Review on Post-esophagectomy Anastomotic leakage Dr. PC Wong Department of Surgery Queen Mary Hospital

I. Introduction II. Risk factor and Prevention III. Management

Post-esophagectomy leakage Leakage rate 5-30% Mortality up to 50% Ladak et al, Surg Endosc, 2019

I. Introduction II. Risk factor and Prevention III. Management

Surgical-related factor Reason for leakage Patient factor Surgical-related factor

Patient factor Diabetes BMI (<18.5kg/m2, p=0.01) Smoking Preoperative optimization of nutritional status Better patient selection Diabetes BMI (<18.5kg/m2, p=0.01) Smoking Neoadjuvant CTRT Previous irradiation to H&N Other medical co-morbidities: liver cirrhosis, renal impairment, immunosuppressants Higher leakage in irradiated field of esophagus Drug Immunosuppressant Previous irradiation to Head and neck Whole stomach / narrow tube Surgical related factor Tension – level of anastomosis Preop optimization of nutrition: Paper Retrospective review of 483 patients BMI >18.5 kg/m2 associated with less leakage (p=0.01) Shichinohe et al, Ann Surg Oncol, 2019 Li et al, Dis Esophagus, 2017 Gao et al, Medicine (Baltimore), 2018 Roh et al, Korean J Thorac Cardiovasc Surg, 2019

Surgical-related factor Tension Blood supply Tissue

Surgical-related factor: 1. Surgical approach MIE vs Open No difference in leakage (5.7% vs 5.3%) No difference in recurrent laryngeal nerve palsy (20.1% vs 18.7%) MIE is superior to Open in terms of Wound infection (3.7% vs 10.7%, p = 0.01) Blood loss (220 vs 400ml, p < 0.001) Respiratory complications (29% vs 55%, p<0.001) 724 patients over 22 years 33 per year Handsewn vs stapled QMH + slide for ischemic preconditioning Narrow tube stomach Super-charge (inferior thyroid, internal mammary) Ileal interposition Routine colonic interposition Chan et al, Dis Esophagus, 2018

Surgical-related factor: 2. Anastomosis Level of anastomosis Cervical (12%) vs Intrathoracic (9.8%); OR 0.56, p=0.021 Handsewn vs Circular stapler2 Meta-analysis of 12 RCTs No difference in leakage rate Higher rate of anastomotic stricture in CS (OR 1.67, p=0.006) Handsewn vs Linear stapler3 Meta-analysis of 3 RCTs + 12 comparative studies Lower rate of anastomotic leakage (OR 0.51, p<0.00001) and stricture (OR 0.56, p<0.00001) in LS 1. Ryan et al, Ann Surg Oncol, 2017 2. Honda et al, Ann Surg, 2015 3. Deng et al, World J Gastroenterol, 2015

Surgical-related factor: 3. Route of reconstruction Controversial Retrosternal Posterior mediastinal Less tumor bed recurrence in conduit Shorter distance Avoid conduit irradiation Less tension Less complication of anastomotic leakage Less angulation Better gastric emptying Residual / R2 Resection Less mediastinitis Ease of drainage and reoperation Urschel et al, Am J Surg, 2001

Surgical-related factor: 4. Choice of conduit Narrow gastric tube vs Whole stomach Meta-analysis of 3 RCT + 3 retrospective studies No difference in anastomotic leakage and stricture Gastric tube has less reflux esophagitis (OR 0.36, p=0.01) Zhang et al, PLoS One, 2017

Surgical-related factor: 5. Blood supply Intraoperative ICG fluorescence angiography Sensitivity: 78%; Specificity: 74% Intervention Resection of devitalized segment Addition of vessel anastomosis Leak rate 5.7% (ICG group) vs 22.9% (control group) Absolute risk reduction 69% (OR 0.31, p=0.001) Ischemia: one of the most important risk factor for leakage Colour temperature pulsation Sample size 20-200Limitation Observational cohort study, small sample size Use: before / after anastomosis ICG Cutoff Outcome: clinical / radiological leak Ladak et al, Surg Endosc, 2019

I. Introduction II. Risk factor and Prevention III. Management

Management principles Pus / air / saliva from neck drain Pulmonary complication, Mediastinitis Early recognition OGD Contrast swallow / CT with IV + oral contrast Confirm diagnosis Resuscitation, Ventilatory support, Nutrition Broad spectrum antibiotics Control sepsis & organ support Radiological / Endoscopic / Surgical Drainage Endoscopic / Surgical Repair Control sepsis – Broad spectrum antibiotics Drainage Radiological: Percutaneous drainage of neck / pleural collection Endoscopic: Gastric conduit Surgical: Exploration and drainage Wound dressing Negative pressure therapy (For neck wound) Nutritional support Enteral nutrition: Nasojejunal tube feeding, Feeding jejunostomy Parenteral nutrition

Neck wound exploration Anastomotic leakage Cervical Drainage Neck wound exploration VAC Septic Intrathoracic Exploration: Open vs VATS Conduit healthy Primary repair Conduit ischemia  Resection Adequate length Re-anastomosis Inadequate length Stable Immediate reconstruction Esophagostomy Delayed reconstruction QMH usual protocol Jejunal interposition Conduit in abdomen and feeding jejunostomy Conduit in subcutaneous and free jejunum / flap reconstruction

Neck wound exploration Anastomotic leakage Cervical Drainage Neck wound exploration VAC Septic Intrathoracic Exploration: Open vs VATS Conduit healthy Primary repair Conduit ischemia  Resection Adequate length Re-anastomosis Inadequate length Stable Immediate reconstruction Esophagostomy Delayed reconstruction QMH usual protocol Jejunal interposition Conduit in abdomen and feeding jejunostomy Conduit in subcutaneous and free jejunum / flap reconstruction

Stable but persistent defect: Consider Endoscopic treatment Anastomotic leakage Cervical Drainage Neck wound exploration VAC Septic Intrathoracic Exploration: Open vs VATS Conduit healthy Primary repair Conduit ischemia  Resection Adequate length Re-anastomosis Inadequate length Stable Immediate reconstruction Esophagostomy Delayed reconstruction QMH usual protocol Jejunal interposition Conduit in abdomen and feeding jejunostomy Conduit in subcutaneous and free jejunum / flap reconstruction Stable but persistent defect: Consider Endoscopic treatment

Endoscopic treatment Mechanism Success rate Limitation Complication Esophageal stenting Self-expanding covered metal stent 60-90% 1-10 weeks Migration Bleeding Perforation Stricture Clip Full thickness closure 60-70% Small defect Vacuum-assisted closure Sponge within abscess cavity Decrease bacterial load and edema Promote granulation >90% 1-6 weeks Exchange every 3-5 days Stent 20-70 patients Clip: small case series for anastomotic leakage Persson et al, Dis Esophagus, 2017; Plum et al, World J Surg, 2019; Hwang et al, Medicine (Baltimore), 2016; Pines et al, J Laparoendosc Adv Surg Tech A, 2018; Haito-Chavez et al, Gastrointest Endosc, 2014

Summary Post-esophagectomy anastomotic leakage leads to significant morbidity and mortality Preoperative optimization and systematic management strategies are crucial Emerging intraoperative techniques and endoscopic treatment yield promising results Intraoperative ICG with subsequent intervention has potential in reducing leakage rate Endoscopic therapy is associated with good success rate in clinically stable patients with minor leakage

Reference Ladak et al, Indocyanine green for the prevention of anastomotic leakage following esophagectomy. Surg Endosc. 2019 Gao et al, Impact of high body mass index on surgical outcomes and long-term survival among patient undergoing esophagectomy. Medicine (Baltimore). 2017 Li et al, Diabetes mellitus and risk of anastomotiic leakage after esophagectomy. Dis Esophagus. 2017 Deng et al. Hand-sewn vs linearly stapled esophagogastric anastomosis for esophageal cancer. World J Gastroenterol. 2015 Boostma et al, Towards optimal intraoperative conditions in esophageal surgery. Int J Surg. 2018 Messager et al. Recent improvements in the management of esophageal anastomotic leak after surgery for cancer. EJSO. 2016