Hirotada Nishie

Reintervention for stent occlusion after bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction

Endoscopic reintervention for stent occlusions following bilateral self‐expandable metallic stent (SEMS) placement for malignant hilar biliary obstruction (MHBO) is challenging, and time to recurrent biliary obstruction (RBO) of the revisionary stent remains unclear. We aimed to clarify a suitable reintervention method for stent occlusions following bilateral SEMS placement for MHBO.

Long-term outcomes of endoscopic gallbladder stenting in high-risk surgical patients with calculous cholecystitis (with videos)

BACKGROUND AND AIMS Recently, endoscopic gallbladder stenting (EGBS) has been performed to prevent recurrences in high-risk surgical patients with cholecystitis. However, evidence regarding the long-term outcomes of EGBS is sparse. We investigated the cholecystitis recurrence rate in high-risk surgical patients with acute calculous cholecystitis and compared the cholecystitis recurrence rates in patients in whom EGBS was performed with those in patients who were observed after percutaneous drainage. METHODS We studied 64 consecutive high-risk surgical patients with acute calculous cholecystitis who required gallbladder decompression between 2007 and 2014. We divided the patient cohort into patients who underwent observation after percutaneous drainage between 2007 and 2011 (OAPD group) and those who underwent EGBS between 2012 and 2014 (EGBS group), and we compared the groups. RESULTS The technical success rate of EGBS was 82.9% based on the intention-to-treat analysis. The cholecystitis recurrence rates were 17.2% in the OAPD group and 0% in the EGBS group, a difference that was significant (P = .043). There was also a significant difference between the groups with respect to the time to recurrent cholecystitis, which was determined by using Kaplan-Meier analysis (P = .015). The overall biliary event rates were 24.1% in the OAPD group and 9.1% in the EGBS group, and no significant difference was noted (P = .207). CONCLUSION EGBS reduced the recurrence of cholecystitis in high-risk surgical patients with calculous cholecystitis. However, stent-related adverse events may occur, and modifications are necessary to reduce these.

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.

Local administration of amphotericin B and percutaneous endoscopic necrosectomy for refractory fungal-infected walled-off necrosis: a case report and literature review.

AbstractWalled-off necrosis (WON) caused by fungal infection is very rare, and its treatment is more difficult than that of bacterial infection. We present the first case of a patient with refractory fungal-infected WON treated with percutaneous endoscopic necrosectomy and local administration of amphotericin B.A Japanese man in his 30s was hospitalized with severe necrotizing pancreatitis and multiple organ failure. Computed tomography imaging of the abdomen 1 month after the onset of pancreatitis revealed infected WON. Percutaneous drainage revealed purulent necrotic fluid, and culture of the fluid revealed the presence of Candida albicans and C glabrata. WON was treated by percutaneous endoscopic necrosectomy and local administration of amphotericin B. Consequently, the patients condition improved, and Candida species were not detected in subsequent cultures.The combination of endoscopic necrosectomy with local administration of amphotericin B may be effective in treating refractory fungal-infected WON.

A next-generation bifunctional photosensitizer with improved water-solubility for photodynamic therapy and diagnosis

Photodynamic therapy (PDT) exploits light interactions and photosensitizers to induce cytotoxic reactive oxygen species. Photodynamic diagnosis (PDD) uses the phenomenon of photosensitizer emitting fluorescence to distinguish some tumors from normal tissue. The standard photosensitizer used for PDD is 5-aminolevulinic acid (5-ALA), although it is not entirely satisfactory. We previously reported glucose-conjugated chlorin (G-chlorin) as a more effective photosensitizer than another widely used photosensitizer, talaporfin sodium (TS); however, G-chlorin is hydrophobic. We synthesized oligosaccharide-conjugated chlorin (O-chlorin) with improved water-solubility. We report herein on its accumulation and cytotoxicity. O-chlorin was synthesized and examined for solubility. Flow cytometric analysis was performed to evaluate O-chlorin accumulation in cancer cells. To evaluate the intracellular localization of photosensitizer, cells were stained with O-chlorin and organelle-specific fluorescent probes. We then measured the in vitro fluorescence of various photosensitizers and the half-maximal inhibitory concentrations to evaluate effects in PDD and PDT, respectively. Xenograft tumor models were established, and antitumor and visibility effects were analyzed. O-chlorin was first shown to be hydrophilic. Flow cytometry then revealed a 20- to 40-times higher accumulation of O-chlorin in cancer cells than of TS, and a 7- to 23-times greater fluorescence than 5-ALA. In vitro, the cytotoxicity of O-chlorin PDT was stronger than that of TS PDT, and O-chlorin tended to accumulate in lysosomes. In vivo, O-chlorin showed the best effect in PDT and PDD compared to other photosensitizers. O-chlorin was hydrophilic and showed excellent tumor accumulation and fluorescence. O-chlorin is promising as a next-generation bifunctional photosensitizer candidate for both PDT and PDD.

Assessment of Factors Affecting the Usefulness and Diagnostic Yield of Core Biopsy Needles with a Side Hole in Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Background/Aims A barbed puncture needle with a side hole was recently developed to improve sample quality and quantity in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In this study, we retrospectively assessed the usefulness of this puncture needle. Methods Factors affecting diagnostic yield, safety, and diagnostic accuracy were investigated in 76 patients who consecutively underwent EUS-FNA for neoplastic lesions at our hospital between January and December 2013. Results The procedure was successful in all cases; the rates of sample collection and determination of the correct diagnosis were 92.1% and 89.5%, respectively. The mean number of needle passes required for diagnosis was 1.1. Complications included mild intraluminal bleeding in two patients (2.6%). Multivariate analysis revealed that lesion size (≤20 mm) was significantly associated with a decreased chance of determining the correct diagnosis. Conclusions Core biopsy needles with a side hole are safe and provide a satisfactory diagnostic yield. However, the side hole may potentially reduce the rate of making the correct diagnosis in small lesions.

Long-Term Efficacy of Adalimumab in Patients With Intestinal Behcet’s Disease: Eight Consecutive Cases

The long-term efficacy and safety of adalimumab (ADA) for the treatment of intestinal Behcet’s disease (BD) in the clinical setting have not been evaluated previously. This retrospective study evaluated the 52-week efficacy of ADA in BD patients. A total of eight patients who were refractory to conventional therapy were given ADA (160/80/40 mg every other week). Marked improvement (MI) was achieved by 10 weeks in five patients (62.5%), and by 52 weeks in six patients (75%). In addition, complete remission was obtained in two patients (25%) at both 10 and 52 weeks. Improvement of global gastrointestinal (GI) symptoms to score 0 was observed in three patients (37.5%) at 10 weeks and four patients (50%) at 52 weeks. Moreover, improvement of endoscopic assessment to score 0 was also seen in four patients (50%) at both 10 and 52 weeks. No adverse events were observed in any patients during the 52 weeks. In conclusion, ADA offers an effective, well-tolerated treatment for intestinal BD in patients who are refractory to conventional therapy.

Combination Therapy With Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis

Background The efficacy and safety of combination therapy with adalimumab (ADA) plus intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions per week) for the treatment of refractory ulcerative colitis (UC) have not been previously evaluated. Methods This retrospective study evaluated the 10-week efficacy of combination therapy with ADA plus intensive GMA on refractory UC patients, on clinical outcomes over 52 weeks under subsequent maintenance monotherapy of ADA, and the effect of combined azathioprine (AZA) with ADA at failure to achieve clinical remission at 10 weeks and at flare-up by 52 weeks. Ten patients were given initial combination therapy of ADA (160/80/40 mg every other week) plus intensive GMA. One patient received total colectomy because of poor response. Results Of nine patients who received this combination therapy, 55.6% displayed cumulative clinical remission at 10 weeks and 33.3% displayed such remission at 52 weeks under subsequent maintenance monotherapy of ADA. The percentage of patients with mucosal healing at 10 weeks (endoscopy subscore ≤ 1) was 66.7%. Adverse events were observed in three patients (pneumonia, cerebral infarction and headache). Conclusion It was concluded that combination therapy with ADA plus intensive GMA is useful for induction of clinical remission in refractory UC patients, and is well tolerated.

Solid Pseudopapillary Neoplasm of the Pancreas Associated with Familial Adenomatous Polyposis

A man in his thirties visited our hospital for an evaluation of a 12×10-mm pancreatic solid tumor that was accidentally detected on computed tomography performed for follow-up of familial adenomatous polyposis (FAP). We diagnosed the patient with a solid pseudopapillary neoplasm (SPN) based on endoscopic ultrasound-guided fine-needle aspiration, and he underwent pancreaticoduodenectomy. Small SPN tumors appear as solid tumors, without typical features of SPN, making the definitive diagnosis more difficult. The genetic background of FAP patients can predispose them to SPN, and imaging of the pancreas should be performed at prescribed intervals in FAP patients.

Ectopic Gastric and Intestinal Phenotypes, Neuroendocrine Cell Differentiation, and SOX2 Expression Correlated With Early Tumor Progression in Colorectal Laterally Spreading Tumors

Micro‐Abstract We analyzed 105 colorectal laterally spreading tumors (LSTs) resected by endoscopic submucosal dissection and investigated clinicopathologic differences among LST subtypes to identify factors indicative of malignant transformation and invasion. Ectopic gastric and intestinal phenotypes, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade in colorectal LSTs, and these markers are correlated with early tumor progression in each LST subtype. Introduction: The significance of the ectopic gastric phenotype remains unclear in patients with colorectal laterally spreading tumors (LSTs). We investigated clinicopathologic differences among LST subtypes, aiming to identify factors indicative of malignant transformation and invasion that are linked to ectopic gastric phenotype and tumor progression. Materials and Methods: We analyzed the morphologic characteristics of 105 colorectal LSTs resected by endoscopic submucosal dissection. LSTs were classified into 2 subtypes: granular (G‐LST) and nongranular (NG‐LST). Resected LSTs were analyzed histologically and were immunohistochemically stained for MUC5AC, MUC6, chromogranin A, CD10, and SOX2. Results: The 105 LSTs included 60 G‐LSTs and 45 NG‐LSTs. By histology, G‐LSTs comprised 5 adenomas with low‐grade dysplasia (LAs), 45 adenomas with high‐grade dysplasia (HAs), and 10 adenocarcinomas invading the submucosa (SMs). NG‐LSTs comprised 8 LAs, 25 HAs, and 12 SMs. MUC5AC positivity was significantly higher in G‐LSTs compared to NG‐LSTs (P = .002), and MUC5AC positivity in HA lesions was significantly higher than in LA lesions (P = .01). MUC6 and SOX2 positivity in SM G‐LSTs, and chromogranin A positivity in SM NG‐LSTs were significantly higher than in HAs (P = .01, .01, and .03, respectively). CD10 positivity in SM NG‐LSTs was significantly higher than in HAs and LAs (P = .02 and .01, respectively). Conclusion: Ectopic gastric and intestinal phenotypes, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade in colorectal LSTs, and these markers are correlated with early tumor progression in each LST subtype.