Whether to change adjuvant regimen after ineffective neoadjuvant chemotherapy in locally advanced gastric cancer (LAGC) remains unclear. We conducted an exploratory study on whether graded histologic regression (GHR) < 50

ObjectivesTo explore hypermethylated gene markers in cervical scraped cells that may be associated with endometrial cancer and validate their diagnostic role in endometrial cancer.MethodsIn an exploratory cohort consisting of 40 paired endometrial tissue and cervical scraping samples, high-performance methylation-targeted genes associated with endometrial cancer were identified. In training and validation sets with 347 and 149 participants, respectively, methylated markers from cervical cytology together with other epidemiological and clinical parameters were assessed to determine their accuracy in detecting endometrial cancer. A decision tree was constructed using methylation markers, bleeding symptoms and endometrial thickness on transvaginal ultrasound (TVS).ResultsIn this exploratory study, eleven genes highly related to endometrial cancer were evaluated using a methylation array. In the training cohort, the highest AUC values for detecting endometrial cancer were 0.93, 0.91, and 0.89 for hypermethylated CDO1, NEFM, and CELF4, respectively. In the validation set, combining methylated CDO1, CELF4, and NEFM achieved a sensitivity of 94.6% (95% confidence interval 85.1-98.9) and a specificity of 92.8% (89.3-95.5) for detecting endometrial cancer. Integration of the endometrial thickness of TVS slightly improved the diagnostic specificity with very low sensitivity.ConclusionsCervical cytological DNA methylation assays of CDO1, CELF4 and NEFM provide a reliable and safe strategy for detecting endometrial cancer and are superior to other noninvasive evaluation methods or parameters.

Little is known about the oncologic results of patients with low-grade endometrial stromal sarcoma (LGESS) with fertility preservation. This study investigated the prognosis of fertility-sparing surgeries and relevant obstetrical outcomes. All eligible patients in the study center were retrospectively reviewed if they consented to surgical treatment for primary LGESS from February 2012 to June 2019 in the study center. Follow-up of fertility and oncologic outcomes was carried out until June 1, 2020. Among 135 patients who underwent surgical therapy for primary uterine LGESS, 21 (15.6

Cronkhite–Canada syndrome (CCS) is a rare non-inherited hamartomatous polyposis syndrome with unknown pathogenesis. To investigate this, we performed single-cell RNA sequencing, spatial in situ sequencing, and bulk RNA-seq on colon biopsies from CCS patients and healthy controls, along with cytokine profiling and organoid/cell line experiments. Multi-omics analysis revealed goblet cell hyperplasia and increased mucin secretion, spatially associated with an inflammatory niche consisting of TNF⁺ Th1 cells, FCN1+ monocytes, and IL1B+ macrophages, all highly active in CCS. Functional assays showed that low-dose TNF-α drives monocyte differentiation into IL-1β-secreting macrophages, while IL-1β induces epithelial PGE2 production, which further amplifies IL-1β secretion, establishing a self-reinforcing loop. An independent cohort confirmed mild elevation of peripheral TNF-α and TNF/IL-1 pathway activation. These findings delineate a pathogenic circuit linking adaptive immune dysregulation, innate remodeling, and epithelial changes, positioning the TNF-α/IL-1β/PGE2 axis as the driver of mucus accumulation and hamartoma formation, offering new potential therapies for CCS. Key features distinguishing Cronkhite–Canada syndrome (CCS) hamartomatous polyps from healthy intestinal tissues and crosstalk among CD4+ T-helper 1 TNF+ cells, FCN1+ monocytes, IL1B+ macrophages, and altered epithelial lineage establish a unique immune microenvironment in CCS. This interaction network drives the accumulation of mucus and remodeling of epithelial lineages via paracrine signaling (e.g., TNF-α/IL-1β/PGE2 axis), collectively forming a pathogenic triad that underpins the development of CCS lesions.

Background The role of neoadjuvant therapy in the treatment of locally advanced colon cancer has become increasingly prominent. However, radiographic assessment rarely provided an accurate prediction of pathological complete response. This study aims to improve preoperative clinical evaluation by investigating the histopathological differences in colon cancer after neoadjuvant therapy. Method This was a prospective observational study conducted at Peking Union Medical College Hospital. Patients were eligible for inclusion if they were locally advanced colon adenocarcinoma and treated with neoadjuvant therapy. Surgical specimens after neoadjuvant therapy were carefully examined by pathologists. According to the standard sampling method, the location of the tumor bed was identified and all tissues of the tumor bed were sent for microscopic examination. Results Of 32 patients, 16 (50%) were included in dMMR group. The difference in tumor location between these two groups was statistically significant (P<0.05). The dMMR group had a better pathological response, with a pCR rate of 62.5% and 3 cases (18.75%) of near pCR (TRG grade 1). In pMMR group, only 12.5% achieved pCR and 6.25% near pCR. The difference between the two groups was statistically significant (P<0.05). There was no statistical difference in gross findings of the surgical specimen between the two groups. However, there was a significant difference in the maximum diameter of residual tumor between the two groups ( P <0.05). Histopathological examination revealed mucinous pools was predominant in 50% of dMMR tumors and fibrosis was the predominant pattern in 87.5% of pMMR tumors ( P <0.05). Conclusions For patients with dMMR after neoadjuvant immunotherapy, histologic manifestations more frequently included large mucinous pools, leading to a gross overestimation of residual tumor.

Here, we report the case of a 30-year-old male who presented with acute right calf muscle pain. Computed tomography angiography revealed a popliteal artery aneurysm in the midsection. Popliteal fossa muscle tissue evaluation revealed that the popliteal artery aneurysm was located beneath an anomalous muscle bundle. Thus, the patient was diagnosed with type III popliteal artery entrapment syndrome and treated surgically. The patient was asymptomatic at rest and during physical activity 4 months after surgery with unobstructed bloodstream in the right popliteal artery. Popliteal artery entrapment syndrome should be considered in young male patients with popliteal artery pseudoaneurysms without atherosclerosis, hereditary diseases, or infections and treated surgically.

OBJECTIVE:DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3). METHODS:The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. RESULTS:For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. CONCLUSIONS:PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

To evaluate cytological DNA methylation testing methods for risk stratification in women with non-16/18 HPV, focusing on high-risk HPV (hrHPV) genotyping. This study compared the triage performance of liquid-based cytology (LBC) testing, hrHPV genotyping, and PAX1/JAM3 gene methylation (CISCER) testing. The absolute risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), grade 3 or worse (CIN3+), and colposcopy referral rates were calculated. The CISCER test showed a CIN3+ risk of 39.1% for positive and 0.9% for negative results. In comparison, LBC ≥ ASCUS and HPV33/35 genotyping had CIN3+ risks of 9.8% and 19.3%, respectively, for positive result. The colposcopy referral rates were 17.4% for CISCER+, 61.9% for LBC ≥ ASCUS, and 8.9% for HPV33/35+ genotyping. The CIN3+ risks were 40.0% and 50.0% when CISCER+ was combined with LBC ≥ ASCUS and HPV33/35+, respectively. The CIN3+ risks were 0.0% and 1.0% when CISCER- was combined with LBC with no intraepithelial lesions or malignancy (NILM) and non-HPV33/35, respectively. Our analysis of CIN2+ patients yielded similar results. DNA methylation testing outperformed LBC in triaging women with non-16/18 hrHPV infections, significantly reducing unnecessary colposcopy referrals, particularly when combined with HPV33/35 genotyping.

Endometrial carcinoma (EC) with deficient DNA mismatch repair (dMMR) is a specific molecular entity with unique clinicopathological features. Herein, we depicted the mutation profile of dMMR ECs and explored the molecular heterogeneity among dMMR subgroups with different etiologies. Next-generation sequencing (NGS) based on a 1021-gene panel was applied to 74 dMMR ECs and 43 proficient DNA mismatch repair (pMMR) ECs. In addition, methylation-specific Polymerase Chain Reaction (PCR) was applied for accessing MLH1 promoter hypermethylation (MLH1me+) in dMMR cases. The mutation rates of PTEN, ARID1A, KRAS, and MSH2 were significantly higher in dMMR group, while the CTNNB1 and MSH3 mutations were more commonly observed in pMMR group (p<0.05). Compared to pMMR ECs, dMMR ECs had significantly higher alteration frequencies in WNT, NOTCH, Cell Cycle and MMR, HRR and BER pathway (p<0.05). Remarkably, the interaction patterns within and across pathways were different between dMMR and pMMR groups. Intriguingly, no CTNNB1 mutation were found in dMMR ECs, while half of the WNT-activated pMMR ECs were CTNNB1 mutated, which were generally mutually exclusive with other WNT pathway key genes. The median tumor mutational burden (TMB) of dMMR ECs was significantly higher than pMMR ECs. However, ultra-high TMB value was related to pathogenic POLE mutation both in dMMR and pMMR ECs. As for dMMR subgroups (MLH1me+, Lynch and Lynch-like), KEAP1 and FBXW7 mutations, which may have potential predictive effect of immunotherapy, were enriched in the Lynch subgroup. dMMR ECs has distinctive genomic profile with molecular heterogeneity, which may have potential prognostic and therapeutic implications.

Autoimmune enteropathy (AIE) and common variable immunodeficiency (CVID) can both manifest as chronic diarrhea and small intestinal villous atrophy, making their differentiation challenging. To explore the similarities and differences in the clinical manifestations, laboratory tests, pathological features, and long-term prognoses between these two diseases. This retrospective study included 26 AIE patients and 29 CVID patients with gastrointestinal (GI) involvement who were admitted to our center from June 2012 to May 2024, with all their medical records reviewed. Differences between the two diseases were evaluated via statistical tests. Compared with CVID patients, AIE patients experienced a shorter duration of severe diarrhea, greater weight loss, and more severe hypoalbuminemia and electrolyte imbalances. Furthermore, CVID patients exhibited a notable history of recurrent respiratory infections; significantly lower serum levels of IgG, IgM, and IgA; a marked decrease in B-cell and CD4 + T-cell counts; and a significant inversion of the CD4 + /CD8 + ratio within peripheral blood lymphocyte subsets. Endoscopically, AIE patients are more likely to present with active inflammatory changes, such as erosions and hyperemia. On the basis of histopathological analysis of 23 AIE patients and 24 CVID patients, AIE patients presented with reduced goblet and Paneth cells, pronounced neutrophilic infiltration, and more frequent apoptotic bodies, while CVID patients demonstrated reduced plasma cells and deep crypt lymphocytosis. The diagnostic efficiency of the five pathological items in the duodenum (AUC 0.937), which includes goblet cell and Paneth cell reduction, was greater than that of the four-item combination (AUC 0.622). Long-term follow-up indicated that patients with both conditions were prone to diarrhea relapse, and CVID patients showed a slightly longer median relapse-free survival than did AIE patients. Although AIE patients and CVID patients share many similarities, they exhibit significant differences. A thorough medical history, laboratory tests, and endoscopic and histopathological results provide compelling evidence for their differential diagnosis.

Uterine myomas are the most prevalent benign gynecological tumors,affecting over 70％of women[1].They are often associated with significant morbidity,including anemia and infertility.

This study investigated BRCA1/2 and homologous recombination repair (HR) pathway gene variants in Chinese epithelial ovarian cancer (EOC) patients. Germline and somatic variants in 21 HR-related genes were analyzed in 229 patients using a 21-gene ovarian panel and in 141 patients using a 508-gene pan-cancer panel. BRCA1, BRCA2, and HR-related gene mutation rates were 17.9%, 3.5%, and 23.1%, respectively, with TP53 as the most frequent somatic mutation (66.4%). Combined germline and somatic BRCA1/2 mutation rates rose to 23.6 and 6.1%. Survival analysis (n = 200) demonstrated longer overall survival (OS) in patients carrying BRCA1/2 or HR mutations. Notably, strategies including likely pathogenic (LP) and variants of uncertain significance (VUS) showed improved OS, especially in BRCA2 and BRCA1/2 somatic carriers. These findings suggest that integrating germline, somatic, and VUS data enhances survival prediction and guides treatment decisions in Chinese EOC patients.

OBJECTIVE:To appraise whether the completion hysterectomy after concurrent chemoradiotherapy (CCRT) would improve the survival outcomes for patients with locally advanced cervical adenocarcinoma (LACA). METHODS:This study was conducted based on a large cohort including more than 200 LACA patients from Peking Union Medical College Hospital. The included patients were divided into the CCRT alone and CCRT + surgery groups, where overall survival (OS), progression-free survival (PFS), loco-regional-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two groups before and after propensity scoring matching (PSM). Cox regression analysis was performed in the CCRT alone group to identify the risk factors impairing the survival probability. The survival outcomes were further compared between the CCRT alone and the CCRT + surgery group in different risk subgroups identified from Cox regression analysis. RESULTS:CCRT + surgery was observed to outperform CCRT alone in OS, PFS, LRFS, and DMFS before PSM (all P < 0.05), while the benefit of surgery could not be maintained after PSM except for DMFS (3-year DMFS: 76.8 vs. 60.2%, P = 0.035). Uterus involvement (UI) was identified as the only risk factor for the CCRT alone group. Surgery was found to increase the survival probability for patients with UI (all P < 0.05), while it did not bring additional survival benefit for patients without UI (all P > 0.05). In the CCRT + surgery group, patients with pathological residual disease (RD) ≥ 1/2 myometrial infiltration (MI) had significantly decreased survival compared to patients with RD<1/2MI or patients without RD (all P < 0.05). Furthermore, postoperative chemotherapy didn't improve survival outcomes in patients with RD<1/2MI, while it seemed to bring additional benefit for patients with RD≥1/2MI in terms of PFS with marginal significance ( P = 0.055). CONCLUSION:Completion hysterectomy after CCRT could increase DMFS for LACA patients, while not every LACA patient would retain OS benefit from surgery, except for those with positive UI. Survival differences existed in different degrees of RD among patients receiving post-radiation surgery and postoperative chemotherapy, demonstrating a trend toward PFS benefit for patients with RD≥1/2MI.

OBJECTIVES:To explore the role of a DNA methylation assay for managing minimally abnormal cervical cancer screening results in a prospective cohort undergoing opportunistic cervical cancer screening. METHODS:In the cohort of the METHY2 and METHY3 screening studies of women undergoing opportunistic cervical cancer screening, cervical cytology samples were sent for high-risk human papillomavirus (hrHPV) DNA assays, cytologic pathology and methylation assays of PAX1/JAM3 (CISCER). This study evaluated the discriminative power of CISCER in managing women with minimally abnormal cervical cancer screening results for CIN3+. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. RESULTS:A total of 1857 women with minimally abnormal cervical cancer findings had cervical histologic outcomes and were included in the analysis. In women with a minimally abnormal cervical cancer result, the sensitivity and specificity of CISCER was 74.9% (95% confidence interval [CI], 68.3%-81.4%) and 89.1% (95% CI 87.6%-90.6%) for detecting CIN3+. CISCER analysis discriminated well for minimally abnormal cervical cancer results, yielding a CIN3+ risk of 40.5% (95% CI 34.9%-46.2%) after a positive result and a CIN3+ risk of 2.7% (95% CI 2.0%-3.6%) after a negative result. CONCLUSIONS:In women with a minimally abnormal cervical cancer screening result, the CISCER provides excellent detection of CIN3+. The use of CISCER in women with a minimally abnormal cervical cancer screening result can lead to a substantial reduction in the number of direct colposcopy referrals.

BACKGROUND A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.