Recurrent Gastric Cancer Research Articles

Glucose Transporter-1 and Tumor Size Affect Assessment in Gastric Cancer on SPECT

Background: GLUT-1 expression is the crucial parameter affecting gastric cancer 18-FDG absorption is still controversial. This study is to explore the significance of GLUT-1 in gastric cancer 18-FDG SPECT. Material/Methods: The gastric cancer samples of 134 patients with preoperative 18-FDG SPECT were assessed by GLUT-1 immunohistochemi­cal staining. The clinicopathological information of enrolled patients were analyzed with univariate and regression analyses. Results: The SUVmax in positive GLUT-1 expression was significantly higher than that in negative expression (5.136±3.088 vs 4.003±3.604, p=0.004). Tumor diameter (OR 1.415, p=0.005) and GLUT-1 expression level(OR 1.683, p=0.041) were the factors associated with imaging results by visual assessment, independently. Tumor diameter was independent factor associated with SUVmax in positive imaging cases (p=0.029). Tumor diameter(p=0.003) and tumor differentiation(p=0.026) were independent factors related to SUVmax in differentiated carcinoma cases. Conclusions: GLUT-1 expression level is major factor determining 18-FDG uptake of gastric cancer on SPECT. It is necessary to verify the result with PET/CT. Further investigation on analysis GLUT-1 expression in lesions of gastric cancer metastases and recurrences is required.

Prognostic Impact of Visceral Pleural Invasion in Resected Solitary Lung Metastases from Gastric Cancer.

Pulmonary resection of metastases from gastric cancer is extremely rare because gastric cancer metastasis to the lungs or thoracic cavity occurs as multiple pulmonary metastases, carcinomatous lymphangitis, or carcinomatous pleurisy. Therefore, the significance of surgery for pulmonary metastasis of gastric cancer remains unclear. This study aimed to investigate the surgical outcomes and prognostic factors for survival after the resection of pulmonary metastases from gastric cancer. From 2007 to 2019, 13 patients with pulmonary metastasis of gastric cancer underwent metastasectomy. Surgical outcomes were analyzed to determine the prognostic factors for recurrence and overall survival (OS). All the patients underwent pulmonary resection for solitary metastases. At the median follow-up time of 45.6 months (range, 4.8-106.8 months), five patients experienced a recurrence of gastric cancer after metastasectomy. The 5-year recurrence-free survival rate was 44.4%, and the 5-year OS rate after pulmonary resection was 45.3%. Univariate analysis revealed that visceral pleural invasion (VPI) was an unfavorable prognostic factor for both recurrence-free and OS. Pulmonary resection of solitary metastases from gastric cancer may be an effective therapeutic option to improve survival. VPI in gastric cancer metastasis is a negative prognostic factor.

Identification of metabolism-related genes for predicting peritoneal metastasis in patients with gastric cancer

ObjectiveThe reprogramming of metabolism is an important factor in the metastatic process of cancer. In our study, we intended to investigate the predictive value of metabolism-related genes (MRGs) in recurrent gastric cancer (GC) patients with peritoneal metastasis.MethodsThe sequencing data of mRNA of GC patients were obtained from Asian Cancer Research Group (ACRG) and the GEO databases (GSE53276). The differentially expressed MRGs (DE-MRGs) between a cell line without peritoneal metastasis (HSC60) and one with peritoneal metastasis (60As6) were analyzed with the Limma package. According to the LASSO regression, eight MRGs were identified as crucially related to peritoneal seeding recurrence in patients. Then, disease free survival related genes were screened using Cox regression, and a promising prognostic model was constructed based on 8 MRGs. We trained and verified it in two independent cohort.ResultsWe confirmed 713 DE-MRGs and the enriched pathways. Pathway analysis found that the MRG-related pathways were related to tumor metabolism development. With the help of Kaplan–Meier analysis, we found that the group with higher risk scores had worse rates of peritoneal seeding recurrence than the group with lower scores in the cohorts.ConclusionsThis study developed an eight-gene signature correlated with metabolism that could predict peritoneal seeding recurrence for GC patients. This signature could be a promising prognostic model, providing better strategy in treatment.

Histology Classification Highlights Differences in Efficacy of S-1 versus Capecitabine, in Combination with Cisplatin, for HER2-Negative Unresectable Advanced or Recurrent Gastric Cancer with Measurable Disease.

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40-60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.

Prognostic Impact of Hepatic Steatosis Evaluated by CT on Immunotherapy for Gastric Cancer: Associations with Sarcopenia, Systemic Inflammation, and Hormones

Introduction: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). Also, hepatic steatosis has been reported to be associated with cancer cachexia and is expected to be a cancer biomarker. The purpose of this study was to evaluate prognostic impact of hepatic steatosis in ICI therapy for GC. Methods: Unresectable or recurrent GC treated with ICIs was investigated. Using unenhanced CT, the liver-to-spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia and inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease-specific survival (DSS) and progression-free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated. Results: A total of 70 patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenic ones (p = 0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (p = 0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with a higher level of serum IGF-1 (p = 0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both p < 0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both p = 0.01). ROC analysis demonstrated that LSR >1.263 was a good predictive marker for favorable DSS (>5.3 months) with an AUC of 0.80. Conclusion: Hepatic steatosis can be a promising prognostic biomarker for ICI therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Our data suggested that GC with steatohepatitis might be less responsive to ICI therapy.

Benefits of an Immunogenic Personalized Neoantigen Nanovaccine in Patients with High-Risk Gastric/Gastroesophageal Junction Cancer.

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumor immune response. Here, a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy is generated. PNVAC triggers superior protective efficacy against tumor recurrence and promotes longer survival than free neoantigens, especially when combined with anti-PD-1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) is initiated to evaluate the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high-risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy of postsurgical resection. The one- and two-year disease-free survival rates are significantly higher than historical record. PNVAC induces both CD4+ and CD8+ T cell responses as well as antigen-experienced memory T cell phenotype. Furthermore, the immune response is persistent and remains evident one year after the vaccination. This work provides a safe and feasible strategy for developing neoantigen vaccines to delay gastric cancer recurrence after surgery.

120P Clinical implication of DNA damage response gene in advanced gastric cancer stage IV and recurrent gastric cancer patients after gastrectomy treated palliative chemotherapy

This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and clinical outcomes of patients with in gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated palliative 1st line chemotherapy.

The Prognostic Nutritional Index as a Predictor of Gastric Cancer Progression and Recurrence.

Gastric cancer can recur soon after treatment. We evaluated the prognostic nutritional index (PNI), a predictor of postoperative complications, and examined the association of PNI with progression and recurrence of gastric cancer. We retrospectively investigated data from 697 patients who had undergone surgery for gastric carcinoma (excluding those with stage IV disease) and analyzed associations of age, sex, performance status (PS), American Society of Anesthesiologists (ASA) classification, diabetes, depth of main tumor (T), lymph node metastasis, postoperative complications, recurrence, and survival with PNI. We also performed multivariate analysis to identify factors associated with survival. PNI significantly decreased with age and was significantly lower in women. PNI was significantly positively correlated with PS. PNI was significantly lower for ≥T2 cancers and in patients with lymph node metastasis. There was no association between postoperative complications and PNI. PNI was significantly lower for patients who developed recurrence than for those who did not. The survival rate was examined for groups with a PNI of ≥45 (high PNI) and <45 (low PNI). Both 5-year overall survival (OS) and cancer-specific survival (CS) were significantly worse for the low PNI group. Multivariate analysis showed that PNI was an independent predictor of OS and CS. PNI was associated with progression and recurrence of gastric cancer.

Delayed pharyngocutaneous fistula caused by molecular targeted therapy: a case report

BackgroundMolecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy.Case presentationCase 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved.ConclusionsAlthough the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

Clinical Features and Postoperative Recurrence of Remnant Gastric Cancer: Experience of 321 Cases

Clinical Features and Postoperative Recurrence of Remnant Gastric Cancer: Experience of 321 Cases

Low SP1 SUMOylation-dependent SNHG17 upregulation promotes drug resistance of gastric cancer through impairing hsa-miR-23b-3p-induced Notch2 inhibition.

Specificity protein 1 (SP1), a transcription factor mediated by SUMOylation modifiers, is upregulated in gastric cancer (GC) and shares negative correlation with patient prognosis. Here, we paid main attention to the role of SP1 SUMOylation in the drug resistance of GC cells and the possible long non-coding RNA (lncRNA) SNHG17/microRNA-23b-3p (miR-23b-3p)/Notch2 network engaged in this process. Tumor tissues and non-tumor tissues were isolated from GC patients who received treatment with capecitabine and cisplatin (DDP). Co-immunoprecipitation was utilized to detect the SUMOylation level of SP1. Using gain- and loss-of-function approaches, we assessed the impacts of SNHG17/miR-23b-3p/Notch2 on sensitivity of DDP-resistant GC cells in vitro and in vivo. A series of assays such as luciferase activity detection and RNA pull-down were conducted for mechanistic exploration. SP1 expression was increased due to low SP1 SUMOylation level in the recurrent GC tissues. This increase led to upregulated SNHG17 expression and SP1 binding sites existed in the SNHG17 promoter. In addition, SNHG17 could bind to miR-23b-3p while miR-23b-3p targeted Notch2. Loss of SNHG17 reduced the resistance of DDP-resistant GC cells to DDP, which was achieved through miR-23b-3p-dependent Notch2 inhibition. Finally, SP1 silencing attenuated the resistance of GC to DDP in mice. Low SP1 SUMOylation induces SNHG17 upregulation and blocks miR-23b-3p-induced Notch2 inhibition, contributing to the resistance of GC to DDP. This study may aid in the development of therapeutic targets overcoming the chemoresistance of GC.

Predicting the Recurrence of Gastric Cancer Using the Textural Features of Perigastric Adipose Tissue on [18F]FDG PET/CT.

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.

S3700 Role of Immunotherapy in the Treatment of Recurrent Hereditary Diffuse Gastric Cancer

Introduction: Gastric cancer is the third leading cause of cancer related deaths worldwide. Majority of cases are sporadic although 10% demonstrate familial clustering, of which 1-3% arise from inherited cancer syndromes. Hereditary diffuse gastric cancer is a rare cancer caused by CDH1 genetic mutation, inherited in an autosomal dominant fashion. Immunotherapy has been shown to increase overall response rates in gastrointestinal cancers especially in those subgroups with DNA mismatch repair-deficient or microsatellite-instable tumors. We herein, present a case of recurrent hereditary diffuse gastric cancer with good response to chemoimmunotherapy. Case Description/Methods: This is a 41-year-old asian female with past medical history of stage IIB signet ring type gastric cancer diagnosed 12 years ago, status post subtotal gastrectomy with a block transverse colectomy followed by concurrent chemoradiation, who presented with disease recurrence after 10 years, when she was treated with neoadjuvant 5-fluorouracil based chemotherapy followed by surgical resection and adjuvant chemotherapy. Her genetic screening showed CDH1 mutation, with high risk for breast and gastric cancers. She was monitored closely with regular breast magnetic resonance imaging (MRI) and esophagogastroduodenoscopy (EGD). During one of her regular endoscopy assessments recently, she was found to have erythema of her gastric mucosa which upon biopsy confirmed recurrence of her poorly differentiated adenocarcinoma, diffuse type with signet ring features. She underwent treatment with oxaliplatin based chemotherapy combined with Nivolumab for six cycles. She responded well to chemoimmunotherapy as evidenced by positron emission tomography and computed tomography (PET CT) scan and esophagogastroduodenoscopy (EGD). She is awaiting surgical resection followed by adjuvant therapy with chemotherapy either alone or in combination with immunotherapy. Discussion: Gastrectomy and chemotherapy are the mainstay treatments for hereditary diffuse gastric cancer. Nivolumab has been shown to be effective in heavily pretreated gastric cancers. The combination therapy of nivolumab plus chemotherapy achieved a clinically meaningful overall survival benefit in the first line setting in all advanced gastric adenocarcinoma. Clinical trials and research encompassing antibody treatments, such as targeted anti-PD1 antibodies, are ongoing and could offer additional treatment options in patients with advanced gastric cancer.

Role of Nivolumab in the Management of First-Line Unresectable Advanced or Recurrent Gastric Cancer in Combination with Chemotherapy: Lessons from the Japanese Experience.

Recently, immune checkpoint inhibitor (ICI), such as anti-programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) monoclonal antibodies, has provided clinical benefits in various cancer types including advanced gastric cancer (AGC). Nivolumab, a monoclonal anti-PD-1 antibody, firstly showed an improvement in the overall survival (OS) in patients with AGC in the ATTRACTION-2 trial. Recently, chemotherapy plus nivolumab, as a first-line treatment for AGC, showed both OS and progression-free survival (PFS) benefits in patients with PD-L1 combined positive score (CPS) ≥5 in the global CheckMate-649 trial, and demonstrated PFS benefit irrespective of CPS status in the Asian ATTRACTION-4 trial. Based on these results, chemotherapy plus nivolumab in a first-line treatment was approved worldwide. However, the approval requirements and recommendations are different according to the approval agent or country. Thus, this review summarized the clinical trials of chemotherapy plus anti-PD1 antibody as a first-line treatment and focused on the role of nivolumab combined with chemotherapy mainly from the viewpoint of the Japanese experience.

Long-term outcome of the endoscopic submucosal dissection of early gastric cancer: A comparison between patients with and without liver cirrhosis.

Gastric cancer (GC) and liver cirrhosis (LC) have high incidence rates, particularly in Eastern Asia; however, the long-term clinical outcomes or recurrence of GC following endoscopic submucosal dissection (ESD) in patients with comorbid LC remain unclear. The present study aimed to compare the long-term efficacy and safety of ESD in patients with GC, with and without LC. Patients with early GC (EGC) who had underlying LC and underwent endoscopic treatment (LC-EGC group) were enrolled in the present study. In addition, patients with EGC without LC (non-LC-EGC group) were matched at a ratio of 1:3 via propensity score matching. The clinical outcomes and histopathological data of both groups were analyzed. No significant differences were observed in procedure type, complications [intraprocedural bleeding (11.8%) and perforation (0.0%)], en bloc resection rate (94.1%) and complete resection rate (100%) between the two groups. Multivariate Cox regression analysis demonstrated that procedure time was significantly associated with procedure-associated bleeding [adjusted hazard ratio (HR), 1.017; 95% confidence interval (CI), 1.001-1.032; P=0.033]. Furthermore, LC was significantly associated with cancer recurrence (adjusted HR, 5.482; 95% CI, 1.102-27.279; P=0.038). Taken together, the results of the present study suggest that endoscopic resection of EGC in patients with LC is an effective and safe treatment method. However, further studies are required to assess recurrence.

Association of serum Interleukin-8 level with lymph node metastasis and tumor recurrence in gastric cancer.

The level of pretherapeutic serum interleukin-8 (sIL-8) has been demonstrated to correlate with chemoresistance in gastric cancer. However, its clinicopathological significance of sIL-8 in gastric cancer remains unknown. Herein, a total of 335 patients diagnosed with gastric adenocarcinoma were enrolled. The clinicopathological features were collected, and the sIL-8 levels were measured using enzyme-linked immunosorbent assay. The sIL-8 levels ranged from 1.48 pg/ml to 1025.22 pg/ml with > 15.41 pg/ml defined as high according to the receiver operating characteristic analysis. sIL-8 levels were strongly associated with Lauren classification and tumor recurrence. High sIL-8 correlated with lymph node metastasis (LNM) in the intestinal- and diffuse-type tumors and acted as an independent risk factor for LNM in both types. Patients with high sIL-8 levels had worse relapse-free survival than those with low sIL-8 levels. High sIL-8 level was associated with tumor relapse in the intestinal- and diffuse-type tumors, and was also an independent risk factor in the intestinal- and mixed-type tumors. Further analysis revealed that sIL-8 levels were positively associated with LNM and tumor relapse in patients with negative carcinoembryonic antigen (CEA), but not in those with elevated serum CEA levels. In conclusion, this retrospective study demonstrated that the pretherapeutic sIL-8 level has predictive value for LNM and tumor recurrence, and may serve as a potential tumor marker in gastric cancer.

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer

Introduction: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. Methods: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. Results: The overall survival (OS) was 16.8 months (95% CI: 14.0–19.6) and 9.3 months (95% CI: 7.8–11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15–3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23–3.22), low albumin concentration (OR 2.24; 95% CI: 1.14–4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05–3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6–27.9), respectively. Conclusions: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

Effects of plant-based medicinal food on postoperative recurrence and lung metastasis of gastric cancer regulated by Wnt/β-catenin-EMT signaling pathway and VEGF-C/D-VEGFR-3 cascade in a mouse model

BackgroundThe plant-based medicinal food (PBMF) is a functional compound extracted from 6 medicinal and edible plants: Coix seed, L. edodes, A. officinalis L., H. cordata, Dandelion, and G. frondosa. Our previous studies have confirmed that the PBMF possesses anti-tumor properties in a subcutaneous xenograft model of nude mice. This study aims to further investigate the effects and potential molecular mechanisms of the PBMF on the recurrence and metastasis of gastric cancer (GC).MethodsPostoperative recurrence and metastasis model of GC was successfully established in inbred 615 mice inoculated with mouse forestomach carcinoma (MFC) cells. After tumorectomy, 63 GC mice were randomly divided into five groups and respectively subject to different treatments for 15 days as below: model control group, 5-Fu group, and three doses of PBMF (43.22, 86.44, 172.88 g/kg PBMF in diet respectively). The inhibition rate (IR) of recurrence tumor weights and organ coefficients were calculated. Meanwhile, histopathological changes were examined and the metastasis IR in lungs and lymph node tissues was computed. The mRNA expressions related to the canonical Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition (EMT) and lymphangiogenesis were detected by RT-qPCR in recurrence tumors and/or lung tissues. Protein expressions of β-catenin, p-β-catenin (Ser33/37/Thr41), GSK-3β, p-GSK-3β (Ser9), E-cadherin, and Vimentin in recurrence tumors were determined by Western Blot. LYVE-1, VEGF-C/D, and VEGFR-3 levels in recurrence tumors and/or lung tissues were determined by immunohistochemistry staining.ResultsThe mRNA, as well as protein expression of GSK-3β were up-regulated and the mRNA expression of β-catenin was down-regulated after PBMF treatment. Meanwhile, the ratio of p-β-catenin (Ser33/37/Thr41) to β-catenin protein was increased significantly and the p-GSK-3β (Ser9) protein level was decreased. And PMBF could effectively decrease the mRNA and protein levels of Vimentin while increasing those of E-cadherin. Furthermore, PBMF markedly reduced lymphatic vessel density (LVD) (labeled by LYVE-1) in recurrence tumor tissues, and mRNA levels of VEGF-C/D, VEGFR-2/3 of recurrence tumors were all significantly lower in the high-dose group.ConclusionsPBMF had a significant inhibitory effect on recurrence and lung metastasis of GC. The potential mechanism may involve reversing EMT by inhabiting the Wnt/β-catenin signaling pathway. Lymphatic metastasis was also inhibited by PBMF via down-regulating the activation of the VEGF-C/D-VEGFR-2/3 signaling cascade.

Clinical Impact of Surgical Sarcopenia on Long-term Survival.

Preoperative sarcopenia is associated with various cancers and affects the long-term prognosis of patients. After gastrectomy for gastric cancer, dynamic changes in body composition occur, and sarcopenia becomes more apparent after surgery than before surgery. However, the relationship between sarcopenia in the early postoperative period and long-term survival is not fully understood. The aim of this study was to determine the effects of surgical sarcopenia on long-term outcomes of patents with gastric cancer. We included 408 patients who underwent curative gastrectomy (distal or total gastrectomy) for gastric cancer at the Kanagawa Cancer Center from December 2013 to November 2017. Sarcopenia was defined using the skeletal muscle index (SMI), using computed tomography (CT) one month after gastrectomy. We compared the long-term outcomes between patients with and without sarcopenia. The 5-year overall survival (OS) rates were 83.2% and 91.4% in the surgical and non-surgical sarcopenia groups, respectively. The hazard ratio (HR) of surgical sarcopenia for OS was 2.410 (95% confidence interval (CI)=1.321-4.396). In addition, surgical sarcopenia was associated with non-cancer-related deaths and deaths from other cancers. Patients with surgical sarcopenia after gastrectomy should be carefully monitored not only for gastric cancer recurrence but also for the occurrence of other diseases, including other cancers.

ПРЕДИКТИВНА НОМОГРАМА РИЗИКУ ІНТРАПЕРИТОНЕАЛЬНОГО РЕЦИДИВУ ПІСЛЯ РАДИКАЛЬНОЇ ХІРУРГІЇ РАКУ ШЛУНКА

Background and objectives. Peritoneal relapse (PR) is the most common pattern of gastric cancer (GC) recurrence after radical treatment. Currently, a variety of adjuvant intraperitoneal chemotherapy methods are being tested for their efficacy in reducing the level of PR. Methods. The radical treatment results of 226 patients with localized and locally-advanced GC have been analyzed. In order to select a group of patients with indications for adjuvant intraperitoneal therapy, a study of independent predictive factors and the development of a predictive PR nomogram for gastric cancer was completed. Results. As a result of the analysis of about three dozen potential factors in mono- and multivariate analysis, the impact on PR risk was confirmed by 4 independent predictive factors, namely: serosal invasion and its size (HR 9.36, p &lt;0.001), morphological type according to Lauren (HR 5.3, p &lt;0.001), index of regional lymph node involvement (HR 2.23, p = 0.015) and localization of the tumor in the stomach (HR 3.98, p &lt;0,001). Conclusions. A predictive PR risk nomogram of gastric cancer after radical surgical treatment has been developed based on the identified independent factors, and it is of great clinical importance as a tool for segregating patients who require adjuvant intraperitoneal chemotherapy.