Background
Cold snare polypectomy (CSP) has not undergone sufficient histopathological evaluation. This study aimed to clarify the histopathological features of CSP specimens, including resection ...depth and layer, as compared with endoscopic mucosal resection (EMR).
Methods
Polyps were recruited retrospectively. Sessile, semi-pedunculated, and 0-IIa polyps of ≤ 9 mm were selected by propensity score matching and classified as either a complete resection or one with an unevaluable/positive (X/+) margin. Resection depth and layer were estimated and the risk factors for an X/+ margin were evaluated.
Results
A total of 1072 polyps were enrolled. After matching, 184 polyp pairs were selected. An X/+ margin was seen in 105/184 (57%) vs. 70/184 (38%) CSP vs. EMR specimens (
p
< 0.001): specimen damage was 53/184 (29%) vs. 30/184 (16%) (
p
< 0.01) and vertical margin (VM) X/+ was 11/184 (6%) vs. 2/184 (1%) (
p
< 0.05). Among 193 completely resected specimens, resection depth from the muscularis mucosae in CSP vs. EMR was 76 vs. 338 µm (
p
< 0.001) and resection layer was the submucosa in 7/79 (9%) vs. 105/114 (92%) (
p
< 0.001). In multivariate analysis, CSP was a risk factor for procedure-associated VMX/+ odds ratio (OR) 6.80, 95% confidence interval (CI) 1.33–34.69,
p
< 0.05. Sessile serrated adenoma/polyp (SSA/P) was a risk factor for VMX/+ margin in CSP specimens (OR 58.36, 95% CI 7.45–456.96,
p
< 0.001).
Conclusions
SSA/P and colorectal cancer may not be suitable for CSP adoption.
Background
Since “Helicobacter pylori (H. pylori) infection” was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori ...gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the “Guidelines for diagnosis and treatment of H. pylori infection” for the first time in 7 years.
Methods
The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method.
Results
There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X‐ray examination were added to the diagnostic methods. The effects of 1‐week triple therapy consisting of potassium‐competitive acid blocker (P‐CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P‐CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P‐CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication.
Conclusion
We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.
Aims
Claudin 18 (CLDN18) is a member of the claudin family of cell surface proteins, which are widely expressed in epithelial cells and play a role in cell–cell adhesion. CLDN18 isoform 2 (CLDN18.2) ...is specifically expressed in gastric epithelial cells, and is frequently expressed at high levels in gastric adenocarcinoma. On the basis of this, zolbetuximab, a targeted monoclonal antibody, has been developed for patients with CLDN18.2‐positive gastro‐oesophageal adenocarcinoma. Colitis‐associated colorectal adenocarcinomas (CACs) tend to lose intestinal markers and show aberrant gastric mucin expression. Furthermore, clinical trials of human epidermal growth factor receptor 2 (HER2) inhibitor therapy for colorectal carcinoma are ongoing. However, the expression profile of CLDN18.2 and HER2 has not been described in a series of human CACs.
Methods and results
We performed immunohistochemistry for CLDN18 and HER2 on 56 consecutive CACs from 55 inflammatory bowel disease patients, and compared the expression profile with that of a control group of 56 sporadic colorectal adenocarcinomas (CRCs). CLDN18.1 expression and CLDN18.2 expression were validated by reverse transcription polymerase chain reaction (PCR) in paraffin‐embedded CRC tissues. CLDN18 was positive in 27% (15/56) of CACs and in 5% (3/56) of sporadic CRCs (P = 0.004), and CLDN18‐positive CACs were more likely to have lymph node metastasis than CLDN18‐negative CACs (67% versus 36%; P = 0.017). CLDN18 expression was significantly associated with MUC5AC expression (P < 0.001) and loss of special AT‐rich sequence‐binding protein 2 expression (P = 0.005) in CACs. CLDN18.2 was expressed in CRCs that were immunoreactive for CLDN18. Only 4% of CACs were immunoreactive for HER2, and no differences were identified in sporadic CRCs.
Conclusions
These findings suggest that certain CAC cases may be candidates for targeted zolbetuximab therapy.
The special AT-rich sequence binding protein 2 (SATB2) is a sensitive and specific diagnostic marker for colorectal adenocarcinoma and reduced expression of SATB2 is associated with a poor prognosis. ...Colitis-associated colorectal adenocarcinoma often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the SATB2 expression profile in colitis-associated carcinoma has not been defined. We performed immunohistochemistry for SATB2 as well as CDX2, MUC5AC, MUC6 and mismatch repair proteins on 60 consecutive colitis-associated carcinomas from 58 inflammatory bowel disease patients and compared the expression profile to a control group of 32 sporadic colorectal carcinomas. Only 26 (43%) colitis-associated carcinomas expressed SATB2, compared to 29 (91%) sporadic colorectal carcinomas (p < 0.0001). MUC5AC expression was more frequently observed in colitis-associated carcinomas than sporadic colorectal caracinomas (52% and 25% respectively; p = 0.013). Eight (13%) cases of colitis-associated carcinoma showed loss of CDX2 expression, which was retained in all of the sporadic controls (p = 0.047). In colitis-associated carcinoma, 50% of SATB2 negative cases had lymph node metastasis compared to only 15% of SATB2 positive cases (p = 0.007). Loss of SATB2 was particularly frequent in mucinous-type tumors, occurring in 83% of these cases. There was no significant association between SATB2 expression and mismatch repair protein status. These data show that the immunoprofile of colitis-associated carcinoma is different than that seen in sporadic cases. In particular, SATB2 is significantly less sensitive in colitis-associated carcinoma and it should be interpreted cautiously as a marker of colorectal origin in colitis patients. The association between loss of SATB2 and lymph node metastasis suggests that it may have similar prognostic value in the setting of inflammatory bowel disease as in sporadic cases.
Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is ...increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC.
RNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. Immunohistochemistry for beta-catenin and SATB2 was performed on the 30 CACs.
LGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p = 0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75-3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00-2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p < 0.001). Nuclear translocation of beta-catenin was strongly associated with LGR5 expression (p = 0.003), however no significant association was identified between SATB2 expression and LGR5 expression status in CACs.
These findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.
Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) ...protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC).
In 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and β-catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by the RNAscope assay in tissue microarrays.
LGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases (P = 0.0033). Nuclear β-catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases (P = 0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r = 0.6796, P < 0.001). Even in MMR-D and MMR-P cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r = 0.7180, P < 0.0085 and r = 0.6574, P < 0.003, respectively). MMR-D CRC cases showed low expression of LGR5, which may be due to low activation of the Wnt/β-catenin signaling pathway.
Our results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.
Gastric-type adenocarcinoma (GA) is an aggressive subtype of cancer of the uterine cervix. Several immunohistochemical markers for gastric mucins, such as mucin 6 (MUC6) and
N
-acetylglucosamine α1 → ...4galactose → R (αGlcNAc-R), which is recognized by HIK1083 antibody, have been introduced for diagnosis of GA and lobular endocervical glandular hyperplasia (LEGH). However, MUC6 is also expressed in normal endocervical glands and HIK1083 antibody has limited availability. Trefoil factor family 2 protein (TFF2) is secreted by gastric, but not normal endocervical glands. Here, we evaluated TFF2 immunostaining for detection of a gastric immunophenotype in endocervical glandular lesions. We compared TFF2, αGlcNAc-R, and MUC6 expression in 103 endocervical glandular lesions: LEGH (
n
= 23), adenocarcinoma in situ/microinvasive adenocarcinoma (AIS–MIA) (
n
= 29), and invasive adenocarcinoma (usual type UA,
n
= 26; GA,
n
= 11; intestinal type IA,
n
= 2; signet ring cell type Sig,
n
= 2; and mucinous adenocarcinoma not otherwise specified NOS,
n
= 10). TFF2 and αGlcNAc-R expression was completely concordant in each subtype: LEGH (100%), AIS–MIA (44.8%), UA (26.9%), GA (90.9%), IA (100%), Sig (0%), and NOS (20%). TFF2 staining scores were significantly correlated with those of αGlcNAc-R in these lesions. TFF2 and αGlcNAc-R immunoreactivity was present in cytoplasmic mucins and luminal secretions. TFF2 and αGlcNAc-R were not expressed in the normal endocervical glands. MUC6 was frequently expressed in normal endocervical glands and endocervical glandular lesions. Endocervical adenocarcinomas sometimes stained only for MUC6. TFF2 is a promising immunohistochemical marker and its identification in uterine cervical secretion is a potentially useful diagnostic test for endocervical glandular lesions with gastric differentiation.
Materials and Methods: This was a retrospective study of young Japanese adults (aged 19-30 years) who underwent esoph agoga strod uoden oscop y between 2006 and 2020. The indications were upper ...gastrointestinal symptoms and anemia. Changes in the appearance of the esophago--gastric junction (i.e., the Z line and distal esophagitis) and gastric mucosa were examined. Endoscopic Barrett's esophagus was defined using the Japanese criteria. Results: One thousand eight hundred forty-five patients were examined: 848 from 2006 to 2012 400 males, mean age 26.5 years (range 19-30) and 997 from 2013 to 2020 433 males, mean age 26.2 years (range 19-30). The proportion showing endoscopic Barrett's esophagus and gastric fundic gland polyps increased significantly between the 2 periods (12.5% vs. 22.4%, P < .001; 3.4% vs. 7.2%, P < .001) with a significant correlation between the prevalence trends for endoscopic Barrett's esophagus and gastric fundic gland polyps (r = 0.789, P = .0008). Pathological examination showed that the prevalence of traditional fundic gland polyps unrelated to the use of proton pump inhibitors significantly increased from 40% (4/10) to 81% (25/31) between the 2 periods (P = .04). Conclusion: The prevalence of both endoscopic Barrett's esophagus and gastric fundic gland polyps among young Japanese adults significantly increased in the last 15 years. The trend in endoscopic Barrett's esophagus was significantly correlated with that of nonproton pump inhibitor-related gastric fundic gland polyps. Keywords: Reflux esophagitis, endoscopic Barrett's esophagus, gastric fundic gland polyp
A classification system for invasive endocervical adenocarcinoma (ECA) focusing on high-risk human papillomavirus (HPV) detection has been recently developed. However, precursor lesions of each ECA ...subtype and immunohistochemical markers that effectively subcategorize ECAs with gastric and intestinal differentiation have not been fully described. Here, we aimed to subcategorize endocervical adenocarcinoma in situ (AIS) by immunophenotype and to characterize the histopathology of each AIS subtype. We immunohistochemically analyzed 36 AIS and 25 lobular endocervical glandular hyperplasia (LEGH) samples using three cell lineage–specific markers (CLDN18, gastric epithelial cells; CDH17, intestinal epithelial cells; and PAX8, Müllerian epithelial cells). The AISs were immunophenotypically classified as gastric-type (G-AIS;
n
= 2), intestinal-type (I-AIS;
n
= 10), gastrointestinal-type (GI-AIS;
n
= 3), Müllerian-type (M-AIS;
n
= 18), and AIS, not otherwise specified (AIS-NOS;
n
= 3). All 25 LEGHs were categorized as gastric-type. G-AIS had pale eosinophilic or clear cytoplasm with a small amount of apical mucin and fewer mitotic bodies. I-AIS comprised various numbers of goblet cell-type tumor cells. GI-AIS showed intermediate or mixed features of G-AIS and I-AIS. M-AIS, as with the usual-type ECA, was typically characterized by mucin depletion; however, several lesions had abundant cytoplasmic mucin. High-risk HPV was detected in most AISs but was negative in 100% (2/2) of G-AIS, 10% (1/10) of I-AIS, and 6% (1/18) of M-AIS lesions. In summary, the AIS subtypes defined by immunophenotype had distinct histopathological and etiological characteristics. Thus, immunophenotyping with CLDN18, CDH17, and PAX8 might improve the diagnostic accuracy of histopathological classifications of ECAs.
In 2020, the WHO published a new system for classifying invasive endocervical adenocarcinoma based on histological features and high-risk human papillomavirus (HPV) infection. However, ...immunophenotypes of each histological subtype require further investigation. We immunohistochemically analyzed 66 invasive endocervical adenocarcinomas using three cell-lineage–specific markers: claudin 18 (CLDN18) for gastric, cadherin 17 (CDH17) for intestinal, and PAX8 for Müllerian epithelial cells. We identified five immunophenotypes of endocervical adenocarcinoma: gastric (21%); intestinal (14%); gastrointestinal (11%); Müllerian (35%); and not otherwise specified (NOS) (20%). Adenocarcinomas with gastric immunophenotype, characterized by aging (
p
= 0.0050), infrequent HPV infection (
p
< 0.0001), concurrent lobular endocervical glandular hyperplasia (
p
= 0.0060), lymphovascular invasion (
p
= 0.0073), advanced clinical stage (
p
= 0.0001), and the poorest progression-free (
p
< 0.0001) and overall (
p
= 0.0023) survivals, were morphologically compatible with gastric-type adenocarcinoma of the WHO 2020 classification. Conversely, most adenocarcinomas with Müllerian (91%) and intestinal (89%) immunophenotypes were HPV associated and morphologically compatible with usual- or intestinal-type adenocarcinomas of the WHO 2020 classification. The morphology of adenocarcinomas with gastrointestinal immunophenotype was intermediate or mixed between those of gastric and intestinal immunophenotypes; 57% were HPV associated. Adenocarcinomas with NOS immunophenotype were mainly HPV associated (85%) and histologically poorly differentiated. Multivariate analysis revealed that gastric (
p
= 0.008), intestinal + gastrointestinal (
p
= 0.0103), and NOS (
p
= 0.009) immunophenotypes were independent predictors of progression-free survival. Immunophenotypes characterized by CLDN18, CDH17, and PAX8 exhibited clinicopathological relevance and may improve the diagnostic accuracy and prognostic value of conventional histological classification.
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