- Email: [email protected]
What’s New in General Thoracic Surgery
WHAT’S NEW IN SURGERY
What’s New in General Thoracic Surgery Joseph B Zwischenberger, MD, FACS, Brannon R Hyde, MD, Juan C Escalon, MD “What’s New in Surgery” evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons’ Advisory Councils for the Surgical Specialties. This feature is now presented in issues of the Journal throughout the year.
ulum. A recently published prospective randomized trial tested resident acceptance and educational impact.1 From residents who matriculated in 2002, 138 agreed to participate in the study. Sixty-nine residents were randomized to receive a CD-ROM access key, and 69 received the curriculum outline only. Using the Internet, the system was designed to track resident use and performance. Based on the American Board of Thoracic Surgery In-Training Exam performance, resident selfassessments, and program directors’ assessments, the system and content have been well received. There is a trend toward improved resident performance with more frequent use of the e-learning system. The system is being updated and expanded to include a complete core curriculum to be used throughout the residency.
“What’s new” articles are cultivated from selected analysis of the past year’s peer-reviewed literature. Although our knowledge and understanding of general thoracic surgical issues increased last year, enthusiasm is bridled by the few changes actually assimilated into clinical practice. Highlights of the past year include new trends in resident education, significant trials in adjuvant therapy for lung cancer, and continued controversy in both adjuvant therapy for esophageal carcinoma and noninvasive staging for lung cancer. Thoracic surgery education
Spring 2005 will mark graduation of the first thoracic surgery residents who will not require American Board of Surgery certification. Currently, the American Board of Thoracic Surgery requires completion of either a full residency in general surgery followed by an Accreditation Council for Graduate Medical Education– approved thoracic surgery residency (pathway one) or completion of a 6-year categorical-integrated thoracic surgery residency (pathway two) developed along Thoracic Surgery Directors Association (TSDA) guidelines and approved by the Accreditation Council for Graduate Medical Education (RRC-TS). Graduates this year will also be the second group privy to the Thoracic Surgery Directors Association’s new educational endeavors. In 2001, the Thoracic Surgery Directors Association Prerequisite Curriculum Committee developed and implemented a didactic curriculum for residents to study before starting their thoracic surgery residency. The Internet CD-ROM thoracic surgery e-learning system was implemented to access the curric-
Esophagus Achalasia
Controversy continues regarding primary treatment of achalasia. First-line treatment options include esophagomyotomy, pneumatic dilation, and botulinum toxin injections. We reviewed three prospective trials and two retrospective studies of different treatment modalities for both early-stage and late-stage achalasia (megaesophagus). Zaninotto and colleagues2 reported a prospective, randomized controlled trial of newly diagnosed achalasia patients assigned to either botulinum toxin injection (Botox [Allergan], 100 units injected twice, 1 month apart, at the gastroesophageal junction, n ⫽ 40) or laparoscopic cardiomyotomy and fundoplication (anterior partial or Nissen, n ⫽ 40). For myotomy patients, median hospital stay was 6 days, but Botox patients were discharged the same day. There was no mortality in either group. At 6 months, symptom scores in myotomy patients were significantly better than those in Botox patients (p ⬍ 0.05). Reduction in esophageal diameter (19% myotomy versus 5% Botox, p ⬍ 0.05) and the probability of being symptom free at 2 years followup
Received April 25, 2005; Accepted April 25, 2005. From the Department of Surgery, The University of Texas Medical Branch, Galveston, TX. Correspondence address: Joseph B Zwischenberger, MD, Division of Cardiothoracic Surgery, Department of Surgery, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555.
© 2005 by the American College of Surgeons Published by Elsevier Inc.
90
ISSN 1072-7515/05/$30.00 doi:10.1016/j.jamcollsurg.2005.04.028
Vol. 201, No. 1, July 2005
Zwischenberger et al
Abbreviations and Acronyms
CR ⫽ contrast ratio FDG-PET ⫽ positron emission tomography with 18 fluorodeoxyglucose GER ⫽ gastroesphageal reflux HR ⫽ hazard ratio LVRS ⫽ lung volume reduction surgery NSCLC ⫽ non-small cell lung cancer P-CRT ⫽ preoperative chemoradiation therapy UFT ⫽ uracil-tegafur VATS ⫽ video-assisted thoracic surgery
(87.5% myotomy versus 34% Botox, p ⬍ 0.05) also significantly favored myotomy. There was no significant difference in posttreatment lower esophageal pressure between groups. The authors concluded that Botox does not have a safety advantage over laparoscopic myotomy and requires multiple attempts to achieve lesser results. But, we note Botox injections are less invasive with a significantly decreased length of hospital stay. Clearly, a longer followup period would add to the risk/benefit assessment. In a prospective outcomes study, Gockel and colleagues3 reported on 19 patients who had unsuccessful repeated pneumatic dilation for achalasia and subsequently underwent a Heller myotomy. Outcomes were compared with those in patients who underwent successful pneumatic dilation (n ⫽ 34) or dilations (n ⫽ 14). Based on the 0-to-12-point clinical classification of achalasia scale (0 to 3 points each are given to weight loss, dysphagia, retrosternal pain, and regurgitation), the 10-year remission rate (defined as a score of less than 3 for 6 months) was 77% in the myotomy group compared with 72% in the single pneumatic dilation group and 45% in the multiple dilation group. The prognosis of patients in whom pneumatic dilations failed and who subsequently underwent myotomy was at least as favorable as that in patients who responded to a single pneumatic dilation. Also observed were eventual myotomy risks of 70% if diagnosed at age 15, 35% if diagnosed at age 40, and 8% at age 70. Duration of symptoms, symptom score, lower esophageal sphincter pressure, and diameter of the esophageal body were not predictors of the eventual need for operation. Previous dilations (maximum 3) also did not affect operation or outcomes. The authors plea for a randomized trial comparing pneumatic dilation to laparoscopic myotomy with stratification of patient groups according to age. We note that
What’s New in General Thoracic Surgery
91
with either Botox or pneumatic dilatations, one-third to two-thirds of patients can achieve meaningful palliation of their disease. To assess the incidence of postoperative gastroesophageal reflux (GER), Richards and colleagues4 reported on patients with achalasia randomized to either Heller myotomy (n ⫽ 21) or Heller myotomy with Dor (180degree anterior) fundoplication (n ⫽ 22). Within 6 months postoperatively, patients completed a questionnaire concerning the severity and frequency of their postoperative dysphagia. At the same visit, they underwent manometry and 24-hour pH monitoring. There were no significant differences in preoperative age, gender, preoperative lower esophageal sphincter pressure, or preoperative dysphagia score between the two groups. Pathologic GER (pH ⬍ 4 for more than 4.2% of a 24-hour period) occurred in 47.6% of the Heller group and in 9.1% of the Heller-Dor group (p ⫽ 0.005), corresponding to a ninefold risk reduction of pathologic GER for the Heller-Dor group. Median distal acid exposure time was also lower in the Heller-Dor group than in the Heller-alone group (0.4% versus 4.9%). There was no difference observed in lower esophageal sphincter pressure or postoperative dysphagia between the two groups. The authors recommended Dor partial fundoplication for control of pathologic reflux. In a retrospective study of 51 consecutive patients who underwent laparoscopic myotomy with (n ⫽ 29) or without (n ⫽ 22) anterior hemifundoplication, Dempsey and associates5 concluded that the addition of the partial wrap does not change clinical outcomes in terms of symptomatic reflux or patient satisfaction. The risk/ benefit of controlling pathologic GER after myotomy is still undefined. Management of late-stage (sigmoid) achalasia, or megaesophagus, continues to evoke controversy. Some surgeons recommend myotomy; others proceed directly to esophagectomy. In a series of 14 patients with sigmoid achalasia treated with Heller myotomy and anterior fundoplication through an open (n ⫽ 8) or laparoscopic (n ⫽ 6) approach, longterm outcomes (median followup, 85 months) were assessed.6 Myotomy with partial fundoplication achieved at least “satisfactory” symptom relief in 12 of 14 patients. Esophageal width decreased by 10 mm (p ⫽ 0.003) and lower esophageal sphincter pressure by 17 mmHg (p ⫽ 0.001). Dysphagia and regurgitation scores (1 ⫽ no symptoms; 4 ⫽ persistent symptoms) decreased from a median of 4.0 to 1.0 (p ⬍ 0.003).
92
Zwischenberger et al
What’s New in General Thoracic Surgery
These results did not differ from those in a group of 37 patients with an earlier-stage achalasia who were also treated with a Heller myotomy. This study was limited by the absence of a homogenous approach to the myotomy (open versus laparoscopic) and the absence of a myotomy alone or an esophagectomy group. We agree that myotomy techniques should be considered initially to preserve the native esophagus. Different approaches to myotomy for achalasia were also studied during the past year. Douard and colleagues7 prospectively studied patients with achalasia who underwent a Heller-Dor myotomy by laparoscopy (n ⫽ 52) or laparotomy (n ⫽ 30). There was no difference in “excellent” or “satisfactory” results between groups. GER rates were 10% with the laparoscopic approach and 7% with the open approach. Kesler and colleagues8 compared 38 patients who underwent thoracoscopy-assisted Heller myotomy with 19 historic controls who underwent open transthoracic Heller myotomy. In the thoracoscopy-assisted Heller myotomy group, four required conversion to an open procedure and four required further endoscopic or surgical intervention (including two esophagectomies). Twenty-nine of the 32 patients at followup (mean 17 months) had improved dysphagia. The thoracoscopyassisted Heller myotomy group had shorter operative time (97 versus 139 minutes, p ⬍ 0.01), less blood loss (80 versus 156 mL, p ⬍ 0.01), fewer postoperative days on narcotic medication (8 versus 20 days, p ⫽ 0.02), and shorter time to normal activity (20 versus 73 days, p ⬍ 0.01). Paraesophageal hernia
Many have proposed a laparoscopic approach for paraesophageal hiatal hernia repair. In a retrospective review of Orringer’s 25-year experience, Patel and associates9 reported on 240 patients treated with a primary transthoracic paraesophageal hernia repair to provide a “benchmark” against which minimally invasive approaches could be measured. There were 92% type III hernias and 8% type IV hernias. All patients also had an antireflux procedure, with a Collis-Nissen in 96%. The antireflux procedure reduced the incidence of symptomatic reflux from 68% to 0.1%. Operative mortality was 1.7%, with major postoperative complications in 8.5%. Reoperation was required early in 5% for anatomic recurrence, stenosis, or hemorrhage. Late reoperation was required in four patients for recurrent
J Am Coll Surg
herniation and two for stenosis. At followup (average 42 months), 85% were satisfied, with the most common complaint being mild to moderate dysphagia. Sixty-nine patients (29%) required postoperative dilatation. Median length of stay was 7 days (range 4 to 50 days). The authors contended that transthoracic exposure allows for an improved ability to resect the entire hernia sac and to more accurately assess esophageal length for a tension-free repair. Staging of esophageal carcinoma
Positron emission tomography with 18fluorodeoxyglucose (FDG-PET) is playing an increasing role in esophageal cancer management. Vrieze and colleagues10 reviewed data from 30 patients with advanced esophageal carcinoma to determine the value of FDG-PET in radiotherapy planning. Differences between CT, endoscopic ultrasonography, and FDG-PET were found in 47%. Based on the high false-negative rate but high specificity of FDG-PET, the authors recommended that the clinical target volume in radiotherapy planning be increased, but not decreased, based on PET results. In 69 patients with esophageal squamous cell carcinoma at the Samsung Medical Center in Seoul, Korea, Choi and colleagues11 reviewed the prognostic implications of FDG-PET before a curative esophagectomy. Multivariate analysis showed that tumor length by PET (hazard ratio [HR] ⫽ 2.74, p ⫽ 0.01) and the number of PET-positive nodes (HR ⫽ 1.71, p ⬍ 0.05) were independent prognostic indicators of overall survival. They suggested that revision of the TNM classification system consider tumor length and the number of positive lymph nodes. Heeren and coworkers12 studied 74 patients who underwent FDG-PET and CT as initial staging modalities. Fifty-two also had endoscopic ultrasonography. In 24 patients with pathologic distant nodal disease, PET identified 71% compared with 29% by combined CT and endoscopic ultrasonography (p ⫽ 0.021). The sensitivities to detect distant nodal or metastatic disease were 78% with PET and 37% with CT (p ⫽ 0.012). PET correctly upstaged 20%, falsely upstaged 7%, and falsely downstaged 4%. Treatment of esophageal carcinoma
Neoadjuvant chemoradiotherapy for advanced-stage esophageal cancer has become common practice in many centers despite lack of evidence-based support. Over the last year, only one prospective, randomized trial, by Lee and colleagues,13 specifically addressed out-
Vol. 201, No. 1, July 2005
Zwischenberger et al
comes in the setting of perioperative chemoradiotherapy versus esophagectomy-alone. The trial (101 patients with resectable squamous cell carcinoma, 50 esophagectomy only, and 51 chemoradiotherapy plus esophagectomy) was closed prematurely because of the excessive locoregional failure rate in the chemoradiotherapy plus surgery group. The chemoradiotherapy regimen consisted of cisplatin (60 mg/m2) on days 1 and 22, 5-fluorouracil (1,000 mg/m2) on days 2 to 5, and radiation therapy (45.6 Gy total) on days 1 to 28. There was no statistically significant difference in overall survival between the two groups (27.3 months esophagectomy only versus 28.2 months chemoradiotherapy plus esophagectomy; p ⫽ 0.69). In a retrospective review from the Mayo Clinic Group,14 75 patients with clinical stage III adenocarcinoma of the esophagus underwent either preoperative chemoradiation therapy (P-CRT) followed by esophagectomy (n ⫽ 47) or esophagectomy alone (n ⫽ 28). Clinical staging was by CT and endoscopic ultrasonography. Standard P-CRT consisted of radiation 5 days a week (5,040 cGy total) plus 5-fluorouracil (1,000 mg/ m2/day) and cisplatin (75 mg/m2/day) on the first and last 4 days of radiation therapy. There was no significant difference between P-CRT with esophagectomy versus esophagectomy-alone in terms of 3-year survival (42% in both) or 3-year disease-free survival (29% versus 33%). The 3-year survival rate was consistent with previous prospective, randomized trials.15,16 Interestingly, there was no survival advantage demonstrated in the P-CRT group despite a complete pathologic response in 26%. In a retrospective experience at Loyola University Medical Center,17 123 patients with esophageal squamous cell carcinoma and adenocarcinoma (stage IIB or III) underwent a transthoracic esophagectomy alone (n ⫽ 65) or with neoadjuvant (n ⫽ 31) or adjuvant (n ⫽ 27) chemoradiotherapy. Chemotherapy regimens consisted of combined fluorouracil, carboplatin, and paclitaxel or combined fluorouracil and cisplatin. Total radiotherapy dose was 4,500 rad. There were no significant differences between the esophagectomy-alone group and the groups receiving neoadjuvant or adjuvant chemoradiotherapy in terms of morbidity, operative mortality, or 3-year survival. This retrospective study was criticized for having two different chemotherapy regimens, two different radiation treatment planning methods, three different histologic types, and two different staging mo-
What’s New in General Thoracic Surgery
93
dalities. But this is one of the only series that “supports” (by a 3-year survival “trend” with a nonsignificant difference, p ⫽ 0.15) so far unduplicated results of the infamous 1996 Walsh report,16 which showed a significant survival advantage for chemoradiation and surgery compared with surgery alone. Armanios and colleagues18 reported the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected, pathologic stages IIB and III adenocarcinoma of the distal esophagus, gastroesophageal junction, or gastric cardia in a multicenter phase II trial. Chemotherapy consisted of four cycles of paclitaxel (175 mg/m2) followed by cisplatin (75 mg/ m2) every 21 days. Two-year survival was 60% compared with a historic control19 value of 38% with surgery alone (one-sided p ⫽ 0.0008). Patients were selected for adjuvant therapy only after they recovered from resection and demonstrated improved nutritional status. These four studies13,14,17,18 indicate the need for prospective, randomized, multicenter trials that focus on one stage, one histology, and one coherent staging and selection algorithm in the setting of esophagectomy alone versus esophagectomy plus preoperative or postoperative chemoradiotherapy. Techniques in esophageal carcinoma
Esophagectomy operative techniques continue to evolve. Hsu and colleagues20 carried out a prospective, randomized trial to compare a hand-sewn method of cervical esophagogastric anastomosis with a mechanical circular stapler method in patients undergoing curative esophagectomy with cervical esophagogastrostomy. The circular stapler significantly decreased operative time (524 versus 447 min, p ⬍ 0.001), but was equivalent by all other measures to the hand-sewn method. Notably, reinforcement stitches were added to the mechanical anastomoses routinely. In a prospective study of 421 patients who underwent resection for squamous cell carcinoma of the esophagus at the University of Hong Kong Medical Centre,21 major pulmonary complications (bronchopneumonia, aspiration pneumonia, and respiratory failure) occurred in 15.9% and were considered responsible for 55% of hospital deaths. The hospital mortality rate was 4.8% over 12 years, but 1.1% in the latter 6 years (p ⫽ 0.001 compared with the first 6 years of the study). Age, operation duration, and proximal tumor location (above the carina) were identified as independent risk factors for
94
Zwischenberger et al
What’s New in General Thoracic Surgery
pulmonary complications. Patients with tumors above the level of the carina had a 3.5-fold higher rate of pulmonary complications. Advanced age and higher blood loss were predictive of mortality. Chemoradiation was not associated with worse outcomes. Patient selection (lower resection rate, fewer palliative operations, lower pathologic stage distribution), evolving operative technique (fewer transhiatal operations and the advent of thoracoscopic esophagectomy), and modifications in perioperative care may have played a role in the decreased mortality rate in the latter half of the observation period. Palliative care for unresectable carcinoma of the esophagus has continued to focus on relief from dysphagia. In a prospective, randomized trial, Homs and colleagues22 treated 30 patients with carcinoma of the distal esophagus or gastric cardia with either a windsock-type valve stent (n ⫽ 15) or the same stent without the valve (n ⫽ 15). The valve stent failed to prevent reflux, and there was no significant difference between the two groups by any demographic or outcomes measure. In a multicenter randomized trial in The Netherlands, metal stent placement was also compared with single-dose brachytherapy (12 Gy) for the palliation of dysphagia in esophageal cancer.23 With 100 patients per group, stent placement provided more rapid relief of dysphagia, but brachytherapy provided more longterm relief. There was no difference between groups regarding persistent or recurrent dysphagia. Stent placement had more complications (mostly late hemorrhage) than brachytherapy (33% versus 21%, respectively, p ⫽ 0.02). Lung CT screening
More than 1,500 participants (more than 50 years old with a greater than 20 pack per year smoking history) enrolled in a lung cancer low-dose spiral CT screening trial at the Mayo Clinic in Rochester, MN. Of the 3,130 indeterminate (absence of benign pattern of calcification) pulmonary nodules found in 1,112 participants, only 1.5% of the nodules were cancer. Crestanello and associates24 reviewed the 60 operations performed on 55 of the participants who had suspicious pulmonary nodules, mediastinal adenopathy, or a spontaneous pneumothorax. Lung cancer (seven different histologies) was found in 82%, benign disease in 18%. Operative mortality was 1.7%. Complications occurred in 27% and included prolonged air leak, atrial arrhythmias, pneu-
J Am Coll Surg
monia, ileus, and cerebral vascular accident. Followup from this series has been too short to assess the cost/ survival benefit of spiral CT screening. Staging of non-small cell lung cancer
The role of positron emission tomography in the staging and management of non-small cell lung cancer (NSCLC) continues to provoke controversy ranging from universal application to triage by assessment of cost, benefit, and availability. Nomori and colleagues25 reported on a small series (n ⫽ 44) evaluating lymph node metastasis and tumor invasiveness using FDGPET in patients with NSCLC. All patients were clinical stage IA by FDG-PET and CT; eight were eventually upstaged. A contrast ratio (CR) (between the tumor and contralateral lung tissue) of 0.5 was used as the cutoff for predicting tumor invasiveness. All 22 lesions with a CR ⬍ 0.5 were T1 N0 M0, but 8 of 22 with a CR ⬎ 0.5 were more advanced. Adenocarcinomas with CR ⬍ 0.5 had less lymphatic invasion (p ⫽ 0.006), less vascular invasion (p ⫽ 0.004), less pleural involvement (p ⫽ 0.02), did not show an increased serum level of CEA (p ⫽ 0.001), and were more frequently well differentiated (p ⬍ 0.001). These findings suggest FDG-PET could be used to limit lung resection, lymph node dissection, or mediastinoscopy. In a prospective outcomes study of stages I and II NSCLC in the setting of staging with FDG-PET, Viney and colleagues26 randomized patients before operation into FDG-PET (n ⫽ 91) or conventional staging (n ⫽ 92) groups. The sensitivity (73%) and specificity (90%) of FDG-PET in its ability to identify mediastinal disease resulted in upstaging in 20%. The addition of FDGPET to conventional staging demonstrated a change in clinical management in 13% of patients but did not lead to a significant reduction in the number of thoracotomies avoided (p ⫽ 0.2). Although FDG-PET provided useful information to predict staging, its addition did not change treatment in the predominantly stage I population of this study. Concerning the accuracy of PET in restaging after induction chemotherapy in NSCLC, Port and associates27 performed a prospective study in 25 patients. The positive predictive value for PET determination of major pathologic response (defined as no disease or microscopic disease only in the primary tumor) was 43%, and nodal status was 48%. In Dr Schil’s invited commentary, he noted that tissue-based staging continues to re-
Vol. 201, No. 1, July 2005
Zwischenberger et al
main necessary after induction chemotherapy. Conversely, Hellwig and associates28 reported on 47 patients with resectable NSCLC who underwent preoperative PET after induction chemotherapy. The negative predictive values were 58% for tumor viability and 85% for persistent mediastinal disease. Median survival rates after primary resection were greater than 56 months for standard uptake value less than 4, and 19 months for standard uptake value greater than 4 (p ⬍ 0.001), implying standard uptake value as a prognostic indicator. The authors concluded that the “high” negative predictive value of PET in mediastinal restaging allows for the omission of repeat mediastinoscopy. Obviously, studies are still needed for a consensus on the incorporation of PET into staging and restaging in NSCLC. Cerfolio and colleagues29 conducted a prospective, blinded, lung cancer staging trial in which 129 consecutive patients underwent integrated PET-CT scanning. A single radiologist read the PET-CT and assigned T, N, and M status. The same radiologist, blinded, read the PET alone within 2 weeks and assigned T, N, and M status. Compared with PET alone, integrated PET-CT was a better predictor of stage I (52% versus 33%, p ⫽ 0.03), stage II (70% versus 36%, p ⫽ 0.04), T status (70% versus 47%, p ⫽ 0.001), and N status (78% versus 56%, p ⫽ 0.008). For N1 and N2 nodes, PET-CT had higher accuracy (90% versus 80% for N1; 96% versus 93% for N2), sensitivity (94% versus 53% for N1; 69% versus 62% for N2), specificity (89% versus 82% for N1), and positive predictive value (43% versus 22% for N1; 49% versus 42% for N2) (p ⬍ 0.05 for all). The negative predictive value difference was not significant for N2 disease. This study was unique in its delineation of sensitivities and accuracy at individual nodal stations. In the first report on real-time endobronchial ultrasonography-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes under local anesthesia, Yasufuku and associates30 successfully obtained samples from 58 mediastinal and 12 hilar nodes in 70 patients. Diagnoses included lung cancer (n ⫽ 35), metastases (n ⫽ 5), thyroid cancer, esophageal cancer, lymphoma, mesothelioma, and benign disease (n ⫽ 25). In distinguishing benign from malignant disease, endobronchial ultrasonography-guided transbronchial needle aspiration had a high sensitivity (96%), specificity (100%), and accuracy (97%). The authors noted several limitations to their study, including the technical challenges of the procedure itself, the inaccessibility of the
What’s New in General Thoracic Surgery
95
subaortic and paraesophageal nodes, and the potential inadequacies of sampling through a 22-gauge needle, but concluded that the procedure is safe and has a good diagnostic yield. For surgical staging, Lim and colleagues31 performed a prospective study to determine the prognostic implications of positive pleural lavage cytology in patients undergoing thoracotomy for NSCLC. Lavage was performed by irrigating the lung surface with 100 mL of saline immediately after entering the chest. Of 292 patients who met criteria (no effusion, extreme adhesions, or lateral chest wall invasion), samples from 13 were positive for malignancy. Median survivals were 13 months for the positive lavage group and 49 months for the negative lavage group (median followup 15 months) (p ⫽ 0.002). Where positive lavage cytology fits into conventional lung cancer staging remains unclear. Keller and colleagues32 addressed revision of the TNM staging of NSCLC from the Eastern Cooperative Oncology Group prospective randomized trial of adjuvant therapy in stages II and IIIa disease. Survival with left upper lobe NSCLC and metastases to single-level N2 nodes was not different from survival of N1 disease. Isolated N2 skip lesions had higher survival than concomitant N1 and N2 disease. The authors encouraged stratification of lung cancer by lobe of primary and metastatic pattern, with the eventual goal of revising the TNM staging system. Treatment of non-small cell lung cancer
Several major trials were published in 2004 regarding the role of adjuvant chemotherapy after complete resection of NSCLC. In a prospective trial from the International Adjuvant Lung Cancer Trial Collaborative Group (IALT), Arriagada and colleagues33 evaluated survival advantage in patients with completely resected stage I, II, or III NSCLC randomized to cisplatin plus etoposide or a vinca alkaloid versus no chemotherapy. A total of 1,867 patients from 148 centers in 33 countries were enrolled and followed for a median of 56 months. The chemotherapy group (n ⫽ 932) showed a significantly higher overall survival benefit at 5 years of 4.1% (44.5% versus 40.4%; HR for death 0.86; p ⬍ 0.03) and a disease-free survival benefit at 5 years of 5.1% (39.4% versus 34.3%, HR 0.83; p ⬍ 0.003). This study supports the use of three to four cycles of cisplatin-based chemotherapy after complete surgical resection. From the multicenter Big Lung Trial in Great Britain,
96
Zwischenberger et al
What’s New in General Thoracic Surgery
Waller and associates34 reported on a prospective randomized study (n ⫽ 381) comparing cisplatin-based chemotherapy with no chemotherapy for resected NSCLC (stages I to III). Complete resection was achieved in 95%. Neoadjuvant chemotherapy was given in 3% and radiotherapy in 14%. With a median followup of only 35 months, this trial failed to show a survival benefit. Differences in results of this trial compared with the International Adjuvant Lung Cancer Trial Collaborative Group may be attributed to improper staging (eg, ⬍ 50% 2-year survival of stage II patients), small sample size with inadequate power (ie, a cisplatin-based chemotherapy survival benefit of 5% would require approximately 4,000 patients to confirm), more toxic chemotherapy, and unclear use of neoadjuvant versus adjuvant chemotherapy in some patients. The Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy studied uracil-tegafur (UFT) (250 mg/m2/day for 2 years) after complete resection of stage I lung adenocarcinoma (n ⫽ 488) versus no additional treatment.35 Results showed overall 5-year survivals (median followup 72 months) of 88% for UFT and 85% for no treatment (p ⫽ 0.04; HR ⫽ 0.71). In subgroup analysis, a significant overall 5-year survival benefit for patients with T2 lesions only was seen for UFT (85%) versus no treatment (74%) (p ⫽ 0.005; HR ⫽ 0.48). Finally, a metaanalysis of 19 randomized clinical trials of adjuvant chemotherapy after complete resection (n ⫽ 7,200) by Sedrakyan and associates36 revealed an improved survival benefit. The metaanalysis demonstrated a 13% relative reduction in mortality (p ⬍ 0.0001, HR ⫽ 0.87) with adjuvant chemotherapy compared with surgery alone. Subgroup analysis showed that cisplatinbased chemotherapy achieved an 11% relative reduction in mortality (p ⫽ 0.004) compared with a surgery-alone control group survival of 45% at 5 years; UFT chemotherapy showed a 17% relative reduction in mortality (p ⫽ 0.006) compared with a surgery-alone control group survival of 80% at 5 years. Absolute improvements in survival were 4% for cisplatin-based chemotherapy and 3.5% for UFT. Apparently, a benefit can be gained by providing adjuvant chemotherapy to completely resected stage I and II NSCLC, but the number of cycles and optimal chemotherapeutic agent are debatable. UFT has fewer toxic side effects than cisplatin and should be further evaluated when it becomes available in the United States.
J Am Coll Surg
Techniques in lung cancer treatment
Ohtsuka and coworkers37 reviewed their experience with video-assisted thoracic surgery (VATS) pulmonary resection in 106 patients with clinical stage I NSCLC. Operations consisted of lobectomy (n ⫽ 86), segmentectomy (n ⫽ 8), and bilobectomy (n ⫽ 1). Eleven patients required conversion to an open procedure. Postoperative complications occurred in 9% (including 1 death secondary to pneumonia). Mean hospital stay was 7.6 days (range 4 to 15 days) among patients without complications. The 3-year survival rate among patients with pathologic stage I disease was 89%. Local recurrence was seen in 6%. More experience with VATS lobectomy is necessary before the risk/benefit of this more technically challenging approach can be endorsed. Control of air leaks postoperatively continues to warrant study. In a prospective, randomized trial of 145 patients who underwent lobectomy, 72 patients were placed on water seal on the first postoperative morning and 73 were maintained on ⫺20 cm H2O suction.38 Air leak duration was equivalent between the two groups (6.5 days for water seal versus 6.3 days for suction; p ⫽ 0.9). Prolonged air leak incidence (27.8% seal versus 30.1% suction; p ⫽ 0.8) and length of hospital stay also were not different. The results of this trial contrast with those from previous studies39,40 showing a decreased incidence of prolonged air leak on water seal. Previous observations have amalgamated wedge resections, segmentectomies, and lobectomies together. In the current study 80% also had a pleural tent procedure, perhaps negating the advantages of water seal. Czerny and colleagues41 published a prospective, randomized two-by-two factorial design trial comparing TachoComb (a local hemostyptic agent, Torii Pharmaceutical Co) with one of two low molecular weight heparin anticoagulation arms (enoxaparin or dalteparin) to conventional surgical hemostasis with the same agents (4 groups total) in 80 patients undergoing resection and complete mediastinal node dissection for stage I or II NSCLC. Patients receiving the combination of TachoComb and dalteparin had statistically significant lower chest drainage on days 1, 2, and 3 individually and cumulatively (498 mL over 4 days versus 1,000 mL for TachoComb with enoxaparin, 924 mL for dalteparin only, and 895 mL for enoxaparin only; p ⬍ 0.05). There were also fewer chest tube days in the TachoComb plus dalteparin group (1.78 days versus 2.96 days for TachoComb with enoxaparin, 2.93 days for dalteparin only, and 3.06 days for
Vol. 201, No. 1, July 2005
Zwischenberger et al
enoxaparin only; p ⫽ 0.019). The authors concluded that use of a local hemostyptic agent with dalteparin may decrease postoperative bleeding in patients with prophylactic perioperative anticoagulation. Emphysema
Previous reports from the multicenter National Emphysema Treatment Trial showed that lung volume reduction surgery (LVRS) provides functional improvement for patients with upper lobe emphysema and increases survival among the same cohort with a low baseline exercise capacity. National Emphysema Treatment Trial data were subsequently analyzed to determine the safety and efficacy of median sternotomy (n ⫽ 359) versus VATS (n ⫽ 152) for LVRS.42 Mortality, complication rates (including air leak after 7 days), and changes in exercise capacity and quality of life were similar between the two groups. Median hospital stays were 10 days for sternotomy and 9 days for VATS (p ⫽ 0.02). The sternotomy group also had more intensive care unit days. Operative and overall costs were less for VATS (p ⬍ 0.01). Laghi and colleagues43 reported their 2-year followup of patients who showed an increase in diaphragmatic neuromechanical coupling (tidal volume to change in transdiaphragmatic pressure ratio) 3 months after LVRS. At 2 years, the 8 patients who completed the study showed continued improvement in 6-minute walking distance (p ⬍ 0.05) despite the fact that lung volumes had relapsed to preoperative values. Choong and associates44 reported on their experience with 21 emphysema patients who underwent concomitant cancer resection and LVRS. Patient selection criteria included no evidence of N2 disease, heterogeneous, severe emphysema with suitable target areas, and often (9 in 21) tumor within the emphysematous lobe itself. Preoperatively, their patients had a mean FEV1 of 0.7 ⫾ 0.2L (29% predicted), residual volume of 5.5 ⫾ 1.0L (271%), and diffusing capacity for carbon monoxide of 8.0 ⫾ 2.2 mL/min/mmHg (34% predicted). Prolonged air leak occurred in 11 patients and reintubation in 2. Survivals (Kaplan-Meier estimation) at 1, 3, and 5 years were 100%, 74%, and 63%, respectively, comparing well with bilateral lung volume reduction and predicted outcomes relative to staging.45 The authors cautioned against applying their experience to all patients with resectable lung cancer and severe emphysema.
What’s New in General Thoracic Surgery
97
Metastatic soft tissue sarcoma
Porter and colleagues46 reported on the cost effectiveness of a four-treatment-arm model of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcomas in the combined experience of the University of Texas MD Anderson and Memorial Sloan-Kettering Cancer Centers. Data from 889 patients who had no treatment showed a median survival of 13 months. The cost of the no-treatment group was considered supportive care that would be required for all patients, so was set at zero. There were 235 consecutive patients who underwent complete resection of soft tissue sarcoma pulmonary metastases, with median survival of 31 months at a cost of $20,339 per patient ($14,357 per life-year gained). Subsequently, the analysis assumed a “generous” 12-month improved survival for adding chemotherapy (4 cycles of doxorubicin and ifosfamide). The chemotherapy-alone group would have a median survival of 25 months at a cost of $99,033 per patient ($104,210 per life-year gained), and the chemotherapy plus surgery group would survive 43 months for $119,732 per patient ($51,159 per life-year gained). The authors concluded that pulmonary resection was the most cost-effective treatment. Mesothelioma
Sugarbaker and colleagues47 published one of the largest experiences on treatment of malignant pleural mesothelioma by extrapleural pneumonectomy. In 496 consecutive patients who underwent extrapleural pneumonectomy (444 for mesothelioma), operative (30-day) mortality was 4.0%. In 328 consecutive patients with mesotheliomas, the morbidity rate was 60.4%. The most common postoperative complication was atrial fibrillation (44.2%), with no success in reduction despite prophylactic treatment. Other serious complications were cardiac tamponade (3.6%), acute respiratory distress syndrome (3.6%), cardiac arrest (3%), inflammatory epicarditis (2.7%), and myocardial infarction (1.5%). Previously reported mortality rates since the 1980s have ranged from 6% to 15%. The authors attributed their relatively low mortality and complication rates to improved surgical technique (such as diaphragmatic and pericardial reconstructions) and prevention (anticoagulation, screening for vocal cord paralysis, and liberal use of bronchoscopy). The risk/benefit ratio of extrapleural pneumonectomy still appears narrow.
98
Zwischenberger et al
What’s New in General Thoracic Surgery
J Am Coll Surg
Transplant
REFERENCES
Lung transplantation management has evolved over the past 20 years but remains site specific. In a survey of lung transplant practice in North America published this past year, 50 of 65 active centers responded to a 64-question survey designed by The Transplant/Immunology Network of the American College of Chest Physicians.48 Generally, patient selection criteria were remarkably consistent. But this snapshot of current practice demonstrated considerable variance in posttransplant management. The survey reviewers suggest that future collaborative studies focus on optimal postoperative management guidelines. In a review of single- and double-lung transplantation at the Toronto General Hospital from 1983 to 2003, de Perrott and colleagues49 found that survivals for all recipients were 55% at 5 years, 35% at 10 years, and 27% at 15 years. The most common causes of death were sepsis and bronchiolitis obliterans. The best longterm survival was in patients with primary pulmonary hypertension (59% at 10 years) or cystic fibrosis (B cepacia negative) (52% at 10 years). The lowest survival was in patients with B cepacia positive cystic fibrosis (15% at 10 years). Future management will focus on reducing infection and preventing chronic graft dysfunction or bronchiolitis obliterans. Living lobar lung transplantation provides patients unable to await cadaveric transplantation a lifesaving procedure, but with considerable risk (up to a 60% complication incidence including postpericardiotomy syndrome, atrial fibrillation, and surgical reexploration) to 2 donors. From the seminal institution for this procedure, Starnes and associates50 reported on their 10-year experience with 128 living lobar transplantations (84 adults, 39 children) at the USC Keck School of Medicine and Children’s Hospital. The 5-year actuarial survival was 45%. Primary causes of mortality were infection (53%), bronchiolitis obliterans (13%), and primary graft dysfunction (8%). The authors concluded that risk to the donors coupled with poor outcomes in patients on ventilators preoperatively (increased risk of death odds ratio ⫽ 3.06; p ⫽ 0.03) and those with previous transplantations (odds ratio ⫽ 2.50) is perhaps too high to justify living lobar transplantation in these subgroups. For other suitable recipients whose condition is worsening, living lobar transplantation continues to be a viable lifesaving operation.
1. Gold JP, Begg WB, Fullerton D, et al. Successful implementation of a novel internet hybrid surgery curriculum: the early phase outcome of thoracic surgery prerequisite curriculum e-learning project. Ann Surg 2004;240:499–509. 2. Zaninotto G, Annese V, Costantini M, et al. Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia. Ann Surg 2004;239:364–370. 3. Gockel I, Junginger T, Bernhard G, Eckardt VF. Heller myotomy for failed pneumatic dilation in achalasia: how effective is it? Ann Surg 2004;239:371–377. 4. Richards WO, Torquati A, Holzman MD, et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 2004;240:405–415. 5. Dempsey DT, Delano M, Bradley K, et al. Laparoscopic esophagomyotomy for achalasia: does anterior hemifundoplication affect clinical outcome? Ann Surg 2004;239:779–787. 6. Mineo TC, Pompeo E. Long-term outcome of Heller myotomy in achalasic sigmoid esophagus. J Thorac Cardiovasc Surg 2004; 128:402–407. 7. Douard R, Gaudric M, Chaussade S, et al. Functional results after laparoscopic Heller myotomy for achalasia: A comparative study to open surgery. Surgery 2004;136:16–24. 8. Kesler KA, Tarvin SE, Brooks JA, et al. Thoracoscopy-assisted Heller myotomy for the treatment of achalasia: results of a minimally invasive technique. Ann Thorac Surg 2004;77:385–392. 9. Patel HJ, Tan BB, Yee J, et al. A 25-year experience with open primary transthoracic repair of paraesophageal hiatal hernia. J Thorac Cardiovasc Surg 2004;127:843–849. 10. Vrieze O, Haustermans K, De Wever W, et al. Is there a role for FDG-PET in radiotherapy planning in esophageal carcinoma? Radiother Oncol 2004;73:269–275. 11. Choi JY, Jang HJ, Shim YM, et al. 18F-FDG PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: prognostic implications. J Nucl Med 2004;45:1843– 1850. 12. Heeren PA, Jager PL, Bongaerts F, et al. Detection of distant metastases in esophageal cancer with (18)F-FDG PET. J Nucl Med 2004;45:980–987. 13. Lee JL, Park SI, Kim SB, et al. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol 2004;15:947– 954. 14. Donington JS, Miller DL, Allen MS, et al. Preoperative chemoradiation therapy does not improve early survival after esophagectomy for patients with clinical stage III adenocarcinoma of the esophagus. Ann Thorac Surg 2004;77:1193–1199. 15. Urba SG, Orringer MB, Turrisi A, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19: 305–313. 16. Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462–467. 17. Malaisrie SC, Untch B, Aranha GV, et al. Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer: experience at a single institution. Arch Surg 2004;139:532–539. 18. Armanios M, Xu R, Forastiere AA, et al. Adjuvant chemotherapy for resected adenocarcinoma of the esophagus, gastro-
Vol. 201, No. 1, July 2005
19.
20.
21. 22.
23.
24. 25.
26.
27.
28.
29.
30. 31.
32. 33. 34.
Zwischenberger et al
esophageal junction, and cardia: phase II trial (E8296) of the Eastern Cooperative Oncology Group. J Clin Oncol 2004;22:4495–4499. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345: 725–730. Hsu HH, Chen JS, Huang PM, et al. Comparison of manual and mechanical cervical esophagogastric anastomosis after esophageal resection for squamous cell carcinoma: a prospective randomized controlled trial. Eur J Cardiothorac Surg 2004; 25:1097–1101. Law S, Wong KH, Kwok KF, et al. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg 2004;240:791–800. Homs MY, Wahab PJ, Kuipers EJ, et al. Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc 2004;60:695– 702. Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364:1497–1504. Crestanello JA, Allen MS, Jett JR, et al. Thoracic surgical operations in patients enrolled in a computed tomographic screening trial. J Thorac Cardiovasc Surg 2004;128:254–259. Nomori H, Watanabe K, Ohtsuka T, et al. Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma. J Thorac Cardiovasc Surg 2004;128:396–401. Viney RC, Boyer MJ, King MT, et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 2004;22:2357–2362. Port JL, Kent MS, Korst RJ, et al. Positron emission tomography scanning poorly predicts response to preoperative chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2004;77:254– 259. Hellwig D, Graeter TP, Ukena D, et al. Value of F-18fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 2004;128:892–899. Cerfolio RJ, Ojha B, Bryant AS, et al. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer. Ann Thorac Surg 2004; 78:1017–1023. Yasufuku K, Chiyo M, Sekine Y, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. Chest 2004;126:122–128. Lim E, Ali A, Theodorou P, et al. Intraoperative pleural lavage cytology is an independent prognostic indicator for staging nonsmall cell lung cancer. J Thorac Cardiovasc Surg 2004;127: 1113–1118. Keller SM, Vangel MG, Wagner H, et al. Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease. J Thorac Cardiovasc Surg 2004;128:130–137. Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected nonsmall-cell lung cancer. N Engl J Med 2004;350:351–360. Waller D, Peake MD, Stephens RJ, et al. Chemotherapy for
35. 36.
37.
38. 39. 40. 41.
42.
43. 44.
45.
46.
47.
48. 49.
50.
What’s New in General Thoracic Surgery
99
patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 2004;26:173–182. Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004;350:1713–1721. Sedrakyan A, Van Der Meulen J, O’Byrne K, et al. Postoperative chemotherapy for non-small cell lung cancer: A systematic review and meta-analysis. J Thorac Cardiovasc Surg 2004;128: 414–419. Ohtsuka T, Nomori H, Horio H, et al. Is major pulmonary resection by video-assisted thoracic surgery an adequate procedure in clinical stage I lung cancer? Chest 2004;125:1742– 1746. Brunelli A, Monteverde M, Borri A, et al. Comparison of water seal and suction after pulmonary lobectomy: a prospective, randomized trial. Ann Thorac Surg 2004;77:1932–1937. Cerfolio RJ, Bass C, Katholi CR. Prospective randomized trial compares suction versus water seal for air leaks. Ann Thorac Surg 2001;71:1613–1617. Marshall MB, Deeb ME, Bleier JI, et al. Suction vs water seal after pulmonary resection: a randomized prospective study. Chest 2002;121:831–835. Czerny M, Fleck T, Salat A, et al. Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma. Ann Thorac Surg 2004;77: 1028–1032. McKenna RJ Jr, Benditt JO, DeCamp M, et al. Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery. J Thorac Cardiovasc Surg 2004;127:1350–1360. Laghi F, Jubran A, Topeli A, et al. Effect of lung volume reduction surgery on diaphragmatic neuromechanical coupling at 2 years. Chest 2004;125:2188–2195. Choong CK, Meyers BF, Battafarano RJ, et al. Lung cancer resection combined with lung volume reduction in patients with severe emphysema. J Thorac Cardiovasc Surg 2004;127:1323– 1331. Ciccone AM, Meyers BF, Guthrie TJ, et al. Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J Thorac Cardiovasc Surg 2003;125:513– 525. Porter GA, Cantor SB, Walsh GL, et al. Cost-effectiveness of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcoma: a combined analysis from the University of Texas M. D. Anderson and Memorial Sloan-Kettering Cancer Centers. J Thorac Cardiovasc Surg 2004;127:1366–1372. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 2004;128:138–146. Levine SM. A survey of clinical practice of lung transplantation in North America. Chest 2004;125:1224–1238. de Perrot M, Chaparro C, McRae K, et al. Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival. J Thorac Cardiovasc Surg 2004;127:1493–1501. Starnes VA, Bowdish ME, Woo MS, et al. A decade of living lobar lung transplantation: recipient outcomes. J Thorac Cardiovasc Surg 2004;127:114–122.
What’s New in General Thoracic Surgery Joseph B Zwischenberger, MD, FACS, Brannon R Hyde, MD, Juan C Escalon, MD “What’s New in Surgery” evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons’ Advisory Councils for the Surgical Specialties. This feature is now presented in issues of the Journal throughout the year.
ulum. A recently published prospective randomized trial tested resident acceptance and educational impact.1 From residents who matriculated in 2002, 138 agreed to participate in the study. Sixty-nine residents were randomized to receive a CD-ROM access key, and 69 received the curriculum outline only. Using the Internet, the system was designed to track resident use and performance. Based on the American Board of Thoracic Surgery In-Training Exam performance, resident selfassessments, and program directors’ assessments, the system and content have been well received. There is a trend toward improved resident performance with more frequent use of the e-learning system. The system is being updated and expanded to include a complete core curriculum to be used throughout the residency.
“What’s new” articles are cultivated from selected analysis of the past year’s peer-reviewed literature. Although our knowledge and understanding of general thoracic surgical issues increased last year, enthusiasm is bridled by the few changes actually assimilated into clinical practice. Highlights of the past year include new trends in resident education, significant trials in adjuvant therapy for lung cancer, and continued controversy in both adjuvant therapy for esophageal carcinoma and noninvasive staging for lung cancer. Thoracic surgery education
Spring 2005 will mark graduation of the first thoracic surgery residents who will not require American Board of Surgery certification. Currently, the American Board of Thoracic Surgery requires completion of either a full residency in general surgery followed by an Accreditation Council for Graduate Medical Education– approved thoracic surgery residency (pathway one) or completion of a 6-year categorical-integrated thoracic surgery residency (pathway two) developed along Thoracic Surgery Directors Association (TSDA) guidelines and approved by the Accreditation Council for Graduate Medical Education (RRC-TS). Graduates this year will also be the second group privy to the Thoracic Surgery Directors Association’s new educational endeavors. In 2001, the Thoracic Surgery Directors Association Prerequisite Curriculum Committee developed and implemented a didactic curriculum for residents to study before starting their thoracic surgery residency. The Internet CD-ROM thoracic surgery e-learning system was implemented to access the curric-
Esophagus Achalasia
Controversy continues regarding primary treatment of achalasia. First-line treatment options include esophagomyotomy, pneumatic dilation, and botulinum toxin injections. We reviewed three prospective trials and two retrospective studies of different treatment modalities for both early-stage and late-stage achalasia (megaesophagus). Zaninotto and colleagues2 reported a prospective, randomized controlled trial of newly diagnosed achalasia patients assigned to either botulinum toxin injection (Botox [Allergan], 100 units injected twice, 1 month apart, at the gastroesophageal junction, n ⫽ 40) or laparoscopic cardiomyotomy and fundoplication (anterior partial or Nissen, n ⫽ 40). For myotomy patients, median hospital stay was 6 days, but Botox patients were discharged the same day. There was no mortality in either group. At 6 months, symptom scores in myotomy patients were significantly better than those in Botox patients (p ⬍ 0.05). Reduction in esophageal diameter (19% myotomy versus 5% Botox, p ⬍ 0.05) and the probability of being symptom free at 2 years followup
Received April 25, 2005; Accepted April 25, 2005. From the Department of Surgery, The University of Texas Medical Branch, Galveston, TX. Correspondence address: Joseph B Zwischenberger, MD, Division of Cardiothoracic Surgery, Department of Surgery, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555.
© 2005 by the American College of Surgeons Published by Elsevier Inc.
90
ISSN 1072-7515/05/$30.00 doi:10.1016/j.jamcollsurg.2005.04.028
Vol. 201, No. 1, July 2005
Zwischenberger et al
Abbreviations and Acronyms
CR ⫽ contrast ratio FDG-PET ⫽ positron emission tomography with 18 fluorodeoxyglucose GER ⫽ gastroesphageal reflux HR ⫽ hazard ratio LVRS ⫽ lung volume reduction surgery NSCLC ⫽ non-small cell lung cancer P-CRT ⫽ preoperative chemoradiation therapy UFT ⫽ uracil-tegafur VATS ⫽ video-assisted thoracic surgery
(87.5% myotomy versus 34% Botox, p ⬍ 0.05) also significantly favored myotomy. There was no significant difference in posttreatment lower esophageal pressure between groups. The authors concluded that Botox does not have a safety advantage over laparoscopic myotomy and requires multiple attempts to achieve lesser results. But, we note Botox injections are less invasive with a significantly decreased length of hospital stay. Clearly, a longer followup period would add to the risk/benefit assessment. In a prospective outcomes study, Gockel and colleagues3 reported on 19 patients who had unsuccessful repeated pneumatic dilation for achalasia and subsequently underwent a Heller myotomy. Outcomes were compared with those in patients who underwent successful pneumatic dilation (n ⫽ 34) or dilations (n ⫽ 14). Based on the 0-to-12-point clinical classification of achalasia scale (0 to 3 points each are given to weight loss, dysphagia, retrosternal pain, and regurgitation), the 10-year remission rate (defined as a score of less than 3 for 6 months) was 77% in the myotomy group compared with 72% in the single pneumatic dilation group and 45% in the multiple dilation group. The prognosis of patients in whom pneumatic dilations failed and who subsequently underwent myotomy was at least as favorable as that in patients who responded to a single pneumatic dilation. Also observed were eventual myotomy risks of 70% if diagnosed at age 15, 35% if diagnosed at age 40, and 8% at age 70. Duration of symptoms, symptom score, lower esophageal sphincter pressure, and diameter of the esophageal body were not predictors of the eventual need for operation. Previous dilations (maximum 3) also did not affect operation or outcomes. The authors plea for a randomized trial comparing pneumatic dilation to laparoscopic myotomy with stratification of patient groups according to age. We note that
What’s New in General Thoracic Surgery
91
with either Botox or pneumatic dilatations, one-third to two-thirds of patients can achieve meaningful palliation of their disease. To assess the incidence of postoperative gastroesophageal reflux (GER), Richards and colleagues4 reported on patients with achalasia randomized to either Heller myotomy (n ⫽ 21) or Heller myotomy with Dor (180degree anterior) fundoplication (n ⫽ 22). Within 6 months postoperatively, patients completed a questionnaire concerning the severity and frequency of their postoperative dysphagia. At the same visit, they underwent manometry and 24-hour pH monitoring. There were no significant differences in preoperative age, gender, preoperative lower esophageal sphincter pressure, or preoperative dysphagia score between the two groups. Pathologic GER (pH ⬍ 4 for more than 4.2% of a 24-hour period) occurred in 47.6% of the Heller group and in 9.1% of the Heller-Dor group (p ⫽ 0.005), corresponding to a ninefold risk reduction of pathologic GER for the Heller-Dor group. Median distal acid exposure time was also lower in the Heller-Dor group than in the Heller-alone group (0.4% versus 4.9%). There was no difference observed in lower esophageal sphincter pressure or postoperative dysphagia between the two groups. The authors recommended Dor partial fundoplication for control of pathologic reflux. In a retrospective study of 51 consecutive patients who underwent laparoscopic myotomy with (n ⫽ 29) or without (n ⫽ 22) anterior hemifundoplication, Dempsey and associates5 concluded that the addition of the partial wrap does not change clinical outcomes in terms of symptomatic reflux or patient satisfaction. The risk/ benefit of controlling pathologic GER after myotomy is still undefined. Management of late-stage (sigmoid) achalasia, or megaesophagus, continues to evoke controversy. Some surgeons recommend myotomy; others proceed directly to esophagectomy. In a series of 14 patients with sigmoid achalasia treated with Heller myotomy and anterior fundoplication through an open (n ⫽ 8) or laparoscopic (n ⫽ 6) approach, longterm outcomes (median followup, 85 months) were assessed.6 Myotomy with partial fundoplication achieved at least “satisfactory” symptom relief in 12 of 14 patients. Esophageal width decreased by 10 mm (p ⫽ 0.003) and lower esophageal sphincter pressure by 17 mmHg (p ⫽ 0.001). Dysphagia and regurgitation scores (1 ⫽ no symptoms; 4 ⫽ persistent symptoms) decreased from a median of 4.0 to 1.0 (p ⬍ 0.003).
92
Zwischenberger et al
What’s New in General Thoracic Surgery
These results did not differ from those in a group of 37 patients with an earlier-stage achalasia who were also treated with a Heller myotomy. This study was limited by the absence of a homogenous approach to the myotomy (open versus laparoscopic) and the absence of a myotomy alone or an esophagectomy group. We agree that myotomy techniques should be considered initially to preserve the native esophagus. Different approaches to myotomy for achalasia were also studied during the past year. Douard and colleagues7 prospectively studied patients with achalasia who underwent a Heller-Dor myotomy by laparoscopy (n ⫽ 52) or laparotomy (n ⫽ 30). There was no difference in “excellent” or “satisfactory” results between groups. GER rates were 10% with the laparoscopic approach and 7% with the open approach. Kesler and colleagues8 compared 38 patients who underwent thoracoscopy-assisted Heller myotomy with 19 historic controls who underwent open transthoracic Heller myotomy. In the thoracoscopy-assisted Heller myotomy group, four required conversion to an open procedure and four required further endoscopic or surgical intervention (including two esophagectomies). Twenty-nine of the 32 patients at followup (mean 17 months) had improved dysphagia. The thoracoscopyassisted Heller myotomy group had shorter operative time (97 versus 139 minutes, p ⬍ 0.01), less blood loss (80 versus 156 mL, p ⬍ 0.01), fewer postoperative days on narcotic medication (8 versus 20 days, p ⫽ 0.02), and shorter time to normal activity (20 versus 73 days, p ⬍ 0.01). Paraesophageal hernia
Many have proposed a laparoscopic approach for paraesophageal hiatal hernia repair. In a retrospective review of Orringer’s 25-year experience, Patel and associates9 reported on 240 patients treated with a primary transthoracic paraesophageal hernia repair to provide a “benchmark” against which minimally invasive approaches could be measured. There were 92% type III hernias and 8% type IV hernias. All patients also had an antireflux procedure, with a Collis-Nissen in 96%. The antireflux procedure reduced the incidence of symptomatic reflux from 68% to 0.1%. Operative mortality was 1.7%, with major postoperative complications in 8.5%. Reoperation was required early in 5% for anatomic recurrence, stenosis, or hemorrhage. Late reoperation was required in four patients for recurrent
J Am Coll Surg
herniation and two for stenosis. At followup (average 42 months), 85% were satisfied, with the most common complaint being mild to moderate dysphagia. Sixty-nine patients (29%) required postoperative dilatation. Median length of stay was 7 days (range 4 to 50 days). The authors contended that transthoracic exposure allows for an improved ability to resect the entire hernia sac and to more accurately assess esophageal length for a tension-free repair. Staging of esophageal carcinoma
Positron emission tomography with 18fluorodeoxyglucose (FDG-PET) is playing an increasing role in esophageal cancer management. Vrieze and colleagues10 reviewed data from 30 patients with advanced esophageal carcinoma to determine the value of FDG-PET in radiotherapy planning. Differences between CT, endoscopic ultrasonography, and FDG-PET were found in 47%. Based on the high false-negative rate but high specificity of FDG-PET, the authors recommended that the clinical target volume in radiotherapy planning be increased, but not decreased, based on PET results. In 69 patients with esophageal squamous cell carcinoma at the Samsung Medical Center in Seoul, Korea, Choi and colleagues11 reviewed the prognostic implications of FDG-PET before a curative esophagectomy. Multivariate analysis showed that tumor length by PET (hazard ratio [HR] ⫽ 2.74, p ⫽ 0.01) and the number of PET-positive nodes (HR ⫽ 1.71, p ⬍ 0.05) were independent prognostic indicators of overall survival. They suggested that revision of the TNM classification system consider tumor length and the number of positive lymph nodes. Heeren and coworkers12 studied 74 patients who underwent FDG-PET and CT as initial staging modalities. Fifty-two also had endoscopic ultrasonography. In 24 patients with pathologic distant nodal disease, PET identified 71% compared with 29% by combined CT and endoscopic ultrasonography (p ⫽ 0.021). The sensitivities to detect distant nodal or metastatic disease were 78% with PET and 37% with CT (p ⫽ 0.012). PET correctly upstaged 20%, falsely upstaged 7%, and falsely downstaged 4%. Treatment of esophageal carcinoma
Neoadjuvant chemoradiotherapy for advanced-stage esophageal cancer has become common practice in many centers despite lack of evidence-based support. Over the last year, only one prospective, randomized trial, by Lee and colleagues,13 specifically addressed out-
Vol. 201, No. 1, July 2005
Zwischenberger et al
comes in the setting of perioperative chemoradiotherapy versus esophagectomy-alone. The trial (101 patients with resectable squamous cell carcinoma, 50 esophagectomy only, and 51 chemoradiotherapy plus esophagectomy) was closed prematurely because of the excessive locoregional failure rate in the chemoradiotherapy plus surgery group. The chemoradiotherapy regimen consisted of cisplatin (60 mg/m2) on days 1 and 22, 5-fluorouracil (1,000 mg/m2) on days 2 to 5, and radiation therapy (45.6 Gy total) on days 1 to 28. There was no statistically significant difference in overall survival between the two groups (27.3 months esophagectomy only versus 28.2 months chemoradiotherapy plus esophagectomy; p ⫽ 0.69). In a retrospective review from the Mayo Clinic Group,14 75 patients with clinical stage III adenocarcinoma of the esophagus underwent either preoperative chemoradiation therapy (P-CRT) followed by esophagectomy (n ⫽ 47) or esophagectomy alone (n ⫽ 28). Clinical staging was by CT and endoscopic ultrasonography. Standard P-CRT consisted of radiation 5 days a week (5,040 cGy total) plus 5-fluorouracil (1,000 mg/ m2/day) and cisplatin (75 mg/m2/day) on the first and last 4 days of radiation therapy. There was no significant difference between P-CRT with esophagectomy versus esophagectomy-alone in terms of 3-year survival (42% in both) or 3-year disease-free survival (29% versus 33%). The 3-year survival rate was consistent with previous prospective, randomized trials.15,16 Interestingly, there was no survival advantage demonstrated in the P-CRT group despite a complete pathologic response in 26%. In a retrospective experience at Loyola University Medical Center,17 123 patients with esophageal squamous cell carcinoma and adenocarcinoma (stage IIB or III) underwent a transthoracic esophagectomy alone (n ⫽ 65) or with neoadjuvant (n ⫽ 31) or adjuvant (n ⫽ 27) chemoradiotherapy. Chemotherapy regimens consisted of combined fluorouracil, carboplatin, and paclitaxel or combined fluorouracil and cisplatin. Total radiotherapy dose was 4,500 rad. There were no significant differences between the esophagectomy-alone group and the groups receiving neoadjuvant or adjuvant chemoradiotherapy in terms of morbidity, operative mortality, or 3-year survival. This retrospective study was criticized for having two different chemotherapy regimens, two different radiation treatment planning methods, three different histologic types, and two different staging mo-
What’s New in General Thoracic Surgery
93
dalities. But this is one of the only series that “supports” (by a 3-year survival “trend” with a nonsignificant difference, p ⫽ 0.15) so far unduplicated results of the infamous 1996 Walsh report,16 which showed a significant survival advantage for chemoradiation and surgery compared with surgery alone. Armanios and colleagues18 reported the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected, pathologic stages IIB and III adenocarcinoma of the distal esophagus, gastroesophageal junction, or gastric cardia in a multicenter phase II trial. Chemotherapy consisted of four cycles of paclitaxel (175 mg/m2) followed by cisplatin (75 mg/ m2) every 21 days. Two-year survival was 60% compared with a historic control19 value of 38% with surgery alone (one-sided p ⫽ 0.0008). Patients were selected for adjuvant therapy only after they recovered from resection and demonstrated improved nutritional status. These four studies13,14,17,18 indicate the need for prospective, randomized, multicenter trials that focus on one stage, one histology, and one coherent staging and selection algorithm in the setting of esophagectomy alone versus esophagectomy plus preoperative or postoperative chemoradiotherapy. Techniques in esophageal carcinoma
Esophagectomy operative techniques continue to evolve. Hsu and colleagues20 carried out a prospective, randomized trial to compare a hand-sewn method of cervical esophagogastric anastomosis with a mechanical circular stapler method in patients undergoing curative esophagectomy with cervical esophagogastrostomy. The circular stapler significantly decreased operative time (524 versus 447 min, p ⬍ 0.001), but was equivalent by all other measures to the hand-sewn method. Notably, reinforcement stitches were added to the mechanical anastomoses routinely. In a prospective study of 421 patients who underwent resection for squamous cell carcinoma of the esophagus at the University of Hong Kong Medical Centre,21 major pulmonary complications (bronchopneumonia, aspiration pneumonia, and respiratory failure) occurred in 15.9% and were considered responsible for 55% of hospital deaths. The hospital mortality rate was 4.8% over 12 years, but 1.1% in the latter 6 years (p ⫽ 0.001 compared with the first 6 years of the study). Age, operation duration, and proximal tumor location (above the carina) were identified as independent risk factors for
94
Zwischenberger et al
What’s New in General Thoracic Surgery
pulmonary complications. Patients with tumors above the level of the carina had a 3.5-fold higher rate of pulmonary complications. Advanced age and higher blood loss were predictive of mortality. Chemoradiation was not associated with worse outcomes. Patient selection (lower resection rate, fewer palliative operations, lower pathologic stage distribution), evolving operative technique (fewer transhiatal operations and the advent of thoracoscopic esophagectomy), and modifications in perioperative care may have played a role in the decreased mortality rate in the latter half of the observation period. Palliative care for unresectable carcinoma of the esophagus has continued to focus on relief from dysphagia. In a prospective, randomized trial, Homs and colleagues22 treated 30 patients with carcinoma of the distal esophagus or gastric cardia with either a windsock-type valve stent (n ⫽ 15) or the same stent without the valve (n ⫽ 15). The valve stent failed to prevent reflux, and there was no significant difference between the two groups by any demographic or outcomes measure. In a multicenter randomized trial in The Netherlands, metal stent placement was also compared with single-dose brachytherapy (12 Gy) for the palliation of dysphagia in esophageal cancer.23 With 100 patients per group, stent placement provided more rapid relief of dysphagia, but brachytherapy provided more longterm relief. There was no difference between groups regarding persistent or recurrent dysphagia. Stent placement had more complications (mostly late hemorrhage) than brachytherapy (33% versus 21%, respectively, p ⫽ 0.02). Lung CT screening
More than 1,500 participants (more than 50 years old with a greater than 20 pack per year smoking history) enrolled in a lung cancer low-dose spiral CT screening trial at the Mayo Clinic in Rochester, MN. Of the 3,130 indeterminate (absence of benign pattern of calcification) pulmonary nodules found in 1,112 participants, only 1.5% of the nodules were cancer. Crestanello and associates24 reviewed the 60 operations performed on 55 of the participants who had suspicious pulmonary nodules, mediastinal adenopathy, or a spontaneous pneumothorax. Lung cancer (seven different histologies) was found in 82%, benign disease in 18%. Operative mortality was 1.7%. Complications occurred in 27% and included prolonged air leak, atrial arrhythmias, pneu-
J Am Coll Surg
monia, ileus, and cerebral vascular accident. Followup from this series has been too short to assess the cost/ survival benefit of spiral CT screening. Staging of non-small cell lung cancer
The role of positron emission tomography in the staging and management of non-small cell lung cancer (NSCLC) continues to provoke controversy ranging from universal application to triage by assessment of cost, benefit, and availability. Nomori and colleagues25 reported on a small series (n ⫽ 44) evaluating lymph node metastasis and tumor invasiveness using FDGPET in patients with NSCLC. All patients were clinical stage IA by FDG-PET and CT; eight were eventually upstaged. A contrast ratio (CR) (between the tumor and contralateral lung tissue) of 0.5 was used as the cutoff for predicting tumor invasiveness. All 22 lesions with a CR ⬍ 0.5 were T1 N0 M0, but 8 of 22 with a CR ⬎ 0.5 were more advanced. Adenocarcinomas with CR ⬍ 0.5 had less lymphatic invasion (p ⫽ 0.006), less vascular invasion (p ⫽ 0.004), less pleural involvement (p ⫽ 0.02), did not show an increased serum level of CEA (p ⫽ 0.001), and were more frequently well differentiated (p ⬍ 0.001). These findings suggest FDG-PET could be used to limit lung resection, lymph node dissection, or mediastinoscopy. In a prospective outcomes study of stages I and II NSCLC in the setting of staging with FDG-PET, Viney and colleagues26 randomized patients before operation into FDG-PET (n ⫽ 91) or conventional staging (n ⫽ 92) groups. The sensitivity (73%) and specificity (90%) of FDG-PET in its ability to identify mediastinal disease resulted in upstaging in 20%. The addition of FDGPET to conventional staging demonstrated a change in clinical management in 13% of patients but did not lead to a significant reduction in the number of thoracotomies avoided (p ⫽ 0.2). Although FDG-PET provided useful information to predict staging, its addition did not change treatment in the predominantly stage I population of this study. Concerning the accuracy of PET in restaging after induction chemotherapy in NSCLC, Port and associates27 performed a prospective study in 25 patients. The positive predictive value for PET determination of major pathologic response (defined as no disease or microscopic disease only in the primary tumor) was 43%, and nodal status was 48%. In Dr Schil’s invited commentary, he noted that tissue-based staging continues to re-
Vol. 201, No. 1, July 2005
Zwischenberger et al
main necessary after induction chemotherapy. Conversely, Hellwig and associates28 reported on 47 patients with resectable NSCLC who underwent preoperative PET after induction chemotherapy. The negative predictive values were 58% for tumor viability and 85% for persistent mediastinal disease. Median survival rates after primary resection were greater than 56 months for standard uptake value less than 4, and 19 months for standard uptake value greater than 4 (p ⬍ 0.001), implying standard uptake value as a prognostic indicator. The authors concluded that the “high” negative predictive value of PET in mediastinal restaging allows for the omission of repeat mediastinoscopy. Obviously, studies are still needed for a consensus on the incorporation of PET into staging and restaging in NSCLC. Cerfolio and colleagues29 conducted a prospective, blinded, lung cancer staging trial in which 129 consecutive patients underwent integrated PET-CT scanning. A single radiologist read the PET-CT and assigned T, N, and M status. The same radiologist, blinded, read the PET alone within 2 weeks and assigned T, N, and M status. Compared with PET alone, integrated PET-CT was a better predictor of stage I (52% versus 33%, p ⫽ 0.03), stage II (70% versus 36%, p ⫽ 0.04), T status (70% versus 47%, p ⫽ 0.001), and N status (78% versus 56%, p ⫽ 0.008). For N1 and N2 nodes, PET-CT had higher accuracy (90% versus 80% for N1; 96% versus 93% for N2), sensitivity (94% versus 53% for N1; 69% versus 62% for N2), specificity (89% versus 82% for N1), and positive predictive value (43% versus 22% for N1; 49% versus 42% for N2) (p ⬍ 0.05 for all). The negative predictive value difference was not significant for N2 disease. This study was unique in its delineation of sensitivities and accuracy at individual nodal stations. In the first report on real-time endobronchial ultrasonography-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes under local anesthesia, Yasufuku and associates30 successfully obtained samples from 58 mediastinal and 12 hilar nodes in 70 patients. Diagnoses included lung cancer (n ⫽ 35), metastases (n ⫽ 5), thyroid cancer, esophageal cancer, lymphoma, mesothelioma, and benign disease (n ⫽ 25). In distinguishing benign from malignant disease, endobronchial ultrasonography-guided transbronchial needle aspiration had a high sensitivity (96%), specificity (100%), and accuracy (97%). The authors noted several limitations to their study, including the technical challenges of the procedure itself, the inaccessibility of the
What’s New in General Thoracic Surgery
95
subaortic and paraesophageal nodes, and the potential inadequacies of sampling through a 22-gauge needle, but concluded that the procedure is safe and has a good diagnostic yield. For surgical staging, Lim and colleagues31 performed a prospective study to determine the prognostic implications of positive pleural lavage cytology in patients undergoing thoracotomy for NSCLC. Lavage was performed by irrigating the lung surface with 100 mL of saline immediately after entering the chest. Of 292 patients who met criteria (no effusion, extreme adhesions, or lateral chest wall invasion), samples from 13 were positive for malignancy. Median survivals were 13 months for the positive lavage group and 49 months for the negative lavage group (median followup 15 months) (p ⫽ 0.002). Where positive lavage cytology fits into conventional lung cancer staging remains unclear. Keller and colleagues32 addressed revision of the TNM staging of NSCLC from the Eastern Cooperative Oncology Group prospective randomized trial of adjuvant therapy in stages II and IIIa disease. Survival with left upper lobe NSCLC and metastases to single-level N2 nodes was not different from survival of N1 disease. Isolated N2 skip lesions had higher survival than concomitant N1 and N2 disease. The authors encouraged stratification of lung cancer by lobe of primary and metastatic pattern, with the eventual goal of revising the TNM staging system. Treatment of non-small cell lung cancer
Several major trials were published in 2004 regarding the role of adjuvant chemotherapy after complete resection of NSCLC. In a prospective trial from the International Adjuvant Lung Cancer Trial Collaborative Group (IALT), Arriagada and colleagues33 evaluated survival advantage in patients with completely resected stage I, II, or III NSCLC randomized to cisplatin plus etoposide or a vinca alkaloid versus no chemotherapy. A total of 1,867 patients from 148 centers in 33 countries were enrolled and followed for a median of 56 months. The chemotherapy group (n ⫽ 932) showed a significantly higher overall survival benefit at 5 years of 4.1% (44.5% versus 40.4%; HR for death 0.86; p ⬍ 0.03) and a disease-free survival benefit at 5 years of 5.1% (39.4% versus 34.3%, HR 0.83; p ⬍ 0.003). This study supports the use of three to four cycles of cisplatin-based chemotherapy after complete surgical resection. From the multicenter Big Lung Trial in Great Britain,
96
Zwischenberger et al
What’s New in General Thoracic Surgery
Waller and associates34 reported on a prospective randomized study (n ⫽ 381) comparing cisplatin-based chemotherapy with no chemotherapy for resected NSCLC (stages I to III). Complete resection was achieved in 95%. Neoadjuvant chemotherapy was given in 3% and radiotherapy in 14%. With a median followup of only 35 months, this trial failed to show a survival benefit. Differences in results of this trial compared with the International Adjuvant Lung Cancer Trial Collaborative Group may be attributed to improper staging (eg, ⬍ 50% 2-year survival of stage II patients), small sample size with inadequate power (ie, a cisplatin-based chemotherapy survival benefit of 5% would require approximately 4,000 patients to confirm), more toxic chemotherapy, and unclear use of neoadjuvant versus adjuvant chemotherapy in some patients. The Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy studied uracil-tegafur (UFT) (250 mg/m2/day for 2 years) after complete resection of stage I lung adenocarcinoma (n ⫽ 488) versus no additional treatment.35 Results showed overall 5-year survivals (median followup 72 months) of 88% for UFT and 85% for no treatment (p ⫽ 0.04; HR ⫽ 0.71). In subgroup analysis, a significant overall 5-year survival benefit for patients with T2 lesions only was seen for UFT (85%) versus no treatment (74%) (p ⫽ 0.005; HR ⫽ 0.48). Finally, a metaanalysis of 19 randomized clinical trials of adjuvant chemotherapy after complete resection (n ⫽ 7,200) by Sedrakyan and associates36 revealed an improved survival benefit. The metaanalysis demonstrated a 13% relative reduction in mortality (p ⬍ 0.0001, HR ⫽ 0.87) with adjuvant chemotherapy compared with surgery alone. Subgroup analysis showed that cisplatinbased chemotherapy achieved an 11% relative reduction in mortality (p ⫽ 0.004) compared with a surgery-alone control group survival of 45% at 5 years; UFT chemotherapy showed a 17% relative reduction in mortality (p ⫽ 0.006) compared with a surgery-alone control group survival of 80% at 5 years. Absolute improvements in survival were 4% for cisplatin-based chemotherapy and 3.5% for UFT. Apparently, a benefit can be gained by providing adjuvant chemotherapy to completely resected stage I and II NSCLC, but the number of cycles and optimal chemotherapeutic agent are debatable. UFT has fewer toxic side effects than cisplatin and should be further evaluated when it becomes available in the United States.
J Am Coll Surg
Techniques in lung cancer treatment
Ohtsuka and coworkers37 reviewed their experience with video-assisted thoracic surgery (VATS) pulmonary resection in 106 patients with clinical stage I NSCLC. Operations consisted of lobectomy (n ⫽ 86), segmentectomy (n ⫽ 8), and bilobectomy (n ⫽ 1). Eleven patients required conversion to an open procedure. Postoperative complications occurred in 9% (including 1 death secondary to pneumonia). Mean hospital stay was 7.6 days (range 4 to 15 days) among patients without complications. The 3-year survival rate among patients with pathologic stage I disease was 89%. Local recurrence was seen in 6%. More experience with VATS lobectomy is necessary before the risk/benefit of this more technically challenging approach can be endorsed. Control of air leaks postoperatively continues to warrant study. In a prospective, randomized trial of 145 patients who underwent lobectomy, 72 patients were placed on water seal on the first postoperative morning and 73 were maintained on ⫺20 cm H2O suction.38 Air leak duration was equivalent between the two groups (6.5 days for water seal versus 6.3 days for suction; p ⫽ 0.9). Prolonged air leak incidence (27.8% seal versus 30.1% suction; p ⫽ 0.8) and length of hospital stay also were not different. The results of this trial contrast with those from previous studies39,40 showing a decreased incidence of prolonged air leak on water seal. Previous observations have amalgamated wedge resections, segmentectomies, and lobectomies together. In the current study 80% also had a pleural tent procedure, perhaps negating the advantages of water seal. Czerny and colleagues41 published a prospective, randomized two-by-two factorial design trial comparing TachoComb (a local hemostyptic agent, Torii Pharmaceutical Co) with one of two low molecular weight heparin anticoagulation arms (enoxaparin or dalteparin) to conventional surgical hemostasis with the same agents (4 groups total) in 80 patients undergoing resection and complete mediastinal node dissection for stage I or II NSCLC. Patients receiving the combination of TachoComb and dalteparin had statistically significant lower chest drainage on days 1, 2, and 3 individually and cumulatively (498 mL over 4 days versus 1,000 mL for TachoComb with enoxaparin, 924 mL for dalteparin only, and 895 mL for enoxaparin only; p ⬍ 0.05). There were also fewer chest tube days in the TachoComb plus dalteparin group (1.78 days versus 2.96 days for TachoComb with enoxaparin, 2.93 days for dalteparin only, and 3.06 days for
Vol. 201, No. 1, July 2005
Zwischenberger et al
enoxaparin only; p ⫽ 0.019). The authors concluded that use of a local hemostyptic agent with dalteparin may decrease postoperative bleeding in patients with prophylactic perioperative anticoagulation. Emphysema
Previous reports from the multicenter National Emphysema Treatment Trial showed that lung volume reduction surgery (LVRS) provides functional improvement for patients with upper lobe emphysema and increases survival among the same cohort with a low baseline exercise capacity. National Emphysema Treatment Trial data were subsequently analyzed to determine the safety and efficacy of median sternotomy (n ⫽ 359) versus VATS (n ⫽ 152) for LVRS.42 Mortality, complication rates (including air leak after 7 days), and changes in exercise capacity and quality of life were similar between the two groups. Median hospital stays were 10 days for sternotomy and 9 days for VATS (p ⫽ 0.02). The sternotomy group also had more intensive care unit days. Operative and overall costs were less for VATS (p ⬍ 0.01). Laghi and colleagues43 reported their 2-year followup of patients who showed an increase in diaphragmatic neuromechanical coupling (tidal volume to change in transdiaphragmatic pressure ratio) 3 months after LVRS. At 2 years, the 8 patients who completed the study showed continued improvement in 6-minute walking distance (p ⬍ 0.05) despite the fact that lung volumes had relapsed to preoperative values. Choong and associates44 reported on their experience with 21 emphysema patients who underwent concomitant cancer resection and LVRS. Patient selection criteria included no evidence of N2 disease, heterogeneous, severe emphysema with suitable target areas, and often (9 in 21) tumor within the emphysematous lobe itself. Preoperatively, their patients had a mean FEV1 of 0.7 ⫾ 0.2L (29% predicted), residual volume of 5.5 ⫾ 1.0L (271%), and diffusing capacity for carbon monoxide of 8.0 ⫾ 2.2 mL/min/mmHg (34% predicted). Prolonged air leak occurred in 11 patients and reintubation in 2. Survivals (Kaplan-Meier estimation) at 1, 3, and 5 years were 100%, 74%, and 63%, respectively, comparing well with bilateral lung volume reduction and predicted outcomes relative to staging.45 The authors cautioned against applying their experience to all patients with resectable lung cancer and severe emphysema.
What’s New in General Thoracic Surgery
97
Metastatic soft tissue sarcoma
Porter and colleagues46 reported on the cost effectiveness of a four-treatment-arm model of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcomas in the combined experience of the University of Texas MD Anderson and Memorial Sloan-Kettering Cancer Centers. Data from 889 patients who had no treatment showed a median survival of 13 months. The cost of the no-treatment group was considered supportive care that would be required for all patients, so was set at zero. There were 235 consecutive patients who underwent complete resection of soft tissue sarcoma pulmonary metastases, with median survival of 31 months at a cost of $20,339 per patient ($14,357 per life-year gained). Subsequently, the analysis assumed a “generous” 12-month improved survival for adding chemotherapy (4 cycles of doxorubicin and ifosfamide). The chemotherapy-alone group would have a median survival of 25 months at a cost of $99,033 per patient ($104,210 per life-year gained), and the chemotherapy plus surgery group would survive 43 months for $119,732 per patient ($51,159 per life-year gained). The authors concluded that pulmonary resection was the most cost-effective treatment. Mesothelioma
Sugarbaker and colleagues47 published one of the largest experiences on treatment of malignant pleural mesothelioma by extrapleural pneumonectomy. In 496 consecutive patients who underwent extrapleural pneumonectomy (444 for mesothelioma), operative (30-day) mortality was 4.0%. In 328 consecutive patients with mesotheliomas, the morbidity rate was 60.4%. The most common postoperative complication was atrial fibrillation (44.2%), with no success in reduction despite prophylactic treatment. Other serious complications were cardiac tamponade (3.6%), acute respiratory distress syndrome (3.6%), cardiac arrest (3%), inflammatory epicarditis (2.7%), and myocardial infarction (1.5%). Previously reported mortality rates since the 1980s have ranged from 6% to 15%. The authors attributed their relatively low mortality and complication rates to improved surgical technique (such as diaphragmatic and pericardial reconstructions) and prevention (anticoagulation, screening for vocal cord paralysis, and liberal use of bronchoscopy). The risk/benefit ratio of extrapleural pneumonectomy still appears narrow.
98
Zwischenberger et al
What’s New in General Thoracic Surgery
J Am Coll Surg
Transplant
REFERENCES
Lung transplantation management has evolved over the past 20 years but remains site specific. In a survey of lung transplant practice in North America published this past year, 50 of 65 active centers responded to a 64-question survey designed by The Transplant/Immunology Network of the American College of Chest Physicians.48 Generally, patient selection criteria were remarkably consistent. But this snapshot of current practice demonstrated considerable variance in posttransplant management. The survey reviewers suggest that future collaborative studies focus on optimal postoperative management guidelines. In a review of single- and double-lung transplantation at the Toronto General Hospital from 1983 to 2003, de Perrott and colleagues49 found that survivals for all recipients were 55% at 5 years, 35% at 10 years, and 27% at 15 years. The most common causes of death were sepsis and bronchiolitis obliterans. The best longterm survival was in patients with primary pulmonary hypertension (59% at 10 years) or cystic fibrosis (B cepacia negative) (52% at 10 years). The lowest survival was in patients with B cepacia positive cystic fibrosis (15% at 10 years). Future management will focus on reducing infection and preventing chronic graft dysfunction or bronchiolitis obliterans. Living lobar lung transplantation provides patients unable to await cadaveric transplantation a lifesaving procedure, but with considerable risk (up to a 60% complication incidence including postpericardiotomy syndrome, atrial fibrillation, and surgical reexploration) to 2 donors. From the seminal institution for this procedure, Starnes and associates50 reported on their 10-year experience with 128 living lobar transplantations (84 adults, 39 children) at the USC Keck School of Medicine and Children’s Hospital. The 5-year actuarial survival was 45%. Primary causes of mortality were infection (53%), bronchiolitis obliterans (13%), and primary graft dysfunction (8%). The authors concluded that risk to the donors coupled with poor outcomes in patients on ventilators preoperatively (increased risk of death odds ratio ⫽ 3.06; p ⫽ 0.03) and those with previous transplantations (odds ratio ⫽ 2.50) is perhaps too high to justify living lobar transplantation in these subgroups. For other suitable recipients whose condition is worsening, living lobar transplantation continues to be a viable lifesaving operation.
1. Gold JP, Begg WB, Fullerton D, et al. Successful implementation of a novel internet hybrid surgery curriculum: the early phase outcome of thoracic surgery prerequisite curriculum e-learning project. Ann Surg 2004;240:499–509. 2. Zaninotto G, Annese V, Costantini M, et al. Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia. Ann Surg 2004;239:364–370. 3. Gockel I, Junginger T, Bernhard G, Eckardt VF. Heller myotomy for failed pneumatic dilation in achalasia: how effective is it? Ann Surg 2004;239:371–377. 4. Richards WO, Torquati A, Holzman MD, et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 2004;240:405–415. 5. Dempsey DT, Delano M, Bradley K, et al. Laparoscopic esophagomyotomy for achalasia: does anterior hemifundoplication affect clinical outcome? Ann Surg 2004;239:779–787. 6. Mineo TC, Pompeo E. Long-term outcome of Heller myotomy in achalasic sigmoid esophagus. J Thorac Cardiovasc Surg 2004; 128:402–407. 7. Douard R, Gaudric M, Chaussade S, et al. Functional results after laparoscopic Heller myotomy for achalasia: A comparative study to open surgery. Surgery 2004;136:16–24. 8. Kesler KA, Tarvin SE, Brooks JA, et al. Thoracoscopy-assisted Heller myotomy for the treatment of achalasia: results of a minimally invasive technique. Ann Thorac Surg 2004;77:385–392. 9. Patel HJ, Tan BB, Yee J, et al. A 25-year experience with open primary transthoracic repair of paraesophageal hiatal hernia. J Thorac Cardiovasc Surg 2004;127:843–849. 10. Vrieze O, Haustermans K, De Wever W, et al. Is there a role for FDG-PET in radiotherapy planning in esophageal carcinoma? Radiother Oncol 2004;73:269–275. 11. Choi JY, Jang HJ, Shim YM, et al. 18F-FDG PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: prognostic implications. J Nucl Med 2004;45:1843– 1850. 12. Heeren PA, Jager PL, Bongaerts F, et al. Detection of distant metastases in esophageal cancer with (18)F-FDG PET. J Nucl Med 2004;45:980–987. 13. Lee JL, Park SI, Kim SB, et al. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol 2004;15:947– 954. 14. Donington JS, Miller DL, Allen MS, et al. Preoperative chemoradiation therapy does not improve early survival after esophagectomy for patients with clinical stage III adenocarcinoma of the esophagus. Ann Thorac Surg 2004;77:1193–1199. 15. Urba SG, Orringer MB, Turrisi A, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19: 305–313. 16. Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462–467. 17. Malaisrie SC, Untch B, Aranha GV, et al. Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer: experience at a single institution. Arch Surg 2004;139:532–539. 18. Armanios M, Xu R, Forastiere AA, et al. Adjuvant chemotherapy for resected adenocarcinoma of the esophagus, gastro-
Vol. 201, No. 1, July 2005
19.
20.
21. 22.
23.
24. 25.
26.
27.
28.
29.
30. 31.
32. 33. 34.
Zwischenberger et al
esophageal junction, and cardia: phase II trial (E8296) of the Eastern Cooperative Oncology Group. J Clin Oncol 2004;22:4495–4499. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345: 725–730. Hsu HH, Chen JS, Huang PM, et al. Comparison of manual and mechanical cervical esophagogastric anastomosis after esophageal resection for squamous cell carcinoma: a prospective randomized controlled trial. Eur J Cardiothorac Surg 2004; 25:1097–1101. Law S, Wong KH, Kwok KF, et al. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg 2004;240:791–800. Homs MY, Wahab PJ, Kuipers EJ, et al. Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc 2004;60:695– 702. Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364:1497–1504. Crestanello JA, Allen MS, Jett JR, et al. Thoracic surgical operations in patients enrolled in a computed tomographic screening trial. J Thorac Cardiovasc Surg 2004;128:254–259. Nomori H, Watanabe K, Ohtsuka T, et al. Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma. J Thorac Cardiovasc Surg 2004;128:396–401. Viney RC, Boyer MJ, King MT, et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 2004;22:2357–2362. Port JL, Kent MS, Korst RJ, et al. Positron emission tomography scanning poorly predicts response to preoperative chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2004;77:254– 259. Hellwig D, Graeter TP, Ukena D, et al. Value of F-18fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 2004;128:892–899. Cerfolio RJ, Ojha B, Bryant AS, et al. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer. Ann Thorac Surg 2004; 78:1017–1023. Yasufuku K, Chiyo M, Sekine Y, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. Chest 2004;126:122–128. Lim E, Ali A, Theodorou P, et al. Intraoperative pleural lavage cytology is an independent prognostic indicator for staging nonsmall cell lung cancer. J Thorac Cardiovasc Surg 2004;127: 1113–1118. Keller SM, Vangel MG, Wagner H, et al. Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease. J Thorac Cardiovasc Surg 2004;128:130–137. Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected nonsmall-cell lung cancer. N Engl J Med 2004;350:351–360. Waller D, Peake MD, Stephens RJ, et al. Chemotherapy for
35. 36.
37.
38. 39. 40. 41.
42.
43. 44.
45.
46.
47.
48. 49.
50.
What’s New in General Thoracic Surgery
99
patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 2004;26:173–182. Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004;350:1713–1721. Sedrakyan A, Van Der Meulen J, O’Byrne K, et al. Postoperative chemotherapy for non-small cell lung cancer: A systematic review and meta-analysis. J Thorac Cardiovasc Surg 2004;128: 414–419. Ohtsuka T, Nomori H, Horio H, et al. Is major pulmonary resection by video-assisted thoracic surgery an adequate procedure in clinical stage I lung cancer? Chest 2004;125:1742– 1746. Brunelli A, Monteverde M, Borri A, et al. Comparison of water seal and suction after pulmonary lobectomy: a prospective, randomized trial. Ann Thorac Surg 2004;77:1932–1937. Cerfolio RJ, Bass C, Katholi CR. Prospective randomized trial compares suction versus water seal for air leaks. Ann Thorac Surg 2001;71:1613–1617. Marshall MB, Deeb ME, Bleier JI, et al. Suction vs water seal after pulmonary resection: a randomized prospective study. Chest 2002;121:831–835. Czerny M, Fleck T, Salat A, et al. Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma. Ann Thorac Surg 2004;77: 1028–1032. McKenna RJ Jr, Benditt JO, DeCamp M, et al. Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery. J Thorac Cardiovasc Surg 2004;127:1350–1360. Laghi F, Jubran A, Topeli A, et al. Effect of lung volume reduction surgery on diaphragmatic neuromechanical coupling at 2 years. Chest 2004;125:2188–2195. Choong CK, Meyers BF, Battafarano RJ, et al. Lung cancer resection combined with lung volume reduction in patients with severe emphysema. J Thorac Cardiovasc Surg 2004;127:1323– 1331. Ciccone AM, Meyers BF, Guthrie TJ, et al. Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J Thorac Cardiovasc Surg 2003;125:513– 525. Porter GA, Cantor SB, Walsh GL, et al. Cost-effectiveness of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcoma: a combined analysis from the University of Texas M. D. Anderson and Memorial Sloan-Kettering Cancer Centers. J Thorac Cardiovasc Surg 2004;127:1366–1372. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 2004;128:138–146. Levine SM. A survey of clinical practice of lung transplantation in North America. Chest 2004;125:1224–1238. de Perrot M, Chaparro C, McRae K, et al. Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival. J Thorac Cardiovasc Surg 2004;127:1493–1501. Starnes VA, Bowdish ME, Woo MS, et al. A decade of living lobar lung transplantation: recipient outcomes. J Thorac Cardiovasc Surg 2004;127:114–122.