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Abstract We developed a novel clamping device for laparoscopic surgery, free from conventional pinch structure, capable of uniformly occluding any ductal organ. This study aimed to evaluate performance of the new clamper compared to the pinch-type clamper. The new clamper consists of two metal bars with ties at each end, which enables parallel clamping. A resected porcine stomach was used, with an infusion tube at the anal end to increase intra-luminal pressure. The oral side of the stomach was clamped with either the new clamper or the pinch-type clamper, and their performances were evaluated in qualitative and semi-quantitative manner. Qualitative evaluation involved imaging the clamping site at intra-gastric pressures from 0 to 15 mmHg using microfocus computed tomography. The new clamper showed no gap even under increased intra-luminal pressure, while the pinch-type clamper showed a gap on the distal side. Quantitative evaluation measured bursting pressure under continuous air insufflation. Air leakages were observed in the new clamper at higher intra-luminal pressures than in the pinch-type clamper (46.1 mmHg vs. 13.6 mmHg, P

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 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 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 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.

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 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 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.

Background and study aims The risk of aerosolization of body fluids during endoscopic procedures should be evaluated during the COVID-19 era, as this may contribute to serious disease transmission. Here, we aimed to investigate if use of endoscopic tools during flexible endoscopy may permit gas leakage from the scope or tools. Material and methods Using a fresh 35-cm porcine rectal segment, a colonoscope tip, and manometer were placed intraluminally at opposite ends of the segment. The colonoscope handle, including the biopsy valve, was submerged in a water bath. Sequentially, various endoscopic devices (forceps, clips, snares, endoscopic submucosal dissection (ESD) knives) were inserted into the biopsy valve, simultaneously submerging the device handle in a water bath. The bowel was slowly inflated up to 74.7 mmHg (40 inH2O) and presence of gas leakage, leak pressure, and gas leakage volume were measured. Results Gas leakage was observed from the biopsy valve upon insertion and removal of all endoscopic device tips with jaws, even at 0 mmHg (60/60 trials). The insertion angle of the tool affected extent of gas leakage. In addition, gas leakage was observed from the device handles (8 of 10 devices) with continuous gas leakage at low pressures, especially two snares at 0 mmHg, and an injectable ESD knife at 0.7 ± 0.8 mmHg). Conclusions Gas leakage from the biopsy valve and device handles commonly occur during endoscopic procedures. We recommend protective measures be considered during use of any tools during endoscopy.

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.

Background and study aims: One of the challenges in performing endoscopic submucosal dissection (ESD) is the lack of counter traction during submucosal dissection. MASTER (Master and Slave Transluminal Endoscopic Robot) was designed to allow performance of complex endoluminal procedures using two arms with excellent control. This study aimed to compare the performance of ESD between endoscopists and novices using MASTER. Methods: This is a prospective study comparing the differences in performing ESD using MASTER in an ex vivo porcine stomach model among individuals with or without experience in surgery and endoscopy. Multiple standardized lesions of 20 mm2 were pre-marked on an ex vivo porcine stomach. Each participant received basic training in controlling MASTER before the ESD procedure. The operative time and size of specimen obtained by each participant were noted. Results: Nine individuals (three ESD expert endoscopists, three ESD non-expert endoscopists, and three non-clinician novices) participated in the experiment. All participants completed the ESD procedure for en bloc resection of standardized lesions using EndoMASTER without perforation. The mean times (mean ± SD) taken by ESD expert endoscopists, ESD non-expert endoscopists, and novices to complete Robotic ESD were 122 ± 58 s, 203 ± 150 s, and 561 ± 496 s, respectively. There was no statistically significant difference in the mean operative time to complete the ESD between the three groups (P = 0.242). When the performance of the six endoscopists was compared to that of the three novices, the endoscopists took an average of 162 ± 111 s to complete the ESD, while the non-clinicians required an average of 561 ± 496 s (P = 0.085). Conclusions: There was a trend to shorter operative time when comparing endoscopists to non-endoscopists in performing ESD using MASTER. The use of MASTER enabled the novice without endoscopy experience to complete the ESD procedure.

Background: Living swine has a high degree of coagulation and aggregation, and training for managing intraoperative bleeding during endoscopic submucosal dissection (ESD) is unsatisfactory. This study aimed to identify the appropriate heparin dose in an intraoperative bleeding model and validate its applicability. Methods: First, we explored the dose of heparin required for a swine bleeding model in which the activated clotting time reached and maintained the upper limit of measurement (1500 s) after 10 min. Second, we compared intraoperative bleeding and hematoma frequency during ESD for 2 cm lesions between the heparinized bleeding model and control groups. Intraoperative bleeding was classified according to the Forrest classification. Results: The combination of a bolus (300 U/kg), continuous infusion (300 U/kg/h), and a bolus dose (150 U/kg) of heparin 10 min after the first infusion was identified as the dose of the bleeding model. Five ESDs were performed in each heparinized bleeding model and the control group. The median number of intraoperative bleeding was significantly higher in the heparinized model than in the control group (5 [interquartile range {IQR}, 4–7] vs. 3 [IQR, 0–4], p = 0.028). All intraoperative bleeding events were not spurting (Forrest Ia) but oozing (Forrest Ib). The median number of hematomas was significantly higher in the heparinized model group than in the control group (3 [IQR, 1–4] vs. 0 [IQR, 0–1], p = 0.023). Conclusion: High doses of heparin significantly increased intraoperative bleeding and hematoma during swine ESD.

Cisplatin is one of the most predominant drugs for the chemotherapy of esophageal squamous cell carcinoma (ESCC); however, the underlying resistance mechanisms are still almost unknown. The present study performed RNA sequencing of human circular RNA (circRNA) in TE11 cells and cisplatin-resistant TE11 cells (TE11R). The expression profiles determined using CIRCexplorer2 revealed that the expression of circ_0004365, mapped on the Semaphorin 3C gene, was significantly greater in TE11R compared with in TE11. In reverse transcription-quantitative PCR, circ_0004365 expression was observed in human ESCC and non-tumor tissues and was significantly upregulated in ESCC tumor tissues after chemotherapy. Circ_0004365 expression was significantly upregulated in patients with poor pathological response (P=0.02). Furthermore, patients with advanced pT stage showed an upregulation in circ_0004365 expression after chemotherapy (P=0.02). The MTT assay revealed that knockdown of circ_0003465 in TE11 significantly decreased resistance to cisplatin. In conclusion, the present study suggested that circ_0004365 was associated with cisplatin resistance in ESCC and can be used as both a novel biomarker and a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate primary tumor (PT) and lymph node (LN) responses to neoadjuvant chemotherapy (NACT) for predicting long-term survival in patients with metastatic esophageal cancer (EC). Background: In evaluating NACT responses in patients with EC, imaging modalities typically target the PT in the esophagus, which is unmeasurable. Targeting measurable organs, like positive LNs, might provide more accurate assessments. Methods: We enrolled 251 patients with EC and clinically positive LNs that underwent curative resections, after triplet NACT. The percent reduction of PT area was measured with bidimensional computed tomography. The LN response was defined as the percent reduction of the sum of the short diameters in all positive LNs. Results: NACT reduced PTs and LNs by (median, range) 58.0% (38.1–94.9) and 34.5% (46.2–68.2), respectively. Based on the receiver-operating characteristic analyses for predicting a histological response and a 10% stepwise cutoff analyses of recurrence-free survival (RFS), responder/nonresponder cutoff values were ≥60% for PT area reductions and ≥30% for LN size reductions. 39.6% of patients showed discordant PT and LN responses. Compared with PT-responders, LN-responders had significantly less advanced pN (P < 0.0001) and pM (P = 0.015) in addition to less advanced pT (P < 0.0001) and better histological responses (P < 0.0001), and closer correlations to lymphatic, distant metastases and dissemination. A multivariate analysis of RFS identified 2 independent prognostic factors: the LN response [hazard ratio (HR) = 2.51, 95% confidence interval (CI) = 1.63–3.95, P < 0.0001] and the pN (HR = 2.72, 95% CI = 1.44–5.64, P = 0.0016), but not the PT response. Conclusions: The LN response to NACT predicted long-term survival more precisely than the PT response in patients with metastatic EC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance. Background: NAC is a standard treatment for locally advanced esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown. Methods: One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin- eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis. Results: Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types. Conclusions: After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29-4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target. [ABSTRACT FROM AUTHOR]

Programmed death‑ligand 1 (PD‑1/PD‑L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD‑L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair‑deficient tumors are associated with improved survival, although they are not sensitive to 5‑fluorouracil‑based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD‑L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD‑L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD‑L1 expression. The 5‑year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (P<0.0001). The frequency of high PD‑L1 expression was 11.4% in the high MLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD‑L1 expression. [ABSTRACT FROM AUTHOR]

Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses. HSF1 protein and mRNA expression were assessed in resected specimens from 270 patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression were also assessed in 55/270 patients. Patients with high HSF1 expression had a significantly worse OS than those with low HSF1 expression in both cohorts. In multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73; 95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64; P=0.0002) were statistically significant independent prognostic factors. Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1 expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27 and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC. [ABSTRACT FROM AUTHOR]

Esophageal cancers frequently metastasize to recurrent laryngeal nerve lymph nodes (RLNNs). Knowledge of anatomic metastatic RLNN (mRLNN) distributions is needed for lymph node dissection during esophageal cancer surgery. Among 189 patients with esophageal cancer who underwent esophagectomy between 2008 and 2010, 51 (27.0%) had mRLNN. Sixty-four mRLNNs (right, 31; left, 33) were identified via preoperative computed tomography (CT); more than 2 unilateral metastases and/or nodes with unclear boundaries were excluded. Anatomical characteristics, including vertical distance from the sternal notch level, circumferential angle to the mid-sagittal tracheal plane, and short and long axes, were measured via CT. Respective mean right and left vertical distances from the sternal notch were +2.0±13.1 mm and -14.5±23.8 mm (p=0.0006). Left mRLNNs existed in vertically wider and inferior areas along recurrent laryngeal nerve, compared to right mRLNNs. The respectivemean right and left circumferential angles around the trachea (from the anterior mid-sagittal plane) were 137.2±11.2 and 94.3±31.6 (p<0.0001). LeftmRLNNs were distributed more widely around the trachea, especially anteriorly. The short axes were larger for right mRLNNs than for left mRLNNs (8.6 mm vs. 6.8 mm, p=0.026). Compared with the right side, left mRLNNs were smaller and had a vertically longer and circumferentially wider distribution. Careful attention should be given to the left side during curative RLNN dissection. [ABSTRACT FROM AUTHOR]

Background and study aims: Gastric reflux into the remnant esophagus after subtotal or partial esophagectomy is associated with impairment in patient quality of life.We evaluated the feasibility, safety, and potential effectiveness of a novel procedure using a new endoscopic suturing device to create an anti-reflux valve (funnel) in pigs after esophagectomy with gastric tube reconstruction. Methods: The endoscopic procedure was performed in four pigs using a semi-full-thickness endoscopic suturing system (OverStitch; Apollo Endosurgery, Austin, Texas, USA). The operating time, funnel height, ratio of the height of the funnel to the diameter of the gastric tube, and adverse events associated with the procedure were evaluated. The "reflux angle" was measured morphologically and functionally during a reflux induction test, using contrast medium or artificial gastric fluid, by tilting the operating table gradually from a head up to a head down position. Reflux angles before and after funnel creation were compared. Results: The procedure was successful in all four animals. The median operating time was 43 minutes, and the median funnel height was 17mm (56.7% of gastric tube diameter). There were no adverse events associated with the procedure. The reflux angle was lower after the procedure compared with before in both morphological and functional assessments in all four cases. Conclusions: Endoscopic anti-reflux funnel creation using OverStitch was feasible, safe, and potentially effective. [ABSTRACT FROM AUTHOR]

Background and Aims: Automatic smoke evacuation has not been feasible inside the gastrointestinal tract as evacuation collapses pneumoviscera. As previously reported, steady pressure automatically controlled endoscopy (SPACE) may resolve this problem. The aims of this study were to clarify the potential dangers of surgical smoke, and to evaluate the feasibility and potential usefulness of automatic smoke evacuation in flexible gastrointestinal endoscopy. Methods: Seven pigs were enrolled. SPACE was established by using a flexible endoscope, an overtube, and a surgical CO2 insufflator. Smoke was generated by gastric mucosal ablation for component analysis and was evacuated by a commercially available surgical-use smoke evacuator connected to an additional line attached to the endoscope. Endoscopic images with evacuation were evaluated subjectively in comparison to those from cases without evacuation. After each session, the residual intraluminal smoke was collected by a smoke testing device for objective evaluation. Results: Ten chemical compounds were detected. Smoke evacuation was achieved without collapse of the pneumostomach. Smoke was significantly reduced with the use of evacuation. Conclusions: Surgical smoke generated inside the gut lumen was potentially hazardous. Automatic evacuation was feasible and potentially useful in conjunction with SPACE technology. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Substantial differences in endoscopic strategy for gastric cancer exist between Western and Eastern countries, owing to clinicoepidemiological diversity, including differences in the prevalence of gastric cancer. This international multicenter study involved German and Japanese institutions and aimed to evaluate the influence of reviewers' clinical backgrounds on interpreting probe-based confocal laser endomicroscopy (pCLE) findings for diagnosis of superficial gastric lesions.Patients and Methods: 39 reviewers answered questionnaires about their clinical background and then reviewed 30 sets of white light endoscopy (WLE) and pCLE video clips via an online questionnaire. For each set of clips, reviewers were asked to classify lesions as neoplastic or non-neoplastic. RESULTS of video reviews were compared with the final histopathological diagnosis for each lesion. The accuracy of diagnosis based on WLE + pCLE was compared with that based on WLE alone for each aspect of clinical background.Results: The overall accuracy of diagnosis based on WLE + pCLE was higher than that based on WLE alone (73.93 % vs. 65.64 %, P = .0002). Outcomes of expert gastroenterologists were better than those of pathologists (P = .038 for WLE, P = .002 for WLE + pCLE) and outcomes of reviewers at Japanese institutions were better than those of reviewers at German institutions (P = .001 for WLE, P < .001 for WLE + pCLE).Conclusions: Reviewers from Japanese institutions and expert gastroenterologists performed well in the pCLE interpretation. Substantial experience in conventional endoscopy is important for interpreting pCLE images for the diagnosis of gastric cancer.University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; www.umin.ac.jp/ctr/index.htm) number UMIN 000013437). [ABSTRACT FROM AUTHOR]

There is increasing evidence that the expression of microRNA (miRNA) in cancer is associated with chemosensitivity but the mechanism of miRNA-induced chemoresistance has not been fully elucidated. The aim of this study was to examine the role of extracellular miRNA in the response to chemotherapy in esophageal cancer. First, serum expression of miRNAs selected by miRNA array was measured by quantitative reverse transcription-polymerase chain reaction in 68 patients with esophageal cancer who received cisplatin-based chemotherapy to examine the relationship between miRNA expression and response to chemotherapy. The serum expression levels of 18 miRNAs were different between responders and non-responders by miRNA array. Of these, high expression levels of miR-27a/b correlated with poor response to chemotherapy in patients with esophageal cancer. Next, in vitro assays were conducted to investigate the mechanism of miRNA-induced chemoresistance. Although transfection of miR-27a/b to cancer cells had no significant impact on chemosensitivity, esophageal cancer cells cultured in supernatant of miR-27a/b-transfected normal fibroblast showed reduced chemosensitivity to cisplatin, compared with cancer cells cultured in supernatant of normal fibroblast. MiR-27a/b-transfected normal fibroblast showed α-smooth muscle actin (α-SMA) expression, a marker of cancer-associated fibroblasts (CAF) and increased production of transforming growth factor-p (TGF-β). Chemosensitivity recovered after administration of neutralizing antibody of TGF-β to the supernatant transfer experiments. Our results indicated that miR-27a/b is involved in resistance to chemotherapy in esophageal cancer, through miR-27a/b-induced transformation of normal fibroblast into CAF. [ABSTRACT FROM AUTHOR]

Background In this study, we evaluated the technical feasibility of mucosal approximation of large ulcers via an endoscopic suturing system after endoscopic submucosal dissection (ESD), assessed the durability of these sutures, and compared this technique with serosal apposition of fullthickness gastric wall defects using the same device. Methods Post-ESD ulcers were closed with mucosal apposition in 7 pigs, and endoscopic fullthickness resection (EFTR) defects were closed with serosal apposition in 3 pigs. Pigs recovered for 1 week; they were then euthanized and necropsies were performed. Results Primary defect closure was achieved in 85.7% of the post-ESD closures and in 100% of the post-EFTR closures (p = 0.67). All pigs survived for 1 week. At necropsy, sutures had loosened in the post-ESD animals, although only minor deformity of the ulcer edges was observed in all repaired post-ESD ulcers. Meanwhile, all of the post-EFTR defect closures were sustained for 1 week. Conclusions Primary closure of post-therapeutic defects can be accomplished using the device. Inverted serosal apposition provides a more durable and reliable repair than everted mucosal apposition. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-II mRNA-binding protein-3 (IMP3) is an important factor in carcinogenesis, although its clinical significance in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study investigated the associations between IMP3 expression and the clinicopathological parameters. IMP3 expression was assessed in 191 resected ESCC specimens, and the associations between IMP3 expression in ESCC, the clinicopathological parameters and patient prognosis were examined. Using immunohistochemistry, 113 (59.2%) tumors were identified as IMP3-positive. IMP3 positivity correlated significantly with high pathological (p)Stage, pT stage and pN stage. The IMP3-positive patients exhibited a poorer prognosis compared with the IMP3-negative patients. In univariate analyses, histology [hazard ratio (HR), 1.94; 95% confidence interval (CI), 1.18-3.49; P=0.0082], pT (HR, 2.34; 95% CI, 1.55-3.62; P<0.0001), pN (HR, 2.85; 95% CI, 1.81-4.69; P<0.0001), lymphatic invasion (HR, 2.08; 95% CI, 1.26-3.70; P=0.0036), venous invasion (HR, 1.79; 95% CI, 1.21-2.64; P=0.0039), neoadjuvant chemotherapy (NAC) (HR, 2.01; 95% CI, 1.35-3.00; P=0.0005) and IMP3 expression (HR, 2.12; 95% CI, 1.40-3.29; P=0.0003) were significantly associated with overall survival. Using multivariate analyses, histology (HR, 1.87; 95% CI, 1.13-3.29; P=0.014), pN (HR, 2.19; 95% CI, 1.36-3.66; P=0.0010), NAC (HR, 1.88; 95% CI, 1.24-2.86; P=0.0028) and IMP3 expression (HR, 1.84; 95% CI, 1.18-2.93; P=0.0064) were significant prognostic factors. IMP3 may therefore be a prognostic factor for patients with ESCC who have undergone a curative resection. [ABSTRACT FROM AUTHOR]

Background and study aims: Steady pressure automatically controlled endoscopy (SPACE) is a new insufflation system that provides constant carbon dioxide (CO2) insufflation pressure during prolonged procedures. The system consists of an overtube, a surgical insufflator, and a newly developed leak-proof valve. The aims of this study were to validate the feasibility and safety of SPACE for esophageal endoscopic submucosal dissection (ESD). Patients and methods: This was a clinical phase I trial, involving 10 patients who underwent esophageal ESD. The primary end point was the rate of adverse events within 30 days (grade 0 to 4). Secondary end points were changes in partial pressure of carbon dioxide (PaCO2) and vital signs during ESD, completion rate of ESD, and degree of abdominal distension by patient assessment and radiographic grading. Results: All adverse events were Grade 2 or less. Mild PaCO2 elevation after ESD was noted; however, no associated symptoms were reported. The procedure was completed under SPACE alone in 8 of 10 patients. Minimal post-procedural bowel distension was observed. Conclusions: In this small pilot study, SPACE was feasible and appeared to be safe. Further study with larger case numbers is required to demonstrate efficacy and safety. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer associated with Crohn's disease (CD) is increasing in proportion to the number of patients with CD in Japan. There are two subtypes of colorectal cancer with CD: sporadic cancer and colitis-associated cancer. Early diagnosis of colitis-associated cancer is sometimes difficult; when colorectal cancer is found in patients with CD, both colitisassociated cancer and sporadic cancer should be kept in mind. Here, we describe a case of metachronous, colitis-associated rectal cancer that developed after the complete resection of an adenoma that became a sporadic adenocarcinoma in a patient with longstanding CD. To the best of our knowledge, this is the first report of colitis-associated cancer in a patient with CD after removal of a sporadic cancer. Case presentation We describe a 51-year old man with CD who had difficulty in defecation. A rectal polyp was detected and a transanal resection of the polyp was performed. A histopathological examination showed an adenoma with sporadic adenocarcinoma. After three years, a followup colonoscopy revealed a reddish, elevated lesion in the patient's rectum. A colonoscopic biopsy showed a signet ring cell carcinoma. We performed an abdominoperineal resection of the rectum and a bilateral pelvic lymph node dissection. A histopathological examination revealed a mucinous adenocarcinoma with signet ring cell carcinoma and lymph node metastasis. The patient received adjuvant chemotherapy with oral uracil 224 mg combined with tegafur 100 mg plus leucovorin. No signs of recurrence were noted at a follow-up 18 months after the third surgery and 60 months after the second surgery. [ABSTRACT FROM AUTHOR]

Background Hand-assisted laparoscopic surgery (HALS) has gained wide clinical acceptance as a practical alternative to laparoscopically assisted surgery (LAP) for the surgical treatment of complex colorectal diseases (e.g., ulcerative colitis and diverticulitis). However, its role in the further challenging operation for Crohn's colitis (i.e., subtotal or total colectomy) has yet to be established. This study aimed to evaluate the feasibility, safety, and potential benefit of HALS subtotal and total colectomy for Crohn's colitis. Methods The study reviewed 38 consecutive patients who underwent subtotal or total colectomy as their initial abdominal surgery for Crohn's extensive colitis (involvement of 3 or more colonic segments) between 1992 and 2006. The patients were divided into three groups (open, LAP, and HALS), and their background and postoperative data were retrospectively analyzed. Results The reviews included 14 open, 6 LAP, and 18 HALS cases. The groups were comparable in terms of age at surgery, gender, body mass index, extent and type of disease, indications, and procedures. The median operative time was significantly longer for LAP (330 min; range, 154-540 min) than for HALS (251 min; range, 165- 340 min) or open surgery (200 min; range, 172-315 min). The blood loss was significantly less with LAP (170 ml; range, 115-257 ml) and HALS (225 ml; range, 35-890 ml) than with open surgery (438 ml; range, 280-780 ml). No difference was seen in postoperative complications, and no mortality occurred in the series. Conclusions The findings showed that HALS subtotal and total colectomies are feasible and safe. The HALS procedure currently seems potentially beneficial for patients with extensive Crohn's colitis by reducing the operative time for laparoscopic surgery while retaining its less invasiveness. [ABSTRACT FROM AUTHOR]

Background Intraoperative endoscopy (IOE) is a useful adjunct during laparoscopic gastrointestinal (GI) surgery. However, one potential hazard of IOE is a prolonged bowel distension due to insufflated air, which may cause obstructed surgical exposure and increased postoperative abdominal pain. Recently, carbon dioxide (CO2), with its rapid absorptive nature, has been proven effective to minimize prolonged bowel distension in ambulatory/intraoperative colonoscopy. The objectives were to assess the feasibility, safety, and efficacy of CO2-insufflating upper GI IOE during laparoscopic surgery. Methods A historical comparison study was performed on the initial ten consecutive patients who underwent CO2- insufflating upper GI IOE (CO2-IOE) during laparoscopic surgery. The control group consisted of the past 12 consecutive patients who underwent conventional air-insufflating upper GI IOE (air-IOE) during laparoscopic surgery. The following parameters were compared between the two groups: (1) patient demographics; (2) feasibility (% completion of IOE); (3) safety (complications related to IOE, impacts on cardiopulmonary status, including systemic blood pressure, heart rate, and end-tidal CO2); (4) efficacy (postoperative residual intestinal gas, time to resume oral intake, and bowel movement). The amounts of post-IOE residual intestinal gas were evaluated and classified on the immediate postoperative abdominal radiographs in a blinded manner. Results Patient demographics were comparable between the two groups. IOE was completed in both groups without complications. Adverse effects on cardiopulmonary status were not observed during simultaneous intraperitoneal and intraluminal CO2 insufflation. In the air-IOE group, one patient was converted to open surgery because of inadequate surgical exposure from prolonged distension of the downstream bowel. The patients in the CO2-IOE group had significantly lower grade of postoperative bowel distension than the control group. Postoperative oral intake was resumed earlier in the CO2-IOE group. Conclusion CO2-insufflating upper GI IOE during laparoscopic surgery is feasible, safe, and has a practical advantage in minimizing post-IOE bowel distension compared with conventional air-insufflating upper GI IOE. [ABSTRACT FROM AUTHOR]