Qin Huang

Objective: Gastric carcinoma with lymphoid stroma is a rare subtype of gastric carcinoma. The clinicopathological features and prognosis of early gastric carcinoma with lymphoid stroma (EGCLS) remain elusive, especially in Chinese populations. Methods: In this study, we investigated 42 consecutive EGCLSs and compared its clinicopathological, molecular, and prognostic characteristics with those of concurrent 1275 Non-EGCLSs with the same pT1b stage, and those of exactly matched Non-EGCLSs in a 1:1 ratio. Results: Compared to Non-EGCLS, EGCLS displayed significantly higher frequencies of the depressed macroscopic type, deep submucosal (SM2) invasion, poor tumor differentiation, and intermediate tumor budding grade, but significantly lower frequency of lymph node metastasis (LNM). After propensity score matching, EGCLS still demonstrated a significantly lower frequency of LNM than Non-EGCLS. Independent risk factors of LNM in submucosal early gastric carcinomas included Non-EGCLS histology, female sex, tumor size ≥ 3.1 cm, elevated and depressed macroscopic types, non-cardiac location, SM2 invasion, lymphovascular invasion, and intermediate-high tumor budding grades. Compared to the exactly matched Non-EGCLSs, EGCLS demonstrated a significantly higher prevalence of either Epstein-Barr virus (EBV) positivity or mismatch repair protein deficiency, wild-type P53 expression, PD-L1 positivity, the depressed macroscopic type, but significantly lower frequencies of lymphovascular invasion. The 5-year overall survival rate was significantly higher in EGCLS (97.1%) than in the matched Non-EGCLSs (91.9%, P = 0.011). Conclusions: Despite poor tumor differentiation and deep invasion, EGCLS showed a low LNM rate, favorable prognosis, and a high proportion of cases with PD-L1 positivity.

Background Superficial basaloid esophageal squamous cell carcinoma (SBSCC) is a rare variant of early esophageal squamous cell carcinoma. Its clinicopathological characteristics remain poorly defined. This study retrospectively investigates SBSCC cases treated with endoscopic submucosal dissection (ESD), comparing them to superficial conventional squamous cell carcinoma (SCSCC). Methods Patients who underwent ESD for superficial esophageal squamous cell carcinoma at Nanjing Drum Tower Hospital between January 2014 and December 2019 were reviewed. Based on histopathological findings, cases were classified into SBSCC and SCSCC groups. Clinical, endoscopic, and pathological data were collected and outcomes analyzed. Results Out of 477 patients, 31 (6.5%) had SBSCC and 446 (93.5%) had SCSCC. SBSCC patients were more likely to be male (P = 0.027). No significant differences were found in age, smoking, alcohol use, tumor size, location, or ESD-related complications. However, SBSCC was associated with lower complete (74.2% vs. 91.5%; P = 0.006) and curative (58.1% vs. 75.6%; P = 0.031) resection rates, deeper invasion (P = 0.018), and more frequent vertical margin involvement (P = 0.010). Both overall survival (OS) and disease-free survival (DFS) were significantly lower in the SBSCC group compared to the SCSCC group (OS: 87.1% vs. 95.0%, P = 0.042; DFS: 76.7% vs. 94.2%, P < 0.05). Post-ESD surgery, chemoradiation, and recurrence were more frequent in SBSCC (P < 0.05). Multivariate analysis identified SBSCC as an independent risk factor for DFS (HR: 4.6; 95% CI 1.990–10.650; P < 0.001), while lymphovascular invasion and complete resection were significant for OS. Conclusions ESD is effective for both SBSCC and SCSCC with low complication rates. However, SBSCC presents with deeper invasion, lower curative resection rates, and worse DFS, highlighting the need for careful post-ESD management.

Gastric cardiac carcinoma (GCC), also known as gastroesophageal junction (GEJ) carcinoma, is a slow‐growing fatal cancer that arises in gastric cardiac mucosa in a region of about 2 cm above and 3 cm below the GEJ line. This carcinoma shows clinicopathologic and genomic features similar, but not identical, to gastric noncardiac carcinoma (GNCC). In contrast, GCC is much more complicated than esophageal adenocarcinoma (EA) in clinicopathology, genomics, and prognosis. GCC is heterogeneous geographically, accounting for 20%–50% of all gastric carcinomas in endemic regions in China. Compared with EA, GCC shows a much broader histopathologic spectrum and worse prognosis. Although detailed mechanisms of GCC pathogenesis remain elusive, advanced age, Helicobacter pylori infection, and gastroesophageal reflux disease are key risk factors. Intriguingly, goblet cell intestinal metaplasia may not be an essential initial step toward carcinogenesis in all GCC cases. At present, an accurate diagnosis of early GCC with prompt curative resection is the only realistic hope for dramatically improving patient outcomes. The recently developed liquid biopsy technology for serum cell‐free DNA is a promising tool for the detection of early GCC, though many challenges remain and an in‐depth investigation is required. Given the recent rapid advances in artificial intelligence, endoscopic technology, and a better understanding of endoscopists for subtle mucosal/vascular changes in early GCC, accurate detection of early GCC in a high proportion of cases would be possible.

Aims: Alpha‐fetoprotein (AFP)‐producing colorectal adenocarcinoma (AFPCRA) is uncommon, with obscure clinicopathological features and prognosis.Methods and Results: In this retrospective comparison study on surgically resected colorectal adenocarcinomas (CRA, n = 2389), we investigated and compared clinicopathological and prognostic features between AFPCRA cases with elevated pre‐operative serum AFP levels, as the AFPCRA study group (n = 49, 2.1%), and the exact sex‐, age‐ and stage‐matched CRA cases as the control group at a 1:2 ratio during the study period from 2011 to 2021. The AFPCRA group was further divided into low and high serum AFP‐level subgroups at the cut‐off of 8.4 ng/ml. Compared to the control group, the AFPCR group showed a significantly higher frequency in extramural venous invasion, intermediate/high tumour budding grade, poor tumour differentiation, liver and distant metastases, mixed and hepatoid adenocarcinomas. The 5‐year overall survival rate was significantly lower in the AFPCRA group (69.2%) than in the control (87.2%) (P = 0.002). The high AFP‐level AFPCRA subgroup displayed a significantly higher prevalence of the left colon location than the low AFP‐level subgroup. Risk factors of overall survival for the AFPCRA group included lymphovascular, perineural and extramural venous invasion, poor tumour differentiation, tumour budding grade, distant metastasis, pN, pM and pathological summary stages, while distant metastasis was the only independent prognostic risk factor.Conclusions: AFPCRA was rare and may be associated with aggressive behaviour and poor prognosis. These preliminary findings in this single‐centre study remain to be validated by future studies with larger samples.

Differences in risk factors (RF) of lymph node metastasis (LNM) and prognosis between submucosal early gastric cardiac (SEGCC) and noncardiac (SEGNCC) carcinomas remain unclear. In this study, we investigated and compared RF of LNM and prognosis in 891 patients with radical gastrectomy for SEGCC (n=217) or SEGNCC (n=674). Compared with SEGNCC, SEGCC displayed significantly higher proportion of elderly patients (70 y or above), the elevated macroscopic type, well/moderately differentiated tubular and low-grade papillary adenocarcinomas, as well as low-grade tumor budding, but lower prevalence of the depressed macroscopic type, poorly differentiated tubular adenocarcinoma, mixed adenocarcinoma, poorly cohesive carcinoma, lymphovascular invasion (LVI), perineural invasion, and high-grade tumor budding. By univariate analysis, significant RF for LNM of the cohort included female sex, poor differentiation, SM2 invasion, LVI, intermediate-grade and high-grade tumor budding, whereas tumor size, histology type, and perineural invasion were the significant RF for LNM in SEGNCC. By multivariate analysis, significant independent RF for LNM included female sex and LVI in SEGCC but were female sex, mixed adenocarcinoma, LVI, and high-grade tumor budding in SEGNCC. The 5-year overall survival was significantly worse in SEGCC than in SEGNCC for patients with LNM, but not for those without. For overall survival, LNM was the only significant independent RF in SEGCC, whereas age 70 years or above and LNM were independent RF in SEGNCC. The results of our study provided the clinicopathologic evidence for individualized clinical management strategies for these 2 groups of patients and suggested different pathogenesis mechanisms between SEGCC and SEGNCC.

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man. CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett’s esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in P53 and CHEK2 genes. The patient was alive without evidence of the disease 36 mo after ESD. CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Objectives: We followed The Cancer Genome Atlas (TCGA) grouping criteria and conducted a clinicopathological cohort study in a unique patient population to gain insight into the pathobiology of esophageal adenocarcinoma (EAC) and adenocarcinoma of the gastroesophageal junction (AGEJ).Methods: We studied and statistically compared the clinicopathological and prognostic features of both cancers in 303 consecutive patients treated at the Veterans Affairs Boston Healthcare System over a 20‐year period using uniform criteria and standardized routines.Results: Over 99% of patients were white men with a mean age of 69.1 years and an average body mass index (BMI) of 28.0 kg/m². No significant differences were detected in age, gender, ethnicity, BMI, and history of tobacco abuse between the two groups. Compared to AGEJ patients, a significantly higher proportion of EAC patients had gastroesophageal reflux disease, long‐segment Barrett's esophagus, common adenocarcinoma type, smaller tumor size, better differentiation, more stages I or II but fewer stages III or IV diseases, scarcer lymph node invasion, fewer distant metastases, and better overall, disease‐free, and relapse‐free survival. The 5‐year overall survival rate was significantly higher in EAC patients than in AGEJ patients (41.3% vs 17.2%, P < 0.001). This improved survival among EAC patients remained significant after censoring all cases detected during endoscopic surveillance, suggesting different pathogenesis mechanisms between EAC and AGEJ.Conclusions: EAC patients showed significantly better outcomes than AGEJ patients. Our results require validation in other patient populations.

Background: Readmission shortly after discharge is indicative of an increased disease severity for patients with ulcerative colitis (UC) and ineffectiveness to medical therapy, which may contribute to a dismal prognosis. Objectives: This study aimed to explore prognostic variables with a nomogram to predict unplanned UC-related readmission within 1 year after discharge. Design: A retrospective cohort study. Methods: Electronic medical records of all UC patients treated at our center between 1 January 2014 and 31 June 2021 were reviewed. A comprehensive analysis of various characteristics, such as demographics, comorbidities, medical history, follow-up appointments, admission endoscopy, histopathologic features, etc., was used to determine the primary end point, which was unplanned UC-related calendar year readmission. Results: We found that the unplanned UC-related readmission rate within 1 year was 20.8%. In multivariable cox analysis, the predictors of the Elixhauser comorbidity index [Hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.93–6.37], regular follow-up (HR: 0.29, 95% CI: 0.16–0.53), any history of corticosteroid use (HR: 3.38, 95% CI: 1.83–6.27), seral level of C-reactive protein (HR: 1.01, 95% CI: 1.00–1.02), and the UC endoscopic index of severity (HR: 1.29, 95% CI: 1.05–1.57) independently predicted calendar year readmission after discharge. The established nomogram had a consistently high accuracy in predicting calendar year readmission in the training cohort, with a concordance index of 0.784, 0.825, and 0.837 at 13, 26, and 52 weeks, respectively, which was validated in both the internal and external validation cohorts. Therefore, UC patients were divided into clinically low-, high-, and extremely high-risk groups for readmission, based on the calculated score of 272.5 and 378. Conclusion: The established nomogram showed good discrimination and calibration powers in predicting calendar year readmission in high-risk UC patients, who may need intensive treatment and regular outpatient visits.