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Although airway, arterial, and venous connections required for lung transplantation appear simple, in practice we have encountered morbid early stenosis and obstructions, which are now avoided by technical modifications gradually made since 1985 in 134 cases (60 single lung and 74 double lung). Our initial eight double lung transplant procedures were done with tracheal anastomoses and omental wraps, but ischemic disruption, with a 75% (6 of 8) rate of complications, resulted in the subsequent use of bibronchial connections. A total of 192 bronchial anastomoses were reviewed (60 single lung, 66 double lung). Although all anastomoses were constructed between the donor trimmed to one to two rings above the upper lobe origin and the host divided at its emergence from the mediastinum, the suture technique has evolved. Nine (32%) of 28 cases with early bronchial anastomoses with end-to-end suture and intercostal muscle wrap had ischemic or stenotic complications, but the telescoping technique without wrap in 164 bronchial anastomoses reduced the problem to 12% (19 of 164). Twelve anastomoses required temporary intraluminal stenting. Vascular anastomotic obstructions occurred in five arterial (excessive length 2, short allograft artery 1, restrictive suture or clot 2) and two venous (excessive length 1, restrictive suture or clot 1) connections. Suspicion of arterial obstruction was prompted by persisting pulmonary hypertension and reduced flow to the allograft measured by postoperative nuclear scan and hypoxia. Venous obstructions were suggested by persisting radiographic and clinical pulmonary edema. Modifications of earlier techniques have improved our early success in lung transplantation and might be considered by others entering this demanding field. (J T HORAC CARDIOVASC SURG 1994;107:743-54)

Small cell lung carcinoma (SCLC) is rarely treated with resection, either alone or combined with other modalities. This study evaluated the role of surgical resection in the treatment of stage I and II SCLC.We queried the Surveillance, Epidemiology, and End Results (SEER) database for patients from 1988 to 2007 with SCLC. Survival was determined by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazard model identified relevant survival variables.We identified 3,566 patients with stage I or II SCLC. Lung resection was performed in 895 (25.1%), wedge resection in 251 (28.0%), lobectomy or pneumonectomy in 637 (71.2%), and lung resection not otherwise specified in 7 (0.78%). Median survival was 34.0 months (95% confidence interval [CI], 29.0 to 39.0 months) vs 16.0 months (95% CI, 15.3 to 16.7; p0.001) in nonsurgical patients. Median survival after lobectomy or pneumonectomy was 39.0 months (95% CI, 30.7 to 40.3) and significantly longer than after wedge resection (28.0 months; 95% CI, 23.2 to 32.8; p=0.001). However, survival after wedge resection was still significantly longer than survival in nonsurgical patients (p0.001). Sex (p=0.013), age, stage at diagnosis, radiotherapy, and operation (all p0.001) significantly affected survival. In the surgical patients, sex (p=0.001), age (p0.001), final stage (p0.001), and type of resection (p=0.01) were important determinants of survival.Surgical resection as a component of treatment for stage I or II SCLC is associated with significantly improved survival and should be considered in the management of early-stage SCLC.

Purpose The survival of patients with non–small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.

TECHNIQUE Port placement is described in Table 1 and Figure 1. This standardized port configuration can be used for all segmental resections. On the left, the port arrangement is shifted slightly posterior to account for the heart/mediastinum. A metal 10-mm port is introduced for the camera at the level of the 7th interspace in the midaxillary line. Instruments/staplers are introduced through the remaining incisions without ports, unless required. Rib spreading is avoided.1

Collis gastroplasty is an important component of laparoscopic giant paraesophageal hernia (GPEH) repair in patients with persistent shortened esophagus after aggressive laparoscopic mobilization. Concerns remain, however, regarding symptomatic outcomes compared with fundoplication alone. This study assessed the impact of Collis gastroplasty on quality of life after laparoscopic GPEH repair.We performed 795 nonemergent laparoscopic GPEH repairs with fundoplication (with Collis, n = 454; fundoplication alone, n = 341). Radiographic follow-up and symptom assessment were obtained a median 22 months and 20 months, respectively, after fundoplication alone and 36 and 33 months, respectively, after Collis (p0.001). Radiographic recurrence, reoperation for recurrent hernia or intolerable symptoms, overall symptom improvement, and quality of life were examined.Compared with fundoplication alone, Collis patients had significantly larger GPEH (p = 0.027) and fewer comorbidities (p = 0.002). Radiographic recurrences were similar (p = 0.353). Symptom improvement was significant for both (p0.001), although Collis was associated with better pain resolution (p0.001) and less gas bloat (p = 0.003). Quality of life was good to excellent in 88% (90% Collis versus 86% fundoplication alone, p = 0.17).Symptomatic outcomes after laparoscopic fundoplication with Collis gastroplasty are excellent and comparable with those of fundoplication alone. These results confirm that utilization of Collis gastroplasty, based on intraoperative assessment for shortened esophagus, is not detrimental to the overall outcome or quality of life associated with the laparoscopic approach to GPEH. Collis gastroplasty is recommended as an important procedure in the surgeon's armamentarium for laparoscopic repair of GPEH.

Tumor-infiltrating lymphocytes (TILs) have been found to increase survival in many forms of cancer, including, endometrial, bile ductal, colonic, esophageal, and urothelial cancers, as well as melanoma and follicular lymphoma. The relevance of TILs in the prognosis of non-small-cell lung cancer (NSCLC), however, still remains controversial. We compared the outcomes of stage 1A NSCLC with and without tumor infiltrating lymphocytes to evaluate the effects of TILs on recurrence and survival patterns.From 2000 to 2009, 273 anatomic segmentectomies and lobectomies were performed on stage 1A NSCLC. Patients were stratified into TIL- and TIL+ cohorts based on pathologic evaluation. Further investigation was conducted on the effects of TILs in patients with and without angiolymphatic invasion. Variables analyzed include overall survival, recurrence-free survival, and type of recurrence.Overall 5-y survival was not affected by TIL status (65% versus 60%, P = 0.469). Five-year recurrence-free survival (RFS) was significantly increased in the TIL+ group versus the TIL- group (87% versus 73%, P = 0.011), most significantly in women (P = 0.016). The presence of angiolymphatic invasion (ALI) was associated with decreased 5-y RFS versus patients without ALI (61% versus 85%, P0.001). Interestingly, in the ALI negative group, TIL+ patients experienced a significantly increased 5-y recurrence-free survival versus TIL- patients (93% versus 80%, P = 0.036).High levels of intratumoral TILs are associated with improved recurrence-free survival in stage 1A NSCLC patients as well as a reduced likelihood of systemic recurrence. When angiolymphatic invasion is not present, the beneficial effects of TILs become even more profound.

As with any operative procedure, careful preoperative and intraoperative planning are vital to achieving a safe and effective video-assisted thoracic surgical intervention. We outline some of our basic strategies for enhancing the success of this approach in the management of thoracic surgical problems.

Cervical mediastinoscopy is useful for the diagnosis of paratracheal lymph node metastasis from bronchogenic carcinoma. Access to adenopathy in the aorticopulmonary window, anterior mediastinal, periazygos, and subcarinal lymph nodes is difficult with this technique. Operative visibility in these locations through anterior mediastinotomy, the Chamberlain procedure, is limited. We have used thoracoscopic mediastinal exploration in 40 patients with computed tomographic scan evidence of enlarged aorticopulmonary window (n = 30) or enlarged right periazygos or subcarinal lymph nodes (n = 10). This procedure was used primarily as an adjunct to cervical mediastinoscopy in the staging of bronchogenic carcinoma. Adjunctive thoracoscopic nodal sampling was 100% sensitive and 100% specific in diagnosing the mediastinal adenopathy. It did not significantly delay thoracotomy in cases of benign adenopathy. Visibility of the ipsilateral pleural space and mediastinum was excellent. Thoracoscopic exploration with mediastinal nodal sampling is a valuable diagnostic adjunct for assessment of adenopathy inaccessible to cervical mediastinoscopy and can overcome many of the limitations of anterior mediastinotomy.

Significant advances in surgical equipment, video monitoring, and endoscopic surgical techniques have expanded the role of thoracoscopy to include pulmonary resection. One limitation of the thoracoscopic technique is the loss of manual palpation to identify the nodule that is either too small or too deep beneath the pleural surface. We describe the techniques used in 300 thoracoscopic pulmonary resections that have aided in identification of pulmonary nodules. These techniques include careful preoperative assessment of the computed tomogram, preoperative injection of methylene blue, or a needle localizing system to identify the nodule. Intraoperative techniques include instrument palpation, digital palpation, and intraoperative ultrasonography. It should be possible to identify the majority of pulmonary nodules at the time of thoracoscopy with these localizing techniques. All nodules were successfully identified in our last 200 thoracoscopic resections.

Thoracoscopic techniques were used to perform a pericardiectomy in 35 patients with purely effusive pericardial disease after medical management and pericardiocentesis had failed to be effective. There were no intraoperative complications and postoperative complications were few. Two cases of dysrhythmia and 2 cases of pneumonia occurred postoperatively. Malignancy was identified as the cause in 18 patients and there were benign causes in the remaining 17. The hospital stay in the group with benign effusions was 4.6 days. There were no recurrences of pericardial effusions and no constrictive changes developed during a mean follow-up of 9 months. Fourteen (40%) patients had pleural or pulmonary abnormalities that were managed simultaneously thoracoscopically. These abnormalities included 2 pleural masses, 2 pulmonary nodules, and 12 pleural effusions. In 8 instances, the pericardiectomy was performed from the right pleural cavity in order to address the pleural or pulmonary problem. Thoracoscopic pericardial resection has proved safe and effective. It allows a wider pericardial resection than that usually permitted by the subxiphoid route, and should lessen the pain and the number of pulmonary complications, compared with open thoracotomy. An additional advantage is that it allows the visualization and management of simultaneous pleural and pulmonary abnormalities.

Pulmonary lesions in patients with malignancy often require resection to provide prognostic information and to dictate further therapy. Metastasectomy may also favorably influence survival in select patients with favorable tumor histologies. Seventy-two patients with a history of malignancy and new lung lesions identified by high resolution computed tomography underwent thoracoscopic resection. The operative approach was with standard techniques using two or three trocar sites. Preoperative needle localization was used in 13 patients with small lesions that were not immediately subpleural. All target lesions were identified at thoracoscopy. Exploratory thoracoscopy was followed by parenchymal sparing wedge resection with the endoscopic stapler, the neodymium:yttrium-aluminum garnet laser, or both. Histologic analysis revealed metastatic disease in 63 patients and benign disease in 9 patients. The mean diameter of the lesions was 1.6 cm. The mean duration of chest tube drainage and postoperative hospital stay were 2.1 and 4.1 days, respectively. Thoracoscopic resection appears to be a valid approach for diagnostic resection of presumed metastases. The role of thoracoscopy in therapeutic metastasectomy remains to be defined.

Surgical management of symptomatic benign and malignant effusive pericarditis is often required. Twenty-two patients with medically recalcitrant effusive, nonconstrictive pericarditis underwent pericardial resection by a video-assisted thoracoscopic surgical (VATS) technique (9 malignant, 13 benign). Pericardiectomy, resulting in complete drainage of the pericardial space and control of patient symptoms was accomplished routinely. Ipsilateral pleural effusions, originally present in 11 patients, were also managed. The VATS pericardiectomy was well tolerated even by gravely ill patients. This approach should be considered as an alternative to lateral thoracotomy or subxiphoid pericardial window for the surgical management of patients with symptomatic benign and malignant pericardial effusions.

Video-assisted thoracoscopy has recently evolved as an alternative to thoracotomy for several thoracic disorders. Spontaneous pneumothorax may be ideally suited for thoracoscopic management. Stapling of apical blebs and pleurodesis or pleurectomy can now be performed thoracoscopically in a fashion identical to the standard operation done through a lateral or axillary thoracotomy. We compared our results with thoracoscopic management of spontaneous pneumothorax in 26 patients (group I) with a group of 20 patients previously subjected to axillary thoracotomy (group II). Indications for operation, sex distribution, and average age (group I, 32.3 years; group II, 33.7 years) were comparable. Hospital stay was less in group I (2.88 ± 0.99 days versus 4.47 ± 1.07 days; p = 0.07), as was the use of parenteral narcotics after 48 hours (2/26 = 7.7 % versus 14/20 = 70%; p = 0.01). There have been no recurrences to date (mean follow-up, 8 months) in the thoracoscopic group. Video-assisted thoracoscopic management of spontaneous pneumothorax allows performance of the standard surgical procedure while avoiding the thoracotomy incision. Video-assisted thoracoscopic management is safe and offers the potential benefits of shorter hospital stays and less pain.

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.

NSCLC arises in the complex environment of chronic inflammation. Depending on lung immune polarization, infiltrating immune cells may either promote or suppress tumor growth. Despite the importance of the immune microenvironment, current staging techniques for NSCLC do not take into consideration the immune milieu in which the neoplasms arise. T-cell subset content was compared between paired tumor-bearing and contralateral lungs, patient and control peripheral blood. The relationship between T-cell subset distribution and survival were evaluated. CD4 and CD8+ T cells were subsetted by CD45RA/CD27 and analyzed for expression of activation, adhesion, and homing markers. Strikingly, T-cell content was indistinguishable between lungs. Compared with peripheral blood, naive CD4 and CD8 T cells were rare in BAL. CD4+ BAL T cells showed increased CD95 (higher apoptotic potential) and CD103 expression (epithelial adhesion), but decreased CD38 (activation) and CCR7 expression (lymph node homing). CD8+ BAL T cells showed increased CD103 expression and decreased CD28 expression (co-stimulation). Differences in CD28, CD95, and CCR7 expression were more pronounced within memory cells, while differences in CD4+ CD103 expression were more prominent in effector/memory cells. Of these populations, the absence of lung CD4 T cells with an effector-like phenotype (CD45RA+/CD27−) emerged as a predictor of favorable outcome. Patients with a low proportion (≤0.44%) had 90% 5-year survival (n = 10, median survival 2,343 days), compared with 0% (n = 9, median survival 516 days) of patients with a higher proportion. Further study is required to confirm this association prospectively and define the function of this subpopulation.

Purpose: Steroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome. Experimental Design: Primary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor α and β-1 (ERα and ERβ), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR). Results: Tumors expressed higher levels of ERβ compared to matched normal lung, whereas the reverse was true of PR. High cytoplasmic ERβ expression was identified as an independent negative prognostic predictor of overall survival (OS; HR = 1.67), and low total PR was identified as an independent negative predictor of time to progression (TTP; HR = 1.59). After adjusting for stage, age, sex, and smoking, combined high cytoplasmic ERβ and low total PR showed enhanced effects on OS (HR = 2.64) and on TTP (HR = 6.02). Further effects on OS were observed when EGFR expression was included (HR = 5.32). Patients with low cytoplasmic ERβ, low aromatase, low EGFR, and high total PR had shorter OS than patients with the opposite pattern (HR = 6.60). Contribution of these markers to survival showed no significant sex differences in a multivariable model. ERα was elevated in tumors but was not predictive of survival, and appears to represent a variant ERα protein that is only recognized by a C-terminal antibody. Conclusions: Hormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ERβ-1/low PR may define patients with aggressive biology. A validation study is necessary to fully assess the predictive value of these markers. Clin Cancer Res; 17(1); 154–64. ©2010 AACR.

Background We present the perioperative outcomes of patients undergoing an anterior "extended Chamberlain" minithoracotomy as an alternative approach to a hemi-clamshell sternotomy or extended lateral thoracotomy for safe and reliable access to the pulmonary hilum and subsequent anatomic pulmonary resection. Methods This study is a retrospective review of 162 patients undergoing anatomic lung resection through a mini anterior thoracotomy from 2002 to 2010. An 8-cm anterior thoracotomy was performed with the patient in a supine position, entering the chest through the second intercostal space. The pectoralis muscle fibers were split with preservation of the mammary artery medially and the thoracoacromial neurovascular bundle laterally. Primary outcome variables included hospital course, complications, and mortality rate. Results The mean age was 63.9 (range, 20 to 85 years); female to male ratio was 71:91. Neoadjuvant therapy was used in 49 (30.2%) patients. Proposed resections were successful in 161 of 162 (99%) patients. Conversion to hemi-clamshell was required in 1 patient for vascular control. Complications occurred in 48 (29.6%) patients. Three (1.9%) perioperative deaths (2 pneumonectomies [6.3%], 1 lobectomy [1.0%]) occurred. Median length of stay was 8 days. Conclusions The "extended Chamberlain" mini anterior thoracotomy provides direct and expeditious, less-invasive access to the pulmonary hilum. This approach preserves muscle function and avoids partial sternotomy or extended lateral thoracotomy, and their associated incisional-related morbidity.

Background Anatomic segmentectomy has been proposed as a reasonable alternative to lobectomy in the management of small early-stage non-small cell lung cancers. We reviewed our outcomes with anatomic segmentectomy versus lobectomy for stages IA and IB non-small cell lung cancer stratified by age and stage. Methods We conducted a retrospective review of prospectively-collected data analyzing outcomes after anatomic segmentectomy (n = 305) for stage IA (n = 187) or IB (n = 118) NSCLC from 1999 to 2010. Lobectomy was performed in 594 patients for stage IA (n = 290) and IB (n = 304) disease during the same period. Surgical approach was stratified by stage and by the following age groups: less than 70, 70 to 79, and 80 or greater. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Mean follow-up was 37 months. Results Segmentectomy was associated with reduced complications (43.6% vs 58.7%) and mortality (0% vs 7.8%) in patients greater than 80 years old, without a difference in recurrence rates. There was no difference in complications or mortality in the younger age groups. Freedom from recurrence was similar between segmentectomy and lobectomy for stage IA tumors across all age groups. A reduced recurrence-free survival was seen with segmentectomy for stage IB tumors, especially with visceral pleural invasion (median 22.7 vs 29.6 months), p = 0.048). Conclusions Segmentectomy appears to be a reasonable approach for early-stage NSCLC in patients 80 years of age or greater due to reduced morbidity and mortality with equivalent freedom from recurrence. Although equivalent survival was seen in all age groups for stage IA, these data further support the use of lobectomy for resection of stage IB tumors.

Chylothorax is a rare but potentially lethal complication of esophagectomy. This study evaluated the rate of postesophagectomy chylothorax, identified associated risk factors, and compared postoperative outcomes in patients with and without chylothorax.We reviewed 892 consecutive patients who underwent esophagectomy (1997 to 2008). Preoperative, operative, and postoperative details, including adverse outcomes and mortality, were analyzed.Postesophagectomy chylothorax occurred in 34 patients (3.8%). Chylothorax was significantly associated with 30-day major complications (85% vs 46%; p0.001), including an increased likelihood of sepsis (p=0.001), pneumonia (p=0.009), reintubation (p=0.002) or reoperation (p0.001), and death (17.7% vs 3.9%, p0.001). Median length of stay was 17 vs 8 days (p=0.005). Median time to chylothorax diagnosis was 5 days. Thoracic duct ligation was performed in 21 (62%) at a median 13 days after esophagectomy. Two patients required repeat duct ligation for persistent chylothorax. Squamous cell cancer histology (9 of 34; 26%) was an independent predictor of postoperative chylothorax (odds ratio, 4.18; 95% confidence interval, 1.39 to 12.6). Odds of chylothorax were 36 times greater with average daily chest tube output exceeding 400 mL in the first 6 postoperative days (odds ratio, 35.9; 95% confidence interval, 8.2 to 157.8).Postoperative chylothorax is associated with significant postoperative morbidity and mortality. Patients with squamous cell cancer may be at increased risk. In addition, average daily chest tube output exceeding 400 mL in the early postoperative period should prompt fluid analysis for chylothorax to facilitate early diagnosis and consideration of thoracic duct ligation.

The number of new cases of esophageal cancer in the United States in 2000 likely will exceed the 12,000 annually recorded in previous years. Although two histologic subtypes exist, the incidence of adenocarcinoma of the distal esophagus in the last two decades has been increasing dramatically throughout North America and Europe.1–3 The primary risk factor is chronic heartburn leading to a sequence of esophagitis, Barrett’s esophagus, and ultimately adenocarcinoma. The overall 5-year survival rate is a disappointing 5% to 10%. However, in patients who present early in the course of the disease where the tumor is confined solely to the esophagus, the 5-year survival can be as high as 85%, thus emphasizing the importance of accurate staging at the initial evaluation.4

Lymph node status is a major determinant of stage and survival in patients with lung cancer; however, little information is available about the expected yield of a mediastinal lymphadenectomy.The American College of Surgeons Oncology Group Z0030 prospective, randomized trial of mediastinal lymph node sampling vs complete mediastinal lymphadenectomy during pulmonary resection enrolled 1,111 patients from July 1999 to February 2004. Data from 524 patients who underwent complete mediastinal lymph node dissection were analyzed to determine the number of lymph nodes obtained.The median number of additional lymph nodes harvested from a mediastinal lymphadenectomy following systematic sampling was 18 with a range of one to 72 for right-sided tumors, and 18 with a range of four to 69 for left-sided tumors. The median number of N2 nodes harvested was 11 on the right and 12 on the left. A median of at least six nodes was harvested from at least three stations in 99% of patients, and 90% of patients had at least 10 nodes harvested from three stations. Overall, 21 patients (4%) were found to have occult N2 disease.Although high variability exists in the actual number of lymph nodes obtained from various nodal stations, complete mediastinal lymphadenectomy removes one or more lymph nodes from all mediastinal stations. Adequate mediastinal lymphadenectomy should include stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4L, 5, 6, 7, 8, and 9 for left-sided cancers. Six or more nodes were resected in 99% of patients in this study.ClinicalTrials.gov; No.: NCT00003831; URL: clinicaltrials.gov.

Cervical esophagogastric anastomotic disruption following transhiatal esophagectomy (THE) is a significant problem. Gastric tip ischemia is a primary cause of anastomotic failure. We examined gastric tip blood flow when laparoscopic “ischemic preconditioning” was attempted by selectively ligating the short gastric (SG) vessels or both the left and short gastric (LG/SG) vessels prior to THE. Seventeen (25 kg) mongrel dogs underwent laparoscopy followed 3 weeks later by THE. Three groups were studied: control group = laparoscopy only, no preconditioning (n = 6); SG group = laparoscopic ligation of SG vessels only (n = 5); and LG/SG group = laparoscopic ligation of LG and SG vessels (n = 6). Tissue blood flow was assessed using the fluorescent microsphere method. The initial microsphere injections occurred prior to pneumoperitoneum and upon completion of the laparoscopy. At the second operation, transhiatal esophagectomy was performed and microsphere blood flow assessment occurred after induction of anesthesia, after mobilization of the stomach, and after completion of the cervical esophagogastric anastomosis. The animals were euthanized and regional gastric tissue was analyzed for microsphere estimates of blood flow. Differences in blood flow were evaluated using Student’s t test. The mean baseline gastric blood flow was 0.58 ml/min/g. After THE, the proximal gastric blood flow fell to 16% of baseline in control and 22% in SG, but was reduced to only 60% of baseline in LG/SG. This relative preservation of blood flow among the LG/SG group approached significance compared with the laparoscopy-only (control) group (P = 0.07). Ligation of SG vessels alone provided no preservation of proximal gastric blood flow following THE. Preoperative “ischemic preconditioning” through ligation of both the short and left gastric vessels may achieve preservation of blood flow to the gastric tip. Preconditioning during laparoscopic staging of esophageal carcinoma may be considered to reduce anastomotic complications following esophagectomy.

Adipose-derived stem cells (ASCs) have been proposed to stabilize autologous fat grafts for regenerative therapy, but their safety is unknown in the setting of reconstructive surgery after mastectomy. Both bone marrow mesenchymal stem cells (MSCs) and ASC have been shown to enhance tumorigenesis of established breast cancer cell lines, but primary patient material has not been tested. Here, we ask whether ASC promote the in vitro growth and in vivo tumorigenesis of metastatic breast cancer clinical isolates. Metastatic pleural effusion (MPE) cells were used for coculture experiments. ASC enhanced the proliferation of MPE cells in vitro (5.1-fold). For xenograft experiments (100 sorted cells/injection site), nonhematopoietic MPE cells were sorted into resting and active populations: CD90+ resting (low scatter, 2.1% ≥2N DNA), CD90+ active (high scatter, 10.6% ≥2N DNA), and CD90−. Resting CD90+ MPE cells were tumorigenic in 4/40 sites but growth was not augmented by ASC. Active CD90+ MPE cells were tumorigenic (17/40 sites) only when coinjected with ASC (p = 0.0005, χ2 test). The multilineage potentiality and MSC-like immunophenotype of ASC were confirmed by flow cytometry, differentiation cultures, and immunostaining. The secretome profile of ASC resembled that reported for MSC, but included adipose-associated adipsin and the hormone leptin, shown to promote breast cancer growth. Our data indicate that ASC enhance the growth of active, but not resting tumor cells. Thus, reconstructive therapy utilizing ASC-augmented whole fat should be postponed until there is no evidence of active disease.

Background: A variety of markers have been proposed to identify breast cancer stem cells. Here, we used immunohistostaining and flow cytometry to analyze their interrelationships and to sort cells for tumorigenicity studies. Methods: Cytokeratin, CD44, and CD90 were localized to primary breast cancer and normal breast (NB) tissue by immunohistostaining and related to CD117 and CD133 expression by flow cytometry. Immunodeficient NOD.CB17-Prkdcscid/J and NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used to test tumorigenicity of sorted CD90+ low-light scatter, CD90+ high-light scatter, and CD90neg tumor cells. Results: NB basal cells coexpressed CD44 and CD90. As cells transited luminally, CD44 was retained and downmodulated, and CD90 was lost and cytokeratin increased. In breast tumors, basal-like CD44+/CD90+ cells were localized to the tumor periphery, adjacent to CD90+ stroma. Like normal luminal cells, interior tumor cells were CD44+/CD90−. Immunophenotyping (CD44/CD90/CD117/CD133) of cytokeratin+ cells revealed no significant difference in expression between tumors and tumor-free breast. In both, CD133 was distributed approximately equally among CD44/CD90 subsets, whereas CD117 expression was highest in the basal-associated CD44+/CD90+ subset. Sorted CD90+ pleural effusion cells with lymphoid light scatter, 49% of which were CD44+, were uniquely tumorigenic in immunodeficient mice (100 cells/injection). Conclusions: Our data demonstrate that all tumors contain a small population of CD44+/CD90+ cells, mimicking the phenotype of ductal-basal cells. These are localized to the tumor periphery, adjacent to CD90+ stroma. Among the nonhematopoietic, nonmesothelial cells found in metastatic pleural effusions, low-light scatter CD90+ cells are most potently tumorigenic, compared to high-scatter CD90+ cells and CD90− cells. © 2010 International Clinical Cytometry Society

The use of sublobar resection techniques (anatomic segmentectomy; extended wedge) in the treatment of early-stage non-small cell lung cancer has been associated with increased local recurrence rates compared with lobectomy. Recent data, however, have suggested that sublobar resection of smaller tumors (especially thoseor =2 cm) can be performed with no significant difference in local recurrence or long-term survival. These findings have particular relevance in elderly patients and in those patients who may be at high risk for lobectomy because of underlying medical comorbidities. Careful patient selection on the basis of individualized assessment of specific patient and tumor characteristics will aid in selecting the optimal approach. For larger tumors, or when adequate surgical margins are not obtainable, lobectomy should be performed. Currently, active, prospective, randomized studies (Cancer and Leukemia Group B [CALGB] 140503 and American College of Surgeons Oncology Group [ACOSOG] Z4032) will provide critical insights in delineating the efficacy of sublobar resection techniques in early-stage non-small cell lung cancer.

Background The development of anastomotic leaks and/or strictures can be associated with considerable morbidity and impairment of quality of life. In the current study, we evaluated the outcomes of patients who developed anastomotic complications after esophagectomy to elucidate the impact of these events on morbidity, mortality, and subsequent need for dilation. Methods We analyzed retrospectively the clinical course of 235 patients who underwent transhiatal esophagectomy for cancer from 2001 to 2009. Patients with confirmed anastomotic leaks were identified and classified with the following scale: class 1: Radiographic leak only, no intervention; class 2: leak requiring opening of the wound, cervical and/or percutaneous drainage; class 3: disruption of anastomosis (10–50% circumference) with perianastomotic abscess requiring video-assisted thoracoscopic surgery or thoracotomy; and class 4: gastric tip necrosis with anastomotic separation (>50% circumference). Results Anastomotic leaks were encountered in 30 patients (13%). Anastomotic leaks were associated with greater morbidity (70% vs 47%; P = .02) and stricture formation (57% vs 19%; P = .0001). Mortality was not different. Increasing leak class was associated with an increased need for postoperative anastomotic dilations ( P = .016). Conclusion Anastomotic integrity after esophagectomy has a substantial impact on perioperative course and long-term swallowing. A more formal radiographic and endoscopic leak classification system seems justified.

Esophageal cancer continues to be a lethal disease with the majority of patients presenting at an advanced stage. The incidence of adenocarcinoma is rising. Although Barrett’s esophagus has been well characterized, specific pathways to the development of adenocarcinoma remain undefined. Current treatments for locoregional esophageal cancer include surgery, chemotherapy, radiation therapy, or a combination of these modalities. Optimal surgical treatment strategies include appropriate patient selection, accurate staging and risk assessment, selection of an appropriate surgical approach, and the use of multimodality treatment. This article provides an update on the myriad of options for managing esophageal cancer and outlines the surgical technique for minimally invasive esophagectomy used at our center.

Background With an increase in the performance of laparoscopic antireflux procedures, more patients with a failed primary antireflux operation are being referred to thoracic surgeons for complex redo procedures. The objective of this study was to evaluate our results of redo antireflux surgery. Methods We conducted a retrospective review of patients who underwent redo surgery for failed fundoplication. The primary endpoint was failure of the redo operation; other endpoints included gastroesophageal reflux disease-health-related quality of life (HRQOL) after redo fundoplication. Results A total of 275 patients (median age, 52 years; range, 17 to 88 years; men 82, women 193) underwent redo antireflux surgery. The most common pattern of failure of the initial operation was transmediastinal migration-recurrent hernia in 177 patients (64%). Redo surgery included Nissen fundoplication in 200 (73%), Collis gastroplasty in 119 (43%), and partial fundoplication in 41 (15%). There was no perioperative mortality. At a median follow-up of 39.6 months, 31 patients (11.2%) had a failure of the redo surgery, requiring reoperation. The two-year estimated probability of freedom from failure was 93% (95% confidence interval 89% to 96%). The HRQOL scores, available for 186 patients, were excellent to satisfactory in 85.5%, and poor in 14.5%. Conclusions Redo antireflux surgery can be performed safely in experienced centers with outcomes that are similar to published open results. Complete takedown and reestablishment of the normal anatomy, recognition of a short esophagus, and proper placement of the wrap are essential components of the procedure. Thoracic surgeons with significant laparoscopic and open esophageal surgical experience can perform minimally invasive, complex redo esophageal antireflux procedures safely with good results.

Objective To describe the use of thoracoscopic techniques to achieve parenchymal sparing wedge resection of peripheral lung lesions in patients with a history of malignancy, and to describe the morbidity, mortality, and hospital course associated with this approach. Design Case series. Setting University hospital. Participants Patients with a history of malignancy and lesions on computerized tomography in the outer one third of the lung parenchyma. Main outcome measurements Histologic analysis of resected lung lesions, operative findings, operative time, duration of chest tube drainage and hospital stay, operative morbidity, and mortality. Results Twenty-one thoracoscopic resections of pulmonary parenchymal lesions were performed on 15 patients. All peripheral lesions identified by computerized tomography were found at thoracoscopy and successfully resected with the Nd:YAG laser (n = 7), an endoscopic stapler (n = 10), or both (n = 4). The mean diameter of the lesions was 0.8 cm (range 0.2 to 1.5 cm). Histologic analysis revealed metastatic disease in 13 patients and benign disease in 2 patients. All resection margins were free of tumor. The mean duration of chest tube drainage and postoperative hospital stay were 1.8 ± 0.1 and 3.3 ± 0.1 days, respectively. Mean operative time was 111 min (range 45 to 155 min). One patient who underwent a right thoracoscopic resection developed a transient left vocal cord paresis. There were no other complications and no deaths. Conclusion Thoracoscopy was successful in identifying peripheral lung lesions and allowed for parenchymal sparing resection identical in extent to that performed with open approaches. For select patients with peripheral lung nodules felt to be metastases, thoracoscopic resection may result in reduced morbidity, cost, hospital stay and allow for more rapid institution of therapy for the primary disease.

Video-assisted thoracic surgery is emerging as a viable approach to a number of intrathoracic disorders. Technical difficulties related to improper instrument selection and suboptimal intercostal operative access can reduce the utility of, and the enthusiasm for, the video-assisted thoracic surgical approach. This report describes the intercostal access strategy and the instrument positioning that we now prescribe for many video-assisted thoracic surgical procedures. These approaches have become refined during the course of our experience with 467 patients undergoing video-assisted thoracic operations over the last 18 months.

Advances in endoscopic surgical equipment and laser technology have expanded the role of thoracoscopy to include thoracoscopic pulmonary resection. Eighty-five thoracoscopic pulmonary resections were performed on 61 consecutive patients with small lesions (less than 3 cm) in the outer third of the lung. Patients with preoperative histologic evidence of bronchogenic carcinoma were excluded unless there was impairment of cardiopulmonary function, advanced age, or concomitant extrathoracic malignancy. These thoracoscopic pulmonary resections were accomplished with the neodymium:yttrium-aluminum garnet laser (31), endoscopic stapler (29), or both (25). The mean diameter of the lesions was 1.3 cm (range, 0.4 to 2.7 cm). There has been one late death (38th postoperative day) unrelated to the operation. Morbidity consisted of postoperative atelectasis (2), pneumonia (2), bleeding requiring transfusion (1), and bronchopleural fistula of greater than 7 days duration (3). There were no wound problems. The mean period of chest tube drainage was 3.3 +/- 3.0 days. Mean postoperative stay was 5.7 +/- 4.9 days. The pathologic diagnosis was benign disease in 28 patients (interstitial fibrosis/pneumonitis, 15; radiation fibrosis, 1; sclerosing hemangioma, 1; rheumatoid nodules, 1; granuloma, 2; nocardia, 1; infarct, 1; hamartoma, 4; scar, 1; cytomegalovirus pneumonia, 1), metastatic malignancy in 20 patients, and bronchogenic carcinoma in 13 patients. Five patients found at thoracoscopic pulmonary resection to have bronchogenic cancer had adequate pulmonary function and therefore underwent formal segmentectomy (3) or lobectomy (2). Thoracoscopic pulmonary resection was the only operation performed on patients with benign disease, patients with metastatic lesions, and selected patients with limited stage bronchogenic carcinoma at increased risk for thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

The reported clinical use of the Sarns centrifugal pump (Sarns, Inc./3M, Ann Arbor, Mich.) as a cardiac assist device for postcardiotomy ventricular failure is limited. During a 25-month period ending November 1988, we used 40 Sarns centrifugal pumps as univentricular or biventricular cardiac assist devices in 27 patients who could not be weaned from cardiopulmonary bypass despite maximal pharmacologic and intraaortic balloon support. Eighteen men and nine women with a mean age of 60.4 years (28 to 83) required assistance. Left ventricular assist alone was used in 12 patients, right ventricular assist in 2, and biventricular assist in 13. The duration of assist ranged from 2 to 434 hours (median 45). Centrifugal assist was successful in weaning 100% of the patients. Ten of 27 patients (37%) improved hemodynamically, allowing removal of the device(s), and 5 of 27 (18.5%) survived hospitalization. Survival of patients requiring left ventricular assist only was 33.3% (4/12). Complications were common and included renal failure, hemorrhage, coagulopathy, ventricular arrhythmias, sepsis, cerebrovascular accident, and wound infection. During 3560 centrifugal pump hours, no pump thrombosis was observed. The Sarns centrifugal pump is an effective assist device when used to salvage patients who otherwise cannot be weaned from cardiopulmonary bypass. Statistical analysis of preoperative patient characteristics, operative risk factors, and postoperative complications failed to predict which patients would be weaned from cardiac assist or which would survive. (J T horac C ardiovasc S urg 1992;104:554-60)

The purpose of this study was to determine the most appropriate site of biopsy in patients with diffuse infiltrative lung disease (DILD). Twenty patients were evaluated. During open lung biopsy, a representative region (inflamed and least fibrotic) of the radiographically most involved lobe was identified and a biopsy done. A second biopsy specimen was obtained from an adjacent accessible lobe. The biopsy specimen from each lobe was processed separately, and a descriptive histologic report was generated for each of the two lobes. Tissue was cultured for bacteria, fungi, and mycobacteria. In 17 patients, the second biopsy site had fewer roentgenographic abnormalities than the radiographically most involved lobe. In 3 patients, the number of radiographic abnormalities was equal in all lobes. The same pathologic diagnosis was reached by histologic examination of the two biopsy specimens in 8 of 10 patients with acute DILD and in 10 of 10 patients with chronic DILD. In 2 patients, the biopsy specimen from the radiographically most involved lobe showed pathologic features not seen in the other specimen. Cultures from both biopsy specimens were grown separately in 6 patients. Fungi (n = 2) and bacteria (n = 1) were isolated from the radiographically most involved lobe (n = 2) or from the lobe of initial lung infiltration (n = 1) in 3 patients. When biopsy specimens are obtained from a representative region of the radiographically most involved lobe in patients with DILD, biopsy of other lobes is unnecessary.

Paraesophageal herniation is a potentially devastating condition of the gastroesophageal hiatus commonly manifesting in patients of advanced age with other significant medical problems. Surgical treatment is generally indicated to avoid catastrophe related to gastric volvulus. The operative approach utilized should be individualized to the patient's pathophysiologic condition rather than attempting to apply a single repair for all patients with this heterogeneous clinical problem.

Background . The vast majority of parathyroid glands in hyperparathyroidism can be resected through a cervical approach. In approximately 2% of the cases, the ectopic gland is in the mediastinum in a location that requires a thoracic approach. Methods . We report 7 such cases that were resected using video-assisted thoracic surgery to avoid the need for an open surgical procedure. Results . All glands were successfully identified preoperatively and subsequently resected. Hospital stay averaged less than 3 days with only one minor complication. Conclusions . Ectopic mediastinal parathyroid glands may be safely and accurately resected using video-assisted thoracic surgery to avoid open approaches.

In the current study, we analyze the impact of pathologic variables (angiolymphatic invasion, visceral pleural invasion, and tumor inflammation) upon survival outcomes after segmentectomy or lobectomy for stage I non-small cell lung cancer.A retrospective review was made of 524 patients undergoing resection of stage I non-small cell lung cancer through either lobectomy (n = 285) or anatomic segmentectomy (n = 239). Primary outcome variables include recurrence-free and overall survival. Statistical comparisons were performed with the t test and Fisher's exact test. Recurrence-free and overall survival was estimated utilizing the Kaplan-Maier method, with statistical significance being assessed by the log rank test.The incidence of angiolymphatic invasion, visceral pleural invasion, and degree of tumor inflammation, as well as morbidity, mortality, and length of stay were similar between segmentectomy and lobectomy. The presence of angiolymphatic invasion or visceral pleural invasion was associated with a significant decrease in recurrence-free survival (p0.01) and overall survival (p0.01). There was a trend for decreased recurrence with increasing tumor inflammation (mild versus severe, p = 0.066). There was no difference in rates of local recurrence (5.6% versus 7.9%, p = 0.59) or survival (p = 0.455) between segmentectomy and lobectomy, respectively.Angiolymphatic and visceral pleural invasion appear to be strong adverse prognostic factors after anatomic resection by segmentectomy or lobectomy for stage I non-small cell lung cancer. Overall survival is not affected by the extent of anatomical surgical resection. These data may have implications regarding the role of adjuvant systemic therapy after surgical resection for tumors with these pathologic characteristics.

The high mortality rate of lung cancer is largely due to the spread of disease to other organs. However, the molecular changes driving lung cancer invasion and metastasis remain unclear. In this study, we identified fibulin-5, a vascular ligand for integrin receptors, as a suppressor of lung cancer invasion and metastasis. Fibulin-5 was silenced by promoter hypermethylation in a majority of lung cancer cell lines and primary tumors. It inhibited lung cancer cell invasion and down-regulated matrix metalloproteinase-7 (MMP-7), which promoted lung cancer cell invasion. Knockdown of fibulin-5 was sufficient to stimulate cell invasion and MMP-7 expression. The expression levels of fibulin-5 and MMP-7 were inversely correlated in lung tumors. Suppression of MMP-7 expression by fibulin-5 was mediated by an integrin-binding RGD motif via the extracellular signal-regulated kinase (ERK) pathway. Furthermore, overexpression of fibulin-5 in H460 lung cancer cells inhibited metastasis in mice. Collectively, these results suggest that epigenetic silencing of fibulin-5 promotes lung cancer invasion and metastasis by activating MMP-7 expression through the ERK pathway. [Cancer Res 2009;69(15):6339–46]

Preservation of esophageal and gastric function is a hallmark principle in ensuring optimal surgical outcomes after gastric fundoplication. In this study, we evaluated the impact of fundoplication on esophageal transit and gastric emptying using scintigraphy studies and related these functional findings to symptomatic outcomes. A total of 106 consecutive patients (37 women, 69 men) with both preoperative and 6-month postoperative nuclear scintigraphy studies undergoing partial (Toupet) fundoplication at a single institution were analyzed. Primary variables included alterations in esophageal transit and gastric emptying times after fundoplication (1 = rapid; 2 = normal; 3 = mild delay; 4 = severe delay). Symptomatic variables included heartburn, regurgitation, dysphagia, pulmonary symptoms, and bloating. Mean age was 57.2 years. Symptomatic improvement was achieved in 91.5% of patients. Significant reduction of all symptoms (heartburn, regurgitation, pulmonary symptoms, and dysphagia) was noted after fundoplication, except gas bloating (4.7 vs. 20.8%). There were no significant differences in preoperative and postoperative esophageal transit (2.53 vs. 2.52) and gastric emptying (2.13 vs. 2.06) scores after fundoplication. Interestingly, 17% of esophageal transit times and 18% of gastric emptying times improved after fundoplication. However, worsening scores were seen in 16 and 12%, respectively. There was no significant postoperative dysphagia, even in patients with impaired transit times. Nuclear scintigraphic assessment of esophageal transit and gastric emptying are valuable, user-friendly tools to identify and avoid functional motility problems in the setting of fundoplication. These studies seem to be a reasonable alternative to manometry in assessing esophageal function before surgery in this setting. Postoperative symptoms may be related to objective changes in esophageal transit or gastric emptying. The causes may be iatrogenic in nature or related to vagal denervation with associated changes in esophagogastric compliance. Awareness of these physiologic changes may prompt further technical precautions at the time of surgery to avoid vagal injury and also may facilitate postoperative medical management.

Background Short-term outcomes of laparoscopic Heller myotomy (LHM) for achalasia have been excellent, although the long-term durability of this operation remains to be established. The aim of this study was to evaluate the long-term outcomes of LHM. Methods A single-institution review of patients undergoing LHM between 1992 and 2003 with ≥5 years follow-up. Failure was defined as symptom recurrence requiring reoperation. Univariate and multiple regression analysis were performed to identify preoperative variables predictive of long-term success. Results A total of 46 patients underwent LHM with Toupet (n = 42) or Dor (n = 4) fundoplication. At a mean follow-up of 6.4 years, 37 (80%) patients remained free from failure. Mean time to symptom recurrence in those failing LHM was 21.3 months (range, 0.5–77). Causes of failure included nonfunctioning end-stage esophagus (n = 4), fibrotic narrowing at the gastroesophageal junction (n = 4), and tight wrap (n = 1). Univariate analysis identified high preoperative lower esophageal sphincter pressure (LESP), no prior therapy, short duration of symptoms, and absence of sigmoidal esophagus as predictors of long-term success (P ≤ .044 each). High LESP remained the only predictor of long-term durability in multiple regression analysis (P = .043). Reoperations included redo myotomy (n = 2), esophagectomy (n = 6), or both (n = 1). At final follow-up, 44 (96%) patients reported significant symptom improvement compared with pre-LHM severity. Conclusion LHM is associated with an 80% long-term success rate. Successful LHM may be predicted by high LESP, no prior therapy, short symptom duration, or absence of sigmoidal esophagus. In this series, failures of LHM underwent reoperation (redo myotomy or esophagectomy) with good results.

Kyphoscoliosis is seen in approximately 1.4-15% of the octogenarian population of the US. We hypothesized that patients with kyphoscoliosis are affected with a reduced intra-abdominal volume and progressive laxity of the diaphragmatic hiatal sling musculature leading to an increased risk of hiatal hernia formation and progression over time.We retrospectively reviewed the clinical history and roentgenographic data of 320 paraesophageal hernia patients from 2003 to 2007. The prevalence of kyphoscoliosis among this patient cohort and the outcomes of surgical management were compared to paraesophageal hernia patients without kyphoscoliosis.Ninety-three of the 320 patients (29.1%) were found to have significant K/S (mean age 74; 83% female). Laparoscopic repair of paraesophageal hernia with fundoplication was performed in 91% of these patients. There was one death (1.1%; aspiration pneumonia) and 17.2% major postoperative morbidity. Mean length of hospital stay was 8 days (median = 4; range 2-71). Prolonged stays were related mainly to marginal pulmonary status. Kyphoscoliosis was associated with increased peri-operative pulmonary morbidity (16.1%) compared to patients without kyphoscoliosis (7.0%, p = 0.02).Kyphoscoliosis may contribute to the development and progression of paraesophageal hernias. Surgeons approaching paraesophageal hernia repair should be aware of the increased pulmonary morbidity and the postoperative care required in managing these patients.

We have performed a retrospective study of patients undergoing coronary artery bypass grafting for postinfarction angina in an effort to determine the influence of recency of myocardial infarction and unstable angina on operative mortality. Time from myocardial infarction to bypass was arbitrarily divided into five intervals. Nine hundred ninety-three patients having isolated coronary bypass for postinfarction angina were analyzed, and a significant trend of increased operative mortality with recency of myocardial infarction was found (p

Evidence of regional myocardial perfusion and contractile function after direct CO2 laser myocardial revascularization (DLR) is lacking. We examined myocardial segment shortening, adenine nucleotide concentrations, and regional blood flow after DLR of the left anterior descending coronary artery (LAD) distribution before and after its proximal ligation in seven anesthetized conditioned dogs. Sonomicrometry assessed myocardial fiber shortening and radioactive microspheres were used to estimate baseline regional blood flows. Cardiopulmonary bypass was followed by cardioplegia arrest. Laser channels (1 mm diameter) were made every 3 to 5 mm in the LAD region with an 80 watt Laser-sonics CO2 unit. Bypass was terminated, the LAD occluded, and parameters reassessed. Core samples of myocardium from the lased LAD and control circumflex area were taken to assess adenine nucleotides. After occlusion, LAD distribution blood flow and myocardial shortening were reduced to pre-lasting ischemic controls. Adenine nucleotides were reduced in the LAD region relative to the control CMX area. DLR cannot be relied upon to acutely revascularize the ischemic myocardium.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSEinduced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1 2/2 mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

Lung cancer is the most common cause of cancer-related mortality in the USA. Surgical resection is the standard treatment for resectable disease; however, a significant percentage of patients with otherwise resectable lung cancer may have other comorbidities, precluding surgical resection. In patients with Stage I non-small-cell lung cancer, conventional external-beam radiotherapy is typically offered as treatment in medically inoperable, high-risk patients with reported 5-year survival rates of 10-30%. An emerging technology in the treatment of lung tumors is radiofrequency ablation, which is a thermal ablative technique and may be applicable in high-risk patients with lung cancer. In this article we will review the principles of radiofrequency ablation, the common devices in use, the experimental background, the results of 'ablate and resect' studies and the clinical experience with radiofrequency ablation in the treatment of lung neoplasm.