Completion pneumonectomy (CP) refers to the complete

Similar documents
Impact of Positive Nodal Metastases in Patients with Thymic Carcinoma and Thymic Neuroendocrine Tumors

Lung cancer is the leading cause of cancer-related deaths in

CheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer

Efficacy of Pembrolizumab in Patients With Advanced Melanoma With Stable Brain Metastases at Baseline: A Pooled Retrospective Analysis

Supplementary Online Content

P (RCC) was first done in the late 1930s and reported in

Lung cancer is the leading cause of cancer death worldwide, EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas

Esophageal carcinoma is the eighth most common cancer

Clinical manifestations in patients with alpha-fetoprotein producing gastric cancer

T.S. Kurki a, *,U.Häkkinen b, J. Lauharanta c,j.rämö d, M. Leijala c

Retrospective Study of Postoperative Pulmonary Complications in Patients with Cervical Spine Pathology

Patient Survival After Surgical Treatment of Rectal Cancer

Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with nonmetastatic

Supplementary Online Content

PNEUMOVAX 23 is recommended by the CDC for all your appropriate adult patients at increased risk for pneumococcal disease 1,2 :

Community. Profile Powell County. Public Health and Safety Division

Preoperative prediction of prolonged mechanical ventilation following coronary artery bypass grafting

Emerging Options for Thromboprophylaxis After Orthopedic Surgery: A Review of Clinical Data

One of the most important biological mechanisms of

Community. Profile Yellowstone County. Public Health and Safety Division

Community. Profile Lewis & Clark County. Public Health and Safety Division

Community. Profile Missoula County. Public Health and Safety Division

Community. Profile Big Horn County. Public Health and Safety Division

Positive Heparin-Platelet Factor 4 Antibody Complex and Cardiac Surgical Outcomes

Age related differences in prognosis and prognostic factors among patients with epithelial ovarian cancer

Community. Profile Anaconda- Deer Lodge County. Public Health and Safety Division

Breast-Conserving Surgery Under Local Anesthesia in Elderly Patients with Severe Cardiorespiratory Comorbidities: A Hospital-Based Case-Control Study

Opioid Use and Survival at the End of Life: A Survey of a Hospice Population

Community. Profile Carter County. Public Health and Safety Division

CHEST. Thyroid transcription factor 1 (TTF-1) is an important. Original Research

BENIGN ulceration along the greater curvature of the pars media of the

American Joint Committee on Cancer Staging and Clinicopathological High-Risk Predictors of Ocular Surface Squamous Neoplasia

IMpower133: Primary PFS, OS, and safety in a Ph1/3 study of 1L atezolizumab + carboplatin + etoposide in extensive-stage SCLC

Perforation Following Colorectal Endoscopy: What Happens Beyond the Endoscopy Suite?

MOLECULAR AND CLINICAL ONCOLOGY 5: , 2016

Systematic review of actual 10-year survival following resection for hepatocellular carcinoma

Relationship Between Hospital Performance on a Patient Satisfaction Survey and Surgical Quality

Analysis of Risk Factors for the Development of Incisional and Parastomal Hernias in Patients after Colorectal Surgery

C hest physiotherapy is routinely used after major

Impact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting

Invasive Pneumococcal Disease Quarterly Report. July September 2017

Clinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number

Hospital readmission after a pancreaticoduodenectomy: an emerging quality metric?

Original Article. Breast Care 2016;11: DOI: /

A review of the patterns of docetaxel use for hormone-resistant prostate cancer at the Princess Margaret Hospital

Metformin and breast cancer stage at diagnosis: a population-based study

Diaphragmmatic eventration: long-term follow-up and results of open-chest plicature

Radiation therapy (RT) for cancer that involves the thorax

Abstract. Background. Aim. Patients and Methods. Patients. Study Design

The Role of Intraoperative Radiation Therapy (IORT) in the Treatment of Locally Advanced Gynecologic Malignancies

Perioperative Hyperglycemia and Postoperative Infection after Lower Limb Arthroplasty

Natural History and Treatment of Wilms's Tumour : An Analysis of 335 Cases Occurring in England and Wales

Asian Journal of Andrology (2017) 19,

R Martino 1, P Romero 1, M Subirá 1, M Bellido 1, A Altés 1, A Sureda 1, S Brunet 1, I Badell 2, J Cubells 2 and J Sierra 1

Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications

Journal of Hainan Medical University.

The burden of cirrhosis and impact of universal coverage public health care system in Thailand: Nationwide study

EOSINOPHILIC PLEURAL EFFUSION IN ADULTS AT SRINAGARIND HOSPITAL

European Journal of Internal Medicine

A community-based comparison of trauma patient outcomes between D- and L-lactate fluids,

Inhaled Corticosteroid Is Associated With an Increased Risk of TB in Patients With COPD

Prognostic factors in tongue cancer relative importance of demographic, clinical and histopathological factors

Significance of Expression of TGF- in Pulmonary Metastasis in Non-small Cell Lung Cancer Tissues

Using Paclobutrazol to Suppress Inflorescence Height of Potted Phalaenopsis Orchids

Original Article. D. Mège, a M. N. Figueiredo, a,b G. Manceau, a L. Maggiori, a Y. Bouhnik, c Y. Panis a. Abstract. 1.

Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

Biliary tract cancer treatment: 5,584 results from the Biliary Tract Cancer Statistics Registry from 1998 to 2004 in Japan

Time spent on the waiting list due to graft size incompatibility

SYNOPSIS Final Abbreviated Clinical Study Report for Study CA ABBREVIATED REPORT

Mortality of patients with multiple sclerosis: a cohort study in UK primary care

Fertility in Norwegian testicular cancer patients

Estimating the impact of the 2009 influenza A(H1N1) pandemic on mortality in the elderly in Navarre, Spain

Summary of Clinical Data for IFU EN (Zenith Dissection Endovascular System) 1

Thrombocytopenia after aortic valve replacement with the Freedom Solo stentless bioprosthesis

EVALUATION OF DIFFERENT COPPER SOURCES AS A GROWTH PROMOTER IN SWINE FINISHING DIETS 1

The Association of Gender With Quality of Health in Peripheral Arterial Disease Following Peripheral Vascular Intervention

A cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence, risk factors and impact of anti-tuberculosis

The Outcomes of Superior Cavopulmonary Connection Operation: a Single Center Experience

Changing Risk of Perioperative Myocardial Infarction

Introduction. These patients benefit less from conventional chemotherapy than patients identified as MMR proficient or microsatellite stable 3-5

Metabolic Syndrome and Health-related Quality of Life in Obese Individuals Seeking Weight Reduction

Do Statins Reduce Atrial Fibrillation After Coronary Artery Bypass Grafting?

Increased Relative Mortality in Women With Severe Oxygen-Dependent COPD

Medical Thoracoscopy vs CT Scan-Guided Abrams Pleural Needle Biopsy for Diagnosis of Patients With Pleural Effusions

DA XU *, XIAOFENG LIU *, LIJUN WANG and BAOCAI XING

Efficacy of Sonidegib in Patients With Metastatic BCC (mbcc)

27 June Bmnly L. WALTER ET AL.: RESPONSE OF CERVICAL CANCERS TO IRRADIATION

Clinical statistics analysis on the characteristics of pneumoconiosis of Chinese miner population

Risk factors for HodgkinÕs disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents

Registre des Tumeurs Digestives du Calvados, CJF INSERM 96-03, Faculté de Médecine, Avenue de Côte de nacre, Caen cedex, France;

University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA

Department of Surgery, Central Hospital of Central Finland, Jyväskylä, Finland 2

XII. HIV/AIDS. Knowledge about HIV Transmission and Misconceptions about HIV

Rheumatoid-susceptible alleles of HLA-DRB 1 are genetically recessive to non-susceptible alleles in the progression of bone destruction in the wrists

Original Article Serum tumor markers used for predicting esophagogastric junction adenocarcinoma in esophageal malignancy

Risk of Colorectal Cancer by Subsite in a Swedish Prostate Cancer Cohort

BMI and Mortality: Results From a National Longitudinal Study of Canadian Adults

Transcription:

ORIGINAL ARTICLE Completion Pneumonectomy in Ptients with Cncer Postopertive Survivl nd Mortlity Fctors Myeul Tbutin, MD, MSc,* Sébstien Courud, MD, MSc, Benoit Guibert, MD, Pierre Mulsnt, MD, Pierre-Jen Souquet, MD, nd Frnçois Tronc, MD, PhD* Objective: To describe postopertive complictions nd long-term outcomes of completion pneumonectomy nd highlight prognostic fctors. Method: We retrospectively reviewed the records of 46 ptients (38 men, 8 women) who underwent completion pneumonectomy for lung cncer between 1995 nd 2009 in one of two thorcic surgery deprtments. Most were current or former smokers (n = 41; 89%) nd did not undergo chemotherpy (n = 38; 83%) or rdiotherpy (83%) before surgery. Results: Complictions fter surgery were respirtory filure (n = 11; 24.4%), bronchopleurl fistul (n = 6; 13%, with no side preference), nd empyem (n = 6; 13%). Blood trnsfusion ws necessry for 43% of the cses (n = 20). The dy 90 deth rte ws 15.2% (n = 7). Postopertive stging showed mostly limited disese. Ten ptients (21.7%) underwent opertion for second primry cncer, 25 for locl recurrence (54.3%), five for microscopiclly incomplete resection, nd six for other resons.medin overll survivl fter completion surgery ws 30 months (medin follow-up: 46.5 months). Among the 15 living ptients (33%), 11 re free of disese (24%). In Cox regression model, fctors negtively influencing overll survivl were: ge older thn 65 yers (odds rtio [OR] = 2.47; p = 0.012), current smoker sttus (OR = 2.285; p = 0.033), postopertive pulmonry (OR = 5.144; p = 0.004), crdic (OR = 3.404; p = 0.033), or prietl wound complictions (OR = 5.439; p = 0.016). Conclusion: Despite its incresed postopertive complictions nd mortlity compred with stndrd pneumonectomy, completion pneumonectomy offers encourging long-term results. Five min fctors seem predictive of shorter overll survivl. Key Words: Completion pneumonectomy, Lung cncer, Bronchopleurl fistul, Postopertive hemorrhge, Thorcic surgery. (J Thorc Oncol. 2012;7: 1556 1562) *Thorcic Surgery Deprtment, Hospices Civils de Lyon, Hôpitl Louis Prdel, 28 venue du doyen Lépine, Bron, Frnce; Lyon Sud Chrles Mérieux Medicl Fculty, Clude Bernrd Lyon I University, Oullins, Frnce; Respirtory Medicine nd Thorcic Oncology Deprtment, nd Thorcic Surgery Deprtment, Centre Hospitlier Lyon Sud, Hospices Civils de Lyon, CH Lyon Sud, Pierre Bénite Cedex, Frnce. Drs. Tbutin nd Courud hve contributed eqully to this study. Disclosure: The uthors declre no conflict of interest. Address for correspondence: Myeul Tbutin, MD, MSc, Chirurgie Thorcique, Hôpitl Louis Prdel, 28 venue du Doyen Lépine, 69500 Bron, Frnce. E-mil: myeul.tbutin@chu-lyon.fr Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer ISSN: 1556-0864/12/0710-1556 Completion pneumonectomy (CP) refers to the complete removl of remining lung fter n initil ipsilterl prtil resection. 1 Compred with stndrd pneumonectomy, CP runs greter risk of postopertive morbidity nd mortlity, lrgely becuse of the technicl difficulties induced by the need to free ll the remining lung tissue nd itertively dissect the lung hilum. 2 Most of the studies published to dte hve confirmed these chrcteristics, 3 7 nd thus recommend tht this intervention be performed only by experienced surgeons 8,9 on crefully selected ptients. 10,11 Some dt suggest tht postopertive mortlity my be greter in ptients operted for benign lesions compred with those operted for neoplsi, 2,8,12,13 lthough it should be noted tht this fcet remins controversil. 14 16 There re currently little dt on fctors influencing long-term survivl nd postopertive mortlity. Thus our objective in this retrospective multicenter study ws to ssess survivl in ptients who underwent CP for neoplstic events only (primry or metsttic to the lung) nd report fctors ssocited with survivl or postopertive mortlity. PATIENTS AND METHODS Methods All CP ptient cses from Jnury 1, 1995, to December 31, 2009, in two thorcic surgery deprtments in Lyon (Frnce) were reviewed. Only those cses flling within the neoplstic context were retined for nd included in this retrospective study, tht is one or both of the surgicl interventions ws/ were for neoplsi. Cses in which both surgicl interventions were for nonmlignnt cuses were excluded, s were those with incomplete files. All dt used in the study were retrieved from the rchived ptient medicl files. When lcking in the medicl files, survivl dt (dtes of deth) were collected from ptients primry cre physicins or birthplce city hll records. In ddition to hbitul demogrphic dt nd dt on the neoplstic disese nd pertinent ptient history, we lso gthered informtion specific to the surgery nd postopertive complictions. Medin follow-up ws 46.5 months (0 178) since CP, nd 102, 7 months since first surgery (12 320). Sttisticl Anlyses Sttisticl nlyses were performed with SPSS v17.0 (IBM Corp., Armonk, NY). Proportion comprisons were 1556 Journl of Thorcic Oncology Volume 7, Number 10, October 2012

Journl of Thorcic Oncology Volume 7, Number 10, October 2012 Completion Pneumonectomy in Ptients with Cncer done with Person s χ 2 test or Fisher s F test s needed. The Kpln Meier method ws used for survivl nlyses. Survivl comprisons were clculted using the log-rnk test. For multivrite nlyses, Cox regression ws used for fctors linked to survivl nd binry logistic regression for postopertive mortlity. A p vlue of 0.05 or less ws considered sttisticlly significnt. Popultion Forty-six of the 51 initilly reviewed cse files met the study inclusion criteri (2 exclusions for nonmlignncy nd 3 for incomplete files). Chrcteristics of included ptients re provided in Tble 1. Forced expirtory volume (FEV1) ws evluted for ll ptients. If preopertive FEV1 ws inferior to 80% nd/or diffusion cpcity inferior to 80%, pulmonry ventiltion/ perfusion scn ws performed to evlute prticiption of the removed lung. A predictive postopertive FEV1 less thn 35% ws considered s contrindiction for surgery. Exercise testing before opertion ws not relized in this series. Opertive Technique The first tsk of the surgeon ws to crefully red the surgicl report on the ptient s previous procedure. All opertions were done by reopening the previously used thorcotomy incision. Section of the posterior prt of the fifth rib, to provide esier ccess to the pleurl spce, ws done if necessry. Excessive bleeding from the chest wll ws prevented by mobiliztion of the lung through the intrpleurl spce whenever possible. This prt of the procedure ws prticulrly difficult nd hemorrgic when the first opertion hd been done extrpleurlly. Once the lung ws freed, the pulmonry blood vessels were ligted extrpericrdilly if possible (Tble 2). The pericrdium ws opened when extrpericrdil dissection ws not possible. If the pericrdil cvity ws completely obliterted, we tried to isolte nd divide the bronchus first nd then ligte the pulmonry blood vessels. The bronchus ws trnscted s close s the trchel bifurction s possible. The stump ws lmost never covered with flp when surgery ws performed on the left side, becuse it ws buried deeply under the ort. On the right side, it ws often covered with vible tissue (n = 17) such s pleur from the rch of the zygos, pericrdium, or intercostl muscle. In mny cses, fibrin glue ws generously pplied on the bronchil stump. RESULTS Events resulting in CP nd technicl spects re provided in Tble 2. Histologiclly, denocrcinom ws the most common entity (45.2%; n = 21). Antomicl pthology findings were identicl between the initil surgery nd CP in more thn three qurters of the cses (76.9%; n = 30). Expressed by the tumor, lymph node, nd metstsis clssifiction (7th edition, 2009), 17 the neoplsms were generlly smll (T1: 30.8%, n = 12; T2: 48.7%, n = 19), without medistinl lymph node involvement (N0: 79.5%; n = 31) nd without metstsis (M0: 97.5%; n = 39). Consequently, there were more frequently erly stges (stge I: 55%, n = 22; II: 22.5%, n = 9; IIIA: 20%, n = 8) thn lte ones (stge IIIB: 0; IV: 2.5% [1 ptient presenting pleurl crcinosis]). Long-term survivl ccording to the stge is presented in Figure 1. Most ptients (68.9%; n = 31) did not receive djuvnt tretments fter CP. Tble 3 presents the principle postopertive outcomes. Cuses of mortlity in the first 90 dys were: bronchopleurl fistul (42, 8%: n = 3), respirtory filure (28, 6%; n = 2), nd uncler (28, 6%; n = 2: 1 deth t home in context of cute respirtory filure nd 1 in intensive cre ttributed to multiple cerebrl septic emboli). Bronchopleurl fistul (BPF) cused the deth of three of the six ffected ptients. The three others were successfully treted, two by endoscopic ppliction of tissue dhesive nd one by thorcostomy nd ltissimus dorsi myoplsty. In this series, the men hospitl sty ws 19.6 dys (rnge, 7 169), of which men 5.2 dys were spent with chest drin in plce. At the end of the follow-up period (September 1, 2010) 15 ptients (32.6%) were still live. Five-yer cturil survivl ws 47%. The cuses of deth for the 31 other ptients were: lung cncer (30.4%; n = 14), CP (15.2%, n = 7; corresponding to the dy-90 [D90] mortlity rte), nd other or unknown (21.8%; n = 10). The medin of post-cp progression-free survivl (PFS) ws 16 months (95% confidence intervl [CI] = 9.614 22.386). Twenty-one ptients (50%) presented recurrence t the end of the follow-up period. In univrite nlyses, no demogrphic or preopertive criteri (including cncer stge nd comorbidity) ws found to be ssocited with postopertive mortlity before D90 (Tble 4). Fctors ssocited with risk of deth t D90 were inferior lobe (left or right) CP (43.6% versus 100%; p = 0.01), postopertive, respirtory complictions nd/or more thn two complictions (12.8% versus 100%; p < 0.0001; 28.2% versus 83.3%; p = 0.017, respectively), nd fistul formtion (7.7% versus 50%; p = 0.024). Fctors influencing overll survivl were lso nlyzed. Agin in univrite nlyses, fctors significntly ssocited with improved survivl were: ge less thn 65 yers (65 versus 21 months; p = 0.013), never or former smoker sttus (44 versus 8 months; p = 0.011), lymphdenectomy during CP (44 versus 6 months; p = 0.015), bsence of respirtory complictions (44 versus 0 months; p < 0.0001), nd bsence of thorcotomy wound complictions (44 versus 4 months; p = 0.023). Femle sex (p = 0.052), bsence of crdic complictions (p = 0.053) nd bsence of reintubtion (p = 0.069) provided nonsignificnt tendency towrd better survivl. The type of CP (inferior lobe versus other) ws not found to be ssocited with overll survivl. Multivrite nlyses were done with demogrphic nd postopertive criteri, significnce showing trend for incresed mortlity in univrite nlysis (Tble 4). Fctors ssocited with postopertive mortlity were: pulmonry compliction (p < 0.00001), BPF (p = 0.024), more thn two postopertive complictions (p = 0.017), nd CP on the lower lobe (p = 0.01). Age younger thn 65 yers remined fctor of good prognosis (hzrd rtio [HR] = 2.665 [1.139 6.238], p = 0.024) s did never or former smoker sttus (HR = 2.270 [1.058 4.870], p = 0.035). For postopertive criteri, the bsence of respirtory, crdic nd wound Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer 1557

Tbutin et l. Journl of Thorcic Oncology Volume 7, Number 10, October 2012 TABLE 1. Min Chrcteristics of the Popultion Chrcteristic n % Demogrphic criteri Sex Mle 38 82.6 Femle 8 17.4 Men ge (yrs) (± SD) 59.2 (± 9) Smoking sttus Nonsmoker 5 10.9 Former smoker 24 52.2 Current smoker 17 37 Men FEV1 (± SD) in % (n = 41) 71.1% (± 13.46%) Men predicted postopertive lung volume 63.7% (± 16.79%) (±SD) in % on pulmonry ventiltion/ perfusion scn (n = 21) First surgery chrcteristics Cuse for first surgery Primry lung cncer 43 93.4 Lung metstses 2 4.4 Aspergillom 1 2.2 Pthology (n = 45) Adenocrcinom 17 37.8 Squmous cell crcinom 25 55.6 Lrge cell crcinom 1 2.2 Typicl crcinoid 1 2.2 Fibrosrcom 1 2.2 Lymph node dissection (n = 43) 42 97.7 Men durtion between first surgery nd CP (± SD; mx min) Preopertive comorbidities before CP Number of comorbidities 54.6 mos (±64.9; 0 310) None 10 21.7 2 31 67.5 > 2 5 10.8 Type of comorbidity COPD b 26 70.3 Coronry rtery disese 8 17.4 Hert filure 1 2.2 Dibetes 8 17.4 Renl filure c 5 13.2 Corticosteroid or IS use 1 2.2 Peripherl rteril disese 2 4.3 Preopertive ntineoplstic tretment Chemotherpy < 3 mos 8 17.4 Medistinl rdiotherpy (ny time) 8 17.4 ASA score 2 37 80.4 3 9 19.6 Defined s quit smoking 12 months go or longer. b Defined s FEV1/VC < 70%. c Defined s cretinine clernce < 60 ml/mn. FEV1, forced expired volume in 1 second; COPD, chronic obstructive pulmonry disese; CP, completion pneumonectomy; IS, immunosuppressive tretment; ASA, Americn Society of Anesthesiology. TABLE 2. Min Chrcteristics of the Completion Surgery Chrcteristic N % Cuse of the CP Mlignnt disese 42 91.2 Secondry primry NSCLC 10 (1 crcinoid) 21.7 Recurrent NSCLC b 25 54.3 R1 fter 1st surgery 5 (1 in situ) 10.9 Metstses 2 4.3 Benign disese 3 6.6 Persistnt telectsis fter initil 1 2.2 surgery Aspergillom 1 2.2 Hemngiom 1 2.2 NC c 1 2.2 Loction of the CP Right/left lung completion 28/18 61/39 Upper/lower/both lobe(s) 21/24/1 46/52/2 Employed surgicl techniques Intrpericrdil dissection 19 41 Chest wll resection 1 2 Vsculr resection 0 0 Bronchil stump covered with 17 37 flp ll Pleur 14 82 Pericrdi 2 12 Muscle 1 6 Lymphdenectomy 38 83 Hospitl cre Medin hospitl length of sty 11 (7 169) (dys; min mx) Medin durtion of thorcic dringe(dys; min mx) 5 (2 15) Defined s the ppernce of cncer histologiclly different from tht of the initil surgery, or histologiclly identicl 5 yrs or more fter the initil surgery. b Defined s the ppernce of cncer histologiclly identicl to tht of the initil surgery within 5 yrs fter the surgery. c First surgery for spergillom. NSCLC, non smll-cell lung cncer; R1, presence of microscopic residue fter the initil surgery; CP, completion pneumonectomy; NC, not counted. complictions were ll good prognosis fctors with respective HR of 5.144 (1.662 15.919; p = 0.004), 3.404 (1.101 10.527; p = 0.033), nd 5.439 (1.373 21.539; p = 0.016). No dditionl fctors ssocited with improved overll survivl were found when postopertive deths (< D90) were excluded. Similrly, smoking sttus ws the only fctor significntly ssocited with overll survivl from the dte of the initil surgery. None of these fctors were ssocited with PFS. Disese-descriptive fctors (T > 1, N > 0, nd stge > 1) were ssocited with neither overll survivl nor PFS, probbly becuse of the size of the test popultion. For periopertive fctors, only lymphdenectomy during CP ws significntly ssocited in nondjusted nlysis, but its ssocition disppered fter djustment for stge nd lymph node sttus. For postopertive complictions, fter exclusion of postopertive deths, only wound complictions remined significntly ssocited with survivl (HR: 5.793 [1.219 27.538]; p = 0.027). 1558 Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer

Journl of Thorcic Oncology Volume 7, Number 10, October 2012 Completion Pneumonectomy in Ptients with Cncer FIGURE 1. Overll survivl fter completion pneumonectomy regrding stge of the tumor. OS, overll survivl. Finlly, there ws no influence of ntineoplstic neodjuvnt tretments on postopertive course, specificlly for BPF, or pulmonry complictions. DISCUSSION In our series, we found elevted rtes of postopertive mortlity (15.2%) nd morbidity (55.6%) comprble with those of other published CP series (Tble 5). Similrly, our CP mortlity nd morbidity rtes were higher thn those of stndrd pneumonectomy. This is gin comprble with the mjority of literture dt, 18,19 lthough some uthors hve found similr rtes for the two interventions. 12,14 For comprison, Thibout et l. 20 studied ptients who underwent pneumonectomy fter chemotherpy; their popultion ws tken from the sme thorcic surgery deprtments s ours (nd involved the sme surgeons). They found much lower rtes of D90 mortlity nd BPF thn we did: 9.2% versus 15.2% nd 7% versus 13%, respectively. The percentge of ptients trnsfused with more thn two red blood pcks ws lso much lower in the study by Thibout et l. 20 thn in ours (8% versus 35%), confirming the hemorrhgic nture of CP. 5,21 The development of BPF or respirtory filure emerged in our study s risk fctor for postopertive mortlity. This ws not unexpected, s similr results hve been reported in the literture for stndrd pneumonectomy. 22,23 However, contrry to other studies, 8,12,24 our study did not find tht right-sidedness in CP ws mortlity risk fctor, but this my be explined by the smll size of our study popultion. Furthermore, we did not find BPF to occur more frequently in the right lung thn in the left. Surprisingly, our results indicted tht inferior lobe CP ws significntly ssocited with incresed postopertive mortlity. This spect tends not to pper in the literture, with the exception of the study by Mssrd et l. 4 who described incresed, but sttisticlly insignificnt, periopertive bleeding in inferior lobe CP. We hypothesize tht this my be explined by the incresed difficulty encountered when dissecting the root bronchus in the ftermth of superior lobectomy. Whtever the cse my be, this finding should be confirmed in lrger series. Overll, our findings concerning long-term survivl were encourging. We did not perform subgroup nlysis compring ptients with lung metstses (n = 2) with the others, but the results of two retrospective studies focused uniquely on this popultion my suggest tht CP is not tretment of choice for lung metstses, given the poor long-term survivl nd significnt surgicl risks. 10,24 The study of prognosis fctors is lrgely lcking in the literture: on one hnd, the smll number of ptients in most series mkes their sttisticl nlysis difficult, nd on the other, the studies on lrge cohorts hve been predominntly focused on fctors involved in BPF formtion 12,13 or postopertive mortlity. 5,8 In multivrite nlyses to determine risk fctors for postopertive mortlity, Chtigner et l. 8 pointed to chronic renl filure, wheres Miller et l. 5 indicted preopertive corticosteroid use nd low preopertive hemoglobin. To our knowledge, no studies hve reported on fctors influencing long-term survivl. In our cohort, ge older thn 65 yers, current smoker sttus t CP, nd postopertive respirtory, crdic, or prietl wound complictions negtively influence long-term survivl. Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer 1559

Tbutin et l. Journl of Thorcic Oncology Volume 7, Number 10, October 2012 TABLE 3. Postopertive Outcomes Event n % Mortlity Mortlity before D30 6 13 Cuse of deth before D30 v BPF 2 33.3 Respirtory filure 2 33.3 Unspecified 2 33.3 Mortlity before D90 7 15.2 Complictions / morbidity Men of blood cell pcks trnsfused in 1.97 (0 14) periopertive period (min mx) Types of complictions b Hemorrhge c 11 24.4 Reopertion c 3 6.7 Crdic compliction (ischemic/ 4 (2 / 2) 8.8 rhythmic) c Respirtory filure c 11 24.4 Reintubtion d 5 11.4 Prietl wound compliction c 3 6.7 Chylothorx c 0 0 Recurrent nerve prlysis c 2 4.4 Empyem c 6 13 Thromboembolic disese c 0 0 BPF c 6 13 Number of complictions/ptient c None 20 44.4 2 13 28.9 > 2 12 26.1 Survivl Medin OS* fter CP (mos) (CI = 95%) d 30 (5.299 54.701) Medin OS fter initil surgery (mos) 79 (55.931 102.069) (CI = 95%) Medin OS fter CP (mos), excluding 73 (0 155.643) postopertive deths (CI = 95%) d Medin PFS* (mos) fter CP (IC95%) e 16 (9.614 22.386) Progression Recurrence 21 50 Locl 6 14.3 Distnt 15 35.7 No recurrence 21 50 n = 20 ptients trnsfused. b Complictions cn be cumultive. c n = 1 missing vlues. d 2 missing vlues (4 = 15 censored dt). e n = 9 censored dt.* OS, overll survivl; PFS, progression-free survivl; CI, confidence intervl; CP, completion pneumonectomy; BPF, bronchopleurl fistul. An originl spect is the significnt prognostic influence tht we found for prietl wound complictions. An ltered generl or nutritionl stte present t CP nd ffecting the ptient s overll survivl expectncy is possible explntion for this. 25 The precise evlution of postopertive morbidity (55.6%) is difficult retrospectively. Complictions re dominted by respirtory nd hemorrhgic disorders (the ltter identified s significnt periopertive bleeding indicted in the opertive report or s significnt bleeding observed postopertively in the pneumonectomy cvity, necessitting or not new surgicl intervention) nd the development of BPF. More thn 43% of the ptients in our study received periopertive trnsfusions, lthough we found no ssocition between the number of trnsfusion pcks nd postopertive mortlity or long-term survivl. This ltter spect is in contrdiction with Thoms et l. 26 who, in lrger cohort of pneumonectomy ptients, found significnt link between the quntity of dministered blood pcks nd postopertive mortlity. Nevertheless, these observtions nd those of other surgicl series finding reduced long-term survivl in trnsfused ptients 27 29 illustrte how the hemorrhgic nture of CP continues to be mjor issue in ptients operted for cncer. Tking into ccount the erly stge of lung cncer in the mjority of our ptients, less invsive therpeutic options such s chemordition nd stereotctic rdiotherpy could be discussed. Those techniques hve lower morbidity nd mortlity, 30 nd long-term survivl seems interesting. 31,32 However, long-term survivl compred with redo surgery in cse of locl recurrence hs not yet been evluted prospectively. Moreover, in their retrospective study on postrecurrence survivl in completely resected stge I non smll-cell lung cncer with locl recurrence, Hung et l. 32 conclude tht surgicl resection should be considered in selected cndidtes with resectble locl recurrent disese, becuse reoperted ptients survived longer thn ptients treted with chemotherpy nd/or rdiotherpy. A prospective study on the subject could be useful. CONCLUSION Our present retrospective study confirms tht CP, compred with stndrd pneumonectomy, is burdened with higher postopertive morbidity nd mortlity. We found tht bleeding remins mjor issue in this intervention s does the incresed risk of BPF formtion. Risk fctors for postopertive mortlity detected were BPF formtion, respirtory filure, more thn two complictions (mong those nlyzed in the study) nd, more originlly, CP in n inferior lobe. Prognosis fctors ffecting overll survivl were ge older thn 65 yers, current smoker sttus t CP, nd postopertive respirtory, crdic or prietl wound complictions. Long-term survivl remins encourging nd justifies the interest in this surgery. CP is rre surgicl intervention; this explins the frequently smll popultions in the vrious retrospective studies nd thus their lck of sttisticl power to demonstrte congruent prognostic fctors. Improving current knowledge of these fctors is nevertheless vitl to permit more precise selection of ptients ble to benefit from surgery. A met-nlysis to ddress these weknesses would thus be welcome ddition to the literture. 1560 Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer

Journl of Thorcic Oncology Volume 7, Number 10, October 2012 Completion Pneumonectomy in Ptients with Cncer TABLE 4. Fctors Influencing Postopertive Mortlity nd Long-Term Survivl Deth D90 Overll Survivl Fctor Considered n Ded/n in Ct. (%) p Medin (in mos) (95%CI) P Hzrd rtio (95% CI) by Cox Model p Demogrphic criteri Age (yrs) < 65 5/34 (14.7%) 0.058 65.6 (18.1 112.2) 0.012 1 0.024 65 2/12 (16.7%) 21.2 (5.9 54.9) 2.7 (1.0 6.2) Tobcco smoking sttus Never or former smoker 3/29 (10.3%) 0.0216 44.9 (10.8 79.0) 0.013 1 0.035 Current smoker 4/17 (23.5%) 8.279 (3.6 13.0) 2.3 (1.1 4.9) Surgery complictions Bronchopleurl fistul No 3/39 (7.7%) 0.024 44.9 (11.2 78.6) 0.347 Yes 3/6 (50%) 1.3 (0.0 26.4) Pulmonry compliction No 0/34 (0%) < 0.00001 65.15 (34.3 96.0) < 0.00001 1 0.004 Yes 6/11 (54.5%) 1.3 (0.0 7.8) 5.1 (1.7 15.9) Crdic compliction No 4/41 (9.8%) 0.080 44.9 (10.1 79.8) 0.047 1 0.033 Yes 2/4 (50%) 0.6 (0.0 18.2) 3.4 (1.1 10.5) Prietl wound compliction No 5/42 (11.9%) 0.356 44.9 (5.9 84.0) 0.023 1 0.016 Yes 1/3 (33.3%) 4.9 (0.0 10.7) 5.4 (1.4 21.6) Number of complictions < 2 1/29 (3.4%) 0.017 44.9 (5.8 84.1) 0.231 2 5/16 (31.3%) 11.4 (0.0 28.0) Surgery criteri CP on the lower lobe 7/24 (29.2%) 0.01 21.2 (1.8 40.6) 0.390 CP elsewhere 0/22 (0%) 44.9 (10.6 79.2) n = 1 missing vlue. CI, confidence intervl; CP, completion pneumonectomy TABLE 5. Comprison between our Study nd Others Concerning Postopertive Mortlity (D90 Deth in our Study), Bronchopleurl Fistul Occurrence, nd Intr nd Postopertive Trnsfusions Series Yr N n with Mlignnt Disese Postopertive Mortlity Rte for Cncer Ptients (%) Bronchopleurl Fistul (%) Periopertive Blood Trnsfusions (%) Mc Govern et l. 2 1988 113 84 9.4 11.7 Grégoire et l. 14 1993 60 41 11.6 13.3 Mssrd et l. 4 1995 37 32 17.3 2.7 54 l-kttn et l. 11 1995 38 26 0 0 Verhgen et l. 7 1996 37 33 15.6 5.4 Muysoms et l. 6 1998 138 80 13.2 4.3 Regnrd et l. 13 1999 80 62 6.4 3.8 66 Tronc et l. 1 1999 77 57 10.5 10.4 Fujimoto et l. 15 2001 66 49 2.3 7.6 Terzi et l. 9 2002 59 59 3.4 52.4 Miller et l. 5 2002 115 58 17.6 7 Guggino et l. 12 2004 55 42 13.2 12.7 30 Jungrithmyr et l. 3 2004 86 41 10 10.4 Chtigner et l. 8 2007 69 47 12.8 10 19 Current study 2011 46 46 15 13 43 Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer 1561

Tbutin et l. Journl of Thorcic Oncology Volume 7, Number 10, October 2012 REFERENCES 1. Tronc F, Grégoire J, Rouleu J, Desluriers J. Techniques of pneumonectomy. Completion pneumonectomy. Chest Surg Clin N Am 1999;9: 393 405, xi. 2. McGovern EM, Trstek VF, Pirolero PC, Pyne WS. Completion pneumonectomy: indictions, complictions, nd results. Ann Thorc Surg 1988;46:141 146. 3. Jungrithmyr W, Hsse J, Olschewski M, Stoelben E. Indictions nd results of completion pneumonectomy. Eur J Crdiothorc Surg 2004;26:189 196. 4. Mssrd G, Lyons G, Wihlm JM, et l. Erly nd long-term results fter completion pneumonectomy. Ann Thorc Surg 1995;59:196 200. 5. Miller DL, Deschmps C, Jenkins GD, Bernrd A, Allen MS, Pirolero PC. Completion pneumonectomy: fctors ffecting opertive mortlity nd crdiopulmonry morbidity. Ann Thorc Surg 2002;74:876 883. 6. Muysoms FE, de l Rivière AB, Defuw JJ, et l. Completion pneumonectomy: nlysis of opertive mortlity nd survivl. Ann Thorc Surg 1998;66:1165 1169. 7. Verhgen AF, Lcquet LK. Completion pneumonectomy. A retrospective nlysis of indictions nd results. Eur J Crdiothorc Surg 1996;10:238 241. 8. Chtigner O, Fdel E, Yildizeli B, et l. Fctors ffecting erly nd longterm outcomes fter completion pneumonectomy. Eur J Crdiothorc Surg 2008;33:837 843. 9. Terzi A, Lonrdoni A, Flezz G, et l. Completion pneumonectomy for non-smll cell lung cncer: experience with 59 cses. Eur J Crdiothorc Surg 2002;22:30 34. 10. Grunenwld D, Spggiri L, Girrd P, Bldeyrou P, Filire M, Dennewld G. Completion pneumonectomy for lung metstses: is it justified? Eur J Crdiothorc Surg 1997;12:694 697. 11. l-kttn K, Goldstrw P. Completion pneumonectomy: indictions nd outcome. J Thorc Crdiovsc Surg 1995;110(4 Pt 1):1125 1129. 12. Guggino G, Doddoli C, Brlesi F, et l. Completion pneumonectomy in cncer ptients: experience with 55 cses. Eur J Crdiothorc Surg 2004;25:449 455. 13. Regnrd JF, Icrd P, Mgdeleint P, Juffret B, Frés E, Levsseur P. Completion pneumonectomy: experience in eighty ptients. J Thorc Crdiovsc Surg 1999;117:1095 1101. 14. Grégoire J, Desluriers J, Guojin L, Rouleu J. Indictions, risks, nd results of completion pneumonectomy. J Thorc Crdiovsc Surg 1993;105:918 924. 15. Fujimoto T, Zbour G, Fechner S, et l. Completion pneumonectomy: current indictions, complictions, nd results. J Thorc Crdiovsc Surg 2001;121:484 490. 16. Sirmli M, Krsu S, Gezer S, et l. Completion pneumonectomy for bronchiectsis: morbidity, mortlity nd mngement. Thorc Crdiovsc Surg 2008;56:221 225. 17. Groome PA, Bolejck V, Crowley JJ, et l.; IASLC Interntionl Stging Committee; Cncer Reserch nd Biosttistics; Observers to the Committee; Prticipting Institutions. The IASLC Lung Cncer Stging Project: vlidtion of the proposls for revision of the T, N, nd M descriptors nd consequent stge groupings in the forthcoming (seventh) edition of the TNM clssifiction of mlignnt tumours. J Thorc Oncol 2007;2:694 705. 18. Powell ES, Perce AC, Cook D, et l.; UKPOS Co-ordintors. UK pneumonectomy outcome study (UKPOS): prospective observtionl study of pneumonectomy outcome. J Crdiothorc Surg 2009;4:41. 19. Drling GE, Abdurhmn A, Yi QL, et l. Risk of right pneumonectomy: role of bronchopleurl fistul. Ann Thorc Surg 2005;79:433 437. 20. Thibout Y, Guibert B, Bossrd N, et l. Is pneumonectomy fter induction chemotherpy for non-smll cell lung cncer resonble procedure? A multicenter retrospective study of 228 cses. J Thorc Oncol 2009;4:1496 1503. 21. Terzi A, Furln G, Terrini A, Mgnnelli G. Completion pneumonectomy: experience with 47 cses. Thorc Crdiovsc Surg 1995;43:52 56. 22. Alexiou C, Beggs D, Rogers ML, Beggs L, Asop S, Slm FD. Pneumonectomy for non-smll cell lung cncer: predictors of opertive mortlity nd survivl. Eur J Crdiothorc Surg 2001;20:476 480. 23. Joo JB, DeBord JR, Montgomery CE, et l. Periopertive fctors s predictors of opertive mortlity nd morbidity in pneumonectomy. Am Surg 2001;67:318 321. 24. Jungrithmyr W, Hsse J, Stoelben E. Completion pneumonectomy for lung metstses. Eur J Surg Oncol 2004;30:1113 1117. 25. Tewri N, Mrtin-Ucr AE, Blck E, et l. Nutritionl sttus ffects long term survivl fter lobectomy for lung cncer. Lung Cncer 2007;57:389 394. 26. Thoms P, Michelet P, Brlesi F, et l. Impct of blood trnsfusions on outcome fter pneumonectomy for thorcic mlignncies. Eur Respir J 2007;29:565 570. 27. Tchibn M, Tbr H, Kotoh T, et l. Prognostic significnce of periopertive blood trnsfusions in resectble thorcic esophgel cncer. Am J Gstroenterol 1999;94:757 765. 28. Busch OR, Hop WC, Hoynck vn Ppendrecht MA, Mrquet RL, Jeekel J. Blood trnsfusions nd prognosis in colorectl cncer. N Engl J Med 1993;328:1372 1376. 29. Nosotti M, Rebull P, Riccrdi D, et l. Correltion between periopertive blood trnsfusion nd prognosis of ptients subjected to surgery for stge I lung cncer. Chest 2003;124:102 107. 30. Bongers EM, Hsbeek CJ, Lgerwrd FJ, Slotmn BJ, Senn S. Incidence nd risk fctors for chest wll toxicity fter risk-dpted stereotctic rdiotherpy for erly-stge lung cncer. J Thorc Oncol 2011;6:2052 2057. 31. Sur S, Yorke E, Jckson A, Rosenzweig KE. High-dose rdiotherpy for the tretment of inoperble non-smll cell lung cncer. Cncer J 2007;13:238 242. 32. Hung JJ, Hsu WH, Hsieh CC, et l. Post-recurrence survivl in completely resected stge I non-smll cell lung cncer with locl recurrence. Thorx 2009;64:192 196. 1562 Copyright 2012 by the Interntionl Assocition for the Study of Lung Cncer