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Abstract Access to accurate statistical data is paramount in the pursuit of effective cancer control activities, including research, policy development, and clinical care. This paper presents a comprehensive statistical report on the incidence, mortality, survival, and treatment of major digestive organ cancers, including those of the esophagus, stomach, colon, rectum, liver, extrahepatic biliary tract, and pancreas, in Japan. We compiled data from the National Cancer Center's “Cancer Information Services” and government “e‐Stat” websites and offered a succinct overview of basic statistics by using tables and graphical presentations. Our findings underscore the critical role of the National Cancer Registry introduced by the Cancer Registry Act of 2016, which mandates hospitals across Japan to report cancer cases. This system ensures more accurate incidence statistics. Mortality data sourced from the National Vital Statistics System and survival rates derived from hospital‐based cancer registries offer insights into the outcomes and efficacy of treatment modalities. These data indicate a downward trend in mortality for stomach and liver cancers and stable or declining rates for other cancers except pancreatic cancer, which has the lowest survival rate. Treatment patterns indicate an increase in endoscopic procedures for esophageal and stomach cancers, with stable treatment approaches for colorectal cancer. This statistical overview aims to improve the understanding and inform research, policy, and clinical decisions in the field of digestive organ cancers.

Abstract Background Conversion surgery (CS) is a highly anticipated strategy for stage IV advanced gastric cancer (AGC) with a good response to chemotherapy. However, prognostic factors limiting R0 resection remain unclear. In this multi‐institutional study, we investigated the clinical outcomes of CS for stage IV AGC and the prognostic factors of CS‐limiting R0 resection and analyzed them according to metastatic patterns. Methods Clinical data on 210 patients who underwent CS for stage IV AGC at six institutions between 2007 and 2017 were retrospectively retrieved. The patient background, preoperative treatment, operative outcomes, and survival times were recorded. Prognostic factors for overall and recurrence‐free survival were investigated using univariate and multivariate analyses for patients who underwent R0 resection. Results R0 resection was achieved in 146 (70%) patients. The median survival time was 32 months, and the 3‐year survival rate was 45%. Patients who achieved R0 resection had significantly longer survival than those with R1/2 resection (median survival time: 41.5 months vs. 20.7 months). Multivariate analysis identified pathological N positivity for overall and relapse‐free survival and pathological T4 for relapse‐free survival as significant independent poor prognostic factors of R0 resected patients. There was no significant difference in survival among the peritoneum, liver, and lymph node groups regarding the initial metastatic sites. Conclusions CS with R0 resection for patients with stage IV AGC can lead to longer survival. Patients with pathological T4 and pathological N positivity were eligible for intensive adjuvant therapy after CS with R0 resection.

Abstract Background The COVID‐19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID‐19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID‐19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID‐19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web‐based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity‐leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot‐assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre‐pandemic period. Conclusions Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID‐19 pandemic.

Abstract Purpose The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer.

Abstract Aim To compare the effects of open (OG) and laparoscopic gastrectomy (LG) on body composition and muscle strength. Methods This study performed a propensity score matching analysis using cases from a large‐scale, multicenter, phase III randomized controlled trial concerning oral nutritional supplements after gastrectomy and analyzed both the whole and matched cohorts. Measurements of body composition and hand grip strength (HGS) were performed at baseline (preoperatively) and at 1, 2, 3, 6, and 12 months after gastrectomy. Results Of 835 patients, 275 and 560 underwent OG and LG, respectively. Skeletal muscle mass (SMM) and HGS loss were significantly lesser in the LG group than in the OG group. The propensity score‐matched analysis, including 120 pairs of patients, confirmed that the % SMM loss values at 1, 2, 3, 6, and 12 POM were −4.5%, −4.0%, −4.7%, −4.6%, and −5.8% in the OG group and −3.0%, −1.9%, −2.4%, −2.2%, and −2.7% in the LG group, respectively. The % SMM loss was significantly lesser in the LG group than in the OG group (repeated measures ANOVA p

Abstract Aim Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien–Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results Fifty‐one patients developed SBO (median follow‐up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562–6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683–2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Abstract Background A diaphragmatic hernia is a prolapse of the abdominal organs into the thoracic cavity through a hole in the diaphragm. Traumatic diaphragmatic injuries are rare and usually occur after blunt or penetrating thoracic or abdominal traumas. Blunt diaphragmatic rupture rarely accounts for immediate mortality and may go clinically silent until complications occur which can be life threatening. It usually present late with intrathoracic herniation of abdominal viscera and carry a high mortality rate. We experienced a very rare case who showed repeated colon incarcerations 7 years after injury. And, we operated laparoscopically. Case presentation A 64-year-old man presented with multiple left rib fractures that occurred during an accident. After 7 years, he visited the emergency department with the chief complaint of left shoulder pain and epicardial pain after eating. He was diagnosed with transverse colon incarceration due to a left diaphragmatic hernia by computed tomography (CT) and X-ray imaging. Surgical repair was recommended, but he refused as the symptoms improved. Fourteen months later, the patient revisited the hospital in similar symptoms and improved spontaneously. He consulted our hospital for the surgical indication. We recommended that he undergo surgery, showing images of the X-ray and CT when his transverse colon was obstructed and he felt pain and when symptoms improved. Finally, he decided to undergo surgery. We performed diaphragmatic hernia repair with laparoscopic direct suturing in good view. The patient experienced an uneventful postoperative recovery period. The absence of diaphragmatic herniation recurrence was confirmed seven months after surgery. Conclusions We experienced a traumatic diaphragmatic hernia with repeated colon incarcerations 7 years after injury and performed surgical repair laparoscopically.

Abstract Objectives Flexible endoscopy does not have a system that can automatically evacuate surgical smoke generated in the gastrointestinal lumen. We aimed to investigate the feasibility and potential usefulness of automatic smoke evacuation systems in flexible endoscopy. Methods [Bench] After surgical smoke generated in the stomach was evacuated by the evacuator, the degree of residual smoke and gastric luminal collapse were evaluated to optimize the evacuator settings. [Animal] Insufflation, suction, and total operation time to complete the protocol of 10 cauterizations of the gastric mucosa were measured in three groups: “manual suction only,” “manual suction with automatic evacuation (50% force),” and “manual suction with automatic evacuation (70% force).” The stability of endoscopic visualization and operability was evaluated by 10 endoscopists blinded to those suction settings, and the number of manual suctions, insufflations, and total operation time were measured. Results [Bench] The degree of residual smoke and gastric luminal collapse were inversely correlated. [Animal] When the automatic evacuator was partially used, there was no difference in the insufflation time, but the suction time (vs 50%; p = 0.011, vs. 70%; p = 0.011) and total operation time (vs. 50%; p = 0.012, vs. 70%; p = 0.036) were significantly reduced compared to manual operation only. Furthermore, manual suction with automatic evacuation (50% force) significantly improved the stability of endoscopic visualization and operability compared to manual operation only (p = 0.041, p = 0.0085). Conclusions The automatic smoke evacuation in flexible gastrointestinal endoscopy was potentially feasible and useful by improving the device setting.

Abstract Background and aims In our previous study, we visualized and systematically evaluated gas leakage from the forceps plug of the gastrointestinal endoscope system using the Schlieren system. In order to minimize the potential risk of infection from gas leakage from the gastrointestinal endoscope, the development of a new forceps plug was considered urgent. In this study, we analyzed the structure of commercially available forceps plugs and attempted to develop new forceps plugs with improvements. Methods Microfocus computed tomography was used to nondestructively analyze the structural changes that occur when forceps are inserted into a commercially available forceps plug. Based on the findings, the basic structure of the newly developed forceps plug was set. We examined the airtightness of these newly developed plugs using the Schlieren system and also compared their fractional resistance with those of commercially available plugs. Results As a result of the nondestructive analysis, all of the commercially available plugs had a single valve, and the cleavage created in the valve during forceps, insertion was large in the case of plugs with slit‐type entrances. In the newly developed forceps plugs, all four types of plugs showed less gas leakage and similar or better usability compared to the commercially available plugs. Conclusions The structural weaknesses of the existing gastrointestinal endoscopic forceps plugs were identified. Based on the findings, we froze the design of a prototype of a new forceps plug that was airtight and not inferior in usability compared to commercially available plugs.

Abstract Treatment strategy for locally advanced gastric cancer differs worldwide. Neoadjuvant chemotherapy (NAC) is considered one of the promising treatment options for locally advanced gastric cancer, even in Japan, and clinical trials have been conducted or are ongoing. A consensus meeting was organized at the 77th general meeting of the Japanese Society of Gastroenterological Surgery in 2022, in which the current status and future prospects of NAC for locally advanced gastric cancer were discussed. Participants at the meeting looked forward to the results of the JCOG1509 trial, providing solid evidence regarding NAC. The optimal indications and regimens for NAC were also debated. Patients with cStage III gastric cancer are the main targets of NAC in Japan, and a doublet regimen of S‐1 and oxaliplatin was preferred by the participants. However, the feasibility of a triplet regimen with S‐1, oxaliplatin, and docetaxel, and that with 5‐FU, leucovorin, oxaliplatin, and docetaxel has been demonstrated, and these could become treatment options in Japan. Other points of discussion include perioperative chemotherapy to avoid peritoneal recurrence and for patients with dMMR/MSI‐high tumors. The panel regarded NAC as a promising treatment option, and NAC will become the standard treatment for cStage III gastric cancer in Japan if an ongoing clinical trial successfully demonstrates its efficacy.

Abstract Aim Tumor rupture has been indicated as a risk factor for recurrence of gastrointestinal stromal tumors (GISTs). The universal definition of tumor rupture was proposed. This study evaluated whether the universal definition was more accurate in identification of GISTs with high recurrent risk than subjective judgment. Methods The study included 507 patients with high‐risk GISTs who underwent complete resection between December 2012 and December 2015. We conducted a questionnaire survey in participating institutes to re‐diagnose tumor rupture based on the universal definition according to their surgical and pathological findings. We compared the clinical outcomes of tumor rupture based on the definition to those based on the surgeon's judgment and clarified the clinical importance of the rupture. Results Sixty‐four patients were initially registered to have tumor rupture by surgeon's judgment, and it became 90 patients who had tumor rupture after reevaluation. Although there were significant differences in recurrence‐free survival (RFS) between no rupture and rupture for both initial registration and reevaluation (p = 0.002,

Abstract Background Severe scoliosis can cause reflux esophagitis, and is a risk factor for Barrett's adenocarcinoma of the esophagus. Severe scoliosis is associated with respiratory dysfunction, impaired operative tolerance, and anatomical difficulty in surgical manipulation, and is, therefore, considered a high surgical risk. In this report, we describe the case of a young patient with Barrett's esophageal adenocarcinoma with severe scoliosis who underwent salvage surgery after radical chemoradiotherapy. Case presentation The patient was a 39-year-old male. Although he had severe scoliosis and paraplegia of both lower limbs since childhood, he was independent in activities of daily living. His previous doctor, who diagnosed the esophageal cancer, determined that surgery was not indicated due to the coexistence of severe scoliosis, so he underwent chemoradiotherapy with curative intent. After chemoradiotherapy, the patient was referred to our hospital for a second opinion because of a tumor remnant. After various additional examinations, thoracoscopic and laparoscopic subtotal esophagectomy for esophageal cancer was performed, along with ante-thoracic route reconstruction using a narrow gastric tube. Although the patient had symptoms associated with postoperative reflux, he recovered well overall and was discharged home about 4 weeks after surgery. Conclusions We report the case of an esophageal cancer patient with severe scoliosis at high surgical risk who underwent successful minimally invasive esophagectomy.

Abstract Background Familial gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the digestive tract caused by germline gain-of-function mutations in the KIT gene or platelet-derived growth factor receptor alpha gene (PDGFRA). These mutations cause not only multiple GISTs but also diffuse hyperplasia of interstitial cells of Cajal (ICCs), which is related to esophageal motility disorder. Case presentation A 53-year-old man was referred to our hospital because of anemia and dysphagia. Fifteen years earlier, he had undergone a laparoscopic partial gastrectomy for multiple gastric GISTs with a germline mutation in exon 17 of the KIT gene. An upper gastrointestinal endoscopy revealed that the patient had multiple gastric GISTs and a large esophageal diverticulum directly above the esophagogastric junction. The largest gastric tumor was 7 cm, with a delle that might cause bleeding. Because the patient presented with dysphagia, we performed video-assisted thoracic esophagectomy and laparoscopic-assisted proximal gastrectomy simultaneously. The patient had survived without metastasis for 4 years after surgery and dysphagia had improved. Conclusions This is the first report of successful laparoscopic–thoracoscopic surgery for a patient with familial gastric GISTs accompanied with a large esophageal diverticulum.

Abstract Background Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. Methods We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien–Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. Discussion This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. Trial registration The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

Abstract In recent years, important clinical trials for gastric cancer (GC) and esophagogastric junction cancer (EGJC) have been reported, changing the strategies of surgical and perioperative treatment. Although laparoscopic gastrectomy has already been shown to be effective for early‐stage cancer, recent evidence from both Asia (JLSSG0901, CLASS‐01 and KLASS‐02) and Europe (LOGICA and STOMACH trials) has demonstrated that it is useful for advanced GC. Robotic surgery has been rapidly gaining popularity in recent years, and randomized controlled trials are ongoing to evaluate its efficacy. A prospective nationwide multicenter study mapped sites with frequent metastasis and revealed lymphatic flow specific to EGJC, thus establishing the optimal lymph node dissection area and surgical approach based on esophageal involvement. Perioperative chemotherapy, the mainstay of treatment in Europe, also has been established in Asia by the PRODIGY and RESOLVE studies. New clinical trials have been conducted to evaluate the efficacy of combining immunotherapy or molecular‐targeted therapy with perioperative chemotherapy or chemoradiotherapy. In this review, we present important recent clinical trials regarding the treatment of GC and EGJC published in 2021 or 2022.

Abstract Aim This study aimed to evaluate the impact of the coronavirus disease (COVID‐19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database. Methods We retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups. Results In 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot‐assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020. Conclusion The number of endoscopic surgeries decreased in 2020 as a result of the COVID‐19 pandemic. However, the procedures were performed safely in Japan.

Abstract Background Exon 18 D842V, which is a point mutation from aspartic acid to valine at codon 842, is the most frequent mutation in Platelet-Derived Growth Factor Receptor alpha (PDGFRA)-mutated gastrointestinal stromal tumor (GIST). In the Japanese GIST guidelines, no standard systematic therapy is available for this type of GIST, which is refractory after recurrence. Recently, pimitespib (PIMI), a novel heat shock protein 90 (HSP90) inhibitor, was approved for the treatment of advanced GIST in a phase III study. This report presents a case of a long-term response to PIMI in GIST with PDGFRA D842V mutation. Case presentation A 55-year-old woman was diagnosed with primary GIST of the stomach and underwent partial gastrectomy. Eight years after the operation, recurrent GISTs were identified as multiple recurrent peritoneal GISTs in the upper right abdomen and pelvic cavity. We administered tyrosine kinase inhibitors, but they achieved poor effects. After failure of the standard treatment, PIMI was administered and achieved a partial response in the patient. The highest reduction rate was 32.7%. After PIMI failed, we performed multiplex gene panel testing, which revealed the PDGFRA D842V mutation. Conclusions We report the first case of long-term response to PIMI in PDGFRA D842V mutant GIST. Pimitespib may be effective for treating GIST harboring this mutation by inhibiting HSP90.

Abstract Background Although perioperative treatment has been the standard of care for resectable gastric cancer in the West, postoperative adjuvant chemotherapy is still the standard in Japan. We conducted the first phase 2 trial to investigate the efficacy and safety of neoadjuvant docetaxel, oxaliplatin, and S‐1 (DOS) chemotherapy for cStage III gastric or esophagogastric junction (EGJ) adenocarcinoma in Japan. Methods Eligibility criteria included cStage III adenocarcinoma of the stomach or EGJ. Patients received docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), or S‐1 (80 mg/m2, days 1–14) during a 3‐week cycle. After two or three cycles of DOS, patients underwent surgical resection. The primary endpoint was progression‐free survival (PFS). Results Between June 2015 and March 2019, 50 patients were enrolled from four institutions. Of 48 eligible patients (37 gastric and 11 EGJ adenocarcinoma), 42 (88%) completed two or three DOS cycles. Grade 3–4 neutropenia and diarrhea occurred in 69% and 19% of patients, respectively, but there were no treatment‐related deaths. R0 resection was achieved in 44 (92%) patients, and the pathological response rate (≥ grade 1b) was 63% (30/48). The 3‐year PFS, overall survival, and disease‐specific survival rates were 54.2%, 68.7%, and 75.8%, respectively. Conclusion Neoadjuvant DOS chemotherapy had a sufficient antitumor effect and tolerable safety profile in patients with gastric or EGJ adenocarcinoma. The survival benefit of a neoadjuvant strategy using our DOS regimen should be validated in phase 3 trials.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most severe cancers and is characterized by chemotherapy resistance and poor prognosis associated with epithelial-mesenchymal transition (EMT). In a previous study, a low mitochondrial DNA (mtDNA) copy number was associated with poorer prognosis and induced EMT in ESCC. However, the detailed mechanism related to mtDNA copy number and EMT is unclear. The aim of this study was to clarify the mechanism by which a change in mtDNA copy number contributes to EMT and to examine treatment of chemotherapy resistance in ESCC. Methods The association between low mtDNA copy number and chemotherapy resistance was investigated using specimens from 88 patients who underwent surgery after neoadjuvant chemotherapy. Then, the mtDNA content of human ESCC cell lines, TE8 and TE11, was depleted by knockdown of mitochondrial transcription factor A expression. The present study focused on modulation of mitochondrial membrane potential (MMP) and DNA methylation as the mechanisms by which mtDNA copy number affects EMT. mRNA and protein expression, chemotherapy sensitivity, proliferation, MMP and DNA methylation were evaluated, and in vitro and in vivo assays were conducted to clarify these mechanisms. Results ESCC patients with decreased mtDNA copy number who underwent R0 resection after neoadjuvant chemotherapy had significantly worse pathological response and recurrence-free survival. Additionally, low mtDNA copy number was associated with resistance to chemotherapy in vitro and in vivo. mtDNA controlled MMP, and MMP depolarization induced EMT. Depletion of mtDNA and low MMP induced DNA methylation via a DNA methylation transcription factor (DNMT), and a DNMT inhibitor suppressed EMT and improved chemotherapy sensitivity in mtDNA-depleted ESCC cells, as shown by in vitro and in vivo assays. Conclusion This study showed that decreased mtDNA copy number induced EMT via modulation of MMP and DNA methylation in ESCC. Therapeutic strategies increasing mtDNA copy number and DNMT inhibitors may be effective in preventing EMT and chemosensitivity resistance.

Abstract Background Large type 3 and type 4 gastric cancers have extremely poor prognoses. To address this, neoadjuvant chemotherapy may be a promising approach. The phase III JCOG0501 study, conducted to confirm the superiority of neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy over upfront surgery, showed no survival benefit for neoadjuvant S-1 plus cisplatin. In Korea, the PRODIGY study, which was a phase III study of neoadjuvant docetaxel plus oxaliplatin plus S-1 (DOS) followed by surgery and adjuvant S-1 versus surgery and adjuvant S-1 for gastric cancer of T2-3N+ or T4Nany, showed that progression-free survival (PFS) was significantly superior in the neoadjuvant DOS arm. Therefore, DOS therapy may be a promising candidate for preoperative chemotherapy for large type 3 or type 4 gastric cancer. Methods Preoperative docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 will be intravenously administered on day1 every three weeks. S-1 will be orally administered 80 mg/m2 on days 1–14 of a 21-day cycle. Patients will receive three courses of treatment and gastrectomy with ≥D2 lymph node dissection. Postoperative S-1 plus docetaxel therapy (DS) will be administered according to the JACCRO GC-07 (START-2) study. The primary endpoint is the 3-year PFS rate. Secondary endpoints include PFS time, overall survival time, pathological response rate, response rate according to RECIST version1.1, proportion of completion of neoadjuvant chemotherapy, R0 resection rate, proportion of completion of surgery, proportion of completion of protocol treatment, proportion of negative conversion of CY, adverse event occurrence rate, and nutritional evaluation. The null hypothesis for the 3-year PFS rate is 45% and the expected value is 60%. The total sample size is 46 considering that the registration period and follow-up period are two and three years, respectively. Discussion This is a prospective, multicenter, single-arm, open-label, phase II trial assessing the efficacy and safety of preoperative DOS and postoperative DS for large type 3 or type 4 gastric cancer. The results will inform future phase III trials and are expected to lead to new treatment strategies for large type 3 or type 4 gastric cancer. Trial registration Registered with Japan Registry of Clinical Trials on October 11, 2019 ( jRCTs051190060 ).

Abstract Background Although docetaxel plus S-1 adjuvant chemotherapy after gastrectomy with D2 lymphadenectomy has been a standard of treatment for stage III gastric cancer, there is no established chemotherapy for patients with recurrence during or within six months after the completion of adjuvant docetaxel plus S-1 therapy. Methods The OGSG 1901 trial is a prospective, open-label, multicenter, phase II trial evaluating ramucirumab plus irinotecan for gastric cancer patients with early relapse after adjuvant docetaxel plus S-1 therapy. The key eligibility criteria were: 1) histologically confirmed gastric adenocarcinoma 2) patients who were on docetaxel plus S-1 adjuvant chemotherapy after the confirmation of pathological stage III, 3) patients with early relapse, i.e., recurrence during or within 6 months after the completion of docetaxel plus S-1 therapy, and 4) patient with Eastern Cooperative Oncology Group performance status of 0–1. Irinotecan (150 mg/m2, day 1) and ramucirumab (8 mg/kg, day 1) will be administered every 2 weeks. The primary endpoint is overall survival, and the secondary endpoints are overall response rate, progression-free survival, and safety. The number of patients has been set at 40 based on the threshold and expected median survival times of 7 and 11 months, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods are 2 and 1.5 years, respectively. Discussion The results of this trial will indicate whether the ramucirumab with irinotecan regimen has the potential to be a recommended treatment regimen for patients with recurrence gastric cancer during or within 6 months after the completion of adjuvant docetaxel plus S-1 therapy. Trial registration This study was registered in the Japan Registry of Clinical Trials ( jRCTs05119071 , October 6, 2019).

Summary: Introduction: Peripherally inserted central venous catheter (PICC) has a risk of causing phlebitis and thrombus occlusion. We coated the surfaces of the PICC with a specialized coating material (SEC-1) which may prevent thrombogenicity and phlebitis. This study aimed to evaluate SEC-1 coating PICCs using big animal. Methods: SEC-1 coating was used to both the internal and external surface of the catheter. In internal coating evaluation, the swine blood was filled up to 10 cm from the tip of the catheter into both non-coated and SEC-1-coated PICC (4Fr). Then we attempted to release the catheter occlusion at 5, 15 and 30 min while measuring the occlusion pressure by a digital pressure gauge. In external coating evaluation, after optimizing the phlebitis model using milk vein in swine, both PICCs inserted at a depth of 15 cm in the vein were forcibly withdrawn a distance of 5 cm and re-inserted 100 times. After 2days, we assessed inflammatory cell infiltration by histological evaluation. Result: The catheter occlusion release pressure at 5 min was measured at the non-coated: 2 and SEC-1-coated PICC:2 kPa. At 15 min, 7 and 4 kPa (p=0.38). At 30 min, 30 and 4 kPa (p=0.01). In external coating evaluation, there was no clear difference between the non-coated and the SEC-1-coated PICC in terms of inflammatory cell infiltration. Conclusion: The results of this study suggest that antithrombotic coating (SEC-1 coating) of PICC catheters may inhibit thrombogenicity. However, we were unable to confirm that it was effective in the control of phlebitis.

Abstract The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P

Abstract Aim Post‐surgical weight loss influences chemotherapy compliance and may be a risk factor for survival. Intake of an oral elemental nutritional supplement (OENS) can reduce weight loss after gastric cancer (GC) surgery. We assessed whether therapy completion levels would increase in patients receiving postoperative adjuvant chemotherapy in combination with an OENS. Methods This was a multicenter, open‐label, single‐arm, phase II study in GC patients who underwent curative total or distal gastrectomy (TG/DG) and received adjuvant S‐1 chemotherapy. The primary endpoint was the S‐1 completion rate for 1 year with a relative performance (RP) value of ≥70%; secondary endpoints included factors affecting the completion rate of S‐1, RP value after eight S‐1 courses, S‐1 and OENS persistence rates, nutritional index, OENS compliance, and safety. Results In 71 efficacy‐evaluable patients, the S‐1 completion rate was 69.0% (TG, 68.0%; DG, 69.6%) and the RP value was 87.5 (TG, 89.1; DG, 87.5). Over eight treatment courses, median persistence rates were 89.0% for S‐1 and 93.8% for the OENS. The mean OENS compliance was 81.8% at the fourth S‐1 course and 52.9% at the eighth course. The incidence of Grade 3 or 4 adverse events was 27.2%, most commonly neutropenia (12.3%). Conclusions The completion rate of S‐1 for 1 year in patients who could take the OENS exceeded the pre‐defined threshold level. Randomized controlled trials are warranted to confirm the role of OENS in adjuvant chemotherapy.

Abstract Aim Osteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy. Methods Of the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L‐BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates. Results There was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L‐BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (−25.6% vs −1.6%, P

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the deadliest of all human squamous cell carcinomas and is characterized by chemotherapy resistance and poor prognosis associated with the epithelial–mesenchymal transition (EMT). A subset of ESCC displays loss‐of‐function mutations in genes encoding Notch receptor family members, including NOTCH3. Although Notch signaling regulates EMT in ESCC cells, the role of NOTCH3 in EMT and chemotherapy resistance remains elusive. This study aimed to examine the role of NOTCH3 in EMT and chemotherapy resistance, and determine whether NOTCH3 expression can be used to predict the response to chemotherapy. Methods In vitro and in vivo assays were conducted to clarify the contribution of NOTCH3 to chemotherapy resistance. Using specimens from 120 ESCC patients treated with neoadjuvant chemotherapy, we compared the expression levels of NOTCH3 and genes involved in EMT according to the degree of chemotherapy sensitivity. Results In ESCC cells, chemotherapy resistance was associated with NOTCH3 downregulation and concurrent activation of EMT. RNA interference to silence NOTCH3 resulted in induction of the EMT marker Vimentin (VIM), leading to chemotherapy resistance in ESCC cells. Conversely, ectopic expression of the activated form of NOTCH3 suppressed EMT and sensitized cells to chemotherapy. Results of chromatin immunoprecipitation assays suggested that NOTCH3 may repress transcription of the VIM. Conclusions Our findings suggest that NOTCH3 may control chemotherapy sensitivity by regulating EMT. NOTCH3 may serve as a novel biomarker to predict better clinical outcomes in ESCC patients.

Abstract Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.

Abstract Aim We previously reported in a randomized controlled trial that Billroth I and Roux‐en‐Y reconstructions were generally equivalent regarding body weight change and nutritional status 1 year after distal gastrectomy for gastric cancer. We describe the long‐term follow‐up data 5 years after distal gastrectomy. Methods We analyzed consecutive gastric cancer patients who were randomly assigned to undergo Billroth I or Roux‐en‐Y reconstruction after distal gastrectomy. We evaluated body weight change, nutritional status, late complications, quality of life (QOL) using the European Organization for Research and Treatment of Cancer Core QOL Questionnaire, and dysfunction using the Dysfunction After Upper Gastrointestinal Surgery for Cancer, 5 years after surgery. Results A total of 228 patients (Billroth I = 105; Roux‐en‐Y = 123) were eligible for efficacy analyses in this study. Body weight loss 5 years after surgery did not differ significantly between the Billroth I and Roux‐en‐Y groups (10.0% ± 7.9% and 9.6% ± 8.4%, respectively; P = .70). There were no significant differences in other aspects of nutritional status between the two groups. Reflux esophagitis occurred in 19.0% of the patients in the Billroth I group vs 4.9% in the Roux‐en‐Y group (P = .002). Regarding QOL, Billroth I was significantly inferior to Roux‐en‐Y on the diarrhea scale (Billroth I: 28.6, Roux‐en‐Y: 16.0; P = .047). Regarding dysfunction, no score differed significantly between the two groups. Conclusions Billroth I and Roux‐en‐Y reconstructions were generally equivalent regarding body weight change, nutritional status, and QOL 5 years after distal gastrectomy, although Roux‐en‐Y more effectively prevented reflux esophagitis and diarrhea.

Abstract Background Self‐assembling peptides (TDMs) comprise synthetic amphipathic peptides that immediately react to changes in pH and/or inorganic salts to transform into a gelatinous state. The first generation of these peptides (TDM‐621) is currently used as a hemostatic agent in Europe. However, TDM‐621 exhibits slow gel‐formation and low retention capabilities on tissue surfaces. The second generation (TDM‐623) was therefore developed to encourage faster gel‐formation and better tissue‐sealing capabilities. Aim The aim of this study was to verify the efficacy of TDM‐623 in terms of its hemostatic effect in endoscopic surgery. Materials and methods Evaluation of the hemostatic effect in endoscopic surgery (animal study) was performed using eight porcine in spine position. Following systemic heparinization, we established a “bleeding model” by endoscopic grasping forceps on the anterior walls of the stomach and duodenum. In the hemostasis method, an endoscope with a distal hood was brought into contact with the bleeding point, and 1 ml TDM‐623 was applied to the wound. After TDM‐623 gelation, the endoscope was removed, and the acute hemostatic effect (after 2 min) was confirmed. Result In the endoscopic bleeding model, 17 of the 23 cases (74%) showed complete hemostatic effects on the anterior wall of the stomach, and 18 of the 20 cases (80%) on the anterior wall of the duodenum, respectively. None of the applied gels were displaced from the anterior walls of the stomach and duodenum. Conclusion The new self‐assembling peptide (TDM‐623) showed high hemostatic effects. TDM‐623 had potential usefulness for upper gastrointestinal endoscopic surgery.

Abstract Introduction Animal experiments with large living animals are essential for the development of medical devices and the training of surgical procedures. Swine are frequently used in animal experiments due to their similar size and anatomy compared to humans. However, it is well known that swine has less local bleeding than humans. The aim of the study was to verify whether animal models with appropriate local bleeding capability could be established. Methods The activated clotting time (ACT) was measured for eight swine (piglet, 35 kg) under general anesthesia. The flexible endoscope was advanced orally, and the gastric mucosa was intentionally traumatized to bleed by biopsy forceps, and the time until spontaneous hemostasis was obtained (mucosal bleeding time). Then, heparin (50 U/kg) was administered intravenously. After 10 min, the ACT was remeasured, and the gastric mucosa was again damaged to bleed by biopsy forceps. The mucosal bleeding time was remeasured. The above measurements were repeated until the ACT exceeded 200 s. Results The median ACT values (seconds) were 83 (no heparin), 155 (50 U/kg heparin), and 204 (100 U/kg heparin), which were significantly increased. The median mucosal bleeding times (seconds) were 152 (no heparin), 283 (50 U/kg), and 423 (100 U/kg), which were significantly extended. Conclusion A bleeding animal model for surgical and endoscopic training was successfully established by bolus heparin administration.

Abstract Objectives Endoscopic submucosal dissection (ESD) has become popular, but complications such as postoperative bleeding remain an issue. Although some methods of closing a mucosal defect with a snare and clips have been reported to be effective and safe, the snare is not a dedicated device, and the procedure is difficult and time‐consuming. We aimed to find an alternative method for defect closure after ESD by developing a dedicated device. Methods We have improved five prototypes. The load on the stopper when starting to tighten and loosen a loop and the maximum load on the stopper and the movement distance of the thread when sliding the stopper were measured five times for each prototype. With the 5th prototype, we finalized the design and named it FLEXLOOP. Additionally, the material and shape of the outer tube were improved. Then, the usability of FLEXLOOP was evaluated in pigs. The operation time for closing mucosal defects with the snare or FLEXLOOP was measured five times. Results We made FLEXLOOP, which had a lower load when sliding and a higher load when loosening than the snare. The improvement of the outer tube significantly reduced the load on the sheath when sliding it. We confirmed the feasibility of mucosal defect closure with FLEXLOOP in pigs. The median operation time was 563 s (range 340–679 s) with the snare and 355 s (range 303–455 s) with FLEXLOOP (p = 0.047). Conclusions FLEXLOOP can be a promising option for defect closure after ESD.

Abstract Background Systemic lupus erythematosus (SLE), an autoimmune disease characterized by systemic inflammatory lesions, is often associated with obesity. Obesity aggravates symptoms of SLE; however, these symptoms can be improved by weight loss through diet therapy and bariatric surgery. However, there are only a few reports regarding the effectiveness of bariatric surgery in obese patients with SLE. Herein, we discuss the laparoscopic sleeve gastrectomy (LSG) performed in an obese patient with SLE while undergoing long-term steroid therapy. Case presentation A 36-year-old female, suffering from SLE for 10 years with effects on the central nervous system, developed diabetes mellitus (DM) triggered by the steroid therapy for SLE. The patient was undergoing steroid therapy (6 mg/day) for SLE since a long time. For DM management, her HbA1c level was maintained at 7.4%. She was 158 cm tall and 91.6 kg in weight. Her body mass index was 36.7. She could not work and depended on welfare services. To improve her obesity and DM, physicians suggested that she should undergo bariatric surgery in our hospital. Eventually, she underwent LSG, which lasted for 185 min, with minimal blood loss and without complications. Her blood glucose level stabilized immediately after the surgery; hence, her antidiabetic medication was discontinued. She was discharged 8 days after surgery, and her weight decreased steadily. In the first year after surgery, her weight was 54.4 kg, and she had lost approximately 37 kg from her initial weight. Her steroid requirement had also reduced to 4 mg/day. Through weight loss, she could begin to work and became a part of society again. Conclusion LSG was safely performed in an obese patient with SLE undergoing long-term steroid therapy. We noted substantial weight loss, improved DM condition, and reduced requirement of SLE therapy after surgery. Hence, surgical risks must be carefully examined before patients undergo bariatric surgery.

Abstract Background A cytotoxic chemotherapeutic regimen is not routinely recommended for frail elderly patients with unresectable colorectal cancer (CRC) because of susceptibility to treatment. Panitumumab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Use of panitumumab as first-line therapy is expected to be well tolerated and to improve survival rates, even in patients who are not eligible for intensive chemotherapy. However, the efficacy and safety of panitumumab as the first-line therapy for the frail elderly patients with unresectable CRC have not been yet studied. Methods We plan to conduct a prospective multi-center phase II study. Patients with wild-type RAS unresectable CRC aged ≥76 years or ≥ 65 who are not considered eligible for intensive chemotherapy will be included in the study. A total of 36 patients will be enrolled from Osaka Gastrointestinal Cancer Chemotherapy Study Group for over 2 years. Panitumumab 6 mg/kg IV infusion will be administered every 2 weeks. The purpose of this trial is to assess the efficacy of panitumumab as first-line therapy for patients with unresectable CRC. The primary endpoint is to determine the disease control rate. Secondary endpoints include progression-free survival, overall survival, response rate, time to treatment failure, and the incidence of grade 3/4 toxicities. Discussion This is a prospective phase II trial assessing the efficacy of panitumumab monotherapy in the elderly patients with wild-type RAS unresectable CRC. Trial registration The ethics committee of the Osaka Medical College approved this study on November 7, 2016. The trial registration number of the government was UMIN000024528 on December 1, 2016. It was registered prospectively (the day of enrollment of the first participant was February 9, 2017).

Abstract Background Diaphragmatic hernias (DH) are generally classified as either congenital or acquired. Acquired DH are generally of traumatic cause, being a rare complication after hepatectomy. Although repair of a DH can be performed via laparotomy, laparoscopy, or thoracoscopy, the use of laparoscopy is rare after hepatectomy owing to the formation of scar tissue. In this case, we describe our successful attempt at laparoscopic repair of a recurrent DH after hepatectomy. Case presentation A 30-year-old man underwent right hepatectomy for trauma and thoracotomy via the eighth intercostal space, with direct closure of the diaphragm by suturing. The patient subsequently developed a right DH, with strangulation ileus of the small intestine. He underwent laparotomy 3 months after the initial surgery. The defect was observed to be clearly separate from the previously sutured area of the diaphragm. Five years after treatment, the patient developed abdominal pain and vomiting due to incarceration of the transverse colon in the right intrathoracic space (detected via abdominal computed tomography and radiography). The patient was again diagnosed with DH and underwent laparoscopic repair of the hernia with direct closure. The patient was discharged 11 days after surgery without further complication. Conclusions A laparoscopic approach was feasibly and safely used to repair a recurrent DH after hepatectomy. The surgical approach will need to be decided in a patient-specific manner.

Abstract Background Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Ramucirumab either alone or in combination with paclitaxel (PTX) has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is gastrointestinal (GI) perforation. Case presentation We report the case of a 67-year-old man who developed a ramucirumab-related GI perforation while undergoing treatment for gastric cancer with small bowel metastasis. He underwent laparoscopic total gastrectomy following neoadjuvant chemotherapy in January 2015 and was diagnosed with hepatic and bone recurrence in October 2015. Ramucirumab in combination with PTX was administered for one and half months after first-line chemotherapy failure. He presented with abdominal pain 7 days after the last ramucirumab dose, and emergency exploratory surgery revealed a small intestinal perforation. Pathological findings indicated that it occurred in a zone containing a small intestinal tumor, which was found to be metastasis of the gastric cancer. He had no postoperative complications, but chemotherapy was not reintroduced and he died 3 months later. Conclusion We present a recent case of ramucirumab-related gastrointestinal perforation in gastric cancer with small bowel metastasis. This case is rare, but important to consider.

Abstract Background Epiphrenic esophageal diverticulum is a rare condition that is often associated with a concomitant esophageal motor disorder. Some patients have the chief complaints of swallowing difficulty and gastroesophageal reflux; traditionally, such diverticula have been resected via right thoracotomy. Here, we describe a case with huge multiple epiphrenic diverticula with motility disorder, which were successfully resected using a video-assisted thoracic and laparoscopic procedure. Case presentation A 63-year-old man was admitted due to dysphagia, heartburn, and vomiting. An esophagogram demonstrated an S-shaped lower esophagus with multiple epiphrenic diverticula (75 × 55 mm and 30 × 30 mm) and obstruction by the lower esophageal sphincter (LES). Esophageal manometry showed normal peristaltic contractions in the esophageal body, whereas the LES pressure was high (98.6 mmHg). The pressure vector volume of LES was 23,972 mmHg2 cm. Based on these findings, we diagnosed huge multiple epiphrenic diverticula with a hypertensive lower esophageal sphincter and judged that resection might be required. We performed lower esophagectomy with gastric conduit reconstruction using a video-assisted thoracic and hand-assisted laparoscopic procedure. The postoperative course was uneventful, and the esophagogram demonstrated good passage, with no leakage, stenosis, or diverticula. Conclusions The most common causes of mid-esophageal and epiphrenic diverticula are motility disorders of the esophageal body; appropriate treatment should be considered based on the morphological and motility findings.

Aims: The reflux of duodeno-gastric contents into the remnant esophagus (gastric tube-esophageal reflux: GTER) is a significant issues in long-term esophageal cancer survivors after radical esophagectomy. We attempted endoscopic valve (funnel) creation for prevention for GTER using OverStitch endoscopic suturing system. Methods: The OverStitch was mounted onto a standard double-channel endoscope. Under general anesthesia, the funnel creation was attempted by placing semi-full thickness sutures on the gastric wall, at 3 cm distal to the primary esophago-gastric anastomosis. The postoperative outcomes were also evaluated. Results: In total, 4 sutures were needed and the operating time was 62 minutes without complication. The endoscopic and swallowing studies, as well as pH profile, were all improved postoperatively. The patient’s quality of life was dramatically improved with complete disappearance of night-time reflux in spine position. Conclusions: Endoscopic antireflux funnel creation was feasible and safe. This procedure may become a useful treatment for patients with severe GTER after esophagectomy.

Alterations in mitochondrial DNA (mtDNA) copy numbers in various human cancers have been studied, but any such changes in esophageal squamous cell carcinoma (ESCC) are not established. In the present study, we investigated the correlation of mtDNA copy number with clinicopathologic features, prognosis, and malignant potential of ESCC. MtDNA copy numbers of resected specimens from 80 patients treated with radical esophagectomy were measured by quantitative real-time PCR analyses. Human ESCC cells, TE8 and TE11, were cultured, and depletion of mtDNA content was induced by knockdown of mitochondrial transcription factor A expression or treatment with ethidium bromide. The mRNA and protein expression, proliferation, invasion, and cell cycle were investigated. The results showed that the mtDNA copy number of cancerous portions was 56.0 (37.4-234.5) percent that of non-cancerous parts and significantly lower (p

In the original publication of this article [1], the author found Fig. 1c has a redundant arrow.