A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Thoracic endovascular aortic repair for esophageal cancer invading the thoracic aorta: a questionnaire survey study.

BACKGROUND: Locally advanced esophageal cancer occasionally invades the aorta, and hemorrhage from the esophagoaortic fistula can cause sudden death. Thoracic endovascular aortic repair (TEVAR) enables hemostasis in such cases, and prophylactic TEVAR can prevent fatal hemorrhagic events during treatment. However, its efficacy in Japan has not been evaluated. This study aimed to clarify the clinical significance of TEVAR in esophageal cancer patients. METHODS: The Japan Esophageal Society conducted a questionnaire survey targeting authorized or semi-authorized member institutes of the Authorized Institutes for Board Certified Esophageal Surgeons. Patients who underwent TEVAR for esophageal cancer were identified from 19 institutes. Data on patient demographics, treatment performed, and survival rate were obtained using the questionnaire. The Kaplan-Meier method was used for survival analysis and to compare differences in survival rates between those who underwent TEVAR for hemorrhage and those for preoperative prophylaxis. RESULTS: Of the 41 patients identified, 20 patients underwent TEVAR for hemorrhage or impending hemorrhage from the esophagoaortic fistula, while 21 patients underwent TEVAR as preoperative prophylaxis. The median survival time after TEVAR was 135 days in the hemorrhage or impending hemorrhage group and 378 days in the preoperative prophylaxis group. Eighteen patients underwent esophagectomy after TEVAR. No hemorrhagic event was observed during the perioperative period. The median survival time of the patients who underwent esophagectomy was 373 days. Some patients who achieved R0 resection obtained long-term survival. CONCLUSION: TEVAR is an efficacious modality to control a life-threatening hemorrhage from esophagoaortic fistula and helps to prolong the survival of patients with locally advanced esophageal cancer invading the aorta.

Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy.

BACKGROUND/AIMS: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). METHODS: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. RESULTS: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients' survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387-17.110, p = 0.013) was the only independent factor influencing overall survival. CONCLUSION: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

[A Case of Advanced Gastric Cancer with Multiple Bone Metastases, Virchow Lymph Node and Para-Aortic Lymph Node Metastases That Responded to Combined Modality Therapy and Underwent Conversion Surgery].

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.

Phase II Study of Docetaxel, Nedaplatin, and 5-Fluorouracil Combined Chemotherapy for Advanced Esophageal Cancer.

BACKGROUND: We performed a prospective, multi-institutional, phase-II, clinical trial of a docetaxel, nedaplatin, and 5-fluorouracil (DNF) regimen in patients with unresectable esophageal cancer. Our goal was to determine the efficacy and feasibility of this DNF protocol. METHODS: Thirty-four patients with unresectable esophageal cancer were enrolled and received DNF therapy. The DNF regimen was repeated every 4 weeks for up to 8 weeks, based on the following recommended doses: docetaxel, 60 mg/m(2) (day 1); nedaplatin, 70 mg/m(2) (day 1); and 5-fluorouracil, 700 mg/m(2) (days 1-5). The primary endpoint was the response rate. The secondary endpoints were overall survival and chemotherapy toxicities. RESULTS: The complete response rate and response rate were 5.9 and 47.1 %, respectively. The 2-year overall survival rate and progression-free survival rate were 44.3 and 27.3 %, respectively. The median survival time was 594 days. The median progression-free time was 277 days. No treatment-related deaths occurred. Thirty patients (30/34) with grade 3, 4 neutropenia improved relatively quickly with administration of granulocyte colony-stimulating factor. CONCLUSIONS: DNF combination chemotherapy is a useful regimen with relatively minor adverse events and may serve as an effective protocol in patients with unresectable esophageal cancer.

Long-term comparison of boomerang-shaped jejunal interposition and Billroth-I reconstruction after distal gastrectomy.

BACKGROUND: Billroth-I (BI) is a simple, physiological method of reconstruction following distal gastrectomy. In actuality, postoperative QOL is by no means favorable due to the high incidence of post-gastrectomy syndrome. The aim of this study is to assess the safety and efficacy of boomerang-shaped jejunal interposition (BJI) after distal gastrectomy. METHODS: Sixty-six patients with early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after distal gastrectomy, following which they were compared for 5 years. Tumor characteristics, operative details, postoperative complications and complaints, number of meals, and body weight were analyzed. Patients were followed up by endoscopy every 12 months. RESULTS: There were no significant differences in the incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %, P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower in the BJI cases. Endoscopic findings revealed significantly lower incidences of reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P < 0.0001) in the BJI group. The incidence of food stasis was low in both groups (12 vs. 15 %). In the BJI group, 30 patients (90 %) were eating 3 meals/day within 12 months, whereas in the BI group, 16 patients (48 %) were still eating 5 meals/day at 12 months or later. CONCLUSIONS: BJI is as safe as BI, but is better in terms of improvement in bile reflux and food intake without stasis. This procedure, therefore, appears to be a useful method for reconstruction after distal gastrectomy.

Planned Esophagectomy after Neoadjuvant Hyperthermo-Chemoradiotherapy using Weekly Low-Dose Docetaxel and Hyperthermia for Advanced Esophageal Carcinomas.

BACKGROUND/AIMS: The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo-chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma. METHODOLOGY: Twenty-four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated. RESULTS: In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842). CONCLUSIONS: Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT.

Effectiveness of sternocleidomastoid flap repair for cervical anastomotic leakage after esophageal reconstruction.

BACKGROUND/AIMS: The purpose of this study was to investigate the effectiveness of sternocleidomastoid (SCM) flap repair for anastomotic leakage after esophagectomy. METHODS: A refractory cutaneous fistula from the gastric stump developed in 8 patients with esophageal cancer who underwent esophagogastric anastomosis after esophagectomy. All patients underwent SCM flap repair. The cutaneous fistula was removed and resutured. The sternal head of the left SCM was dissected from the manubrium of the sternum and sutured onto the repaired gastric stump. RESULTS: The operative duration was 80-220 min (median, 120 min). The amount of intraoperative bleeding ranged from 5 to 182 g (median, 15 g). The absence of recurrent anastomotic leakage was confirmed after the SCM flap repair in every patient. Oral intake was initiated 7-15 days (median, 10 days) after the repair operation without discomfort. CONCLUSIONS: SCM flap repair is an effective and minimally invasive treatment method for cervical anastomotic leakage after esophageal reconstruction. This method may be considered in patients with refractory leakage of the gastric stump after staple anastomosis.

MUTYH-associated colorectal cancer and adenomatous polyposis.

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

[Image-enhanced endoscopy and magnifying endoscopy for esophageal cancer].

Image diagnoses for esophageal cancer are progressing. With regard to endoscopic examination, chrome endoscopy using iodine have been performed so far to identify the range of lesion and to detect multiple primary cancers. In addition to that, endoscopic ultrasonography is used to diagnose the depth of tumor invasion and to identify lymph node metastasis. Recently, image-enhanced endoscopy (IEE) [e.g. Flexible spectral Imaging Color Enhancement (FICE), i-scan, Narrow Band Imaging (NBI), Autofluorescence imaging (AFI)] has developed. IEE is useful to detect superficial lesion, and is being utilized for diagnosing the tumor depth of invasion by using magnifying endoscopy( ME) together. In this literature, recent progress of endoscopic diagnosis, especially about IEE and ME, is reviewed. In addition to that, a way of endoscopic examination using IEE and ME is introduced.

MiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1.

The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR-150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial-mesenchymal-transition (EMT)-inducer, as a target gene of miR-150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR-150 in ESCC, and to investigate miR-150's EMT-regulatory ability. Quantitative RT-PCR was used to evaluate miR-150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR-150 via degradation of ZEB1. MiR-150 expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P < 0.001). Low expression of miR-150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (P < 0.05). In vitro assays showed that EMT-inducer-ZEB1 is a new direct target of miR-150. Moreover, miR-150 induced MET-like changes in TE-8 cells through ZEB1 degradation (e.g., E-cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC.

CD24 expression is associated with progression of gastric cancer.

BACKGROUND/AIMS: Mortality rates due to gastric cancer are high in Japan. To improve patient prognosis, new biomarkers for diagnosis and treatment are urgently required. In this study we investigated the role of CD24, a cell adhesion glycoprotein implicated in tumor cell proliferation, which is used as a prognostic marker in various cancers. METHODOLOGY: We analyzed CD24 expression in 173 gastric adenocarcinomas by immunohistochemistry and compared the data with clinicopathological parameters and patient overall survival. Furthermore, we performed Western blotting analysis of CD24 in six human gastric adenocarcinoma cell lines, Kato III, MKN1, MKN28, MKN45, MKN74, and HGC-27. RESULTS: CD24 up-regulation was significantly correlated with depth of invasion (p=0.005) and pathological high stages (p=0.043). We observed a relationship between high CD24 expression and lymph node metastasis, venous invasion and lymphatic invasion. CD24 expression tended to be higher in cell lines derived from differentiated gastric carcinoma, including those derived from lymph node metastasis. CONCLUSIONS: Our study suggests that gastric cancer patients with high CD24 expression should be closely monitored for recurrence following resections. CD24 expression is a potential biomarker for gastric cancer prognosis and provides a new molecular target for therapeutic strategies.

Management of Barrett's esophageal carcinoma.

Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA.

Surgical treatment for nonspecific esophageal motility disorders.

PURPOSE: Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD. METHODS: The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively. RESULTS: The patients included 2 males and 2 females with a median age of 48 years (range 21-74 years). The median duration of NEMD symptoms was 58 months (range 4-108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210-476 min). The median time before starting oral feeding was 2.5 days (range 2-22 days). All patients achieved a significant improvement of their previous condition. CONCLUSIONS: The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.

[Reoperation for the local recurrence of esophageal cancer].

Survivals of the esophageal cancer patients underwent esophagectomy is becoming well. However, the 5-year survival rate after esophagectomy in Japan is 50.2% according to the examination by Japan Esophageal Society. The most reason of cancer death is disease recurrence. Most of recurrent lesions can't be removed by surgical procedures because of the various degrees of the disease progressions, whereas there must be a few cases that the curability is acquired by surgery. There are few evidences about the efficacy of reoperations for recurrent lesions after esophagectomy. Therefore, the indication of the surgical therapies for the recurrent lesions after radical esophagectomy should be carefully decided after due consideration about the status of the recurrent lesion and the patient's general condition. Now in this article, we will give an outline of the surgeries for the recurrent lesions, especially about lymph node recurrence.

Therapeutic strategy aiming at R0 resection for borderline-resectable esophageal squamous cell carcinoma using induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil.

OBJECTIVE: Treatment for borderline resectable (cT3br) esophageal squamous cell carcinoma (SCC) is currently undefined. This study aimed to analyze the outcome of treatment strategies including induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) against T3br esophageal SCC. METHODS: A total of 32 patients with cT3br esophageal SCC enrolled in this study were treated with two cycles of DCF induction therapy. RESULTS: The overall response rate to DCF induction therapy was 62.5%, while the disease control rate was 93.8% (complete response (CR), three; partial response (PR), 17; stable disease (SD), 10; progressive disease (PD), 2). After DCF induction chemotherapy, 27 patients underwent conversion surgery (CS) and five patients underwent definitive chemoradiotherapy (CRT). Out of 27 patients who underwent CS, 17 underwent transthoracic esophagectomy and 10 underwent thoracoscopic esophagectomy. Anastomotic leakage occurred in five patients (18.5%) and pneumonia in four (14.8%). Recurrent laryngeal nerve paralysis and arrhythmia were observed in two patients (7.4%). The R0 resection rate was 81.5%. Among the five patients who underwent definitive CRT, only one patient (20.0%) achieved CR. Two patients (40.0%) had PR and two (40.0%) had PD. Salvage esophagectomy was performed in one patient after definitive CRT. The 1-, 3-, and 5-year overall survival rates were 75.0, 50.6, and 46.4%, respectively, whereas the 1-, 3-, and 5-year disease-free survival rates were 54.9, 38.8, and 38.8%, respectively. CONCLUSION: DCF induction therapy and subsequent CS or definitive CRT are promising treatment strategies for cT3br esophageal SCC.

Laparoscopic Heller myotomy with Dor fundoplication for esophageal achalasia treatment after distal gastrectomy and Billroth-II reconstruction.

Laparoscopic Heller myotomy with Dor fundoplication is the standard surgical treatment for esophageal achalasia. However, there are few reports on the use of this method after gastric surgery. We report a case of a 78-year-old man who underwent laparoscopic Heller myotomy with Dor fundoplication for achalasia after distal gastrectomy and Billroth-II reconstruction. After the intraabdominal adhesion was sharply dissected using an ultrasonic coagulation incision device (UCID), Heller myotomy was performed 5 cm above and 2 cm below the esophagogastric junction using the UCID. To prevent postoperative gastroesophageal reflux (GER), Dor fundoplication was performed without cutting the short gastric artery and vein. The postoperative course was uneventful, and the patient is in good health without symptoms of dysphagia or GER. Although per-oral endoscopic myotomy is becoming the mainstay of treatment for achalasia after gastric surgery, laparoscopic Heller myotomy with Dor fundoplication is also an effective strategy.

Segmental cervical esophagectomy with free jejunal flap reconstruction for cervical esophageal cancer in patients with previous history of gastric surgery: a report of two cases.

Although free-flap jejunal reconstruction is frequently performed after cervical esophagectomy for cervical esophageal cancer, the procedure after gastric surgery has not been reported. We encountered two patients with esophageal cancer and previous gastric surgeries who eventually underwent segmental esophagectomy with free-flap jejunal reconstruction. Case one involved a 75-year-old man who underwent abdominal abscess and duodenal ulcer perforation surgeries (abdominal drainage and subsequent gastrojejunal bypass). A type 0-IIa tumor was located posterior to the cervical esophagus's right wall, 21 cm from the incisor, without lymph node swelling or distant metastasis. The left lobe of the thyroid gland was mobilized to ensure an oral resection margin. Severe abdominal adhesions required careful adhesiolysis to harvest the jejunum (20 cm long) 40 cm from the jejunojejunostomy. An end-to-side and side-to-end esophagojejunostomy were performed for the proximal and distal ends, respectively. Case two involved a 75-year-old male with a history of distal gastrectomy with Billroth I reconstruction for early gastric cancer. A submucosal tumor-like lesion was located on the cervical esophageal wall on the left side, 21 cm from the incisor. The distal esophagus required additional segmental resection because the anal resection line was close to the tumor. Jejunum (10 cm long) 30 cm from Ligament of Treitz was harvested. An end-to-side and end-to-end esophagojejunostomy for the proximal and distal ends, respectively, was performed. This surgery requires a thorough preoperative examination to ensure an adequate surgical margin and a careful free-flap harvest based on post-gastric surgery anatomy.

Buried bumper syndrome in percutaneous endoscopic gastrostomy with a jejunal extension tube in patients undergoing levodopa-carbidopa intestinal gel treatment.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) treatment is an effective Parkinson's disease (PD) treatment that requires percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG-J). Buried bumper syndrome (BBS) is an uncommon but significant complication of PEG-J for LCIG. Case presentation A 71-year-old man had been undergoing LCIG therapy for PD since a PEG-J was implemented at our department two years previously. He presented with appetite loss. Computed tomography showed that the gastrostomy bumper was buried in the gastric wall. The patient was surgically treated with the simultaneous removal and replacement of PEG-J. Postoperative gastrocutaneous fistula occurred, which was conservatively treated. CONCLUSIONS: Notably, patients and medical staff should be aware that patients with PD on LCIG treatment have a high risk of BBS in PEG-J and that there might be some patients with latent BBS. When simultaneous removal and replacement surgery is performed, establishing a new route at the stomach and abdominal wall is recommended.

Successful combined laparoscopic and thoracoscopic surgery for esophago-mediastinal fistulae.

Minimally invasive surgeries have been developed, not only for gastrointestinal cancer, but also for benign or emergency cases. We report the case of a 62-year-old male who underwent laparoscopic and thoracoscopic combined surgery for an esophago-mediastinal fistula caused by a press-through package. In the initial laparoscopic phase, transhiatal dissection of the lower thoracic esophagus and harvesting of the greater omentum were performed. In the thoracoscopic phase, resection of the fistula and esophageal wall closure were performed. Thereafter, the greater omentum was lifted via the esophageal hiatus and wrapped around the repaired part of the esophagus for reinforcement. The total operative time was 371 min, with 163 and 208 min for the laparoscopic and thoracoscopic phases, respectively. In total, 20 ml of blood was lost. No perioperative complications or recurrences were observed. Laparoscopic and thoracoscopic combined omentoplasty was effective for refractory esophago-mediastinal fistula.