Glioma-derived exosome Lncrna Agap2-As1 promotes glioma proliferation and metastasis by mediating Tgf-ß1 secretion of myeloid-derived suppressor cells.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-ß1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-ß1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-ß1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-ß1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-ß1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

Comparison of manual sutures and laparoscopic stapler for pancreatic stump closure techniques in robotic distal pancreatectomy: a single-center experience.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) are prevalent and major postoperative complications of distal pancreatectomy (DP). There are numerous ways to manage the pancreatic stump. However, no single approach has been shown to be consistently superior. Moreover, the potential role of robotic systems in reducing POPFs has received little attention. METHODS: The clinical data of 119 patients who had consecutively received robotic distal pancreatectomy between January 2019 and December 2022 were retrospectively analyzed. Patients were divided into two groups according to the method of handling the pancreatic stump. The attributes of the patients and the variables during the perioperative period were compared. RESULTS: The analysis included 72 manual sutures and 47 stapler procedures. The manual suture group had a shorter operative time (removing installation time) than the stapler group (125.25 ± 63.04 min vs 153.30 ± 62.03 min, p = 0.019). Additionally, the manual suture group had lower estimated blood loss (50 mL vs 100 mL, p = 0.009) and a shorter postoperative hospital stay. There were no significant differences in the incidence of clinically relevant POPFs between the two groups (18.1% vs 23.4%, P > 0.05). No perioperative death occurred in either group. CONCLUSION: The manual suturing technique was shown to have an incidence of POPFs similar to the stapler technique in robotic distal pancreatectomy and to be safe and feasible.

SLC11A2: a promising biomarker and therapeutic target in ovarian cancer.

Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC-MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.

Dualistic classification of high grade serous ovarian carcinoma has its root in spatial heterogeneity.

INTRODUCTION: Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC. OBJECTIVES: We performed whole-exome sequencing in multiple regions of matched primary and metastatic HGSOC specimens to reveal the genetic mechanisms of ovarian tumourigenesis and malignant progression. METHODS: 63 samples (including ovarian carcinoma, omentum metastasis, and normal tissues) were used. We analyzed the genomic heterogeneity, traced the subclone dissemination and establishment history and compared the different genetic characters of cancer evolutionary models in HGSOC. RESULTS: We found that HGSOC had substantial intra-tumour heterogeneity (median 54.2, range 0 âˆ¼ 106.7), high inter-patient heterogeneity (P < 0.001), but relatively limited intra-patient heterogeneity (P = 0.949). Two COSMIC mutational signatures were identified in HGSOCs: signature 3 was related to homologous recombination, and signature 1 was associated with aging. Two scenarios were identified by phylogenetic reconstruction in our study: 3 cases (33.3 %) showed star topology, and the other 6 cases (66.7 %) displayed tree topology. Compared with star topology group, more driver events were identified in tree topology group (P < 0.001), and occurred more frequently in early stage than in late stage of clonal evolution (P < 0.001). Moreover, compared with the star topology group, the tree topology group showed higher rate of intra-tumour heterogeneity (P = 0.045). CONCLUSION: A dualistic classification model was proposed for the classification of HGSOC based on spatial heterogeneity, which may contribute to better managing patients and providing individual treatment for HGSOC patients.

Protein Panel of Serum-Derived Small Extracellular Vesicles for the Screening and Diagnosis of Epithelial Ovarian Cancer.

Although ovarian cancer, a gynecological malignancy, has the highest fatality rate, it still lacks highly specific biomarkers, and the differential diagnosis of ovarian masses remains difficult to determine for gynecologists. Our study aimed to obtain ovarian cancer-specific protein candidates from the circulating small extracellular vesicles (sEVs) and develop a protein panel for ovarian cancer screening and differential diagnosis of ovarian masses. In our study, sEVs derived from the serum of healthy controls and patients with cystadenoma and ovarian cancer were investigated to obtain a cancer-specific proteomic profile. In a discovery cohort, 1119 proteins were identified, and significant differences in the protein profiles of EVs were observed among groups. Then, 23 differentially expressed proteins were assessed using the parallel reaction monitoring in a validation cohort. Through univariate and multivariate logistic regression analyses, a novel model comprising three proteins (fibrinogen gamma gene (FGG), mucin 16 (MUC16), and apolipoprotein (APOA4)) was established to screen patients with ovarian cancer. This model exhibited an area under the receiver operating characteristic curve (AUC) of 0.936 (95% CI, 0.888-0.984) with 92.0% sensitivity and 82.9% specificity. Another panel comprising serum CA125, sEV-APOA4, and sEV-CD5L showed excellent performance (AUC 0.945 (95% CI, 0.890-1.000), sensitivity of 88.0%, specificity of 93.3%, and accuracy of 89.2%) to distinguish malignancy from benign ovarian masses. Altogether, our study provided a proteomic signature of circulating sEVs in ovarian cancer. The diagnostic proteomic panel may complement current clinical diagnostic measures for screening ovarian cancer in the general population and the differential diagnosis of ovarian masses.

Spontaneous healing after conservative treatment of isolated grade IV pancreatic duct disruption caused by trauma: A case report.

BACKGROUND: Trauma is a common cause of pancreatic duct disruption. Surgical treatment is recommended in current clinical guidelines for adult pancreatic injury because non-surgical treatments have higher risks of serious complications or even death compared with surgical treatment. CASE SUMMARY: A 22-year-old woman was admitted to Tiantai People's Hospital of Zhejiang Province after 1-h duration of abdominal pain and distension following trauma. The diagnosis was "traumatic pancreatic rupture". The patient's symptoms were not severe, her vital signs were stable, and signs of peritonitis were not obvious. Therefore, conservative treatment could be considered, with the possibility of emergency surgery if necessary. After 2 mo of conservative treatment with duct drainage, the pancreatic duct healed spontaneously with no significant complications. CONCLUSION: We report a case of pancreatic duct disruption in the head and neck caused by trauma that was treated conservatively and healed spontaneously, providing a new choice for clinical practice. For isolated pancreatic injury with rupture of the pancreatic duct in the head and neck, conservative treatment under close observation is feasible.

Clinical effect of trans-areolar resection and minimally invasive mammotome biopsy in the treatment of breast fibroadenoma and its impact on the quality of life of patients.

OBJECTIVE: To explore the effects of trans-areolar resection and minimally invasive mammotome biopsy on therapeutic effect. METHODS: A total of 131 patients with breast fibroadenoma were selected as the research subjects. Among them, 58 patients were treated by trans-areolar resection and included in group A (GA), and 73 patients were treated by minimally invasive mammotome biopsy and included in group B (GB). The changes of blood pressure, intraoperative blood loss and incision length in patients were detected before anesthesia, during resection and after operation. The pain score and operation time of patients were analyzed. The incidence of postoperative complications and the therapeutic effect were compared in the two groups. The Vancouver Scar Scale (VSS) was used to assess scar condition of patients in the two groups, and the lower the score, the more normal the skin. After operation, the satisfaction with breast appearance was assessed, and the quality of life was compared between the two groups. RESULTS: During resection, DBP and SBP indexes of blood pressure in GA were lower than GB . The intraoperative blood loss in GA was greater than GB, and the incision length was also greater than GB. The VAS pain score in GA was higher than GB (P<0.05), and operation time was also longer than GB. The incidence of complications in GB was significantly lower than GA. The total effective rate in GB was significantly higher than GA. The scar score in GA was significantly higher than GB. The satisfaction in GB was significantly higher than GA, and the quality of life in GB was higher than GA. All P<0.05. CONCLUSION: Compared with trans-areolar resection, minimally invasive mammotome biopsy has a better therapeutic effect on patients with breast fibroadenoma, and it can improve their quality of life more significantly.

Clinicopathological Significance and Molecular Mechanism of AKT/GSK3ß Pathway-based Fibrillin-1 Expression in Gastric Cancer Progression.

This research was developed to explore the significance of fibrillin-1 (FBN1) in the progression of gastric cancer and its relationship with the activation of the AKT/glycogen synthase kinase-3beta (GSK3ß) pathway. For this aim, immunohistochemical assays were adopted to detect FBN1 expression in chronic superficial gastritis, chronic atrophic gastritis, gastric cancer, and normal mucosa. The expression of FBN1 in gastric cancer and adjacent tissue samples was detected by reverse transcription-quantitative (RT-q) PCR and Western blot, and the relationship between FBN1 and the clinicopathological features of gastric cancer patients was analyzed. Lentivirus was utilized to construct SGC-7901 gastric cancer cell lines stably overexpressing and silencing FBN1, and the effects on cell proliferation, colony formation, and apoptosis were analyzed. AKT, GSK3ß, and their phosphorylated proteins were detected by Western blot. Results showed that the positive expression rate of FBN1 increased successively in chronic superficial gastritis, chronic atrophic gastritis, and gastric cancer. FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of tumor invasion. Overexpression of FBN1 promoted the proliferation and colony formation of gastric cancer cells, inhibited apoptosis, and promoted the phosphorylation of AKT and GSK3ß. Silencing FBN1 expression inhibited the proliferation and clonal formation of gastric cancer cells, promoted apoptosis, and inhibited the phosphorylation of AKT and GSK3ß. In conclusion, FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of gastric tumor invasion. FBN1 silencing inhibited the progression of gastric cancer through the AKT/GSK3ß pathway.

A Genotype Signature for Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer.

PURPOSE: To construct and validate a predicting genotype signature for pathologic complete response (pCR) in locally advanced rectal cancer (PGS-LARC) after neoadjuvant chemoradiation. METHODS AND MATERIALS: Whole exome sequencing was performed in 15 LARC tissues. Mutation sites were selected according to the whole exome sequencing data and literature. Target sequencing was performed in a training cohort (n = 202) to build the PGS-LARC model using regression analysis, and internal (n = 76) and external validation cohorts (n = 69) were used for validating the results. Predictive performance of the PGS-LARC model was compared with clinical factors and between subgroups. The PGS-LARC model comprised 15 genes. RESULTS: The area under the curve (AUC) of the PGS model in the training, internal, and external validation cohorts was 0.776 (0.697-0.849), 0.760 (0.644-0.867), and 0.812 (0.690-0.915), respectively, and demonstrated higher AUC, accuracy, sensitivity, and specificity than cT stage, cN stage, carcinoembryonic antigen level, and CA19-9 level for pCR prediction. The predictive performance of the model was superior to clinical factors in all subgroups. For patients with clinical complete response (cCR), the positive prediction value was 94.7%. CONCLUSIONS: The PGS-LARC is a reliable predictive tool for pCR in patients with LARC and might be helpful to enable nonoperative management strategy in those patients who refuse surgery. It has the potential to guide treatment decisions for patients with different probability of tumor regression after neoadjuvant therapy, especially when combining cCR criteria and PGS-LARC.

Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Patients With Stage IIB-IVA Cervical Cancer: A Randomized Phase III Trial.

BACKGROUND: In this trial, we aimed to assess the efficacy and safety of radiotherapy with nedaplatin or cisplatin in patients with locally advanced cervical cancer. METHODS: We conducted an open-label, non-inferiority, phase III, randomized, controlled trial. Eligible patients with stage IIB-IVA cervical carcinoma were randomly assigned to receive either nedaplatin or cisplatin for two cycles concurrently with radiotherapy. We reported the therapy-associated harms and survival. The study was registered with chictr.org.cn, number ChiCTR1800020527. RESULTS: We randomly assigned 68 patients to nedaplatin-based or cisplatin-based concurrent chemoradiotherapy. Study treatment was stopped early after a data analysis found a higher number of patients suffered severe hematologic harms in the nedaplatin group than in the cisplatin group. Patients in the nedaplatin group had a significantly higher frequency of grade 3-4 neutropenia (19·4% vs. 13%; P < 0·001), severe thrombocytopenia (16·1% vs. 4·3%), and grade 1-2 anemia (51·6% vs. 43·5%) than patients in the cisplatin group. The 1-year PFS and OS in the nedaplatin and cisplatin groups were similar. CONCLUSION: Our findings showed that nedaplatin-based concurrent chemoradiotherapy expressed remarkably higher severe hematologic harms which were mortal. Though the results were negative, the experiences and lessons we learned from it were important.

Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China.

BACKGROUND: The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC. METHODS: We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018. RESULTS: A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0-61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10-8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12-7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02-20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07-8.74, p = 0.038) predicted overall survival (OS). CONCLUSIONS: T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression.

BACKGROUND: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. RESULTS: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. CONCLUSIONS: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

Long-Term Survival and Prognostic Factors in Locoregionally Advanced Nasopharyngeal Carcinoma Patients Treated with TPF Induction Chemotherapy followed by Cisplatin-Combined Concurrent Chemoradiotherapy.

Purpose: The objective of this study was to report long-term results of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and identify prognostic factors for this group of patients. Materials and Methods: From December 2010 to January 2015, 109 patients with locoregionally advanced (III-IVB) NPC were included. Patients were scheduled to complete TPF induction chemotherapy followed by cisplatin based CCRT. Failure-free survival (FFS), overall survival (OS), locoregional failure-free survival (LRFFS) and distant failure-free survival (DFFS) served as clinical outcomes. Kaplan-Meier method, Cox proportional hazards model and receiver operating characteristic (ROC) curves were used for analyzing. Results: With a median follow-up of 60.2 months (range, 7.9-91.6 months), 3-year FFS, OS, LRFFS, and DFFS were 76.8%, 85.1%, 88.3%, and 84.1%, respectively. The highest incidence rate of recurrence and metastasis were in the first year after treatment. Multivariate analyses showed that age, total time of radiation therapy (RTT), and total time of therapy (TTT) were independent prognostic factors for FFS and OS. Body mass index (BMI), RTT and TTT were significant variables predicting DFFS. TTT was the only independent prognostic factor for LRFFS. Conclusion: This study indicated that TPF regimen produced encouraging results in Asian patients with locoregionally advanced nasopharyngeal carcinoma. Toxicity was tolerable and reversible. However, overall treatment time is an important factor that we should take into consideration when make plans of induction chemotherapy related treatment.

Development and external validation of a nomogram for predicting the overall survival of patients with stage II nasopharyngeal carcinoma after curative treatment.

Objective: To facilitate decision-making support for individual patients, development and external validation of a nomogram was undertaken to reveal prognostic factors and predict the value of concurrent chemoradiotherapy (CCRT) compared with radiotherapy (RT) for stage-II nasopharyngeal carcinoma (NPC) patients. Methods: Clinical data of 419 and 309 patients with American Joint Committee on Cancer (2017) stage-II NPC in two institutions in China were collected retrospectively. Overall survival (OS) and progression-free survival were compared using Kaplan-Meier estimates. Cox regression analysis was used to identify the prognostic factors for building the nomogram. Predictive accuracy and discriminative ability were measured using the Concordance Index. Results: Finally, there were 24 and 20 deaths in the development and validation group, respectively. Patients with stage T2N1, N1 stage, involvement of retropharyngeal and unilateral cervical lymph nodes, and who had RT alone had worse OS (P=0.019, 0.035, 0.003 and 0.010, respectively; log-rank test) than patients with stage T1N1 and T2N0, N0 stage, involvement of retropharyngeal or unilateral cervical lymph nodes, and CCRT, respectively. After multivariate analysis of the training set, age, neutrophil-to-lymphocyte ratio, therapy type, and pretreatment plasma concentration of Epstein-Barr virus DNA were independent prognostic factors of OS. A nomogram was established externally by involving all the factors stated above. The Concordance Index for the established nomogram to predict the OS of the training set was 0.793 (95% CI 0.689-0.897), and 0.803 (95% CI 0.696-0.910) in the validation set. Conclusion: These data suggest that the nomogram was validated externally, could predict long-term outcome accurately, and enable accurate stratification of risk groups for stage-II NPC. Our model facilitated individualized care of NPC patients.

Does Lymphadenectomy with at Least 15 Perigastric Lymph Nodes Retrieval Promise an Improved Survival for Gastric Cancer: A Retrospective Cohort Study in Southern China.

Background: Specific guidelines recommend at least 15 or 16 lymph nodes (LNs) be examined to adequately assess nodal category of gastric cancer (GC), but the requirement for minimum number of regional LNs retrieval is not mentioned. This study aims to investigate survival significance from various numbers of perigastric (N1) LNs retrieval and to determine an optimal number harvested in such region. Study design: From April 1994 to March 2012, 1003 resectable GC patients with at least 15 LNs examined were included. Patients with at least 15 N1 nodes retrieval were assigned into study group, with the rest into control group. The 5-year overall survival (OS) rate was compared between two groups, and an optimal number of examined N1 nodes was detected by a survival joinpoint analysis. Results: 635 (63.3%) patients in study group had median 22 (range, 15-75) N1 nodes and 3 (range, 0-74) positive N1 nodes retrieval, with median 10 (range, 0-14) N1 nodes and 1 (range, 0-29) metastatic N1 nodes examined in control group. The number of N1 nodes retrieval was associated with tumor location (P=0.007), tumor stage (P<0.001) and total number of harvested LNs ( r =0.691, P<0.001). Median survival time (79.0 vs. 72.0 months, P=0.462) and actual 5-year OS rate (41.0% vs. 39.2%, P=0.463) were slightly improved in study group compared with control group, with significance obtained via stage-by-stage analysis. The joinpoint analysis indicated that at least seven N1 nodes retrieval achieved survival significance (81.0 vs. 35.0 months, P=0.036), with survival superiority remained until reaching up to 15 N1 nodes. Conclusion: Adequate retrieval of perigastric LNs is essential for radical gastrectomy. A harvest of at least 7-15 perigastric LNs could achieve long-term survival benefit for GC patients.

Effect of CRP and Kinetics of CRP in Prognosis of Nasopharyngeal Carcinoma.

Baseline C-reactive protein (CRP) has been determined as a prognostic factor in nasopharyngeal carcinoma (NPC). This study was designed to further evaluate the impact of CRP kinetics on NPC patients. Thousand three hundred and seventy eight NPC patients from February 2001 to June 2011 were retrospectively reviewed. CRP were measured at beginning, middle, and the end of the treatment. The endpoints were overall survival (OS) and distant metastasis free survival (DMFS). Patients were divided into three groups according to baseline CRP and CRP kinetics: (1) continuously normal group: patients whose baseline CRP normal and never elevated, (2) ever-elevated group: patients whose CRP ever elevated regardless time points, (3) continuously elevated group: patients whose baseline CRP elevated and never normalized. Baseline CRP, CRP after treatment, and CRP kinetics were correlated with TNM stage, T stage, and N stage. Univariate and multivariate analysis identified that elevated baseline CRP and CRP after treatment had significant association with worse survival than normal CRP. Oppositely, elevated CRP during treatment was not associated with survival. Patients with continuously elevated CRP significantly had poor OS and DMFS (HR:2.610, 95%CI: 1.592-4.279, p < 0.001; HR:2.816, 95%CI: 1.486-5.302, p = 0.001, respectively). In multivariate analysis, CRP kinetics assessment is an independent prognostic factor for OS and DFMS in NPC patients (HR:2.512, 95%CI: 1.452-4.346, p = 0.001; HR:3.389, 95%CI: 1.734-6.625, p = 0.001, respectively). In conclusion, elevated CRP at baseline and after treatment are predictive factors of poor prognosis for NPC. The study of CRP kinetics shows that continuously elevated CRP during treatment might indicate an unfavorable prognosis for NPC.

Intracellular activation of complement C3 in Paneth cells improves repair of intestinal epithelia during acute injury.

AIM: To explore whether Paneth cells (PCs) and complement system collaborate in the repair of enteric epithelia during acute gastrointestinal injury (AGI). METHODS: Wild-type C57BL/6 mice were employed to induce AGI by performing colon ascendens stent surgery, with sham-operated as control. Exogenous C3 treatment was applied at 6-h postsurgery. After 48 h, overall survival, intestinal damage severity, and C3 intracellular activation were assessed in both epithelial cells and PCs. RESULTS: AGI caused a high mortality, while C3 therapy significantly attenuated epithelial damages and improved survival. Besides, exogenous C3 in vitro enhanced the proliferation and activity of PCs. Importantly, intracellular C3 activation was observed inside of PCs under C3 co-stimulation in vitro. CONCLUSION: C3 immunotherapy might play a valuable role in turnover of gut epithelia through intracellular activation in PCs.

Nephrotoxicity and long-term survival investigations for patients with peritoneal carcinomatosis using hyperthermic intraperitoneal chemotherapy with cisplatin: A retrospective cohort study.

BACKGROUND & PURPOSE: Cytoreductive surgery (CRS) plus Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for peritoneal carcinomatosis. The cisplatin (CP) applied in HIPEC carries a risk of kidney injury. This study aims to investigate CP-induced nephrotoxicity post HIPEC and to explore its risk factors. METHODS: From January 2012 to July 2013, 99 patients undergoing CRS + HIPEC were retrospectively reviewed. Patients were divided into CP and Non-CP HIPEC groups. The RIFLE classification was used to assess the severity of acute kidney injury (AKI). Renal and hepatic function, concentrations of tumor markers, and postoperative outcomes were compared between groups. RESULTS: 47 (47.5%) patients were in the CP HIPEC group, with 52 (52.5%) patients in the Non-CP HIPEC group. 11 (11.1%) patients developed AKI, with 10 of them from the CP HIPEC group. Two patients with CP-contained HIPEC developed acute renal failure. Plasma levels of both urea nitrogen and creatinine were significantly increased in the CP HIPEC group compared with the Non-CP HIPEC group (P < 0.01). However, postoperative pain (scaled score, 4.2 vs. 3.8; P = 0.279), length of hospital stay (18.1 vs. 20.2 days; P = 0.285), hospital costs ($1 3182 vs. $12 640; P = 0.465) and incidence of postoperative complication (25.5% vs. 17.3%; P = 0.337) were similar in both groups, with comparable 3-year overall survival observed (38.6% vs. 31.8%, P = 0.319). A multivariate analysis indicated that use of CP was an independent risk factor for AKI (P = 0.017, 95% CI: 1.277-4.155). CONCLUSIONS: Application of CP during HIPEC is associated with an increased risk of nephrotoxicity, without promising long-term survival benefit.

The efficiency of electronic list-based multidisciplinary team meetings in management of gastrointestinal malignancy: a single-center experience in Southern China.

BACKGROUND: The multidisciplinary team (MDT) discussion has earned increasing popularity for the delivery of cancer care. However, MDT meeting (MDTM) is time and resource intensive, and some efforts to optimize discussion processes are required. This study aims to investigate the efficiency of electronic list-based MDTM in treatment of gastrointestinal (GI) malignancy. METHODS: Between January 2015 and December 2016, patients with GI cancers were retrospectively reviewed. Patients permitting an MDTM with our novel technique (eMDT group) were compared with those undergoing a traditional discussion (cMDT group). The efficiency of MDT working, including time cost per meeting or case and overall number of reviewed cases, was checked, with accuracy of clinical staging and other outcomes explored meanwhile. RESULTS: Three thousand six hundred seventy-four patients were included, with 2156 (58.7%) and 1518 (41.3%) cases for eMDT and cMDT groups, respectively. Comparisons in age (P = 0.529), gender (P = 0.844), cancer type (P = 0.218), treatment plan (P = 0.737), and pathological stage (P = 0.098) were not significant between groups. However, the average time cost in both each meeting (149.4 vs. 205.1 min; P < 0.001) and each case (3.1 vs. 6.2 min; P < 0.001) was markedly reduced. Besides, this novel technique was associated with improved accuracy of clinical staging (P = 0.070) and reduced hospital stay (P < 0.001) compared with the traditional approach, with similar incidence of complications observed (P = 0.243). CONCLUSIONS: The MDT working based on an intelligent checklist could save considerable time while not affecting treatment of GI malignancies. The improved efficiency also earns an increased capacity of hospital admission and in-patient care.

External validation of a modified 8th AJCC TNM system for advanced gastric cancer: Long-term results in southern China.

BACKGROUND: The 8th edition of AJCC TNM staging manual for gastric cancer (GC) has been validated by several studies. A modified staging system based on it and total harvested number of lymph nodes (LNs; cutoff: 30) is suggested to improve predictive capacities for advanced GC. This study is designed to validate the modified method using a single-center database in Southern China. METHODS: Clinical data from 684 GC patients with stage II and III according to the 7th edition between 2001 and 2012 were reviewed. A modified staging system was applied to restage the cohort. The three staging systems were compared in terms of prognostic performance on long-term survival. RESULTS: The median follow-up period of this cohort was 52 (range, 6-180) months, with a median 5-year overall survival rate of 52.4%. Stage migration was observed in 159 (23.2%) patients according to the 8th edition of TNM staging, and another migration was observed in 108 (15.8%) patients according to the modified TNM staging system. Compared with the modified staging system, both 7th and 8th edition of AJCC TNM staging systems did not prove survival concordance on stage IIIA (7th edition) and stage IIIC (8th edition) when <30 LNs were examined. The survival performance between two AJCC staging systems had no significant improvement (c-index, 0.607 vs. 0.609), with the best prognostic stratification obtained using the modified staging method (c-index, 0.631). CONCLUSIONS: The modified staging system on basis of the 8th AJCC classification and the number of harvested LNs could provide an optimal predictive capacities for advanced gastric cancer.