A first-in-human clinical study of laparoscopic autologous myoblast sheet transplantation to prevent delayed perforation after duodenal endoscopic mucosal dissection.

BACKGROUND: The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. METHODS: To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period. RESULTS: Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient's postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis. CONCLUSIONS: This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future. TRIAL REGISTRATION: jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

High serum alpha-fetoprotein and positive immunohistochemistry of alpha-fetoprotein are related to poor prognosis of gastric cancer with liver metastasis.

Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.

[Sixteen Cases of Appendiceal Mucinous Neoplasm].

Appendiceal mucinous neoplasm is a relatively rare disease. It is classified as mucinous adenocarcinoma(MACA)and low- grade appendiceal mucinous neoplasm(LAMN). We retrospectively evaluated 16 cases of appendiceal mucinous neoplasm (LAMN: 13 cases, MACA: 3 cases)that were surgically resected in our hospital between January 2010 and July 2021. There were 7 men and 9 women, with a median age of 61 years(27-85 years). The most common chief complaint was abdominal pain(12 patients), while 3 cases were incidental findings following medical checkups for other diseases and without a chief complaint. Colonoscopy was performed for 9 cases. Of these, 5 revealed abnormal findings. The preoperative diagnosis was appendicitis in 7 patients and appendiceal tumor in 8 patients. The surgical procedures were planned for 8 cases and performed as emergencies in 8 cases. The procedures included laparoscopic surgery(n=6)and laparotomy(n=10). The resection range included appendectomy(n=9), partial cecal resection(n=4), and ileocecal resection(n=3). Surgical margins were negative in all cases. Metastases were not observed in patients who underwent lymph node dissections (2 patients with MACA and 1 patient with LAMN). The median follow-up was 17 months(1-43 months). Recurrence including peritoneal pseudomyxoma was not detected in any of the patients.

Double vision approach applied by two teams for retrosternal gastric conduit for gastric tube cancer.

Gastric tube cancer is classically treated with resection through a midline sternal incision. However, because of its invasiveness and limited reconstructive potential, transdiaphragmatic laparoscopic or thoracoscopic dissection of the gastric tube has been investigated. As resection from only the abdominal or thoracic cavity is difficult, we performed surgery with a thoracic surgeon approaching from the thoracic cavity and an abdominal surgeon simultaneously approaching from the cervical and abdominal regions. The gastric tube may be tightly adhered to the back of the sternum, cervicothoracic transition or thoracoabdominal transition. Dissection can be safely performed by operating from two directions simultaneously, the neck and chest or chest and abdomen, to successfully withdraw the gastric tube from the abdominal cavity. We performed this surgery in four cases. This collaborative operation provided a good surgical view and allowed for safe dissection of the gastric tube without requiring sternotomy.

Sepsis following acute pyelonephritis caused by Trueperella bernardiae: a case report and literature review.

BACKGROUND: Trueperella bernardiae is a coryneform, gram-positive bacterium that is a commensal of the skin and upper respiratory tract. It is treated as a contaminant and rarely causes infections. Blood, urine, and abscesses have been previously reported as the most common sites of infection. Infections caused by T. bernardiae are rarely reported in bedridden very old patients with reduced activities of daily living (ADL). In this report, we describe a case of sepsis due to acute pyelonephritis caused by T. bernardiae in a very old patient with impaired ADL. CASE PRESENTATION: A 94-year-old woman had a home visit from her local physician. She was bedridden and used diapers. On the day of admission, she presented with fever and dyspnea and was admitted with a diagnosis of sepsis associated with acute pyelonephritis. T. bernardiae was detected in blood and urine cultures; furthermore, multiple bacteria were detected in a urine culture. She was treated with ampicillin/sulbactam 3 g every 12 h on the day of admission. The fever was controlled, and inhaled oxygen 1 L/min via a nasal cannula was administered for dyspnea until hospitalization day 2. On hospitalization day 2, her fever resolved to 36 °C. Antimicrobials were de-escalated and changed to cephazolin and then to cephalexin on hospitalization days 9 and 16, respectively, and were continued until day 22. On hospitalization day 28, the urinary tract infection flared up; however, her fever resolved by hospitalization day 38 after the re-administration of antimicrobial agents. She was discharged on hospitalization day 60. CONCLUSIONS: We encountered a rare case of sepsis following acute pyelonephritis caused by T. bernardiae infection. When bedridden, diaper-using, very old patients present with urinary tract infections caused by multiple bacteria, the presence of rare opportunistic organisms, such as T. bernardiae, should be considered.

Endoscopic mucosal ischemic index for predicting anastomotic complications after esophagectomy: a prospective cohort study.

BACKGROUND: Postoperative complications related to gastric conduit reconstruction are still common issues after McKeown esophagectomy. A novel endoscopic mucosal ischemic index is desired to predict anastomotic complications after McKeown esophagectomy. AIMS AND METHODS: The purpose of this study was to prospectively evaluate the safety and efficacy of endoscopic examinations of the anastomotic region in the acute period after esophagectomy. Endoscopic examinations were performed on postoperative days (PODs) 1 and 8. The severity of ischemia was prospectively validated according to the endoscopic mucosal ischemic index (EMII). RESULTS: A total of 58 patients were included after evaluating the safety and feasibility of the endoscopic examination on POD 1 in 10 patients. Anastomotic leakage occurred in 6 patients. Stricture occurred in 13 patients. A greater than 67% circumference and lesion length greater than 20 mm of anastomotic ischemic area (AIA) on POD 1 were associated with developing anastomotic leakage after esophagectomy (OR: 14.5; 95% CI: 1.8-306.5; P = 0.03, OR: 19.4; 95% CI: 1.7-536.8; P = 0.03). More than 67% circumferential ischemic mucosa and ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were associated with developing anastomotic strictures after esophagectomy (OR: 6.4; 95% CI: 1.4-31.7; P = 0.02, OR: 5.9; 95% CI: 1.2-33.1; P = 0.03). Patients with either more than 67% circumferential ischemic mucosa or ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were defined as EMII-positive patients. The sensitivity, specificity, and positive and negative predictive values of EMII positivity on POD 1 for leakage were 100%, 78.8%, 35.3%, and 100%, respectively. The sensitivity, specificity, and positive and negative predictive values of the EMII positivity on POD 1 for strictures were 69.2%, 82.2%, 52.9%, and 90.2%, respectively. CONCLUSIONS: The application of an endoscopic classification system to mucosal ischemia after McKeown esophagectomy is both appropriate and satisfactory in predicting anastomotic complications. TRIAL REGISTRATION: Clinical Trial.gov Registry, ID: NCT02937389, Registration date: Oct 17, 2015.

Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial.

INTRODUCTION: Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies. METHODS AND ANALYSIS: This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×108/person; cohort 2, MU-MA402C 2×109/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1. ETHICS AND DISSEMINATION: This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences. TRIAL REGISTRATION NUMBER: jRCT2043210077.

Rapid and chronological expression of angiogenetic genes is a major mechanism involved in cell sheet transplantation in a rat gastric ulcer model.

Introduction: Cell sheet technology has been applied in the treatment of patients with severe cardiac failure. Although the paracrine effect of cell sheets accelerating angiogenesis is thought to be the intrinsic mechanism for improvement of cardiac function, little is known about how a cell sheet would function in the abdomen. Methods: We used acetic acid-induced gastric ulcer rat model to elucidate the mechanisms of myoblast sheet transplantation in the abdomen. Myoblast sheet was implanted onto the serosal side of the gastric ulcer and the effect of sheet transplantation was analyzed. The maximal diameter of the ulcer and the changes in the gene expression of various growth factors in transplanted site was analyzed. The progenitor marker CD34 was also examined by immunohistochemistry. Results: Cell sheet transplantation accelerated the ulcer healing. qPCR showed that angiogenic growth factors were significantly upregulated around the ulcer in the transplantation group. In addition, at first, HIF-1a and SDF-1 continued to increase from 3 h after transplantation to 72 h, then VEGF increased significantly after 24 h with a slight delay. An immunohistochemical analysis showed a statistically significant increase in CD34 positivity in the tissue around the ulcer in the transplantation group. Conclusion: Myoblast sheet secreted various growth factors and cytokines immediately after transplantation onto the serosal side of artificial ulcer in the abdomen. Autonomous secretion, resulting in the time-dependent and well-orchestrated gene expression of various growth factors, plays a crucial role in the cell sheet function. Cell sheet transplantation is expected to be useful to support angiogenesis of the ischemic area in the abdominal cavity.

Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model.

Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early esophageal cancer. However, large mucosal defects after esophageal ESD result in refractory strictures. In the present study, we histologically evaluated the endoscopic transplantation of allogeneic epidermal cell sheets (ECSs) as a feasible therapy for preventing esophageal stricture after circumferential ESD in a porcine model. Methods: Epidermal cells were isolated from the skin tissue of allogeneic pigs and cultured on temperature-responsive cell culture inserts for 2 weeks. Transplantable ECSs were harvested by reducing the temperature and endoscopically transplanting the sheets to ulcer sites immediately after esophageal ESD. The engraftment of transplanted ECSs was then evaluated in two pigs at 7 days after transplantation. Next, ten pigs were divided into two groups to evaluate the endoscopic transplantation of allogeneic ECSs for the prevention of esophageal strictures after ESD. Allogeneic ECSs were transplanted immediately after esophageal ESD in the transplantation group (n = 5), whereas the control group (n = 5) did not undergo transplantation. Results: Most of the transplanted allogeneic ECSs were successfully engrafted at the ulcer sites in the early phase. Fluorescence in situ hybridization analysis revealed that several allogeneic cells were present in the transplanted area at 7 days after ESD. At 14 days after ESD, significant differences in body weight loss, dysphagia scores, and mucosal strictures were observed between the control and transplantation groups. Transplanting allogeneic ECSs after esophageal ESD promotes mucosal healing and angiogenesis and prevents excessive inflammation and granulation tissue formation. Conclusions: Endoscopic and histological analyses revealed that allogeneic ECSs promoted artificial ulcer healing after ESD, preventing esophageal strictures after ESD.

Validation study of a skill assessment tool for education and outcome prediction of laparoscopic distal gastrectomy.

BACKGROUND: The Japanese operative-rating scale for laparoscopic distal gastrectomy (JORS-LDG) was developed through cognitive task analysis together with the Delphi method to measure intraoperative performance during laparoscopic distal gastrectomy. This study aimed to investigate the value of this rating scale as an educational tool and a surgical outcome predictor in laparoscopic distal gastrectomy. METHODS: The surgical performance of laparoscopic distal gastrectomy was assessed by the first assistant, through self-evaluation in the operating room and by video raters blind to the case. We evaluated inter-rater reliability, internal consistency, and correlations between the JORS-LDG scores and the evaluation methods, patient characteristics, and surgical outcomes. RESULTS: Fifty-four laparoscopic distal gastrectomy procedures performed by 40 surgeons at 16 institutions were evaluated in the operating room and with video recordings using the proposed rating scale. The video inter-rater reliability was > 0.8. Participating surgeons were divided into the low, intermediate, and high groups based on their total scores. The number of laparoscopic surgeries and laparoscopic gastrectomy procedures performed differed significantly among the groups according to laparoscopic distal gastrectomy skill levels. The low, intermediate, and high groups also differed in terms of median operating times (311, 266, and 229 min, respectively, P < 0.001), intraoperative complication rates (27.8, 11.8, and 0%, respectively, P = 0.01), and postoperative complication rates (22.2, 0, and 0%, respectively, P = 0.002). CONCLUSIONS: The JORS-LDG is a reliable and valid measure for laparoscopic distal gastrectomy training and could be useful in predicting surgical outcomes.

Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

High Pretreatment Mean Corpuscular Volume Can Predict Worse Prognosis in Patients With Esophageal Squamous Cell Carcinoma who Have Undergone Curative Esophagectomy: A Retrospective Multicenter Cohort Study.

Objective: To establish the prognostic value of mean corpuscular volume (MCV) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone esophagectomy. Background: The MCV increases in patients with high alcohol and tobacco consumption. Such a lifestyle can be a risk factor for malnutrition, comorbidities related to those habits, and multiple primary malignancies, which may be associated with frequent postoperative morbidity and poor prognosis. Methods: This study included 1673 patients with ESCC who underwent curative esophagectomy at eight institutes between April 2005 and November 2020. Patients were divided into normal and high MCV groups according to the standard value of their pretreatment MCV. Clinical background, short-term outcomes, and prognosis were retrospectively compared between the groups. Results: Overall, 26.9% of patients had a high MCV, which was significantly associated with male sex, habitual smoking and drinking, multiple primary malignancies, and malnutrition, as estimated by the body mass index, hemoglobin and serum albumin values, and the Geriatric Nutritional Risk Index. Postoperative respiratory morbidity (P = 0.0075) frequently occurred in the high MCV group. A high MCV was an independent prognostic factor for worse overall survival (hazard ratio, 1.27; 95% confidence interval, 1.049-1.533; P = 0.014) and relapse-free survival (hazard ratio, 1.23; 95% confidence interval, 1.047-1.455; P = 0.012). Conclusions: A high MCV correlates with habitual drinking and smoking, malnutrition, and multiple primary malignancies and could be a surrogate marker of worse short-term and long-term outcomes in patients with ESCC who undergo esophagectomy.

Highly feasible procedure for laparoscopic transplantation of cell sheets under pneumoperitoneum in porcine model.

INTRODUCTION: Cell sheet technology is one of the most successful methodologies in regenerative medicine. Various applications of cell sheets have been introduced in first-in-human studies in several clinical fields. When transplanting a cell sheet into internal organs, a relatively large incision is required for delivery due to difficulty handling the sheet. We developed a laparoscopic delivery procedure for safe and easy transplantation of cell sheets in a porcine model. METHODS: Pneumoperitoneum was established by inflation with CO2. First, to increase the strength during handling, fibrin was sprayed onto the surface of the cell sheet, and then a myoblast sheet was placed onto the newly developed carrier. The sheets were pinched with laparoscopic forceps to insert into the abdominal cavity through the laparoscopic port. Myoblast sheets were then applied to the surface of the liver, colon, small intestine, and stomach, and procedure times were measured. At three days post transplantation, a histopathological examination was performed to confirm engraftment of the sheet. The function and engraftment were also analyzed in a duodenal endoscopic submucosal dissection (ESD) model. RESULTS: The fibrin-processed myoblast sheet was able to be managed with conventional laparoscopic forceps without breaking. Despite the drastic change in air pressure by passing through the laparoscopic port, the sheets suffered no apparent damage. The transplantation procedure times did not markedly differ among transplant sites. A histopathological examination revealed thin-layered, desmin-positive cells at each transplant site. With transplantation following ESD, the engrafted myoblast sheets effectively prevented delayed perforation. CONCLUSIONS: Our procedure is simple, and the system involves a carrier made of medically fit silicon, commercially available fibrin glue and conventional laparoscopic forceps. Our procedure is a powerful tool for laparoscopical cell sheet transplantation.

Impact of endoscopic submucosal dissection and epithelial cell sheet engraftment on systemic cytokine dynamics in patients with oesophageal cancer.

The tumour microenvironment (TME) plays an important role in cancer development, progression, and metastasis. Various cytokines are present in the TME in oesophageal cancer. Oesophageal stricture is a major complication of endoscopic submucosal dissection (ESD) for oesophageal cancer, and inflammatory cytokines are closely related to its pathogenesis. However, the cytokine crosstalk involved in the oesophageal cancer TME and post-ESD stricture has not been fully elucidated. This study investigated the comprehensive cytokine dynamics following ESD in patients with oesophageal cancer. In addition, the effect of a novel preventive technique for post-ESD stricture, autologous cell sheet engraftment, on cytokine levels was evaluated. Various pro-inflammatory and anti-tumorigenic cytokines were elevated in patients with oesophageal cancer, and ESD transiently influenced cytokine concentrations. IL-1ß and TNF-α, two major pro-inflammatory cytokines that induce oesophageal stricture, were significantly suppressed by cell sheet engraftment. In conclusion, this study revealed the distinct cytokine dynamics after ESD in patients with oesophageal cancer, together with the effect of autologous cell sheet engraftment on cytokine fluctuation. These results can accelerate research on the TME and therapeutic strategies for oesophageal cancer.

[Case Report of an Elderly Patient with Interstitial Pneumonia Caused by the Administration of Trastuzumab plus Anastrozole for the Treatment of Inflammatory Breast Cancer].

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.

[A Case of Unresectable Gastric Cancer with Paraaortic Lymph Node Metastasis Treated with Conversion Therapy].

We present a case of advanced gastric cancer with paraaortic lymph node metastasis successfully treated by conversion therapy. The patient was a 71‒year‒old male. Because of paraaortic lymph node metastasis, we initiated intensive chemotherapy with S‒1, oxaliplatin, and trastuzumab. After 6 courses, CT examination revealed that the size of the primary tumor decreased, suggesting a complete response(CR). Furthermore, the metastatic lymph nodes decreased in both number and size, suggesting a partial response(PR). We continued chemotherapy, changing to S‒1 and trastuzumab only because of Grade 3 neutropenia, and conducted continuous infusion chemotherapy. After 5 courses, we performed an upper gastrointestinal endoscopy. The primary tumor recurred, suggesting a progressive disease(PD), while metastasis to the paraaortic lymph nodes disappeared. We decided that a curative resection was possible and performed distal gastrectomy with D2 and paraaortic lymph node dissection. The postoperative courses were uneventful, and the patient was discharged from the hospital 12 days postoperation. The patient is well without any recurrence of cancer at 1 year 3 months postoperation. Conversion therapy may offer the possibility of prolonged survival for patients with gastric cancer previously considered unresectable.

Aberrant common hepatic artery from the left gastric artery and with no connection to the gastroduodenal artery: Risky vascular anomaly in gastrectomy.

Knowledge of anatomical variations of the celiac axis is important in upper abdominal surgery. Aberrant common hepatic artery originating from the left gastric artery without connecting the gastroduodenal artery is extremely rare. Preoperative vascular anatomy assessment using reconstructions of CT images may be useful for safe surgical procedure.

Establishment of an in-vivo porcine delayed perforation model after duodenal endoscopic submucosal dissection.

OBJECTIVES: Duodenal endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal epithelial tumors has a significant incidence rate of delayed perforation. Although several methods have been proposed to prevent delayed perforation, the most appropriate methods remain unclear. Currently, there is no appropriate animal model to validate methods for preventing duodenal delayed perforation. This study aimed to establish an in-vivo porcine delayed perforation model after duodenal submucosal dissection. METHODS: Two porcine models underwent either ESD or surgical submucosal dissection. In the surgical dissection model, an inverted duodenal mucosa was resected with electrosurgical energy. In the ESD model, a gauze was placed behind the duodenum with grasped transverse part to improve endoscopic maneuverability. The mucosal defects after dissection were treated with omental coverage without suture in both models. All models were euthanized 0-5 days after procedure. Body weight; resection size; procedure dissection time; presence of intraoperative perforation and delayed perforation; and adhesion score were assessed. RESULTS: There were no significant differences in body weight and adhesion score between the two models. Resection size was significantly larger in the surgical dissection models than in the ESD models (19 mm vs 14.3 mm, P < 0.01). Procedure time was significantly longer in the ESD models than in the surgical models (45.2 minutes vs 4.5 minutes, P < 0.01). Delayed perforation rates in the surgical dissection models and the ESD models were 0% (0/5) and 100% (5/5), respectively (P < 0.01). CONCLUSIONS: This study indicated that our in-vivo porcine duodenal ESD model is beneficial to evaluate a prevention strategy for delayed perforation.

Downstaging and Histological Effects Might Be Reliable Predictors of the Efficacy of DOC+CDDP+5-FU (DCF) as Neoadjuvant Therapy for Stage III or Borderline Resectable Esophageal Cancer: a Single Institute Experience.

PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.

The Efficacy of Autologous Myoblast Sheet Transplantation to Prevent Perforation After Duodenal Endoscopic Submucosal Dissection in Porcine Model.

The recent advent of endoscopy has enabled the endoscopic submucosal dissection (ESD) of superficial nonampullary duodenal epithelial tumors. However, the substantially thin wall and presence of bile and pancreatic juice make it technically difficult to perform duodenal ESD without perforation, which leads to lethal complications. The present study evaluated the efficacy of autologous myoblast sheet transplantation for the prevention of late perforation after duodenal ESD in a porcine model. Two weeks before ESD, skeletal muscle was surgically excised from the femur of pigs, and myoblasts were isolated and seeded in temperature-responsive culture dishes to prepare sheets. Immediately after ESD, the autologous myoblast sheets were attached to the serosal surface at the ESD site with omentopexy. The pigs were divided into two groups: the autologous myoblast sheet group (n = 5), where the myoblast cell sheet was attached to the ESD ulcer part from the duodenal serous side, and the Omentum group (n = 5), where only the omentum was used. The pigs were sacrificed and analyzed macroscopically and histologically on postoperative day 3. The macroscopic examination of the abdominal cavity revealed perforation in the ESD ulcer area and leakage of bile in the Omentum group but no perforation in the Sheet group. A histopathological examination revealed that continuity of the duodenal wall at the ESD site was maintained with dense connective tissue in the Sheet group. In conclusion, autologous myoblast sheets were useful for preventing perforation after duodenal ESD.