Liver transplantation is a life-saving procedure for

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1 Surgical Resection of Pulmonary Malignant Tumors After Living Donor Liver Transplantation Fumihiro Shoji, MD, Daigo Kawano, MD, Toru Ikegami, MD, Yuji Soejima, MD, Akinobu Taketomi, MD, Tokujiro Yano, MD, and Yoshihiko Maehara, MD Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Background. The aim of this study is to report on patients who developed tumor recurrence of the lung or de novo pulmonary malignancies after living donor liver transplantation (LDLT) and to show the benefit of a surgical resection for these pulmonary malignant tumors. Methods. A total 246 patients who underwent LDLT were investigated. Results. Pulmonary malignant tumors after LDLT were observed in 12 (4.9%) of 246 patients studied. These patients included 9 tumor recurrences and 3 de novo malignancies. The frequency of pulmonary recurrence was 9.4% (9 of 96 patients) and that of pulmonary de novo malignancies including 2 primary lung cancer and 1 mucosa-associated lymphoid tissue (MALT) lymphoma, was 1.2% (3 of 246 patients). Four of 9 recurrent patients could undergo surgical resections and the survival range in patients who received surgery was 17 to 56 months with a mean of 36 months after LDLT; on the other hand, the survival range in patients that could not undergo a surgical resection was 4 to 26 months with a mean of 18 months. Among the de novo malignancies, only the MALT lymphoma patient could undergo a surgical resection. Repeated surgical resections of pulmonary malignant tumors could be performed in 3 patients and all these patients have been long-term survivors. Conclusions. These results suggest a surgical resection of pulmonary malignancies including tumor recurrences or de novo malignancies after LDLT is a feasible procedure and may prolong survival in selected patients, even under immunosuppressive conditions. (Ann Thorac Surg 2009;88:206 11) 2009 by The Society of Thoracic Surgeons Liver transplantation is a life-saving procedure for patients with unresectable or untreatable fatal liver diseases such as hepatocellular carcinoma (HCC), fulminant hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis with or without limited liver functional reserves. Recipients after liver transplantation have a good prognosis; nevertheless, one of the limitations to long-term survival after liver transplantation is tumor malignancies, including tumor recurrence or de novo malignancies. In particular, the rate of HCC recurrence is high even after liver transplantation [1] and the most common site of recurrence of HCC after liver transplantation is the lung [2]. Moreover, the incidence of de novo cancers is also increased in patients who undergo liver transplantation. Among the de novo malignancies, pulmonary malignant tumors are among the fatal diseases that limit the long-term survival after liver transplantation. In addition, the treatment for these diseases is limited by the immunosuppressive therapy after living donor liver transplantation (LDLT). Therefore, it is very important to evaluate the treatment of pulmonary malignant tumors after liver transplantation. A surgical resection of pulmonary malignant tumors is aggressively performed in selected patients after liver transplantation, Accepted for publication March 25, Address correspondence to Dr Shoji, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, , Japan; fshoji@surg2.med.kyushuu.ac.jp. thus resulting in favorite results. Therefore, the aim of this study is to report on patients who developed tumor recurrence of the lung or de novo pulmonary malignancies after liver transplantation and to demonstrate the benefits of a surgical resection for these pulmonary malignancies. Patients and Methods Patients This study was approved by the Ethics Committee of Kyushu University. A total of 277 consecutive patients underwent LDLT at Kyushu University Hospital from October 1992 to April Among the 277 patients, 246 patients were considered adults ( 18 years old). Therefore, 246 patients were selected for this study. This study included 119 males and 127 females, ranging from 18 to 73 years of age with a mean age of 50 years. The indications for LDLT were HCC in 96 patients, fulminant hepatic failure in 44 patients, primary biliary cirrhosis (PBC) in 39 patients, liver cirrhosis in 37 patients, primary sclerosing cholangitis in 10 patients, biliary atresia in 7 patients, and the others in 13 patients. The indications for LDLT at Kyushu University Hospital include HCC with neither extrahepatic metastasis nor macroscopic vascular invasion in conventional imaging studies. No limitations were set regarding the size and number of tumors. The pretransplant work-up for HCC consisted of a combination of ultrasonography, dynamic computed tomographic 2009 by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg SHOJI ET AL 2009;88: SURGICAL RESECTION OF PULMONARY TUMORS AFTER LDLT 207 Table 1. Profiles of Patients With Pulmonary Malignancies After LDLT Patient Gender/Age Liver Disease Type of Pulmonary Malignancies Month to Transplant Number of Metastatic Lesions Other Organs Involvement 1 Male/44 HCC Recurrence 8 Multiple Liver, bone 2 Male/66 HCC Recurrence 5 Multiple None 3 Female/49 HCC Recurrence 16 Multiple None 4 Male/62 HCC Recurrence 2 Solitary Bone 5 Female/46 HCC Recurrence 11 Multiple Bone 6 Female/55 HCC Recurrence 25 Solitary None 7 Female/60 HCC Recurrence 15 Solitary None 8 Male/51 HCC Recurrence 7 Solitary None 9 Male/51 EHE Recurrence 9 Multiple Liver 10 Male/65 HCC De novo (lung cancer) 33 Multiple None 11 Male/62 HCC De novo (lung cancer) 14 Solitary None 12 Female/56 PBC De novo (MALT lymphoma) 28 Multiple None EHE epithelioid hemangioendothelioma; HCC hepatocellular carcinoma; LDLT living donor liver transplantation; MALT lymphoma mucosa-associated lymphoid tissue lymphoma; PBC primary biliary cirrhosis. (CT) scans, magnetic resonance imaging, CT angiography, and CT during arterial portography where possible. The exclusion of patients with extrahepatic metastasis was made by head and chest CT scans and bone scintigraphy. Adjuvant chemotherapy and immunosuppressive therapy have been previously described [3]. The posttransplant follow-up consisted of abdominal CT, chest CT, and bone scan imaging studies at 3-month intervals during the first year and yearly thereafter. Tumor markers including alpha-fetoprotein were checked monthly during the first year and at 3-month intervals thereafter. Indication for Surgical Resection of Pulmonary Recurrence After LDLT Principally, a wedge resection using either thoracoscopy or an open thoracotomy was the surgical procedure of choice; however, the surgical procedure such as segmentectomy or lobectomy was considered based on the anatomic characteristics of the pulmonary lesions. Although thoracoscopic surgery allowed for repeat surgery to treat metachronous recurrence, an open thoracotomy was adopted for some specific lesions that were centrally located or recurrent lesions with dense pleural adhesion caused by previous surgery. Statistical Analysis An analysis of patient survival was performed using the Kaplan-Meier method. The statistical analysis was performed using the Statview software program version 5.0. Results Frequency of Pulmonary Malignant Tumors in Patients After LDLT The median follow-up was 33 months (range, 0 to 138 months) and 186 (75.6%) patients are currently still living. The actuarial overall 1-, 3-, 5-, and 10-year patient survival rates were 83.6, 76.8, 74.4, and 65.3%, respectively. Pulmonary malignant tumors after LDLT were observed in 12 (4.9%) of 246 patients studied. These patients ranged from 44 to 65 years of age (mean, 55 years) and included 7 men and 5 women, with 9 tumor recurrences (8 patients had HCC and the other had epithelioid hemangioendothelioma: EHE), and 3 de novo malignancies including 2 primary lung cancers and 1 mucosaassociated lymphoid tissue (MALT) lymphoma (2 patients had had HCC and the other had PBC). Pulmonary Recurrence of the Tumor After LDLT and Overall Survival The profiles of tumor recurrent patients are summarized in Table 1. The rate of pulmonary recurrence of HCC or EHE was 9.4% (9 of 96 patients). All 8 cases of HCC recurrences did not meet the Milan criteria. The time from LDLT to the diagnosis of the tumor recurrence ranged from 2 to 25 months, with a mean of 11 months. Four cases were solitary pulmonary metastases and the remaining 5 cases were multiple. Four cases involved other organs such as the liver and bone. De Novo Malignancies of the Lung After LDLT and Overall Survival The profiles of pulmonary de novo malignancies are also shown in Table 1. The rate of pulmonary de novo malignancies was 1.2% (3 of 246 patients). The time from the diagnosis of de novo malignancies to LDLT ranged from 14 to 33 months, with a mean of 25 months. Both patient 10 and patient 11 had primary lung cancers, while patient 12 had MALT lymphoma. The two patients who developed lung cancer were former smokers. Application of Surgical Resections for Pulmonary Malignancies Among the patients with pulmonary malignancies, 5 patients could undergo surgical resections. The remaining 7 patients could not receive the surgery. Table 2 showed the contraindications for pulmonary resection. In

3 208 SHOJI ET AL Ann Thorac Surg SURGICAL RESECTION OF PULMONARY TUMORS AFTER LDLT 2009;88: Table 2. Contraindications for Pulmonary Resections Contraindications Number of Patients Tumor recurrences 5 Systemic recurrence 4 Impossible complete resection 1 De novo malignant tumors 2 Unresectable lung cancer 1 Lung cancer unresectable maxillary cancer 1 patients with pulmonary recurrences, 4 patients (patients 1, 4, 5, and 9) had systemic recurrences including the liver and bone. Patient 2 had numerous pulmonary recurrent sites in the bilateral lungs, which suggested that it would have been impossible to achieve a complete surgical resection. In the patients with de novo malignancies, patient 10 had a non-small cell lung cancer with malignant effusion and multiple pulmonary metastases (clinical-stage T4N0M1). Patient 11 had both non-small cell lung cancer (clinical stage T2N0M0) and unresectable advanced maxillary cancer. As a result, only 1 patient (patient 12) could receive surgical resection. Treatment and Overall Survival in Patients With Pulmonary Malignancies Based on the contraindications for surgery shown in Table 2, a total of 5 patients underwent surgery (Table 3). Among the remaining 7 patients, 4 patients received the best supportive care and 3 patients received chemotherapy or radiotherapy. Patient 11 had both non-small cell lung cancer (clinical T2N0M0) and unresectable advanced maxillary cancer and received radiotherapy for both cancers. This therapy was effective for both lesions; as a result, the patient died 25 months after radiotherapy. All 5 patients who underwent a surgical resection are still alive, although 6 of the 7 patients who could not receive a surgical resection died (Fig 1). The survival range in the patients who underwent a surgical resection was 22 to 61 months with a mean of 42.8 months after LDLT (7 to 45 months with a mean of 24.6 months after the diagnosis of pulmonary malignancies). On the other hand, the survival range in those that could not receive a surgical resection was 4 to 39 months with a mean of 24.1 months (0 to 25 months with a mean of 12.4 months after the diagnosis of the pulmonary malignancies). Details of Patients Who Received Pulmonary Resections After LDLT Table 4 shows the surgical results of 5 patients who underwent pulmonary resections. The mean tumor size was 12 mm (range, 5 to 20 mm). Four patients (patients 3, 6, 7, and 8) had HCC recurrence and the other (patient 12) had a MALT lymphoma. Three of 5 patients (patients 6, 7, and 8) had solitary pulmonary metastasis. Among these patients, 2 patients (patients 6 and 7) underwent wedge resections and the other (patient 8) underwent a right basal segmentectomy. Patient 6 underwent wedge resection of the left S4 and patient 7 also underwent wedge resection of the right S8. In patient 8, the tumor was located at the right hilar area with adjacent basal pulmonary artery. We could not reserve the basal pulmonary artery and therefore performed a right basal segmentectomy. The others (patients 3 and 12) had multiple pulmonary lesions. In patient 3, all of the lesions were located in the peripheral area and thus could be resected completely by wedge resections. Patient 12 received a right lower lobectomy because all of the lesions (S7 and S9) were located in a central area, but only in the right lower lobe. The mean time of the operations was 186 minutes (range, 80 to 273 minutes) and the mean volume of blood loss was 177 g (range, 17 to 737 g). The postoperative course of the five patients is also shown in Table 4. All 5 patients have received immunosuppressive therapy with a combination of Neoral (Novartis Pharmaceuticals Corporation, East Hanover, NJ), CellCept (Roche Pharmaceuticals, Basel, Switzerland), tacrolimus, and Predonine (Shionogi and Co., Ltd., Table 3. Treatment and Overall Survival in Patients With Pulmonary Malignancies After LDLT Patient Indication for Surgery Treatment Months After LDLT Months After Diagnosis of Pulmonary Malignancies Prognosis 1 No Best supportive care Dead 2 No Chemotherapy Dead 3 Yes Surgery Alive 4 No Best supportive care 4 2 Dead 5 No Chemotherapy Alive 6 Yes Surgery Alive 7 Yes Surgery 22 7 Alive 8 Yes Surgery Alive 9 No Best supportive care Dead 10 No Best supportive care 33 0 Dead 11 No Radiotherapy Dead 12 Yes Surgery Alive LDLT living donor liver transplantation.

4 Ann Thorac Surg SHOJI ET AL 2009;88: SURGICAL RESECTION OF PULMONARY TUMORS AFTER LDLT 209 first pulmonary resection. There were no problems or complications during the perioperative course in any of the repeated pulmonary resections. Fig 1. Comparison of the overall survival in patients who could (line) or who could not (dot) receive pulmonary resections after living donor liver transplantation (LDLT). Osaka, Japan). All of the patients stopped these immunosuppressive therapies 1 day before operation and restarted the immunosuppressive therapy on postoperative day 1 (POD 1). The thoracic tube was removed during POD 3 (mean, POD 1.6; range, POD 1 to 3). There were no serious complications and the mean hospital stay was 9.4 days (range, 7 to 11 days). Second or More Recurrence of the Tumors After Initial Pulmonary Resections After the initial pulmonary resections, 4 of 5 patients (3 HCC recurrences and 1 MALT lymphoma) had a second pulmonary recurrence (Table 5). Among these patients, 3 patients (patients 3, 6, and 12) had only a pulmonary recurrence again 10.6 months after (range, 7 to 15 months) and therefore all 3 patients underwent pulmonary resections (all procedures were wedge resections). Patient 6 had systemic metastases including the lung, liver, and bone 10 months after the pulmonary resection and was treated with chemoradiotherapy. Patient 3 underwent a total of 4 wedge resections for pulmonary recurrences 15, 25, 38, and 43 months after the first pulmonary resection, respectively. Patient 8 underwent a wedge resection for a third pulmonary recurrence 10 months after the first pulmonary resection; however, chemoradiotherapy was needed for a systemic recurrence including the lung and bone 11 months after the Comment Recurrence of HCC or EHE After LDLT According to recent reports concerning pulmonary recurrence of HCC after liver transplantation, the pulmonary recurrence rate is 3.8 to 7.4% [4 6]. In these reports, most recurrences after liver transplantation develop during the first year after liver transplantation. Therefore, both the frequency and period of pulmonary HCC recurrences were consistent in the current study. Park and colleagues [5] reported that survival time after tumor recurrence is 9.1 months (0.8 to 27.9 months) and only 2 patients (28.6%) could receive chemotherapy, and another could not receive any therapy due to hepatic dysfunction. Escartin and colleagues [6] reported that the median survival after recurrence is 7 months. In the current experience, the survival after tumor recurrence in the patients could not undergo surgical resections was 12.4 months (2 to 20 months) which is similar to those in these studies. Epithelioid hemangioendothelioma is a rare mesenchymal tumor of the liver. Zhang and colleagues [7] reported 5 EHE patients underwent liver transplantation. While this tumor is thought to be a low-grade malignant tumor, 1 of 5 patients experienced tumor recurrence in that report. Our case in the current series also showed a rapid recurrence and poor prognosis. De Novo Malignancies Including Primary Lung Cancers and MALT Lymphoma After LDLT Recent studies reported that the incident rate of primary lung cancers is 0.3 to 0.8% [8 10]. Sanchez and colleagues [8] reported that the time to the diagnosis of lung cancers was 47 months and 8 of 11 patients (72.7%) were dead within 7.4 months after the cancer diagnosis. Peyregne and colleagues [9] reported that only 1 (0.3%) of 330 patients developed small-cell lung cancer 71 months after liver transplantation and that patient died 15 months after the cancer diagnosis despite receiving chemotherapy. Aseni and colleagues [10] reported that 3 (0.6%) of 464 patients developed primary lung cancers 53 months after liver transplantation. Among the 3 patients, Table 4. Surgical Results of Patients Who Underwent a Pulmonary Resection for Malignant Tumors After LDLT Patient Tumor Size (mm) Location Procedure Complications Hospital Stay (Days) 3 5, 9, 7 rt. S3, rt. S5, lt. S4 Wedge resection None lt. S4 Wedge resection None rt. S8 Wedge resection None rt. S8 Basal segmentectomy None , 19 rt. S7, rt. S9 Right lower lobectomy Slight elevation of transamynase 11 LDLT living donor liver transplantation; lt left; rt right.

5 210 SHOJI ET AL Ann Thorac Surg SURGICAL RESECTION OF PULMONARY TUMORS AFTER LDLT 2009;88: Table 5. Second or More Recurrence of the Tumors After Initial Pulmonary Resections Patient Recurrence Times Recurrent Sites Months After Initial Pulmonary Resection Treatment 3 Yes 2 nd Lung 7 Surgery (wedge resection) 3 rd Lung 15 Surgery (wedge resection) 4 th Lung 25 Surgery (wedge resection) 5 th Lung 38 Surgery (wedge resection) 6 th Lung 43 Surgery (wedge resection) 6 Yes 2 nd Lung, liver, bone 10 Chemoradiotherapy 7 No Yes 2 nd Lung 5 Surgery (wedge resection) 3 rd Lung 10 Surgery (wedge resection) 4 th Lung, bone 11 Chemoradiotherapy 12 Yes 2 nd Lung 15 Surgery (wedge resection) only 1 patient could undergo a surgical resection and was alive although the others were dead 3 months after the cancer diagnosis. The frequency (2 of 246 patients, 0.8%) of primary lung cancers in the current study was almost the same as those of recent reports. However, the time to the diagnosis of primary lung cancer after LDLT in the current study was shorter than that in these previous reports. Notably, the present study included a pulmonary MALT lymphoma. The MALT lymphoma is considered to be an extremely rare form of posttransplant lymphoproliferative disease. This pulmonary MALT lymphoma after LDLT is the first reported case, although MALT lymphoma that originated from the stomach and salivary gland has been reported [11]. Validity of Pulmonary Resections for Tumor Recurrence and De Novo Cancer After LDLT The incidence of pulmonary metastasectomies from primary epithelial tumors including HCC was recently reviewed [12]. This review noted several reports of a pulmonary metastasectomy for HCC with good results. Specifically, a surgical resection of a resectable pulmonary metastasis from HCC is justified in selected patients to achieve a prolonged survival [13, 14]. In addition, Tomimaru and colleagues [15] noted that a patient with recurrent HCC should undergo surgery if any solitary pulmonary metastasis encountered is resectable, to prolong their survival. The question remains in regard to whether a metastasectomy for HCC recurrence is acceptable even after liver transplantation. Recently, Bates and colleagues [16] reported successful cases of pulmonary metastasectomy in patients after liver transplantation. The average time for survival from transplant was 44 months and the average time for survival from the pulmonary metastasectomy was 27.5 months. Although the number of patients in this study is small, the liver transplant patients with pulmonary recurrence of HCC who underwent a surgical resection demonstrated survival times similar to those with HCC treated with liver resection. In the present series, the mean survivals from transplant and pulmonary resection were 42.8 months (range, 22 to 61 months) and 24.6 months (range, 7 to 45 months), which were similar to the previous report. Notably, this survival time was approximately twofold greater than that in patients who could not receive surgical resections. Moreover, all of the patients who could receive surgical resections survived; 80% of the patients who could not receive surgical resections died. Moreover, the perioperative course demonstrated that the patients who received pulmonary resections had no serious complications. As a result, surgical resections for pulmonary malignancies are feasible even after LDLT. The current data showed that 3 of 4 patients (75%) with an initial pulmonary malignant tumor after LDLT underwent a second pulmonary resection of a second pulmonary recurrence without any other recurrent site except the lung. Moreover, 2 patients underwent multiple pulmonary resections to resect 3rd or 3rd to 6th pulmonary metastases. In both cases video-assisted thoracic surgery, which is noninvasive and the newest approach to pulmonary metastases [17], allowed repeated surgery. Sternberg and Sonett [17] noted that repeated pulmonary metastasectomies showed a 10% survival benefit at 5 years. Because the patients in the current study were long-term survivors, repeated pulmonary resections for pulmonary metastasis might be a safe and promising therapy in selected patients. Finally, a posttransplant imaging follow-up at 3-month intervals during the first year and yearly thereafter was performed. However, we should change the interval of imaging follow-up in the second year after LDLT and observe the patients more carefully because some of the tumors occurred in the second year. In conclusion, this present study showed the frequency and surgical results of pulmonary malignant tumors after LDLT. Although this study was limited by the small number of cases studied, these results suggest that a surgical resection of pulmonary malignant tumors including tumor recurrence or de novo malignancies after LDLT is a feasible procedure and may prolong survival in selected patients.

6 Ann Thorac Surg SHOJI ET AL 2009;88: SURGICAL RESECTION OF PULMONARY TUMORS AFTER LDLT 211 The authors thank Dr Brian Quinn for critical comments on the manuscript. References 1. Ferris JV, Baron RL, Marsh JW Jr, Oliver JH 3rd, Carr BI, Dodd GD 3rd. Recurrent hepatocellular carcinoma after liver transplantation: spectrum of CT findings and recurrence patterns. Radiology 1996;198: Freise CE, Ferrell L, Liu T, Ascher NL, Roberts JP. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma. Transplantation 1999;67: Soejima Y, Taketomi A, Yoshizumi T, et al. Extended indication for living liver donor transplantation in patients with hepatocellular carcinoma. Transplantation 2007;83: Pérez-Saborido B, de los Galanes SJ, Menéu-Díaz JC, et al. Tumor recurrence after liver transplantation for hepatocellular carcinoma: recurrence pathway and prognostic factors. Transplant Proc 2007;39: Park JW, Lee KW, Kim SJ, et al. Outcome of patients with recurrent hepatocellular carcinoma in liver transplantation. Transplant Proc 2006;38: Escartin A, Sapisochin G, Bilbao I, et al. Recurrence of hepatocellular carcinoma after liver transplantation. Transplant Proc 2007;39: Zhang W, Jambulingam PS, Silva MA, et al. Orthotopic liver transplantation for epithelioid haemangioendothelioma. Eur J Surg Oncol 2007;33: Sanchez EQ, Marubashi S, Jung G, et al. De novo tumors after liver transplantation: a single-institutional experience. Liver Transplantation 2002;8: Peyregne V, Ducerf C, Adham M, et al. De novo cancer after orthotopic liver transplantation. Transplant Proc 1998;30: Aseni P, Vertemati M, De Carlis L, et al. De novo cancers and post-transplant lymphoproliferative disorder in adult liver transplantation. Pathol Int 2006;56: Hsi ED, Singleton TP, Swinnen L, Dunphy CH, Alkan S. Mucosa-associated lymphoid tissue-type lymphomas occurring in post-transplantation patients. Am J Surg Oncol 2000;24: Yano T, Shoji F, Maehara Y. Current status of pulmonary metastasectomy from primary epithelial tumors. Surg Today 2009;39: Lam CM, Lo CM, Yuen WK, Liu CL, Fan ST. Prolonged survival in selected patients following surgical resection for pulmonary metastasis from hepatocellular carcinoma. Br J Surg 1998;85: Viola C, Asselah T, Samuel D, et al. Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma. World J Gastroenterol 2006;12: Tomimaru Y, Sasaki Y, Yamada T, et al. The significance of surgical resection for pulmonary metastasis from hepatocellular carcinoma. Am J Surg 2006;192: Bates MJ, Farkas E, Taylor D, McFadden PM. Pulmonary resection of metastatic hepatocellular carcinoma after liver transplantation. Ann Thorac Surg 2008;85: Sternberg DI, Sonett JR. Surgical therapy of lung metastases. Semin Oncol 2007;34: Member and Individual Subscriber Access to the Online Annals The address of the electronic edition of The Annals is If you are an STS or STSA member or a non-member personal subscriber to the print issue of The Annals, you automatically have a subscription to the online Annals, which entitles you to access the full-text of all articles. To gain full-text access, you will need your CTSNet user name and password. Society members and non-members alike who do not know their CTSNet user name and password should follow the link Forgot your user name or password? that appears below the boxes where you are asked to enter this information when you try to gain full-text access. Your user name and password will be ed to the address you designate. In lieu of the above procedure, if you have forgotten your CTSNet username and/or password, you can always send an to CTSNet via the feedback button from the left navigation menu on the homepage of the online Annals or go directly to We hope that you will view the online Annals and take advantage of the many features available to our subscribers as part of the CTSNet Journals Online. These include inter-journal linking from within the reference sections of Annals articles to over 350 journals available through the HighWire Press collection (HighWire provides the platform for the delivery of the online Annals). There is also crossjournal advanced searching, etoc Alerts, Subject Alerts, Cite-Track, and much more. A listing of these features can be found at We encourage you to visit the online Annals at ats.ctsnetjournals.org and explore by The Society of Thoracic Surgeons Ann Thorac Surg 2009;88: /09/$36.00 Published by Elsevier Inc