adenoca esofagus

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Indications and outcome of salvage surgery for oesophageal cancer

Xavier-Benoit DJourno a, Pierre Michelet b, Laetitia Dahan c, Christophe Doddoli a,d,Jean-Francois Seitz c, Roger Giudicelli a, Pierre A. Fuentes a, Pascal A. Thomas a,d,*

a Department of Thoracic Surgery, Ste Marguerite University Hospital, Marseille, Franceb Intensive care Unit, Ste Marguerite University Hospital, Marseille, Francec Department of Digestive Oncology, La Timone Hospital, Marseille, Franced UMR 6020, IFR 48, University of the Mediterranean, Marseille, France

Received 30 July 2007; received in revised form 6 January 2008; accepted 16 January 2008; Available online 14 March 2008

Abstract

Objective: Somepatients with localised oesophageal cancer are treated with definitivechemoradiotherapy(CRT) rather than surgery. A subsetof these patients experiences local failure, relapse or treatment-related complication without distant metastases, with no other curativetreatment option but salvage oesophagectomy. The aim of this study was to assess the benefit/risk ratio of surgery in such context. Methods:

Review of a single institution experience with 24 patients: 18 men and 6 women, with a mean age of 59 years (9). Histology was squamous cellcarcinoma in 18 cases and adenocarcinoma in 6. Initial stages were cIIA ( n= 5), cIIB (n= 1) and cIII (n= 18). CRT consisted of 26 sessions of theassociation 5-fluorouracil/cisplatin concomitantly with a 5075 Gy radiation therapy. Salvage oesophagectomy was considered for the followingreasons: relapse of the disease with conclusive (n= 11) or inconclusive biopsies (n= 7), intractable stenosis (n= 3), and perforation or severeoesophagitis (n= 3), at a mean delay of 74 days (14240 days) following completion of CRT. Results:All patients underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy. Thirty-day and 90-day mortalityrates were21% and 25%, respectively. Anastomotic leakage(p= 0.05), cardiac failure (p= 0.05), lengthof stay (p= 0.03)and thenumber of packed redblood cells (p = 0.02) weremore frequent in patientswho received more than 55 Gy, leading to a doubled in-hospital mortality when compared to that of patients having received lower doses. A R0resection was achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was observed in 3 patients (12.5%). Overall anddisease-free 5-year survival rates were35% and 21%, respectively. Therewas no long-term survivor followingR1R2 resections. Functional resultswere good in more than 80% of the long-termsurvivors. Conclusion: Salvage surgery is a highly invasive andmorbid operation after a volumedoseof radiation exceeding 55 Gy. The indication must be carefully considered, with care taken to avoid incomplete resections. Given that long-termsurvival with a fair quality of life can be achieved, such high-risk surgery should be considered in selected patients at an experienced centre.# 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Keywords: Oesophageal neoplasms; Chemotherapy; Radiotherapy; Oesophagectomy

1. Introduction

Ongoing controversy surrounds the question of whetherlocally advanced cancer of the oesophagus should be resectedor treated with non-surgical methods. The largest and mostcomplete meta-analysis of randomised neoadjuvant treat-ment trials done so far in patients with oesophageal cancerprovides evidence supporting surgery following inductionconcurrent chemoradiation therapy (CRT) as the standard oftreatment for fit patients with locally advanced oesophageal

cancer, especially in cases of adenocarcinoma[1]. The role ofsurgery in the multimodal approach to locoregional oesopha-geal cancer, however, has recentlybeen questioned. Results of

two randomised trials suggest that in cases of squamous cellcancer there is no clear survival advantage favouring surgery,even if local tumour control is significantly improved afterresection [2,3]. Furthermore, the risks of surgery in thiscontext reflect a significant effect of CRT on postoperativemortality within 90 days, due to three main adverse events:respiratory complications, heart failure, and anastomotic leak[4]. As a result, the view that completion CRT is an alternativeto surgery in patients with squamous-cell carcinomas whoshow a morphological response to induction CRT is growingly

shared by oncologists, because such treatment strategy seemsto produce a similar overall survival, but with less post-treatment morbidity, and last but not least, similar quality oflife[5]. In other words, full-dose CRT (definitive CRT) tends tobe preferred for responders to a half-dose of CRT as much asoesophagectomy, whereas oesophagectomy is likely to bepreferred for non-responders.

Unfortunately, crude locoregional control rate remainsquite poor with definitive CRT, and roughly half of the

www.elsevier.com/locate/ejctsEuropean Journal of Cardio-thoracic Surgery 33 (2008) 11171123

Presented at the 15th European Conference on General Thoracic Surgery,

Leuven, Belgium, June 36, 2007.

* Corresponding author. Address: Department of Thoracic Surgery, Ste Mar-

guerite Hospital, CHU Sud, 270 Bvd Ste Marguerite, 13274 Marseille Cedex 9,

France. Tel.: +33 491 744 680; fax: +33 491 744 590.

E-mail address: [email protected] (P.A. Thomas).

1010-7940/$ see front matter # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.ejcts.2008.01.056


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patients present with a persistent or a relapsing tumour atthe primary site within 1 year [6,7]. Accordingly, oesopha-gectomy stands out as a possible opportunity of cure for fitpatients without distant metastases. Besides, local compli-cations of definitive CRT such as intractable strictures, ulceror perforation, may lead to a rescue surgery. Finally, thedebate over definitive CRT versus neoadjuvant CRT andsurgery may be reworded in terms of salvage versus plannedoesophagectomy. Although both types of surgery are done inthe setting of previous CRT, one may anticipate that they aredifferent in several ways. Very few studies have addressedthis issue[812]. Preliminary data suggest that despite anincreased morbidity and mortality, a subset of patients willbe offered a second chance of cure [812]. The selection ofthe winners however, remains challenging. The presentreport aims to add some information on the topic.

2. Materials and methods

We conducted a retrospective review of all patientshaving undergone oesophageal resection (n= 268) between1996 and 2006 at our institution, and selected those patientswho received salvage surgery (n= 24). Patient charts wereidentified by screening of a database into which data wereentered prospectively for any patient undergoing surgery forthoracic malignancy at our department. Salvage oesopha-gectomy was defined as an operation performed afterdefinitive concurrent chemoradiation which included plati-num-based chemotherapy and more than or equal to 50 Gyradiotherapy, and selectively indicated for isolated localfailures and recurrences, or treatment-related complica-tions. In almost all patients, the initial treatment wasplanned at an outside centre. Once referred at ourinstitution, a multidisciplinary decision-making process wasfollowed. The operation was proposed to patients who weredeemed physiologically amenable to surgery, whose tumourwas thought to be resectable and who had no evidence ofdistant metastases at the work-up revaluation.

Hospital records were reviewed for age, sex, body massindex, initial clinical stage of the disease, American Society ofAnesthesiology risk classification, preoperative medical his-tory, pulmonary function test performances, tumour location,histology, residual pathologic stage graded according to theTNM classification [13], and results of preoperative laboratoryand imaging studies (Table 1). All medical charts were alsoreviewed for details regarding the initial CRT. There were 6females and 18 males whose mean age was 59 9 years(range: 3370). Tumour types included 8 adenocarcinomaslocated to the lower oesophagus (classified as Siewert I and II)and 16 squamouscell carcinomas predominantly located in themiddle (n= 9) and the lower oesophagus (n= 7). At pretreat-ment evaluation, 18 patients presented with a locallyadvanced stage cIIb or cIII disease. Three high-risk patientspresented with a stage cIIA disease. One patient was classifiedas having a stage cIVB due to the presence of a single lungmetastasis. In 2 cIIA patients, the justification of the first-lineCRT was unclear. CRT consisted of the association of 5-fluorouracil and cisplatin, and concurrent radiotherapy. Theaverage number of cycles was 2.88 (range: 26). The averagedoseof fractionated radiation delivered to the oesophaguswas

56 Gy. This value served as cut-off to split the patientspopulation in 2 groups: 14 patients had received 5055 Gy,while 10 had received 5675 Gy.

Preoperative disease restaging was based on the results ofbarium swallow, whole-bodycomputed tomography (CT) scanand oesophagoscopy in all patients. Patients with asupracarinal oesophageal tumour underwent routine fiber-optic bronchoscopy to rule out any invasion of thetracheobronchial tree. Nine of the patients received positronemission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose or integrated CT-PET for initial staging or preopera-tive restaging. Endoscopic ultrasonography (EUS) was carriedout in 22 patients with no attempt of fine needle aspiration(FNA), and was not feasible in 2. CT scan findings providedsome arguments in favour of the presence of an oesophagealtumour in 16 patients whereas EUS, when available,displayed in all cases a high suspicion of persistent orrecurrent disease. However, preoperative confirmation ofmalignancy was obtained histologically in 12 patients only(Table 2). Finally, indications for salvage surgery were asfollows: documented or suspected residual or recurrentdisease in 18 patients, and treatment-related local compli-cations in 6: intractable stenosis in 3, perforation in 2, andradiation-induced oesophagitis in 1.

The average time between salvage surgery and comple-tion of CRT was 74 days (range: 14240 days). Surgicaltechnique consisted of an en-bloc transthoracic oesopha-gectomy with two-field lymphadenectomy in all cases.According to the location of the tumour, 15 patients receivedan Ivor Lewis procedure (intrathoracic anastomosis) and 9 aMac Keown operation (cervical anastomosis). In all cases, agastric tube reconstruction was performed in the posteriormediastinum. Intrathoracic anastomoses were performedwith a circular stapler while cervical anastomoses were handfashioned. Pyloroplasty and feeding jejunostomy wereperformed routinely.

X.-B. DJourno et al. / European Journal of Cardio-thoracic Surgery 33 (2008) 111711231118

Table 1

Characteristics of the patients

Variables n %

Sex, F/M 6/18 25/75

Adenocarcinoma/squamous cell 8/16 33/66

Mac Keown/Ivor Lewis 9/15 37/63

Initial clinical stage

IIA 5 21

IIB 1 4

III 17 70

IVA 0 0

IVB 1 4

Mean SD

AGE 59 9

ASA score 2.4 0.6

NYHA score 2.2 0.6

Performance status 1.1 0.9

Body mass index 21 3.7

FEV1 (l) 2.5 0.9

FVC (l) 3.4 0.9

FEV1/FVC (%) 75 10

Hb (g/dl) 12.5 2

Mean and standard deviation are presented.FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; Hb: hae-

moglobin.


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Medical and surgical complications were recorded.Respiratory complications were defined by all medical eventsconcerning the lung parenchyma (i.e. pneumonia, airwaycongestion, atelectasis, acute lung injury, and acuterespiratory distress syndrome) in the absence of surgicalcomplications requiring reoperation. Surgical complicationsincluded anastomotic leakage, laryngeal paralysis, chy-lothorax, pleural effusion, empyema and bleeding. Earlymortality was checked 30 and 90 days after surgery.

All patients were seen at the outpatient clinic at intervalsof three months during the first two years and every sixmonths thereafter. Symptoms, body weight and imagingfindings were routinely recorded. A self-rated scale from 1(worse results) to 10 (best results) was used to assess thepatients digestive comfort. For patients lost to medicalfollow-up, missing survival data were obtained by consultingthe City Hall registry. Statistical analysis included the Mann-Whitney test, the Pearson x2 test, and Fishers exact testwhen appropriate. Overall survival was measured from thedate of operation and survivorship calculated according tothe KaplanMeier method, including the operative mortality.Disease-free survival was counted up to the date of firstrelapse or death with cancer. Software used included Excel(Microsoft Corporation, Redmond, Wash), and SPSS (SPSSInc., Chicago, Ill).

3. Results

3.1. Pathological findings

The absence of viable cancer cells was observed on theoperative specimen in 3 patients (12.5%). Three additionalpatients (12.5%) had no residual oesophageal tumour butpresented with invaded regional lymph nodes. A lungmetastatic disease was found intraoperatively in threepatients (stage yp IVB) and distant lymph node involvementwas found in two (stage yp IVA). A complete R0 resection wasachieved in 21 patients (87.5%). In all three cases ofincomplete resection, the tumour was located above thelevel of the carina (Table 4).

3.2. Mortality and morbidity

Thirty-day and 90-day mortality rates were 21% (n= 5) and25% (n= 6), respectively. Among the 6 patients who diedwithin 90 days, 3 were operated on for treatment-relatedlocal complications. There was a high rate of medicalcomplications (45%), and respiratory events appeared as themost common morbidity (41%). There was no significantdifference in early mortality according to the type of surgery:Thirty-day and 90-day mortality rates were 20% and 26%,respectively following Ivor Lewis operations, and 22% and

22%, respectively following Mac Keown operations. Mortalityand morbidity were related to the radiation dose (Table 3).Anastomotic leakage (p= 0.05) and cardiac failure (p= 0.05)were more common in patients who received more than55 Gy. In turn, median duration of stay in the intensive careunit (5 days vs 18 days,p= 0.005), length of hospital stay (22days vs 32 days, p= 0.03) and number of packed red bloodcells (1 unit vs 6 units, p = 0.02) were significantly higher inthis subset of patients. Thirty-day mortality rates were twiceas high in patients who received more than a 55 Gy radiationdose when compared to that of patients who received lowerdoses, but the difference did not reach statistical signifi-cance. Causes of early death were directly linked to surgeryin two patients (leakage), to respiratory complications inthree, and to cardiac failure in one.

3.3. Survival, recurrence and quality of life

Overall 5-year survival rate was 35%, with 4 patients alivemore than 3 years after the operation and 1 patient alivemore than 5 years after surgery (Fig. 1). Five year disease-free survival rate was 21%. With a median follow-up of 17months, 2 of the 18 patients who survived the operation diedfrom non-cancer-related causes. Eight patients experiencedcancer recurrences: one died from locoregional recurrenceand two from distant metastasis whereas the five remainingpatients were alive and concurrently treated for locoregional(n= 1) or distant relapse (n= 4). At last follow-up, eight

X.-B. DJourno et al. / European Journal of Cardio-thoracic Surgery 33 (2008) 11171123 1119

Table 2

Preoperative work up revaluation

CT scan, n = 24 Oesophagoscopy, n = 2 4 Histologica l documenta tion

(oesophageal biopsy), n = 23

Echoendoscopy,n = 22

No evidence of malignancy 8 (33%) 9 (37%) 11 negative (48%) 0

Features of malignancy 16 (66%) 15 (63%) 12 positive (52%) 22 (100%)

Table 3

Complications after salvage oesophagectomy

55 Gy,

n= 14

% >56 Gy,

n= 10

% p

Hospital mortality 2 14 3 30 0.61

Thirty-day mortality 2 14 3 30 0 .61

Ninety-day mortality 3 21 3 30 0.66

Medical complication 6 42 6 60 0 .68

Respiratory complication 4 28 6 60 0.21

Pneumonia 4 28 3 30 1

ARDS 2 14 2 20 1

Tracheotomy 2 14 5 50 0.08

Cardiac failure 0 0 3 30 0.05

Surgical complication 4 28 6 60 0.21

Pleural effusion 1 7 4 40 0.12

Anastomotic leakage 0 0 3 30 0 .05

Laryngeal paralysis 1 7 1 10 1

Chylothorax 2 14 0 0 0.49

Median Range Median Range

L eng th of hospital sta y (days) 2 2.5 1 7 4 32 .5 2 16 5 0. 03

Length of USI stay (days) 5 174 18.5 497 0.005

Packed red blood cells (units) 1 024 6 019 0.02

Statistical analysis included the Mann-Whitney test and Fishers exact test as

appropriate. Median and range are presented.


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patients were still alive and well. At univariate analysis, thelymph node status did not affect overall survival: mediansurvival time and 5-year survival rates were 21 months and32%, versus 27 months and 28% in ypN0 and ypN1 patients,respectively (p= 0.43). Accordingly, there was no differenceaccording to the disease stage when comparing stages yp Iand yp II to stages yp III and yp IV: median survival times and5-year survival rates were 29 months and 28% vs 27 monthsand 34%, respectively (p= 0.72). Best 5-year survival rates

were observed in case of complete R0 resections whencompared to that of R1R2 resections (36% vs 0%; p = 0.66)corresponding to median survival times of 27 months and 11months, respectively (Table 4).

3.4. Functional assessment

We looked specifically at the 13 long-term survivors (8 whowere free of disease,and 5 with disease) to assesstheir qualityof life at last follow-up. Two patients required repeatedendoscopic dilations. Eleven patients (84.6%) had a stable(variation within 10% of the preoperative value) or improved(>10%) body weight; whereas 2 patients lost more than 10% oftheir body weight. Eleven patients self-rated their digestivecomfort among whom 9 had a score exceeding 5/10 (82%).There was a clear although not significant difference betweenthose patients whowere free of disease (n= 7; 7 patients witha score higher than 5/10) and those who were not (n= 4; 2patients with a score higher than 5/10).

4. Discussion

Our results, combined to those of the available literature(Table 5), clearly show that salvage oesophagectomy is ahighly morbid operation, providing an early mortality rangingfrom 15% to 25% at 3 months. Two types of complicationsdominate the spectrum of postoperative adverse events:anastomotic fistulas and pulmonary complications.

The very high incidence of anastomotic leakage, exceedingbasically 25% in almost all series, is likely to be theconsequence of a fragile irradiated stomach and oesophagusand impaired blood supply. It seemed that the technique of theanastomosis by itself, stapled or hand-fashioned, didnot reallyinfluence the healing in this setting. Conversely, our teamrecently demonstrated that thoracic epidural analgesiaimproved the microcirculation of the gastric tube in the earlypostoesophagectomy period[14], and was associated with adecrease in occurrence of anastomotic leakage [15]. In thepresent study, the incidence of anastomotic failure was closelylinked to theoverall dose of radiation received, with no fistula


Fig. 1. Overall and disease-free survival curves, including operative mortality

(KaplanMeier method).

Table 4

Pathologic findings on resected specimen

Variable n %

Resection R0/R1R2 21/3 87/12

yp Stage

0 3 12

I 1 4

IIA 10 42

IIB 2 8

III 3 12

IVA 2 8

IVB 3 16

Table 5

Summary of the literature

Author Year Nb

Patients

Hi sto logy Chemo therapy Radi oth erapy

(mean) (Gy)

Delay (range

in months)

Complete pathological response

and R0 resections (%)

Meunier 1998 6 SCC 5FU- Platinum 60 317 0NA

Swisher 2002 13 SCC and ADK 5FU- Platinum 56.7 456 077.2

Nakamura 2004 27 SCC NS 60 115 1166.7

Tomimaru 2006 24 SCC 5FU- Platinum 62 125 45.866.7

Oki 2007 14 SCC 5FU- Platinum 64.6 134 050

Present series 2008 24 SCC and ADK 5FU- Platinum 56 0.58 12.587.5

Thirty-day

mortality (%)

Ninety-day

mortality (%)

Anastomotic

leak (%)

Respiratory

complications (%)

Five-year

survival (%)

Good functional

results (%)

0 16.7 33.3 33.3 0 66.7

15 NA 38 62 25 NA

3.7 NA 22.2 11.1 30 NA

4.2 12.5 20.8 20.8 33 NA

0 14.3 28.6 21.4 32 100

21 25 12.5 41 35 >80

SCC: squamous cell carcinoma; ADK: adenocarcinoma; Gy: gray; NA: not available.


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below 55 Gy. Even if this information is weakened by theretrospective nature of the study and the post hoc determina-tion of this cut-off value, it suggests at least that a promisingway to reduce this kind of complication is probably to bettertarget the tumour and the involved lymph nodes to decreasethe radiation doseadministered to surrounding normal tissues.Modern radiotherapy delivery nowadays relies on tridimen-sional, conformal techniques. Gold standard imaging modalityremains computed-tomography scanner. However, the intrin-sic lack of contrast between soft tissues leads to highvariabilities in target definition. The fusion of the differentimaging modalities, including positron emission tomographycould theoretically achieve this goal[16].

Severe pulmonary complications exceed 3040% in inci-dence commonly in this setting. Respiratory complicationsremain the major concern after oesophagectomy, with orwithout previous chemoradiation. Reasons for this pulmonarymorbidity are multifaceted, and those due specifically to theneoadjuvant treatment are probably very difficult to segre-gate from those due to the surgical procedure, to theperioperative anaesthetic management, to the patienthimself and to the toxicity of the preoperative treatment.However, concurrent CRT was shown to be associated withsignificant worsening of the diffusion capacity of the lung forcarbon monoxide (DLCO) [17]. In a recent retrospective study,dosimetric factors but not clinical factors were found to bestrongly associated with the incidence of postoperativepulmonary complications. The volume of the lung sparedfrom doses of 5 Gy and higher was the only independent factorin multivariate analysis[18]. As hypothesised for anastomoticcomplications, this suggests that restraining the radiationfields thus ensuring an adequate volume of lung unexposed toradiation might reduce the incidence of postoperativepulmonary complications.

Given the high risks associated with surgery in this setting,the question arises of which categories of patients canbenefit from such a hazardous operation. Our results suggestthat oesophagectomy should probably be avoided wheneverpossible in case of treatment-related local complicationssince 90-day mortality reached 50% in this patient group.Aside from these particular circumstances, one selectionapproach would be to avoid operating on patients without aproven residual or recurrent disease. Unfortunately, diag-nosis of complete pathological response by imaging is difficultand often possible merely by oesophageal resection. The onlyeasily reproducible modality for determination of response isendoscopic visualisation with biopsies of suspicious areas.Obviously, endoscopy alone cannot detect a viable diseaseconfined to the regional lymph nodes, a frequent event evenin the absence of any residual oesophageal tumour asdemonstrated by the present series. Endoscopy also failed toprovide conclusive tissue biopsies in 7 of the 18 patients (39%)in whom the analysis of the operative specimen found viablecells inside the oesophageal wall. The assessment oflocoregional tumour extension by EUS-FNA is thoughtcurrently the most reliable method. FDG PET guided EUSFNA is advocated in PET-positive nodes, particularly at thecoeliac region[19]. A recent study, however, demonstratedthat a complete absence of PETsignal cannot be equated witha complete pathological response: the accuracy of the 100%reduction in maximum standardised uptake value after

neoadjuvant treatment as a predictor of a completepathological response was only 15% [20]. When combiningimaging modalities with FDG PET, CT, and EUS it is notpossible to confirm the absence of residual viable disease inthe primary site in 2540% of the cases[21].

In most series, long-term survival reaches roughly 3035%at 5 years, a non-negligible rate in such a disastrous disease.Functional aspects of the surgical results are seldomaddressed. Even if our functional evaluation method wasapproximate, our data suggest that the quality of oral intakewas fair in more than 80% of the patients. Health-relatedquality of life seemed to be predominantly impaired byprogression of the disease. We found that the residual TNMwas not an accurate prognosticator although the smallnumber of patients precluded a comprehensive analysis ofsurvival. Basically, patients who may benefit most fromsurgery are those in whom a complete R0 resection could beperformed. Indeed, R0 resection can serve as an immediatesurrogate for outcome since patients who are left with grossor microscopic residual tumour will almost always diepromptly from progressive disease, as in our experience.The link between local recurrence and margin of normaltissue surrounding a resected cancer is well established. Incontrast with longitudinal clearance which is easily pre-dictable on the basis of both endoscopic inspection withLugols stain screening for a multifocal disease, and EUSexamination of the proximal oesophagus looking at sub-mucosal spreading, circumferential clearance is hard toanticipate. In the absence of serosa, there is no specificfascial boundary to circumferential spread of oesophagealcancer. In a prospective study, the finding of a tumour within1 mm of the circumferential margin of the fixed resectionspecimen of patients undergoing what would have beenregarded as a potentially curative resection was found as ahighly significant predictor of both local recurrence andsurvival[22]. The role of the surgeon should therefore be toresect the oesophagus with as wide a margin of uninterruptednormal tissue as possible around it. This goal is amenable inmost cancers located below the level of the carina, even incases of bulky tumours. In contrast, the upper and middleoesophagus is surrounded closely by vital structures thatcannot be resected en-bloc. EUS does not add to theestimation of locoregional respectability after RCT becauseof disorganising fibrotic sequelae at the level of the tumourand its surroundings [23]. We set up our decision to operateornot on the basis of CT scan and barium swallow findingsmainly, with a high suspicion index of unresectability in casesof lumen deviation, tumour height >5 cm, aortic contact>908, loss of the fat plane between tumour and neighbouringorgan, or tumour indenting neighbouring organ at CTscan, asthoroughly described after neoadjuvant CRT by Piessen et al.[24]. As a result, our 87.5% R0 resection rate comparesfavourably with those of the literature.

Nevertheless, our firm belief is that the indication forsalvage surgery should be limited to patients with an initiallyresectable tumour. Current treatment strategies for locallyadvanced cancers currently favour neoadjuvant chemother-apy or chemoradiotherapy followed by surgery for adeno-carcinomas, but chemoradiotherapy alone in patients withSCC who have shown a morphological response afterinduction treatment[25]. We want to add a word of caution



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concerning salvage oesophagectomy that should not beregarded as a routine rescue procedure in case of failure ofdefinitive CRT. In turn, indications for non-surgical treatmentstrategies should be decided on solid grounds, and reservedto those patients thoroughly investigated with EUS FNA andintegrated PET-scan, and presenting with a supracarinaloesophageal tumour deemed consensually to be non-resectable. We, as oesophageal surgeons inside a multi-disciplinary team, should be pivotal partners of the primarydecision to keep surgery or not in the treatment plan, as weare when a salvage surgery is evoked.

In conclusion, this study confirmed increased morbidityand mortality after salvage oesophagectomy performed afterdefinitive chemoradiation therapy. The increased risksseemedto be predominantly related to radiotherapy deliverymodalities, and the management of local treatment-relatedcomplications is indubitably the worse situation in which suchrisky operation may be performed. Nevertheless, somepatients were cured, and long-term survival appeared tobe associated primarily with R0 resection. These data suggestthat salvage oesophagectomy is an elective therapeuticoption for carefully selected patients at experienced referralcentres.

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Appendix A. Conference discussion

Dr R. Berrisford(Exeter, UK): I would just like to ask the audience to put

your hand upwhen youconsidera patient foroesophagectomy youuse this kind

of concept of salvage oesophagectomy (very few members of the audience

raised their hand). That is reassuring because in our MDTs we dont usually use

that concept. I was very interested to see that in your definition of these you

include patients who had chemotherapy who are node positive. We include

patients who are node positive after chemotherapy quite routinely but we

dont think that they aresalvage patients,maybewe shoulddo. So what do you

think your definition of salvage oesophagectomy should really include?



7/7

Dr DJourno: Thank you very much for your question. It is a problem of

definition. Firstly it is important to note that all these patients were initially

treated at an outside institutionso we didnt participatein the initial treatment

strategies. We included patients with a persistence or relapse of tumour after

definitivechemoradiotherapy. Webelieve thatin thisvery selected subgroupsof

patients, surgery provides the unique alternative option to rescue them from a

fatal issue. In fact there is no other possibility of treatment such as a palliative

chemotherapy. The unique curative option is just surgery.

The main result of our study is probably that morbidity and mortality were

related to volume of radiation. So when you propose a patient for a salvageoesophagectomy, maybe you have to look on the volume of radiation. For a

volumedose ofradiationup to 50 Gy, theoperative risk is probably prohibitive.

Dr J.Duffy(Nottingham, UK): Just looking at the group you operated on, 2

of them with an oesophageal perforation. Did they survive?

Dr DJourno: No.

Dr Duffy: So you are quite hard on yourself in your results. I am sure many

other series would have excluded the patients with oesophageal perforation.

The second question is, why did these patients have chemoradiotherapy as

opposedto surgery in thefirst place andwhy wasnt surgery partof that plan of

treatment?

Dr DJourno: I dont know because the treatment strategy was given at

another institution. We didntparticipatein the initialdiscussion.The patients

were referred to our hospital, maybe 3 or 6 months after completion of the

definitive chemoradiotherapy.Dr Duffy: In your 5-year survival are you including surgical mortality?

Dr DJourno: Yes, we included the operative mortality. But it is difficult to

draw some conclusions on long-term survival because its a very small series.


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