[Show abstract][Hide abstract] ABSTRACT: Background Photoimmunotherapy (PIT) is a novel type of molecular optical imaging-guided cancer phototherapy based on a monoclonal antibody conjugated to a photosensitizer, IR700, in combination with near-infrared (NIR) light. PIT rapidly causes target-specific cell death by inducing cell membrane damages and appears to be highly effective; however, we have previously demonstrated that tumor recurrences were eventually seen in PIT-treated mice, likely owing to inhomogeneous mAb-IR700 conjugate distribution in the tumor, thus limiting the effectiveness of PIT as a monotherapy. Here, we examined the effects of human epidermal growth factor-2 (HER2)-targeted PIT in combination with 5-fluorouracil (5-FU) compared to PIT alone for HER2-expressing human gastric cancer cells. Methods NCI-N87 cells, HER2-positive human gastric cancer cells, were used for the experiments. Trastuzumab, a monoclonal antibody directed against HER2, was conjugated to IR700. To assess the short-term cytotoxicity and examine the apoptotic effects upon addition of 5-FU in vitro, we performed LIVE/DEAD and caspase-3 activity assays. Additionally, to explore the effects on long-term growth inhibition, trypan blue dye exclusion assay was performed. NCI-N87 tumor xenograft models were prepared for in vivo treatment studies and the tumor-bearing mice were randomized into various treatment groups. Results Compared to PIT alone, the combination of HER2-targeted PIT and 5-FU rapidly induced significant cytotoxicity in both the short-term and long-term cytotoxicity assays. While both 5-FU and/or trastuzumab-IR700 conjugate treatment induced an increase in caspase-3 activity, there was no additional increase in caspase-3 activity upon NIR light irradiation after incubation with 5-FU and/or trastuzumab-IR700. The combination of HER2-targeted PIT and 5-FU resulted in greater and longer tumor growth inhibition than PIT monotherapy in vivo. This combined effect of PIT and 5-FU is likely owing to their different mechanisms of inducing tumor cell death, namely necrotic membrane damage by PIT and apoptotic cell death by 5-FU and trastuzumab. Conclusions PIT in combination with 5-FU resulted in enhanced antitumor effects compared to PIT alone for HER2-expressing human gastric cancer in vitro and in vivo. This combination photoimmunochemotherapy represents a practical method for treating human gastric cancer and should be investigated further in the clinical setting.
[Show abstract][Hide abstract] ABSTRACT: In this review, we discuss the features of conventional endoscopy, magnified endoscopy involving image enhanced endoscopy and endoscopic ultrasonography (EUS) using illustrations for submucosal deeply invasive colorectal cancer (SM-Ca). First, the typical features of SM-Ca were observed, including fold convergence, stiffness, depression (ulceration) and elevated lesions in depressed areas. Magnified endoscopic findings using NBI showed dilated, irregularly shaped micro-capillary vessels. In addition, VI and VN pits were clearly visible using crystal violet staining. In contrast, using EUS, at the third layer we found a layer that was thin compared to the surrounding normal mucosa, which suggested the existence of SM-Ca.
No preview · Article · Dec 2015 · Clinical Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: 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.
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 mm(2) 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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: We report a case of a patient with acquired immunodeficiency syndrome (AIDS) and ileocecal ulcer. A 31-year-old man was admitted with chief complaints of decreased body weight and abdominal pain. Colonoscopy revealed a round punched-out ulcer on the ileocecal valve. Initially, we suspected entero-Behçet's disease and simple ulcer as the cause of the ileocecal ulcer. However, after histologic examination of tissue biopsies obtained during colonoscopy, we diagnosed the patient as having cytomegalovirus (CMV) enteritis. Based on the patient's white blood cell depletion and CMV enteritis, we performed a human immunodeficiency virus (HIV) antibody test The test was positive, and the diagnosis of AIDS was established. The number of patients with AIDS has been increasing in Japan; thus, we should consider the possibility of CMV enteritis and AIDS in young adult patients affected by ileocecal ulcer with no notable history.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown the high diagnostic accuracy of narrow-band imaging magnifying endoscopy (NBI-ME) and Lugol chromoendoscopy with pink-color sign assessment (LCE-PS) for superficial esophageal squamous cell carcinoma (SESCC). However, there has been no controlled trial comparing these two diagnostic techniques. We conducted a randomized noninferiority trial to compare the diagnostic accuracy of NBI-ME and LCE-PS. We recruited patients with, or with a history of, squamous cell carcinoma in the head and neck region or in the esophagus. They were randomly assigned to either NBI-ME or LCE-PS. When lesions > 5 mm in diameter were found as brownish areas on NBI or as Lugol-voiding lesions (LVL), they were evaluated to determine whether they are SESCC on the basis of the findings of NBI-ME or PS in the LVL. NBI-ME and LCE-PS were completed in 147 patients each. There was no significant difference in all diagnostic values between the two techniques. Compared with LCE-PS, NBI-ME showed a significantly shorter examination time but a larger number of misdiagnosed lesions especially in patients with many irregularly shaped multiform LVLs. Compared with LCE-PS, NBI-ME might be similarly accurate and less invasive, but less reliable in patients with many LVLs, in the diagnosis of SESCC.
Full-text · Article · Aug 2015 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy (IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps (HPs), traditional serrated adenomas (TSAs), and sessile serrated adenoma/polyps (SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging (AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging (NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as II-dilatation pit (II-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.
[Show abstract][Hide abstract] ABSTRACT: Second-generation ultrasonographic contrast has been developed and it has made possible contrast-enhanced harmonic EUS (CE-EUS) based on low mechanical index. CE-EUS enables visualization of vascular structures and hemodynamics in the lesion in real time. A meta-analysis showed that CE-EUS could detect pancreatic carcinoma with high sensitivity, specificity and accuracy. Pancreatic carcinoma is typically hypoenhancing with heterogeneous, distribution of contrast on CE-EUS. It was reported that CE-EUS was useful in the differential diagnosis of malignant gallbladder lesions including polyps and wall thickness. Malignant gallbladder wall typically showed a heterogeneous distribution pattern of contrast. Moreover, software to quantify the findings of CE-EUS is now available. Thus, CE-EUS might be an indispensable diagnostic modality for pancreaticobiliary pathologies.
No preview · Article · Jun 2015 · Gastroenterological Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Ulcerative colitis (UC) is a representative clinical manifestation of inflammatory bowel disease that causes chronic gastrointestinal tract inflammation. Dextran sulfate sodium (DSS)-induced colitis mice have been used to investigate UC pathogenesis, and in this UC model, disturbance and impairment of the mucosal epithelium have been reported to cause colitis. However, how DSS sporadically breaks down the epithelium remains unclear. In this study, we focused on the colonic microcirculation and myenteric neurons of DSS-induced colitis. Moreover, we examined the potential of myenteric neurons as a target to prevent exacerbation of colitis. Fluorescent angiographic and histopathological studies revealed that DSS administration elicited blood vessel disruption before epithelial disorders appeared. Ischemic conditions in the lamina propria induced inducible nitric oxide synthase (iNOS) expression in myenteric neurons as colitis aggravated. When neuronal activity was inhibited with butylscopolamine, neuronal iNOS expression decreased, and the exacerbation of colitis was prevented. These results suggested that DSS-induced colitis was triggered by microcirculatory disturbance in the mucosa, and that excessive neuronal excitation aggravated colitis. During remission periods of human UC, endoscopic inspection of the colonic microcirculation may enable the early detection of disease recurrence, and inhibition of neuronal iNOS expression may prevent the disease from worsening.Laboratory Investigation advance online publication, 4 May 2015; doi:10.1038/labinvest.2015.60.
Full-text · Article · May 2015 · Laboratory Investigation
[Show abstract][Hide abstract] ABSTRACT: Peroral endoscopic myotomy (POEM) is a less invasive alternative to standard surgery for the treatment of achalasia. Previous studies have demonstrated that submucosal injections of mesna soften tissues and facilitate endoscopic submucosal dissection.
We studied the technical feasibility of a chemically assisted POEM procedure with mesna injection (CA-POEM) in ten pigs compared with POEM with saline injection in five pigs. We also compared two dissection techniques in CA-POEM, diathermy needle knife dissection (n = 5) and balloon mechanical dissection (n = 5). A 10 cm esophageal submucosal tunnel was created with a needle knife or with balloon mechanical dissection following mesna or saline submucosal injection. Approximately 5 cm of inner circular muscle was then dissected within the tunnel. The tunnel was closed with endoclip application at the mucosal endoscopic entry point. Pigs were sacrificed one week post procedure.
All procedures were successful and all pigs survived for one week. Submucosal tunneling time was significantly shorter in the mesna group (363.8 sec for needle knife dissection and 294.2 sec for balloon dissection) than in the saline group (640 sec), regardless of the dissection method (p < 0.05).
Our study demonstrated the technical feasibility of CA-POEM.
No preview · Article · Apr 2015 · Minimally invasive therapy & allied technologies: MITAT: official journal of the Society for Minimally Invasive Therapy