Histopathological Investigation of Progressive Encephalomyelitis with Rigidity and Myoclonus: An Autopsy Case Characterized by Oculomotor Dysfunction and Autonomic Failure.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disease associated with the presence of anti-glycine receptor (GlyR) antibodies. We herein report an autopsy case of an 80-year-old man diagnosed with anti-GlyR antibody-positive PERM who presented with symptoms of oculomotor dysfunction and autonomic failure. Despite intensive immunotherapy, the neurological symptoms showed almost no improvement, and the patient succumbed to aspiration pneumonia and bacterial translocation. Postmortem pathology revealed mild inflammatory changes and neuronal loss that were disproportionate to a severe clinical presentation. These results suggest that the clinical symptoms of PERM may result from antibody-mediated GlyR internalization, leading to neuronal disinhibition, rather than a neuroinflammatory signature.

Gastric dysplastic lesions in Helicobacter pylori-naïve stomach: Foveolar-type adenoma and intestinal-type dysplasia.

Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.

Relapsing sclerosing mesenteritis with multiple strictures of the small intestine.

Sclerosing mesenteritis (SM) is a rare disorder that involves the mesenteric adipose tissue with chronic fibrosing inflammation. Few reports mention the natural history of severe SM cases. Here, we report a severe and relapsing SM case in which a long-term natural history could be followed. The patient had undergone surgery for small bowel stenosis of unknown cause 10 years earlier. He had stopped visiting the hospital at his discretion. He was admitted to the hospital 10 years later due to recurrent symptoms, and a close examination revealed multiple small intestinal strictures; thus, surgery was performed again. The pathological results revealed that the patient had SM, corticosteroid administration dramatically improved his symptoms, and he has maintained remission for a long time.

Characteristic endoscopic findings in early-stage autoimmune gastritis.

Background and study aims Until recently, autoimmune gastritis (AIG) was usually diagnosed at late stages based on typical endoscopic findings, including corpus-dominant advanced atrophy. Early-stage AIG prior to complete gastric atrophy had rarely been diagnosed due to a lack of knowledge about its endoscopic characteristics. The present study sought to identify the endoscopic characteristics of early-stage AIG, enabling its early diagnosis. Patients and methods The clinical and endoscopic findings of 12 patients diagnosed with early-stage AIG between 2016 and 2021 were retrospectively evaluated. Patients were included if they were: (1) positive for serum anti-parietal cell antibody; (2) diagnosed with histological early-stage AIG; and (3) endoscopically positive for folds on the greater curvature of the gastric corpus. Results Two characteristic endoscopic findings of early-stage AIG were identified: longitudinal alignment of pseudopolyps (i.e., a bamboo joint-like appearance) and swelling of gastric areas with erythema (i.e., a salmon roe-like appearance). Conclusions Endoscopic findings characteristic of early-stage AIG include a bamboo joint-like appearance and a salmon roe-like appearance. Studies in large numbers of patients with long-term follow-up are needed to confirm these findings.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

A case of early gastric cancer with metastatic recurrence following curative endoscopic submucosal dissection.

A 70-year-old man was diagnosed with early gastric cancer with ulcerative findings. Endoscopic submucosal dissection as an absolute indication was performed, and en bloc resection was achieved. Pathological examination revealed a well-differentiated adenocarcinoma, 3 × 2 mm in size, intramucosal, with an ulcerative scar, no lymphovascular invasion, and a tumor-free margin. We diagnosed it as a curative resection and followed up with annual endoscopy. Sixteen months after endoscopic submucosal dissection, esophagogastroduodenoscopy revealed a singular ulcer scar; however, serum carcinoembryonic antigen level was elevated. Computed tomography scan showed wall thickening of the gastric antrum and an irregular mass on the dorsal side. Additionally, 18F-fluorodeoxyglucose positron emission tomography/coomputed tomography showed 18F-fluorodeoxyglucose uptake in the gastric antrum, irregular mass, and liver. Endoscopic ultrasonography revealed an internally heterogeneous mass in the gastric antrum region extending from the submucosal layer to the muscularis propria layer. Using an endoscopic ultrasonography-guided fine needle biopsy with a 22-gauge needle for the mass, we diagnosed local recurrence with the submucosal tumor-like appearance, lymph node metastasis, and liver metastases. Unfortunately, the patient died of gastric cancer 3 months after the diagnosis. Here, we report a rare case of local recurrence in the submucosal layer, lymph node metastasis, and liver metastases 16 months after curative endoscopic submucosal dissection.

Histopathologic diagnosis of ultra-early autoimmune gastritis: A case report.

We describe an ultra-early stage of autoimmune gastritis (AIG) that occurs prior to the well-known early-stage AIG. The key pathology is the shortening of the second layer with degenerated parietal cells. In the management of patients with autoimmune diseases, AIG should be considered even if the endoscopy findings are normal.

Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

[A Case of Laparoscopic Abdominoperineal Resection with TpTME for Adenocarcinoma of Anal Canal with Pagetoid Spread].

A man in his 80s was referred to our hospital with the chief complaint of perianal erosion. Colonoscopy revealed a peripheral flat lesion in the anal canal. Since immunohistological examination showed positive for CK20 and negative for GCDFP15, we made a preoperative diagnosis of anal canal cancer with Pagetoid spread. It was diagnosed as cT1bN0M0, cStage Ⅰ by TNM classification, and laparoscopic abdominoperineal resection with TpTME was performed. Negative biopsy of the perianal skin was confirmed both preoperation and during the operation. The postoperative course was uneventful, and no urinary dysfunction was observed. The patient was discharged 15 days after the operation. The histopathological diagnosis was negative margin. The patient is alive without recurrence 1 year after the operation. Adenocarcinoma of anal canal with Pagetoid spread is rare, and differentiation from Paget's disease is important for determining treatment policy. By conducting a detailed examination of the extent of tumor progression and using TpTME together, it was possible to perform surgery that both secured the CRM and preserved urinary function.

Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan.

The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.

Regression of Autoimmune Gastritis after Eradication of Helicobacter pylori.

We report a case of autoimmune gastritis (AIG) in which gastric mucosal atrophy improved with Helicobacter pylori eradication. Based on endoscopic findings (advanced gastric atrophy with vascular visibility and diffuse redness in remnant oxyntic mucosa), a woman in her 40s was suspected of having AIG coexisting with an active H. pylori infection. This was confirmed by a positive anti-parietal cell antibody (PCA, 1:160), an elevated serum gastrin level (638 pg/mL), and positive anti-H. pylori antibody (Hp Ab, 15.5 U/mL) and H. pylori stool antigen tests. Seven months after eradication, reduced vascular visibility and disappearance of diffuse redness on endoscopy and reduced PCA (1:40) and Hp Ab (5.1 U/mL) titers were observed, although histopathological findings (basal-predominant lymphocytic infiltration, destruction of parietal and chief cells, pseudopyloric metaplasia, and enterochromaffin-like cell hyperplasia) were consistent with AIG. Endoscopy 26 months after eradication showed further improvement in atrophic findings in the gastric corpus and histopathological recovery of parietal and chief cells in fundic glands. Serum gastrin levels returned to normal (64 pg/mL), and the PCA titer fell further (1:20).

Clinicopathological Features and the Prevalence of Oxyntic Gland Neoplasm: A Single-center Retrospective Study.

Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs). Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic. Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between December 1, 2017, and March 31, 2021. Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients (11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection, whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30 lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, none of the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up. Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.

Increase in the frequency of community-acquired methicillin-resistant Staphylococcus aureus clones among inpatients of acute care hospitals in the Kyoto and Shiga regions, Japan.

BACKGROUND: Specific epidemic clones of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) are responsible for the worldwide spread of MRSA. However, in recent years, the isolation of community-acquired MRSA (CA-MRSA) clones has been increasing. We investigated the latest molecular epidemiology trends of HA-MRSA and CA-MRSA clones in the Kyoto and Shiga regions, Japan. MATERIALS AND METHODS: All nonduplicate MRSA isolates obtained from the clinical specimens of inpatients at four acute care hospitals in the Kyoto and Shiga regions between 2014 and 2019 were typed using the PCR-based open reading frame typing (POT) method. CA-MRSA and HA-MRSA were classified according to the POT1 values. We performed whole-genome sequencing analysis for representative isolates displaying common POT types. RESULTS: A total of 2413 isolates were included in the study, comprising 1730 nosocomial and 683 nonnosocomial isolates. The rates of HA-MRSA decreased from 50.2% in 2014 to 19.0% in 2019, while those of CA-MRSA increased from 44.7% to 76.4% (p < 0.001). Isolates belonging to the most common 10 POT types (CA-MRSA, n = 6; HA-MRSA, n = 4) accounted for 42% of the isolates studied and were obtained from 3 or more hospitals. Whole-genome sequencing analysis showed that the common CA-MRSA isolates with POT types 106-137-80, 106-9-80, 106-9-2, and 106-137-2, those with POT types 106-183-37 and 106-129-5, and HA-MRSA isolates with POT types 93-191-103, 93-157-127, 93-137-103, and 93-223-111 belonged to ST8-SCCmecIV, ST1-SCCmecIV, and ST764-SCCmecII, respectively. CONCLUSION: A recent clonal shift from HA-MRSA to CA-MRSA occurred, and specific regional clones were prevalent among inpatients in the Kyoto and Shiga regions.

Rapid Progression of Autoimmune Gastritis after Helicobacter pylori Eradication Therapy.

We herein report a case of autoimmune gastritis (AIG) with rapid progression after Helicobacter pylori eradication therapy. The patient's previous gastritis had followed the course of type B gastritis before eradication therapy for many years. Immediately after eradication, we diagnosed her with AIG and carefully followed changes in the endoscopic and histopathological findings and serum markers. All of these clinical findings showed significant atrophic progression in the corporal area for approximately three years. We concluded that H. pylori eradication therapy exacerbated AIG in this case.

Autoimmune Gastritis with a Long-term Course of Type B Gastritis: A Report of Two Cases.

Autoimmune gastritis (AIG) typically exhibits the characteristics of type A gastritis and has been classified as a separate disease from type B gastritis that corresponds to Helicobacter pylori gastritis. However, many reports have suggested the involvement of H. pylori infection in the pathogenesis of AIG. In our two cases, the patients' previous gastritis exhibited a clear pattern in which H. pylori gastritis had progressed over many years, but ultimately transitioned to AIG with its spontaneous disappearance. These findings suggest that some cases of AIG might originate from long-standing H. pylori gastritis.

Bovine lactoferrin suppresses inflammatory cytokine expression in endometrial stromal cells in chronic endometritis.

Chronic endometritis (CE) is a type of chronic inflammation in the endometrium that is associated with infertility, which is primarily due to implantation failure. Antibiotics are the most common treatment for CE. However, some patients with CE are resistant to antibiotic treatment, while others refuse this treatment. Therefore, we focused on lactoferrin (Lf), which exhibits antimicrobial and anti-inflammatory properties, and studied its effect on inflammation in endometrial stromal cells (ESCs) from patients with CE. Endometrial tissue was collected from patients with CE, and ESCs were isolated and cultured. When ESCs were cultured with bovine lactoferrin (bLf: 1 mg/mL), the mRNA expression of TNF-α (p < 0.05) and IL-1ß (p < 0.01) was significantly decreased compared with that in cells cultured without bLf. The level of TNF-α protein in the culture medium was significantly decreased (p < 0.01), while that of IL-1ß was also decreased, but not significantly (p < 0.10), when 1 mg/mL of bLf was added to the culture medium. When more inflammation was induced artificially by adding 0.1 ng/mL of TNF-αto ESCs, the addition of bLf (1 mg/mL) to ESCs decreased IL-6 and IL-1ß mRNA expression to levels similar to those in ESCs without TNF-α treatment. Furthermore, it was revealed that the actions of bLf are mediated by the AKT and MAPK intracellular signaling pathways, which are mechanisms by which the increase in TNF-α-induced cytokine expression is suppressed in ESCs. bLf suppresses the expression of inflammatory cytokines in human ESCs and may be a new therapeutic candidate for CE.