Recurrent Gastric Cancer Research Articles

A scoring model for predicting early recurrence of gastric cancer with normal preoperative tumor markers: A multicenter study

IntroductionPrognostic factors for postoperative early recurrence (ER) of gastric cancer (GC) in patients with normal or abnormal preoperative tumor markers (pre-TMs) remain unclear. Materials and methods2875 consecutive patients with GC who underwent radical gastrectomy (RG) between January 2010 and December 2016 were enrolled and randomly divided into training and internal validation groups. ER was defined as recurrence within two years of gastrectomy. Normal pre-TMs were defined as CEA≤5 ng/mL and CA199 ≤ 37 U/mL. Least absolute shrinkage selection operator (LASSO) Cox regression analysis was used to screen ER predictors. The scoring model was validated using 546 patients from another hospital. ResultsA total of 3421 patients were included. Multivariate Cox analysis showed that pre-TMs was an independent prognostic factor for ER. Survival after ER was equally poor in the normal and abnormal pre-TMs groups (P = 0.160). Based on LASSO Cox regression, the ER of patients with abnormal pre-TMs was only associated with the pT and pN stages; however, in patients with normal pre-TMs, it was also associated with tumor size, perineural invasion, and prognostic nutritional index. Scoring model constructed for patients with normal pre-TMs had better predictive performance than TNM staging (concordance-index:0.826 vs. 0.807, P < 0.001) and good reproducibility in both validation sets. Moreover, through risk stratification, the scoring model could not only identify the risk of ER but also distinguish ER patterns and adjuvant chemotherapy benefit subgroups. Conclusionpre-TMs is an independent prognostic factor for ER in GC after RG. The established scoring model demonstrates excellent predictive performance and clinical utility.

Notum enhances gastric cancer stem-like cell properties through upregulation of Sox2 by PI3K/AKT signaling pathway

PurposeConsiderable evidence suggests that tumor cells with stemness features contribute to initiation, progression, recurrence of gastric cancer (GC) and resistance to therapy, but involvement of underlying regulators and mechanisms remain largely unclear. However, the clinical significance and biological function of Notum in GC tumor sphere formation and tumorigenesis remain unclear.MethodsBioinformatics analysis, RT-qPCR, western blot and imunohistochemistry staining were applied to characterize Notum expression in GC specimens. The early diagnostic value of Notum was analyzed by logistic regression analysis method. Cancer stemness assays were used in Notum knockdown and overexpressing cells in vitro and in vivo. RNA-seq was employed to reveal the downstream effectors of Notum.ResultsNotum is highly expressed in early stage of GC patients and stem-like GC cells. For discriminating the early-stage and advanced GC patients, the joint analysis had a better diagnostic value. Overexpression of Notum markedly increased stemness features of GC cells to promote tumor sphere formation and tumorigenesis. Conversely, Notum knockdown attenuated the stem-like cell properties in vitro and in vivo. Mechanically, Notum upregulates Sox2 through activating the PI3K/AKT signaling pathway. Notum inhibitor Caffeine exhibited a potent inhibitory effect on stemness features by impairing the PI3K/AKT signaling pathway activity and targeting Sox2.ConclusionOur findings confer a comprehensive and mechanistic function of Notum in GC tumor sphere formation and tumorigenesis that may provide a novel and promising target for early diagnosis and clinical therapy of GC.

Efficacy of multi-slice spiral computed tomography in evaluating gastric cancer recurrence after endoscopic submucosal dissection.

Recurrence is the major challenge facing endoscopic submucosal dissection (ESD)-based treatment therapies for early gastric cancer (EGC). Urgent development of simple and easy surveillance approaches will enhance clinical treatment of the disease. To explore the role of computed tomography (CT) recurrence in evaluating EGC after ESD treatment. We retrospectively recruited patients from our endoscopy department, between January 2002 and December 2015, and analyzed their basic characteristics, including symptoms, CT results, and results of endoscopy with biopsy, among others. Among a total of 2150 patients EGC patients surveyed, 1362 met our inclusion and exclusion criteria and were therefore enrolled in our study. The cohort's sensitivity of CT for recurrent GC and specificity were 44.22% and 43.86%, respectively, with negative and positive predictive values of 40.15% (275/685) and 48.01% (325/677), respectively. The area under the curve of arterial and venous CT values for recurrent EGC were 0.545, and 0.604, respectively. Receiver operating characteristic curve revealed no statistically significant differences between arterial and venous CT values for recurrent EGC. Enhanced CT has superior diagnostic efficacy, but less accuracy, compared to gold standard techniques in patients with recurrent EGC.

A practical recurrence risk model based on Lasso-Cox regression for gastric cancer.

Gastric cancer remains huge cancer threat worldwide. Detecting the recurrence of gastric cancer after treatment is especially important in improving the prognosis of patients. We aim to fit different risk models with different clinical variables for patients with gastric cancer, which further provides applicable guidance to clinical doctors for their patients. We collected the primary data from the medical record system in Lanzhou University Second Hospital and further cleaned the primary data via assessing data integrity artificially; meanwhile, detailed conclusion criteria and exclusion criteria were made. We used R software (version 4.1.3) and SPSS 25.0 to analyze data and build models, in which SPSS was used to analyze the correlation and difference of different items in the training set and testing set, and different R packages were used to run LASSO regression, Cox regression and nomogram for variable selection, model construction and model validation. A total of 649 patients were included in our data analysis and model building. In LASSO regression selection, seven variables, pathological stage, tumor size, the number of total lymph nodes, the number of metastatic lymph nodes, intraoperative blood loss (IBL), the level of AFP and CA199, showed their correlation to the dependent variable. The multivariable Cox regression model fitted using these seven variables showed medium prediction ability, with an AUC of 0.840 in the training set and 0.756 in the testing set. Pathological stage, tumor size, the number of total lymph nodes, the number of metastatic lymph nodes, IBL, the level of AFP and CA199 are significant in identifying recurrence risk for gastric cancer patients after radical gastrectomy.

Knowledge, attitude, and practice of monitoring early gastric cancer after endoscopic submucosal dissection.

Early gastric cancer (EGC) is typically treated with endoscopic submucosal dissection (ESD). However, recurrence may occur after ESD, requiring surveillance. To examine the knowledge, attitude, and practice (KAP) of EGC survivors following ESD regarding gastric cancer recurrence. This cross-sectional study was conducted between June 1, 2022 and October 1, 2022 in Zhejiang, China. A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital, Zhejiang University School of Medicine participated in this study. A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD. The average scores for KAP were 3.34, 23.76, and 5.75 out of 5, 30, and 11, respectively. Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude, knowledge and practice, and attitude and practice (r = 0.405, 0.511, and 0.458, respectively; all P < 0.001). Multivariate logistic regression analysis showed that knowledge, attitude, 13-24 mo since the last ESD (vs ≤ 12 mo since the last ESD), and ≥ 25 mo since the last ESD (vs ≤ 12 mo since the last ESD) were independent predictors of proactive practice (odds ratio = 1.916, 1.253, 3.296, and 5.768, respectively, all P < 0.0001). EGC survivors showed inadequate knowledge, positive attitude, and poor practices in monitoring recurrences after ESD. Adequate knowledge, positive attitude, and a longer time since the last ESD were associated with practice.

Chinese expert consensus on the diagnosis and treatment of peritoneal metastasis of gastric cancer (2023 edition)

China is a country with a high incidence of gastric cancer, and the majority of patients are in the advanced stage. The peritoneum is the most common site of metastasis and recurrence in advanced gastric cancer. Attention to the standardized diagnosis and treatment of peritoneal metastases of gastric cancer is expected to significantly improve the prognosis and quality of life of some patients. Based on evidence-based medicine and the internationally accepted Delphi method, this consensus revises the Chinese expert consensus on the prevention and treatment of peritoneal metastasis of gastric cancer (2017 edition), reaches a preliminary consensus on the definition, classification, risk factors, diagnosis and prediction, grade assessment, prevention, treatment and management of complications of peritoneal metastasis of gastric cancer, and provides guidance for clinical work.

Perioperative radiotherapy on local-advanced gastric cancer--From the perspective of failure pattern

Distant metastasis, peritoneal recurrence and locoregional recurrence are the three major patterns of gastric cancer (GC) recurrence after surgery and the causes of patients'death. Among them, distant organ metastasis or peritoneal recurrence after surgery is more common and occurs earlier, while locoregional failure alone occurs later with a relatively lower incidence. Several studies have confirmed that preoperative radiotherapy can shrink tumors and increase R0 resection rates, and postoperative radiotherapy helps reduce local recurrence. However, whether perioperative radiotherapy can further improve patient survival is still controversial.. We believe that this is partly due to the characteristics of recurrence and metastasis. As a local treatment, radiotherapy is complement to the inadequacy of surgery. Thus, we believe that perioperative radiotherapy is not recommended for patients with standard R0 surgery and adequate lymph node dissection, but rather requires accurate prediction of their recurrence and metastasis patterns based on accurate clinical and pathological staging, and thus screening of those who may benefit from radiotherapy.

Diagnostic performance of F-18 FDG PET or PET/CT for detection of recurrent gastric cancer: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for the detection of disease recurrence after curative resection of gastric cancer. The PubMed and Embase databases, from the earliest available date of indexing through November 30, 2019, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT to detect recurrent disease after gastric cancer surgery. Across 17 studies (1,732 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.82 (95% confidence interval [CI], 0.74-0.88) with heterogeneity of I2=76.5 (p<0.001), and the specificity was 0.86 (95% CI, 0.78-0.91) with heterogeneity of I2=94.2 (p<0.001). Likelihood ratio (LR) tests gave an overall positive LR of 6.0 (95% CI, 3.6-9.7) and negative LR of 0.2 (95% CI, 0.14-0.31). The pooled diagnostic odds ratio was 29 (95% CI, 13-63). The summary receiver operating characteristic curve indicates that the area under the curve was 0.91 (95% CI, 0.88-0.93). The current meta-analysis showed good sensitivity and specificity of F-18 FDG PET or PET/CT for detecting recurrent disease after curative resection of gastric cancer despite heterogeneity in ethnicity, recurrence rate, histology, and interpretation method.

Phase I/II clinical trial of nivolumab in combination with oligo-fractionated irradiation for unresectable advanced or recurrent gastric cancer

BackgroundAlthough immune checkpoint inhibitors (ICI) targeting for PD-1 axis is a promising approach for advanced gastric cancer (GC) patients, the response rate is still limited. Induction of synergistic effect of irradiation with ICI targeting for the PD-1 axis can be an attractive strategy. The aim of this study was to assess the effect of the combination of irradiation with anti-PD-1 therapy for advanced GC.MethodsWe conducted a single-arm, phase I/II trial in GC patients treated with a combination of nivolumab and oligo-fractionated irradiation (22.5 Gy/5 fractions/5 days) (NCT03453164). Eligible patients (n = 40) had unresectable advanced or recurrent GC which progressed after primary and secondary chemotherapy with more than one lesion. The primary endpoint is the disease control rate (DCR) of non-irradiated target lesions and the secondary endpoints are the median survival time (MST), safety, and DCR of irradiated lesions.ResultsWe observe that the DCR for the non-irradiated target as the abscopal effect is 22.5% (90% confidence interval (CI), 12.3–36.0), and the DCR for the irradiated lesion is 40.0% (90% CI, 26.9–54.2). The median survival time is 230 days (95% CI, 157–330), and grade 3 and higher adverse events (AEs) are observed in 16 patients (39 %) with no obvious additional AEs when adding irradiation.ConclusionsThe present study suggests that the combination of nivolumab with oligo-fractionated irradiation has the potential to induce a promising anti-tumor effect for advanced GC.

Formulation and characterization of cisplatin-loaded hydroxyl functionalized single-walled carbon nanotubes for targeting gastric cancer stem cells

Chemotherapy is the most commonly used therapeutic method for treating many malignancies including gastric cancer. Due to their non-specific and non-targeted drug delivery, it causes resistance leading to cancer progression, relapse, and metastasis of cancer. To overcome this problem we carried out a study aimed to develop a new cisplatin (Cisp) loaded hydroxyl functionalized single-walled carbon nanotube (OH-SWCNT) nanocarrier system to selectively eliminate gastric cancer stem cells. To our understanding, this is the first study of the non-covalent interaction of cisplatin loaded on the surface of hydroxyl-functionalized single-walled carbon nanotubes by ultrasonication. The physical and morphological characterization was carried out by UV–Vis, FTIR spectroscopy, and TEM. A sustained and controlled release of cisp from OH-SWCNT at all three pHs 3.5, 5.5, and 7.4 was observed. Gastric cancer stem cells were isolated from primary cells and were identified by using CD133+ and CD44+ specific markers. Cisplatin-loaded OH-SWCNT nanocarrier was capable of limiting the self-renewal capacity of both CD133+ and CD44+ populations and also decreasing the number of tumorspheres in gastric CSCs. The cell viability percent of AGS cells was 20% at 250 μg/ml concentration. The IC50 value was less than 50% mol/L at both 200 μg/ml and 250 μg/ml of cisplatin-loaded OH-SWCNT. Our findings suggest that cisplatin-loaded OH-SWCNT nanocarrier complexes could target gastric CSCs and also could provide a potential strategy for selectively targeting and efficiently eliminating gastric CSCs. This could be a promising approach to prevent gastric cancer recurrence and metastasis and also improve gastric cancer therapy.

Association of perioperative allogeneic blood transfusions and long-term outcomes following radical surgery for gastric and colorectal cancers: systematic review and meta-analysis of propensity-adjusted observational studies.

Previous meta-analyses reporting significant associations between perioperative allogeneic blood transfusions and poor prognosis in gastric cancer or colorectal cancer had a high risk of confounding bias. This meta-analysis explored this issue using observational studies that applied propensity score analysis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for manuscripts published between 2013 and 2022. Studies applying propensity score analysis were included to investigate the association between perioperative allogeneic blood transfusions and prognosis in gastric cancer or colorectal cancer after radical surgery. Pooled HRs for overall survival and disease-free survival were calculated using a fixed-effect model or random-effect model according to heterogeneity. Twelve retrospective cohort studies with 17 607 patients reported were included. Ten studies applied propensity score matching and two applied inverse probability of treatment weighting using propensity score. A total of 5962 patients were analysed after propensity score adjustment. After propensity score adjustment, perioperative allogeneic blood transfusions did not correlate with disease-free survival in gastric cancer (HR 1.16; 95 per cent c.i. 0.96-1.39; heterogeneity was assessed by the chi-squared test and inconsistency index (I2) = 57 per cent) or colorectal cancer (HR 1.12; 95 per cent c.i. 0.84-1.49; I2 = 54 per cent). However, after propensity score adjustment, perioperative allogeneic blood transfusions were significantly associated with worse overall survival in gastric cancer (HR 1.20; 95 per cent c.i. 1.08-1.32; I2 = 25 per cent) and colorectal cancer (HR 1.40; 95 per cent c.i. 1.06-1.85; I2 = 52 per cent). Subgroup analyses showed that perioperative allogeneic blood transfusions did not correlate with overall survival in colorectal cancer when major postoperative complications were balanced after propensity score. Perioperative allogeneic blood transfusion is not correlated with recurrence of gastric cancer and colorectal cancer. Perioperative allogeneic blood transfusions are significantly associated with worse overall survival in gastric cancer and colorectal cancer, which may be attributable to unbalanced major postoperative complications after propensity score adjustment.

Resection of Late Recurrence of Gastric Cancer with Duodenal and Bile Duct Strictures 22 Years after Surgery for Gastric Cancer

Resection of Late Recurrence of Gastric Cancer with Duodenal and Bile Duct Strictures 22 Years after Surgery for Gastric Cancer

Comparison of survival outcomes between de novo and recurrent stage IV gastric cancers: A retrospective cohort study

Purpose: This study analyzes the characteristics and prognosis of patients with &lt;i&gt;de novo&lt;/i&gt; and recurrent metastatic gastric cancers.Methods: This retrospective study included 301 advanced, pathologically confirmed gastric cancer patients who received palliative chemotherapy between 2012 and 2022. The &lt;i&gt;de novo&lt;/i&gt; cohort included patients who presented with distant metastasis at diagnosis, and the recurrent metastatic cohort was composed of patients with metastasis after curative gastrectomy. We analyzed prognostic association by Cox regression and compared survival time of both cohorts using the Kaplan-Meier survival analysis.Results: The study included 167 &lt;i&gt;de novo&lt;/i&gt; and 112 recurrent patients. No differences were noted among the patients with &lt;i&gt;de novo&lt;/i&gt; disease and recurrent metastatic disease concerning age, sex, Eastern Cooperative Oncology Group scores, primary cancer location, and pathologic features. Patients in the recurrent group versus the &lt;i&gt;de novo&lt;/i&gt; group had a longer duration of chemotherapy (1.16±1.18 years vs. 0.85±0.84 years, P= 0.01) and lower mean body mass index (20.22±2.78 kg/m&lt;sup&gt;2&lt;/sup&gt; vs. 21.93±3.38 kg/m&lt;sup&gt;2&lt;/sup&gt;, P&lt; 0.001). The median overall survival in the &lt;i&gt;de novo&lt;/i&gt; group was 11.6 versus 14.4 months in the recurrent group (P= 0.02).Conclusion: &lt;i&gt;De novo&lt;/i&gt; and recurrent metastatic gastric cancer are characterized by distinct subpopulations. Advanced gastric cancer patients with recurrence have significantly better survival versus those in the de novo cohort. The differences between de novo and recurrent gastric cancer patient outcomes could facilitate discussions about the selection of the clinical trial of each patient and help with their personalized treatment.

Reminiscence therapy-based care program alleviates anxiety and depression, as well as improves the quality of life in recurrent gastric cancer patients.

Reminiscence therapy is a non-drug method that eases psychological burden and enhances quality of life by memories and communications in cancer patients. This study aimed to evaluate influence of reminiscence therapy-based care program on anxiety, depression, and quality of life in recurrent gastric cancer patients. Totally, 96 recurrent gastric cancer patients were randomly assigned as 1:1 ratio into reminiscence therapy-based care group (N = 48) and usual care group (N = 48) to receive 12-week corresponding interventions. Besides, all patients were follow-up for 6 months. Hospital Anxiety and Depression Scales-anxiety score at 4th month (p = 0.031) and 6th month (p = 0.004), Hospital Anxiety and Depression Scales-depression score at 6th month (p = 0.018), and anxiety severity at 4th month (p = 0.041) and 6th month (p = 0.037) were lower in reminiscence therapy-based care group than in usual care group. Quality of Life Questionnaire-Core 30 global health status score at 2nd month (p = 0.048), 4th month (p = 0.036), and 6th month (p = 0.014), Quality of Life Questionnaire-Core 30 function score at 4th month (p = 0.014) and 6th month (p = 0.021) were higher, while Quality of Life Questionnaire-Core 30 symptoms score at 2nd month (p = 0.041) and 4th month (p = 0.035) were lower in reminiscence therapy-based care group than in usual care group. Furthermore, reminiscence therapy-based care was more effective on improving mental health and quality of life in recurrent gastric cancer patients with anxiety or depression at baseline than those without. Reminiscence therapy-based care serves as an effective intervention, which relieves anxiety and depression, and improves quality of life in recurrent gastric cancer patients.

Yiwei decoction promotes apoptosis of gastric cancer cells through spleen-derived exosomes.

Yiwei decoction (YWD) is a formula of traditional Chinese medicine (TCM) that is clinically effective for the prevention and treatment of gastric cancer recurrence and metastasis. According to the theory of TCM, YWD tonifies the body and strengthens the body's resistance to gastric cancer recurrence and metastasis potentially via the immune regulation of the spleen. The aims of the present study were to investigate whether YWD-treated spleen-derived exosomes in rats inhibit the proliferation of tumor cells, to elucidate the anticancer effects of YWD, and to provide evidence supporting the use of YWD as a new clinical treatment for gastric cancer. Spleen-derived exosomes were obtained by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. The location of the exosomes in tumor cells was then determined by immunofluorescence staining. After tumor cells were treated with different concentrations of exosomes, the effect of exosomes on cell proliferation was determined by cell counting kit 8 (CCK8) and colony formation assays. Tumor cell apoptosis was detected by flow cytometry. Particle analysis and western blot analysis identified the material extracted from spleen tissue supernatant as exosomes. Immunofluorescence staining showed that spleen-derived exosomes were taken up by HGC-27 cells, and the CCK8 assay confirmed that the relative tumor inhibition rate of YWD-treated spleen-derived exosomes in the 30μg/mL reached 70.78% compared to control exosomes in the 30μg/mL (p < 0.05). Compared to control exosomes in the 30μg/mL, the colony formation assay indicated that YWD-treated spleen-derived exosomes in the 30μg/mL colonies have decreased by 99.03% (p < 0.01). Moreover, flow cytometry analysis showed that treatment with YWD-treated exosomes in the 30μg/mL increased the apoptosis rate to 43.27%, which was significantly higher than that of the control group in the 30μg/mL (25.91%) (p < 0.05). In conclusion, spleen-derived exosomes from YWD-treated animals inhibit the proliferation of HGC-27 cells via inducing apoptosis, suggesting that spleen-derived exosomes are involved in mediating the antitumor effect of YWD. These results demonstrated a novel exosome-mediated anticancer effect of YWD as a TCM formula, thereby supporting the use of YWD-treated exosomes as a new approach for the clinical treatment of gastric cancer.

Comparison of efficacy between immune checkpoint inhibitors and irinotecan-based chemotherapy as third-line treatment for patients with advanced gastric cancer: A Korean real-world multicenter study (KCSG ST22-06).

e16047 Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy are frequently used after paclitaxel plus ramucirumab as second-line treatment for patients with recurrent and/or metastatic gastric cancer (RMGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with RMGC. Methods: We retrospectively reviewed patients with RMGC, whose third-line treatment started between July 2019 and June 2021 at 17 centers in South Korea. The ICI group included patients who received nivolumab or pembrolizumab and the irinotecan-based chemotherapy group included those patients who received irinotecan or FOLFIRI. Results: A total of 363 patients (129 in the ICI group and 234 in the irinotecan-based chemotherapy group) were analyzed. The median progression-free survival (PFS) was 2.2 and 2.9 months in the ICI and irinotecan-based chemotherapy groups, respectively. The median overall survival (OS) was 5.5 months (95% CI, 3.6-7.4) in the ICI group and 6.0 months (95% CI, 4.8-7.0) in the irinotecan-based chemotherapy group [HR 0.97 (95% CI, 0.75-1.25); P=0.786]. Multivariable Cox-regression analysis showed that weight loss, peritoneal metastasis, low serum sodium, low serum albumin and short duration of second-line treatment were associated with inferior OS ( P&lt;0.05), meanwhile microsatellite instability-high (MSI-H)/mismatch repair-deficient (MMR-D) tumor was an independent prognostic factor for superior OS. The ICI group showed significantly longer OS than the irinotecan-based chemotherapy group in patients without peritoneal metastasis [HR 0.54 (95% CI 0.30-0.99); P=0.047)]. Whereas the irinotecan-based chemotherapy group showed significantly longer OS in patients without PD-L1 expression [HR 1.62 (95% CI 1.03-2.55); P=0.037] than the ICI group. Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for patients with RMGC. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.

Risk stratification for predicting postoperative recurrence of gastric cancer by grade of venous invasion

BackgroundVenous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading.Methods157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1−3; v2, 4−6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed.ResultsRecurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers.ConclusionsVI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan.

Late recurrent gastric carcinoma 12 years after surgery with attenuation of CD44 variant 9 expression

BackgroundLate recurrence of gastric cancer at 10 years post-gastrectomy is extremely rare, and the underlying mechanism remains unclear. We report a para-aortic lymph node metastasis case that recurred 12 years postoperatively.Case presentationA 44-year-old woman pathologically diagnosed with moderately to poorly differentiated adenocarcinoma with pT2(SS)pN2cM0pStageIIIA according to the Japanese Classification of Gastric Carcinoma (the 13th Edition) underwent laparoscopic distal gastrectomy with D1 + lymph node dissection. She received adjuvant chemotherapy with tegafur-uracil (400 mg/day) for 2 years. At postoperative year (POY) 5, a swollen lymph node was detected in the No.16b1lat lymph node station. However, positron emission tomography (PET) revealed normal uptake, and the levels of tumor markers were within normal limits; hence, the possibility of metastasis was considered low, and the patient was placed under observation. At POY 12, computed tomography revealed an enlargement of the No.16b1lat lymph node station, and PET showed abnormal uptake. Endoscopic ultrasound-guided fine-needle aspiration revealed a moderately differentiated adenocarcinoma. Hence, a diagnosis of recurrence of gastric cancer was made. The patient underwent para-aortic nodal dissection (PAND) of No.16b1lat & int stations. Immunochemical staining results also suggested the recurrence of gastric cancer. However, the expression of CD44 variant 9 (CD44v9), a cancer stem cell marker for gastric adenocarcinoma, was attenuated in the recurrent lesions compared with that in the primary lesions. Postoperatively, she received chemotherapy with tegafur–gimeracil–oteracil (80 mg/day) for 1 year. Bone metastasis was observed at POY 4 after PAND, and the IHC analysis showed a HER2 score of 3 + in a needle biopsy specimen of bone metastasis. The expression of CD44v9 was slightly positive. The patient is being treated with chemotherapy with FOLFOX + trastuzumab.ConclusionsA defense mechanism against reactive oxygen species has been reported as a mechanism causing recurrence of CD44v9-positive gastric cancer. Consequently, CD44v9-positive gastric cancer grows in metastatic organs, repeatedly self-renews, and proliferates to form recurrent lesions. In the present case, the degree of CD44v9 staining in recurrent lesions was suggested to be related to the recurrence time.

Pan-Cancer Analysis of the Tumorigenic Effect and Prognostic Diagnostic Value of FAM111B in Human Carcinomas.

FAM111B (FAM111 trypsin-like peptidase B) gene mutations have been linked to a hereditary fibrosing poikiloderma disorder known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). Overexpression of FAM111B has been associated with an increased risk of certain cancers with a poor prognosis, although the relationship between FAM111B and other tumors is still unclear, and the molecular mechanism of its action is not fully understood. We investigated the biological functions of FAM111B in 33 solid tumors using multi-omics data. We further recruited 109 gastric cancer (GC) patients for a clinical cohort study to confirm the effect of FAM111B on early tumor recurrence. Furthermore, we assessed the role of FAM111B in GC cell proliferation and migration via EdU incorporation, CCK8 and transwell assays in vitro. We found that FAM111B can enhance oncogenesis and progression in multiple tumor types. The clinical cohort of GC showed that upregulation of FAM111B is associated with early recurrence of GC, and knockdown of the FAM111B gene can inhibit the proliferation and migration of GC cells. Gene enrichment analysis indicates that FAM111B promotes cancer through immune system process, chromosome instability, DNA repair, and apoptosis regulation. Mechanistically, FAM111B appears to promote the growth cycle of malignant tumor cells while inhibiting apoptosis. FAM111B may serve as a potential pan-cancer biomarker for predicting the prognosis and survival of malignant tumor patients. Our study elucidates the role of FAM111B in the occurrence and development of various cancers, and highlights the need for future research on FAM111B in cancers.

EUS Kılavuzluğundaki Hepatikojejunostomi Sırasında Öngörülemeyen Olay

Endoscopic ultrasound (EUS)-guided biliary drainage is a therapeutic alternative method in patients with cholestasis where the ampulla of Vater cannot be reached because several reasons. An unfortunate complication during EUS-guided biliary drainage was presented in this report. A 53-year-old male patient presented with jaundice and pruritus. He had a history of total gastrectomy due to gastric cancer. An abdominal tomography scan detected a tumoral mass in the common bile duct due to the recurrence of gastric cancer. We decided to perform EUS-guided hepaticojejunostomy because biliary drainage cannot be obtained by conventional methods and percutaneous drainage impairs patient comfort. A double pigtail plastic stent was placed from the jejunum into the segment-3 bile duct towards the hilus. After that echoduodenoscope was removed to the outside gently. We noticed that the stent was stuck in the echoduedonoscope elevator. We reached into the bile duct again and placed a double-pigtail plastic stent successfully.