Search Results (449)

Background and Clinical Significance: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to the lung, bone, brain, and adrenal, and rarely to other places; Case presentation: A 74-year-old Arab male presented with symptomatic anemia and melena and was admitted for investigation of the cause. The patient was found to have a large retrosternal goiter and gastric tumor. CT scan showed a pedunculated, nonobstructive mass, suggestive of a GIST or leiomyoma. The neck mass presented with compressive symptoms. He underwent a combined neck and abdominal surgical resection based on a multidisciplinary team decision, as prior biopsies were not conclusive. The final pathology report identified similar tumors in the two specimens and suggested an anaplastic thyroid carcinoma as the primary tumor with metastasis to the stomach. Furthermore, the workup, including a PET scan 2 weeks post-surgery, revealed widespread metastases in the bone, lung, and liver, and the treatment was palliative. He was followed up in the outpatient clinic for 4 and a half months post-operatively. The patient developed sepsis and cardiopulmonary arrest and died; Conclusions: ATC can metastasize to many places in the body, including the stomach (as shown in our case), which can cause significant upper gastrointestinal bleeding and anemia. Metastatic ATC carries a poor prognosis; thus, physicians need to keep a high index of suspicion in approaching similar cases. A multidisciplinary approach for the management is of utmost importance for appropriate treatment. This disease’s pathology, behavior, and targeted new treatment modalities must be explored further. Full article

Gastric cancer peritoneal metastasis is not simply an extension of the primary tumor into the abdominal cavity. It represents a biologically distinct disease context shaped by interactions between disseminated tumor cells, peritoneal fluid, mesothelial surfaces, submesothelial stroma, extracellular matrix, immune populations, and malignant ascites. In this narrative review, we examine peritoneal metastasis as a transition between three related but physiologically different states: the primary gastric tumor, free-floating tumor cells or spheroids in the peritoneal fluid, and established mesothelial or submesothelial metastatic implants. We discuss how tumor cells acquire dissemination competence in the primary tumor, survive detachment and fluid-phase stress, adhere to remodeled mesothelium, recruit stromal and immune support, and adapt to ascites-mediated signaling. We also review how the peritoneal niche may contribute to biomarker discordance, immune exclusion, therapeutic resistance, and limitations of conventional response assessment. Where relevant, we distinguish evidence derived directly from gastric cancer peritoneal metastasis from preclinical data, extrapolation from other peritoneal malignancies, and hypothesis-generating interpretation. Finally, we summarize practical implications for tissue sampling, ascites and lavage analysis, biomarker interpretation, translational modeling, and peritoneal-directed therapeutic strategies. A clearer understanding of the biological divergence between the primary tumor, the fluid-phase compartment, and peritoneal implants may improve the study and clinical management of gastric cancer peritoneal metastasis. Full article

Background and Clinical Significance: Clear cell renal cell carcinoma (ccRCC) is notorious for its aggressiveness and great propensity to metastasize to virtually any organ, with a dismal five-year survival rate. While metastases from ccRCC typically occur in the lungs, lymph nodes, bones and liver, involvement of atypical locations such as the breast, pituitary gland and stomach is extremely rare. These unusual metastases can masquerade as primary tumours at their respective sites, posing significant diagnostic challenges. Case Presentation: Here, we describe three cases of metastatic ccRCC to unusual anatomical sites following nephrectomy: (1) a patient who presented with a suspicious left-sided breast mass and synchronous liver and lung metastases six months following the initial diagnosis of ccRCC; (2) a patient who presented with diplopia, found to have a pituitary lesion four months after nephrectomy; and (3) a patient with known pre-existing lung metastases who developed upper gastrointestinal bleeding one year post-nephrectomy, in whom oesophagogastroduodenoscopy (OGDS) revealed an 8 mm pedunculated gastric polyp. Histopathological examination following biopsies of these lesions showed compact nests and sheets of malignant cells with clear to eosinophilic cytoplasm and distinct membranes. Immunohistochemically, these malignant cells demonstrated CD10 immunopositivity, and were negative for CK7 and CK20, in keeping with the diagnosis of metastatic ccRCC. Conclusions: This case series illustrates the rare metastatic behaviour of ccRCC with its potential to spread to uncommon sites. Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis. Full article

Background: The clinical significance of lymphatic invasion in mucosal early gastric cancer (EGC) treated with endoscopic submucosal dissection (ESD) remains unclear. We evaluated clinicopathologic features and long-term outcomes in patients with lymphatic invasion as the sole non-curative factor. Methods: We retrospectively reviewed 9117 patients who underwent ESD for EGC at Samsung Medical Center between 2001 and 2022. Among patients with mucosal disease and lymphatic invasion as the sole non-curative factor, long-term clinical outcomes were summarized using an outcome flowchart, and characteristics of lymph node-positive cases were analyzed in relation to curative resection criteria. Results: Among 7444 patients with mucosal EGC treated with ESD, lymphatic invasion was identified in 154 patients (2.1%). Among the 117 patients with lymphatic invasion as the sole non-curative factor, the overall rate of pathologically confirmed or clinically suspected lymph node metastasis (LNM) was 4.3% (5/117). Specifically, LNM was identified in 3.2% (3/95) of patients who underwent additional surgery, and in 9.0% (2/22, including one clinically suspected case) managed with observation alone during a median follow-up of 58.0 months. LNM was observed exclusively in lesions involving the muscularis mucosae or in lesions larger than 2 cm, whereas no LNM occurred in tumors confined to the lamina propria measuring ≤ 2 cm. Conclusions: Despite mucosal confinement, lymphatic invasion was associated with a clinically meaningful risk of LNM, whereas no LNM was observed in lesions ≤ 2 cm confined to the lamina propria. For patients with mucosal EGC in whom lymphatic invasion is the sole non-curative factor, careful, individualized decision-making is warranted. Full article

Background: Aspirin, initially recognized for its anti-inflammatory, antipyretic and analgesic properties, holds a prominent role in the treatment of cardiovascular disease. The utility of aspirin in cancer therapeutics has been explored and stratified into COX-dependent and -independent mechanisms. COX2 gene expression has been demonstrated to be significantly upregulated in colorectal cancer and various other gastrointestinal malignancies including pancreatic, esophageal, and gastric cancer. This study investigates the relationship of aspirin use and outcomes in patients with colorectal cancer. Methods: The Nationwide Inpatient Sample (NIS) database from 2017 to 2022 was analyzed for patients age > 18 who were hospitalized for colorectal cancer and its decompensations using ICD-10 diagnostic codes. These patients were further stratified based on the long-term use of aspirin. The principal outcome of this investigation are the odds of in-hospital mortality, with secondary outcomes including odds of pulmonary embolism, portal vein thrombosis, acute kidney injury, septic shock, requiring an ICU level of care and odds of hepatic, pulmonary, gastrointestinal and peritoneal or retroperitoneal metastatic disease. Multivariate logistic regression accounting for hospital and patient characteristics was implemented for analysis, with the Charlson Comorbidity Index used to adjust for coexisting comorbidity burden; a p-value (p) of <0.05 was considered statistically significant. Results: In our analysis of the NIS, 596,160 patients were identified with colorectal cancer and 11.7% (69,750) of this population were identified with long-term use of aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.530, p value < 0.001 95% CI (confidence interval): 0.460–0.617. Patients with aspirin use also demonstrated significantly reduced odds of adverse outcomes and gastrointestinal, hepatic, pulmonary and retroperitoneal/peritoneal metastasis; (aOR 0.606, 95% CI: 0.564–0.653, p < 0.001), (aOR 0.628, 95% CI: 0.582–0.678, p < 0.001), (aOR 0.676, 95% CI: 0.605–0.755, p < 0.001) and (aOR 0.751, 95% CI: 0.685–0.825, p < 0.001) respectively. Conclusions: In recent years, there has been an alarming increase in incidence of colorectal cancer, particularly amongst younger individuals with increased associated mortality. This mortality increase, albeit alarming, is a driving force for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. COX2-mediated signaling serves as a key promotor of tumorigenic molecular signaling that directly contributes to tumor cell proliferation, angiogenesis and metastasis in colorectal cancer. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced odds of in-hospital mortality. Aspirin use is also associated with significantly reduced odds of developing metastatic disease to the liver, gastrointestinal system, lungs and peritoneum in patients with colorectal cancer. These findings convey that aspirin use reduces the likelihood of in-hospital mortality, major comorbid conditions and of developing metastatic disease as compared to those who do not use aspirin. Full article

Background and Objectives: Malignant ascites reflects the tumor microenvironment and provides valuable insights into peritoneal metastasis. This study aimed to assess soluble immune system-related molecules in the ascites fluid of advanced gastrointestinal cancer patients with peritoneal carcinomatosis and to explore potential therapeutic opportunities. Methods: This multicenter prospective cohort study included 48 patients with gastrointestinal adenocarcinoma (17 colorectal, 16 gastric, and 15 pancreatic) with malignant ascites and 15 patients for comparison who required benign ascites drainage for advanced heart failure. Blood samples for routine parameters and ascites fluid for cytokine and soluble immune checkpoint analysis were collected. Parameters were compared between cancer patients and the comparison group, across cancer subgroups, and in correlation with survival. Results: The mean age of participants was 60.2 ± 14.9 years, with a female-to-male ratio of 11:20. The median survival of cancer patients was 84.0 days. Compared with heart failure-associated transudative ascites, malignant ascites demonstrated higher levels of TNF-α, IL-6, IL-10, IL-12p70, IL-18, IL-23, s4-1BB, and TGF-β1, while albumin levels were lower. Significant intergroup differences were observed in TNF-α, IL-6, IL-8, IL-10, IL-12p70, IL-23, 4-1BB, TGF-β1, and PD-L1 levels. In exploratory multivariable analysis, IL-10 and soluble 4-1BB emerged as potential predictors of shorter survival, although these findings require validation in larger cohorts. Survival was negatively correlated with PD-L1, TNF-α, IL-6, and IL-10 in colorectal cancer; 4-1BB, TGF-β1, IL-8, and IL-10 in gastric cancer; and TGF-β1, IL-6, and IL-10 in pancreatic cancer. Conclusions: These exploratory findings indicate that the immunosuppressive milieu in malignant ascites in gastrointestinal cancers may be mediated by cancer subtype-specific pathways, warranting further mechanistic and translational investigation. Full article

Background/Objectives: Tumor suppressor genes are often inactivated by genetic and epigenetic mechanisms. However, whether genetic alterations of these genes, including CDKN2A/P16, are coupled with epigenetic changes in cancer development and progression is unknown. Methods: Freshly frozen gastric carcinoma (GC) samples, paired noncancer surgical margin (SM) samples, white blood cell (WBC) samples, and clinicopathological information were collected from 200 patients. The copy number (CN) of the CDKN2A/P16 gene in these samples was determined by a P16-Light assay and normalized to that in white blood cells (WBCs). The DNA methylation level of the P16 promoter in GC and SM samples was determined by a 115 bp P16-specific MethyLight assay. Results: Both the P16 copy number and the DNA methylation level were significantly lower in GC samples than in SM samples (median, 1.94 vs. 2.14, p < 0.001 for P16 CN; 0.0004 vs. 0.0013, p = 0.002 for P16 methylation) and were associated with GC metastasis. The normalized P16 copy number was significantly lower in GCs without vs. with P16 methylation (p = 0.007). Similarly, more P16 somatic copy number deletions (SCNdel) were detected in GCs without vs. with P16 methylation (38.6% vs. 24.1%, p = 0.027). Conclusions: Somatic P16 copy number variations are closely coupled with P16 promoter DNA methylation during GC development. SCNdel and promoter DNA methylation complementarily inactivate P16 in GC development and promote GC metastasis. Full article

Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with abundant mucin production and high metastatic propensity. However, scarcity of specific biomarkers has impeded clinical diagnosis and mechanistic research. This study systematically compares GSRCC and gastric adenocarcinoma (AC) to identify biomarkers and elucidate molecular basis of GSRCC’s aggressive behavior. Methods: We performed single-cell RNA sequencing (scRNA-seq) on surgically resected primary GC tissues, validating our findings using public datasets and functional experiments. Results: We identified expansion of a mucin-secreting epithelial subcluster (Mucous_muc5ac) in GSRCC, characterized by high MUC5AC, TFF1, and other prognosis-associated genes. Within this population, a MUCL3⁺ subpopulation (Cluster 1) spatially corresponded with classic signet-ring morphology, validating MUCL3 as a specific marker for these cells. Multi-omics analysis revealed that MUCL3⁺ signet-ring cells exhibit genomic instability, dedifferentiation, and enrichment of TNF-α/NF-κB, TGF-β/EMT, and hypoxia pathways, with elevated metastasis/angiogenesis gene scores and high TFF1 expression. Functional validation confirmed that TFF1 was associated with increased gastric cancer cell migration. Conclusions: Our study characterizes the MUCL3⁺ signet-ring cell subpopulation, highlighting the diagnostic utility of MUCL3 and suggesting TFF1 as a candidate for further investigation. These findings establish a foundation for advancing precision diagnosis and mechanistic understanding of GSRCC. Full article

Tumor budding is increasingly recognized as a histopathologic feature associated with invasive behavior in gastrointestinal malignancies. While its prognostic value is well established in colorectal carcinoma, its significance in gastric adenocarcinoma remains less clearly defined because of marked morphologic heterogeneity, variable growth patterns, and the absence of gastric-specific assessment criteria. Multiple studies have associated high budding density with adverse clinicopathologic features, including lymph node metastasis, lymphovascular invasion, advanced tumor stage, and poorer survival, particularly in intestinal-type tumors. However, these associations are more difficult to interpret in diffuse-type and mixed carcinomas, where intrinsic discohesion and architectural variability complicate the distinction between true budding and baseline growth patterns. Beyond prognostic assessment, tumor budding has been linked to localized alterations in cell adhesion, cytoskeletal organization, tumor–stroma interaction, and partial epithelial–mesenchymal transition. Emerging evidence also suggests that its biological significance may differ across molecular subtypes of gastric cancer. This review examines the current evidence on the definition, morphologic spectrum, methodological limitations, and biologic context of tumor budding in gastric adenocarcinoma. We propose that, in gastric cancer, tumor budding is best interpreted not as a uniformly applicable scoring parameter, but as a context-dependent morphologic indicator of invasive tumor remodeling whose meaning varies according to tumor architecture, stromal interface, and molecular subtype. Full article

Background/Objectives: Peritoneal metastasis represents the most frequent and prognostically unfavorable metastatic pattern in gastric cancer, largely due to limited sensitivity of conventional imaging, delayed diagnosis, and insufficient response assessment. The aim of this review is to provide an overview of the current evidence on the diagnosis and treatment of gastric cancer with peritoneal metastases and to address current treatment limitations and options. Methods: This review was designed as a narrative review and is based on an extensive literature search in established databases. Results: Systemic chemotherapy remains the cornerstone of palliative treatment, improving the survival and quality of life compared with the best supportive care; however, outcomes in peritoneally metastatic disease remain poor. Advances in molecularly targeted and immune-based therapies have extended survival in selected patient populations, yet favorable molecular profiles are mainly unknown in peritoneal metastases. Staging laparoscopy and semi-quantitative assessment using the Peritoneal Cancer Index (PCI) are therefore essential for accurate diagnosis, prognostication, and treatment selection. Growing evidence from retrospective studies, multi-institutional cohorts, and selected randomized trials suggests that a multimodal approach—combining systemic therapy with intraperitoneal or bidirectional chemotherapy—may improve survival and quality of life. In carefully selected patients whose primary gastric tumor and peritoneal lesions respond to systemic treatment, complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) may further enhance outcomes and, in rare cases, achieve long-term survival. These potential benefits appear to be limited to highly selected patients with a low peritoneal tumor burden (PCI ≤ 6–7), positive cytology, good performance status, controlled extraperitoneal disease, and a high likelihood of achieving complete macroscopic cytoreduction (CC-0). Conclusions: Although the treatment intent in metastatic gastric cancer remains primarily palliative, carefully selected patients with limited peritoneal metastases may benefit from intensified multimodal treatment strategies when managed in specialized centers. Interdisciplinary evaluation, accurate staging, and individualized treatment planning are essential to optimize outcomes in this challenging disease setting. Full article

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

Background/Objectives: Gastric-type endocervical adenocarcinoma (G-EAC) is a rare, aggressive, and HPV-independent subtype of cervical cancer with a poor prognosis. Due to its rarity, existing literature is often limited by small sample sizes, which hinders the development of evidence-based clinical management strategies. This study aims to evaluate the clinicopathological features, prognostic factors, and responses to postoperative adjuvant therapy in a large cohort of G-EAC patients compared with those with usual endocervical adenocarcinoma (UEA). Methods: We conducted a nested case–control study within a prospectively maintained surgical cohort at a national referral center in China. The study population included 195 pathologically confirmed G-EAC cases and 765 UEA cases. Patients were followed longitudinally with comprehensive clinical and survival data collection. One-to-one propensity score matching (PSM) was performed to balance demographic, clinical, and treatment variables between the groups. Survival outcomes were compared using Kaplan–Meier analysis, and independent prognostic factors were identified via Cox regression. Results: G-EAC patients demonstrated significantly worse survival outcomes than matched UEA patients, with 3-year progression-free survival (PFS) of 66.1% vs. 79.8% (p = 0.014) and 3-year overall survival (OS) of 74.9% vs. 84.6% (p = 0.033). Parametrial involvement and pelvic lymph node metastasis were identified as independent risk factors for both recurrence and death (p < 0.05). Regarding adjuvant treatment, combined radiotherapy and chemotherapy significantly improved survival compared with single-modality treatments (PFS: 65.2% vs. 43.6%; OS: 74.3% vs. 54.5%; p < 0.05); however, G-EAC remained less responsive to these therapies than UEA. Conclusions: G-EAC exhibits more aggressive clinical behavior and poorer survival outcomes compared to UEA. While combined radiotherapy and chemotherapy offer survival benefits, outcomes remain suboptimal. These findings underscore the urgent need for early detection strategies and the development of more effective targeted therapies for this specific subtype. Full article

Background and Aim: Lymphovascular invasion (LVI) is a negative prognostic factor for gastric cancer, but detection limitations hinder its clinical utility and subtype analysis. This study aimed to explore the predictive value of LVI and its subtypes in the prognosis and recurrence patterns of gastric cancer using our enhanced detection method. Methods: We reviewed 2057 patients who underwent gastrectomy in 2018, of whom 1073 met the inclusion criteria. Propensity score matching (PSM) was performed to balance baseline clinicopathological characteristics. Results: After PSM, 311 patients were assigned to the LVI+ group and 311 to the LVI- group. The LVI+ group demonstrated a poorer prognosis. Subtype analysis revealed that lymphatic invasion (LI), but not venous invasion (VI), was associated with poor prognosis in the matched cohort. Stratified by pathological tumor-node-metastasis (TNM) stage, LVI+ and LI+ patients had worse prognosis in Stages I and III, while VI+ patients had worse prognosis in Stage III. Stratified by lymph node status, LVI+ predicted poorer prognosis in both node-negative (N0) and node-positive (N+) patients, and LI+ was also associated with worse prognosis among N+ patients, whereas VI+ was not significantly associated with prognosis in either subgroup. Recurrence analysis indicated that LVI+ was associated with distant and peritoneal metastases, whereas LI+ was associated with local recurrence, distant and peritoneal metastases. Conclusions: Lymphovascular invasion was associated with adverse prognosis in resectable gastric cancer, with lymphatic invasion showing a stronger prognostic impact than venous invasion. These findings indicate that refined assessment of lymphovascular invasion may complement conventional TNM staging in postoperative risk stratification. Full article

Background: Hepatitis B virus infection has been linked to liver cancer and may influence metastasis in other malignancies, but its role in gastric cancer liver metastasis (GCLM) is unclear. Methods: We retrospectively analyzed 776 gastric cancer patients with HBV testing. HBV infection was defined as HBsAg+ (chronic HBV, CHB) or HBsAg− with HBcAb/HBeAb+ (occult HBV, OHB). Among the 776 patients, 300 (38.6%) were classified as HBV+. The association between HBV infection and GCLM was evaluated, and propensity score matching (PSM) was performed to adjust for age and gender. Furthermore, the impact of HBV infection on overall survival (OS) was analyzed. Results: GCLM occurred in 19.5% of patients. HBV+ patients had a higher GCLM prevalence than HBV− patients (25.3% vs. 15.8%; p = 0.001), persisting after PSM (25.3% vs. 15.3%; p = 0.002). HBV infection was an independent risk factor for GCLM (OR = 2.563, p < 0.001). Both OHB and CHB groups showed significantly higher GCLM rates than HBV− patients in univariate and multivariate analyses. However, OS did not differ between groups (p = 0.737). Conclusion: HBV infection significantly increases the risk of liver metastasis in gastric cancer. Enhanced surveillance for liver metastasis is warranted in these patients. Full article

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8⁺ T cells and regulatory FOXP3⁺ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3⁺ T lymphocyte density and lower CD8⁺/FOXP3⁺ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3⁺ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3⁺ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC. Full article