Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.

BACKGROUND: Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown. METHODS: The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers. RESULTS: Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS. CONCLUSION: The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.

Oxyntic Gland Neoplasms - From Adenoma to Advanced Gastric Cancer: A Review of 29 Cases.

PURPOSE: Oxyntic gland neoplasm (OGN) is a rare condition that can be classified as oxyntic gland adenoma (OGA) or gastric adenocarcinoma of fundic-gland type (GA-FG). GA-FG primarily presents as early gastric cancer, with only a few reported cases of advanced gastric cancer (AGC). We aimed to investigate the clinicopathological features of OGN and describe an aggressive variant. MATERIALS AND METHODS: We investigated a total of 29 cases, including a patient with double primary cases, diagnosed with OGN or differentiated-type adenocarcinoma with GA-FG morphology, between November 2016 and April 2022. We analyzed 54 pathological specimens and reviewed their clinicopathological, endoscopic, and histological features. The lesions were reclassified as OGA or GA-FG, and immunohistochemical (IHC) staining for MUC-5AC and MUC-6 was performed on available resected GA-FG cases. RESULTS: The median patient age was 65 years and males accounted for 58.6% of patients. Most cases occurred in the body horizontally (69.0%) and on the greater curvature side cross-sectionally (48.3%). Endoscopically, type 0-IIa (41.4%) and a subepithelial tumor-like appearance (24.1%) were the most common findings. Histologically, there were 8 cases of OGA (27.6%) and 21 cases of GA-FG (72.4%). In GA-FG, MUC-6 was positive in 13 cases (81.3%), whereas MUC-5AC was positive in 8 cases (50.0%). Three cases presented as AGCs. CONCLUSIONS: Although OGNs are generally considered low-grade, they can present as AGCs and may exhibit features of lymphovascular or perineural invasion. Recognizing the clinicopathological features and accurately diagnosing OGN are important for providing adequate treatment.

Erratum: Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

This corrects the article on p. 327 in vol. 24, PMID: 38960891.

Optimal Diagnostic and Treatment Response Threshold of the Eosinophilic Esophagitis Endoscopic Reference Score: A Single-Center Study of 102 Patients With Eosinophilic Esophagitis.

Background/Aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE. Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established. This study aims to establish these thresholds for the first time among Asian patients with EoE. Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 and November 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology were available for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold (sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). Conclusions: The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3, respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, 3 gastric MANECs, and 1381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2019. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion: We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Transcranial motor-evoked potentials disappear with pons transection.

Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons.

The Potential of Molecular Remission: Tissue Neutrophil Elastase Is Better Than Histological Activity for Predicting Long-Term Relapse in Patients With Ulcerative Colitis in Endoscopic Remission.

BACKGROUND: Growing interest exists in deep remission, beyond clinical and endoscopic remission, to enhance long-term prognosis in patients with ulcerative colitis (UC). Our study aimed to evaluate the risk of relapse according to tissue expression levels of calprotectin and neutrophil elastase (NE) in patients with quiescent UC. METHODS: Rectal biopsies were performed on 218 patients with UC in clinical and endoscopic remission. Histological activity was prospectively scored using the Robarts Histological Index. Tissue calprotectin and NE levels were evaluated using immunohistochemistry. Optimal tissue calprotectin and NE cutoffs for relapse were determined using log-rank analysis. Cox proportional hazard analyses evaluated relapse risk factors. RESULTS: Tissue calprotectin and NE levels were significantly higher in patients with histological activity than in those in histological remission (P < .001). The optimal cutoffs of tissue calprotectin and NE for relapse were 10.61 and 22.08 per mm2, respectively. The 3-year clinical relapse risk was significantly lower in the low-tissue NE group than in the high-tissue NE group (P = .009); however, it did not differ between the low- and high-tissue calprotectin group (P = .094). In multivariate analyses, a low level of tissue NE expression was independently associated with a lower risk of 3-year clinical relapse (adjusted hazard ratio = 0.453, 95% confidence interval = 0.225-0.911, P = .026), unlike histological index and tissue calprotectin. CONCLUSIONS: In patients with UC who have achieved clinical and endoscopic remission, tissue expression of NE is a better predictor of long-term relapse than histological activity.

The tissue expression of neutrophil elastase is a better predictor of long-term relapse than histological activity in patients with ulcerative colitis who achieved clinical and endoscopic remission.

Specific bacterial co-abundance groups are associated with inflammatory status in patients with ulcerative colitis.

BACKGROUND AND AIMS: While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. METHODS: Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease, available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n=166) and activity (n=46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and in a Korean UC cohort. RESULTS: CAG3 and CAG8, dominated by bacteria from family Lachnospiraceae, were associated with remission. Low CAG8 and elevated Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida, however Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. CONCLUSIONS: Lachnospiriceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may help to inform the design of candidate consortia for microbiome-based therapeutics.

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer.

Claudin 18.2 has emerged as a viable therapeutic target in gastric cancer (GC), but little is known about the heterogeneity of its expression in GC. This study investigated the heterogeneity of claudin 18.2 expression in 166 patients with metastatic GC whose surgical or paired primary-metastatic specimens were available. The prevalence of claudin 18.2 positivity (moderate-to-strong expression in ≥ 75% by the 43-14A clone) was 47.0%. Claudin 18.2-positive tumors exhibited more frequent peritoneal metastasis and a lower incidence of hepatic and distant lymph node involvement. Survival outcomes were comparable between patients with claudin 18.2-positive and -negative tumors. Intratumoral heterogeneity was noted in 38.5% of surgical specimens. Paired primary-metastatic site analysis revealed that 25.2% of patients had discordant results for claudin 18.2 positivity. Across different metastatic organ categories, peritoneal lesions showed the highest positivity rate (44.3%) and positive concordance rate (31.4%), whereas liver lesions had the lowest positivity rate (17.9%) and concordance rate (12.8%). In conclusion, claudin 18.2 expression exhibits intratumoral and intrapatient spatial heterogeneity in metastatic GC. Claudin 18.2 positivity is associated with more frequent peritoneal metastasis, and peritoneal lesions are more likely to have positively concordant claudin 18.2 results with the primary site than other metastatic sites.

Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

PURPOSE: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. MATERIALS AND METHODS: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). RESULTS: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. CONCLUSIONS: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma.

Objective: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. Methods: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns-classified as local, diffuse, distant, or multifocal-and time to recurrence were compared between patients with and without VO. Results: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7-38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35). Conclusion: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.

Tubular adenoma arising in tubular colonic duplication: a case report.

Colonic duplication constitutes a rare congenital anomaly, characterized by the presence of hollow cystic or tubular structures exhibiting an epithelial-lined intestinal wall. Diagnostic challenges persist due to its low incidence and manifestation of nonspecific symptoms such as abdominal pain or constipation, resulting in a reluctance to pursue surgical resection. As associated malignancies in colonic duplication are rare, the inherent malignant potential of these anomalies remains undetermined. Additionally, despite reported instances of associated malignancies in colonic duplication, there is an absence of reports in the literature detailing tubular adenoma within these cases. The histologic features of the presented case are particularly noteworthy, situated at the precancerous stage, intimating potential progression towards adenocarcinoma within colonic duplication.

Characterization of HIF-1α Knockout Primary Human Natural Killer Cells Including Populations in Allogeneic Glioblastoma.

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA-Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR-Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.

Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.

Background: Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.

Differences in treatment efficacy between thiopurine and methotrexate in patients with Crohn's disease who were not treated with biologics Immunomodulators (IMMs) used in the treatment of Crohn's disease (CD) include medications such as thiopurine and methotrexate (MTX). Although IMMs are widely prescribed for patients with CD, it remains unclear whether treatment outcomes differ according to the specific types and dosages of IMMs and administration routes of MTX. In this study, we investigated the risk of treatment failure between thiopurines and MTX in CD patients not undergoing biologic treatment. Patients treated with MTX had a higher risk of maintenance failure than those treated with thiopurines. There was no difference in the risk of treatment failure according to the dosage of thiopurine. However, the risk of maintenance failure was higher in patients receiving standard-dose MTX than in those receiving low-dose MTX. There was no difference in the risk of maintenance failure according to the administration route of MTX. Our study enriches the knowledge regarding the treatment efficacy of thiopurines and MTX for patients with CD and may help clinicians develop appropriate treatment plans.

SMARCA4-deficient undifferentiated gastric carcinoma: a case series and literature review.

Undifferentiated gastric carcinoma, characterized by anaplastic cells lacking distinct features of cytological or architectural differentiation, poses diagnostic and therapeutic challenges. Recent studies have suggested an association between this carcinoma and deficiencies in the SWI/SNF complex, particularly mutations in subunits such as SMARCA4. We herein report six cases of SMARCA4-deficient undifferentiated gastric carcinoma with molecular findings, highlighting the rarity and diagnostic pitfalls of this malignancy. Predominantly occurring in males over 50 years, these cases presented with nonspecific symptoms and were often diagnosed at an advanced stage. Histologically, the tumors exhibited a sheet-like growth pattern, reduced or absent epithelial markers, and loss of BRG-1 expression, with molecular analysis confirming SMARCA4 gene mutations. The response to conventional chemotherapy was poor, underscoring the importance of complete surgical resection and the development of alternative treatment modalities.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

Background/Aims: : A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusions: : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair.

BACKGROUND: We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy). METHODS: This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes. RESULTS: Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5. CONCLUSION: Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.

Management Approaches and Patient Outcomes for Giant Pituitary Neuroendocrine Tumors Classified as Knosp Grade 3 and 4.

Background Treatment of patients with a giant pituitary neuroendocrine tumor (GPitNET) is challenging. Here, we present the methods used for the clinical management of patients who underwent GPitNET resection mainly via endoscopic endonasal surgery along with multimodal support to avoid surgical complications, which can affect the outcomes. Methodology The medical records of 25 patients with a GPitNET who underwent endonasal endoscopic surgery were retrospectively reviewed. Complications were analyzed and factors affecting the extent of resection were evaluated. Results Gross total resection was achieved in six (24%), near-total resection (>90%) in nine (36%), and partial resection in 10 (40%) patients. Multivariate analyses revealed that tumors invading the middle fossa had negative effects on the extent of resection (odds ratio = 0.092, p = 0.047). Postoperative vision improved or normalized in 16 (64%), remained stable in eight (32%), and worsened in one (4%), while a new hormonal deficit was noted in seven (28%) patients. Complications included permanent oculomotor nerve palsy in one (4%) and transient oculomotor palsy in one (4%), apoplexy of the residual tumor resulting in ischemic stroke in one (4%), postoperative cerebrospinal fluid leakage in one (4%), and permanent diabetes insipidus in six (24%) patients. Conclusions For GPitNETs that extend into the middle fossa, our study underscored the difficulties in surgical extraction and the necessity for tailored treatment approaches. To ensure the safest and most complete removal possible, the surgical strategy must be specifically adapted to each case. Additionally, employing a comprehensive support approach is essential to reduce the chance of complications in patients impacted by this condition.