Health-Related Quality of Life in Patients With Locally Advanced Gastric Cancer Undergoing Perioperative or Postoperative Adjuvant S-1 Plus Oxaliplatin With D2 Gastrectomy: A Propensity Score-Matched Cohort Study.

Background: Some high-quality clinical trials have proven the efficacy and safety of perioperative and postoperative S-1 with oxaliplatin (peri-SOX and post-SOX) for patients with locally advanced gastric cancer (LAGC) undergoing D2 gastrectomy. However, little is known about how health-related quality of life (HRQOL) changes over time in patients receiving peri-SOX or post-SOX chemotherapy. Methods: A prospective observational cohort (NCT04408859) identified 151 eligible patients with LAGC who underwent D2 gastrectomy with at least six cycles of peri-SOX or post-SOX chemotherapy from 2018 to 2020. HRQOL was assessed using the EROTC QLQ-C30 and its gastric module, QLQ-STO22, at indicated measurements, including the baseline, 1st, 3rd, 6th and 12th month after initiation of therapy. Baseline characteristics, therapeutic effects, and longitudinal HRQOL were compared between the peri-SOX and post-SOX groups after propensity score matching. HRQOL changes over time and the risk factors for scales with severe deterioration were further analyzed. Results: No statistically significant differences in longitudinal HRQOL were observed between patients in the peri-SOX and post-SOX groups, with comparable surgical outcomes and adverse chemotherapy events. Scales of social functioning, abnormal taste, and anxiety improved earlier in the peri-SOX group than in the post-SOX group. Score changes in both groups indicated that general deterioration and slower recovery usually occurred in the scales of physical, social, and role functioning, as well as symptoms of fatigue, reflux, diarrhea, and anxiety. Conclusion: Peri-SOX showed a longitudinal HRQOL comparable to post-SOX in patients with LAGC who underwent D2 gastrectomy. The peri-SOX group had better performance in social functioning, abnormal taste, and anxiety at some measurements.

Quadruple-editing of the MAPK and PI3K pathways effectively blocks the progression of KRAS-mutated colorectal cancer cells.

Mutated KRAS promotes the activation of the MAPK pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of the PI3K pathway strongly attenuates the efficacy of MAPK suppression in KRAS-mutated CRC. The development of a novel strategy targeting a dual pathway is therefore highly essential for the therapy of KRAS-mutated CRC. In this study, a quadruple-depleting system for the KRAS, MEK1, PIK3CA, and MTOR genes based on CRISPR/SaCas9 was developed. Adenovirus serotype 5 (ADV5) was integrated with two engineered proteins, an adaptor and a protector, to form ADV-protein complex (APC) for systemic delivery of the CRISPR system. Quadruple-editing could significantly inhibit the MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, quadruple-editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor specifically targeting EpCAM and the hexon-shielding protector could dramatically enhance ADV5 infection efficiency to CRC cells and significantly reduce off-targeting tropisms to many organs except the colon. Moreover, quadruple-editing intravenously delivered by APC significantly blocked the dual pathway and tumor growth of KRAS-mutated CRC cells, without influencing normal tissues in cell- and patient-derived xenograft models. Therefore, APC-delivered quadruple-editing of the MAPK and PI3K pathways shows a promising therapeutic potential for KRAS-mutated CRC.

Effects of laparoscopic-assisted gastrectomy on elderly patients with gastric cancer.

PURPOSE: Although the acceptance of laparoscopy-assisted gastrectomy (LAG) for the treatment of gastric cancer (GC) has been increasing, it is still controversial that LAG is an applicable treatment method for elderly patients since elderly patients are usually complicated with other diseases. Therefore, this study aimed to investigate the prognostic differences between elderly patients and non-elderly patients after receiving LAG. METHODS: Patients (n = 306) who received LAG for the treatment of GC from April 2009 to December 2014 were included in the study. The patients were divided into the elderly group (≥ 65 years old, n = 120) and the non-elderly group (< 65 years old, n=186). The postoperative outcomes as well as the morbidity and the survival rates were compared between the two groups. RESULTS: American Society of Anesthesiologists (ASA) score and comprehensive complication index (CCI) score in the elderly group were significantly higher than those in the non-elderly group (p<0.05). In terms of surgical outcomes, there was no significant difference in blood loss or postoperative hospital stay between the elderly group and the non-elderly group. As for postoperative comorbidities, there were significant differences in intraperitoneal hemorrhage and pleural effusion between the elderly group and the non-elderly group. Moreover, the median follow-up time was 38.5 months, and the overall survival of elderly patients with comorbidities was significantly lower than that of the elderly patients without comorbidities (p<0.05). CONCLUSIONS: LAG can be performed safely and successfully in the elderly population with acceptable postoperative and long-term results.

Risk factors for esophagojejunal anastomotic leakage after curative total gastrectomy combined with D2 lymph node dissection for gastric cancer.

OBJECTIVE: To explore the risk factors associated with esophagojejunal anastomotic leakage (EJAL) after curative total gastrectomy combined with D2 lymph node dissection for gastric cancer. METHODS: We reviewed the data for 390 consecutive patients undergoing Roux-en-Y esophagojejunostomy reconstruction after total gastrectomy. Multivariate analysis was performed using a logistic regression model to identify the independent risk factors for EJAL. RESULTS: Of the 390 patients enrolled in this study, EJAL occurred in 10 patients (2.6%), and one patient (1/10) with EJAL died. Univariate analysis identified age, alcohol consumption, pulmonary insufficiency, and intraoperative blood loss as risk factors for EJAL. Of these four risk factors, age and alcohol consumption were retained as independent risk factors by multivariate analysis. CONCLUSION: Surgeons should be very careful regarding anastomotic leakage after esophagojejunal anastomosis, perioperatively, especially in patients with advanced age and a history of alcohol consumption. Pulmonary insufficiency and intraoperative blood loss, although not identified as independent risk factors, should also be considered.

Surgical and oncological efficacy of laparoscopic-assisted total gastrectomy versus open total gastrectomy for gastric cancer by propensity score matching: a retrospective comparative study.

PURPOSE: The application of laparoscopic-assisted total gastrectomy (LATG) for resectable gastric cancer (GC) remains controversial compared with open total gastrectomy (OTG), especially for advanced gastric cancer (AGC) patients according to the inconsistent results demonstrated in the previous studies. The aim of this study was to evaluate the short-term and long-term outcomes between LATG and OTG in a population with more than 80% AGC patients by applying propensity score matching (PSM) method. METHODS: The data of 365 clinical stage I-III GC cases who underwent total gastrectomy with D2 lymphadenectomy were retrospectively collected from January 2011 to April 2018 in the Department of Gastrointestinal Surgery IV of Peking University Cancer Hospital. Propensity scores were generated through taking all covariates into consideration and 131 pairs of patients receiving either LATG or OTG were matched. Intraoperative, postoperative, and survival parameters were compared in the matched groups accordingly. Risk factors for postoperative complications and overall survival were further analyzed. RESULTS: Patient characteristics in the LATG and OTG groups were well balanced after PSM. LATG showed advantages with respect to shorter time to ambulation, first flatus, and first whole liquid diet intake. No significant differences were found between the two groups with regard to postoperative complications as well as overall survival in terms of different pathological stage. Older age was found as an independent risk factor for postoperative complications, and pathological stage for overall survival as well. CONCLUSION: LATG appears to have comparable surgical and oncological safety with OTG by experienced surgeons.

Triggering of Apoptosis in Osteosarcoma 143B Cell Line by Carbon Quantum Dots via the Mitochondrial Apoptotic Signal Pathway.

OBJECTIVES: Carbon-based nanomaterials have gained attention in the field of biomedicine in recent years, especially for the treatment of complicated diseases such as cancer. Here, we report a novel carbon-based nanomaterial, named carbon quantum dots (CQDs), which has potential for cancer therapy. We performed a systematic study on the effects of CQDs on the osteosarcoma 143B cell line in vitro and in vivo. METHODS: Cell counting assay, the neutral red assay, lactic dehydrogenase assay, and fluorescein isothiocyanate (FITC) Annexin V/Propidium iodide (PI) were used to detect the cytotoxicity and apoptosis of CQDs on the 143B cell line. Intracellular reactive oxygen species (ROS) were detected by the oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate. The JC-10 assay was used to detect the mitochondrial membrane potential (MMP) of 143B cells incubated with CQDs. The effects of CQDs on the 143B cell line were evaluated by Western blot and immunofluorescence analysis of apoptosis-related proteins Bax, Bcl-2, cytochrome-C, caspase-3, cleaved-caspase-3, PARP1, and cleaved-PARP1. Male tumor-bearing BALB/c nude mice were used to investigate the antitumor effects of CQDs, and the biosafety of CQDs in vivo was tested in male BALB/c mice by measuring weight changes, hematology tests, and histological analyses of major organs. RESULTS: CQDs exhibited a high cytotoxicity and induced apoptosis toward the 143B cell line. CQDs can also significantly increase the intracellular level of ROS and lower the mitochondrial membrane potential levels of 143B cells. CQDs increase apoptotic protein expression to induce apoptosis of 143B cells by triggering the mitochondrial apoptotic signaling pathway. The tumor volume in the CQD-treated mice was smaller than that in the control group, the tumor volume inhibition rate was 38.9%, and the inhibitory rate by tumor weight was 30.1%. All biosafety test indexes were within reference ranges, and neither necrosis nor inflammation was observed in major organs. CONCLUSIONS: CQDs induced cytotoxicity in the 143B cell line through the mitochondrial apoptotic signaling pathway. CQDs not only showed an antitumor effect but also high biocompatibility in vivo. As a new carbon-based nanomaterial, CQDs usage is a promising method for novel cancer treatments.

Phenotype molding of T cells in colorectal cancer by single-cell analysis.

The majority of patients with microsatellite stable (MSS) colorectal cancer (CRC) do not benefit from the immunotherapies directed at rescuing T-cell functions. Therefore, complete understanding of T-cell phenotypes and functional status in the CRC microenvironment is desirable. Here, we applied single-cell mass cytometry to mold the T-cell phenotype in 18 patients with MSS CRC for better understanding of CRC as a systemic disease and to search for tumor-driven T-cell profile changes. We show interpatient and intrapatient phenotypic diversity of T-cell subsets. We revealed increased immunosuppressive/exhausted T-cell phenotypes at tumor lesions. CD8+ CD28- immunosenescent T cells with impaired proliferation capacity dominate the T-cell compartment. As per the transcriptome and quantitative real time-PCR analysis, the accumulation of immunosuppressive cells is driven by the tumor microenvironment. T-cell profiles are similar between patients at early and late stages, indicating that the immunosuppressive microenvironment is formulated early during CRC development. Mapping of T-cell infiltration and understanding of the mechanisms underlying their regulation may provide valuable information to boost the immune response in patients with MSS CRC.

Safety and efficacy of laparoscopic gastrectomy in obese patients with gastric cancer.

The present study aimed to investigate the safety and short-term outcome of laparoscopy-assisted distal radical gastrectomy in treating gastric cancer among obese patients.Perioperative outcomes were compared between 67 gastric cancer patients with a body mass index (BMI) ≥25 kg/m (obese group) and 198 ones with BMI <25 kg/m (non-obese group). All the cases underwent laparoscopic radical resection between April 2009 and October 2013.The value of BMI was 27.3 ±â€Š2.67 kg/m in the obese group and 21.3 ±â€Š2.64 kg/m in non-obese group. There were no significant differences between 2 groups in age, sex, presence of diabetes, tumor size, number of metastatic lymph nodes, or metastatic lymph node ratio. Postoperative complications did not differ between the 2 groups (P > .05). There were significant differences between the 2 groups in operation time (non-obese: [234.2 ±â€Š67.1] minutes vs obese group: [259.4 ±â€Š78.5]; P = .017), postoperative hospital stay (obese group [19.7 ±â€Š14.8] day vs non-obese [15.4 ±â€Š7.1], P = .002), and retrieved lymph nodes ([27.6 ±â€Š11.0] day vs non-obese [31.9 ±â€Š12.5] day, P = .002).Obesity may prolong operation time and postoperative hospital stay, and cause less retrieved lymph nodes, but does not increase the incidence of postoperative complications. The experienced center can properly conduct laparoscopic assisted radical gastrectomy in obese patients.