Although undifferentiated gastric cancer (UGC) diagnosed after Helicobacter pylori eradication (HPE) carries a poor prognosis, characteristics of post-HPE UGC have not been evaluated in detail ...because of its low incidence. Therefore, we compared the clinicopathologic characteristics of UGC and differentiated gastric cancers (DGC) diagnosed after successful HPE.
GC lesions from patients who had successfully completed HPE and who had undergone upper gastrointestinal endoscopy between January 2004 and March 2016 were analyzed. Tumors were divided into DGC and UGC groups. Clinicopathologic factors of background and tumor characteristics were compared using univariate and multiple logistic analyses.
A total of 129 tumors from 115 patients were evaluated; 113 tumors were in the DGC group and 16 in the UGC group. Depressed-type tumors (P = 0.024) and sub-submucosal invasion (P<0.001) were significantly higher in the UGC group. The UGC group had larger tumor diameters (25.9±7.3 mm) than the DGC group (13.2±10.2 mm) (P<0.001). Multivariate analysis showed that female sex (odds ratio OR 3.24, 95%CI:1.02-10.37; P = 0.047) and absent follow-up (OR 4.99, 95%CI:1.60-15.57; P = 0.006) were significant independent risk factors for UGC. The DGC group showed a gradually decreasing temporal trend by trend test (P = 0.015), while the UGC group showed a relatively constant incidence over time, although the number of cases was small.
UGC was diagnosed even after long time spans following HPE, although the number of cases was small. Female sex, and especially absent follow-up, were risks for post-HPE UGC, suggesting that diligent long-term follow-up after HPE is essential.
We herein report an extremely rare case of adenocarcinoma of the minor duodenal papilla (MiDP) which was successfully treated by endoscopic mucosal resection (EMR). An asymptomatic 84-year-old man ...underwent upper gastrointestinal endoscopy, which revealed a slightly elevated lesion at the MiDP. The biopsy findings were suggestive of adenocarcinoma. Computed tomography, magnetic resonance images and endoscopic ultrasonography did not reveal pancreatic tumor infiltration nor any apparent distant metastases. Therefore, we treated the lesion using EMR with complete resection. No recurrence or metastasis has been detected at 13 months after EMR. Total resection of the MiDP can thus serve as a relatively safe and simple treatment.
Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, ...which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRAB
and GRAB
in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by tissue eosinophilic infiltration and vasculitis. Although EGPA causes multiple organ damage, it causes ...cholecystitis less frequently. We herein report a case of acute cholecystitis associated with EGPA in which successful treatment with glucocorticoid therapy allowed surgery to be avoided. EGPA can present as acute cholecystitis. It is important not to overlook acute cholecystitis associated with EGPA in patients with abdominal pain with peripheral eosinophilia. Furthermore, in cases of mild cholecystitis associated with EGPA that are diagnosed preoperatively, cholecystectomy might be avoided with conservative glucocorticoid treatment.
Anisakidosis is developed by ingesting Anisakis in marine fish, including the chub mackerel, Scomber japonicus, without proper pre-treatment such as cooking or freezing. Two sibling species of ...Anisakis are found in S. japonicus from Japanese waters, and the prevalence and species of Anisakis in the fish depend on the sea area. For example, Anisakis simplex sensu stricto (s.s.) is found in the Pacific stock of S. japonicus, whereas A. pegreffii is found in the Tsushima Warm Current stock. S.japonicus caught in the Bungo Channel, off the coast of Saganoseki in Oita Prefecture, which is branded as Sekisaba, inhabits a very limited area; however, the infection states of Anisakis found in Sekisaba remain unclear. In this study, we compared the infection states of Anisakis in Sekisaba with those in S. japonicus caught in the South Oita area and Nagasaki Prefecture. All Anisakis from the Nagasaki Prefecture were A. pegreffii, while most of them found in Sekisaba and fish from the South Oita area were A. simplex s.s. Interestingly, the prevalence of Anisakis in Sekisaba was significantly lower than that in the other two areas. This may reflect the fact that Sekisaba might belong to a distinct stock of S. japonicus, varying from other stocks.
The cellular interactions in the tumor microenvironment of colorectal cancer (CRC) are poorly understood, hindering patient treatment. In the current study, we investigate whether events occurring at ...the invasion front are of particular importance for CRC treatment strategies. To this end, we analyze CRC tissues by combining spatial transcriptomics from patients with a public single-cell transcriptomic atlas to determine cell-cell interactions at the invasion front. We show that CRC cells are localized specifically at the invasion front. These cells induce human leukocyte antigen G (HLA-G) to produce secreted phosphoprotein 1 (SPP1)+ macrophages while conferring CRC cells with anti-tumor immunity, as well as proliferative and invasive properties. Taken together, these findings highlight the signaling between CRC cell populations and stromal cell populations at the cellular level.
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•Spatial and single-cell atlas of human normal and cancer colorectal tissues•Colorectal cancer cells at the invasive front co-localize with macrophages•Spatial intercellular communication occurs between tumor cells and stromal cells•HLA-G is essential for anti-tumor immunity in colorectal cancer
Ozato et al. utilize a spatial transcriptome analysis approach to identify malignant crosstalk among co-localized cells in the cancer microenvironment. CRC cells localized at the invasion front induce HLA-G to produce SPP1+ macrophages, simultaneously conferring anti-tumor immunity as well as proliferative and invasive properties to CRC cells.
Background
We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model).
Aims
We aimed to investigate ...the characteristics and histogenesis of PACM using a reflux model.
Methods
A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach–jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2.
Results
In all reflux model rats, PACM was observed proximal to the glandular stomach–jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083.
Conclusions
PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration.
Background
Helicobacter pylori
CagA has been found to be immuno-dominant protein and utilized for the diagnosis of the infection with
cagA
-positive strains. It is important to characterize the ...peptide epitopes capable of detecting serum anti-CagA antibodies to understand CagA immunogenicity.
Methods
Sera from 171 Japanese patients were subjected for the epitope mapping study. Eighty seven peptides were designed from the CagA consensus sequence and were used for ELISA protocol to test the serum samples. The reacting anti-CagA IgG amounts to specific peptides were measured and compared.
Results
The study revealed a strong reactivity of two peptides (c7-NNT
EPIYA
QVNKKKAGQAT and c8-AGQATSPE
EPIYA
QVAKKV) in
H. pylori
-infected group. Interestingly, these two peptides contained the well-known EPIYA-A and EPIYA-B region, respectively, which are two out of three CagA phosphorylation domains. Tyrosine-phosphorylation of these peptides reduced their reactivity in most sera. Moreover, additional peptides’ mapping and chimeric-peptides’ experiments indicated that the amino acids (QV and KK) accommodated in right-side flanking regions of both EPIYA-motifs were essential for their strong reactivity, whereas the third EPIYA-motif containing peptide (c12-GRSASP
EPIYA
TIDFDEA) with differing flanking amino acids was not reactive in most cases.
Conclusions
Our results suggest that the amino acid sequences constituted in the two reactive peptides are the important immunogenic regions of CagA which would be useful to develop next-generation peptide-based diagnostic assays.
Pancreatic neuroendocrine tumors(p NETs) are particularly rare. The various forms of PNETs, such as cystic degeneration, make differentiation from other similar pancreatic lesions difficult. We can ...detect small lesions by endoscopic ultrasound(EUS) and obtain preoperative pathological diagnosis by EUS-guided fine needle aspiration(FNA). We describe, here, an interesting case of p NET in a 42-year-old woman with no family history. Computed tomography and magnetic resonance imaging revealed an 18 mm × 17 mm cystic lesion with a nodule in the pancreatic tail. Two microtumors about 7 mm in diameter in the pancreatic body detected only by EUS, cystic rim and nodules all showed similar enhancement on contrast-harmonic EUS. Preoperative EUS-FNA of the microtumor was performed, diagnosing multiple p NETs. Macroscopic examination of the resected pancreatic body and tail showed that the cystic lesion had morphologically changed to a 13-mm main nodule, and 11 new microtumors(diameter 1-3 mm). Microscopically, all microtumors represented p NETs. From the findings of a broken peripheral rim on the main lesion with fibrosis, rupture of the cystic p NET was suspected. Postoperatively, pituitary adenoma and parathyroid adenoma were detected. The final diagnosis was multiple grade 1 p NETs with multiple endocrine neoplasia type 1. To the best of our knowledge, no case of spontaneous rupture of a cystic p NET has previously been reported in the English literature. Therefore, this case of very rare p NET with various morphological changes is reported.