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Management algorithm for failed gastric pull up reconstruction of laryngopharyngectomy defects: case… Butskiy, Oleksandr; Anderson, Donald W; Prisman, Eitan Jul 22, 2016

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CASE REPORT Open AccessManagement algorithm for failed gastricpull up reconstruction oflaryngopharyngectomy defects: case reportand review of the literatureOleksandr Butskiy1,2* , Donald W. Anderson1 and Eitan Prisman1AbstractBackground: Gastric pull up remains a popular reconstructive option for pharyngoesophagectomy defects extendingto thoracic inlet. Gastric necrosis is a dreaded complication of gastric pull up reconstruction and few studies report onmanagement of this complication.MEDLINE, EMBASE, and Web of Science™ databases were searched for publications in the last 25 years ongastric pull up reconstruction following pharyngoesophagectomy. The rates of complications related togastropharyngeal anastomosis were extracted, and methods of managing gastric necrosis were noted.Forty seven case series were identified reporting on the use of gastric pull up for reconstruction ofpharyngoesophageal defects. Mortality rate varied from 0 to 33 % with a weighted average of 8.6 %. In 39 % ofpatients, mortality was either caused or directly related to failure of the gastropharyngeal anastomosis. Thereported rate of gastric necrosis ranged from 0 to 24 % resulting in a 28 % mortality. Options for managinggastric necrosis included: temporary cervical diversion, free jejunum flap, colonic interposition, tubed radialforearm flap, deltopectoralis and pectoralis myocutaneous flaps.Case presentation: We present the first case of an anterolateral thigh flap rescue of gastric necrosis after gastricpull up reconstruction. The case report is followed by a review of literature on management of gastric pull upfailures.Conclusion: Based on the extracted information, we propose an algorithm for managing gastric pull up failurefollowing pharyngoesophageal reconstruction.Keywords: Pharyngoesophagectomy, Gastric pull up, Anterolateral thigh, Head and neck cancer, Head and neckreconstructionBackgroundReconstructing circumferential pharyngoesophagectomydefects remains a challenging procedure for reconstruct-ive surgeons. Despite a multitude of vascularized freetissue transfers options popularized in the 1980s and1990s [1, 2], Gastric pull up (GPU) remains a popularchoice for pharyngoesophageal reconstruction. The robustblood supply offered by the gastric mucosa, requirementfor only one mucosal anastomosis, and lack of micro-vascular anastomosis are noted advantages of the GPU.Despite these advantages, a rare but critical complicationis proximal necrosis of the GPU leading to dehiscence atthe gastropharyngeal anastomosis. If not managedproperly, the dehiscence will result in mediastinitis,sepsis, and death. Thus, all reconstructive surgeons of-fering GPU reconstructions should be familiar with thesurgical management of this dreaded complication. Un-fortunately, the literature on this topic is scant [3]. Tothe best of our knowledge, we present the first case* Correspondence: butskiy.alex@gmail.com1Division of Otolaryngology – Head and Neck Surgery, Department ofSurgery, Vancouver General Hospital & University of British Columbia,Vancouver, BC, Canada2Gordon & Leslie Diamond Health Care Centre, 4th. Fl. 4299B-2775 LaurelStreet, Vancouver, BC V5Z 1M9, Canada© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (, which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( applies to the data made available in this article, unless otherwise stated.Butskiy et al. Journal of Otolaryngology - Head and Neck Surgery  (2016) 45:41 DOI 10.1186/s40463-016-0153-3report of an anterolateral thigh free flap (ALT) rescueof a failed GPU pharyngoesophageal reconstruction. Areview of the available literature and a management al-gorithm of gastro-pharyngeal anastomotic failure followingGPU pharyngoesophageal reconstruction are presented.Case presentationA 69-year-old male presented to the otolaryngology officewith complaints of right sided neck mass and otalgia. Hispast medical history was significant for 50 years of smoking,regular alcohol use, and colonic adenocarcinoma managedwith a colectomy several years prior. He was diagnosedwith T4aN2aM0 hypopharyngeal carcinoma involving theright pyriform sinus with a single 4 cm metastasis to theright level V. He was offered surgical resection followed byGPU reconstruction and planned adjuvant radiotherapy.Of note, during surgical planning, it was felt that themediastinal esophagus was likely not involved with thetumor. Thus, tumor resection was expected to producea circumferential pharyngeal defect extending into thecervical esophagus, but not the mediastinal esophagus.Faced with such a defect, to avoid the morbidity associ-ated with entering the abdominal cavity, many surgeonswould advocate for reconstruction with a tubed cutaneousfree flap rather than with the GPU [1]. However, at our in-stitution one of the authors (D.W.A) working alongsidethe thoracic surgery team has been able to achieve betterfunctional outcomes with the use of GPU as compared toreconstruction with tubed cutaneous free flaps. After care-ful consultation with the thoracic surgery team, a joint de-cision was made to pursue GPU reconstruction.A laryngopharyngectomy and right modified radicalneck dissection were performed without complication.Following the resection, the thoracic surgery team pro-ceeded with the esophagectomy and gastric mobilization.Gastric mobilization was hindered by intrabdominal adhe-sions related to the previous colectomy as well as dilatedgastric veins related to apparent liver cirrhosis. Neverthe-less, a well-vascularized and tensionless gastropharyngealanastomosis was attained and a jejunostomy tube inserted.Postoperatively, the patient was managed in the inten-sive care unit due to difficulty weaning from the ventila-tor. His early postoperative course was complicated bysepsis, and an anastomotic leak was considered despiteserosangouinous neck drains and no wound breakdown.He was managed conservatively with antibiotics untilpostoperative day 7, when he lost vacuum on the nega-tive pressure suction drain in the neck. Dehiscence wasconfirmed using a water-based dye.The patient was then taken to the operating room andfound to have circumferential necrosis of the proximalGPU extending inferiorly into the upper mediastinum(Fig. 1a). The necrosis was debrided until well-vascularizedgastric mucosa was reached. A large defect remained ex-tending from the distal oropharynx to the proximal super-ior mediastinum. The reconstructive options to re-establishthe continuity of the alimentary tract in this patient wereseverely limited. Due to the patient’s history of colonic re-section and recent gastric pull up, intra abdominal tissuetransfer, such as jejunal transfer or colonic interpositionwere not available. The two remaining options included avascularized free tissue transfer or creating a controlledpharyngeal fistula and over sewing the proximal stomach.A 20 cm by 15 cm elliptical ALT flap was chosen as thedonor free tissue transfer, and was folded on itself in conicaldesign to reconstruct a neopharynx (Fig. 1b).Postoperatively, the patient spent 22 days in the inten-sive care unit and another month in the hospital under-going rehabilitation and addressing psychosocial issues.His jejunostomy tube was removed prior to discharge ashe was supporting himself nutritionally with a pureeddiet. An endoscopic view of the ALT anastomosis onemonth post reconstructive surgery is shown in Fig. 2. Atfour months recovery he remains on an oral diet. Hislaryngostoma is shown in Fig. 3.Literature reviewWe searched MEDLINE, EMBASE, and Web of Science™databases for English language case reports and case seriesof GPU reconstruction following pharyngoesophagectomyFig. 1 a Circumferential necrosis of the stomach at the gastropharyngeal anastomosis. b Anterolatral thigh flap folded in a conical designButskiy et al. Journal of Otolaryngology - Head and Neck Surgery  (2016) 45:41 Page 2 of 9published from 1990 to 2014. From these studies we ex-tracted the rates of complications related to gastropharyn-geal anastomotic failure (fistula, anastomotic leak, gastricnecrosis, and anastomotic stricture) and the rates andcauses of in-hospital mortality (Table 1). In addition, wenoted how authors managed gastric necrosis (Table 2).Forty-seven studies were identified reporting on a totalof 1793 patients who were managed with gastric pull upfollowing pharyngoesophagectomy (Table 1). Mortalityrate was reported in 41 studies of 1469 patients. Mortalityrate varied from 0 % [4–13] to 33 % [14] with a weightedaverage of 8.6 % (129 patients). Complications of GPUreconstruction related to pharyngogastric anastomosiswere relatively common and varied greatly between thestudies. The cause of mortality was reported for 108 pa-tients. In 42 patients (39 %) death was either caused byor was directly related to the failure of gastropharyngealanastomosis.The rate of anastomotic leaks was reported to rangebetween 0 % [9] and 23 % [15]. A high index of suspi-cion for an anastomotic leak is required when faced withincreasing edema, erythema, or tenderness of the neckskin flaps that present with a rising white blood cellcount. Majority of authors treated asymptomatic andlimited leaks with a period of conservative managementincluding nasogastric nutrition and external drainage withvariable success. For example, in a retrospective review of208 patients, Shuangba et al. reported an anastomotic leakrate of 9 % (19 patients). With increased nutritionalsupport and conservative treatment, the anastomoticleak resolved in 15 of these patients. The remainder ofthe patients had a limited albeit persistent leak that re-quired repair with a pectoralis major rotation flap [16].Bardini et al. reported on 18 patients treated with con-servative measures for limited leaks. 14 patients weretreated successfully, but 4 patients died as a result ofthe anastomotic leaks [15]. Severe leaks were usuallytreated surgically. For example, Bardini et al. reportedon 4 severe leaks, one successfully managed with directreanastomosis, one with placement of a T tube throughthe defect to drain saliva and eventual skin flap repair,and two patients were managed by resuturing the pos-terior wall of the anastomosis while the anterior walland gastric margins were brought out to the skin [15].As compared to management of anastomotic leaks,where only a portion of the anastomosis has dehisced,fewer studies report on the management of circumferen-tial gastric necrosis following GPU reconstruction ofhypopharngeal defects (Tables 1 and 2). The reportedrate of gastric necrosis after GPU reconstruction ofhypopharyngeal defects ranged from 0 % [4, 9, 17–21] to24 % [22] (Table 1). 15 studies reported on both therate of gastric necrosis and causes of mortality. Out ofFig. 2 Endoscopic view of anastomosis one month following anterolateral thigh rescue of gastric pull up failure. a Pharyngo-cutaneous anastomosis.b cutaneo-gastric anastomosis. c gastric mucosa distant to the anterolateral thigh flap. ***base of the tongueFig. 3 Patient’s laryngostoma three months after the operationButskiy et al. Journal of Otolaryngology - Head and Neck Surgery  (2016) 45:41 Page 3 of 9Table 1 Mortality and gastropharyngeal anastomosis complications after pharyngo-esophagectomy and gastric pull upAuthor year Patients (N) Anastomotic leak Necrosis (%) Anastomotic stricture (%) In-hospital mortality (%) Cause of mortality (N)Mansour [4] -1990 6 1 (17 %) 0 0 0 –El-Naqeeb [5] -1990 24 1 (4 %) – – 0 –Mehta [30] -1990 75 10 (13 %) – – 7 (9 %) Pulmonary sepsis and respiratory failure (2);PE(1); carotid castrophe(1); MI (2); cirrhosis,ascites, septicemia (1)Spiro [31] -1991 120 15 (13 %) 5 (4 %) – 13 (11 %) Anastomotic leakage, tracheal injury, majorarterial bleeding (8); respiratory insufficiency (2);liver failure with sepsis (1); peritonitis after acutepseudomembranous colitis (1); multisystemfailure with massive intrapleural bleeding aftercentral venous line injury (1)Madsen [6] -1992 3 – – – 0 –Carlson [17] -1992 23 6 (26 %) 0 3 (13 %) 2 (9 %) Ruptured innominate artery after fistula formation(1); MI (1)Wight [32] -1992 16 3 (19 %) – – 2 (13 %) Cerebrovascular accident and later dehiscenceof the anterior part of the pharyngo-gastricanastomosis (1); fistula between trachea and thesubclavian artery (1)Marmuse [33] -1994 20 1 (5 %) – – 2 (10 %) MI (2)Cahow [34] -1994 59 2 (3 %) 1 (2 %) 4 (7 %) 3 (5 %) Thoracic duct injury with pneumothorax, MI, heartfailure, cardiogenic shock(1); pneumothorax,pneumonic sepsis, disseminated intravascularcoagulation, multiple organ failure (1); jejunostomytube displacement, peritonitis and sepsis (1)Laterza [35] -1994 49 2 (4 %) 2 (4 %) – 3 (6 %) –Yoshino [7] -1995 4 – – – 0 –Bardini [15] -1995 95 22 (23 %) 10 (11 %) – 14 (15 %) Anastomotic leak (5); gastric necrosis (4); other (5)Shenoy [36] -1996 105 15 (14 %) 10 (10 %) 0 16 (15 %) Intraoperative death due to injury to the posteriortracheal wall injury (1); pharyngocutaneous fistula(5); obsturctive pulmonary disease, pneumotitis orsepticemia (9)Axon [18] -1997 29 3 (10 %) 0 1 (3 %) 4 (14 %) –Azurin [19] -1997 19 1 (5 %) 0 2 (11 %) 1 (5 %) Intraoperatively discovered cirrhosis, anastomoticleak, acute liver failure, multiorgan failure (1)Al Ghamdi [37] -1998 15 6 (40 %) – 2 (13 %) 1 (7 %) Fistula leading to bronchopneumonia (1)Wei [38] -1998 69 6 (9 %) 1 (1 %) – 6 (9 %) Gastric fundus necrosis (1); chest infection andcardiac problems (2); recurrent tumor (2);cerbrovascular accident (1)Dudhat [39] -1999 60 5 (8 %) – 0 5 (8 %) Pulmonary sepsis (1); MI (2); carotid blow outsecondary to anastomotic leak (1); septicaemiarelated to anastomotic leak (1)Butskiyetal.JournalofOtolaryngology-HeadandNeckSurgery (2016) 45:41 Page4of9Table 1 Mortality and gastropharyngeal anastomosis complications after pharyngo-esophagectomy and gastric pull up (Continued)Hartley [40] -1999 41 1 (2 %) – – 3 (7 %) Bronchopneumonia (2); hemorrhage(1)Sullivan [41] -1999 32 10 (32 %) – – 4 (12 %) Multiorgan failure as a result of uncontrolled necksepsis due to anastomotic leak and fistula (2); PE(1); MI (1)Affleck [42] -2000 31 2 (6 %) – – 3 (10 %) –Martins [43] -2000 30 8 (27 %) 2 (7 %) – 6 (20 %) Innominate artery rupture (2); carotid artery rupture(1); pneumonia (1); cardiac arrhythmia (1); pulmpnaryembolus (1)Sagawa [44] -2000 6 1 (17 %) 1 (17 %) 0 1 (17 %) Gastric necrosis leading to arterial bleeding (1)Jones [45] -2001 50 1 (2 %) 4 (8 %) 1 (2 %) – –Triboulet [25]-2001 127 20 (16 %) 2 (2 %) 8 (6 %) – –Ullah [46] -2002 26 4 (15 %) – 5 (19 %) 3 (12 %) Pneumonia (1); congestive heart failure (1); PE (1)Wong [8] -2003 12 1 (8 %) – – 0 –Puttawibul [24]-2004 48 4 (8 %) 1 (2 %) – 1 (2 %) Fundal necrosis, localized infection and carotid arteryblow out(1)Rossi [9] -2005 4 0 0 0 0 –Clark [22] -2006 21 10 (48 %) 5 (24 %) 6 (29 %) –Llorente Pendas [14] -2006 12 6 (50 %) – – 4 (33 %) Cervical Fistual and Sepsis (2); subphrenic abscess (1);general deterioration and multiple organ failure (1)Pesko [20] -2006 29 5 (17 %) 0 – 3 (10 %) Anastomotic leak and systemic sepsis (3)Daiko [47] -2007 19 2 (11 %) 2 (11 %) – 2 (11 %) Necrosis of the stomach (1)Iseli [10] -2007 7 0 – 0 0 –Krdžalić [11] -2007 4 1 (25 %) – – 0 –Ferahkose [48] -2008 38 1 (3 %) 2 (5 %) 0 2 (5 %) Gastric necrsosis with sepsis (2)Keereweer [3] -2010 19 10 (53 %) 2 (11 %) – 3 (16 %) Gastric necrosis and respiratory failure (1); mediastinalhemorrhage (1); carotid blow out (1)Mansour [12] -2011 5 – – – 0 –Shuangba [16] -2011 208 19 (9 %) – 7 (3 %) 4 (2 %) Pneumonitis(1); heart failure(2); hemoperitoneum(1)Tong [49] -2011 70 4 (6 %) 3 (4 %) – 3 (4 %) Pneumonia (3)Camaioni [50] -2012 23 2 (9 %) – – 2 (9 %) –Sreehariprasad [51] - 2012 17 1 (6 %) – – 0 –Joshi [52] -2013 32 – 5 (16 %) – 6 (19 %) –Lambert [13] -2013 9 1 (11 %) – – 0 –Sayles [53] -2013 19 9 (47 %) – – – –Denewer [21] -2014 32 5 (16 %) 0 3 (9 %) – –Sun [54] -2014 48 4 (8 %) – – – –Butskiyetal.JournalofOtolaryngology-HeadandNeckSurgery (2016) 45:41 Page5of940 patients with gastric necrosis in these studies, 11 patientsdied – a rate of 28 %. Given that many studies werenot specific about the cause of death, this mortalityrate for gastric necrosis after GPU reconstruction islikely an underestimate. Options for rescuing failedGPU reconstruction included: temporary cervical di-version, free jejunum flap, colonic interposition, tubedradial forearm flap, deltopectoralis and pectoralis myo-cutaneous flaps (Table 2).DiscussionBased on the literature review and the presented case, adecision tree for managing suspected anastomotic leaksfollowing GPU reconstruction of pharyngo-esophagealdefects is presented (Fig. 4). This decision tree can alsobe used when considering rescue options for failed re-constructions other than GPU.A high index of suspicion is required to recognize ananastomotic leak early. Signs that point to a potentialTable 2 Rescue of gastric pull up necrosis following pharyngo-esophagectomyAuthor year Patients (N) Rescue method OutcomeBardini [15] -1995 10 8 patients: resection of the necrosis, temporary cervicaldiversion and delayed reanastomosis;1 patient: colonic interposition;1 patient: jejunal free transferFour deaths as a result of necrosisWei [38] -1998 1 Initially salvaged by controlled pharyngostomy and gastrotomy Carotid blow out and deathTriboulet [25] -2001 2 Temporary cervical diversion, tubed radial forearm flap –Temporary cervical diversion, deltopectoralis myocutaneous flap –Tong [49] -2011 3 Debridement of necrotic stomach and stagedreconstruction with pectoralis major myocutaneous flapSurvived– : no informationSuspected anastomotic leakBrief trial of conservative management Clinical resolution of the leak confirmed radiologicallyLimited gastric necrosis:1. Debridement and primary closure2. Pectoralis or Deltopectoralis myocutaneous flap3. Microvascular reconstruction using cutaneous flapsCircumferential gastric necrosisMicrovascular reconstructionpreferred:1. Anteriolateral Thigh Free Flap2. Radial Forearm Free Flap3. Free Jejunal TransferMicrovascular reconstruction not possible:1. Colonic Interposition2. Deltopectoralis Myocutaneous Flap3. Wookey ProcedureOperative explorationClinical failure to resolve the leak Resection followed by reconstruction Resection followed by diversionDelayed attempt to reconstruct alimentary continuityFig. 4 A decision tree for managing suspected anastomotic leaks following gastric pull up reconstruction after pharyngoesophagectomy. Decisionsmade in the case report are highlighted in boldButskiy et al. Journal of Otolaryngology - Head and Neck Surgery  (2016) 45:41 Page 6 of 9anastomotic leak are edema, erythema, or tenderness ofthe neck skin flaps that present with a rising white bloodcell count [23]. In the majority of cases, a suspectedanastomotic leak can initially be managed conservativelywith supportive care including nutritional support, anti-biotic therapy, local wound packing and close observa-tion [16]. Clinical judgment is required to decide on thelength of conservative treatment, as prolonged exposureof neck structures or mediastinum to gastric secretionscan lead to devastating consequences such as carotidblow out [24]. Once a trial of conservative treatment hasfailed, the patient has to be taken to the operating roomfor definitive management.Prior to entering the operating room, it is helpful toconsider various reconstructive options available for thepatient. The reconstructive options will be dictated by thedegree of anastomotic necrosis. The majority of anasto-motic leaks result from limited areas of gastric necrosisand subsequent dehiscence [16]. After thorough debride-ment of devitalized tissue, most of the small defects caneither be closed primarily or with local myocutaneousflaps [16].A more challenging scenario is circumferential necrosisat the anastomotic site. In these situations, we advocatefor the use of distant flaps and microvascular reconstruc-tion. For some patients, however, microvascular recon-structive techniques are not possible. This could be due toa lack of healthy donor vessels, hemodynamic instability,or lack of available microvascular expertise. In thesechallenging scenarios, the options for reconstructionwould include colonic interposition [15], deltopectoralismyocutaneous flap [25], Wookey procedure [26] orstoma diversion with delayed reconstruction [2].If microvascular reconstruction is possible, the freetissue donor sites can be further divided as intra-abdominal versus extra-abdominal. The choice of thedonor flap will depend on the length of the defect, theavailable vasculature, and the experience of the recon-structive surgeon. Intra-abdominal based free jejunaltransfer are ideal for reconstructing long segments ofesophagus as it provides peristalsis that later helps withswallowing [2]. However, in the setting of GPU rescue,we recommend against the use of intraabdominal flaps,which necessitate re-entery into a postoperative abdominalcavity. Other disadvantages include restricted trachea-esophageal voice and lower maximal dose of post operativeradiation therapy [27, 28]. In the presented case, anextra-abdominal flap was selected as the patient hadintra-abdominal adhesion, liver cirrhosis, and a remotecolectomy. In the presented case, the ALT proved to bea robust flap for reestablishing alimentary continuity.The ALT flap has been shown to provide up to 40 cmof length for esophageal reconstruction, especially whenfolded in a conical fashion [2, 29]. Radial forearm freeflap is an alternative for extra-abdominal free tissuetransfer.Any flow diagram or a decision tree is an over simplifi-cation of what is often a complex series of clinical deci-sions. Much depends on expert clinical judgment honedby years of clinical experience and availability of expertisein various reconstruction options. Nevertheless, as il-lustrated by the presented case, a general frameworkfor making decisions serves as a helpful starting pointin challenging cases.ConclusionsTo the best of our knowledge, the presented case is thefirst ALT rescue of a failed GPU pharyngoesophageal re-construction. The review of literature suggests that ALTreconstruction of the failed GPU should be one of thereconstructive options considered in the challengingcases of circumferential gastric necrosis.AbbreviationsALT: Anterolateral Thigh Free Flap; GPU: Gastric Pull Up.AcknowledgementsThis research was not funded or supported by grant money.FundingAuthors of the presented report have not received any finding for their workon the report.Availability of data and materialsThe data described in the case report can be found in the records of theVancouver Coastal Health (Vancouver, BC, Canada).Authors’ contributionsThe patient described in the case is the patient of DWA and EP. OB, DWA,and EP conceived the report. OB wrote the report, and DWA and EP editedthe manuscript. All authors read and approved the final manuscript.Authors’ informationDWA – Clinical Professor, Active Staff, Vancouver General Hospital, SpecialInterest: Head and Neck Oncology and Reconstructive SurgeryEP – Clinical Assistant Professor, Active Staff, Vancouver General Hospital,Special Interest: Head and Neck Oncology and Reconstructive SurgeryCompeting interestsThe authors declare that they have no competing interests.Consent for publicationPatient provided informed consent for publication of the case report. Editor-in-chief will be provided with a copy of the consent upon request at anytime.Ethics approval and consent to participateNot applicable.DisclosuresThis manuscript is the original work of the authors. This work was notsupported by grant money, and the findings have not been presented atscientific meetings. The authors declare that they have no conflicts of interest.Received: 13 March 2016 Accepted: 22 June 2016References1. Chan JYW, Wei WI. 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Joshi P, Nair S, Chaturvedi P, Chaukar D, Pai P, Agarwal JP, D’Cruz AK.Hypopharyngeal cancers requiring reconstruction: a single instituteexperience. Indian J Otolaryngol Head Neck Surg. 2013;65:S135–9.53. Abstracts presented at the Laryngology and Rhinology Section Meetings,Royal Society of Medicine, 2 March 2012 and 1 February 2013, London, UK.J. Laryngol. Otol. 2014;128:e2 (4 pages).54. Sun F, Li X, Lei D, Jin T, Liu D, Zhao H, Yang Q, Li G, Pan X. Surgicalmanagement of cervical esophageal carcinoma with larynx preservationand reconstruction. Int J Clin Exp Med. 2014;7:2771–8.•  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript your next manuscript to BioMed Central and we will help you at every step:Butskiy et al. 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