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Purpose: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS. Methods: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period). Results: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p Conclusions: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.

Background Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. Case presentation A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller–Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. Conclusions Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor.

Although the main manifestation of giant paraesophageal hernia (PEH) is disordered meal passage due to gastric torsion, the contents of the hernia sometimes squeeze the heart and lungs and induce the symptoms of respiratory or heart failure. Furthermore, the quality of life (QOL) of patients with a heavy cardiac load deteriorates. In this study, changes in a heart failure marker and symptoms of cases with a giant PEH from before to after laparoscopic surgery were examined. Levels of brain natriuretic peptide (BNP) as a heart failure marker were measured before and after radical laparoscopic surgery in cases of type III, IV type of giant PEH. Changes of the symptoms due to heart failure were also investigated. A total of 75 hiatal hernia surgeries were performed in 2012–2019. Of them, 50 had a giant PEH, and 20 (40.0%) had heart failure symptoms such as fatigue and exertional dyspnea. In the giant PEH cases, BNP could be measured before and after surgery to evaluate the presence of heart failure in 23 cases; postoperative BNP levels decreased from the preoperative values in 18 of them. Furthermore, in many cases, chest symptoms also improved. Radical laparoscopic surgery can reduce heart failure due to giant PEH. Therefore, in addition to conventional surgical indication criteria such as vomiting and food loss, increased cardiac load may be added to the new surgical indication criteria.

Incidence of esophagogastric junction (EGJ) carcinoma has been increasing worldwide. Several studies revealed that the distance from the EGJ to the proximal edge of the primary tumor (esophageal invasion: EI) may be a significant indicator of metastasis in the mediastinal lymph nodes in patients with Siewert type II carcinomas. However, few studies have been conducted in patients with carcinomas located at Siewert type II sequentially to upper carcinomas (Siewert type I) for mediastinal metastasis regardless of histological types. This was a single-center retrospective cohort study. EGJ carcinomas located at Siewert type I and II regions including both squamous cell carcinoma (SCC) and adenocarcinoma were analyzed in terms of lymph node metastasis patterns. We included 121 patients in this study. Thirty-three (27.3%) patients had SCC. In multivariate analysis, the distance of EI (> 20 mm) was an independent risk factor (OR 11.80, p = 0.005) for lower mediastinal lymph node metastasis. In terms of above the middle mediastinal metastasis, the distance of EI (> 30 m), histological type (SCC), and tumor size (> 40 mm) were risk factors in univariate analysis. Furthermore, EI was significant (OR 13.50, p = 0.026) in multivariate analysis. The distance of EI was the independent risk factor for mediastinal lymph node metastasis, especially > 20 mm related with a higher risk for mediastinal lymph node metastasis. Furthermore, EGJ carcinoma patients who have EI > 30 mm, large SCC carcinoma, and multiple lymph node metastasis might be considered the middle-upper mediastinal lymph node dissection by transthoracic approach.

Introduction Intracorporeal Billroth I (B‐I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi‐hand‐sewn (SHS) B‐I reconstruction. Materials and surgical technique After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B‐I anastomosis. All the transection line of the duodenum and one‐third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand‐sewn technique. Discussion SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra‐abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32‐63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.

An aberrant right subclavian artery (ARSA) is one of the famous anatomical abnormalities with a prevalence of 0.16-4.4%. In esophagectomy, anatomical abnormalities of the ARSA could cause complications with some surgical procedures. An 85-year old man was referred to our department for esophageal adenocarcinoma that was at a slightly high position for esophagectomy with the abdominal approach. However, he had a significant past medical history. This risk factor made it difficult to perform thoracoscopic esophagectomy. He underwent mediastinoscopic esophagectomy (ME) with the left cervical and laparoscopic approach. The ARSA presented no difficulties with the ME surgical technique including the dissection of the left recurrent laryngeal nerve lymph node. Although this patient had a respiratory dysfunction and some difficulties in a prone position, ME enabled a safe esophagectomy with lymph node dissection.

Although thoracoscopic esophagectomy in the prone position (TEPP) has become a standard procedure for esophageal cancer surgery, upper mediastinal lymph node dissection (UMLND) on the left side remains an issue. We have recently developed a new standardized approach to left UMLND in TEPP based on the microanatomy of the membranes and layers with the aim of achieving quick and safe surgery. The purpose of this study was to establish and evaluate our new standardized procedure in left UMLND. Patients were divided into 2 groups: a pre-standardization group (n = 100) and a post-standardization group (n = 100). Eventually, 83 paired cases were matched using propensity score matching. In our new standardized procedure, left UMLND was performed while focusing on the visceral sheath, vascular sheath, and the fusion layer between them using a magnified view. The thoracoscopic operative time was significantly shorter (P

Locally advanced esophageal cancer (EC) invading surrounding organs (T4b) is difficult to treat. In general, definitive chemoradiotherapy (d-CRT) has been chosen as treatment for such cases. However, the outcome has not been good. Recently, the effectiveness of d-CRT with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) has been reported. Furthermore, surgery after d-CRT has a better prognosis than d-CRT alone in some reports, although it has a high risk of surgical complications. This study investigated the effectiveness and safety of induction DCF-RT. The subjects were EC patients who underwent induction DCF-RT in Okayama University Hospital between January 2011 and December 2017. Their background characteristics, treatment details, histopathological factors, adverse events during CRT, postoperative complications, and overall survival (OS) were assessed. A total of 16 cases were performed induction DCF-RT. In 10 cases, death occurred, with 9 cancer-related deaths, and 1 death due to other disease. For all cases, OS was 37.5% at 3 years. 12 cases underwent esophagectomy after DCF-RT. Their OS was 50% at 3 years. 13 patients (81.3%) had Grade 3 febrile neutropenia. In 7 cases (62.5%), fasting for the treatment of diarrhea was needed. Three patients (25%) developed anastomotic leakage. Some recurrent laryngeal nerve paralysis was observed in 6 cases (50%). Although the rates of adverse events and surgical complications were slightly higher than in past reports, they were acceptable. It is useful to perform induction DCF-RT for T4b EC.

Purpose: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments. Methods: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Results: Of the 13 patients, 7, 3 and 3 patients were treated with 10(10), 10(11) and 10(12) virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8 thorn cells and increased PD-L1 expression. Conclusion: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. (C) 2021 Elsevier Ltd. All rights reserved.

Multidisciplinary team (MDT) approach has become a standard for perioperative patient care, including in esophageal cancer. In our institution, the Perioperative Management Center (PERiO) has been doing an MDT approach for patients undergoing esophageal cancer surgery since 2009. On the other hand, neoadjuvant therapy has also been becoming standard for many malignancies, including esophageal cancer. In Japan, neoadjuvant chemotherapy (NAC) for esophageal cancer is standard now. However, there have been no reports about when is the best time to start the MDT approach for patients with neoadjuvant therapy. In this study, the best start time for the MDT approach for esophageal cancer patients with NAC was examined from the perspective of adverse events during chemotherapy and perioperative period. All cases underwent thoracoscopic esophagectomy in the prone position (TEPP) after NAC. The PERiO Intervention group that started before NAC (n = 100) was compared with the PERiO Intervention group that started after NAC (n = 77). Eventually, 54 paired cases were matched by propensity score matching. The adverse event rate during chemotherapy, especially oral complications, was significantly decreased in the PERiO Intervention started before the NAC group (P = 0.007). Furthermore, weight loss during the period from chemotherapy to surgery was significantly reduced in the group that started before NAC (P = 0.033). The MDT approach should be started before NAC in patients undergoing esophageal cancer surgery to prevent adverse events during chemotherapy and provide safe perioperative conditions.

Background We have recently standardized upper mediastinal lymph node dissection (UMLND) using a microanatomy-based concept in thoracoscopic esophagectomy in the prone position (TEPP), and introduced robot-assisted minimally invasive esophagectomy (RAMIE) using the same concept as in TEPP while aiming at solo surgery. The purpose of this study was to investigate the outcomes of RAMIE using the microanatomy-based concept in the initial introduction phase. Methods We have performed more than 500 TEPP procedures as minimally invasive esophagectomy (MIE). After performing about 400 cases of MIE, we established a microanatomy-based standardization of UMLND. In October 2018, we introduced RAMIE, and have performed 75 procedures in 20 months. Two groups were analyzed: a group after microanatomy-based standardization in TEPP (100 cases after completing 400 cases of TEPP) and a RAMIE group (75 cases). Finally, 51 paired cases were matched using a propensity score. Furthermore, the change in postoperative short-term outcome for RAMIE in the initial introduction phase was analyzed. Results Although there were no significant differences between the two groups in the number of upper mediastinal lymph nodes dissected, there was a significant decrease (P = 0.036) in intraoperative blood loss volume with RAMIE, representing a definite benefit for patients. The thoracoscopic operative time for RAMIE decreased by almost 100 min following less than 50 cases of experience, reaching the same level as that for recent TEPP, but with only one-tenth the operator experience. There were no significant differences in the total postoperative morbidity rate including the recurrent laryngeal nerve palsy rate. Conclusion RAMIE has been introduced safely and smoothly using the microanatomy-based concept established in TEPP.

Background Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. Case presentation A 70-year-old man was found to have white, irregular esophageal mucosa four years earlier. He had been followed-up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection. He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. First, the esophagostomy and gastrostomy were constructed. The patient then underwent definitive CRT. Four weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. Six weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed complete response to CRT, with no proliferative cancer cells in the specimen. Six months after the first-stage operation, no recurrence has been observed. Conclusions A case of locally advanced VCE that achieved a complete response to CRT was presented. In cases in which local resection would be difficult, CRT might be an appropriate neoadjuvant treatment for VCE.

Background: The postoperative survival rate of patients with esophageal squamous cell carcinoma (ESCC) remains poor compared with other gastrointestinal cancers. We hypothesized that skeletal muscle loss in the postoperative acute phase might be a new predictor for long-term prognosis after highly invasive surgery such as ESCC surgery.Methods: The following items were retrospectively investigated. First, whether skeletal muscle loss occurred in the postoperative acute phase of ESCC was verified. Second, the preoperative and intraoperative factors involved in skeletal muscle loss in the postoperative acute phase of ESCC were investigated. Then, whether skeletal muscle loss in the postoperative acute phase affected long-term prognosis was examined. The medical records of consecutive patients who underwent radical esophagectomy for ESCC between January 2010 and June 2015 were retrospectively reviewed; 72 cases were eligible for this study. The total psoas major muscle mass index (TPI) at the level of the third lumbar vertebra (L3) was measured using computed tomography (CT) before surgery and three days after surgery. The long-term prognosis was estimated by the Kaplan-Meier method and the multivariate logistic regression model.Results: There was already a significant reduction of TPI in the acute phase up to POD 3 after ESCC surgery in comparison with the preoperative baseline TPI (P < 0.001). The TPI reduction rate was significantly milder in cases with less blood loss during surgery and in cases that underwent thoracoscopic esophagectomy than in cases that underwent open esophagectomy. The three-year overall survival rate was significantly different between the TPI reduction rate severe group and the TPI reduction rate mild group.Conclusion: skeletal muscle loss occurred even in the postoperative acute phase. Furthermore, it is very significant that skeletal muscle loss in the postoperative acute phase of ESCC surgery is involved in the long-term prognosis.

Although tracheobronchial diverticulum (DV) rarely cause problems, attention should be paid during esophagectomy, which requires careful dissection around the trachea and bronchi. Here, we retrospectively review cases of tracheobronchial DVs among esophageal cancer patients and report two cases of bronchial DV injury during thoracoscopic esophagectomy that were successfully repaired. The thin-section CT images of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2013 to December 2015 were retrospectively reviewed. The localization, number, and size (largest axial diameter) of all detected DVs were recorded. A total of 180 patients were enrolled in this study. The incidence of tracheal DV was 5.0%, and that of bronchial DV was 40.0%. The median diameter of the tracheal diverticula was 2.45 [interquartile range (IQR) 2.00–8.17] mm and that of the bronchial diverticula was 1.90 (IQR 1.51–2.46) mm. All tracheal diverticula presented at the right tracheal wall 4.5–6.0 cm below the vocal cords; bronchial diverticula presented at the subcarinal lesions. We experienced two cases with bronchial diverticulum injuries during thoracoscopic esophagectomy, which were repaired by primary closure and confirmed that there was no air leak. No postoperative complications associated with bronchial injury occurred in either patient. Since tracheobronchial DVs are not as rare as previously thought, careful evaluation of thin-slice CT scans is necessary before thoracoscopic esophagectomy. If a tracheobronchial DV is injured during surgery, it is important to carefully repair it and confirm that there is no air leak to avoid complications.

Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons' knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan.Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) 5 and PGY 1-5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis.A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1-5: 66, PGY 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY 5 group compared to the PGY1-5 group (79 [75; 83] % vs. 67 [58; 75] %, p 0.001). The differences in performance were due to better scores for PGY 5 group on the sections "equipment," "patient considerations," "abdominal access," "tissue handling," "hemorrhage and hemostasis," "tissue approximation," and "exiting the abdomen." Overall, the median scores in the "energy sources" and "establishment and physiology of the pneumoperitoneum" subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum.Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

AIM: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. METHODS: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. RESULTS: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). CONCLUSION: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

Background Evaluation of the blood supply to gastric conduits is critically important to avoid complications after esophagectomy. We began visual evaluation of blood flow using indocyanine green (ICG) fluorescent imaging in July 2015, to reduce reconstructive complications. In this study, we aimed to statistically verify the efficacy of blood flow evaluation using our simplified ICG method. Study Design A total of 285 consecutive patients who underwent esophagectomy and gastric conduit reconstruction were reviewed and divided into 2 groups: before and after introduction of ICG evaluation. The entire cohort and 68 patient pairs after propensity score matching (PS-M) were evaluated for clinical outcomes and the effect of visualized evaluation on reducing the risk of complication. Results The leakage rate in the ICG group was significantly lower than in the non-ICG group for each severity grade, both in the entire cohort (285 subjects) and after PS-M; the rates of other major complications, including recurrent laryngeal nerve palsy and pneumonia, were not different. The duration of postoperative ICU stay was approximately 1 day shorter in the ICG group than in the non-ICG group in the entire cohort, and approximately 2 days shorter after PS-M. Visualized evaluation of blood flow with ICG methods significantly reduced the rate of anastomotic complications of all Clavien-Dindo (CD) grades. Odds ratios for ICG evaluation decreased with CD grade (0.3419 for CD ≥ 1; 0.241 for CD ≥ 2; and 0.2153 for CD ≥ 3). Conclusions Objective evaluation of blood supply to the reconstructed conduit using ICG fluorescent imaging reduces the risk and degree of anastomotic complication.

Esophageal achalasia is a disorder of the lower esophageal sphincter muscle. Patients present with dysphagia, chest pain, vomiting, and aspiration. Esophageal achalasia had traditionally been treated with esophageal achalasia balloon dilatation and the Heller-Dor method, but in recent years, the use of per-oral endoscopic myotomy (POEM) has increased. Our patient, a 39-yr-old male, began experiencing dysphagia 4 years prior to his referral to our hospital. Based on the results of esophagogastroduodenoscopy, esophageal radiography and high-resolution manometry, we made the diagnosis of esophageal achalasia (Chicago classification type I) . After informed consent from the patient and his family and approval from our hospital's ethics committee were obtained, we performed a POEM. The patient was discharged on the 4th day post-surgery. At the 1-year post-operative examination, no worsening of symptoms and no relapse were observed. POEM is an excellent treatment method for esophageal achalasia from the perspective of therapeutic effect and prevention of invasion. We recommend that it be considered as the first-choice treatment for achalasia. However, accessibility to the procedure itself is limited due to the few adequately trained operators worldwide. POEM should thus be performed by an expert operator at a high-volume center.

Background Esophageal carcinomas are highly malignant tumors with a high frequency of lymph node and distant organ metastasis. Treatment for recurrent tumors is generally decided on an individual basis. Although multidisciplinary treatments involving chemotherapy, surgical resection, and radiation are performed, the prognosis remains poor. Here, we report a case of prolonged recurrence-free survival (38 months) after esophageal carcinoma surgery and subsequent laparoscopic adrenalectomy for right adrenal metastasis. Case presentation An 83-year-old man was diagnosed with type 3 esophageal squamous cell carcinoma (T3N1M0, cStage IIIA, UICC-7), spreading from the lower thoracic esophagus to the abdominal esophagus. He underwent thoracoscopic esophagectomy with a two-field lymph node dissection followed by substernal gastric tube reconstruction. The final diagnosis was moderately differentiated squamous cell carcinoma (T3N2M0, fStage IIIB). Adjuvant chemotherapy was not administered because of the advanced age and postoperative condition of the patient. Computed tomography (CT) at 14 months postoperatively showed a mass with a 2-cm diameter at the right adrenal gland. Positron emission tomography (PET)/CT revealed a high fluorodeoxyglucose (FDG) uptake in the mass. It was suspected that the mass was a metastatic lesion secondary to the primary esophageal carcinoma. No metastases to lymph nodes or other distant organs were identified. The patient underwent laparoscopic right adrenalectomy. The histopathological examination revealed moderately differentiated squamous cell carcinoma, suggesting metastasis from the primary esophageal carcinoma. He has survived without recurrence for 38 months since laparoscopic adrenalectomy to remove the right adrenal metastastic mass after the esophageal carcinoma surgery. Conclusions We describe a very elderly male who survived laparoadrenalectomy for right adrenal metastasis following esophageal cancer surgery without recurrence for 38 months postoperatively. Therefore, surgical resection might be an option for solitary adrenal recurrence.

When planning surgery for achalasia, it is important to plan for adequate myotomy and prevention of reflux. However, achalasia may recur if the procedure was inadequate or in patients with a long-term course. The present case is a 68-year-old woman who underwent myotomy of the lower esophageal sphincter 40 years ago, but recently reported difficulty in swallowing. Dilatation of the thoracic esophagus and stenosis of the abdominal esophagus were identified by examination, and the patient was diagnosed with recurrence of achalasia. After percutaneous endoscopic gastrostomy was performed to recover nutritional status, thoracoscopic esophagectomy was carried out. The patient'spost-operative course was uneventful and oral intake was enabled. At the time of writing, there has been no re-recurrence. There is no standard therapy for post-operative recurrence of achalasia. We believe that thoracoscopic esophagectomy for the recurrence of achalasia is a safe and minimally invasive alternative to conventional surgery.

Aim The purpose of this study is to establish and evaluate our new standardized procedure in left UMLND Background & Methods Although thoracoscopic esophagectomy in the prone position (TEPP) has become a standard surgery for esophageal cancer, upper mediastinal lymph node dissection (UMLND) in left side has been still an issue in TEPP. We have recently developed the standardization of left UMLND in TEPP based on the microanatomy of membranes and layers. Patients were divided into 1 of 2 groups: a pre-standardization group (n = 100) and a post-standardization group (n = 100). Eventually, 83 paired cases were matched using propensity score matching. We perform left UMLND while paying attention to the visceral sheath, vascular sheath and the fusion layer between them using magnified view. Results The thoracoscopic operative time was significantly shorter (P < 0.001) in the post-standardization group [n = 83; 209.0 (176.0 - 235.0) min] than in the pre-standardization group [n = 83; 235.5 (202.8 - 264.5) min]. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the 2 groups. There was a tendency for the total postoperative morbidity to decrease in the post-standardization group. Furthermore, recurrent laryngeal nerve (RLN) palsy rate has significantly decreased in the post-standardization group (18.1% to 8.7%, P = 0.015). Conclusion The microanatomy-based standardization contributes the safe and efficient left UMLND.

Despite the widespread use of surgical energy devices and the potential for rare but serious complications, pilot data from North America suggest that surgeons and surgical trainees have knowledge gaps in their safe use. The purpose of this study was to determine baseline knowledge of general surgeons and surgical trainees regarding the safe use of electrosurgery (ES) across varying levels of experience in Japan.Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of SAGES' Fundamental Use of Surgical Energy™ curriculum. Sections of the examination included: "principles of ES," "ES-related adverse events," "monopolar and bipolar devices," and "pediatric considerations and interference with implantable devices." Scores were compared between PGY5 and PGY 1-5 participants.A total of 145 general surgeons and surgical trainees of all years after medical school (PGY 1-5: 57, PGY5: 88) from ten academic and five community hospitals completed the assessment (mean age 35; 91% male). The mean score in the entire cohort was 58 ± 12% (range 23-83%), with significantly higher scores in the PGY5 group compared to the PGY 1-5 group (60 ± 11 vs. 53 ± 12%, p0.01). Among all participants, 92% were not familiar with best practices when using ES on patients with a pacemaker; 44% believe that ES uses thermal energy from cautery; 19% did not know how to manage an operating room fire; 16% thought that a dispersive electrode should be cut to fit a child; and 27% believe that insulation failure in minimally invasive surgical instruments is mostly visible under careful inspection.General surgeons and trainees at all levels have knowledge gaps in the safe and effective use of energy devices, regardless of years of experience. There is a need for educational curricula to help address these gaps and contribute to safer surgery.

Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. This study was a multicenter, phase II study. Patients with chemotherapy-naive HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS). A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1–10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3–4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%). Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Most cases were males. The median interval from TEC surgery to GTC occurrence was 57 (6.5–107.5) months. Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important.

Esophageal reconstruction using intestine is often performed for esophageal cancer patients in cases where the stomach cannot be used. We have previously performed reconstruction using ileocolon with supercharge and drainage as our first choice in those cases. However, a less invasive, simpler, and safer reconstructive technique using jejunum without vascular anastomosis has recently become popular at our facility. This study describes the technique of esophageal reconstruction with jejunum, compares the surgical outcomes to those of standard reconstruction using ileocolon, and discusses the clinical significance of this new concept. Subjects comprised 53 patients (52 males, 1 female) who underwent esophageal reconstruction using jejunum between January 2008 and July 2013. Patient characteristics, technical details, and outcomes were compared with those of 51 subjects who had undergone esophageal reconstruction using ileocolon. When making the pedicled jejunal flap, the first jejunal vascular arcade was preserved, which in most cases allowed it to be pulled up to the cervical region by processing and transection up to the second jejunal vascular branch. The vascular anastomosis techniques were used in 80.4 % (41/51) of esophageal reconstructions using colon, compared with only 24.5 % (13/53) of reconstructions using jejunum. No difference in the frequency of postoperative adverse effects was seen between groups, but the frequency of diarrhea was significantly lower with reconstruction using jejunum. Esophageal reconstruction using jejunum with the blood vessel processing technique results in both simpler and safer pulling up. Thus the need to perform supercharge and superdrainage is reduced.

Background The neoadjuvant chemotherapy using CDDP and 5-FU(CF) is the standard treatment for advanced esophageal cancer, defined as clinical stage II/III in Japan. However, more powerful chemotherapy has been required for the treatment of cases of cStageIII cases. In 2011, the combination treatment of CF and Docetaxel (DCF) was introduced for the treatment of those cases in our institute. DCF therapy increased chemotherapy remarkable cases. But, adverse events occur at high rates, including high myelosuppression. Therefore, it is necessary to ensure support by early intervention of supportive therapy so as not to exacerbate adverse events. We report about treatment outcome in preoperative DCF therapy cases. Methods We treated 128 esophageal cancer patients who underwent surgery following preoperative DCF therapy between 2011 and July 2017, and preoperative DCF was administered to 128 patients 2 course completely. The neoadjuvant chemotherapy regimen using DCF is Docetaxel:70mg/m2 (day1) + CDDP:70mg/m2 (day1) + 5-FU:700mg/m2 (day1–5). Results In the preoperative DCF group, overall response rate (over PR) was 51.5%. There were 37 cases in 128 cases of pathological tissue effect judgment for Grade 2 and 3. 14 cases of them (14cases/37cases:37.8%) had lymph node metastasis. Therefore it is necessary to control lymph node metastasis by surgery even in a remarkable group. Almost all patients experienced grade 4 adverse events, particularly neutropenia is a high frequency. From the start of chemotherapy, pretreatment of intraoral infection lesion and prevention and treatment of oral mucositis are performed. Considering the degree of myelosuppression during initial chemotherapy, in the second course, we actively administer G-CSF preparation. Conclusion A good prognosis can be expected if preoperative DCF therapy is effective. It is necessary to perform intensive and safe preoperative chemotherapy with appropriate supportive therapy intervention. Disclosure All authors have declared no conflicts of interest.

Background: OBP-301 (telomelysin) is an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase (hTERT) promoter to regulate viral replication. OBP-301 causes selective replication and lysis of a variety of cancer cells, and a phase I study has confirmed the safety and biological activity of OBP-301 alone in patients with advanced solid tumors in the US. We have also completed the preclinical study demonstrating that OBP-301 inhibits the repair of radiation-induced DNA double-strand breaks, leading to radiosensitization. To further determine the feasibility, efficacy, and pharmacokinetics of OBP-301 in combination with radiotherapy, a clinical trial was designed in esophageal cancer patients unfit for standard treatments such as in elderly.Methods: An open-label, phase I dose-escalation study of OBP-301 with radiotherapy (UMIN 000010158) was conducted in 13 histologically confirmed esophageal cancer patients who deemed unfit to receive standard surgery or chemotherapy. Study treatment consisted of intratumoral OBP-301 injections on days 1, 18, and 32 of treatments. Radiation therapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Virus administration was performed by intratumoral needle injection of the primary tumor through a flexible endoscope. Patients were also monitored for virus distribution and shedding into the body fluids. The primary and secondary end points were incidence of dose-limiting toxicities and objective response rate.Results: Of 13 patients, 7, 3, and 3 patients were treated in the cohorts with 10e10, 10e11, and 10e12 virus particles (vp) of OBP-301, respectively. The patients comprised 10 males and 3 females, with median age of 79.7 years (range, 53 to 92 years). Common grade 1 and 2 toxicities included fever, esophagitis, pneumonitis, anorexia, constipation, and gastroesophageal reflux. All patients developed a transient, self-limited lymphopenia. Distribution studies revealed that viral DNA was detected in 5 out of 6 patents received with10e11 and 10e12 vp of OBP-301, but rarely in the gargle, saliva, and urine. Eight patients had local complete response (CR); all of them exhibited pathologically no viable malignant cells in biopsy specimens, and 3 had partial response. The objective response rate was 84.6%. The clinical CR rate was 80.0% in stage I and 66.7% in stage II/III, respectively. Histopathologic examination in post-treatment specimens showed massive infiltration of CD8+ cells in 3 partially responded tumors.Conclusions: Multiple courses of endoscopic OBP-301 injection with radiotherapy were feasible and provided definite clinical benefits in patients with esophageal cancer, especially who are unfit for standard treatments. Citation Format: Toshiyoshi Fujiwara, Shunsuke Tanabe, Hiroshi Tazawa, Nobuhiko Kanaya, Kazuhiro Noma, Shunsuke Kagawa, Shinji Kuroda, Yasuo Urata, Yasuhiro Shirakawa. Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (telomelysin) with radiotherapy in esophageal cancer patients unfit for standard treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT185.

Background: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan. Aim: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI. Methods: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period. Findings: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012). Conclusion: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.

Zenker’s diverticulum carcinoma is a rare disease. Recent technological endoscopic innovation has enabled the detection of early stage Zenker’s diverticulum carcinoma. Here we report a case in which a 56-year-old woman was diagnosed with early stage Zenker’s diverticulum carcinoma. Narrow band imaging (NBI) endoscopic examination was useful for diagnosis and identifying the borders of the carcinoma. A successful surgical treatment was performed using direct observation diverticulectomy. A minimally invasive cervical procedure was used, and the area of the carcinoma was confirmed intraoperatively with Lugol’s solution.

Background: Conventional reconstruction after an esophagectomy uses a gastric tube, which commonly causes several postoperative complaints such as gastric acid reflux in long-term survival cases. Intestinal interposition between the remnant esophagus and the stomach is an option to reduce complaints, and in this study, the advantages of jejunal interposition reconstruction with a stomach preserving esophagectomy (SPE) were assessed. Materials and methods: Eleven cases of jejunal interposition with an SPE and 16 cases with gastric tube reconstruction as a control were subject to a comparison of operation time, amount of bleeding, postoperative quality of life, and endoscopic findings. Results: The SPE group had a longer operation time (SPE: 560 +/- 121 min, control 414 +/- 83 min, P = 0.038), whereas there was no significant difference in blood loss. Postoperative weight loss was significantly recovered in the SPE group (SPE versus control = 94.0 +/- 5.4% versus 87.5 +/- 4.7% at 3 mo, P = 0.017; 97.2 +/- 7.5% versus 85.0 +/- 5.2% at 6 mo, P = 0.010), and there was a significant decrease in the occurrence of reflux symptoms such as heartburn, odynophagia, and cough when jejunal interposition with an SPE was done. Furthermore, reflux esophagitis and Barrett's epithelium were found in six out of 12 cases (50%) of the control group by postoperative endoscopy, while no cases in the SPE group had either condition (P < 0.01). Conclusions: This reconstruction method is a promising option to improve postoperative quality of life, mainly due to the long-term elimination of reflux esophagitis, which assists in the recovery of postoperative weight loss.

Laparoscopic and endoscopic cooperative surgery (LECS) is increasingly applied for gastric submucosal tumors (SMTs) such as gastrointestinal stromal tumors. However, the conventional LECS procedure has the potential risk that gastric contents and even tumor cells could spread into the abdominal cavity because the gastric wall has to be opened during the resection. To avoid this problem, we have developed a modified LECS procedure named “closed LECS.” Ten patients underwent closed LECS for the resection of gastric SMTs. Closed LECS consists of the following steps: endoscopic submucosal layer dissection around the tumor, laparoscopic marking of a resection line on the serosal surface along submucosal dissection line, seromuscular suturing with the marked lesion inverted into the inside of the stomach, endoscopic circumferential seromuscular dissection, and peroral retrieval. In three of the initial five cases, the closed LECS procedure was not completed as planned because of the tumor size and endoscopic inappropriate seromuscular dissection. After modification of the procedure, the entire procedure was successful in all five cases. The mean resected tumor diameter was 24.1 ± 7.6 mm. The mean operation time was 253 ± 45 min. One patient experienced an intra-abdominal abscess potentially related to delayed perforation as a postoperative complication. The closed LECS procedure for gastric SMTs can theoretically be applied without contamination and tumor cell dissemination into the abdominal cavity.

Esophageal carcinomas often have a poor prognosis due to early lymph node metastasis. Epithelial-mesenchymal transition (EMT) is strongly associated with the acquisition of cancer metastasis and invasion. However, there is no established treatment to eliminate the EMT of cancer cells. Iron is an essential element for both normal and cancer cells in humans. Recently, iron depletion has been discovered to suppress tumor growth. Therefore, we hypothesized that decreased iron conditions would regulate EMT phenotypes, as well as suppressing tumor growth. The human TE esophageal cancer cell lines and OE19 were used in our study. Decreased iron conditions were made using an iron-depletion diet in mice and the iron chelator deferasirox for cell studies. Migration and invasion abilities of cells were measured using migration, invasion, and sphere-formation assays. Esophageal subcutaneous tumor growth was suppressed in decreased iron conditions. In vitro study showed that decreased iron conditions inhibited esophageal cancer cell proliferation as well as migration and invasion abilities, with downregulation of N-cadherin expression. Also, migration and invasion abilities were suppressed by inhibiting expression of N-cadherin. In conclusion, decreased iron conditions revealed a profound anticancer effect by the suppression of tumor growth and the inhibition of migration and invasion abilities via N-cadherin.

Purpose Evaluating the status of disease progression is critical for planning a therapeutic strategy for esophageal cancer. In this regard, F-18 fluorodeoxyglucose-labeled positron emission tomography (PET) is one of the most useful diagnostic modalities. However, there is room to improve its diagnostic performance, such as distinguishing lymph nodal metastases from false positives. In this study, we examined the diagnostic accuracy of fluorodeoxyglucose PET accompanied by computed tomography imaging (PET/CT) to detect regional lymph nodal metastasis from esophageal squamous cell carcinoma (ESCC). Methods A total of 102 patients diagnosed as ESCC were subjected to this study. These patients had a preoperative PET/CT examination to evaluate the existence of metastasis. The values of maximum standardized uptake value (SUVmax) in primary tumors and in metastasized lymph nodes were measured to analyze their relationship with various clinicopathologic characteristics including the status of tumor cell proliferation, which was assessed by immunohistochemistry for Ki-67. Results The SUVmax of the primary tumor was positively correlated with tumor size and vessel invasion, and was positively related with the SUVmax of lymph nodal metastasis, especially in cases of poorly differentiated ESCC. The SUVmax of metastasized lymph nodes was higher in larger-sized metastasized lymph nodes, whereas the Ki-labeling index of lymph nodal metastasis was positively related with the SUVmax per unit area (SUVmax/mm). The diagnostic accuracy of PET/CT (87.3%) was higher than that of conventional CT scans (78.4%). Conclusions The improved diagnostic accuracy of PET/CT can be explained by its ability to detect actively progressive metastasis at an early phase regardless of size.

Background Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Methods Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Results Most cases were males. The median interval from TEC surgery to GTC occurrence was 68.1 months (6–190 months). Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. Conclusion GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important. Disclosure All authors have declared no conflicts of interest.

Background Evaluation of the blood supply to gastric conduits is critically important to avoid complications following esophagectomy. We commenced visualized evaluation of blood flow using indocyanine green (ICG) fluorescent imaging from July 2015, to reduce reconstructive complications. In this study, we aimed to statistically verify the efficacy of blood flow evaluation using our simplified ICG method. Methods We analysed and compared two groups, those before and after introduction of ICG evaluation. We performed propensity score matching (PS-M), compared clinical outcomes and analysed how the visualized evaluation reduced the risk of complications. Results Sixty-eight matched pairs were analysed. The leakage rate in the ICG group was significantly lower than the non-ICG group for each severity grade both in the entire cohort (285 subjects) and after PS-M, while the rate of other major complications, including recurrent laryngeal nerve (RLN) palsy and pneumonia, were not different between the two groups in the entire cohort and after PS-M. The duration of postoperative intensive care unit (ICU) stay was approximately one day shorter in the ICG than the non-ICG group in the entire cohort, and approximately two days shorter after PS-M. Visualized evaluation of blood flow with ICG methods significantly reduced the rate of anastomotic complications of all Clavien-Dindo (CD) severity grades. Odds ratio with ICG evaluation decreased with CD grade (0.3419 for CD ≥ 1, 0.241 for CD ≥ 2 and 0.2153 for CD ≥ 3). Conclusion Objective evaluation of blood supply to the reconstructed conduit using ICG fluorescent imaging reduces the risk and degree of anastomotic complication. Disclosure All authors have declared no conflicts of interest.

Sonoda R, Naomoto Y, Shirakawa Y, Fujiwara Y, Yamatsuji T, Noma K, Tanabe S, Takaoka M, Gunduz M, Tsujigiwa H, Nagatsuka H, Ohara N, Yoshino T, Takubo K, Vieth M & Tanaka N (2010) Histopathology 57, 90–100 Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett’s oesophagus and intestinal-type gastric carcinoma Aims: Metaplastic changes secondary to chronic inflammation at the gastro–oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett’s oesophageal adenocarcinoma and intestinal-type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)-2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation-related carcinogenesis. Methods and results: First, expression of HPSE and COX-2 in 78 clinical tissues of Barrett’s oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia–dysplasia sequence with increased neovascularization. Successively, their expression in Barrett’s dysplasia was compared with that of GC (22 cases of diffuse-type and 10 of intestinal-type). Interestingly, the expression pattern in Barrett’s dysplasia was similar to that in intestinal-type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal-type, revealed up-regulated mRNA expression of HPSE and COX-2. Conclusions: HPSE and COX-2 are preferentially up-regulated in Barrett’s oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract.

Mediastinal lymph node metastasis from colorectal cancer is rare, and barely any reports have described resection of this pathology. We report herein a successful thoracoscopic resection of mediastinal lymph node metastasis in a prone position. A 65-year-old man presented with posterior mediastinal lymph node metastasis after resection of the primary rectal cancer and metachronous hepatic metastasis. Metastatic lymph nodes were resected completely using thoracoscopic surgery in the prone position, which provided advantages of minimal invasiveness, good surgical field, and reduced ergonomic burden on the surgeon. Thoracoscopic resection in the prone position was thought to have the potential to become the standard procedure of posterior mediastinal tumors.

This study assessed the techniques of the free jejunal graft for the reconstruction of hypopharynx or cervical esophagus and discussed the main aspects related to those procedures. By using free jejunal grafts, we reconstructed 54 hypopharyngeal and cervical esophageal cancers. In this study, 23 out of 54 patients had a malignant tumor located in the hypopharynx and 31 in the cervical esophagus (27 primary cases and four secondary cases). Despite the multi-step and time-consuming procedure, we did not incur any trans-operative complication. Furthermore, we undertook the larynx preserving cervical esophagectomy and free jejunal graft reconstruction in six patients with cervical esophageal cancer, and those patients acquired a good quality of life. For the reconstruction of hypopharynx or cervical esophagus, the free jejunal graft is a very useful technique and improves the patient’s quality of life.

Background: Cancer associated fibroblasts (CAFs) are activated fibroblasts and an important player in the tumor microenvironment. Their activity promotes cancer cell proliferation, migration, and invasion, and metastasis. The most prognostic factor in tumor progression is metastasis. Cancer metastasis is a multi-step process that tumor cells detach from primary site, survive in the bloodstream, and seed in target organ. Although previous studies have focused on the interaction between CAFs and cancer cells in primary tumor site, the roles of CAFs in blood circulation remain largely unknown. We investigated the effect of CAFs coexisting with cancer cells in bloodstream on tumor metastasis in vivo mouse model, and also examined the effect of CAFs in subcutaneous tumor. Methods: We used female BALB/c-nu/nu mice and BALB/c mice in the experiments. Cancer cells were mouse mammary carcinoma cell lines 4T1 transfected with luciferase, colon cancer cell lines Colon 26 transfected with luciferase. Fibroblast cell lines were mouse embryonic fibroblast MEF and NIH-3T3. In venous injection mouse model, we injected 1 × 106 cancer cells alone or the same number of cancer and fibroblast co-cultured together. When we injected cancer cells transfected with luciferase, the mice were subjected to in vivo imaging system (IVIS) and measured luminescence intensity of metastatic sites. We have also harvested lung and compared its weight and metastatic nodule under microscopy. Furthermore, in subcutaneous tumor metastatic mouse model, cancer cells alone or mixed with cancer cells and CAFs were subcutaneously inoculated into the mice. Results: In the group of mice injected with cancer cells and fibroblasts, luminescent intensity of each lungs were higher than cancer cell alone. Harvested lung weight and the number of metastatic nodules were also higher in the group with cancer cells and fibroblasts.In subcutaneous model, mice inoculated with cancer cells and fibroblast had much more metastatic sites than cancer cells alone. Conclusions: Our data indicate that CAFs promote tumor metastasis by stimulating cancer cells in blood circulation, as well as in primary tumor site.These findings suggest that CAFs in both bloodstream and primary site could be a promising therapeutic target. CAF-targeted therapy could reduce tumor metastasis and improve the prognosis of cancer patients. Citation Format: Hajime Kashima, Kazuhiro Noma, Hiroaki Sato, Yuki Katsura, Takuya Kato, Toshiaki Ohara, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Cancer associated fibroblasts promote tumor metastasis coexisting with cancer cells in blood circulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5905. doi:10.1158/1538-7445.AM2017-5905

Background: Gastric cancer is one of the most common cancers worldwide, especially in Eastern Asia. Scirrhous gastric cancer (SGC), which is characterized by poorly differentiated tumor cells that diffusely infiltrate the gastric wall, accounts for 10% of all gastric cancers, and often causes peritoneal metastasis. Peritoneal carcinomatosis shows the worst prognosis among various metastatic patterns. Since it is difficult to detect peritoneal micrometastasis preoperatively or intraoperatively, SGC patients with peritoneal micrometastasis show the recurrence and refractory to conventional systemic chemotherapy after surgery. In recent year, intraperitoneal (i.p.) administration of paclitaxel (PTX) has been shown to have therapeutic effects against ovarian cancer with peritoneal metastasis. However, the effective treatment option to overcome peritoneal metastasis of SGC has not been developed yet, although i.p. administration of some chemotherapeutic agents has been attempted to SGC. Therefore, a novel therapeutic strategy is required for the treatment of peritoneal metastasis of SGC. Methods: We previously developed a telomerase-dependent replication-selective adenovirus OBP-401 (TelomeScan), which can replicate within the tumor cells selectively and express green fluorescent protein (GFP). Moreover, OBP-401 infection also induces tumor-specific cell death in monotherapy or combination therapy with chemotherapy. In this study, we assessed synergistic effects in combination with novel theranostic agent OBP-401 and chemotherapeutic agent paclitaxel (PTX) using human SGC cell lines (GCIY and KATO III). In vitro experiment, SGC cells and normal human lung fibroblast (NHLF) cells were infected with OBP-401 at various doses. PTX was administrated after 48 hours of virus infection. Twenty-four hours after PTX administration, we evaluated the anti-tumor effect by XTT assay, and analyzed the synergistic effect by CalcuSyn Software. Results: SGC cells were visualized as GFP-positive cells selectively by the infection of OBP-401, whereas NHLF cells were not visualized with OBP-401. In both SGC cell lines, the suppression of cell viability dose-dependently by administration of OBP-401 or PTX alone was confirmed. OBP-401 synergistically suppressed the viability of SGC cells in combination with PTX as compared to monotherapy. Conclusions: These results suggest that OBP-401 has a promising potential to detect peritoneal micrometastasis of SGC intraoperatively and combination of OBP-401 and PTX would be a novel theranostic strategy for the treatment of peritoneal metastasis of SGC. Citation Format: Wataru Ishikawa, Satoru Kikuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara. Novel theranostic strategy against scirrhous gastric cancer; combination of chemotherapy and fluorescence oncolytic adenovirus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2017-1103

Background: Epithelial-mesenchymal transition (EMT) is a biological process, by which epithelial cancer cells acquire mesenchymal phenotype with malignant properties for invasion and metastasis, leading to poor prognosis. Inflammatory microenvironment has been shown to be responsible for the development and progression of colorectal cancer. However, the role of inflammatory microenvironment in the EMT-related tumor progression remains unclear. To explore the relationship between inflammatory microenvironment and EMT, a live imaging system for EMT is a promising strategy on the in vitro and in vivo experiments. In this study, we developed a fluorescence-guided live cell imaging system for the assessment of spatiotemporal dynamics of EMT, and investigated the potential of inflammatory microenvironment for the induction of EMT phenotype in human colorectal cancer. Methods: Two human colorectal cancer cell lines, HCT116 and RKO, were stably transfected with vimentin promoter-driven red fluorescence protein TurboFP635 expression vector. Both cell lines were treated with inflammatory cytokines, IL-1β (1 ng/ml) and TNF-α (20 ng/ml), or co-cultured with mouse macrophage cell line RAW264.7 in the presence of lipopolysaccharide (LPS) (200 ng/ml). The time-lapse live imaging was observed by confocal laser scanning microscope. Migration and invasion properties were examined by transwell chamber assays. The fluorescence intensity was measured by microplate reader and flow cytometric analysis. The expression of EMT-related markers was assessed by Western blot analysis and q-PCR. EMT-induced HCT116 and RKO cells were treated with anti-inflammatory agents, aspirin (1mM) and salicylic acid (1 mM), for the suppression of EMT. Results: Inflammatory cytokines (IL-1β and TNF-α) induced red fluorescence intensity and morphological change like mesenchymal phenotype in HCT116 and RKO cells. Removal of inflammatory cytokines attenuated red fluorescence intensity and morphological change in both cells. Inflammatory cytokines also induced the migration and invasion properties in association with EMT-related markers. Moreover, co-culture with LPS-stimulated inflammatory macrophages also induced red fluorescence intensity and morphological change as well as inflammatory cytokines. Anti-inflammatory agents significantly suppressed the fluorescence-related EMT phenotype under inflammatory microenvironment. Conclusions: These results suggest that inflammatory microenvironment has a great potential for the induction of EMT process during colorectal cancer progression. This unique fluorescence-guided EMT imaging system is useful method for the exploration of inflammation-mediated tumor progression. Citation Format: Takeshi Ieda, Hiroshi Tazawa, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Takeshi Imamura, Toshiyoshi Fujiwara. Fluorescence-guided spatiotemporal dynamics of epithelial-mesenchymal transition under inflammatory microenvironment during colorectal cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5809. doi:10.1158/1538-7445.AM2017-5809