Intraoperative Endoscopic Botox Injection During Total Esophagectomy Prevents the Need for Pyloromyotomy or Dilatation

Abstract

Background:

Esophagectomy may lead to impairment in gastric emptying unless pyloric drainage is performed. Pyloric drainage may be technically challenging during minimally invasive esophagectomy and can add morbidity. We sought to determine the effectiveness of intraoperative endoscopic injection of botulinum toxin into the pylorus during robotic-assisted esophagectomy as an alternative to surgical pyloric drainage.

Materials and Methods:

We performed a retrospective analysis of patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus or gastroesophageal junction who underwent robotic-assisted transhiatal esophagectomy (RATE) without any surgical pyloric drainage. Patients with and without intraoperative endoscopic injection of 200 units of botulinum toxin in 10 cc of saline (BOTOX group) were compared to those that did not receive any pyloric drainage (noBOTOX group). Main outcome measure was the incidence of postoperative pyloric stenosis; secondary outcomes included operative and oncologic parameters, length of stay (LOS), morbidity, and mortality.

Results:

From November 2006 to August 2014, 41 patients (6 females) with a mean age of 65 years underwent RATE without surgical drainage of the pylorus. There were 14 patients in the BOTOX group and 27 patients in the noBOTOX group. Mean operative time was not different between the comparison groups. There was one conversion to open surgery in the BOTOX group. No pyloric dysfunction occurred in the BOTOX group postoperatively, and eight stenoses in the noBOTOX group (30%) required endoscopic therapy (P < .05). There were no differences in incidence of anastomotic strictures or anastomotic leaks. One patient in group noBOTOX required pyloroplasty 3 months after esophagectomy. There was one death in the noBOTOX group postoperatively (30-day mortality 2.4%). Mean LOS was 9.6 days, and BOTOX patients were discharged earlier (7.4 versus 10.7, P < .05).

Conclusion:

Intraoperative endoscopic injection of botulinum toxin into the pylorus during RATE is feasible, safe, and effective and can prevent the need for pyloromyotomy.

Introduction

Esophagectomy is the treatment of choice for most stages of esophageal cancer. While mucosal carcinomas can be resected endoscopically in specialized centers, more advanced cT1b and cT2NxM0 cancers should be treated with esophageal resection.^1–4 Locally advanced esophageal cancer (cT3 and resectable cT4) should be treated with esophagectomy in a multimodal setting or with definitive chemoradiation in selected cases.^4–6 Esophagectomy is considered a high-risk procedure although improvements in surgical techniques and perioperative management contributed to minimizing postoperative morbidity and mortality, such that mortality in large cohorts is <2% in specialized centers. ^7–11 Several studies demonstrated the feasibility and safety of minimally invasive techniques that can be applied to esophageal resection with gastric reconstruction.^11–15 These reports suggest that these techniques can lower the incidence of postoperative pulmonary complications and, thereby, decrease length of stay (LOS).

Robotic-assisted transhiatal esophagectomy (RATE) was first described in 2003.¹⁶ Since its introduction, several small series and case reports of RATE combined with thoracosopic and laparoscopic approaches have been reported.^17–20 Recently, larger case series were published by Dunn et al. and our institution, showing that RATE is a feasible but still evolving oncologic operation with low rates of complications and low hospital mortality.^13,21

Many centers perform a pyloric drainage procedure to help prevent delayed emptying of the gastric conduit following esophagectomy. Delayed emptying can be associated with an increased incidence of mortality or complications requiring an increased LOS. However, it remains unclear if pyloric drainage improves outcomes after esophagectomy, and if so, what technique should be favored.²² Intraoperative laparoscopic botulinum toxin (botox) injection into the pylorus was first proposed in 2007 in a case series, and none of the 12 patients developed gastric outlet obstruction.²³ To our knowledge, botox has only been applied extraluminally during esophagectomy in existing publications, and the type of surgery (open, minimally invasive, transthoracic, and transhiatal) was not standardized.^23–25

We sought to review our own institution's data on patients who underwent RATE to compare those who had intraoperative endoscopic botox injection into the pylorus with those who did not. Our hypothesis is that endoscopic botox injection is feasible, safe, and decreases the incidence of postoperative pyloric dysfunction and delayed gastric emptying.

Material and Methods

Patients

A retrospective review of an ongoing prospective series of patients who underwent surgery between November 2006 and August 2014 was performed. The study was conducted with approval from the Institutional Review Board at the University of California, San Diego. Patients who underwent RATE for adenocarcinoma and squamous cell carcinoma of the distal esophagus or gastroesophageal junction without any surgical pyloric drainage were included in this study. Patients were divided into two groups as follows: group BOTOX underwent intraoperative endoscopic botox injection (as described below) and group noBOTOX had no injection. Each patient underwent preoperative workup, including endoscopic ultrasound to assess depth of tumor penetration and presence of lymph node metastases. A computed tomography scan and positron emission tomography scan of the chest and abdomen were also obtained to exclude the presence of metastatic disease. Intraoperatively, a diagnostic laparoscopy was performed before starting the procedure to confirm the lack of carcinomatosis or occult liver metastases not detected on preoperative imaging.

Intraoperative intraluminal endoscopic botulinum toxin injection and surgical procedure

Our procedure was slightly modified since our last report on RATE.¹³ The patients were placed in a supine split-leg position. Intraluminal pyloric injection was performed using 200 U of botulinum toxin in 10 mL of normal saline using a sclerotherapy needle. Each injection was equally distributed into 50 units per injection in four separate quadrants (Fig. 1). Subsequently, a 12-mm trocar was placed in the left upper quadrant, just left of the midline. Two 8-mm robotic trocars were placed in the left and right upper quadrants, and an 8-mm assistant port was placed in a left lateral position. Another 5-mm port can be inserted on the left lateral side for suction/irrigation if needed. Port placement is depicted in Figure 2. The initial mobilization and dissection were carried out laparoscopically with the patient in a reverse Trendelenburg position. The short gastric vessels were ligated using an ultrasonic scalpel. Careful dissection of the gastroepiploic artery preserved the blood supply to the neo-esophagus while allowing sufficient length for the gastric pull-up. A complete crural dissection was performed with a combination of blunt dissection and ultrasonic scalpel. A Penrose drain placed around the distal esophagus allows an assistant to provide critical traction during the procedure. With the stomach retracted superiorly, the left gastric artery was identified and divided with a stapler at its base.

FIG. 1.

Endoscopic Botox Injection using a sclerotherapy needle.

FIG. 2.

Port placement.

The robotic patient cart was then docked, and a circumferential dissection of the esophagus carried out through transhiatal access. The articulated robotic instruments and three-dimensional robotic camera allow near-complete dissection of the mediastinal esophagus through transhiatal access without thoracoscopy. Care was taken to include all periesophageal tissue, fat, and the contained lymph nodes. Small single defects in the pleura were approximated using polymer vascular clips or silk suture if possible. Chest tubes were not routinely placed at the time of surgery and reserved only for cases, in which patients develop postoperative symptomatic pleural effusions. The esophagus was completely mobilized to the level of the azygous vein to the right with clear visualization of the aorta on the left (Fig. 3).

FIG. 3.

Intraoperative view inside mediastinum (azygos vein, aorta, esophagus, as depicted in screenshot; davinci xi^® robotic system).

Following this, a left neck incision was performed to access the cervical esophagus while taking care to preserve the recurrent laryngeal nerve. Laparoscopically, the stomach was then divided along the lesser curvature to create a tube measuring ∼6 cm in width. The distal extent of the gastric transection was determined by intraoperative endoscopy. Staple loads are routinely reinforced with a biocompatible fibrin copolymer. We did not perform a pyloromyotomy or pyloroplasty in this collective nor did we place a jejunostomy feeding tube. Once the gastric conduit was completely freed from the esophageal and proximal stomach specimen, the specimen was sutured to the conduit to assist in pull-up through the mediastinum and to prevent twisting. A proximal ligation of the esophagus was completed and the specimen removed. A gastroesophageal stapled anastomosis was performed in a side-to-side manner through the left neck incision and an NG tube is placed under direct visualization before closure of the anastomosis.

Postoperative care

Patients were extubated in the operating room and transferred to the intensive care unit for continued care. The nasogastric tube was left in place postoperatively for 2–3 days, depending on output. All patients then completed a contrast swallow study, and if no evidence of extravasation was noted at the anastomotic site, they were advanced to a liquid diet. Delayed gastric emptying was diagnosed clinically if persistent nausea and vomiting was present and confirmed with a contrast swallow study. Pyloric dysfunction was only diagnosed when confirmed endoscopically and required intervention. This definition is consistent with the most recent meta-analysis of the topic.²² Following discharge, patients were followed up in the clinic by an oncologic surgeon. Routine imaging was obtained on a regular basis to evaluate for recurrence or disease progression. Upper endoscopy and a swallow study were performed for any patient complaining of dysphagia or extensive nausea and vomiting.

Data collection and statistical analysis

Data were collected prospectively, including but not limited to, patient demographics, operative and oncologic parameters, conversions, intraoperative complications, postoperative complications, readmissions, length of hospital stay, mortality, and reoperations. Our main outcome measure was the incidence of a postoperative pyloric stenosis. Continuous variables are presented as mean and range. Categorical data were presented as numbers and percentages. The Student's t-test (for continuous variables) and Chi Square test (for nominal or categorical variables) were used for all bivariate analyses. All tests were two sided, with statistical significance set at P ≤ .05. Data were analyzed by Stata 11.0 (StataCorp., College Station, TX).

Results

Forty-one patients (6 females) with a median age of 65 years (range, 40–81 years) underwent RATE without any surgical drainage of the pylorus. Ninety percent of patients underwent neoadjuvant chemoradiation. One patient underwent neoadjuvant chemotherapy without radiation. Three patients with early stage disease went straight to surgery. The majority of patients had adenocarcinoma and high perioperative risk defined by ASA classification.

Fourteen patients underwent intraoperative endoscopic injection of botox (BOTOX group) and 27 did not receive any pyloric drainage (noBOTOX group). Botox injection was feasible in all subjects with intention to treat. Patient demographics and oncologic data are summarized in Tables 1 and 2 with no differences between the two groups. The median lymph node yield was 16 (range, 5–29), and surgical margins were negative for cancer in 40 cases (98%). Nine patients (24.3%) had a complete response (T0N0M0) to neoadjuvant therapy. Median operative time was 210 minutes (range, 181–272) in the BOTOX group and 239 minutes in the noBOTOX group (range, 179–319). This difference was not statistically significant, as one outlier in the noBOTOX group prolonged the median operation room time for this cohort. Blood loss was comparable with 101 mL (range, 25–400, BOTOX) and 118 mL (range, 20–250, noBOTOX). There was one conversion to open surgery in the BOTOX group that was unrelated to the injection of botox.

Table 1.

Demographic Information

Patient demographics
Patients, No.	41
Sex, No. (%)
Women	6 (15)
Men	35 (85)
Age, mean [range], year	65 [40–81]
ASA score, mean [range]	3.0 [2–4]
Body mass index, mean [range]	25 [18–34]

Table 2.

Oncologic Patient Parameters

Oncologic data
Adenocarcinoma [n (%)]	40 (97.6)
R0 Resection [n (%)]	40 (97.6)
Number of resected lymphnodes [mean (range)]	16 (5–29)
Pathological tumor stage [n (%)]
Complete response	9 (22)
T0N1	2 (5)
T1N0	9 (22)
T2N0	6 (15)
T2N1	3 (7)
T2N2	1 (2)
T3N0	8 (20)
T3N1	1 (2)
T3N2	1 (2)
T3N3	1 (2)

Mean follow-up of the patients was 12 months (range, 6–45). No pyloric stenoses occurred in the BOTOX group postoperatively, while eight occurred in the noBOTOX group (30%) and required endoscopic therapy (P < .05). Otherwise, there were no differences in the incidence of complications such as anastomotic strictures, pulmonary and cardiac complications, and anastomotic leaks. The overall leak rate was 9.8%. One patient in the noBOTOX group required pyloroplasty 3 months after esophagectomy due to failed resolution of the pyloric dysfunction with endoscopic treatment. One patient died from pulmonary failure 21 days after surgery in the noBOTOX group (overall 30-day mortality rate for the entire collective: 2.4%). Patients after botox injection started with oral feeding more than 2 days before patients in the noBOTOX group (start of liquid diet 5.5 versus 7.9 days, P < .05). The overall median LOS was 9.6 days (range, 6–37) and was lower in the BOTOX group (7.4 versus 10.7, P < .05). Detailed postoperative data are summarized in Table 3.

Table 3.

Postoperative Information and Group Comparison

Postoperative data by group
	noBOTOX	BOTOX	P
Start of liquid diet, days	7.9 (4–35)	5.5 (3–14)	<0.05
LOS (range), days	10.4 (7–21)	7.4 (6–11)	<0.05
Cardiac complications
Atrial fibrillation	4 (15)	2 (14)	ns
Surgical complications
Pyloric dysfunction	8 (30)	0	<0.05
Anastomotic leak	2 (7)	2 (14)	ns
Anastomotic stricture	7 (26)	3 (21)	ns
Pulmonary complications
Pneumonia	2 (7)	0	ns
Pulmonary embolism	1 (4)	0	ns
Mortality
In hospital	1 (4)	0	ns
30 days	0	0	ns

LOS, length of stay; BOTOX, botulinum toxin.

Discussion

Pyloric drainage is believed to reduce complications from gastric stasis and anastomotic stress applied by stagnant content resulting in a reduced morbidity such as anastomotic leaks.²² In the current study, we found that pyloric drainage due to intraoperative endoscopic botox injection reduced the postoperative incidence of pyloric stenoses to 0% and that patients could be discharged significantly earlier than those who did not have botox injection. Although we did not demonstrate that botox injection leads to a lower incidence of leaks, we feel that the significantly reduced need for postoperative interventions is remarkable. Similarly, Arya et al. were unable to prove a correlation of leak rates and pyloric drainage in their very recent systematic review of 2206 cases containing 30 years of data, confirming the results of an older meta-analysis.^22,26 Pulmonary complications and gastric emptying were also not significantly influenced. The only advantage of intraoperative pyloric drainage might be the reduced need of postoperative interventions. And even if our results are limited by a rather small sample size, we believe that it is worthwhile to add a minimal endoscopic intervention to the whole procedure, especially in the context of impaired postoperative quality of life for esophageal cancer patients.²⁷

The role of botulinum toxin as an agent for pyloric drainage is a source of controversy in literature.^22,23–25 While Eldaif et al. reported negative experiences such as increased incidence of reintervention (pyloric and esophageal dilatations) after botox, none of our botox group patients underwent postoperative reinterventions.²⁵ It is possible that the variation in surgical approach for esophagectomy also played a role in their collective. Our results support the findings of the pilot study and of Martin et al. for pyloric botox injection with no patients suffering from postoperative gastric outlet obstruction.^23,24 Our novel method of intraoperative intraluminal botox treatment compared to extraluminal treatment in existing studies may also play a role for our results, as the anatomical definition of the pylorus might be more easily identified endoscopically. Our technique has only been described in a postoperative setting before.²² Other types of intraoperative pyloric drainage such as pyloromyotomy, pyloroplasty, and finger fracture technique have been proposed in the past, but a systemic review showed that postoperative leak rates tend to be lowest in patients undergoing intraoperative pyloric botox treatment.²² With no procedure showing evidence to be superior, we propose intraoperative endoscopic botox injection as the optimal strategy, adding the smallest risk and the shortest amount of time to the operation with the benefit of fewer postoperative interventions. Botox, usually lasting for 3 months, perfectly bridges in the early postoperative phase, where delayed gastric emptying is a huge problem. We do not expect problems after botox wears out, as the intrinsic gastric motor activity usually recovers despite the division of the vagus nerves over time.²³

Robotic technology is relatively new in esophageal cancer surgery, and the technique has been adapted in different international centers since our first report in 2003.^17–21,28 The learning curve in robotic cancer surgery is reported between 20 and 25 cases, suggesting our results should not be impacted by trends in learning curve in contrast to Dunn's experience from 2013^21,29,30: operative time did not differ significantly when analyzed over the study period and the only change in technique was the addition of endoscopic pyloric Botox injection. Nevertheless, RATE remains an emerging operation. Our latest experience underlines that RATE can be performed with minimal blood loss, similar complications, and shorter LOS compared to open or other minimally invasive procedures. Different types of minimally invasive esophagectomy have been reported in last decade, with the major trade-off being oncologic radicalness versus perioperative morbidity.^14,31,32 We achieved a median lymph node retrieval of 16 nodes in our collective of patients that was mainly treated with neoadjuvant chemoradiation, a factor influencing node retrieval. This meets the current National Comprehensive Cancer Network guidelines, but due to sample size, we are unable to make any clear oncologic conclusions or comparisons to larger minimally invasive series for esophagectomy.³³

Our findings are limited by the retrospective design and limited sample size of our study. Based on our sample size, no clear recommendations can be made and our conclusions may be limited. Despite limitations, our study has unique features. Most important for the purpose of the present trial is the fact that we provide a consistent patient population undergoing one single standardized procedure only performed by two experienced surgeons at a single institution. Existing studies on intraoperative pyloric drainage included various types of esophagectomies, which can obviously be a confounding factor.²² Our standardized operative approach and the novelty of our intraoperative endoscopic approach for botox injection comprise the major strengths of our study. We present the largest series of RATE for cancer in literature with minimal mortality, morbidity, and LOS.

Conclusion

This study demonstrates that intraoperative endoscopic botox injection during RATE is feasible, safe, and reproducible. This novel method for pyloric drainage may minimize the need for postoperative therapeutic interventions for delayed gastric emptying. Therefore, endoscopic pyloric botox injection during esophagectomy should be performed on a routine basis. The question of whether pyloric drainage prevents complications such as anastomotic leaks remains unanswered.

Footnotes

Disclosure Statement

No competing financial interests exist.

References

Pech

, Bollschweiler

, Manner

, Leers

, Ell

, Hölscher

. Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett's esophagus at two high-volume centers. Ann Surg, 2011; 254:67–72.

Pech

, Manner

, Ell

, Bollschweiler

, Hölscher

. Reply to letter: For patients with early esophageal cancer endoscopic mucosa resection is not the end of the story!. Ann Surg, 2013; 257:e22–e23.

Metzger

, Lorenz

, Gockel

, Origer

, Plum

, Junginger

, Drebber

, Hansen

, Krümpelmann

, Fisseler-Eckhoff

, Lang

, Hölscher

, Bollschweiler

. pT2 Adenocarcinoma of the Esophagus: Early or advanced cancer?. Ann Thorac Surg, 2013; 96:1840–1845.

Fuchs

, Hölscher

. Therapeutic decisions in patients with operable, non-metastatic oesophageal cancer. Zentralbl Chir, 2014; 139:32–36.

Hölscher

, Bollschweiler

, Bogoevski

, Schmidt

, Semrau

, Izbicki

. Prognostic impact of neoadjuvant chemoradiation in cT3 oesophageal cancer—a propensity score matched analysis. Eur J Cancer, 2014; 50:2950–2957.

van Hagen

, Hulshof

, van Lanschot

, Steyerberg

, van Berge Henegouwen

, Wijnhoven

, Richel

, Nieuwenhuijzen

, Hospers

, Bonenkamp

, Cuesta

, Blaisse

, Busch

, ten Kate

, Creemers

, Punt

, Plukker

, Verheul

, Spillenaar Bilgen

, van Dekken

, van der Sangen

, Rozema

, Biermann

, Beukema

, Piet

, van Rij

, Reinders

, Tilanus

, van der Gaast A

. OSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med, 2012; 366:2074–2084.

Ando

, Ozawa

, Kitagawa

, Shinozawa

, Kitajima

. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg, 2000; 232:225–232.

Igaki

, Tachimori

, Kato

. Improved survival for patients with upper and/or middle mediastinal lymph node metastasis of squamous cell carcinoma of the lower thoracic esophagus treated with 3-field dissection. Ann Surg, 2004; 239:483–490.

Mariette

, Taillier

, Van Seuningen

, Triboulet

. Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma. Ann Thorac Surg, 2004; 78:1177–1183.

10.

Law

, Wong

, Kwok

, Chu

, Wong

. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg, 2004; 240:791–800.

11.

Luketich

, Pennathur

, Awais

, Levy

, Keeley

, Shende

, Christie

, Weksler

, Landreneau

, Abbas

, Schuchert

, Nason

. Outcomes after minimally invasive esophagectomy: Review of over 1000 patients. Ann Surg, 2012; 256:95–103.

12.

Osugi

, Takemura

, Higashino

, Takada

, Lee

, Kinoshita

. A comparison of video-assisted thoracoscopic oesophagectomy and radical lymph node dissection for squamous cell cancer of the oesophagus with open operation. Br J Surg, 2003; 90:108–113.

13.

Coker

, Barajas-Gamboa

, Cheverie

, Jacobsen

, Sandler

, Talamini

, Bouvet

, Horgan

. Outcomes of robotic-assisted transhiatal esophagectomy for esophageal cancer after neoadjuvant chemoradiation. J Laparoendosc Adv Surg Tech A, 2014; 24:89–94.

14.

Zhang

, Wang

, Liu

, Luketich

, Chen

, Schuchert

. Refinement of minimally invasive esophagectomy techniques after 15 years of experience. J Gastrointest Surg, 2012; 16:1768–1774.

15.

Schröder

, Hölscher

, Bludau

, Vallböhmer

, Bollschweiler

, Gutschow

. Ivor-Lewis esophagectomy with and without laparoscopic conditioning of the gastric conduit. World J Surg, 2010; 34:738–743.

16.

Horgan

, Berger

, Elli

, Espat

. Robotic-assisted minimally invasive transhiatal esophagectomy. Am Surg, 2003; 69:624–626.

17.

van Hillegersberg

, Boone

, Draaisma

, Broeders

, Giezeman

, Borel Rinkes

ICH

. First experience with robot-assisted thoracoscopic esophagolymphadenectomy for esophageal cancer. Surg Endosc, 2006; 20:1435–1439.

18.

Kernstine

, DeArmond

, Shamoun

, Campos

. The first series of completely robotic esophagectomies with three-field lymphadenectomy: Initial experience. Surg Endosc, 2007; 21:2285–2292.

19.

Patriti

, Ceccarelli

, Ceribelli

, Bartoli

, Spaziani

, Cisano

, Cigliano

, Casciola

. Robot-assisted laparoscopic management of cardia carcinoma according to Siewert recommendations. Int J Med Robot, 2011; 7:170–177.

20.

Mori

, Yamagata

, Wada

, Shimizu

, Nomura

, Seto

. Robotic-assisted totally transhiatal lymphadenectomy in the middle mediastinum for esophageal cancer. J Robot Surg, 2013; 7:385–387.

21.

Dunn

, Johnson

, Morphew

, Dilworth

, Krueger

, Banerji

. Robot-assisted transhiatal esophagectomy: A 3-year single-center experience. Dis Esophagus, 2013; 26:159–166.

22.

Arya

, Markar

, Karthikesalingam

, Hanna

. The impact of pyloric drainage on clinical outcome following esophagectomy: A systematic review. Dis Esophagus, 2015; 28:326–335.

23.

Kent

, Pennathur

, Fabian

, McKelvey

, Schuchert

, Luketich

, Landreneau

. A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Surg Endosc, 2007; 21:754–757.

24.

Martin

, Federico

, McKelvey

, Kent

, Fabian

. Prevention of delayed gastric emptying after esophagectomy: A single center's experience with botulinum toxin. Ann Thorac Surg, 2009; 87:1708–1713; discussion 1713–1714.

25.

Eldaif

, Lee

, Adams

, Kilgo

, Gruszynski

, Force

, Pickens

, Fernandez

, Luu

, Miller

. Intrapyloric botulinum injection increases postoperative esophagectomy complications. Ann Thorac Surg, 2014; 97:1959–1964; discussion 1964–1965.

26.

Urschel

, Blewett

, Young

, Miller

, Bennett

. Pyloric drainage (pyloroplasty) or no drainage in gastric reconstruction after esophagectomy: A meta-analysis of randomized controlled trials. Dig Surg, 2002; 19:160–164.

27.

Fuchs

, Hölscher

, Leers

, Bludau

, Brinkmann

, Schröder

, Alakus

, Mönig

, Gutschow

. Long-term quality of life after surgery for adenocarcinoma of the esophagogastric junction: Extended gastrectomy or transthoracic esophagectomy?. Gastric Cancer, 2016; 19:312.

28.

Gutt

, Bintintan

, Köninger

, Müller-Stich

, Reiter

, Büchler

. Robotic-assisted transhiatal esophagectomy. Langenbecks Arch Surg, 2006; 391:428–434.

29.

Yamaguchi

, Kinugasa

, Shiomi

, Sato

, Yamakawa

, Kagawa

, Tomioka

, Mori

. Learning curve for robotic-assisted surgery for rectal cancer: Use of the cumulative sum method. Surg Endosc, 2014; 29:1679.

30.

Patel

, Tully

, Holmes

, Lindsay

. Robotic radical prostatectomy in the community setting—the learning curve and beyond: Initial 200 cases. J Urol, 2005; 174:269–272.

31.

Luketich

, Alvelo-Rivera

, Buenaventura

, Christie

, McCaughan

, Litle

, Schauer

, Close

, Fernando

. Minimally invasive esophagectomy: Outcomes in 222 patients. Ann Surg, 2003; 238:486–494; discussion 494–495.

32.

Biere

, Cuesta

, van der Peet

. Minimally invasive versus open esophagectomy for cancer: A systematic review and meta-analysis. Minerva Chir, 2009; 64:121–133.

33.

Ajani

, D'Amico

, Almhanna

, Bentrem

, Besh

, Chao

, Das

, Denlinger

, Fanta

, Fuchs

, Gerdes

, Glasgow

, Hayman

, Hochwald

, Hofstetter

, Ilson

, Jaroszewski

, Jasperson

, Keswani

, Kleinberg

, Korn

, Leong

, Lockhart

, Mulcahy

, Orringer

, Posey

, Poultsides

, Sasson

, Scott

, Strong

, Varghese

Jr , Washington

, Willett

, Wright

, Zelman

, McMillian

, Sundar

. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw, 2015; 13:194–227.