Richard J. Finley

Probability of Cancer in Pulmonary Nodules Detected on First Screening CT

BACKGROUND Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Factors affecting cervical anastomotic leak and stricture formation following esophagogastrectomy and gastric tube interposition

Following esophagectomy, restoration of swallowing by gastric tube interposition with cervical esophagogastric anastomosis reduces morbidity and mortality associated with intrathoracic anastomoses at the expense of an increased incidence of both anastomotic leak and stricture formation. A retrospective study of 165 patients with either squamous cell carcinoma or adenocarcinoma of the distal esophagus or gastric cardia undergoing esophagogastrectomy with gastric tube interposition and cervical anastomosis at Vancouver, British Columbia, or London, Ontario, was undertaken. Forced-entry multiple logistic regression analysis of factors believed to influence anastomotic outcome was performed. Anastomotic leak occurred in 17% of patients; statistically significant correlation with low preoperative serum albumin (p = 0.005), running suture technique (p = 0.029), high intraoperative blood loss (p = 0.038), and the occurrence of postoperative delayed gastric emptying (p = 0.045) was found. Anastomotic strictures occurred in 31% of patients; a statistically significant correlation was found with preceding anastomotic leak (p = 0.001) and intraoperative blood loss (p = 0.042). Factors including preoperative radiotherapy and diabetes mellitus were not found to be significant.

Thoracoscopic versus laparoscopic modified Heller Myotomy for achalasia: efficacy and safety in 87 patients.

BACKGROUND The ideal treatment for achalasia permanently eliminates the dysfunctional lower esophageal sphincter, relieving dysphagia and regurgitation; prevents gastroesophageal reflux; and has an acceptable morbidity rate. Controversy exists concerning whether the thoracoscopic Heller Myotomy (THM) or laparoscopic Heller myotomy (LHM) technique is the best approach to a modified Heller myotomy for achalasia. STUDY DESIGN We performed a retrospective comparison of the patient characteristics, operative results, postoperative symptoms, and the learning curves for the procedures of 24 patients undergoing THM and 63 patients undergoing LHM between 1991 and 1998. RESULTS Preoperative patient variables in each group revealed similar distributions for age, gender, and prevalence of previous pneumatic dilation. Mean operating room (OR) times were 4.3 hours (range 2.9 to 5.6 hours) for THM and 3.0 hours (range 1.5 to 6.5 hours) for LHM (p = 0.01). Three esophageal perforations occurred in the THM group and two in the LHM group. Conversion to an open procedure took place in five THM operations (21%) and one LHM operation (2%) (p = 0.005). There were no postoperative esophageal leaks. Mean postoperative length of stay (LOS) for THM was 6.1 days (range 1 to 17 days) and for LHM was 4.0 days (range 1 to 12 days) (p = 0.03). Learning-curve analysis of the first 24 LHM patients compared with the most recent 24 revealed greater OR time in the first 24 mean 3.6 hours, (range 2.0 to 6.5 hours) versus mean 2.3 hours, (range 1.5 to 3.7 hours; p = 0.01), and greater LOS mean 5.5 days, (range 3 to 12 days) versus mean 3.1 days, (range 1 to 8 days; p < 0.01). One esophageal perforation occurred in each subgroup. A similar analysis in the first 12 THM patients compared with the most recent 12 revealed no significant improvement in OR times or LOS. Three esophageal perforations occurred in the latter subgroup only. All patients had preoperative daily dysphagia to solids. Followup data for LHM (n = 49) (median 17 months, range 1 to 39 months) and THM (n = 15) (median 42 months, range 1 to 69 months) revealed no or minimal dysphagia in 90% (44 of 49) after LHM and 31% (4 of 13) after THM (p < 0.01). No or minimal heartburn was present in 89% (41 of 46) after LHM and 67% (8 of 12) after THM (p < 0.05). Regurgitation was absent or minimal in 94% (46 of 49) after LHM and 86% (12 of 14) after THM (p = 0.3). CONCLUSIONS LHM was associated with decreased OR time, decreased rate of conversion to an open procedure, and shorter LOS compared with THM. LHM was superior to THM in relieving dysphagia and preventing heartburn. LHM may be the preferred surgical treatment of achalasia in some patients.

Effect of routine fibrin glue use on the duration of air leaks after lobectomy

The effectiveness of fibrin glue as a sealant to reduce postoperative air leaks after pulmonary lobectomy was evaluated in 28 consecutive patients between November 1988 and May 1989. A fibrin glue spray was used in 14 patients, and 14 patients served as controls. Assignment of either group was made before thoracotomy. Nine male and 5 female patients with a mean age of 63.8 years were in the fibrin glue experimental group, and 8 male and 6 female patients with a mean age of 59 years, in the control group. An equal number of complete and incomplete fissures were in each group. All fissures were handled in the same way (stapled). Two milliliters of fibrin glue was applied through a double-syringe delivery system and sprayed on the staple line and any cut surface of the inflated lung just before thoracotomy closure. The fibrin glue-treated group had a mean air leak duration of 2.3 +/- 3.7 days, chest tube drains for 6 +/- 4.1 days, and a postoperative hospitalization of 9.8 +/- 3.1 days. The control group had a mean air leak duration of 3.3 +/- 3.3 days (p = 0.94), chest tube drains for 5.9 +/- 3.9 days (p = 0.95), and a postoperative hospitalization of 11.5 +/- 3.9 days (p = 0.21). We conclude that the routine use of a fixed quantity of fibrin glue is not effective in reducing the duration of air leaks, chest tube drainage, or hospitalization after uncomplicated pulmonary lobectomy.

Lung Nodules: CT-guided Placement of Microcoils to Direct Video-assisted Thoracoscopic Surgical Resection

PURPOSE To prospectively assess the safety and effectiveness of computed tomography (CT)-guided placement of fiber-coated microcoils used to guide video-assisted thoracoscopic surgical (VATS) excision of small peripheral lung nodules, with successful excision as the primary outcome and successful CT-guided microcoil placement and procedural complications as secondary outcomes. MATERIALS AND METHODS The institutional review board approved the study protocol. Informed consent was obtained from all 69 enrolled patients (30 men, 39 women; mean age, 60.7 years +/- 10.1 [standard deviation]) with 75 nodules. At CT, one end of an 80-mm long, 0.018-inch-diameter fiber-coated microcoil was placed deep to the small peripheral lung nodule, and the other end was coiled in the pleural space. VATS excision of lung tissue, nodules, and the microcoil was performed with fluoroscopic guidance. RESULTS Seventy-three (97%) 4-24-mm nodules were successfully removed at fluoroscopically guided VATS excision; two nodules could not be removed. CT-guided microcoil placement was successful in all cases; however, two (3%) of 75 coils were displaced at VATS excision. Pneumothorax requiring chest tube placement occurred in two (3%) patients, and asymptomatic hemothorax occurred in one (1%) patient. The microcoil did not impede intraoperative frozen-section histopathologic analysis, which facilitated accurate clinical management in all patients. For 19 (28%) patients, the preoperative treatment plan based on bronchoscopy, needle biopsy, and positron emission tomography findings changed after VATS excision. CONCLUSION Microcoil localization of small peripheral lung nodules enabled fluoroscopically guided VATS resection of 97% of the nodules, with a low rate of intervention (3%) for procedural complications.

Peripheral Lung Nodules: Fluoroscopically Guided Video-Assisted Thoracoscopic Resection After Computed Tomography-Guided Localization Using Platinum Microcoils

Objectives:We sought to test the safety and efficacy of fluoroscopically guided, video-assisted, thoracoscopic resection after computed tomography (CT)-guided localization using platinum microcoils. Summary Background Data:Video-assisted thoracoscopic (VATS) resection of small pulmonary nodules >5 mm deep to the visceral pleura fails to locate the nodule and requires conversion to open thoracotomy in two thirds of cases. Therefore, we developed a new technique for intraoperative localization of these nodules using CT-guided placement of platinum microcoils. This study tests the safety and efficacy of this technique in a Phase I human study. Methods:Twelve patients with undiagnosed growing pulmonary nodules <20 mm were marked preoperatively using percutaneously placed CT-guided platinum microcoils. The coil was deployed adjacent to the nodule with the distal end of the coil placed deep to the nodule and the superficial end coiled on the pleural surface. The nodule and coil were excised using endostaplers guided by VATS and fluoroscopy. Histopathologic diagnosis was performed immediately after resection. Results:CT-guided microcoil localization was successful in all patients. A small hemothorax and a pneumothorax requiring a chest tube occurred in 2 patients. Mean distance from visceral pleura to the deep edge of the nodule was 30.9 ± 15.4 mm. VATS resection of the nodules (size = 11.8 ± 3.2mm) was successful in all patients. Mean microcoil localization, fluoroscopy, and operative times were 42 ± 14, 3.1 ± 2.0, and 67 ± 27 minutes. A diagnosis of primary nonsmall cell bronchogenic carcinoma was made in 6 patients who then received a completion lobectomy. Six patients (hamartoma: 2, reactive lymph node: 1, bronchoalveolar cell carcinoma: 2, metastatic sarcoma: 1) did not receive further resections. Conclusions:Preoperative localization of pulmonary nodules using percutaneous CT-guided platinum microcoil insertion combined with operative fluoroscopic visualization is a safe, effective technique that increases the success rate of VATS excision.

The results of esophagogastrectomy without thoracotomy for adenocarcinoma of the esophagogastric junction.

Between 1980 and 1988, 98 patients with adenocarcinoma of the esophagogastric junction were seen at the University of Western Ontario. Eighty-two patients underwent resection of the celiac lymph nodes, lesser curve and cardia of the stomach, and thoracic esophagus through abdominal and neck incisions avoiding thoracotomy. The esophagus was replaced by a stomach tube in 80 patients or by a colon tube in two patients. Two of 82 patients died while hospitalized. Early postoperative morbidity included anastomotic leaks that closed spontaneously (13), transient hoarseness (10), myocardial infarction (2), pulmonary embolus (6), and atelectasis or pneumonia (13). Late postoperative complications included delayed gastric emptying (4), symptomatic reflux (4), diarrhea (10), and anastomotic strictures (17). The 2-year survival of 30% was significantly affected by the stage of disease (p = 0.003), depth of tumor penetration (p = 0.02), lymph node metastasis (p = 0.001), tumor differentiation (p = 0.008), and tumor DNA ploidy (p = 0.02). Local recurrences appeared initially in 20 patients: anastomotic (3), peritoneal (14), mediastinal (3); distant metastasis occurred in 27 patients: bone (15), liver (5), brain (2), and multiple organs (5). Swallowing was restored and maintained in 75 patients. Esophagogastrectomy without thoracotomy provides a safe, effective method of restoring swallowing in patients with adenocarcinoma of the esophagogastric junction. This technique provides acceptable survival and local recurrence rates.

Laparoscopic Esophageal Myotomy and Anterior Partial Fundoplication for the Treatment of Achalasia

BACKGROUND The purpose of this study was to determine the initial results of laparoscopic esophageal myotomy and anterior fundoplication in the treatment of 26 patients with achalasia. METHODS Operative time, complications, and length of hospitalization were recorded for each patient. Postoperative outcomes were assessed by a standardized patient questionnaire, 24-hour esophageal pH studies, and esophageal transit studies. RESULTS Twenty-six consecutive patients with class IV dysphagia underwent a laparoscopic esophageal myotomy and anterior partial fundoplication, with a single incidence of intraoperative esophageal perforation. The mean operative time was 3.5 hours. The median length of hospitalization was 5 days. Of the 21 patients for whom follow-up was available (median follow-up, 4 months), 19 (90%) were satisfied and 2 (10%) were somewhat satisfied with their surgery. After operation, 14 of the 21 patients (67%) reported no dysphagia (class I), whereas 6 (28%) had class II dysphagia (less than once per week) and only 1 (5%) had class III dysphagia (greater than once per week). Liquid-phase esophageal transit studies (n = 14) revealed a significant improvement in esophageal clearance in the supine position from 18% before operation to 44% after operation (p = 0.006). Distal esophageal acid exposure was normal in 6 of 7 patients. CONCLUSIONS These early results suggest that laparoscopic esophageal myotomy and anterior partial fundoplication provides efficacious treatment of achalasia.

Matrix Metalloproteinase Expression by Human Alveolar Macrophages in Relation to Emphysema

An abnormal increase in proteolytic enzymes is thought to play a key role in pulmonary emphysema. Alveolar macrophage proteolytic enzymes include cathepsin L, cathepsin S, matrix metalloproteinase 1, 9, and 12, and a number of studies have implicated these proteinases in the alveolar destruction that characterizes emphysema. The aim of this study was to investigate cathepsin L, cathepsin S, matrix metalloproteinase 1, 9, and 12 mRNA expression in alveolar macrophages isolated from patients with varying degrees of emphysema and to correlate their level of expression with measures of emphysema. Alveolar macrophages were isolated from fifty-four patients who underwent surgical resection for lung carcinoma. The level of mRNA expression was determined using real-time PCR. Emphysema was quantified using high-resolution CT scans. Alveolar macrophages were also cultured for 24 h and 48 h; the effect of proinflammatory mediators and promoter polymorphisms on expression was analyzed. There was a significant correlation between matrix metalloproteinase 1 mRNA expression and emphysema. A higher level of matrix metalloproteinase 1 mRNA was associated with more severe emphysema. Matrix metalloproteinase 12 mRNA expression was increased in current smokers as compared with former smokers. Furthermore, there was a negative correlation between matrix metalloproteinase 12 gene expression and carbon monoxide diffusing capacity. The matrix metalloproteinase 9 C-1562T polymorphism significantly influenced matrix metalloproteinase 9 mRNA expression in alveolar macrophages. These results suggest that alveolar macrophage matrix metalloproteinase 1 and 12 may have a role in the lung structural changes leading to the development of emphysema. Furthermore, these data provide evidence to support the concept that multiple proteinases, causing both elastin and collagen degradation, are important in the pathogenesis of pulmonary emphysema.

Catabolic hormones and substrate patterns in septic patients

Abstract Hormone and substrate levels were measured in 22 septic and 12 nonseptic post-operative subjects. Plasma glucagon and total plasma catecholamines were increased in the septic subjects suggesting a possible role of these hormones in the severe catabolism of sepsis. There was no difference in the insulin: glucagon (I:G) molar ratios in the two groups, although both groups have a lower ratio than patients who are anabolic while receiving parenteral nutrition. Lack of correlation between I:G ratio and severity of illness in this study would indicate that factors other than insulin and glucagon are operational in the catabolism of sepsis. Catecholamines may have a significant catabolic effect in septic patients. Increased levels of phenylalanine and low serum albumin point to the possibility of impaired liver function in serious septic illness.