Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution.

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

Short- and long-term comparison of robotic versus laparoscopic gastrectomy for gastric cancer patients with BMI≥30 kg/m2: A propensity score matched analysis.

BACKGROUND: Although minimally invasive surgery (MIS) for gastric patients has gained popularity in recent decades, reports on the comparison of short and long clinical outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer patients with BMI≥30 kg/m2 are still limited. METHODS: A total of 226 obese gastric cancer patients who underwent either RG (n = 81) or LG (n = 145) were enrolled in this study between October 2014 and September 2022. Propensity score matching (PSM) (1:1) was performed to reduce confounding bias. Short-term and long-term outcomes were compared between the RG and LG groups. RESULTS: The clinicopathological characteristics of 156 patients in the RG group (n = 79) and LG group (n = 79) were well balanced after PSM. Compared with the LG group, the RG group had a significantly shorter operation time, less estimated blood loss, more harvested lymph nodes, a faster postoperative recovery course, reduced surgical morbidity, and a shorter postoperative hospital stay. The long-term outcomes were comparable between the two groups. CONCLUSIONS: RG is a safe and feasible approach for gastric cancer with a BMI≥30 kg/m2 and has better short-term clinical outcomes than LG. However, RG is similar to LG in terms of long-term prognosis.

Disulfidptosis-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in colon adenocarcinoma.

BACKGROUND: Disulfidptosis is independent of apoptosis, ferroptosis, and cuproptosis and is associated with cancer progression, treatment response, and prognosis. However, the predictive potential of disulfidptosis-associated lncRNAs in colon adenocarcinoma (COAD) and their features in the tumor immune microenvironment (TIME) require further elucidation. METHODS: RNA transcriptome, clinical information, and mutation data of COAD samples were obtained from the TCGA database. The risk model was first constructed by co-expression analysis of disulfidptosis genes and lncRNAs, and prognostic lncRNAs were screened using Cox regression, followed by least absolute shrinkage and selection operator analysis. Enrichment analyses were performed to explore the underlying biological functions and signaling of model-associated differentially expressed genes (MADEGs). Moreover, TIME of MADEGs was analyzed to assess the immunotherapy. Finally, the expression levels of the lncRNAs were verified by taking specimens of patients with COAD from the Affiliated Hospital of Qingdao University. RESULTS: We constructed a prognosis-related risk model based on four disulfidptosis-associated lncRNAs (ZEB1-AS1, SNHG16, SATB2-AS1, and ALMS1-IT1). By analyzing the survival of patients in the whole, training, and test groups, we found that patients with COAD in the low-risk group had better overall survival than those in the high-risk group. Validation of the model via Cox analysis and clinical indicators demonstrated that the model had a decent potential for predicting the prognosis of patients with COAD. Enrichment analyses revealed that the MADEGs were related to disulfidptosis-associated biological functions and cancer pathways. Furthermore, patients with COAD in the high-risk group had more positive responses to immune checkpoint inhibitors (ICIs) than those in the low-risk group, as confirmed by TIME analysis. ZEB1-AS1, SNHG16, and ALMS1-IT1 were expressed at higher levels in tumor samples than those in the corresponding paracancerous samples (p < 0.05), whereas SATB2-AS1 was upregulated in the paracancerous samples (p < 0.05). CONCLUSIONS: This signature may guide prognosis, molecular mechanisms, and treatment strategies, including ICIs and chemotherapy, in patients with COAD.

A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options.

Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) treatment. Transcriptome, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a Cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas monocytes, M2 macrophages, eosinophils, and neutrophils were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy in patients with STAD.

Postoperative Adjuvant Imatinib Therapy-Associated Nomogram to Predict Overall Survival of Gastrointestinal Stromal Tumor.

Background: Adjuvant imatinib therapy has been shown to improve overall survival (OS) of gastrointestinal stromal tumor (GIST) significantly. Few nomograms combining the use of adjuvant imatinib and clinicopathological characteristics estimate the outcome of patients. We aimed to establish a more comprehensive nomogram for predicting OS in patients with GIST. Methods: In total, 1310 GIST patients undergoing curative resection at four high-volume medical centers between 2001 and 2015 were enrolled. Independent prognostic factors were identified by multivariate Cox analysis. Eligible patients were randomly assigned in a ratio of 7:3 into a training set (916 cases) and a validation set (394 cases). A nomogram was established by R software and its predictive power compared with that of the modified National Institutes of Health (NIH) classification using time-dependent receiver operating characteristic (ROC) curves and calibration plot. Results: Age, tumor site, tumor size, mitotic index, postoperative imatinib and diagnostic delay were identified as independent prognostic parameters and used to construct a nomogram. Of note, diagnostic delay was for the first time included in a prognostic model for GIST. The calibrated nomogram resulted in predicted survival rates consistent with observed ones. And the decision curve analysis suggested that the nomogram prognostic model was clinically useful. Furthermore, time-dependent ROC curves showed the nomogram exhibited greater discrimination power than the modified NIH classification in 3- and 5-year survival predictions for both training and validation sets (all P < 0.05). Conclusions: Postoperative adjuvant imatinib therapy improved the survival of GIST patients. We developed and validated a more comprehensive prognostic nomogram for GIST patients, and it could have important clinical utility in improving individualized predictions of survival risks and treatment decision-making.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

Short- and long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer by the same surgical team: a propensity score matching analysis.

BACKGROUND: Research on short-term outcomes and oncology results after robotic gastrectomy (RG) is still limited, especially from a single surgical team. The purpose of this study was to compare the short-term and long-term outcomes of robotic and laparoscopic gastrectomy (LG). METHODS: Between October 2014 and September 2019, 1686 consecutive patients who underwent MIS gastrectomy were enrolled. The patients were divided into RG and LG groups according to surgical type. Groups were matched at a 1:1 ratio using propensity scores based on the following variables: age, sex, ASA score, primary tumor location, histologic type, pathological stage, and neoadjuvant chemotherapy. The primary outcomes were 3-year overall survival (OS) and relapse-free survival (RFS). The secondary outcomes were postoperative short-term outcomes. RESULTS: Demographic and baseline characteristics were similar between the two groups after matching. Compared to the LG group, the RG group had a significantly higher retrieved lymph node (LN) number (32.15 vs 30.82, P = 0.040), more retrieved supra-pancreatic LNs (12.45 vs 11.61, P = 0.028), lower estimated blood loss (73.67 vs 98.08 ml, P < 0.001), but longer operation time (205.18 vs 185.27 min, P < 0.001) and higher hospitalization costs ($13,607 vs $10,928, P < 0.001) in the matched cohort. In the subgroup analysis, we observed that compared with LG, patients with advanced gastric cancer benefitted more from RG surgery. The matched cohort analysis demonstrated no statistically significant differences for 3-year OS or RFS (log-rank, P = 0.648 and P = 0.951, respectively): 80.3% and 77.0% in LG vs. 81.2% and 76.6% in RG, respectively. CONCLUSION: RG has certain technical advantages over LG, especially in patients with advanced gastric cancer. However, RG does not improve long-term oncology outcomes.

Effects of robotic and laparoscopic-assisted surgery on lymph node dissection and quality of life in the upper third of gastric cancer: A retrospective cohort study based on propensity score matching.

Objective: The objective of this study was compare the effects of robot-assisted and laparoscopic-assisted surgery on lymph node dissection and quality of life in upper third gastric cancer patients undergoing radical total gastrectomy. Methods: The clinical and follow-up data of 409 patients with upper third gastric cancer who underwent total gastrectomy from July 2016 to May 2021 were enrolled. The patients were divided into a robotic group (n = 106) and a laparoscopic group (n = 303). Age, sex, body mass index, American Society of Anesthesiologists score, tumor size and location, pathological type, cT, cN, and cTNM were adjusted to offset selection bias. The patient characteristics, operative procedures, surgical outcomes, oncologic and pathologic outcomes, number of lymph node dissections, quality of life assessment, and nutritional status were compared between the two groups. Results: After propensity score matching, 61 cases were included in the robotic group and 122 cases were included in the laparoscopic group. The number of dissected lymph nodes (37.3 ± 13.5 vs. 32.8 ± 11.8, P = 0.022) significantly differed between the two groups. The number of lower mediastinal and subphrenic lymph nodes in the robotic group was greater than that in the laparoscopic group, and the difference was statistically significant (P < 0.001). Compared with the laparoscopic group, the total score of physical symptoms in the robotic group was significantly lower at 6 and 12 months after surgery (P = 0.03 and P = 0.001, respectively). The total social function score at 6 and 12 months after surgery was higher in the robotic group (P = 0.006 and P = 0.022). The quality of life scores were statistically significant only at 3 months after the operation (P = 0.047). A higher patient-generated subjective global assessment (PG-SGA) score is when the score significantly correlated (P < 0.001) with a higher related physical symptoms score, lower social function score, and lower quality of life score. Conclusion: Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy is safe and feasible. Compared with laparoscopic radical gastrectomy, robotic radical gastrectomy was more refined, was associated with less surgical bleeding, and increased the quality of lymph node dissection. In addition, patients in the robotic group showed better postoperative quality of life.

Clinical outcomes of proximal gastrectomy with gastric tubular reconstruction and total gastrectomy for proximal gastric cancer: A matched cohort study.

Background: Proximal gastrectomy with gastric tubular reconstruction is a surgical procedure that can preserve function in patients with proximal gastric cancer. However, whether gastric tubular reconstruction with proximal gastrectomy has certain advantage in some aspects over total gastrectomy is controversial. To evaluate the benefit of gastric tubular reconstruction after proximal gastrectomy, we compared gastric tubular reconstruction with total gastrectomy for proximal gastric cancer. Method: A total of 351 patients were enrolled. Concurrent total gastrectomy patients matched with the Proximal gastrectomy group in age, sex, body mass index, clinical stage, and ASA score were selected by propensity score matching. Preoperative basic information, perioperative indicators, histopathological features, postoperative complications and nutritional status, reflux were compared between the two groups. Results: There was no significant difference in the incidence of reflux between two groups (14.8% and 6.5% respectively, P = 0.085). There were significant differences between the two groups in bowel function recovery (2.29 ± 1.16 vs. 3.01 ± 1.22; P = 0.039) and start of soft diet (4.06 ± 1.81 vs. 4.76 ± 1.69; P = 0.047). There were no significant differences between the two groups in nutritional status one year after surgery. However, the decrease in serum hemoglobin in the TG group at 3 and 6 months after surgery was significantly higher than that in the PG group (P = 0.032 and 0.046, respectively). One month after surgery, %BW loss in TG group was significantly lower than that in the PG group (P = 0.024). Conclusion: The Proximal gastrectomy group has better clinical outcome and gastric tubular reconstruction is simple, similar complications and reflux rates, gastric tubular reconstruction may be more suitable for proximal gastric cancer.

Self-administered succus entericus reinfusion before ileostomy closure improves short-term outcomes.

OBJECTIVE: The study aims to assess whether reinfusion of succus entericus prior to ileostomy closure can decrease postoperative length of stay and ameliorate low anterior resection score. METHODS: This study is a retrospective analysis based on prospectively collected data. Patients were screened from May 2016 to November 2019. A total of 30 patients who underwent reinfusion with succus entericus (SER) were enrolled in the SER group and 42 patients without SER were enrolled in the non-SER group. RESULTS: There was no significant difference in the incidence of postoperative ileus between succus entericus reinfusion (SER) group and the control group. Time to first passage of flatus or stool after surgery in the SER group (27.9 ± 6.02 h) is significantly shorter than the control group (32.3 ± 6.26, hours p = 0.004). Compared with the control group (5.52 (4.0-7.0) days), postoperative length of stay in the SER group was 4.90 (3.0-7.0)days (p = 0.009). As for low anterior resection score(LARS), the SER group had a lower score 1 week after discharge than the control group (p = 0.034). However, 1 month after discharge, the LARS in the two groups had no significant difference. CONCLUSIONS: Self-administered succus entericus reinfusion is a feasible prehabilitation management for outpatients and can improve better outcomes. Compared with non-reinfusion group, succus enterius reinfusion group displays significantly shorter time for gastrointestinal function recovery and postoperative hospital stay without increasing complication, and it can bring better quality of life in a short term.

Upregulation of TTYH3 promotes epithelial-to-mesenchymal transition through Wnt/ß-catenin signaling and inhibits apoptosis in cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is a highly invasive malignant tumor originating from the bile duct epithelium. Tweety homolog 3 (TTYH3) is a member of the family of calcium-activated chloride channels, which have several biological functions. Here, we aimed to investigate the expression and biological function of TTYH3 in CCA. METHODS: The mRNA and protein expression levels of TTYH3 were investigated in primary human CCA tissues and normal tissues. The DNA methylation levels of three CpG sites in the TTYH3 promoter region were evaluated using pyrosequencing. The effect of TTYH3 expression on proliferation, apoptosis, migration and invasion were assessed in HUCCT1 and QBC939 cells. Xenograft models were developed to substantiate its role in the development of CCA. Western blot analysis was used to investigate the mechanistic role of TTYH3 in regulating CCA progression. RESULTS: We found that TTYH3 was highly expressed both at the mRNA and protein levels in CCA (p = 0.0001) and that the expression levels were significantly related to a poor overall survival of the patients (p = 0.0019). The DNA methylation levels of three CpG sites in the TTYH3 promoter region were significantly lower in CCA tissues compared to normal tissues (p < 0.05). In vitro studies indicated that TTYH3 can promote the proliferation, migration and invasion of the CCA cells. TTYH3 overexpression significantly promoted tumor progression and cellular proliferation in vivo as indicated by Ki-67 expression. In addition, we found that exogenous TTYH3 overexpression induced epithelial-mesenchymal transition (EMT) in CCA as indicated by expression changes in E-cadherin, N-cadherin and vimentin. The EMT process was found to occur through the Wnt/ß-catenin signaling pathway, with simultaneous changes in P-GSK3ß and ß-catenin levels. CONCLUSIONS: Our data indicate that DNA hypomethylation-induced overexpression of TTYH3 regulates CCA development and metastasis through the Wnt/ß-catenin pathway.

miRNA-Based Signature Associated With Tumor Mutational Burden in Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common malignant tumors. Tumor mutation burden (TMB) has become an independent biomarker for predicting the response to immune checkpoint inhibitors (ICIs). miRNAs play an important role in cancer-related immune regulation. However, the relationship between miRNA expression and TMB in COAD remains unclear. Therefore, the transcriptome profiling data, clinical data, mutation annotation data, and miRNA expression profiles for cases of COAD were downloaded from the TCGA database. Subsequently, 323 COAD cases were randomly divided into training and test sets. The differential expression of miRNAs in the high and low TMB groups in the training set was obtained as a signature using the least absolute shrinkage and selection operator (LASSO) logistic regression and verified in the test set. Based on the LASSO method, principal component analysis (PCA), and ROC, we found that the signature was credible because it can discriminate between high and low TMB levels. In addition, the correlation between the 18-miRNA-based signature and immune checkpoints was performed, followed by qRT-PCR, to measure the relative expression of 18 miRNAs in COAD patients. The miRNA-based model had a strong positive correlation with TMB and a weak positive correlation with CTLA4 and CD274 (PD-L1). However, no correlation was observed between the model and SNCA (PD-1). Finally, enrichment analysis of the 18 miRNAs was performed to explore their biological functions. The results demonstrated that 18 miRNAs were involved in the process of immunity and cancer pathways. In conclusion, the 18-miRNA-based signature can effectively predict and discriminate between the different TMB levels of COAD and provide a guide for its treatment with ICIs.

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with a microsatellite stable status in Chinese gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. However, little is known about the combination of HER2 amplification and microsatellite instability (MSI) status in GC. This study aimed to analyze the correlation of HER2 amplification with microsatellite instability (MSI) status, clinical characteristics, and the tumor mutational burden (TMB) of patients. METHODS: A total of 192 gastric cancer (GC) patients were enrolled in this cohort. To analyze genomic alterations (GAs), deep sequencing was performed on 450 target cancer genes. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. RESULTS: The most frequently amplified genes in the GC patients included cyclin E1 (CCNE1), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), cyclin D1 (CCND1), fibroblast growth factor 19 (FGF19), fibroblast growth factor 3 (FGF3), and fibroblast growth factor 4 (FGF4). The frequency of HER2 amplification was 9.38% (18/192). HER2 amplification was higher in females than in males (14.52% vs. 6.92%, respectively, P=0.091), however, MSI was higher in males compared to females (7.69% vs. 4.84%, respectively, P=0.46). HER2 amplification was higher in metastatic loci compared to primary lesions (23.08% vs. 8.38%, respectively, P=0.079) and was lower in patients with high TMB (TMB-H) compared to those with low TMB (TMB-L) (4.0% vs. 11.35%, respectively, P=0.12). While the frequency of MSI in metastatic foci was higher than that in primary lesions (15.38% vs. 6.15%, respectively, P=0.48), MSI status was highly associated with TMB-H (20% vs. 0%, respectively, P=3.66×10-7). Furthermore, HER2 amplification was negatively correlated with MSI status in Chinese GC patients. CONCLUSIONS: HER2 amplification was negatively correlated with TMB-H and MSI status, and MSI status was significantly associated with TMB-H in Chinese GC patients. These data suggested that HER2 amplification might be a negative indicator for GC immunotherapy.

Impact of drinking Chinese green tea on postoperative short outcomes for gastric cancer: a randomized controlled trial.

BACKGROUND: Early intake after surgery can decrease postoperative ileus. Several studies show coffee can stimulate bowel activity and be safe in patients after elective colectomy, mainly due to caffeine. It was postulated that drinking Chinese green tea as rich caffeine beverage after subtotal distal gastrectomy accelerates postoperative recovery in patients. METHOD: This was a single-centre parallel open-label randomized trial. Patients with gastric cancer undergoing robotic or laparoscopic subtotal gastrectomy were randomly allocated to receive drinking Chinese green tea (GT group) or potable water (PW group) after surgery. The primary endpoint was the time to gastrointestinal function recovery and tolerance of solid food, and the secondary endpoints included the incidence of postoperative complications, symptoms of postoperative adverse reaction, length of stay, pain as assessed by analgesic consumption and a visual analogue scale, and fatigue as assessed by a fatigue score model. RESULTS: A total of 80 patients were recruited, 40 to each group. Patient characteristics were similar in both groups. The GT group showed significantly shorter time to gastrointestinal function recovery compared with PW group to first flatus (47.23 ± 13.46 vs. 76.96 ± 20.35, P < 0.001), first bowel motion (78.70 ± 25.77 vs. 125.76 ± 36.25, P < 0.001) and tolerance of solid food (62.20 ± 16.15 vs. 98.66 ± 20.15, P < 0.001). CONCLUSION: Drinking Chinese green tea after robotic or laparoscopic subtotal gastrectomy is safe and promotes postoperative recovery of gastrointestinal function, also was an add method with strengthening analgesia and anti-inflammatory effect in the presence of the Enhance Recovery After Surgery (ERAS) program. Registration number: ChiCTR1800018294 ( http://www.chictr.org.cn ).

Enhanced Recovery after Surgery in Elderly Gastric Cancer Patients Undergoing Laparoscopic Total Gastrectomy.

BACKGROUND: The aim of this study was to evaluate the effects of the enhanced recovery after surgery (ERAS) program versus conventional perioperative care on the short-term postoperative outcomes among elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. METHODS: Elderly patients with gastric cancer (age ≥ 65 y) who are undergoing laparoscopic total gastrectomy were randomized to ERAS or conventional perioperative care groups. Short-term postoperative outcomes, including postoperative hospital stay, mortality, complications, readmission rate, and reoperation rate were compared between the two groups. In addition, blood samples were taken preoperatively (baseline) and on postoperative days 1, 3, and 5. Systemic human leukocyte antigen (HLA)-DR expression on monocytes and C-reactive protein (CRP) were analyzed. RESULTS: Of the 171 eligible patients, 85 patients were assigned to receive ERAS program treatment (ERAS group) and 86 patients to receive conventional care (conventional group). The patients' characteristics were comparable. Postoperative hospital stay was shorter in the ERAS group than in the conventional group (11 [7-11] versus 13 [8-20] d, P < 0.001). Hospital mortality, overall morbidity, morbidity ≥ Clavien-Dindo (C-D) grade II, readmission rate, and reoperation rate did not show significant differences between the two groups. However, morbidity ≥ C-D grade IIIa was lower in the ERAS group than that in the conventional group (8.2% versus 18.6%, P = 0.047). The ERAS program shortened the number of days to postoperative first flatus, first defecation, semifluid diet, and soft bland diet. Moreover, the ERAS program increased the HLA-DR expression on monocytes and decreased the CRP levels on postoperative days 1, 3, and 5. CONCLUSIONS: The ERAS program was feasible and effective for elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. The benefits of ERAS were associated with improvement of impaired immune function and suppression of inflammatory reaction.

Clinical significance and comparison of flotillin 1 expression in left and right colon cancer.

Flotillin 1 (FLOT1) is increasingly implicated in various types of cancer, and has been reported to influence tumorigenesis and cancer progression, leading to poor prognosis for survival time; however, its expression in colorectal cancer (CRC) and its influence on various clinicopathological parameters of this disease remain unknown. In the present study, FLOT1 expression and its effect on different clinicopathological parameters were assessed immunohistochemically and histologically in 81 CRC and 81 non-tumorous colon tissue samples. The immunohistochemical staining was scored semi-quantitatively. The association of FLOT1 expression with various parameters and its effect on overall survival time was also assessed. FLOT1 was upregulated in the CRC tissue, with increased expression in the right colon tissue samples compared with those of left colon. Increased FLOT1 expression in CRC tissue samples was associated with tumor volume, differentiation, tumor grade and poor overall survival time. In the right colon tissue samples in particular, there was a notable association with tumor volume and grade, indicating its effect on proliferation and tumor stage at this site. A multivariate Cox regression hazard analysis revealed that only tumor grade and differentiation were the independent predictors of overall survival time in patients with CRC. Together, the results of the present study suggest that FLOT1 serves important functions in the proliferation and progression of CRC, contributes to decreased survival time, and may serve as a novel therapeutic target for the treatment of CRC.