A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer.

BACKGROUND: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). METHODS: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). RESULTS: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. CONCLUSIONS: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer.

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, naïve 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.

Endoluminal management of bronchogenic carcinoma in 2010: diagnosis, staging, and therapy.

Endoluminal bronchogenic carcinoma, though a minority of lung cancer cases, presents a unique opportunity to utilize techniques for the diagnosis and therapy that are unavailable for more peripheral tumors. This review explores current techniques for the diagnosis, staging, and therapy of endoluminal central bronchogenic tumors and also introduces techniques currently under investigation as potential improvements or replacements for current techniques using recent literature. Additionally, the new staging criteria set forth in the 7th edition of the TMN staging system as a result of the American Joint Committee on Cancer (AJCC), International Union Against Cancer (IUCC), and the International Association for the Study of Lung Cancer (IASLC) are discussed with respect to endoluminal bronchogenic carcinoma.

An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagus.

Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines - namely, tumor necrosis factor alpha and interleukin-2 - in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin-2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin-2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t-test, Fisher's exact test, or Mann-Whitney U test, with a two-tailed P-value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin-2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease.

A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy.

OBJECTIVE: Esophagectomy may lead to impairment in gastric emptying, unless a pyloroplasty or pyloromyotomy is performed. These procedures may be technically challenging during minimally invasive esophagectomy, and they are associated with a small but definable morbidity, such as leakage and dumping syndrome. We sought to determine the results of our early experience with injecting the pylorus with botulinum toxin instead of conventional pyloric drainage. METHODS: Fifteen patients who had undergone esophagectomy and injection of the pylorus with botulinum toxin were identified. Twelve patients had undergone botulinum toxin injection at the time of minimally invasive esophagectomy, and the remaining three had been treated endoscopically after surgery. The latter three patients had undergone esophagectomy with either no pyloric drainage (n = 2) or an inadequate pyloromyotomy (n = 1), and they presented in the postoperative period with delayed gastric emptying. The adequacy of emptying after injection was assessed by the patients' ability to tolerate a regular diet, a barium swallow, and a nuclear gastric emptying study. RESULTS: No patient injected with botulinum toxin during esophagectomy developed delayed gastric emptying or aspiration pneumonia in the perioperative period. Eight of these patients underwent a nuclear emptying scan at a median of 4.2 months after surgery, which showed a mean emptying half-life of 100 min. With a median follow-up of 5.3 months, one patient (8%) required reintervention for symptoms of gastric stasis, presumably after the effect of the toxin subsided. All three patients injected postoperatively demonstrated an improvement in symptoms of gastric outlet obstruction and were able to resume a regular diet. CONCLUSIONS: Injection of the pylorus with botulinum toxin can be performed safely in patients undergoing esophagectomy. Longer-term studies are needed to clarify the efficacy and durability of this technique compared to the accepted procedures of pyloromyotomy or pyloroplasty.

Tumorigenic epithelial stem cells and their normal counterparts.

ABC transporters are highly conserved and represent a major protective mechanism for barrier tissues as well as adult tissue stem cells. Emerging data support the existence of a cancer stem cell that shares features of tissue stem cells, including the ability to self-renew and undergo dysregulated differentiation. Here we show that a rare population of cells coexpressing MDR transporters and stem cell markers is a common feature across therapy-naive epithelial cancers as well as normal epithelial tissue. MDR+ and MDR- candidate tumor stem and progenitor populations were all capable of generating highly anaplastic transplantable human tumors in NOD/SCID. The finding that rare cells bearing stem cell markers and having intrinsic MDR expression and activity are already present within the tumorigenic compartment before treatment with cytotoxic agents is of critical importance to cancer therapy. Just as damaged normal epithelial tissues regenerate after chemotherapy by virtue of highly protected resting tissue stem cells, the existence of malignant counterparts in therapy-naive epithelial cancers suggests a common mechanism by which normal and tumor stem cells protect themselves against toxic injury.

Phase I study of gemcitabine given weekly as a short infusion for non-small cell lung cancer: results and possible immune system-related mechanisms.

PURPOSE: To define the maximum tolerated dose (MTD) and the nature of the toxicities associated with gemcitabine given as a short infusion to patients with non-small cell lung cancer (NSCLC). Secondary objectives were to monitor immunologic response, clinical response, and survival. PATIENTS AND METHODS: Thirty-two patients diagnosed with advanced inoperable NSCLC and performance status of 0 or 1 participated in this study. Patients consisted of 22 males and 10 females whose median age was 62 years (range 32-79). Gemcitabine was administered as a 30 min infusion once weekly for 3 weeks followed by 1 week of rest. Patients were enrolled at six gemcitabine dose levels ranging from 1000 to 3500 mg/m2. Patients completed a median of four cycles (range 1-17). Responses were evaluated after every two cycles. RESULTS: Toxicity was evaluated in all 32 patients. The MTD was not reached as gemcitabine was well tolerated at all dose levels. Grade 4 toxicity occurred in three (9%) patients: pulmonary and lymphocytopenia in one patient each, and both neurocortical and cardiac in one patient. Grade 3 toxicity was found in a total of 20 (63%) patients: pulmonary in 10 (31%) patients; pain in 6 (19%) patients; liver toxicity in 6 (19%) patients; leukopenia and lymphocytopenia in 5 (16%) patients each; anemia, nausea, and cardiac toxicity in 3 (9%) patients each; proteinuria and infection in 2 (6%) patients each; and hemorrhage in 1 (3%) patient. Of the 29 patients evaluable for response, seven objective responses were achieved: six at the 2200 mg/m2 dose level and one at the 2800 mg/m2 dose level. The distribution of responses differed significantly by dose (P = 0.0124 by the exact chi-square test for independence). The overall response rate was 24.1% (95% CI, 10.3-43.5%). At 6 h post-infusion, there was a significant increase in spontaneous tumor necrosis factor (TNF) release and stimulated interleukin (IL)-2 production, and significant decreases in total white blood cell and lymphocyte counts (CD3+, CD8+, and CD16+ lymphocytes) and resting and stimulated superoxide production by formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate, and opsonized zymosan (OPS-Z). At 24 h post-infusion, there were significant decreases in total lymphocyte count, lymphocyte subsets (CD3+, CD4-, CD8+, CD56+, CD19+), and in resting and stimulated superoxide production by fMLP and OPS-Z. There also appeared to be an association between the levels of spontaneous TNF release and the severity of both gastrointestinal (GI) and pulmonary toxicities. CONCLUSION: Gemcitabine given as a short infusion was well tolerated at the dose levels of 1000-3500 mg/m2. The MTD was not reached. Toxicities appeared to be cumulative with multiple cycles. Gemcitabine appears to have activity against NSCLC. Although there was a differential dose-response rate among dose levels, increasing the gemcitabine dose beyond 2200mg/m2 did not show increased clinical response. Gemcitabine appears to modulate the immune response, which may in turn mediate both response and toxicity, although no statistically significant correlation between immune and clinical response was detected.

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.

Laparoscopic repair of large paraesophageal hernia is associated with a low incidence of recurrence and reoperation.

BACKGROUND: Laparoscopic repair of paraesophageal hernia (LRPEH) is a feasible and effective technique. There have been some recent concerns regarding possible high recurrence rates following laparoscopic repair. METHODS: We reviewed our experience with LRPEH from 5/1996 to 8/2002. Large paraesophageal hernia (PEH) was defined by the presence of more than one-third of the stomach in the thoracic cavity. Principles of repair included reduction of the hernia, excision of the sac, approximation of the crura, and fundoplication. Pre- and postoperative symptoms were evaluated utilizing visual analogue scores (VAS) on a scale ranging from 0 to 10. Patients were followed with VAS and barium esophagram studies. Statistical analysis was performed using two-tailed Student's t-test. RESULTS: A total of 166 patients with a mean age of 68 years underwent LRPEH. PEH were type II ( n = 43), type III ( n = 104), and type IV ( n = 19). Mean operative time was 160 min. Fundoplications were Nissen (127), Toupet (23), Dor (1), and Nissen-Collis (1). Fourteen patients underwent a gastropexy. One patient required early reoperation to repair an esophageal leak. Mean hospital stay was 3.9 days. At 24 months postoperatively there was statistically significant improvement in the mean symptom scores: heartburn from 6.8 to 0.5, regurgitation from 5.9 to 0.3, dysphagia from 4.0 to 0.5, chest pain from 3.7 to 0.3. Radiographic surveillance was obtained in 120 patients (72%) at a mean of 15 months postoperatively. Six patients (5%) had radiographic evidence of a recurrent paraesophageal hernia (two required surgery), 24 patients (20%) had a sliding hernia (two required surgery), and four patients (3.3%) had wrap failure (all four required surgery). Reoperation was required in 10 patients (6%); two for symptomatic recurrent PEH (1.2%), four for recurrent reflux symptoms (2.4%), and four for dysphagia (2.4%). Patients with abnormal postoperative barium esophagram studies who did not require reoperation have remained asymptomatic at a mean follow up of 14 months. CONCLUSION: LPEHR is a safe and effective treatment for PEH. Postoperative radiographic abnormalities, such as a small sliding hernia, are often seen. The clinical importance of these findings is questionable, since only a small percentage of patients require reoperation. True PEH recurrences are uncommon and frequently asymptomatic.

Effectiveness of laparoscopic fundoplication in relieving the symptoms of gastroesophageal reflux disease (GERD) and eliminating antireflux medical therapy.

BACKGROUND: Recent reports have suggested that antireflux surgery should not be advised with the expectation of elimination of medical treatment. We reviewed our results with laparoscopic fundoplication as a means of eliminating the symptoms of gastroesophageal reflux disease (GERD), improving quality of life, and freeing patients from chronic medical treatment for GERD. METHODS: A total of 297 patients who underwent laparoscopic fundoplication (Nissen, n = 252; Toupet, n = 45) were followed for an average of 31.4 months. Preoperative evaluation included endoscopy, barium esophagram, esophageal manometry, and 24-h pH analysis. A preoperative and postoperative visual analogue scoring scale (0-10 severity) was used to evaluate symptoms of heartburn, regurgitation, and dysphagia. A GERD score (2-32) as described by Jamieson was also utilized. The need for GERD medications before and after surgery was assessed. RESULTS: At 2-year follow-up, the average symptom scores decreased significantly in comparison to the preoperative values: heartburn from 8.4 to 1.7, regurgitation from 7.2 to 0.7, and dysphagia from 3.7 to 1.0. The Jamieson GERD score also decreased from 25.7 preoperatively to 4.1 postoperatively. Only 10% of patients were on proton pump inhibitors (PPI) at 2 years after surgery for typical GERD symptoms. A similar percentage of patients (8.7%) were on PPI treatment for questionable reasons, such as Barrett's esophagus, "sensitive" stomach, and irritable bowel syndrome. Seventeen patients (5.7%) required repeat fundoplication for heartburn ( n = 9), dysphagia ( n = 5), and gas/bloating ( n = 3). CONCLUSIONS: Laparoscopic fundoplication can successfully eliminate GERD symptoms and improve quality of life. Significant reduction in the need for chronic GERD medical treatment 2 years after antireflux surgery can be anticipated.

Prediction of postoperative gas bloating after laparoscopic antireflux procedures based on 24-h pH acid reflux pattern.

BACKGROUND: Postoperative gas/bloating (G/B) is a common sequelae after laparoscopic fundoplication. Patients with "upright" reflux are thought to have more aerophagic tendencies contributing to their GERD symptoms than patients with significant "supine" patterns of reflux. The risk of postoperative G/B developing was analyzed in relation to patient preoperative patterns of upright, mixed, or supine 24-h pH scores. METHODS: In this study, 339 patients undergoing fundoplication (278 Nissen and 61 Toupet) were evaluated for preoperative G/B symptoms using a 0 to 10 severity visual analogue scale. Reflux patterns were classified as upright, supine, or mixed according to 24-h pH studies. RESULTS: As compared with preoperative values, 46% of the patients with a preoperative G/B score less than 3 and an upright or mixed reflux pattern had a significant increase in their average G/B score at 2 years (upright, from 0.9 to 4.2; mixed, from 1.1 to 4.1). However, the patients with a supine reflux pattern did not have a statistically significant change (from 2.0 to 2.2; p > 0.05). The patients with established aerophagic tendencies preoperatively (G/B score > 3) showed significant improvement in these symptoms at 2 years across all three reflux patterns (average G/B score, from 7.7 preoperatively to 4.8 at 2 years). There was no gender predisposition, nor was there any difference in the incidence of G/B between complete and partial fundoplication. CONCLUSIONS: The pattern of 24-h acid reflux can be predictive of G/B after antireflux surgery. Patients with mild preoperative G/B symptoms (score <3) and upright or mixed patterns of 24-h acid reflux appear to have an increased postoperative risk for chronic G/B as compared with patients who have supine reflux and mild preoperative G/B. Patients with moderate to severe preoperative G/B symptoms (score, 3-10) appear to have a general improvement in G/B symptoms at 2 years after fundoplication.

Outcome analysis of laparoscopic Roux-en-Y gastric bypass for morbid obesity. The first 116 cases.

BACKGROUND: Morbid obesity has been described as a continuing epidemic affecting a growing portion of our population. We report an outcome analysis of our early experience with laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment of morbid obesity. METHODS: Two surgeons performed 116 consecutive LRYGBs at a single institution, creating a 25-ml pouch and a 90- to 150-cm Roux limb. The prospectively collected data included patient demographics, comorbidities, postoperative weight loss, and complications. RESULTS: All eight conversions to an open procedure occurred early during the experience of the surgeons. The mean operating room time for the first 50 cases was 272 min, which decreased to 198 min with experience. The mean length of hospital stay was 3 days. There were 34 complications in 27 patients (23.3%), 14 of which (12%) required reoperation. At 18 months postoperatively, the patients had lost 77% of their excess weight, and their body mass index had decreased from a mean of 49.3 to 32.6 kg/m2. As a result of LRYGB, 25% of the patients were rendered completely free of any pharmacologic treatment for their preexisting comorbidities. CONCLUSIONS: Although technically challenging, LRYGB can be performed safely with excellent long-term results. The mean operating room time and conversion rate improved with experience. As this study showed, LRYGB achieves an excellent rate of weight loss and improvement in preoperative comorbidities with a minimal length of hospital stay and an acceptable complication rate.

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.

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.

Laparoscopic management of giant paraesophageal herniation.

BACKGROUND: Many surgeons have found laparoscopic fundoplication effective management of medically recalcitrant gastroesophageal reflux disease (GERD) associated with sliding type I hiatal hernias. The anatomic distortion and technical difficulty inherent with repair has limited the use of laparoscopy for repair of "giant" paraesophageal hernias (gPH). METHODS: Since July 1993, we have accomplished laparoscopic repair of paraesophageal hiatal hernias in 54 of 60 (90%) patients. Five patients had classic type II hernias with total intrathoracic stomachs, and 53 patients had large sliding/paraesophageal type III herniation. Two patients had true parahiatal hernias. None had gastric incarceration. Median age was 53 years and 28 of 60 (47%) were women. Chest pain and dysphagia were primary complaints from 39 of 60 (65%). Heartburn with or without regurgitation was present in 52 of 60 (85%). Preoperative manometry and prolonged pH testing were obtained on 43 of 60 (72%) and 44 of 60 (73%) patients, respectively. Principles of repair included reduction of the hernia, excision of the sac, crural approximation, and fundoplication over a 54F bougie (Nissen, 41; Dor, 1; Toupet, 18) to "pexy" the stomach within the abdomen and to control postoperative reflux. RESULTS: Mean operative time was 202+/-81 minutes. Conversion to "open" repair was required in 6 patients (iatrogenic esophageal injury in 2 patients and difficult hernia sac dissection in 4 patients). One postoperative mortality occurred as a result of sepsis and multiorgan failure after an intraoperative esophageal perforation. Follow-up barium swallow performed in 44 of 60 patients demonstrated recurrent hiatal hernias in 3 patients. Preoperative symptoms have been relieved in all but 3 patients. Reoperation for recurrent paraesophageal herniation has been required in these latter 3 patients. CONCLUSIONS: Although technically challenging, laparoscopic repair of paraesophageal hiatal hernias is a viable alternative to "open" surgical approaches. Control of the herniation and the patient's symptoms are equivalent and hospitalization and return to full activity are shorter.

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.

Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor growth and metastasis. We investigated the prognostic significance of VEGF overexpression, intratumoral microvessel density (MVD), and angiolymphatic invasion in stage Ia-b non-small cell lung cancer (NSCLC). METHODS: Eighty-five patients undergoing complete surgical resection of pathologic stage Ia-b NSCLC were evaluated. The mean and median clinical follow-up were 37.1 and 39.0 months (range, 30-44 months), respectively. Paraffin-embedded tumor specimens were stained with VEGF and CD31 (a specific endothelial marker) using immunohistochemical methods. VEGF staining was evaluated, by combining both percentage of positive tumor cells and staining intensity, as low (negative and < 20% of tumor cells showing weak positivity), or high (> 20% of tumor cells showing strong positivity). CD31 staining was expressed as MVD per high power field at 400x magnification. Angiolymphatic invasion was expressed as either presence or absence. RESULTS: Low VEGF expression was seen in 25 (29%) patients, and high VEGF expression was seen in 60 (71%) patients. The survival rate in patients with low VEGF expression was significantly higher (80%) than that in those with high VEGF expression (48%, P = .018). The mean MVD in the low VEGF group was 23.7 +/- 5.7 vs. 34.4 +/- 9.3 in the high VEGF group (P = .001). Patients with high MVD also had a significantly lower survival rate than did those with low MVD count (46% vs. 73%, P = .0053). Age, sex, tumor type, and tumor differentiation were not found to be associated with overall survival. The presence of angiolymphatic invasion and T2 stage (i.e., tumor size > 3 cm) were associated with decreased survival. High VEGF expression, tumor size, and angiolymphatic invasion emerged as three independent factors predicting worsening prognosis using multivariate analysis. CONCLUSION: High VEGF expression within stage I NSCLC is closely associated with high intratumoral angiogenesis and poor prognosis. Immunohistochemical evaluation of T stage and VEGF expression along with examination of angiolymphatic invasion perioperatively may aid in predicting prognosis. Adjuvant therapies aimed at retarding tumor angiogenesis may be considered for stage I NSCLC patients with high VEGF levels.

A comparative study of buttressed versus nonbuttressed staple line in pulmonary resections.

BACKGROUND: Prolonged air leak is the major limiting factor in early hospital discharge following pulmonary resection. The purpose of this study was to determine whether the use of bovine pericardial strips as a buttress along the lung staple line would decrease air leaks and hospital stay after lobectomy and segmentectomy. METHODS: This was a multicenter trial consisting of 80 patients undergoing pulmonary resection, randomly assigned to the control group (40 patients) or treatment group (40 patients). The treatment group had reinforcement with bovine pericardium. RESULTS: No statistical differences were noted in the mean intensive care unit length of stay (p = 0.9), number of days with a chest tube (p = 0.6), or total length of stay (p = 0.24). Increased air leak duration was associated with assignment to the control group (r = 0.27, p = 0.02). The mean duration of air leak was 2 days and the mean time to chest tube removal was 5.9 days in patients with a buttressed staple line compared to 3 days and 6.3 days, respectively, for patients with nonbuttressed staple lines. CONCLUSIONS: Within the data of this study, no statistical differences were noted between buttressed and nonbuttressed patients. However, the trend toward shortened air leak time and tube removal time was apparent in the buttressed group. With greater number of patients studied, it is likely that the cost of bovine pericardium would be justified by shorter air leak duration and hospitalization.

The role of video-assisted thoracic surgery for pulmonary metastasectomy.

Management of isolated metastatic deposits to the lungs and the role of surgical resection, specifically video-assisted thoracic surgery (VATS) techniques, have been controversial. The inability to perform a detailed bimanual palpation of the lung for occult lesions has been considered an inherent weakness in this approach. We have performed VATS resection for 205 patients with pulmonary metastatic disease and potentially curative VATS resec-tion for 119 patients. VATS resection was successfully performed for all VATS diagnostic and therapeutic patients, with no perioperative deaths. Longitudinal follow-up demonstrated a mean survival of 20 months in the diagnostic group and 32 months in the therapeutic group. In the VATS therapeutic group, 44 (37%) patients remain free of disease at a mean follow-up of 37 months. Of the 69 recurrences, 6% were local, 25% were regional, and 67% were distant. In this review, the present role of VATS pulmonary metastasectomy will be examined.