Bronchoscopic palliation of primary lung cancer: single or multimodality therapy?

BACKGROUND: An obstructing primary lung cancer is a challenging disease frequently requiring endobronchial interventional therapy. A variety of interventional modalities, including Nd:YAG laser, stenting, photodynamic therapy (PDT), and endoluminal brachytherapy, are utilized to relieve airway obstruction and bleeding. The aim of this study is to compare the effect on patient survival of bronchoscopic palliation for lung cancer utilizing one interventional modality compared to the use of combination of modalities to relieve the airway problem. METHODS. We reviewed our longitudinal experience with interventional bronchoscopy in 75 patients who underwent 176 procedures for the management of endobronchial lung cancer between 1994 and 2002. Indication for intervention was hemoptysis in 24 patients (32%) and airway obstruction in the remaining. Six patients died within 30 days from the first intervention and were excluded. Forty of the surviving 69 patients (58%) were treated with a single interventional modality (group A). In 29 patients (42%) a multimodality endoscopic treatment was utilized (group B). Single-modality treatment in group A included Nd-YAG laser in 60%, stent in 17%, brachytherapy in 20%, and PDT in 3%. A variety of combinations of the aforementioned modalities were used in group B to enhance airway patency. Patient data were compared with the Student's t-test and chi-square test. Survival analysis and the log rank test were used to compare difference in survival between the two groups. A p-value of 0.05 was considered significant. RESULTS: There were 46 males and 23 females, with a mean age of 67 years. The tumor was located in the trachea 9%, in the carina in 7%, and primary bronchial in 84%. Two patients had complications due to stent malposition. There was no significant difference between the two groups in relation to age, gender, tumor location, histology, and type of previous cancer therapy. There was a significant improvement in survival for the multimodality group (p = 0.04). The 1- and 3-year cumulative survival rate for groups A and B was 51.3% versus 50% and 2.3% versus 22%, respectively. CONCLUSIONS: Improvement in survival can be seen with diligent airway surveillance after interventional bronchoscopy and liberal use of a variety of endobronchial treatment modalities for airway obstruction or bleeding. Physicians involved in the management of this difficult problem should be versed in the use of all available treatment modalities to enhance therapeutic outcome.

The presence of colorectal hepatic metastases does not preclude pulmonary metastasectomy.

Hepatic metastases due to colorectal carcinoma have often been felt to preclude pulmonary metastasectomy. With the recent advances in surgical options, should patients with both liver and lung metastases be considered for surgical resection? The current study reviews the impact of such aggressive management on disease-free and overall survival (OS). The clinical course of 63 patients presenting with colorectal metastasis to the lung alone (group 1, n = 45) or combined hepatic and lung metastases (group 2, n = 18) were reviewed. All patients underwent complete resection of their lung metastases. Surgical control of hepatic tumor burden was achieved by tumor ablation, intra-arterial therapy, and/or resection. All patients in group 1 and group 2 were available for a mean follow-up of 27 and 24 months, respectively. The presence of hepatic metastases, the resectability of hepatic tumor burden, and the disease-free interval after pulmonary metastasectomy did not significantly influence survival. These findings demonstrate that aggressive surgical management of pulmonary metastases in the presence of liver metastases offers a similar benefit as compared to patients with pulmonary metastases alone. Therefore, hepatic metastatic disease does not preclude an attempt at pulmonary metastasectomy if hepatic metastases can be resected or remains responsive to therapy. Such an approach achieves comparable OS and mean survival when compared to pulmonary metastasectomy alone.

Bilateral anterior minithoracotomy with video assistance for lung volume reduction surgery and pulmonary metastasectomy.

Incisional access to pulmonary pathology involving both lungs has often involved bilateral standard thoracotomies, median sternotomy, and, recently, sequential lateral video-assisted thoracic surgical approaches. Significant problems are inherent to each of these approaches. We introduce a hybrid technique of bilateral simultaneous minithoracotomy with video assistance as an alternative to these other surgical approaches.

Immediate radiographic assessment following laparoscopic antireflux operations is unnecessary.

BACKGROUND: Laparoscopic antireflux operations (LAP) have become increasingly common for the treatment of gastroesophageal reflux disease (GERD). We sought to determine if routine postoperative barium contrast studies following LAP were clinically efficacious in identifying technical problems and life-threatening complications related to the surgical intervention. METHODS: From January 1996 to December 1997, 112 barium studies were performed following 112 LAP procedures (47 male/65 female patients; mean age, 51 years) (group I). This group was compared to a subsequent cohort of 67 patients who underwent LAP between January 1998 and July 1998 without routine early postoperative barium contrast study (group II). RESULTS: In 111/112 of the barium studies of group I, no radiographic abnormality was identified. The average length of stay (LOS) for these patients was 2.6 days. Routine barium studies were not utilized in group II. The average length of stay for patients in group II was 1.4 days. Twelve group II patients underwent early postoperative barium studies to evaluate suspicious clinical symptoms. None of these 12 postoperative studies identified important problems, nor did they alter the patients' clinical management. However, because of the barium study, their LOS was equivalent to those patients who had undergone routine barium study (2.4 days). There was an increase of $1451.80 in hospital charges in the group of patients who had a barium study, largely as a result of the increased LOS. CONCLUSION: The routine use of these studies results in increased patient charges and a prolongation in the length of hospital stay. Immediate postoperative barium studies following laparoscopic antireflux operations are of little value in determining important postoperative problems among patients undergoing LAO.

Experience and technique of stapled mechanical cervical esophagogastric anastomosis.

BACKGROUND: Anastomotic leak from cervical esophagogastric anastomoses is a serious problem after esophagectomy. We explored the efficacy of partial or total mechanical anastomoses accomplished with the endoscopic linear cutting and stapling device as an alternative to hand-sewn anastomotic techniques. METHODS: During a 42-month period, 93 patients undergoing either transhiatal esophagectomy or a three-incisional approach to esophagectomy underwent either hand-sewn (n = 43), partial mechanical (n = 16), or totally mechanical (n = 34) cervical esophagogastric anastomoses. The occurrence of postoperative anastomotic leak and the development of postoperative anastomotic stricturing requiring dilation therapy were analyzed between these groups using chi2. RESULTS: All patients survived esophagectomy and were available for postoperative follow-up. Anastomotic leak developed in 10 patients (23%) with hand-sewn, 1 patient (6%) with partial mechanical, and 1 patient (3%) with total mechanical anastomoses (p < 0.05). Anastomotic stricture development paralleled the occurrence of anastomotic leak rate with 25 patients (58%) with hand-sewn, 3 patients (19%) with partial mechanical, and 6 patients (18%) with total mechanical anastomoses experiencing strictures requiring dilation therapy (p < 0.05). CONCLUSIONS: These results suggest that partial or mechanical cervical esophagogastric anastomoses created with the endoscopic stapling device may be superior to hand-sewn anastomotic techniques.

Extensive posterior-lateral tracheal laceration complicating percutaneous dilational tracheostomy.

BACKGROUND: An extensive posterior-lateral longitudinal tracheal laceration is an uncommon but serious complication of percutaneous dilational tracheostomy (PDT). We report the successful management of three ventilator-dependent patients whose percutaneous tracheostomy was complicated by an extensive longitudinal posterior-lateral tracheal laceration requiring operative repair. METHODS: A retrospective review of 134 cases of PDT with concurrent bronchoscopy was performed between April 1997 and July 1999 and compared with a review of 124 cases of open tracheostomy. Tracheal lacerations were primarily repaired and augmented with intercostal muscle pedicle buttress. RESULTS: Three cases of an extensive posterior-lateral longitudinal tracheal laceration that required operative repair were reported in the PDT group. None were reported in the open tracheostomy group. The 3 patients were managed with an adult high-frequency oscillating ventilator or pressure control ventilation during the postoperative period to limit barotrauma, and all healed without evidence of tracheal leak or stenosis. CONCLUSIONS: The increasing popularity of PDT, particularly among nonsurgical disciplines, may generate an increasing number of complications requiring operative attention. Thoracic surgeons need to be cognizant of the pitfalls of PDT technique and be prepared to manage these difficult clinical scenarios.

Reoperative laparoscopic antireflux surgery.

BACKGROUND: Laparoscopic antireflux surgery (LAP) is becoming increasingly used for the surgical treatment of medical recalcitrant gastroesophageal reflux disease (GERD). We sought to determine the utility of remedial LAP approaches to antireflux surgery. METHODS: From March 1996 to December 1998, 15 patients underwent remedial LAP to manage medically recalcitrant recurrent GERD after LAP (n = 8) or open antireflux procedure (n = 1) and/or troublesome postfundoplication complications (dysphagia 6, gas bloat 4). The remedial LAP surgery consisted of conversion from Nissen to Toupet fundoplication to manage dysphagia or gas bloat symptoms (n = 7), revision of IAP Nissen fundoplication (n = 7) and LAP revision of a failed open Nissen fundoplication (n = 1) for recurrent reflux. RESULTS: The remedial LAP repair was accomplished in all patients. Findings at operation included disrupted fundoplication (n = 6), incomplete or inappropriately positioned fundoplication (n = 2), paraesophageal hernia (n = 3), or a normal total fundoplication among patients with primary dysphagia (n = 4). Follow-up symptom scoring beyond 3 months of remedial surgery demonstrated a change from the preoperative mean dysphagia, heartburn, gas bloat, and regurgitation score (P < .05). Follow-up GERD testing (manometry, upper gastrointestinal tract, pH testing) was normal in 13 of the 15 patients. CONCLUSIONS: Reoperative antireflux surgery can be accomplished using LAP approaches without compromise of therapeutic intent or increased surgical morbidity. Surgeons sufficiently experienced with these LAP repairs may consider repeat LAP instead of open surgery for patients with recurrent GERD or postfundoplication problems.

Risk management at the heart of the matter: addressing acute coronary care.

Every year, 540,000 patients enter a hospital for myocardial infarction. Of these, 4% to 13% will be misdiagnosed and 11%-25% of them may die as a result. Missed diagnoses are the most expensive claims against emergency department physicians and account for 20% of all losses paid by them. A sound risk management program can save lives and dollars by supporting the effective and safe treatment of patients requiring acute coronary care.

Canine lung transplantation after more than twenty-four hours of normothermic preservation.

BACKGROUND: Consistent clinical results have not been achieved when lung preservation times exceed 6 hours. The aim of this study was to use an alternative normothermic autoperfusion technique for lung preservation and transplantation. METHODS: In six paired dogs, donor lungs were removed, along with the heart, liver, pancreas, duodenum, and both kidneys, and were preserved for 24 to 33 hours in a normothermic autoperfused multiple organ block. Orthotopic left lung transplantation was performed at the end of the preservation period. RESULTS: Lung function was good during the preservation period. With a gas mixture of 50% O2 + 3% CO2 + 47% N2 delivered to the multiorgan block, arterial oxygen tension ranged from 331 +/- 19 to 383 +/- 8 mm Hg; carbon dioxide tension ranged from 18 +/- 5 to 32 +/- 5 mm Hg; and pH ranged from 7.36 +/- 0.02 to 7.45 +/- 0.08. After transplantation, the dogs were kept anesthetized and ventilated for 24 hours with the same gas mixture. The opposite pulmonary artery was occluded 0 to 6 hours after transplantation. Arterial blood pressures were stable after surgery. Arterial oxygen tension was maintained between 205 +/- 39 and 320 +/- 57 mm Hg, and arterial carbon dioxide tension was maintained between 23 +/- 2 and 34 +/- 2 mm Hg. Lung tissue wet/dry weight ratio was 4.94 +/- 0.17 after preservation; this ratio did not differ from that found in normal controls (4.91 +/- 0.10). CONCLUSIONS: This study shows that the lungs were well preserved for more than 24 hours of preservation when the normothermic multiorgan block preparation was used. The transplanted left lung was able to support the anesthetized dog after the opposite pulmonary artery was occluded.

Percutaneous dilational tracheostomy: report of 356 cases.

OBJECTIVE: To evaluate the procedure time, complications, and percutaneous dilational tracheostomy (PDT) charges. DESIGN: Operative data were prospectively collected for 356 PDTs including the initial series of 141 PDTs reported in 1994. Short- and long-term complications were retrospectively identified by review of medical records and patient telephone interviews. MATERIALS AND METHODS: PDT was performed using the "Ciaglia" method of serial dilation over a Seldinger guidewire. Discharged patients (n = 258) were followed for a mean (+/-SD) of 10 +/- 7 months. MEASUREMENTS AND MAIN RESULTS: The mean procedure time was 15 +/- 8 minutes; operative mortality rate, 0.3% (1/356); overall complication rate, 19% (69/356); long-term symptomatic tracheal stenosis rate, 3.7% (8/214). The mean total patient charge for bedside PDT was $1,370; for open tracheostomy in the operating room, $2,675. CONCLUSIONS: Surgeons can rapidly perform PDT at the bedside with a lower risk of complications than open tracheostomy and at a significantly reduced patient charge.

Effects of internal mammary artery pedicle coronary artery bypass grafting on aortic valve leaflet positioning.

Approximately 50% of all patients who require replacement of the aortic valve (AVR) also require coronary artery bypass grafting (CABG) for concomitant coronary artery disease. Internal mammary artery (IMA) pedicle grafts are being used with increasing frequency for this purpose. Since the ostia of the IMA are considerably downstream from the sinus of Valsalva we hypothesized the CABG would change the local coronary flow dynamics and possibly alter the timing of both natural and prosthetic valve opening and closing dynamics. Both IMA'S were dissected as pedicle grafts in five pigs and the animals were put on cardiopulmonary bypass. Anastomotic sites were the proximal 1/3 of the left anterior descending and proximal 1/5 of the right coronary arteries. Aortic root, left ventricular and right ventricular pressures were measured and flowmeter transducers were placed on the aortic root, the left main coronary artery, the right coronary artery, the left IMA and the right IMA for measuring flows. Echocardiographic images of the aortic valve, in the longitudinal view, were recorded with a simultaneous ECG. Time points were defined during each cardiac cycle based upon characteristic points in the native coronary hemodynamics. These were identified at 8, 14 and 22% of the cycle (valve opening) and 38, 45 and 55% of the cycle (valve closing). Calculations were made based upon each cycle being initiated with the ECG R wave peak. Significant alterations in flow patterns were identified and quantitated between native coronary and IMA grafts. Only minor changes in valve positioning were identified. These differences in natural valve leaflet position occurred at 22% and 45% of the cycle.

Coronary vascular and myocardial effects of substance P in hypercholesterolemic rabbits.

Age-matched male New Zealand white rabbits (n = 16) were allocated to two groups: group 1 (n = 8) received a standard rabbit diet; group 2 (n = 8) received a 2% cholesterol-enriched diet. After 8 weeks of prescribed diet, hearts were excised and placed on a constant perfusion pressure Langendorff-type apparatus. Coronary flow, left ventricular pressure, and isovolumic dP/dt were continuously measured. Baseline recordings were made and then a single 5 nmol bolus dose of substance P was delivered into the coronary perfusate. Mean serum cholesterol levels in group 1 were 53 +/- 17 (SEM) mg.dl-1, in group 2 1438 +/- 143 mg.dl-1. In group 1, the injection of substance P caused mean coronary flow to increase 39 +/- 6%, mean coronary vascular resistance to decrease 28 +/- 3%, and mean dP/dt to increase 11 +/- 4%. In group 2, coronary flow increased 57 +/- 13%, coronary vascular resistance decreased 33 +/- 5%, and dP/dt increased 17 +/- 4%. Within groups, values changed significantly from baseline but these changes were not significantly different between groups. The duration of coronary flow response was 113 +/- 20 s in group 1 and 63 +/- 8 s in group 2. Substance P is a potent dilator of coronary resistance vessels and has positive inotropic effects in the rabbit. High levels of cholesterol exposure do not alter the magnitude of substance P-induced vasodilation, but the duration of the response is shortened.

Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P.

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.

Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit carotid arteries.

Careful handling and preparation of freshly harvested vessels from 22 pigs and 12 rabbits revealed a two-phase vasorelaxation response to cumulative doses of substance P (SP). A rapid, transient relaxation was observed during the cumulative dose-response and a new plateau of equilibrium was seen following an increase in developed force after the last dose of SP. The phase 2 response is also produced by submaximal doses of SP and is not altered by pretreatment of the rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L-NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a shift to the right in the phase 1 response to SP and a complete blockade of phase 2. Methylene blue caused nearly complete block of both phases. Nitroglycerin caused a dose-dependent and prolonged vasorelaxation with no phase 2.

Elevations in circulating calcitonin gene-related peptide correlate with hemodynamic deterioration during endotoxic shock in pigs.

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory neuropeptide, which may play a role in vascular dysfunction during septic shock. Sixteen pigs (25-50 kg) were anesthetized with ketamine and isoflurane in O2, and administered 100 micrograms/kg Escherichia coli lipopolysaccharide i.v. (LPS; n = 8) or saline vehicle (n = 8). Pigs were instrumented for hemodynamic determinations and blood sampling for CGRP assay (pg/ml) from the portal vein (PV) and the pulmonary (PA) and carotid (CA) arteries. Blood samples were collected into EDTA and aprotinin before (baseline) and at 60, 120, and 180 min after LPS administration. LPS caused significant deterioration in indices of hemodynamic function and a significant increase in plasma CGRP concentration at all sampling sites by 120 min (P < 0.01). No significant difference between sampling sites was recorded at any time. Plasma CGRP concentrations displayed significant negative correlations with mean arterial pressure, cardiac index, and left ventricular stroke work. These data confirm our previous findings of CGRP elevations in endotoxemic rats, and indicate that 1) LPS is a potent stimulus for the systemic release of CGRP, 2) increasing plasma CGRP concentrations temporally correlates with cardiovascular deterioration during LPS shock, and 3) there is little evidence that the portal circulation is a major source of circulating CGRP levels during LPS shock. Vasoactive neuropeptides, such as CGRP, may interact with other documented mediators of vascular dysfunction in the pathogenesis of septic shock.

N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery.

Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.