Biomedical subjects
Publications and source records attributed to M J Krasna.
Left transthoracic esophagectomy remains an important option in performing esophagectomy. This is especially appropriate for malignancies of the distal esophagus and gastroesophageal (GE) junction. Likewise, resections in patients who have had prior surgery at the GE junction are easily performed through the left chest. The technical details of left transthoracic esophagectomy are described and illustrated.
Loss of heterozygosity (LOH) affecting chromosome 9p has been shown to occur frequently in head and neck cancer, glioma, mesothelioma, melanoma, lung cancer, and numerous other tumor types. Chromosome 9p is therefore presumed to contain a tumor suppressor gene or genes. Since esophageal cancer shares characteristics with some of the above tumor types, we performed a detailed examination of 60 patients with squamous cell carcinoma or adenocarcinoma of the esophagus for LOH at loci D9S162, IFNA, D9S171, D9S126, D9S104, D9S165, and D9S163. Multiplex polymerase chain reactions were performed with the inclusion of one radiolabeled nucleotide, and products were electrophoresed on denaturing polyacrylamide gels. Thirty-six of the 60 patients (60%) exhibited LOH at one or more loci on chromosome 9p. Eight of 17 patients (47%) with adenocarcinoma manifested LOH, while 28 of 43 (65%) with squamous cell carcinoma showed LOH. LOH was most frequent at loci D9S171 (19 of 23, or 83%) and D9S165 (24 of 32, or 75%). These data support the hypothesis that a tumor suppressor gene or genes located on this portion of chromosome 9p exert(s) an effect on esophageal cancer development.
Alterations of microsatellites consisting of extra or missing copies of these sequences occur at relatively high frequencies in sporadic and hereditary colorectal adenocarcinomas, gastric and pancreatic cancers, and at lower frequencies in endometrial, bladder, ovarian, and other carcinomas. We determined the prevalence of microsatellite instability in esophageal adenocarcinoma, Barrett's esophagus, and squamous cell carcinoma of the esophagus. Assays were performed on 105 patients, including 28 subjects with Barrett's metaplasia, 36 with Barrett's-associated adenocarcinoma, and 42 with primary esophageal squamous cell carcinoma. Flow cytometric nuclear sorting based on DNA content was performed on 25 of the adenocarcinomas prior to DNA extraction. Specimens from 11 of the 106 patients (10%) showed instability at 1 or more chromosomal loci. Instability was seen in 2 of 28 patients (7%) with Barrett's metaplasia alone, in 8 of 36 (22%) with adenocarcinoma, and in 1 of 42 (2%) with squamous cell carcinoma. Among the 25 flow cytometrically sorted adenocarcinomas, instability occurred in 8 (32%); sorted diploid nuclei from these tumors showed instability in 4 of 8 cases (50%). These data indicate that microsatellite instability occurs frequently in Barrett's-associated esophageal adenocarcinoma. They also suggest that in esophageal adenocarcinomas, microsatellite instability can develop as an early event in metaplasia and in diploid tumor cells, before aneuploidy occurs.
We investigated the effects of increases in central venous pressure (CVP) and carotid baroreceptor-induced vasodilation on the rate of extravascular fluid uptake during cardiopulmonary bypass in normotensive and Goldblatt hypertensive dogs. Carotid sinus baroreceptors were selectively perfused to control the level of vasodilation. Central venous pressure was controlled by changing the height of the venous outflow cannula. Extravascular fluid uptake was determined from the rate of change in reservoir volume. After 3 hours of bypass, total fluid accumulation was 56.11 +/- 14.16 mL/kg in normotensive dogs, significantly less than in hypertensive dogs (110.90 +/- 23.20 mL/kg) (p < 0.05). Raising CVP from 1 to 5 mm Hg increased the rate of extravascular fluid uptake in both normotensive (from 0.05 +/- 0.25 to 0.85 +/- 0.22 mL.kg-1.min-1; p < 0.05) and hypertensive dogs (from 0.68 +/- 0.28 to 2.57 +/- 0.46 mL.kg-1.min-1; p < 0.01)). At a constant CVP, baroreceptor-induced vasodilation increased the rate of extravascular fluid uptake in normotensive (from 0.25 +/- .15 to 0.81 +/- .22 mL.kg-1.min-1) and in hypertensive dogs (from 0.84 +/- .12 to 1.72 +/- .32 mL.kg-1.min-1; p < 0.05). Hypertensive dogs were more sensitive to changes in CVP and to baroreceptor-induced vasodilation. The results of this study imply that elevations in CVP or the use of vasodilators may lead to increased extravascular fluid uptake during bypass; this effect may be exacerbated in the hypertensive state.
As more complex thoracoscopic procedures are performed, adequate exposure becomes increasingly more important. The insufflation of CO2 has been demonstrated to aid in the compression of lung parenchyma and the effacement of subpleural lesions, and to act as a retractor when combined with changes in patient position. However, a recent study demonstrated that CO2 insufflation during thoracoscopy in the pig had adverse hemodynamic consequences. We prospectively studied 32 patients undergoing thoracoscopy to evaluate the effects of CO2 insufflation in the clinical setting. The end-tidal CO2 pressure, arterial oxygen saturation, mean arterial pressure, heart rate, and central venous pressure were monitored. Measurements were determined at baseline, at the initiation of one-lung ventilation, and at intrapleural pressures of 2 to 14 mm Hg. We found that the insufflation of CO2 of 2 to 14 mm Hg had no significant effect on the end-tidal CO2 pressure, arterial oxygen saturation, heart rate, or mean arterial pressure, but the central venous pressure did rise from 7.00 +/- 1.5 mm Hg to 17.30 +/- 2.53 mm Hg (p < 0.05). We conclude from this that the insufflation of CO2 during thoracoscopy does not have adverse hemodynamic effects in the clinical setting. Therefore, we propose that low-pressure (< 10 mm Hg) insufflation is a safe adjunct to the conduct of routine thoracoscopic surgical procedures.
A patient with bronchopleural fistula was successfully treated by occluding the fistula with an inflated Fogarty catheter balloon packed with oxidized regenerated cellulose (Surgicel) using a fiberoptic bronchoscope. After 48 h, the balloon was deflated, the fistula had sealed, and the patient did well. This simple and relatively noninvasive therapy was effective in this patient who was not a surgical candidate.
Thoracoscopy has become an important tool in the diagnosis and management of intrathoracic disease. Between April 1991 and October 1992, 93 patients underwent thoracoscopy. Lung resection was performed on nineteen patients for diagnoses of interstitial lung disease and on seven patients for pulmonary nodules. Eleven patients underwent therapeutic lung resection for management of pneumothorax or air leaks. Sixteen patients underwent thoracoscopy for pleural disease. This was to diagnose mesothelioma (2), to lyse benign adhesions (2), to drain empyema (2), and to evacuate loculated pleural effusion (10) thoracoscopically. Nine patients underwent thoracoscopic staging for lung cancer. Thirteen patients underwent thoracoscopic staging for esophageal cancer as part of a prospective trial. Other indications for thoracoscopy included pericardiectomy (6), sympathectomy (2), and resection of mediastinal mass (4). Thoracoscopy is an excellent option for patients at high risk from standard thoracotomy and may allow procedures to be performed which would prevent the need for open thoracotomy, resulting in shorter hospital stay and less postoperative pain.
Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.
Solitary nodular pulmonary amyloid tumor is an uncommon benign lesion which is seldom diagnosed prior to surgical extirpation. We present a case of unsuspected nodular pulmonary amyloid tumor diagnosed by fine needle aspiration cytology. A 52-yr-old-black woman, presented with a 3-cm right middle lobe mass. Percutaneous fine-needle aspiration cytology (FNA) of the mass revealed waxy amorphous material that demonstrated apple green birefringence on Congo Red Stain. Thoracotomy for diagnosis may be avoided by using FNA to diagnose these unusual lesions.
The third edition [1988] of the Manual for Staging of Cancer of the American Joint Committee on Cancer (AJCC) was developed to permit finer discrimination between stages than was true of the previous edition [1983]. This study was designed to determine whether or not this goal was achieved. Pathologic staging of the specimens removed from 265 patients with carcinoma of the esophagus or cardia undergoing esophagogastrectomy between 1970 and 1988 was performed according to criteria published in the second and third editions and their survival data compared. The new staging criteria of the AJCC provides no better discrimination of stages according to survival than was true of the earlier version, the 5-year survival of stage IIA patients being similar to that of stage I patients (37.5 +/- 6.7% vs. 50.8 +/- 17.7%), and the survival of stage IIB patients being similar to that of stage III patients (16.2 +/- 8.1% vs. 13.6 +/- 3.7%). However, depth of wall penetration and extent of lymph node involvement were reliable independent predictors of survival. We propose a modified version of the Skinner WNM staging plan that provides a modest increase in staging fragmentation.
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.
With the advent of advanced video and laparoscopic techniques, new applications have been found for thoracoscopy's expanding role in thoracic surgery. Described herein are three cases of thoracoscopic sympathectomy for three different indications. The evaluation and surgical technique are described in detail. Thoracoscopic sympathectomy is an excellent alternative to open transthoracic approach.
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.
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Preoperative staging in esophageal cancer is usually done by noninvasive tests. Currently, in the staging of lung cancer, when lymph nodes are identified preoperatively by CT or MRI to be greater than 1 cm, surgical staging using mediastinoscopy, Chamberlain procedures, or thoracoscopy are employed. We describe herein the use of thoracoscopy in routine preoperative staging of esophageal cancer. With the advent of newer laparoscopic techniques currently available, thoracoscopy plays an increasing role in the management of intrathoracic disease. Staging thoracoscopy as a routine preoperative invasive staging test appears to be a good diagnostic test.
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In conclusion, blunt cardiac trauma is the leading cause of fatalities following motor vehicle accidents. Although many of the patients with anatomic cardiac injuries die at the scene, with improved prehospital care these patients have more likelihood of surviving the first hour and presenting to an emergency room alive for definitive treatment. Prompt recognition of the injury based on the mechanism and a high index of suspicion must lead to immediate surgical intervention in order for these patients to survive. Patients with functional cardiac injuries (myocardial contusion/concussion) usually present a much less urgent scenario. They should be triaged early on the basis of admission ECG and severity of pre-existing or associated injuries to appropriately monitored units. This will allow better allocation of scarce hospital resources rather than blindly pursuing "routine" (expensive) work-ups. The sequelae of these injuries are generally nonfatal. If serious sequelae do arise in the ICU or in the OR, prompt treatment with inotropic support is usually successful.
Gastrointestinal contrast studies were performed in 96 (27 percent) of 342 patients with small-bowel obstruction including 57 upper gastrointestinal and 39 barium-enema examinations. In 34 patients, upper gastrointestinal examination disclosed either obstruction or failure of contrast to reach the cecum in 24 hours; all 34 patients required surgery. The remaining 23 patients who had upper gastrointestinal studies recovered with tube decompression. Barium enema demonstrated obstruction in 13 (33 percent) of 39 cases of suspected small-bowel obstruction and localized obstruction in the colon rather than small bowel in 9 of 13 cases. Barium enema was 100 percent predictive of surgery when obstruction was shown, but was not helpful in predicting surgery when obstruction was not demonstrated. Surgery was required in 42 percent of patients whose barium enema did not show obstruction. Barium enema also was performed in 19 of 23 patients with large-bowel obstruction and showed the level of obstruction in all cases. All patients with large-bowel obstruction required surgery except for three who recovered after barium-enema reduction of intussusception or volvulus. Barium upper gastrointestinal examination is recommended in small-bowel obstruction when plain films are nondiagnostic, and in selected cases of small-bowel obstruction that do not resolve with a short trial of tube decompression. Barium enema is not recommended in suspected small-bowel obstruction but should be performed in all cases of large-bowel obstruction, except when perforation is a possibility or when the cecum measures 10 cm or larger in diameter.