Search Results (36)

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article

Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world effect of NACT on perioperative and oncologic outcomes in a high-volume Western center. Methods: Data from 254 patients who underwent gastrectomy with D2 lymphadenectomy for GC between March 2016 and January 2024 were prospectively collected and retrospectively analyzed. Patients were categorized into an upfront surgery group (n = 144, 56.7%) and a NACT group (n = 110, 43.3%). The primary outcome was to compare the two study groups in terms of perioperative outcomes, as well as overall (OS) and disease-free survival (DFS). Multivariate analyses were conducted to identify factors associated with perioperative complications and long-term survival. Results: Patients in the NACT group were younger (median age 65 vs. 72 years; p = 0.001) and had fewer comorbidities. NACT was associated with a higher incidence of proximal tumors (54–49.1% vs. 37–25.7%; p = 0.001), diffuse-type tumors (27–45.8% vs. 39–31.7%; p = 0.03), and lymph-node metastases (82–74.1% vs. 84–58%; p = 0.007). No significant differences were observed in median hospital stay (9 (7–16) and 10 (8–22) days for the upfront and NACT groups, respectively; p = 0.26), post-operative mortality (11–7.6% and 5–4.5% for the upfront and NACT groups, respectively; p = 0.32), and major complications (30–20.8% and 23–20.9% for the upfront and NACT groups, respectively; p = 0.99). Among patients receiving NACT, the FLOT regimen was associated with a lower rate of complications (12–16.2% vs. 11–30.5% in the non-FLOT cohort; p = 0.05) and reoperations (4–5.4% vs. 8–22.2% in the non-FLOT group; p = 0.008). Tumor location was identified as an independent predictor of perioperative complications (OR 4.7, 95% C.I.: 1.56–14.18; p = 0.006), while non-FLOT regimens were independently associated with higher reoperation rates (OR 0.22, 95% C.I.: 0.06–0.86; p = 0.003). Five-year OS was comparable between the two groups (44.6% in the NACT group vs. 47.7% in the upfront surgery group; p = 0.96). N+ status (OR 2.5, 95% C.I. 1.42–4.40; p = 0.001) and R+ margins (OR 1.89, 95% C.I. 0.98–3.65; p = 0.006) were negative independent prognostic factors for DFS. Conclusions: Although several selection biases limit the generalizability of our findings, our results suggest that NACT prior to gastrectomy for GC does not increase postoperative morbidity and mortality in appropriately selected patients. However, its use in elderly and polymorbid patients should be carefully considered to determine the safest and most effective therapeutic approach, particularly in selecting the appropriate chemotherapy regimen, to minimize the risk of postoperative complications requiring surgical reintervention. Full article

Background: Proximal gastrectomy (PG) with double tract reconstruction (DTR) offers organ preservation for early gastric cancers, leading to reduced vitamin B12 deficiency, less weight loss, and improved quality of life. The JCOG1401 study confirmed excellent long-term outcomes for PG in stage I gastric cancer. However, in locally advanced proximal gastric cancer (LAPGC), preserving the gastric body and lymph node station 4d may compromise margin clearance and adequate lymphadenectomy. Methods: We propose a modified PG that removes the distal esophagus, gastroesophageal junction (GEJ), cardia, fundus, and gastric body, preserving only the antrum and performing DTR. Lymphadenectomy is also adapted, removing stations 1, 2, 3a, 4sa, 4sb, 4d, 7, 8, 9, 10 (spleen preserving), 11, and lower mediastinal nodes (stations 19, 20, and 110), while preserving stations 3b, 5, and 6. Indications for this procedure include GEJ (Siewert type II and III) and proximal gastric cancers with ≤2 cm distal esophageal involvement and ≤5 cm gastric involvement. Results: In our initial experience with 14 patients, we achieved R0 resection in all patients, adequate lymph node harvest (median 24 nodes, IQR 18–38), and no locoregional recurrences at a median follow-up of 18 months. We also found favorable postoperative weight loss, reflux, and anemia in the PG cohort. Conclusion: While larger studies and long-term data are still needed, our early results suggest that modified PG—despite sparing only the antrum—retains the key benefits of PG over total gastrectomy, including better weight maintenance and improved hemoglobin levels, while maintaining oncologic outcomes for LAPGC. Full article

Background: Helicobacter pylori (HP) and Epstein–Barr virus (EBV) coinfection lead to chronic inflammation and contribute to the development of gastric cancer. However, studies examining the association between HP virulence factors and EBV infection in gastric cancer are limited. This study investigated the polymorphisms of HP virulence factors associated with EBV infection and their effects on clinical outcomes in EBV-associated gastric cancer (EBVaGC). Methods: A total of 96 HP isolates from 54 patients with gastric cancer were divided and analyzed based on EBV coinfection status. Polymerase chain reaction amplifications of virulence factors were conducted using DNA extracts from HP isolates cultured from gastric mucosal specimens. Results: EBV infection was significantly associated with gastric carcinoma with lymphoid stroma morphology and a proximal location in the stomach. Most HP strains from patients with gastric cancer were positive for cagA (100.0%), vacA (100.0%), and iceA1 (87.5%). Among HP isolates with EBV coinfection, the prevalence of iceA2 (21.7% vs. 0.0%, p < 0.001) and ureA (21.7% vs. 4.0%, p = 0.009) was significantly more frequent, and that of iceA1 (78.3% vs. 96.0%, p = 0.009) and vacA s1a (4.3% vs. 22.0%, p = 0.012) was less frequent than those of EBV– colonies. Multivariate analysis indicated that ureA (odds ratio, 6.148; 95% confidence interval [CI], 1.221 to 30.958; p = 0.028) was associated with EBVaGC. No significant difference in clinical outcomes was observed based on the presence of ureA expression in EBVaGC. Conclusions: In gastric cancer, regardless of EBV infection, most HP strains were highly virulent, testing positive for cagA, vacA, and iceA1. Although ureA was significantly associated with EBV infection, it did not influence the clinical outcomes of EBVaGC. Full article

Background/Objectives: Gastrectomy is among the most effective treatments for gastric adenocarcinoma. Margin status can be categorized into three types: proximal, distal, and radial margins. While the relationship between proximal and distal margin involvement in specimens and prognosis has been extensively studied, the impact of a radial margin has not been thoroughly investigated. This study was conducted to determine whether a positive radial margin could affect the prognosis of patients with gastric adenocarcinoma undergoing gastrectomy. Methods: This is a retrospective cohort study of patients with stage II/III gastric adenocarcinoma who received gastrectomy from January 2009 to December 2019 at Taichung Veterans General Hospital, Taiwan. The clinicopathologic features and outcomes were compared between groups. Results: Among the 431 patients who underwent gastrectomy, 94 patients (21.8%) had a positive margin. Radial margin positivity accounted for 16.2%. Factors associated with a positive margin included perineural invasion and advanced cancer stage. The factors related to poor overall survival (OS) and disease-free survival (DFS) included advanced Borrmann type, positive nodal disease, higher nodal burden (≥5), and margin status. In the subgroup analysis, radial margin positivity could negatively impact OS and DFS in the advanced T stage subgroup and nodal-positive subgroup. Conclusions: Aggressive tumor biology may result in a positive margin following gastrectomy. A positive radial margin was correlated with poorer OS and DFS. Future investigations should focus on developing tailored treatment plans for patients with a positive radial margin. Full article

Background/Objectives: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a recently discovered autosomal dominant transmission disease. Patients with this condition have a higher risk of developing gastric cancer. There are numerous questions regarding the natural history of this condition, as well as concerning the diagnostic and therapeutic management of these patients. In this systematic review, we aimed to examine the current literature to determine the role of prophylactic gastrectomy in patients diagnosed with gastric adenocarcinoma and proximal polyposis of the stomach. Additional outcomes are Helicobacter pylori (HP) infection, treatment with proton pump inhibitors (PPI), and colonoscopic examination and abdominal imaging examination, as they are important factors in the therapeutic decision. Methods: We performed a systematic review of the articles published in PubMed and Google Scholar, according to the PRISMA 2020 criteria. Results: We obtained 24 studies that included 83 patients diagnosed with GAPPS, of which 42 underwent prophylactic gastrectomy, 24 benefited from endoscopic follow-up, and 17 were diagnosed with gastric cancer at the first gastroscopic examination. In the prophylactic gastrectomy specimens, malignant gastric disease was confirmed in 10% of cases. GAPPS has been diagnosed more frequently in women. Conclusions: So far, the specialized literature includes a limited number of patients diagnosed with GAPPS. There are also no guidelines yet for the diagnosis and treatment of these patients. Prophylactic gastrectomy or endoscopic surveillance are the only options for patients diagnosed with GAPPS without gastric cancer at the initial examination. For prophylactic gastrectomy, the robotic and laparoscopic approach was preferred. For establishing appropriate lymphadenectomy in prophylactic gastrectomy, future research on gastrectomy specimens is necessary. Most of the included studies were deficient in terms of postoperative follow-up of patients. Thus, we consider it useful to include these patients in a single database. For a comprehensive examination of these and making an appropriate therapeutic decision, we consider it necessary to perform a colonoscopic evaluation, take abdominal imaging, and determine the Helicobacter pylori infection status. Full article

Background/Objectives: During laparoscopic pylorus-preserving gastrectomy (LPPG), the preservation of the infra-pyloric artery (IPA) and dissection of the infra-pyloric lymph node (LN) station 6 are essential, underscoring the importance of understanding the anatomical structure of the IPA. This study aimed to investigate anatomical variations in the IPA and surgical outcomes based on data from a multicenter prospective trial. Methods: A post hoc analysis was conducted based on the Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial, in which patients randomly underwent LPPG or laparoscopic distal gastrectomy (LDG). The IPA variations were categorized into three groups: distal, caudal, and proximal. Clinicopathological characteristics and surgical outcomes were analyzed according to the IPA type. Results: Among the 192 patients, the distribution of IPA types was as follows: 45 (23.44%) distal, 74 (38.54%) caudal, and 73 (38.02%) proximal. There were no significant differences in the clinicopathological characteristics between the IPA types. Of the 119 patients who underwent LPPG, a significant difference in operative time was observed based on the IPA type, with a longer duration observed with the distal type compared to that of the proximal type (distal type vs. proximal type: 202.5 (150–275) vs. 170 (105–265) min, p = 0.0300). No significant differences were observed in other surgical outcomes. Conclusions: The distribution of IPA types was more diverse than that reported in previous studies. There was a statistically significant difference in the operating time based on the IPA type. Identifying IPA variations during LPPG may be beneficial for gastric cancer surgeons. Full article

Background: There is an upward shift in the incidence and localization of gastric cancer (GC). Proximal gastrectomy (PG) has been advocated as an alternative operation for upper-third GC. An uneventful postoperative course is currently measured using a well-defined textbook outcome (TO), which represents a composite of surgical quality metrics. The aim of this study was to compare TO after two reconstruction methods following PG: double-tract reconstruction (DTR) and posterior esophagogastrostomy with partial neo-fundoplication (EGF). Materials and Methods: Primary proximal gastric adenocarcinoma patients who had undergone PG with DTR or EGF were included in this study. In a prospectively collected database, DTR and EGF were identified in 30 and 30 patients, respectively. Results: Patients with DTR had a 5.5-fold higher chance of achieving TO compared to those with EGF (OR = 5.67; p = 0.0266). No statistically significant differences in overall survival were noted when both reconstruction methods were compared. Conclusion: In patients with proximal GC undergoing PG, TO is more likely to be achieved using DTR compared to EGF, with similar overall survival. Randomized controlled trials are warranted to indicate the preferred reconstruction technique after PG. Full article

Objectives: Clinical molecular genetic testing and molecular imaging dramatically increase the quantity of clinical data. Combined with the extensive application of electronic health records, a medical data ecosystem is forming, which calls for big-data-based medicine models. We tried to use big data analytics to search for similar patients in a cancer cohort, showing how to apply artificial intelligence (AI) algorithms to clinical data processing to obtain clinically significant results, with the ultimate goal of improving healthcare management. Methods: In order to overcome the weaknesses of most data processing algorithms that rely on expert labeling and annotation, we uniformly adopted one-hot encoding for all types of clinical data, calculating the Euclidean distance to measure patient similarity and subgrouping via an unsupervised learning model. Overall survival (OS) was investigated to assess the clinical validity and clinical relevance of the model. Results: We took gastric cancers (GCs) as an example to build a high-dimensional clinical patient similarity network (cPSN). When performing the survival analysis, we found that Cluster_2 had the longest survival rates, while Cluster_5 had the worst prognosis among all the subgroups. As patients in the same subgroup share some clinical characteristics, the clinical feature analysis found that Cluster_2 harbored more lower distal GCs than upper proximal GCs, shedding light on the debates. Conclusion: Overall, we constructed a cancer-specific cPSN with excellent interpretability and clinical significance, which would recapitulate patient similarity in the real-world. The constructed cPSN model is scalable, generalizable, and performs well for various data types. Full article

Epstein–Barr virus (EBV) is associated with 5–10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001–2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7–68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC. Full article

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer. Full article

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC. Full article

Significant progress has been made in the surgical management of gastric cancer over the years, and previous discrepancies in surgical practice between different parts of the world have gradually lessened. A transition from the earlier period of progressively more extensive surgery to the current trend of a more tailored and evidence-based approach is clear. Prophylactic resection of adjacent anatomical structures or neighboring organs and extensive lymph node dissections that were once assumed to increase the chances of long-term survival are now performed selectively. Laparoscopic gastrectomy has been widely adopted and its indications have steadily expanded, from early cancers located in the distal part of the stomach, to locally advanced tumors where total gastrectomy is required. In parallel, function-preserving surgery has also evolved and now constitutes a valid option for early gastric cancer. Pylorus-preserving and proximal gastrectomy have improved the postoperative quality of life of patients, and sentinel node navigation surgery is being explored as the next step in the process of further refining the minimally invasive concept. Moreover, innovative techniques such as indocyanine green fluorescence imaging and robot-assisted gastrectomy are being introduced in clinical practice. These technologies hold promise for enhancing surgical precision, ultimately improving the oncological and functional outcomes. Full article

Gastroesophageal (GE) junction adenocarcinoma is an aggressive malignancy of growing incidence and is associated with public health issues such as obesity and GERD. Management has evolved over the last two decades to incorporate a multidisciplinary approach, including endoscopic intervention, neoadjuvant chemotherapy/chemoradiation, and minimally invasive or more limited surgical approaches. Surgical approaches include esophagectomy, total gastrectomy, and, more recently, proximal gastrectomy. This review analyzes the evidence for and applicability of these varied approaches in management, as well as areas of continued controversy and investigation. Full article

Hyperspectral imaging (HSI) is a non-invasive and contactless technique that enables the real-time acquisition of comprehensive information on tissue within the surgical field. In this pilot study, we investigated whether a new HSI system for minimally-invasive surgery, TIVITA^® Mini (HSI-MIS), provides reliable insights into tissue perfusion of the proximal and distal esophagogastric anastomotic sites during 21 laparoscopic/thoracoscopic or robotic Ivor Lewis esophagectomies of patients with cancer to minimize the risk of dreaded anastomotic insufficiency. In this pioneering investigation, physiological tissue parameters were derived from HSI measurements of the proximal site of the anastomosis (esophageal stump) and the distal site of the anastomosis (tip of the gastric conduit) during the thoracic phase of the procedure. Tissue oxygenation (StO₂), Near Infrared Perfusion Index (NIR-PI), and Tissue Water Index (TWI) showed similar median values at both anastomotic sites. Significant differences were observed only for NIR-PI (median: 76.5 vs. 63.9; p = 0.012) at the distal site (gastric conduit) compared to our previous study using an HSI system for open surgery. For all 21 patients, reliable and informative measurements were attainable, confirming the feasibility of HSI-MIS to assess anastomotic viability. Further studies on the added benefit of this new technique aiming to reduce anastomotic insufficiency are warranted. Full article