosthetic regurgitation in all patients: pulmonary capillary pressure 29.9 mm Hg +/- 6.7 (standard deviation); V wave 31.5 mm Hg +/- 12.0; left ventricular end-diastolic pressure 18.0 mm Hg +/- 7.8. Comparison of hemolysis indicators in this group to those of asymptomatic patients revealed that the former had a significant elevation in lactic dehydrogenase (p = 0.038) and a lowered hematocrit value (p = 0.017). Waiting for severe symptomatic deterioration to justify reoperation risks the development of left ventricular dysfunction and possible emergency reoperation with a high operative mortality.

Results of gastric interposition for reconstruction of the pharyngoesophagus.

BACKGROUND: Free jejunal transfer has become the standard technique for reconstruction of the proximal pharynx and hypopharynx. Gastric tube interposition is an effective alternative when resection extends below the thoracic inlet. This study was done to determine current indications, review morbidity and mortality rates, and to define clinical and pathologic determinants of survival associated with this procedure. METHODS: We reviewed the records of 32 patients who underwent gastric tube interposition for reconstruction of the pharyngoesophagus from 1987 to 1997. RESULTS: The overall complication rate was 50%. Complications were more frequent in the reoperative group (22% vs 66%, P < .05). The overall fistula rate was 31%. The overall mortality rate was 12%. Ultimately, 71% of patients resumed oral feedings. The 5-year actuarial survival rate was 22%. Unfavorable prognostic factors associated with significantly reduced survival (P < . 05) included margin positive resection, positive lymph node involvement, and operations done for recurrent tumor CONCLUSIONS: Reconstruction of the pharyngoesophagus with gastric tube interposition is indicated for primary tumors of the hypopharynx and cervical esophagus with inferior extension below the thoracic inlet and recurrent tumors or benign strictures in which free jejunal transfer is not feasible or has failed. It can be done with acceptable morbidity and mortality and provides reasonable expectations for long-term survival and resumption of oral intake.

Ectopic pregnancy causing hemothorax managed by thoracoscopy and actinomycin D.

BACKGROUND: Most patients with extratubal ectopic pregnancies present with vaginal bleeding and lower abdominal pain. We report a case of an extratubal ectopic pregnancy with extra-abdominal manifestations. CASE: An ectopic pregnancy implanted on the diaphragm resulted in spontaneous hemothorax due to trophoblastic invasion into the pleura. Thoracoscopic excision followed by actinomycin D chemotherapy provided successful resolution of the ectopic pregnancy. CONCLUSION: Abdominal pregnancies may have bizarre clinical presentations.

Axillary thoracoscopy.

Thoracoscopy can be done safely and effectively through working ports placed in the axilla in patients whose pathology is in the upper half of the thorax. We have used this technique successfully in 37 patients with no complications. Advantages include superior cosmesis, optimal access to the apex of the chest, and, if necessary, easy conversion to axillary thoracotomy.

Acute renal failure in the cardiovascular surgical patient.

Acute renal failure is a known complication of cardiovascular surgery and is associated with a high mortality. Therapy should be aimed at prevention of oliguric renal failure, or at least its conversion to nonoliguric renal failure. Once renal failure is established, early dialysis with nutritional support probably gives the best chance for survival.

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus is a rare disease. A case is reported and the newer diagnostic techniques of immunohistologic identification of the tumor by positive reaction to the HMB-45 antigen, as well as immunoscintigraphy with Technetium-99m-labeled melanoma monoclonal antigen for the demonstration of distant metastasis, is presented. A current review of the literature on this uncommon tumor is presented, and treatment options are discussed. A total esophagectomy remains the treatment of choice. Four long-term (> 5 years) survivors after adequate surgical removal have been recorded in the literature.

Clinical experience with portable cardiopulmonary bypass in cardiac arrest patients.

To evaluate the use of portable cardiopulmonary bypass as a resuscitative tool and its impact on long-term survival of patients in cardiac arrest, we reviewed the results of 32 consecutive patients resuscitated by cardiopulmonary bypass for cardiac arrest or severe hemodynamic compromise at Northwestern Memorial Hospital over a 2-year period. Overall survival was 12.5%. Only 1 (3.4%) of the 29 patients who had cardiac arrest survived and left the hospital. All 3 patients who had severe hemodynamic compromise but not cardiac arrest were long-term survivors. Our study suggests that portable cardiopulmonary support systems used as a resuscitative tool do not prolong the survival of most cardiac arrest patients but may be useful for patients with shock due to mechanical causes and for those with profound hemodynamic compromise due to ischemia or myocardial infarction. Portable heart-lung machines can provide patients with excellent hemodynamic support; however, neurological or cardiac recovery is unlikely once cardiac arrest occurs.

Arch vessel injury during pulmonary artery catheter placement.

We have observed seven instances of unintentional cannulation of major arteries with 8F sheaths during preparation for open-heart operation. When the sheath was removed and the operation delayed, there were no complications; in the two instances in which the open-heart operation was performed immediately after arterial cannulation, there was 1 death due to hemorrhage and 1 false aneurysm of the carotid artery. Elective open-heart operations should be delayed if unintentional cannulation of a major artery occurs.

Lymphoepithelioma-like carcinoma of the lung.

Primary lymphoepithelioma-like carcinoma of the lung is rare; only 26 case reports have been identified in the literature. The present report presents a case of a 67-year-old white man with a T1 N1 M0 lymphoepithelioma-like carcinoma of the lung. He presented with severe arthritic complaints that resolved after resection of the tumor. The majority of these tumors have occurred in Asian patients who have shown evidence of previous exposure to the Epstein-Barr virus.

Baffle obstruction following the Mustard operation: cause and treatment.

Baffle obstruction developed in 11 patients after they had undergone the Mustard procedure. Eight of them required operative revision. The cause of the baffle obstruction seemed to be related to patient age (less than 1 year) and to the use of Dacron for the baffle but not to the shape of the baffle. A technique of revision that involves widely opening the previously placed baffle and enlarging it and the atriotomy with polytetrafluoroethylene was employed for the last 6 patients. All 5 survivors of this operation had good long-term results without recurrence.

A new technique for wrapping the injured spleen with polyglactin mesh.

The introduction of absorbable polyglycolic or polyglactin mesh has added a new dimension to splenic repair. Three patients with splenic disruption caused by blunt abdominal trauma underwent splenic wrapping with polyglactin mesh at the University of Virginia. The technique is described in detail. In all three instances, the spleen was saved, and postoperative nuclear medicine scans confirmed continued splenic function.

Blunt esophagectomy and gastric interposition for tumors of the cervical esophagus and hypopharynx.

Between April 1982 and June 1984, 17 patients underwent blunt esophagectomy and gastric interposition for squamous carcinoma of the cervical esophagus or hypopharynx. There was one operative death; no bleeding complications required thoracotomy or re-exploration. In two patients, a previously unknown carcinoma of the resected esophagus was discovered at the time of surgery. Blunt esophagectomy with gastric interposition is a safe technique for cervical esophageal reconstruction, as it has the added benefit of removing the entire esophagus, which has a propensity for later or synchronous carcinoma in patients with head and neck malignancies.

Application of finite-element analysis with optimisation to assess the in vivo non-linear myocardial material properties using echocardiographic imaging.

An application of finite-element analysis with an optimisation technique to assess the myocardial material properties in diastasis in vivo is described. Using the data collected from an animal model, the three-dimensional geometry of the left ventricular chamber, at several times in diastole, was reconstructed. From the measurement of the ventricular chamber pressure during image acquisition, finite-element analysis was performed to predict the expansion during diastasis. Initially, by restricting the motion of the epicardial nodes and computing the reaction forces, an 'equivalent pericardial pressure' was determined and applied in subsequent analysis. The duration of diastasis was divided into three or four intervals and the analysis was performed at each interval to assess the material properties of the myocardium. Using such a step-wise linear approach, the non-linear material properties of the myocardium during passive expansion was determined. Our results demonstrated that the computed 'equivalent pericardial pressure' increased with and was smaller than the corresponding left ventricular chamber pressure. The passive myocardium exhibited a linear tangent modulus against chamber pressure relationship which is equivalent to an exponential stress/strain relationship, similar to those suggested by in vitro studies.

Partial splenectomy for Gaucher's disease.

Gaucher's disease is an autosomal recessive disorder caused by deficiency of beta glucocerebrosidase, resulting in an accumulation of glucocerebroside in the reticuloendothelial system. These patients have massive splenomegaly and bone pain, but may have normal life expectancy. Traditionally, splenectomy has been used to treat hypersplenism, but may be associated with a high incidence of postsplenectomy sepsis and accelerated hepatic and bone lipid deposition. Two children are reported who had partial splenectomy for symptoms of Gaucher's disease. Both patients had laboratory evidence of hypersplenism. A 90% splenectomy was performed, and the residual splenic fragment was wrapped in Vicryl mesh. Both patients are currently asymptomatic with normal hematologic parameters. Postoperative radionuclide scans demonstrate increase in the size of the residual splenic fragment. Partial splenectomy may benefit patients with Gaucher's disease, but long-term follow-up care is necessary.