Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

Emicizumab as a Promising Form of Therapy for Type A Hemophilia - A Review of Current Knowledge from Clinical Trials.

Hemophilia is a plasma bleeding disorder characterized by a deficiency of certain blood clotting factors. The most common forms of this disease, i.e., type A and type B, affect approximately 400,000 people worldwide. Without appropriate treatment ensuring the proper coagulation cascade, this disease may lead to serious disability. Minimizing patient discomfort is possible via replacement therapy, consisting of the substitution of a missing coagulation factor via intravenous administration. Frequent medication and the risk related to factor inhibitors are significant disadvantages, necessitating the improvement of current therapies or the development of novel ones. This review examines the humanized bispecific antibody Emicizumab which ensures hemostasis by mimicking the action of the coagulation factor VIII, a deficiency of which causes type A hemophilia. The paper outlines the topic and then summarizes available clinical trials on Emicizumab in type A hemophilia. Several interventional clinical trials have found Emicizumab to be effective in decreasing bleeding episodes and raising patient satisfaction among various hemophilia A populations. Current Emicizumab-related trials are forecast to be completed between 2024 and 2030, and in addition to congenital hemophilia A, the trials cover acquired hemophilia A and patients playing sports. Providing a more comprehensive understanding of Emicizumab may revolutionize the management of hemophilia type A and improve quality of life. Conclusively, Emicizumab is a gentler therapy owing to subcutaneous delivery and fewer injections, which reduces injection-site reactions and makes therapy less burdensome, ultimately decreasing hospital visits and indirect costs.

Britanin - a beacon of hope against gastrointestinal tumors?

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties. It also exhibits significant anti-tumor activity, suppressing tumor growth in vitro and in vivo. The current body of research on Britanin includes thirty papers predominantly related to neoplasms, the majority of which are gastrointestinal tumors that have not been summarized before. To drive academic debate, the present paper reviews the available research on Britanin in gastrointestinal tumors. It also outlines novel research directions using data not directly concerned with the digestive system, but which could be adopted in future gastrointestinal research. Britanin was found to counteract liver, colorectal, pancreatic, and gastric tumors, by regulating proliferation, apoptosis, autophagy, immune response, migration, and angiogenesis. As confirmed in pancreatic, gastric, and liver cancer, its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation, as well as Bcl-2-associated X protein upregulation. Moreover, it has been found to induce the Akt kinase and Forkhead box O1 axis, activate the AMP-activated protein kinase pathway, elevate interleukin-2 and peroxisome proliferator-activated receptor-γ levels, reduce interleukin-10, as well as downregulate matrix metalloproteinase-9, Twist family bHLH transcription factor 1, and cyclooxygenase-2. It also inhibits Myc-HIF1α interaction and programmed death ligand 1 transcription by interrupting the Ras/ RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling. Future research should aim to unravel the link between Britanin and acetylcholinesterase, mast cells, osteolysis, and ischemia, as compelling data have been provided by studies outside the gastrointestinal context. Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells, while still being effective against the latter, further in-depth studies with the use of animal models are merited. The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent, which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Clinical significance of tumor deposits in gastric cancer after radical gastrectomy: a propensity score matching study.

OBJECTIVE: The value of tumor deposits (TDs) in the prognosis and staging of gastric cancer (GC) is still under debate. This study aims to evaluate the prognostic value of TDs and the best ways to incorporate TDs in the TNM classification of GC. METHODS: Patients (n = 3460) undergoing curative gastrectomy for GC in the West China Hospital from 2005 to 2017 were retrospectively reviewed and divided into two groups according to the TD status (positive vs. negative). Later, clinicopathological features and overall survival (OS) between the two groups were compared. Thereafter, the associations between the presence of TD and other clinicopathological factors were evaluated through logistic regression. In addition, univariate and multivariate Cox regression were conducted for determining prognostic factors. The possibility of selection bias was reduced through conducting the 1:1 propensity score matching (PSM) analysis. The modified classification systems proposed previously that incorporated TDs into the TNM staging system were assessed. RESULTS: There were 10.5% of patients (362/3460) diagnosed with TDs. TDs were significantly related to unfavorable factors such as advanced T stage and N stage and independently associated with poor prognosis. The 5-year OS of patients with TDs was significantly lower than that of patients without TDs (31.0% vs. 60.9%, P < 0.001), whereas higher than that of patients with peritoneal metastasis (31.0% vs. 5.0%, P < 0.001). In patients receiving chemotherapy, the 5-year OS of patients with TDs was also significantly lower than that of patients without TDs (42.0% vs. 50.9%, P = 0.026). Moreover, the system incorporating TDs in the TNM classification as metastatic lymph nodes outperformed others. CONCLUSIONS: TDs are related to the aggressive characteristics and are an independent prognostic factor for GC. Incorporating TDs in the TNM classification as the metastatic lymph nodes increases the accuracy in predicting prognosis.

Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug-tolerant state without genetic variations. These drug-tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy-resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC-targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.

Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.

The transcription factor family activator protein 2 (TFAP2) is vital for regulating both embryonic and oncogenic development. The TFAP2 family consists of five DNA-binding proteins, including TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E. The importance of TFAP2 in tumor biology is becoming more widely recognized. While TFAP2D is not well studied, here, we mainly focus on the other four TFAP2 members. As a transcription factor, TFAP2 regulates the downstream targets directly by binding to their regulatory region. In addition, the regulation of downstream targets by epigenetic modification, posttranslational regulation, and interaction with noncoding RNA have also been identified. According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response. Moreover, the factors that affect TFAP2 expression in oncogenesis are also summarized. Here, we review and discuss the most recent studies on TFAP2 and its effects on carcinogenesis and regulatory mechanisms.

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications.

In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

Comparison of long-term quality of life between Billroth-I and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: a randomized controlled trial.

BACKGROUND: The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer. METHODS: A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group ( N  = 70) and R-Y group ( N  = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL score was the primary outcome. An intention-to-treat analysis was applied. RESULTS: The baseline characteristics were comparable between the two groups. There were no statistically significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no statistically significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P  = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P  = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistically significant differences (postoperative 1 year: 85.4 ±â€Š13.1 vs . 88.8 ±â€Š16.1, P  = 0.033; postoperative 3 year: 87.3 ±â€Š15.2 vs . 92.8 ±â€Š11.3, P  = 0.028; postoperative 5 year: 90.9 ±â€Š13.7 vs . 96.4 ±â€Š5.6, P  = 0.010), and the reflux (postoperative 3 year: 8.8 ±â€Š12.9 vs . 2.8 ±â€Š5.3, P  = 0.001; postoperative 5 year: 5.1 ±â€Š9.8 vs . 1.8 ±â€Š4.7, P  = 0.033) and epigastric pain (postoperative 1 year: 11.8 ±â€Š12.7 vs. 6.1 ±â€Š8.8, P  = 0.008; postoperative 3 year: 9.4 ±â€Š10.6 vs. 4.6 ±â€Š7.9, P  = 0.006; postoperative 5 year: 6.0 ±â€Š8.9 vs . 2.7 ±â€Š4.6, P  = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points. CONCLUSIONS: Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR-TRC-10001434.

Is No. 12a Lymph Node Dissection Compliance Necessary in Patients Who Undergo D2 Gastrectomy for Gastric Adenocarcinomas? A Population-Based Retrospective Propensity Score Matching Study.

LN dissection is essential for accurately staging and improving GC patient prognosis. However, the compliance rate for No. 12a LND in practice is low, and its necessity is controversial. Data from GC patients who underwent total gastrectomy (TG)/distal gastrectomy (DG) plus D2 lymphadenectomy between January 2000 and December 2017 at West China Hospital, Sichuan University were reviewed. No. 12a LND noncompliance's effect on the long-term prognosis of patients with GC after D2 gastrectomy was explored. Of the 2788 patients included, No. 12a LND noncompliance occurred in 1753 patients (62.9%). Among 1035 patients with assessable LNs from station 12a, 98 (9.5%) had positive LNs detected at station 12a. No. 12a LN metastasis patients (stage IV not included) had significantly better overall survival (OS) than TNM stage IV patients (p = 0.006). Patients with No. 12a LND compliance had a significantly higher OS than those without, both before (p < 0.001) and after (p < 0.001) PSM. Cox multivariate analysis confirmed that No. 12a LND noncompliance was an independent prognostic factor before (HR 1.323, 95% CI 1.171-1.496, p < 0.001) and after (HR 1.353, 95% CI 1.173-1.560, p < 0.001) PSM. In conclusion, noncompliance with No. 12a LND compromised the long-term survival of patients who underwent D2 gastrectomy for GC.

AP-2δ Is the Most Relevant Target of AP-2 Family-Focused Cancer Therapy and Affects Genome Organization.

Formerly hailed as "undruggable" proteins, transcription factors (TFs) are now under investigation for targeted therapy. In cancer, this may alter, inter alia, immune evasion or replicative immortality, which are implicated in genome organization, a process that accompanies multi-step tumorigenesis and which frequently develops in a non-random manner. Still, targeting-related research on some TFs is scarce, e.g., among AP-2 proteins, which are known for their altered functionality in cancer and prognostic importance. Using public repositories, bioinformatics tools, and RNA-seq data, the present study examined the ligandability of all AP-2 members, selecting the best one, which was investigated in terms of mutations, targets, co-activators, correlated genes, and impact on genome organization. AP-2 proteins were found to have the conserved "TF_AP-2" domain, but manifested different binding characteristics and evolution. Among them, AP-2δ has not only the highest number of post-translational modifications and extended strands but also contains a specific histidine-rich region and cleft that can receive a ligand. Uterine, colon, lung, and stomach tumors are most susceptible to AP-2δ mutations, which also co-depend with cancer hallmark genes and drug targets. Considering AP-2δ targets, some of them were located proximally in the spatial genome or served as co-factors of the genes regulated by AP-2δ. Correlation and functional analyses suggested that AP-2δ affects various processes, including genome organization, via its targets; this has been eventually verified in lung adenocarcinoma using expression and immunohistochemistry data of chromosomal conformation-related genes. In conclusion, AP-2δ affects chromosomal conformation and is the most appropriate target for cancer therapy focused on the AP-2 family.

Dissecting the genetic and microenvironmental factors of gastric tumorigenesis in mice.

Gastric cancer (GC) is one of the most frequent and lethal malignancies in the world. However, our understanding of the mechanisms underlying its initiation and progression is limited. Here, we generate a series of primary GC models in mice with genome-edited gastric organoids, which elucidate the genetic drivers for sequential transformation from dysplasia to well-differentiated and poorly differentiated GC. Further, we find that the orthotopic GC, but not the subcutaneous GC even with the same genetic drivers, display remote metastasis, suggesting critical roles of the microenvironment in GC metastasis. Through single-cell RNA-seq analyses and functional studies, we show that the interaction between fibronectin 1 on stomach-specific macrophages and integrin a6ß4 on GC cells promotes remote metastases. Taken together, our studies propose a strategy to model GC and dissect the genetic and microenvironmental factors driving the full-range gastric tumorigenesis.

The Safety and Feasibility of Laparoscopic Gastrectomy after Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

Background: Neoadjuvant chemotherapy is incrementally applied to remedy locally advanced gastric cancer. However, NACT also enhances the difficulty of laparoscopic lymph node dissection. The objective of our study was to evaluate the safety and feasibility of laparoscopic gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy. Methods: From July 2017 to December 2019, 153 patients who received neoadjuvant chemotherapy and underwent the subsequent surgical procedure were retrospectively enrolled and analyzed in the Gastrointestinal Surgery Department of West China Hospital. According to surgical methods, all the patients were sectionalized into two groups: laparoscopic assistant gastrectomy (LAG, 77 patients) and traditional open gastrectomy (OG, 76 patients). The demographic parameters, preoperative, surgical, pathological, and neoadjuvant chemotherapy features were compared between the two groups. Results: A total of 153 patients accepted neoadjuvant chemotherapy and surgical resection in our study. There was no statistically significant difference in demographic parameters and preoperative and neoadjuvant chemotherapy characteristics between the two groups. The LAG group illustrated less intraoperative blood loss (91.1 ± 53.1 ml vs. 125.7 ± 116.9 ml, p=0.010) and shorter postoperative hospital stays (7.9 ± 2.1 days vs. 125.7 ± 116.9 days, p=0.009), when compared to the OG group. Moreover, there was no disparity with respect to operative duration, number of harvested lymph nodes, and postoperative complication rates between the two groups. When considering the Clavien-Dindo classification, no statistically significant difference was indicated in all stratifications with regard to postoperative complications. Conclusion: Laparoscopic gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy is safe and feasible without increasing postoperative adverse events.

Impact of background music on the performance of laparoscopy teams.

BACKGROUND: Acoustic conditions in the operating room have different impacts on surgeon's performance. Their effects on the performance of surgical teams are not well documented. We investigated if laparoscopic teams operating under pleasant acoustic conditions would perform better than under noisy conditions. METHODS: We recruited 114 surgical residents and built 57 two-person teams. Each team was required to perform two laparoscopic tasks (object transportation and collaborative suturing) on a simulation training box under music, neutral, and noisy acoustic conditions. Data were extracted from video recordings of each performance for analysis. Task performance was measured by the duration of time to complete a task and the total number of errors, and objective performance scores. The measures were compared over the three acoustic conditions. RESULTS: A music environment elicited higher performance scores than a noisy environment for both the object transportation (performance score: 66.3 ± 8.6 vs. 57.6 ± 11.2; p < 0.001) and collaborative suturing tasks (78.6 ± 5.4 vs. 67.2 ± 11.1; p < 0.001). Task times in the music and noisy environments was subtracted to produce a music-noisy difference time. Pearson correlation coefficient analysis showed a significant negative relationship between the team experience score and the music-noisy difference time on the object transportation (r = - 0.246, p = 0.046) and collaborative suturing tasks (r = - 0.248, p = 0.044). CONCLUSIONS: As to individuals, music enhances the performance of a laparoscopy team while a noisy environment worsens performance. The negative correlation between team experience and music-noisy difference time suggests that laparoscopy teams composed of experienced surgeons are less likely affected by an acoustic distraction than the noisy teams. Team resistance to acoustic distraction may lead to a new way for assessing team skills.

Assessment of indocyanine green fluorescence lymphography on lymphadenectomy during minimally invasive gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443. RESULTS: A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I2 = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I2 = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54). CONCLUSION: The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue.

Clinical significance of lower perigastric lymph nodes dissection in Siewert type II/III adenocarcinoma of esophagogastric junction: a retrospective propensity score matched study.

PURPOSE: The optimal surgical procedure, whether total gastrectomy (TG) or proximal gastrectomy (PG), for Siewert type II/III adenocarcinoma of esophagogastric junction (AEG) has not been standardised, primarily because the optimal extent of lymph node (LN) dissection for AEG based on the metastatic rate of perigastric LNs remains under debate. The aim of this study was to investigate the metastatic incidence and prognostic significance of lower perigastric lymph nodes (LPLN), including No.4d, 5, 6 and 12a LN stations, in Siewert type II/III AEG. METHODS: A total of 701 patients with Siewert type II/III AEG who received transabdominal open gastrectomy (425 patients with TG and 276 patients with PG) from 2010 to 2015 in West China Hospital were retrospectively included. Based on the clinicopathological information of TG patients, the risk factors of LPLN-positive patients were evaluated, and the metastatic incidence as well as the therapeutic value (TV) index of each LN station was assessed. Moreover, the 5-year overall survival (OS) rates between LPLN-positive and LPLN-negative groups were compared in TG patients, and the postoperative survival difference between TG and PG patients was also compared, using propensity score matching (PSM) method. RESULTS: Tumour size (≥ 5 cm, OR = 1.481, p = 0.002) and pT stage (pT4, OR = 2.755, p = 0.024) were significant risk factors for patients with LPLN metastasis. For patients with tumour size more than 5 cm or pT4 stage, the metastatic rates of LPLN for Siewert type II, III and II/III AEG were 31.67%, 34.69% and 33.03%, whereas the TV indexes of LPLN for them were 5.76, 5.62 and 5.38, respectively. LPLN was a significant independent prognostic factor (HR = 1.422, p = 0.028), and positive LPLN was related to worse prognosis (p < 0.05). For patients with tumour size more than 5 cm or pT4 stage, TG patients were illustrated to have a better prognosis than PG patients, with 5-year OS rates of 58.9% vs 38.2% for Siewert type II AEG (χ2 = 4.159, p = 0.041), 68.9% vs 50.2% for Siewert type III AEG (χ2 = 5.630, p = 0.018) and 65.1% vs 40.3% for Siewert type II/III AEG (χ2 = 12.604, p < 0.001), respectively. CONCLUSIONS: LPLN metastasis is a poor prognostic factor for patients with Siewert II/III AEG. LPLN dissection may improve the long-term survival of patients with tumour size more than 5 cm or pT4 stage, and TG might be more suitable for this kind of cancer.

Impact of Type of Postoperative Complications on Long-Term Survival of Gastric Cancer Patients: Results From a High-Volume Institution in China.

BACKGROUND: This study aimed to evaluate the impact of postoperative complication and its etiology on long-term survival for gastric cancer (GC) patients with curative resection. METHODS: From January 2009 to December 2014, a total of 1,667 GC patients who had undergone curative gastrectomy were analyzed. Patients with severe complications (SCs) (Clavien-Dindo grade III or higher complications or those causing a hospital stay of 15 days or longer) were separated into a "complication group." Univariate and multivariate analyses were performed to reveal the relationship between postoperative complications and long-term survival. A 2:1 propensity score matching (PSM) was used to balance baseline parameters between the two groups. RESULTS: SCs were diagnosed in 168 (10.08%) patients, including different etiology: infectious complications (ICs) in 111 (6.66%) and non-infectious complications (NICs) in 71 (4.26%) patients. Multivariate analysis showed that presence of SCs (P=0.001) was an independent prognostic factor for overall survival, and further analysis by complication type demonstrated that the deteriorated overall survival was mainly caused by ICs (P=0.004) rather than NICs (P=0.068). After PSM, patients with SCs (p=0.002) still had a significantly decreased overall survival, and the presence of ICs (P=0.002) rather than NICs (P=0.067) showed a negative impact on long-term survival. CONCLUSION: Serious complications, particularly of an infectious type, may have a negative impact on overall survival of GC patients. However, additional multicenter prospective studies with larger sample size are required to verify this issue.