Intraoperative Diagnosis of Serosal Invasion in Gastric Cancer by Magnifying Endoscopy with Narrow-Band Imaging for Intraoperative Measurement Decision.

Purpose: To establish a precise diagnostic method for serosal invasion in gastric cancer (GC) during surgery using therapeutic measures, and facilitate quick decision-making. Methods: A total of 19 GC patients treated in the department of gastrointestinal surgery of Fujian Provincial Hospital between April 2019 and December 2020 were enrolled. An electronic gastroscopy with a magnifying endoscope with narrow-band imaging was used to photograph the serosal surface of the GC lesion site and the normal gastric wall around the lesion during surgery. The endoscopic diagnosis was confirmed on the basis of the microvascular phenotype of the serosal surface and validated by comparison with the pathological diagnosis. Results: Under the specific endoscopy, serosal invasion, including subserosal tissue invasion and serosal layer invasion, was diagnosed by observing the capillary morphology change, and capillary diameter and density increase. According to the pathological diagnosis, the accuracy of serosal invasion diagnosis was 94.7%, the sensitivity was 100%, the specificity was 75%, the positive predictive value was 93.8%, and the negative predictive value was 100%. To further distinguish the subserosal tissue invasion and serosal layer invasion, the magnifying endoscope with narrow-band imaging possessed a 78.9% accuracy by distinguishing irregular changes in microvessels. Conclusions: Magnifying endoscope with narrow-band imaging is less time-consuming than pathological diagnosis. Intraoperative diagnosis using microvascular observation can accurately detect serosal invasion. It is of value for the intraoperative diagnosis in GC patients.

Paper-based photoelectrochemical immunoassay for ultrasensitive screening of carcinoembryonic antigen on hollow CdS/CdMoO4-functionalized photoanode.

Lab-based testing systems utilizing photoelectrochemical (PEC) biosensing methodologies for the ultrasensitive carcinoembryonic antigen (CEA) have been developed, although the majority have shown complicated operating procedures and dependence on precise apparatus. Herein, a portable photoelectrochemical split diagnostic platform based on a hollow CdS/CdMoO4 (h-CdS@CdMoO4) shell-shell structured photoanode system was developed for ultrasensitive detection of CEA. Using a small LED flashlight as the excitation light source and a digital multimeter (DMM) as the signal readout device, real-time CEA on a paper-based printed screen electrode developed in-house was quickly detected. The composite h-CdS@CdMoO4 featured a special hollow shell-shell heterojunction structure that optimizes photon usage in the bulk phase on the one hand, and facilitates directed separation of the electrons and holes therein on the other. A split-sandwich immunoassay and detection antibodies for modified glucose oxidase were introduced into the paper-based photoanode test system, and the signals were displayed with a DMM to realize a point-of-care test for CEA. Under optimized conditions, the constructed portable PEC sensing system was sensitive to the target CEA from 0.02 to 50.0 ng mL-1 with a detection limit of 11.3 pg mL-1. Interferent experiments and stability test evaluations demonstrate the specificity and robustness of the constructed paper-based portable PEC sensor. The portable, paper-based PEC immunoassay system developed offers a fresh way of exploring affordable, approachable sensors to satisfy both the relevant community medical testing demands and hospital objectives for quick testing.

Ultrasensitive photoelectrochemical biosensing platform based target-triggered biocatalytic precipitation reactions on a flower-like Bi2O2S super-structured photoanode.

Herein, we reported a novel photoelectrochemical immunoassay method based on a target-triggered on/off signal of the ultra-structured Bi2O2S (BOS) photoanode system for the sensitive testing of carcinoembryonic antigens (CEAs) in serum samples. Well-defined three-dimensional sheet-like self-assembled flower-like Bi2O2S superstructures were obtained using a time-controlled hydrothermal method. Such well-shaped multifaceted surfaces were considered to be good laser cavity mirror surfaces for multifaceted reflection and refraction of excitation light in the material. An elegant enzyme biocatalytic strategy was introduced into the constructed detection model to sensitively detect CEAs. The substrate 4-chloro-1-naphthol (4-CN) was oxidized to 4-chloro-hexadienone (4-CD) under the formation of target-triggered immune complexes against mAb1 and peroxidase-modified mAb2. Subsequently, 4-CD produced by the biocatalytic precipitation reaction was transferred to the photoanodes of Bi2O2S nanoflowers (BOS NFs) to burst their photoelectric signals, thus achieving the quantification of CEAs. Through optimization of the conditions of the immunization protocol, a good negative photocurrent response to the target CEA was found in the wide range of 0.02-50 ng mL-1 with a detection limit of 11.2 pg mL-1. Impressively, the reported biocatalytic PEC sensing strategy on superstructures is comparable, or superior, to the gold standard ELISA kit in terms of sensitivity and the target response range. This study presents a target-mediated PEC immunoassay for biocatalytic precipitation based on a self-assembled superstructure of Bi2O2S, providing a fresh scheme for the analysis of disease-related markers.

Prognostic and predictive value of a pathomics signature in gastric cancer.

The current tumour-node-metastasis (TNM) staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer (GC). Pathomics, which is based on the development of digital pathology, is an emerging field that might improve clinical management. Herein, we propose a pathomics signature (PSGC) that is derived from multiple pathomics features of haematoxylin and eosin-stained slides. We find that the PSGC is an independent predictor of prognosis. A nomogram incorporating the PSGC and TNM staging system shows significantly improved accuracy in predicting the prognosis compared to the TNM staging system alone. Moreover, in stage II and III GC patients with a low PSGC (but not in those with a high PSGC), satisfactory chemotherapy benefits are observed. Therefore, the PSGC could serve as a prognostic predictor in patients with GC and might be a potential predictive indicator for decision-making regarding adjuvant chemotherapy.

Low FNDC5/Irisin expression is associated with aggressive phenotypes in gastric cancer.

Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown. Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients. Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients. Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.

Combination of serum CST4 and DR-70 contributes to early diagnosis of colorectal cancer.

BACKGROUND: Early diagnosis is of great significance for the prognosis of colorectal cancer (CRC) patients. Either serum cystatin S (CST4) or DR-70 has been demonstrated to play an important role on the diagnosis for CRC, however, the diagnostic performances of individual and combined detection of serum CST4 and DR-70 for the patients with CRC at early stage have still not been clarified up to now. METHODS: The performances of CST4 and DR-70 were evaluated by ELISA for the early diagnosis of CRC with 288 retrospective serum samples. A training set comprised of 64 patients with early CRC, 64 patients with colorectal benign lesions (CBL), and 64 healthy controls (HC) was used to develop the predictive model for early CRC. And then, data obtained from an independent validation set was applied to evaluate and validate the predictive model. RESULTS: In the training set, the levels of CST4 and DR-70 in early CRC group were significantly higher than that in CBL group/HC group (P < 0.001); serum CST4 presented the AUC of 0.927 for early CRC patients, with 57.8% sensitivity at 95.3% specificity; serum DR-70 presented the AUC of 0.725 for early CRC patients, with 29.7% sensitivity at 95.3% specificity; combination of serum CST4 and DR-70 presented the AUC of 0.941, with 68.8% sensitivity at 93.8% specificity. Additionally, the combination of serum CST4 and DR-70 showed the AUC of 0.940 for early CRC patients, with 71.9 % sensitivity at 89.1% specificity in the validation set. CONCLUSIONS: Both serum CST4 and DR-70 present the diagnostic value for the patients with early CRC, and the combination of CST4 and DR-70 contributes to the further improvement of the early diagnosis for CRC.

Somatic Alteration Characteristics of Early-Onset Gastric Cancer.

Gastric cancer is one of the most common and deadly cancer types worldwide, which brings millions of dollars of economic loss each year. Patients diagnosed with early-onset gastric cancer were reported to have a worse prognosis compared to other gastric cancer patients, while the mechanisms behind such phenomenon are unknown. To identify age-dependent somatic alternations in gastric cancer, next-generation sequencing targeting 425 genes was performed on 1688 gastric tumor tissues and corresponding plasma samples. In our study, the microsatellite instability (MSI) and chromosomal instability score (CIS) values increased along with the age of patients, which indicates that older patients display a less genomic stability pattern. The differences of somatic alternations between young and old groups were compared. Somatic mutations CDH1 and copy number gains of FGFR2 were identified to enrich in the younger gastric cancer patients, which may contribute to the worse prognosis of early-onset gastric cancer patients.

Association of Tumor-Associated Collagen Signature With Prognosis and Adjuvant Chemotherapy Benefits in Patients With Gastric Cancer.

Importance: The current TNM staging system provides limited information for prognosis prediction and adjuvant chemotherapy benefits for patients with gastric cancer (GC). Objective: To develop a tumor-associated collagen signature of GC (TACSGC) in the tumor microenvironment to predict prognosis and adjuvant chemotherapy benefits in patients with GC. Design, Setting, and Participants: This retrospective cohort study included a training cohort of 294 consecutive patients treated between January 1, 2012, and December 31, 2013, from Nanfang Hospital, Southern Medical University, People's Republic of China, and a validation cohort of 225 consecutive patients treated between October 1, 2010, and December 31, 2012, from Fujian Provincial Cancer Hospital, Fujian Medical University, People's Republic of China. In total, 146 collagen features in the tumor microenvironment were extracted with multiphoton imaging. A TACSGC was then constructed using the least absolute shrinkage and selection operator Cox proportional hazards regression model in the training cohort. Data analysis was conducted from October 1, 2020, to April 30, 2021. Main Outcomes and Measures: The association of TACSGC with disease-free survival (DFS) and overall survival (OS) was assessed. An independent external cohort was included to validate the results. Interactions between TACSGC and adjuvant chemotherapy were calculated. Results: This study included 519 patients (median age, 57 years [IQR, 49-65 years]; 360 [69.4%] male). A 9 feature-based TACSGC was built. A higher TACSGC level was significantly associated with worse DFS and OS in both the training (DFS: hazard ratio [HR], 3.57 [95% CI, 2.45-5.20]; OS: HR, 3.54 [95% CI, 2.41-5.20]) and validation (DFS: HR, 3.10 [95% CI, 2.26-4.27]; OS: HR, 3.24 [95% CI, 2.33-4.50]) cohorts (continuous variable, P < .001 for all comparisons). Multivariable analyses found that carbohydrate antigen 19-9, depth of invasion, lymph node metastasis, distant metastasis, and TACSGC were independent prognostic predictors of GC, and 2 integrated nomograms that included the 5 predictors were established for predicting DFS and OS. Compared with clinicopathological models that included only the 4 clinicopathological predictors, the integrated nomograms yielded an improved discrimination for prognosis prediction in a C index comparison (training cohort: DFS, 0.80 [95% CI, 0.73-0.88] vs 0.78 [95% CI, 0.71-0.85], P = .03; OS, 0.81 [95% CI, 0.75-0.88] vs 0.80 [95% CI, 0.73-0.86], P = .03; validation cohort: DFS, 0.78 [95% CI, 0.70-0.87] vs 0.76 [95% CI, 0.67-0.84], P = .006; OS, 0.78 [95% CI, 0.69-0.86] vs 0.75 [95% CI, 0.67-0.84], P = .002). Patients with stage II and III GC and low TACSGC levels rather than high TACSGC levels had a favorable response to adjuvant chemotherapy (DFS: HR, 0.65 [95% CI, 0.43-0.96]; P = .03; OS: HR, 0.55 [95% CI, 0.36-0.82]; P = .004; dichotomized variable, P < .001 for interaction for both comparisons). Conclusions and Relevance: The findings suggest that TACSGC provides additional prognostic information for patients with GC and may distinguish patients with stage II and III disease who are more likely to derive benefits from adjuvant chemotherapy.

Thionine-doped nanometer-sized silica conjugated with phenylboronic acid: An innovative recognition/signal element for voltammetric aptasensing of colorectal cancer-related carcinoembryonic antigen.

This work reports the proof-of-concept of novel and powerful enzyme-free voltammetric aptasensor of colorectal cancer-related carcinoembryonic antigen (CEA) without the participation of any antibodies. The aptasensor was prepared by means of immobilizing thiolated CEA aptasensor on gold nanoparticle-deposited glassy carbon electrode. Thionine-doped silica nanoparticles were synthesized via reverse micelle method and functionalized with p-aminophenylboronic acid by the epoxy-amino reaction for specific conjugation of subsequent CEA glycoprotein. In the presence of target CEA, the analyte initially reacted with immobilized aptamer on the electrode to generate an aptamer-CEA complex. Then, phenylboronic acid immobilized on silica nanoparticle specifically recognized with CEA glycoprotein based on sugar-boronic acid interaction to form a sandwich-type complex on the electrode. Within the applied potentials, the doped thionine molecules into the silica nanoparticles were used as the electron mediators to produce well-defined voltammetric signals (vs. Ag/AgCl). Under optimum conditions, the voltammetric peak current increased linearly within the CEA concentration in the range from 1.0 pg mL-1 to 10 ng mL-1, and the limit of detection was 0.49 pg mL-1 at 3δ. A repeatability and intermediate precision of ≤8.7% was accomplished at CEA levels in the batch-to-batch mode. The method was highly specific for CEA over other disease-related biomarkers. The accuracy and inter-laboratory validation of this system were evaluated for target CEA detection in human serum specimens, and the results were in accordance with those obtained by a commercial ELISA.

In situ amplified QCM immunoassay for carcinoembryonic antigen with colorectal cancer using horseradish peroxidase nanospheres and enzymatic biocatalytic precipitation.

Methods based on enzyme labels or nano labels have been developed for immunoassays, but most of them have low sensitivity and are unsuitable for low-abundance protein diagnostics and biosecurity. Herein, an innovative quartz crystal microbalance (QCM) immunosensing method was designed for high-efficiency detection of carcinoembryonic antigen (CEA) from serum samples with colorectal cancer patients by using horseradish peroxidase (HRP) nanoparticles as the enhancer, accompanying enzymatic biocatalytic precipitation (EBCP) toward 4-chloro-1-naphthol (4-CN) on an anti-CEA capture antibody-conjugated QCM probe. Initially, HRP nanospheres were synthesized on the basis of the reverse micelle method with the assistance of glutaraldehyde cross-linking, and then covalently conjugated onto polyclonal anti-CEA detection antibodies. The QCM immunosensing probe was prepared by immobilizing monoclonal anti-CEA capture antibodies on an l-cysteine-modified gold substrate. In the presence of target CEA, a sandwich-type immunoreaction was carried out between capture antibody and detection antibody, thereby resulting in the attachment of HRP nanospheres on the gold probe. Upon addition of 4-CN in the QCM cell, the carried HRP nanospheres catalyzed the 4-CN oxidation to produce an insoluble precipitate on the gold electrode, thus causing a change in the frequency. Relative to the conventional HRP-labeled strategy and direct antigen-antibody reaction, improved analytical features were obtained with HRP nanospheres. With the HRP nanosphere labeling method, the factors influencing the performance of the immunoassay were also studied. The covalent conjugation of antibodies with HRP nanospheres and the gold substrate achieved a good repeatability and intermediate precision down to 10.7%. Under optimum conditions, the frequency variation of the QCM immunoassay was proportional to the target CEA concentration within a dynamic linear range of 0.01-100 ng mL-1 with a detection limit (LOD) of 7.8 pg mL-1. In addition, the developed QCM immunoassay showed high specificity and long-term storage stability, and could be used for the analysis of human serum samples with consistent results in comparison with those obtained from the commercial enzyme-linked immunosorbent assay (ELISA) method.

Association of the Collagen Signature in the Tumor Microenvironment With Lymph Node Metastasis in Early Gastric Cancer.

Importance: Lymph node status is the primary determinant in treatment decision making in early gastric cancer (EGC). Current evaluation methods are not adequate for estimating lymph node metastasis (LNM) in EGC. Objective: To develop and validate a prediction model based on a fully quantitative collagen signature in the tumor microenvironment to estimate the individual risk of LNM in EGC. Design, Setting, and Participants: This retrospective study was conducted from August 1, 2016, to May 10, 2018, at 2 medical centers in China (Nanfang Hospital and Fujian Provincial Hospital). Participants included a primary cohort (n = 232) of consecutive patients with histologically confirmed gastric cancer who underwent radical gastrectomy and received a T1 gastric cancer diagnosis from January 1, 2008, to December 31, 2012. Patients with neoadjuvant radiotherapy, chemotherapy, or chemoradiotherapy were excluded. An additional consecutive cohort (n = 143) who received the same diagnosis from January 1, 2011, to December 31, 2013, was enrolled to provide validation. Baseline clinicopathologic data of each patient were collected. Collagen features were extracted in specimens using multiphoton imaging, and the collagen signature was constructed. An LNM prediction model based on the collagen signature was developed and was internally and externally validated. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) of the prediction model and decision curve were analyzed for estimating LNM. Results: In total, 375 patients were included. The primary cohort comprised 232 consecutive patients, in whom the LNM rate was 16.4% (n = 38; 25 men [65.8%] with a mean [SD] age of 57.82 [10.17] years). The validation cohort consisted of 143 consecutive patients, in whom the LNM rate was 20.9% (n = 30; 20 men [66.7%] with a mean [SD] age of 54.10 [13.19] years). The collagen signature was statistically significantly associated with LNM (odds ratio, 5.470; 95% CI, 3.315-9.026; P < .001). Multivariate analysis revealed that the depth of tumor invasion, tumor differentiation, and the collagen signature were independent predictors of LNM. These 3 predictors were incorporated into the new prediction model, and a nomogram was established. The model showed good discrimination in the primary cohort (AUROC, 0.955; 95% CI, 0.919-0.991) and validation cohort (AUROC, 0.938; 95% CI, 0.897-0.981). An optimal cutoff value was selected in the primary cohort, which had a sensitivity of 86.8%, a specificity of 93.3%, an accuracy of 92.2%, a positive predictive value of 71.7%, and a negative predictive value of 97.3%. The validation cohort had a sensitivity of 90.0%, a specificity of 90.3%, an accuracy of 90.2%, a positive predictive value of 71.1%, and a negative predictive value of 97.1%. Among the 375 patients, a sensitivity of 87.3%, a specificity of 92.1%, an accuracy of 91.2%, a positive predictive value of 72.1%, and a negative predictive value of 96.9% were found. Conclusions and Relevance: This study's findings suggest that the collagen signature in the tumor microenvironment is an independent indicator of LNM in EGC, and the prediction model based on this collagen signature may be useful in treatment decision making for patients with EGC.

[Histological study on the safety of the controllable ileostomy with pipe].

OBJECTIVE: To investigate the safety of the controllable ileostomy with pipe in view of histology. METHODS: Twenty-eight Beagle dogs undergoing controllable ileostomy with pipe were studied. The special fistula tube with balloon was placed into the hole locating at the cecal root opposing the mesenteric side, and fixed by double knot compression method. RESULTS: The fistula tube was removed 14 days after surgery, then the safety of the procedure was preliminarily evaluated by gastrointestinal radiography and anatomical observation. The small intestine tissue at the compression suture was used as the experimental segment, and the small intestine tissue at the proximal non-compression suture was used as the control segment. The histological staining and the immunohistochemical staining of S-100 protein, c-kit protein and α-smooth muscle actin(α-SMA) protein between two segment were compared, while quantitative comparison of myenteric plexus, intestinal Cajal cell(ICC) and smooth muscle cells in intestinal wall was carried out. After removal of fistula tube at 14 days postoperative, the dogs were normal in feeding and defecation. The digestive tract radiography showed that the intestine was patent without obvious stenosis and obstruction. The dogs were dissected 21 days after operation. The abdominal sinus ostium was well healed and the internal sinus was well formed. Under gross inspection, blood supply, morphology and motor function of experimental intestine segment were similar from the proximal and distal segments of control intestine. S-100 immunohistochemical staining showed that the morphology and distribution of S-100 protein positive cells and "blank area" cells in the experimental and control segments were consistent. Myenteric plexus counting showed that the experimental segment was 3.62±1.82/field and the control segment was 3.27±1.62/field, whose difference was not statistically significant(t=1.30, P=0.20). Immunohistochemical staining of c-kit showed that the distribution of c-kit positive cells in both segments was consistent. Counting of the number of ICCs in myenteric plexus revealed that experimental segment was 2.96±2.57/plexus, and control segment was 2.49±1.80/plexus without significant difference(t=1.81, P=0.07). Immunohistochemical staining of α-SMA showed that the morphology and distribution of smooth muscle cells in whole intestinal wall(muscle layer, longitudinal muscle, ring muscle) in experimental and control segments were consistent. The average absorbance(A) value of α-SMA staining in ring muscle layer was detected and quantified. The experimental segment was 0.15±0.03 and control segment was 0.14±0.04 without significant difference(t=1.16, P=0.25). CONCLUSION: The technique of controllable ileostomy with pipe is safe in view of histology, which may replace the traditional protective ileostomy.

[Application research of presacral space drainage tube combined with subcutaneous vacuum pressure suction in the laparoscopic-assisted abdominoperineal resection].

OBJECTIVE: To study the management for the perineal incision after laparoscopic-assisted abdominoperineal resection for rectal cancer. METHODS: Clinical data of 87 patients undergoing laparoscopic Miles operation for lower rectal cancer from June 2009 to February 2014 were collected and studied. Presacral space drainage group: presacral space drainage tube was applied in 42 patients. Combined drainage group: presacral space drainage tube combined with subcutaneous vacuum pressure suction was applied in 45 cases. In combined drainage group, except the presacral drainage tube, another drainage tube was placed subcutaneously and connected to a negative pressure ball, which was fixed on the lateral anterior of perineal wound by the further incision and drainage. After subcutaneous tube was placed for 2 weeks, as drainage fluid was limpid and <15 ml/d for 3 days, meanwhile no obvious pelvic fluid was detected by ultrasound, and the wound healed quite well without redness and edema, then the subcutaneous tube with the negative pressure ball could be removed. RESULTS: There were 51 males and 36 females with the mean age of 26-78(56.9±10.8) years old. The laparoscopic Miles operation was successfully completed in all the cases without death and complications. The drainage tube was placed for 4-13(8.0±2.5) days in presacral space drainage group, and for 4-14(6.7±2.4) days in combined drainage group. The subcutaneous tube was placed for 14-24(15.8±3.0) days. The primary healing rate of perineal wound in presacral space drainage group and combined drainage group was 66.7%(28/42) and 91.1%(41/45) respectively, while the perineal wound infection rate was 21.4%(9/42) and 4.4%(2/45) respectively, whose differences between two groups were both significant (χ2=7.911, P=0.005 and χ2=5.674, P=0.017). CONCLUSION: Presacral space drainage tube combined with subcutaneous vacuum pressure suction in laparoscopic-assisted abdominoperineal resection for rectal cancer has better efficacy and lower infection rate for perineal incision, which is worth wide application.

Decreased expression of insulin-like growth factor binding protein 6 is associated with gastric adenocarcinoma prognosis.

The present study aimed to investigate the expression and prognostic significance of insulin-like growth factor binding protein 6 (IGFBP-6) in gastric adenocarcinoma. The expression of IGFBP-6 was examined in 263 specimens from gastric adenocarcinoma patients using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemical (IHC) staining. The association between IGFBP-6 expression, clinicopathological factors and clinical outcomes was investigated. Akaike information criterion (AIC) and Harrell's concordance index (c-index) were used to evaluate the accuracy of the predictive prognosis. RT-qPCR and western blotting results showed that IGFBP-6 mRNA expression was lower in the tumors compared with that in adjacent non-tumor tissues. IGFBP-6 showed significantly decreased expression in 170 out of 263 patients based on IHC data and this was associated with a larger tumor size (P<0.001) and poorly-differentiated adenocarcinoma (P=0.001), as well as with palliative gastrectomy (P=0.015). Additionally, decreased expression of IGFBP-6 was associated with stage T3/4a/4b disease and lymph node-positive metastasis (P<0.001). The association between decreased expression and a poor prognosis was revealed by Kaplan-Meier curves. Cox regression model identified IGFBP-6 as an independent prognostic factor. The prognostic value of the model with IGFBP-6 expression (AIC, 924.881; c-index, 0.878) was superior to that without IGFBP-6 expression (AIC, 947.164; c-index, 0.825). In conclusion, IGFBP-6 involves the development and progression of gastric adenocarcinoma, and its decreased expression predicts poor clinical outcomes.

[Expression of transcriptional coactivator with PDZ-binding motif (TAZ) in colon cancer tissues and its clinical significance].

OBJECTIVE: To investigate the expression of transcriptional coactivator with PDZ-binding motif(TAZ) in colon cancer tissues and its association with clinicopathological parameters and prognosis of patients. METHODS: The expression of TAZ protein was detected in 56 resected colon cancer tissues and matched tumor-adjacent tissues using immunohistochemistry. The positive expression rate of TAZ was compared between patients with different clinicopathological features. The association between TAZ expression and prognosis was analyzed. RESULTS: Expression of TAZ protein located in the nucleolus. The positive expression rate of TAZ in colon cancer tissues was significantly higher than that in matched tumor-adjacent tissues(73.2% vs. 12.5%, P=0.000). Clinicopathological evaluation suggested that the expression of TAZ protein was associated with tumor size(P=0.009), depth of infiltration(P=0.026), lymph node metastasis (P=0.007) and TNM staging(P=0.004). Colon cancer patients with negative expression of TAZ showed a better 5-year survival as compared with those with positive expression of TAZ (66.7% vs. 22.9%, P=0.0017). Multivariate Cox regression analysis revealed that positive TAZ expression was an independent factor for predicting poor prognosis in colon cancer (HR:3.532, 95% CI: 1.3-9.9, P=0.016). CONCLUSION: The expression of TAZ protein is up-regulated in colon cancer tissues and its high expression is associated with poor prognosis of colon cancer patients.

[Comparison of short- and long-term efficacy of three procedures in postoperative digestive tract reconstruction for upper gastric cancer].

OBJECTIVE: To compare the short- and long-term efficacy of three different procedures used for digestive tract reconstruction after radical gastrectomy for upper gastric cancer. METHODS: Clinical data of 191 patients with upper gastric cancer undergoing radical gastrectomy in the Fujian Provincial Hospital between January 2000 and December 2012 were analyzed retrospectively. Surgical procedures were classified as total gastrectomy followed by Roux-en-Y esophagojejunostomy (TG-RY, n=123), proximal gastrectomy followed by esophagogastrostomy (PG-EG, n=40), and proximal gastrectomy followed by jejunal interposition (PG-JI, n=28). Clinicopathological characteristics, perioperative and long-term outcomes were compared among the three groups. RESULTS: The operative time was shorter (178 vs. 248 and 224 min, P<0.05), and the intraoperative blood loss was less (194 vs. 323 and 265 ml, P<0.05) in PG-EG group than those in TG-RY and PG-JI groups. Early postoperative complications and hospital stay were comparable (both P>0.05). With respect to gastrectomy-associated symptoms, reflux and heartburn were more frequent in PG-EG patients, while dumpling syndrome was more frequent after TG-RY. Postoperative weight loss was not significantly different among three procedures (P>0.05), however, hemoglobin and serum albumin levels were lower in TG-RY patients (both P<0.05). The 5-year survival rate was similar (P>0.05). CONCLUSIONS: Surgeons need to choose the proper procedure according to tumor features and patient condition. PG-JI should be the first choice in terms of fewer complaints and better nutrition. TG-RY tends to be used for larger and more advanced tumors. PG-EG is the most minimally invasive procedure and thus may be suitable for older and high-risk patients.

[Expression of miR-146a in colon cancer and its significance].

OBJECTIVE: To investigate miR-146a expression in colonic cancer and its clinical implications. METHODS: Quantitative real-time PCR was employed to detect the levels of miR-146a expression in colonic cancer tissues, pair-matched adjacent normal tissues and different colonic cancer cell lines. MTT essay was used to evaluate the proliferation of colonic cancer SW260 cells transfected with miR-146a mimics, and the cell cycle and apoptosis of the cells were analyzed with flow cytometry. RESULTS: Compared with the normal tissues, 38 of the 43 colonic cancer samples showed down-regulated miR-146a expression, which was associated with poor tumor differentiation. The expression of miR-146a in the tumor tissues was significantly correlated with tumor size and clinical stages. The patients with high miR-146a expression levels had significantly longer total survival time than those with low expression of miR-146a. In SW260 cell cultures, transfection with miR-146a mimics significantly inhibited cell growth (P<0.05) and increased the cell apoptosis rate (11.9% vs 5.9%) but produced no obvious effect on cell cycle. CONCLUSIONS: miR-146a may serve as a potential therapeutic target for colonic cancer for its role in inhibiting colonic cancer cell proliferation.

Role of preoperative atorvastatin administration in protection against postoperative atrial fibrillation following conventional coronary artery bypass grafting.

Atrial fibrillation (AF) is one of the most common postoperative arrhythmias in patients who undergo coronary artery bypass grafting (CABG). The aim of this study was to evaluate the effect of preoperative atorvastatin on postoperative atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass (CCABG). One hundred consecutive patients undergoing elective CCABG, without history of AF or previous statin treatment, were enrolled and randomly assigned to a statin group (atorvastatin 20 mg/d, n = 49) or a control group (placebo, n = 51) starting 7 days preoperatively. The primary endpoint was the occurrence of postoperative AF. C-reactive protein (CRP) levels were assessed in all selected patients before surgery and every 24 hours postoperatively until discharge from hospital. Atorvastatin significantly reduced the incidence of postoperative AF and postoperative peak CRP level versus placebo (18% versus 41%, P = 0.017; 129.3 ± 24.3 mg/L versus 149.3 ± 32.5 mg/L, P < 0.0001). Kaplan-Meier curves confirmed a significantly better postoperative atrial fibrillation-free survival in the statin group (χ(2) = 7.466, P = 0.006). Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF (OR = 0.235, P = 0.007), whereas high postoperative CRP levels were associated with increased risk (OR = 2.421, P = 0.015). Preoperative atorvastatin administration may inhibit inflammatory reactions to prevent atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass.

Short-term effects of double-layer autologous vein graft on restraint of excessive distension and alleviation of neointimal hyperplasia in a porcine saphenous vein graft model.

Although the use of external vein graft support seems a promising approach to prevent neointimal hyperplasia and wall thickening in vein grafts, its extensive clinical application still has a long way to go. The aim of this study was to evaluate short-term effects of self-designed double-layer autologous saphenous vein graft on restraining excessive distension of vein graft and alleviating neointimal hyperplasia in a porcine model. Left and right hind femoral arteries of 24 white pigs were randomly divided into an experimental group (double-layer vein graft) and a control group (single-layer vein graft). After 1 h of implantation, then 1, 2, and 4 weeks later, the mean inner diameter of the vein grafts in the experimental group measured by Doppler-ultrasound was 2.7 ± 0.1, 2.8 ± 0.1, 2.9 ± 0.1, and 3.1 ± 0.1 mm, respectively; mean peak blood flow velocity measured by Doppler-ultrasound was 96.7 ± 12.8, 93.7 ± 11.5, 89.4 ± 9.6 and 84.6 ± 10.1 cm/s, respectively, while the mean neointimal thicknesses were 47.1 ± 7.7, 93.7 ± 15.1, and 177.4 ± 25.5 µm at 1, 2 and 4 weeks, respectively. As compared to the control group, inner diameter and neointimal thickness of vein grafts in the experimental group were significantly lower, while mean peak blood flow velocity was significantly higher at 1, 2, and 4 weeks after implantation. The proliferation index in the experimental group was also significantly lower within 4 weeks after implantation. The self-designed double-layer autologous saphenous vein graft restrains early excessive distension of vein graft and alleviates early neointimal hyperplasia.

Risk factors for late extubation after coronary artery bypass grafting.

OBJECTIVE: To evaluate the independent risk factors for late extubation after coronary artery bypass grafting (CABG). METHODS: Preoperative, intraoperative, and postoperative characteristics of patients undergoing isolated CABG between June 2005 and June 2008 at the Tongji Hospital were retrospectively analyzed. Elapsed time between CABG and extubation of more than 8hours was defined as late extubation. RESULTS: The incidence of late extubation after CABG was 69.23% (288/416). Through univariate and logistic regression analysis, the independent risk factors for late extubation after CABG were older age (odds ratio [OR]=4.804), duration of cardiopulmonary bypass (OR=2.426), perioperative use of intra-aortic balloon pump (OR=1.451), preoperative arterial oxygen partial pressure (OR=.204), and postoperative hemoglobin level (OR=.793). CONCLUSION: Older age, prolonged cardiopulmonary bypass time, perioperative intra-aortic balloon pump requirement, low preoperative arterial oxygen partial pressure, and low postoperative hemoglobin level were identified as the 5 independent risk factors for late extubation after CABG.