A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Clinical Evaluation of Computer-Aided Colorectal Neoplasia Detection Using a Novel Endoscopic Artificial Intelligence: A Single-Center Randomized Controlled Trial.

INTRODUCTION: Computer-aided diagnostic systems are emerging in the field of gastrointestinal endoscopy. In this study, we assessed the clinical performance of the computer-aided detection (CADe) of colonic adenomas using a new endoscopic artificial intelligence system. METHODS: This was a single-center prospective randomized study including 415 participants allocated into the CADe group (n = 207) and control group (n = 208). All endoscopic examinations were performed by experienced endoscopists. The performance of the CADe was assessed based on the adenoma detection rate (ADR). Additionally, we compared the adenoma miss rate for the rectosigmoid colon (AMRrs) between the groups. RESULTS: The basic demographic and procedural characteristics of the CADe and control groups were as follows: mean age, 54.9 and 55.9 years; male sex, 73.9% and 69.7% of participants; and mean withdrawal time, 411.8 and 399.0 s, respectively. The ADR was 59.4% in the CADe group and 47.6% in the control group (p = 0.018). The AMRrs was 11.9% in the CADe group and 26.0% in the control group (p = 0.037). CONCLUSION: The colonoscopy with the CADe system yielded an 11.8% higher ADR than that performed by experienced endoscopists alone. Moreover, there was no need to extend the examination time or request the assistance of additional medical staff to achieve this improved effectiveness. We believe that the novel CADe system can lead to considerable advances in colorectal cancer diagnosis.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Newly developed magnifying endoscopic classification of the Japan Esophageal Society to identify superficial Barrett's esophagus-related neoplasms.

AIM AND METHODS: The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett's esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. RESULTS: The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as "visible" or "invisible." Morphologic features were evaluated for "visible" patterns, and were subsequently rated as "regular" or "irregular," and the histology, non-dysplastic or dysplastic, was predicted. CONCLUSION: We introduce the process and outline of the magnifying endoscopic classification.

Organ Correlation in IgG4-Related Diseases.

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs.

[A case of MALT lymphoma of the colon, stomach, and small intestine].

An 85-year-old man was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma of the colon in 20XX. Although Helicobacter pylori eradication was performed as part of the treatment, it was ineffective. He was followed-up by colonoscopy for 4 years without additional treatment and there was no interval change;however, he was lost to follow-up 6 years after the first visit. Nine years after the initial diagnosis, he presented with new MALT lymphoma lesions in the stomach and small intestine. Genetic analysis showed that a biopsy specimen was positive for API2/MALT1 fusion gene, and IgH rearrangement showed monoclonal banding between colon and stomach. This suggested disseminated monoclonal API2/MALT1-positive MALT lymphoma of the colon, stomach, and small intestine. Careful attention should be paid to the appearance of multiple lesions in MALT lymphoma.

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: a coincidental association.

BACKGROUND/AIMS: Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. METHODS: Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. RESULTS: Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. CONCLUSIONS: In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

Embryological aspects in autoimmune pancreatitis, proposal of autoimmune dorsal pancreatitis.

OBJECTIVE: We examined the anatomy of the pancreatic duct system in patients with autoimmune pancreatitis (AIP) from the standpoint of embryological pancreatic primordial. MATERIAL AND METHODS: The pancreatic duct system involved in 83 AIP patients was embryologically divided into both ventral and dorsal pancreatic ducts (VD type), only the dorsal pancreatic duct (D type), or only the ventral pancreatic duct (V type). RESULTS: The 83 AIP patients were divided into 62 VD type, 20 D type, and 1 V type. Obstructive jaundice was significantly more frequent in VD type (87%) than in D type (0%; p < 0.01), and abdominal pain was more frequent in D type (24%) than in VD type (2%; p < 0.01). Stenosis of the lower bile duct was detected in 98% of VD type and 15% of D type (p < 0.01). In the 67 patients with involvement of the pancreatic head, only the dorsal pancreatic duct was involved with a normal ventral pancreatic duct in four patients (D type). In the four D-type patients, the pancreatic duct system showed complete pancreas divisum (n = 1), incomplete pancreas divisum (n = 2), or normal pancreatic duct system (n = 1). Stenosis of the lower bile duct was seen in three patients, but was mild, resulting in no obstructive jaundice. Three patients reported abdominal pain and one patient developed acute pancreatitis. CONCLUSIONS: We propose a new entity of "autoimmune dorsal pancreatitis" in which only the dorsal pancreas is involved, and involvement of the lower bile duct and obstructive jaundice is rare.

[Successful conservative therapy for mediastinitis caused by multiple esophageal perforations].

A 77-year-old man was admitted to our hospital on a diagnosis of acute mediastinits, 17 days after he had high fever. Computed tomography of the chest revealed an abscess cavity in the left upper mediastinum. Endoscopic examination showed multiple pin-hole perforations in the upper esophagus from 23 to 24cm distal from the incisors and drainage through the perforation. We diagnosed acute mediastinitis caused by multiple esophageal perforations of unknown etiology. We initiated conservative therapy. Oral intake was restarted on the 17th day because radiological examination showed the esophageal perforation had closed. The patient was discharged on the 36th day from admission. Although mediastinitis caused by esophageal perforation often demands surgical treatment, conservative nonoperative therapy was successful in this patient.

[A case of fulminant ulcerative colitis initially presenting as fever of unknown origin].

A 40's man was referred to our hospital for the investigation of fever of unknown origin lasting for a month. The laboratory data showed a prominent inflammatory reaction and a high titer of PR3-ANCA. Despite the various imaging studies and bacteriological examinations, the cause of the fever could not be detected until he complained of abdominal pain with bloody stool that appeared during hospitalization and which prompted colonoscopy, resulting in the diagnosis of moderate ulcerative colitis of the descending colon. Although temporal improvement was achieved by mesalazine administration, the symptom exacerbated again. Then, a combination of steroid administration and the leukocytapheresis (LCAP) was performed, but it was also not effective. His rapidly deteriorating condition with the lesion extending to whole colon necessitated subtotal colectomy. He has been afebrile and in good condition since the operation, which indicates the cause of the fever was due to ulcerative colitis.

Endocytoscopic observation of esophageal squamous cell carcinoma.

The endocytoscopy system (ECS), adapted for clinical use in 2003, is an ultra-high-power magnifying endoscope that allows observations at the cell level. ECS is based on the technology of light-contact microscopy. The most evident use of ECS is for real-time, high-resolution diagnosis of nuclear abnormalities, mainly in patients with esophageal cancer. Up to now, three different types of ECS have been available. This diagnostic tool makes it possible to omit histological examination of biopsy samples in approximately 84% of esophageal squamous cell carcinoma, as evidence for both an increase of cell density and nuclear abnormalities is considered to be convincing proof that a lesion is malignant. Here we describe the features of ECS and the background that led to its development, and review the published literature pertaining to the observation of esophageal neoplasms using ECS.

Fracture of a Colonic Self-expandable Metallic Stent in Malignant Colonic Obstruction.

Self-expandable metallic stents (SEMSs) are used for the management of malignant colorectal obstruction. A patient who underwent colonic uncovered SEMS insertion for extraluminal stenosis in the splenic flexure of the transverse colon due to advanced gastric cancer is herein reported. The patient presented with a fracture of the colonic SEMS 494 days after SEMS insertion. Although various complications of stenting have previously been reported, the details of fractures of colonic SEMSs have not yet been reported. Because the improvement in the prognosis for patients who undergo palliative SEMS insertion leads to long-term SEMS placement, diverse complications can thus be expected, and new events like stent fracture are expected to increase in the future.

[Superficial small cell carcinoma of esophagus treated by endoscopic mucosal resection combined with chemoradiotherapy--a case report].

The patient was a 70-year-old woman who was admitted to our hospital for positive fecal occult blood. Upper gastrointestinal endoscopy revealed a superficial plateau-type (0- I sep) submucosal cancer on the right wall of the esophagus 28 cm from the incisor. Biopsy revealed small cell carcinoma. CT scan detected neither lymph node metastasis, nor distant organ metastasis. Endoscopic mucosal resection (EMR) was performed. Post-EMR chemoradiotherapies were conducted. The patient has lived with no evidence of cancer recurrence for 40 months. This was the first case of esophageal small cell carcinoma treated by EMR combined with chemoradiotherapy.

Prediction of the invasion depth of superficial squamous cell carcinoma based on microvessel morphology: magnifying endoscopic classification of the Japan Esophageal Society.

Predicting invasion depth of superficial esophageal squamous cell carcinoma is crucial in determining the precise indication for endoscopic resection because the rate of lymph node metastasis increases in proportion to the invasion depth of the carcinoma. Previous studies have shown a close relationship between microvascular patterns observed by Narrow Band Imaging magnifying endoscopy and invasion depth of the superficial carcinoma. Thus, the Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. We conducted a prospective study to evaluate the diagnostic values of type B vessels in the pretreatment estimation of invasion depth of superficial esophageal squamous cell carcinomas utilizing JES classification, the criteria of which are based on the degree of irregularity in the microvascular morphology. Type A microvessels corresponded to noncancerous lesions and lack severe irregularity; type B, to cancerous lesions, and exhibit severe irregularity. Type B vessels were subclassified into B1, B2, and B3, diagnostic criteria for T1a-EP or T1a-LPM, T1a-MM or T1b-SM1, and T1b-SM2 tumors, respectively. We enrolled 211 patients with superficial esophageal squamous cell carcinoma. The overall accuracy of type B microvessels in estimating tumor invasion depth was 90.5 %. We propose that the newly developed JES magnifying endoscopic classification is useful in estimating the invasion depth of superficial esophageal squamous cell carcinoma.

p53 Mutation analysis of low-grade dysplasia and high-grade dysplasia/carcinoma in situ of the esophagus using laser capture microdissection.

OBJECTIVES: The aim of this study was to determine the prevalence and to analyze the characteristics of p53 point mutation in esophageal intraepithelial lesions. METHODS: p53 Immunohistochemical and genetic analyses were performed on histopathologically and morphometrically diagnosed lesions. Laser capture microdissection samples were used for increased accuracy. RESULTS: Of the 70 lesions studied, 21 were high-grade dysplasia/carcinoma in situ (HGD/CIS), 21 low-grade dysplasia (LGD), 16 reactive atypical epithelia (RAE) and 12 normal epithelia (NE). Immunohistochemical staining showed p53 protein accumulation in 86% (18/21) of HGD/CIS, 81% (17/21) of LGD, and in none of RAE and NE. p53 point mutation was detected in 71% (15/21) of HGD/CIS, 67% (14/21) of LGD, but in none of RAE and NE. Of HGD/CIS and LGD with p53 protein accumulation, similar percentages had mutations: 83% (15/18) and 82% (14/17), respectively. Of lesions with mutations, 72% (21/29) had mutations at hot spots such as codons 238, 248, 273 and 282. CONCLUSIONS: p53 Point mutation prevalent in HGD/CIS was also present in a large number of LGD. This is strong evidence that LGD is a neoplastic lesion and that p53 point mutation is deeply involved in esophageal carcinogenesis.