A case of refractory immune checkpoint inhibitor-induced colitis improved by the treatment with vedolizumab and granulocyte-monocyte apheresis combination therapy.

A 68-year-old man developed immune-related adverse event (irAE) colitis after the initiation of nivolumab and ipilimumab combination therapy for malignant melanoma. We diagnosed the patient with grade 3 irAE colitis and started prednisolone (1 mg/kg/day). Although the symptom improved once, it worsened along with the tapering of prednisolone. Therefore, we started infliximab (IFX). However, symptoms did not improve after two doses of IFX. We discontinued IFX and initiated vedolizumab (VED). Because VED alone did not improve the symptom, we started granulocyte-monocyte apheresis (GMA). Twelve weeks after the onset, the colitis was in remission. Therefore, in addition to vedolizumab, GMA may be considered in cases refractory to treatment.

Flexible robotic endoscopy for treating gastrointestinal neoplasms.

Therapeutic flexible endoscopic robotic systems have been developed primarily as a platform for endoscopic submucosal dissection (ESD) in the treatment of early-stage gastrointestinal cancer. Since ESD can only be performed by highly skilled endoscopists, the goal is to lower the technical hurdles to ESD by introducing a robot. In some cases, such robots have already been used clinically, but they are still in the research and development stage. This paper outlined the current status of development, including a system by the author's group, and discussed future challenges.

Autoimmune Pancreatitis with Gastric Cancer: Some IgG4-related Diseases May Be Paraneoplastic Syndrome.

A 70-year-old man was referred to our department for the treatment of early gastric cancer. Contrast-enhanced computed tomography (CT) incidentally showed diffuse enlargement of the pancreas with a capsule-like rim, and blood tests showed elevated serum IgG4 levels, leading to a diagnosis of autoimmune pancreatitis (AIP). Endoscopic treatment for gastric cancer was performed, and pathological findings showed adenocarcinoma with abundant IgG4-positive plasma cell infiltration. Thereafter, the serum IgG4 levels normalized, and the findings of AIP disappeared on CT without steroid treatment. These findings suggest that the gastric cancer activated an IgG4-related immune response, resulting in the development of AIP.

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis.

Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment. Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks. Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ≤2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study. Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ≤2 may predict the long-term response of ADA.

Meckel's Diverticulum Bleeding Missed by the First but Detected by the Second Capsule Endoscopy.

A 13-year-old boy was admitted to our hospital because of bloody stools. Although a Meckel's diverticulum (MD) was suspected, capsule endoscopy (CE) revealed no remarkable findings. Seven months later, he was admitted again because of rebleeding. CE was performed again and revealed an elevated lesion and fresh blood in the ileum. A single balloon endoscopic examination revealed a diverticulum with an elevated lesion in it. Histologic findings showed ectopic gastric mucosa, thus we diagnosed this patient as having MD. Although CE is useful for the examination of obscure gastrointestinal bleeding, a single CE is not enough to diagnose MD bleeding. The timing in performing CE and the evaluation of other modalities would be valuable for patients suspected of having MD.

Influence of gastroesophageal flap valve on esophageal variceal bleeding in patients with liver cirrhosis.

OBJECTIVES: Esophageal variceal bleeding can be fatal in patients with liver cirrhosis. The aim of this study was to investigate the relationship between gastroesophageal flap valve (GEFV) and esophageal variceal bleeding. METHODS: Subjects were cirrhotic patients with endoscopically diagnosed esophageal varices treated at our hospital between 2005 and 2019, excluding those with F3 form and red color (RC) signs at first endoscopy. Sixty-five patients with normal GEFV (Hill grade I or II) and 42 with abnormal GEFV (Hill grade III or IV) were enrolled. Propensity score matching eliminated the baseline differences, resulting in a sample size of 30 patients per cohort. The primary endpoint was esophageal variceal bleeding, and the secondary endpoint was variceal bleeding or appearance of RC sign. We analyzed the cumulative incidences and predictors of each endpoint. RESULTS: The 3-, 5-, and 10-year cumulative incidences of the primary endpoints were all 3.4% in the normal GEFV group, and 19.0%, 24.6% and 34.0% in the abnormal GEFV group, respectively (log-rank P = 0.011). Cumulative incidence of the secondary endpoint was 13.8%, 33.1% and 39.2% in the normal GEFV group, and 42.2%, 54.6% and 84.9% in the abnormal GEFV group, respectively (log-rank P = 0.001). In multivariate Cox regression analyses, hazard ratios of abnormal GEFV of the primary and secondary endpoints were 12.79 (95% confidence interval 1.331-122.8) and 3.600 (1.653-7.840), respectively. CONCLUSIONS: Abnormal GEFV was an independent risk factor for esophageal variceal bleeding and appearance of RC sign.

Erratum to "Development of a Novel Gastrointestinal Endoscopic Robot Enabling Complete Remote Control of All Operations: Endoscopic Therapeutic Robot System (ETRS)".

[This corrects the article DOI: 10.1155/2019/6909547.].

Usefulness of magnifying endoscopy and endoscopic ultrasonography for the gastric involvement of follicular lymphoma.

A 61-year-old man received an esophagogastroduodenoscopy for further investigation of mesenteric lymphadenopathy. Esophagogastroduodenoscopy revealed swollen gastric folds and cobble stone mucosa in the gastric body. Magnifying endoscopy with narrow-band imaging showed branched abnormal vessels and the absence or destruction of gastric pits. Endoscopic ultrasonography (EUS) depicted homogeneously hypoechoic thickening of the submucosal layer where the mucosal changes were observed. The patient was diagnosed with follicular lymphoma by biopsy of these lesions. We should recognize that these endoscopic features are consistent with follicular lymphoma involving the stomach and that concurrent EUS is useful for diagnosis and identification of adequate biopsy sites.

Development of a Novel Gastrointestinal Endoscopic Robot Enabling Complete Remote Control of All Operations: Endoscopic Therapeutic Robot System (ETRS).

BACKGROUND AND OBJECTIVE: The master and slave transluminal endoscopic robot and other flexible endoscopy platforms are designed primarily for the remote control of forceps, with manipulation of the endoscope itself still dependent on conventional techniques. We have developed an endoscopic therapeutic robot system (ETRS) that provides complete remote control of all forceps and endoscope operations. METHOD: We carried out endoscopic submucosal dissection (ESD) in porcine stomachs using the ETRS. All procedures were completed with the endoscopist seated at the console the entire time. RESULTS: Total en bloc resection was achieved in all 7 cases with no complications. The mean total procedure time was 36.14 ± 14.98 min, the mean size of the resected specimen was 3.39 ± 0.66 cm × 3.03 ± 0.63 cm, and the mean dissection time was 14.91 ± 8.61 min. CONCLUSION: We successfully used the ETRS to perform completely remote-controlled ESD in porcine stomachs.

Impact of examining additional deeper sections on the pathological diagnosis of endoscopically resected early gastric cancer.

OBJECTIVES: The pathological diagnosis of endoscopically resected early gastric cancer (EGC) is performed by evaluating a few representative sections from the specimen. We aimed to determine whether evaluating twice as many sections as usual by essentially cutting the original sections in half could improve the pathological diagnosis of EGC. METHODS: We retrospectively investigated 85 EGC in 82 patients who had undergone endoscopic resection at our hospital from August 2008 to October 2012. EGC without indications of curative resection were excluded. We re-examined the original paraffin blocks after shaving away approximately half their original thickness, and evaluated whether the pathological diagnoses were affected. This technique essentially doubled the number of sections examined. RESULTS: Ten pathological diagnoses of 68 EGC (14.7%) were changed from curative resection to non-curative resection when we evaluated twice as many sections as in the standard method. The median tumor size was 25 mm in the changed diagnosis group versus 14.5 mm in the no change group (P = 0.03). The univariate analysis also showed that tumor size was a significant predictor of changed diagnosis (P = 0.015). Both the changed diagnosis group and no change group had no recurrence during follow up. CONCLUSIONS: Histological evaluation of twice as many sections as usual changed the initial pathological diagnosis of EGC, although the clinical implication of an additional deeper section was controversial because there was no recurrence. Our analysis also emphasized the importance of detailed histological evaluation to confirm a radical cure in endoscopic resection, especially in the case of larger EGC.

Haptic feedback is useful in remote manipulation of flexible endoscopes.

Background and study aims We developed the Endoscopic Operation Robot (EOR) version 3, offering built-in haptic feedback and manipulation of the entire scope with one hand. Manipulation of the flexible endoscope is done entirely remotely. However, inclusion of haptic feedback places a huge burden on the system. Our purpose in this study was to determine whether haptic feedback is needed in remote manipulation of a flexible endoscope. Methods Five endoscopists performed total colonoscopy using a colonoscopy training model. A trial was conducted in which the endoscope was inserted up to the cecum five times with haptic feedback and five times without haptic feedback. Insertion time, maximum and mean haptic force, and incidence of sigmoid colon overstretching were compared between groups. Results Insertion time was significantly shorter with haptic feedback than without, and overstretching of the sigmoid colon was less frequent. Insertion could thus be performed without using excessive force. Conclusion Haptic feedback is useful for remote control manipulation of flexible endoscopes.

Recombinant Thrombomodulin Used to Successfully Treat Cronkhite-Canada Syndrome with Disseminated Intravascular Coagulation due to Sepsis in a Compromised Patient.

Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by gastrointestinal polyposis, chronic diarrhea, ectodermal dysplasia, skin hyperpigmentation, hair loss and nail atrophy. Although the efficacy of corticosteroid and immunomodulatory agents has been demonstrated, no standard therapy regimen has been established, and the prognosis of CCS is still poor due to various complications. We here in report a CCS patient complicated with severe sepsis and disseminated intravascular coagulation who was successfully treated by combined modality therapies, including recombinant human soluble thrombomodulin.

Flexible robotic endoscopy: current and original devices.

Two current major research topics concern the incorporation of flexible robotic endoscopy systems developed for natural-orifice translumenal endoscopic surgery (NOTES), primarily for the purpose of remote forceps operation, into endoscopic submucosal dissection (ESD) and other flexible endoscopic treatments and the use of robots for the manipulation of flexible endoscopes themselves with the aim of enabling the remote insertion of colonoscopes, etc. However, there are still many challenges that remain to be addressed; the ideal robotic endoscope has not yet been realized. This article reviews the ongoing developments and our own efforts in the area of flexible robotic endoscopy.

[A Case of Acute Superior Mesenteric Artery Occlusion Rescued by Thrombus Aspiration without Bowel Resection].

Acute superior mesenteric artery (SMA) occlusion is rare and associated with high morbidity and mortality.One of the reasons is the difficulty to diagnose the disease soon after the abdominal pain initially occurs. A 79-year-old woman with atrial fibrillation was admitted because of progressive left abdominal pain and nausea. Two hours after the onset, computed tomography revealed an occlusion of the SMA. No signs of intestinal infarction were present. Abdominal angiography revealed complete obstruction from the distal portion of the SMA to the ileocolic artery, so we could have a diagnosis of SMA occlusion early. Continuous per-catheteric thrombus aspiration for the occlusion successfully removed the thrombus and led to complete revascularization laparotomy. We encountered a case of acute mesenteric ischemia due to SMA occlusion with atrial fibrillation. Early diagnosis is necessary to survive without bowel resection.

Serum Albumin Concentrations Predict hypovolaemia Caused by Polyethylene Glycol Plus Ascorbic Acid Prior to Colonoscopy in Elderly Patients.

BACKGROUND: Previous studies have confirmed the safety of polyethylene glycol plus ascorbic acid for healthy middle-aged adults but not for the elderly. The osmotic pressure of polyethylene glycol plus ascorbic acid is approximately twice that of plasma osmolality and may cause dehydration. OBJECTIVE: In this study, we determined whether dehydration was induced in elderly patients by polyethylene glycol plus ascorbic acid, and we analysed the data obtained in order to identify predictors of dehydration. METHODS: This was a prospective, uncontrolled, before-and-after intervention study. All patients older than 65 years who underwent colonoscopies at the Moji Medical Center were administered polyethylene glycol plus ascorbic acid prior to colonoscopy. Clinical variables before and after bowel preparation were measured and analysed statistically. A multiple linear regression analysis was performed to identify predictors of dehydration due to this procedure. RESULTS: Eighty-three patients were assessed for eligibility, and 74 clinical variables were ultimately analysed. A significant increase in the red blood cell count (4.10 versus 4.25 × 10(6)/mm(3)), haemoglobin level (12.4 versus 13.0 g/dL) and haematocrit (38.1% versus 39.4%) suggested the presence of hypovolaemia after the procedure (P < 0.001). The serum concentration of albumin before bowel preparation was identified as the only significant predictor of hypovolaemia (ß = 0.47, P = 0.0001, adjusted R (2) = 0.22). CONCLUSION: The serum concentration of albumin before bowel preparation predicted hypovolaemia caused by polyethylene glycol plus ascorbic acid in elderly patients. Therefore, care is needed in order to prevent hypovolaemia, especially in elderly patients with hypoalbuminaemia. TRIAL REGISTRATION: No. 000015724 (University Hospital Medical Information Network Center).

[Ongoing Development and Directions in Flexible Robotic Endoscopy].

The robotic system for flexible endoscopy was first developed as a platform enabling tissue triangulation in natural-orifice translumenal endoscopic surgery (NOTES). Then endoscopic submucosal dissection (ESD) was introduced and has widely been employed for the treatment of early gastrointestinal carcinoma. Subsequently, endoscopists became well aware of the limitations of their endoscopic manipulations with the conventional flexible endoscopes developed for diagnostic use, which led to the development of robotic systems for upper/lower gastrointestinal tract endoscopes intended for therapeutic use. Most flexible robotic endoscopes have 2 mechanical arms attached to the head, allowing surgeons to perform endoscopic manipulations, such as grasping, traction, incision, excision, and hemostasis. However, there are still many challenges that remain to be addressed: the ideal robotic endoscope has not yet been realized. This article reviews the ongoing developments and our own efforts in the area of flexible robotic endoscopy.

Development of a novel endoscopic manipulation system: the Endoscopic Operation Robot ver.3.

BACKGROUND AND AIMS: The next generation of flexible endoscopy platforms such as The Master and Slave Transluminal Endoscopic Robot (MASTER) is primarily for remote control manipulation of forceps, but manipulation of the flexible endoscope itself still depends on conventional techniques. We have developed the Endoscopic Operation Robot (EOR) ver.3, which incorporates haptic feedback to provide complete remote control flexible-endoscope manipulation. The present study aimed to evaluate the performance of the EOR ver.3. METHOD: A colonoscopy training model was used with scope insertion to the cecum. Force during insertion and insertion time (seconds) to the cecum were evaluated. The data were compared by colon zone and experience level (trainee or expert). RESULTS: The mean insertion time into the cecum was 118.54 ±â€Š89.42 seconds. Stronger force and torque were required for deeper insertion of the scope. Expert and trainee endoscopists differed in the insertion time to the cecum, maximum counterclockwise torque, mean clockwise torque, and mean counterclockwise torque. CONCLUSION: The EOR ver.3 has operability with which endoscopists can easily familiarize themselves.

Usefulness of a novel calibrated hood to determine indications for colon polypectomy: visual estimation of polyp size is not accurate.

PURPOSE: Accurate measurement of polyp size during colonoscopy is important because the size is a surrogate marker of cancer, but a standardized measurement technique to measure polyp size has yet to be determined. We have developed a new device "a novel calibrated hood." We assessed polyp size by visual estimation and measurement using the calibrated hood. METHODS: Patients who underwent polypectomy from November 2012 to September 2013 and who had received screening colonoscopy within 6 months prior to the polypectomy were included in this study. Polypectomy was performed attaching the calibrated hood. The endoscopist measured the polyp size using the calibrated hood. Polyp size was compared between visual estimation and measurement using the calibrated hood. RESULTS: Seventy-five patients with 157 polyps were included. Seventy-seven polyps fulfilled the selection criteria. Mean polyp size by visual estimation was 6.57 ± 2.15, and by using calibrated hood was 5.94 ± 1.73 (p = 0.005). There was a significant difference between measurements using the calibrated hood vs. visual estimation by inexperienced trainees; however, there was no difference in case of well-experienced endoscopists. By visual estimation, 11 of 19 polyps were decided for ≥5 mm despite being less than 5 mm, and 5 of 58 polyps were decided for <5 mm despite being 5 mm or larger in diameter. CONCLUSION: Visual estimation of polyp size is not accurate. It is important to measure the size by an objective way, and the calibrated hood is useful in measuring polyp size, from the standpoint of accurately determining indication for polypectomy.

Development of a Novel Endoscopic Manipulation System: The Endoscopic Operation Robot ver. 2.

BACKGROUND/AIMS: The Endoscopic Operation Robot (EOR) ver. 1 was developed in order to provide robotized operational support for flexible endoscopes, which can be complicated to manipulate. However, total colonoscopy examinations with a colonoscopy training model by proficient operation of the joystick using the EOR ver. 1 took about 6 times longer to reach the cecum than with current manual operation. Thus, EOR ver. 2 is a newly developed robot. METHODOLOGY: The time required total colonoscopy examinations with a colonoscopy training model was performed compared using the EOR ver. 1 and using the EOR ver. 2. RESULTS: The median insertion time (in minutes) was 17.20 ± 3.92 in the EOR ver. 1 group and 9.30 ± 2.13 in the EOR ver. 2 group (p < 0.05). CONCLUSION: The study suggested the possibility of the clinical application Of the EOR.

Endoscopic measurement of polyp size using a novel calibrated hood.

Background. Although the size of colon polyps is an important risk factor for colorectal cancer, a standardized measurement technique has yet to be determined. In clinical practice, most endoscopists estimate polyp size by uncertain visual estimation; however, colonoscopic polypectomy is indicated for adenomatous polyps more than 5 mm in diameter. We have therefore developed a novel calibrated hood that enables accurate measurement of polyp size during colonoscopy. Method. We compared prepolypectomy estimates using the calibrated hood against measurements of preformalin-fixed samples immediately after polypectomy. Results. Sixty-five polyps removed from 44 patients were included in the present study. The mean size of polyps was significantly larger at prepolypectomy (6.06 ± 1.23 mm) than after polypectomy (5.48 ± 1.31 mm, P < 0.05). Conclusion. Accurately measuring the size of polyps during colonoscopy is important, since polyps are shrunk by polypectomy. Attaching the calibrated hood appears useful in the measurement of polyp size to determine indications for polypectomy in patients with colon polyps.