The respiratory epithelium. V. Histogenesis of lung carcinomas in the human.

One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer.

Pericarditis with effusion complicating esophageal perforation.

Among 24 patients with esophageal perforation treated during the past 6 years, 3 patients developed pericarditis with effusion as a life-threatening complication. In the first patient pericarditis was found at autopsy, the diagnosis having been suspected but not proved during life. In the other 2 patients pericardial decompression was performed and both survived. Common denominators in the 3 patients were delayed diagnosis and treatment of the perforation, with resultant empyema. Further, the diagnosis of pericarditis with effusion was difficult and delayed, because mediastinitis and associated pleuritis and pneumonia obscured the cardiac silhouette on chest roentgenogram. It is recommended that a high index of suspicion of pericarditis be maintained in patients with esophageal perforation, especially in those in whom the perforation is diagnosed late.

The association of carcinoma of the esophagus with achalasia.

Among 156 patients with achalasia who were treated during a 13 year period, two developed squamous cell carcinoma of the esophagus. The first, a 33-year-old man, developed a carcinoma of the upper third of the esophagus 2 years after the onset of symptoms of achalasia. He was treated by a Heller myotomy and radiation therapy and survived 16.7 months. The second, a 60-year-old man, had had symptoms of achalasia for 15 years. He is alive with suspected recurrence 6 months after undergoing esophagogastrectomy for a carcinoma of the middle and lower thirds. A summary of the literature regarding carcinoma complicating achalasia is presented. This indicates that carcinoma arises in at least 1 to 7 per cent of patients with achalasia. Delay in diagnosis is common. The treatment need not differ from that of carcinoma without a chalasia, but the prognosis is dismal. Since there is evidence that retention esophagitis is a premalignant condition, it should be possible to prevent the development of carcinoma in achalasia by early cardiomyotomy in cases in which hydrostatic dilatation is not completely effective. A plea is made for closer surveillance of patients with achalasia so that, if carcinoma supervenes, it may be detected at an early stage.

Nitric oxide mediates fluid accumulation during cardiopulmonary bypass.

Fluid accumulation during cardiopulmonary bypass may be related to the production of endogenous vasoactive substances. We investigated the role of nitric oxide in mediating fluid accumulation during cardiopulmonary bypass. Normothermic cardiopulmonary bypass was carried out for 3 hours in male Sprague-Dawley rats with constant, nonpulsatile flow and hemodilution. Fluid accumulation (rate of change of external reservoir volume) was measured under three experimental conditions: saline solution control (n = 8), L-arginine infusion (n = 6), and N-nitro-L-arginine methyl ester infusion (n = 6). At the end of the experiments, body weight and organ wet/dry ratios were examined. Percentage weight gain was 77% greater in the N-nitro-L-arginine methyl ester group and 23% less in the L-arginine group compared with control values. Fluid accumulation was increased with N-nitro-L-arginine methyl ester after 30 minutes (p < 0.01) and reduced with L-arginine after 120 minutes (p < 0.01) compared with control animals. Water content was significantly decreased in the heart, lung, skin, muscle and peritoneum in rats receiving L-arginine. These data suggest that endogenous nitric oxide plays an important role in minimizing fluid accumulation during cardiopulmonary bypass.

Bronchopleural fistula. Thirteen-year experience with 77 cases.

Bronchopleural fistula, although reduced in incidence in recent years, remains a grave complication of pulmonary disease and of pulmonary resection. In a series of 77 patients treated for bronchopleural fistula over a 13 year period, 49 of whom had postresection fistulas, only 44 (57.1 percent) were cured of the fistula and 15 (19.5 percent) died. Prevention assumes great importance. Key factors in prevention are avoidance of pulmonary resection in tuberculous patients with positive sputum; overzealous dissection of the bronchus; a long bronchial stump; tumor in the bronchial stump; contamination of the pleural cavity; and too little tissue left behind to fill the pleural space. Treatment should be surgical. In none of the six patients treated conservatively was the fistula obliterated. Seventy-one patients were treated surgically, and 133 operations were needed to effect fistula obliteration in the 44 patients (62 percent) in whom this was achieved. Adequate surgical drainage has always been the sine qua non of effective treatment, and yet this alone brought about closure of the fistula in only nine patients. Early resuture of the bronchial stump succeeded in only two of five patients. Thoracoplasty combined with drainage effected closure in seven of 11 patients. The highest rate of fistula closure with the lowest mortality occurred among the 20 patients who underwent myoplasty, usually combined with a limited thoracoplasty. In this group, the fistula was obliterated in 16 patients, with one death.

Heparinless partial cardiopulmonary bypass for the repair of aortic trauma.

OBJECTIVE: We hypothesized that partial cardiopulmonary bypass with a heparin-bonded system would be a technically simple, effective adjunct for reducing paraplegia during repair of traumatic aortic rupture. It avoids the risk of heparin, but, unlike left atrial-arterial bypass, it can heat, cool, oxygenate, and rapidly infuse volume if needed. METHODS: A retrospective review was conducted of patients admitted for aortic trauma from July 1994 to December 1999. Bypass consisted of femoral venous (right atrial) cannulation, a centrifugal pump, and an oxygenator-heater/cooler. Arterial return was to the femoral artery or distal aorta. The entire system was heparin-bonded and no systemic heparin was given. RESULTS: Heparin-bonded partial bypass was established in 50 patients (mean age 43 +/- 17 years). Crossclamp time was 32 +/- 11 minutes (range 14-70 minutes), mean flow 3.0 +/- 0.8 L/min, and bypass time 64 +/- 43 minutes. During repair, 58% of patients received volume through the system (mean 1.1 +/- 1.9 L). Core temperature rose slightly (35.9 degrees C +/- 0.7 degrees C to 36.3 degrees C +/- 0.8 degrees C). Three of the 15 patients who underwent percutaneous femoral arterial and venous cannulation concomitant with their angiograms had vessel injury, with one limb loss, and this procedure was discontinued. Thirty-five patients underwent percutaneous femoral vein and direct distal aortic cannulation without event. The mortality rate for patients supported by bypass was 10%, and all deaths were due to other injuries. There were no new cases of paraplegia and no worsening of intracranial or pulmonary injuries. CONCLUSIONS: Heparin-bonded bypass is technically simple to use and avoids the risk of anticoagulation. Paraplegia was avoided. The ability to correct hypothermia, oxygenate, and rapidly infuse volume may simplify management and improve outcomes.

Increased p53 protein expression in human failing myocardium.

BACKGROUND: The p53 gene is a tumor-suppressor gene which involves apoptosis and cell-cycle arrest under certain stress stimulate. However, the status of the p53 gene expression in human myocardium in congestive heart failure (CHF) remains unclear. Therefore, the current study was designed to investigate the expression of the p53 protein in human myocardium in normal subjects and in patients with severe CHF. METHODS: Human ventricular cardiac tissue was obtained from 7 normal subjects and 7 end-stage CHF patients during cardiac transplantation. The expression of p53 protein was determined by immunohistochemical staining. The cardiac apoptosis was determined by TUNEL staining. RESULTS: The p53 protein was minimally stained in normal human ventricular cardiomyocytes. In contrast, the staining density and positive stained nuclear (%) of p53 was significantly increased in ventricular cardiomyocytes of patients with severe CHF. Apoptosis in CHF human myocardium also markedly increased. CONCLUSIONS: The significantly increased expression of p53 in CHF human cardiomyocytes suggests that p53 may play an important pathophysiological role in the process of CHF through mechanisms involving myocardial apoptosis.

Obesity and diabetes as risk factors for postoperative wound infections after cardiac surgery.

During a 30-month period, 20 median sternotomy wound infections or endocarditis occurred after 20 of 1204 (1.7%) cardiac surgery procedures in adults at the University of Maryland Hospital. We examined four risk factors related to the individual undergoing surgery: age, sex, and index of obesity (weight/height), and presence of diabetes mellitus. The odds ratio estimates of the relative risk of infection observed with use of a population control group were as follows: sex (female) 3.5 (p less than 0.05), obesity 2.0, and presence of diabetes mellitus 3.8. For a second control group matched for age, type of operative procedure, and date of operation, the estimated relative risks of infection were sex (female) 2.1, obesity 6.2 (p less than 0.05), and diabetes mellitus 2.0. More precise definition of the relative risk of sternotomy infection associated with obesity and diabetes is required to aid surgeons and patients in making judgments about the relative benefits of surgery and to alert nursing personnel to be particularly aware of early signs of infection in patients at high risk.

Thoracoscopic lymph node staging for esophageal cancer.

Thoracoscopy allows evaluation of the mediastinum and assessment of the local spread of malignancy. Adjuvant therapy trials have shown some increased survival for esophageal cancer although morbidity is high. Preoperative staging may allow appropriate allocation of adjuvant therapy. Patients with esophageal cancer underwent computed tomographic scan, magnetic resonance imaging, and endoesophageal ultrasonography. Thoracoscopic staging was performed through the left chest with biopsy of American Thoracic Society level 5 and 6 and 8 and 9 lymph nodes. Resection at a separate sitting with complete intraoperative lymph node sampling was done. Fourteen patients underwent thoracoscopic lymph node staging. One procedure could not be completed because of adhesions. Of the 13 patients undergoing successful staging, all had correct thoracic lymph node staging confirmed at surgical exploration. Two patients with adenocarcinoma of the distal third/gastroesophageal junction were found at laparotomy to have positive celiac lymph nodes. Two patients who had lymph nodes positive at computed tomographic scan and magnetic resonance imaging were found to have negative lymph nodes at thoracoscopy and subsequent resection. Two patients were found to have pulmonary metastasis at thoracoscopy. Lymph node stage in esophageal carcinoma is an important prognostic indicator. Thoracoscopic lymph node staging provides accurate pre-resection staging information.

Open lung biopsy in diagnosing pulmonary infiltrates in immunosuppressed patients.

From July, 1973, to June, 1977, 25 patients in an immunosuppressed state from underlying reticuloendothelial neoplasm or associated chemotherapy, underwent open biopsy of the lung at the University of Maryland Hospital for diagnosis of unilateral diffuse pulmonary infiltrates. Eight patients were in marked respiratory distress, 13 in moderate distress, and 4 in little or no distress at the time of open lung biopsy. There were 3 postoperative deaths (12%). The operation-related morbidity was 1 out of 25 (4%). Two of the patients who died were found to have irreversible pulmonary fibrosis secondary to bleomycin drug therapy. The subsequent treatment of all 25 patients was influenced by the biopsy findings as follows: upgrading the disease stage or establishing treatment failure in 11 patients; establishing the presence of inflammatory disease in 3 patients; establishing the diagnosis of fibrosis associated with drug treatment without recurrent disease or infection in 11 patients. The preferability of open lung biopsy as opposed to transbronchial or percutaneous techniques is discussed.

A technique to repair type I left ventricular rupture following mitral valve replacement.

Rupture of the posterior left ventricle is a serious complication following mitral valve replacement. A successful method of repair is illustrated. The causes, other methods of repair, and means to prevent this complication are discussed.

Complications of thoracoscopy.

BACKGROUND: The revolution in video technology has led to the acceptance of thoracoscopy as an important tool in thoracic surgery. METHODS: A review of all patients undergoing thoracoscopy at the University of Maryland between November 1991 and March 1995 was performed to identify the incidence of intraoperative and postoperative complications. In addition, the role of computed tomography for predicting intraoperative complications was analyzed. RESULTS: Three hundred forty-eight procedures were performed in 321 patients. Twenty-seven patients required conversion to thoracotomy for various indications. In 12 patients further resection was required after frozen section diagnosis confirmed lung carcinoma. Six patients were opened due to adhesions. Two patients were opened due to inability to find the lesion (this represents 1.6% of all solitary pulmonary nodules). Three cases were converted to thoracotomy for lesions that were too large to remove (representing 2.5% of all solitary pulmonary nodules resected). Two patients required conversion to thoracotomy because of inability to obtain one-lung ventilation. One case required a limited thoracotomy for a lost needle used for needle localization of a solitary intraparenchymal nodule, and 1 patient had emergent exploration for bleeding. Early postoperative complications developed in 10 patients. There were two explorations in the immediate postoperative period for bleeding. Prolonged air leak occurred in 3 patients, empyema in 2, and recurrent pneumothorax, pulmonary edema, and pneumonia in 1 patient each. Computed tomography failed to diagnose adhesions in the majority of patients requiring conversion to thoracotomy. CONCLUSIONS: Thoracoscopy is a safe and effective procedure with low intraoperative and postoperative complication rates.

Transhiatal esophagectomy for carcinoma of the esophagus: experience with 26 patients.

Transhiatal esophagectomy was performed in 26 patients with esophageal carcinoma. The patients were selected for this procedure by means of transhiatal palpation of the tumor at laparotomy. Twenty had squamous cell carcinoma and 6, adenocarcinoma. The tumor locations were the upper third in 8, middle third in 12, and lower third in 6. On postoperative staging, 15 patients had Stage III and 6, Stage IV neoplasms. Among 25 elective resections there was 1 hospital death, which was due to severe coronary artery disease. One patient who had an urgent resection for a perforated carcinoma died of multisystem failure 32 days postoperatively. Complications included splenic injury requiring splenectomy in 5 patients; tracheal laceration in 2 patients (only 1 requiring a thoracotomy); azygos vein laceration requiring sternotomy for repair in 1 patient; chylothorax in 1; recurrent laryngeal nerve paralysis in 3 (temporary in 2); and transient anastomotic leaks in 3. Five patients had pneumonia with transient respiratory failure. Twelve of the operative survivors died of cancer 3.2 to 32 months postoperatively, and 12 are alive 3 to 28 months after operation. The actuarial survival is 53 +/- 11% (+/- standard error) at one year and 46 +/- 12% at two years. Transhiatal esophagectomy is a reasonable, safe operation that should be considered for tumors at all levels of the esophagus.

Use of a zipper in cardiac surgical operations.

A simplified technique to gain repeated access to the median sternotomy incision is presented. The technique involves the use of a sterile polyester zipper attached to the skin edge. The sternum remains open. Unzipping the zipper allows for repeated relief of cardiac tamponade and viewing of cardiac action. Other advantages include prevention of cardiac compression or kinking of assist device cannulas from sternal closure, ease in changing of dressings, and quick removal of ventricular assist devices without reopening the sternum.

On antibiotic prophylaxis in cardiac surgery: a risk factor for wound infection.

During a 30-month period, median sternotomy wound infections or endocarditis developed during the first 60 days postoperatively following 20 of 1,204 (1.7%) adult cardiac procedures at the University of Maryland Hospital. Fifty percent of the infected patients received perioperative clindamycin prophylaxis. A retrospective study was conducted in which the odds ratio estimate of the relative risk of sternotomy infection or endocarditis for patients receiving clindamycin prophylaxis compared with patients receiving cefamandole was found to be 17.0 (p less than .001) using population controls and 8.25 (p less than .001) using matched controls. Seventy-five percent of the organisms causing infections, principally Staphylococcus epidermidis, were resistant in vitro to clindamycin. Perioperative clindamycin administration was not fully effective in preventing wound infection following cardiac surgery at our hospital, thus providing indirect evidence for the efficacy of prophylaxis with cephalosporin-containing regimens. Trials of alternative antibiotics to clindamycin for prophylaxis in penicillin-allergic patients undergoing cardiac surgery are indicated.

Postoperative conduction disturbances: a comparison of blood and crystalloid cardioplegia.

Conduction system disturbances after cardioplegia are well described. Our four-man group changed in mid-1987 from standard crystalloid cardioplegia (35 mEq/L of KCl) to blood cardioplegia (4 parts blood to 1 part cardioplegia) (18 mEq/L of KCl) based on experimental and clinical evidence that blood cardioplegia provides better myocardial protection. Shortly thereafter, we anecdotally noted increased conduction abnormalities. This prompted us to compare serially all patients undergoing coronary artery bypass grafting during 1987 for perioperative and late conduction system disturbances after either crystalloid or blood cardioplegia. Surgeons and techniques including topical cooling did not differ. Forty-one (23%) of 179 patients with crystalloid cardioplegia had conduction disturbances versus 141 (49%) of 289 patients with blood cardioplegia (p less than 0.001). Perioperative complete heart block requiring atrioventricular sequential pacing occurred in 20 patients with crystalloid cardioplegia versus 67 patients with blood cardioplegia (p less than 0.002), and atrioventricular block requiring permanent pacing was present in 4 and 12 patients (p less than 0.001), respectively. Left bundle-branch block was found in 8 patients given crystalloid cardioplegia and 28 patients with blood cardioplegia (p less than 0.05); right bundle-branch block, 12 and 68 patients (p less than 0.001); left anterior hemiblock, 8 and 37 patients (p less than 0.001); and interventricular conduction delay, 15 and 53 patients (p less than 0.005), respectively. Bifascicular block occurred in 4 patients receiving crystalloid cardioplegia versus 23 receiving blood cardioplegia (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic, traumatic pseudoaneurysm of the ascending aorta.

Rupture of the ascending aorta is lethal in virtually all cases. In the recent literature, fewer than 9 cases of chronic, traumatic pseudoaneurysm of the ascending aorta have been documented. Reported herein is such a case, discovered incidentally and repaired successfully under cardiopulmonary bypass using a graft prosthesis. Aortogram remains the diagnostic method of choice in these patients.

Thoracoscopic excision of a posterior mediastinal "dumbbell" tumor using a combined approach.

Up to 10% of neurogenic tumors in the posterior mediastinum demonstrate intraspinal extension. Historically, these lesions have been considered resectable only by a combined thoracic and neurosurgical approach using thoracotomy. Herein, a thoracoscopic excision of a "dumbbell" lesion within the framework of a combined approach is described.

Subarachnoid-pleural fistula after resection of a pancoast tumor with hyponatremia.

Resection of superior sulcus neoplasms is associated with a number of complications resulting from the extensive nature of the resection and the necessity to sacrifice certain adjacent structures. One of the complications of resection is the development of subarachnoid-pleural fistula, with the subsequent appearance of air in the cerebrospinal fluid circulation. We report a case in which a subarachnoid-pleural fistula led to persistent pneumocephaly in a patient who exhibited postoperative hyponatremia, confusion, and gait disturbance.

Open drainage of massive tuberculous empyema with progressive reexpansion of the lung: an old concept revisited.

BACKGROUND: This study examined the results of open drainage of massive tuberculous empyema. METHODS: During a 7-year period 47 patients with primary mixed chronic tuberculous empyema with near or total lung collapse were treated. The initial procedure was chest tube suction drainage, which permitted evaluation of the pleural cavity and the lung parenchyma despite minimal if any reexpansion of the lung. All patients were treated with antibiotics and multidrug regimens of antituberculosis agents. A pleurocutaneous window was established by removing sections of two ribs one intercostal space above the base of the pleural cavity. Irrigation was performed daily with dilute povidone iodine solution. RESULTS: Twenty-eight patients achieved complete reexpansion of the lung after 4 to 30 months of drainage and are cured. Eleven are in various stages of reexpansion and probably will be cured. Eight patients did not achieve reexpansion. Criteria were established retrospectively on an ongoing basis that indicate when pulmonary reexpansion is possible. CONCLUSIONS: These totally collapsed "entrapped" lungs expanded to fill the entire pleural space despite the presence of bronchopleural fistulas and an "open" pleura. Reexpansion was progressive, gradual, and dependent on improved compliance, clearing of bronchial inflammation and obstruction, and pleural cleansing. Criteria are established that identify those patients in whom complete reexpansion may take place and the disease may be cured.