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This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently. [ABSTRACT FROM AUTHOR]

Background: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center.Methods: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000.Results: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis.Conclusion: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs. [ABSTRACT FROM AUTHOR]

The second sentence in the second paragraph under the heading "SMRs" on page 46 should be "SMRs were especially high for small intestinal cancer at 200 (95% CI 34.6-806.7), CRC at 29.7 (95% CI 16.5-53.7), and brain tumor at 12.5 (95% CI 1.8-88.7)". The fourth sentence in the second paragraph under the "SMRs" on page 46-47 should be "However, high SMRs were not observed for many conditions, such as respiratory disease (1.4; 95% CI 0.4-5.7), cardiovascular disease (1.3; 95% CI 0.4-3.9), suicide (1.2; 95% CI 0.4-3.6), and traffic injuries (0.7; 95% CI 0.1-5.1)". [Extracted from the article]

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is an outstanding endoscopic technique in which a colonic lesion can be resected en-bloc. However, the procedure requires a high level of skill and the procedure has yet to be standardized. At the present time, colorectal ESD is only permitted in Japanese institutions that have been certified for advanced medical treatments. Methods: We examined 200 cases of colorectal ESD that were performed in our hospital. Results: Over time, it was found that there was a continuous improvement in the treatment outcomes along with advances in both the procedures and the peripheral equipment utilized. Conclusion: Current results suggest that the colorectal ESD procedure is relatively stable. To ensure colorectal ESD continues to be safe, indications for its use need to be more fully investigated and medical personnel must be trained to carefully perform the procedure. [ABSTRACT FROM AUTHOR]

Background and Aim: No reports on the relative risk of development of colorectal cancer (CRC) in Japanese patients with Crohn's disease (CD) have been published. The present study aimed to investigate the relative risk and the clinical features of CRC complicating CD among patients managed at Fukuoka University Chikushi Hospital, Fukuoka, Japan (a tertiary referral center for inflammatory bowel diseases). Methods: The clinical backgrounds were analyzed of 512 patients with CD who have been treated by our department during the last 20-year period (1985–2005) (total 6212.6 person years at risk). The standardized incidence ratio (SIR) refers to the relative risk of CRC in the subjects as compared with that in a sex- and age-matched healthy population. Results: There were six cases with CRC. The SIR was significantly higher (3.2-fold higher; 95% confidence interval, 1.2–6.9 P < 0.05) in the CD group than in the healthy population. The significant risk factors identified were female sex, mixed small and large bowel type, observation period over 20 years, onset of CD at less than 25 years of age, presence of anal disease, and positive history of surgery. The prognosis for the six cases with CRC was very poor (five cases died within 1.5 years). Conclusion: The risk of CRC in longstanding CD in Japan was similar to that in Western countries. The necessity of surveillance in the management of CD would also need to be discussed in the near future, especially in CD patients with anal lesions or fistulae, and are particularly important in patients with a 20-year or more history of CD. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection.Methods: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed.Results: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002).Conclusions: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics. [ABSTRACT FROM AUTHOR]

We have developed a magnified endoscopic technique for observing the microvascular architecture within the gastric mucosa in units as small as capillary and we have reported the characteristic findings of the microvascular architecture in both normal gastric mucosa and early gastric cancer. The findings in the normal stomach were different depending on the section of the stomach. The body mucosa demonatrated a regular honeycomb-like subepithelial capillary network pattern with a collecting venule, while the antral mucosa demonstrated a regular coil-shaped subepithelial capillary network pattern. The magnified endoscopic findings of early gastric carcinoma were different depending on the types of histological differentiation. The characteristic findings of differentiated carcinoma were (1) the presence of a demarcation line; (2) the disappearance of the regular subepithelial capillary network pattern; and (3) the presence of an irregular microvascular pattern. The findings of undifferentiated carcinoma showed only a reduction in or else the complete disappearance of the regular subepithelial capillary network pattern. In clinical practice, the magnified endoscopic findings of differentiated carcinoma are useful both for determining the margin of early gastric cancer and for making a differential diagnosis between gastritis and gastric cancer in the case of flat reddened lesions. The microvascular architecture as visualized by magnified endoscopy could be a new diagnostic system for the endoscopic diagnosis of early gastric cancer. [ABSTRACT FROM AUTHOR]

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Study Aims: Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG., Patients and Methods: This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail., Results: A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001)., Conclusion: Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Objectives: The purpose of this study was to clarify the clinicopathological characteristics of autoimmune pancreatitis (AIP) in Japanese patients with inflammatory bowel disease (IBD)., Methods: The clinicopathological findings of 7 patients with IBD whose definite AIP was diagnosed in our hospital according to the International Consensus Diagnostic Criteria were reviewed., Results: Five (0.5%) of 961 patients with ulcerative colitis (UC) and 2 (0.3%) of 790 patients with Crohn disease had AIP. All of 7 patients whose AIP was diagnosed were type 2. The rate of elevated values of serum immunoglobulin G4 was 0%. Most patients with the diagnosis of IBD preceded that of AIP, and disease activity of IBD were active. Granulocyte epithelial lesion is similar to the cryptitis seen in colonic tissue of UC. All of 7 patients were given corticosteroids, immunomodulators, and/or biological agents for IBD. One patient had a recurrence., Conclusions: The frequency of AIP in Japanese patients with IBD was low. All cases were type 2 and responded well to corticosteroids, immunomodulators, and biological agents. Autoimmune pancreatitis in UC patients may be an extraintestinal manifestation of UC.

Background/aims: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood., Methods: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared., Results: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018)., Conclusion: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan., (Copyright © 2013 S. Karger AG, Basel.)

Aims: To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease., Methods and Results: Of the 24 cases, four (17%) had large-cell lymphoma (type I), and the remaining 20 (83%) had medium-sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56-positive. Only one (4%) case showed typical CD56- and CD8-negative and CD30-positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy-like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy-like lesions in five (24%) cases expressed T-bet, with no cases of CD30-positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele., Conclusions: Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs., (© 2011 Blackwell Publishing Limited.)

Background: Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC., Methods: SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined., Results: For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m., Conclusions: These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

Background: The diagnostic accuracy of the determination of anti- Saccharomyces cerevisiae antibodies (ASCA) and its clinical significance in Crohn's disease (CD) have been reported in Western countries, but scarcely reported in Japan, where the dietary habits of people differ markedly from those of Western countries. Th present study was undertaken to examine the diagnostic accuracy and clinical significance of ASCA determination in Japanese patients with CD or ulcerative colitis (UC)., Methods: Seventy-five serum samples obtained from 68 patients with CD, 34 serum samples obtained from 30 patients with UC, 35 serum samples from 35 patients with liver cirrhosis, and 31 serum samples from 31 healthy controls were examined. The optical density of each sample was measured by an enzyme-linked immunosorbent assay (ELISA) method to quantify ASCA IgA and IgG., Results: The cutoff level, as determined by discriminant analysis of the data, was 0.1502 for ASCA IgA and 0.156 for ASCA IgG. Of the 68 patients with CD, 31 (45.6%) were ASCA-positive, and of the 30 patients with UC, 4 (13.3%) were ASCA-positive according to these cutoff levels. The sensitivity and specificity of ASCA determination for the differential diagnosis of CD from UC were 45.6% and 86.7%, respectively. When the relationship between ASCA and the clinical features of CD was analyzed, ASCA positivity was found to be correlated with duration of illness., Conclusions: The specificity of ASCA was high; however, the sensitivity was not. ASCA titers were generally low in the Japanese population examined. It would be desirable to determine cutoff levels for ASCA tailored to the Japanese people for the diagnosis of inflammatory bowel disease.

Mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) tumor suppressor- gene mutation is an early event in human hepatocellular carcinoma (HCC) formation in the United States, but its role in hepatocarcinogenesis in Japan is unclear. We therefore determined M6P/IGF2R mutation frequency in HCCs from patients who resided in the southern, central, and northern regions of Japan. Ten single nucleotide polymorphisms were used to identify HCCs and dysplastic liver nodules with M6P/IGF2R loss of heterozygosity. The retained allele in these tumors was also assessed for point mutations and deletions in the M6P/IGF2R ligand binding domains by direct sequencing of polymerase chain reaction (PCR) amplified DNA products. Fifty-eight percent (54 of 93) of the patients were heterozygous at the M6P/IGF2R locus, and 67% (43 of 64) of the HCCs and 75% (3 of 4) of the dysplastic nodules had loss of heterozygosity. The remaining allele in 21% of the HCCs contained either M6P/IGF2R missense mutations or deletions, whereas such mutations were not found in the dysplastic lesions. In conclusion, M6P/IGF2R is mutated in HCCs from throughout Japan with a frequency similar to that in the United States. Loss of heterozygosity in dysplastic liver nodules provides additional evidence that M6P/IGF2R haploid insufficiency is an early event in human hepatocarcinogenesis.