Exploration and advance of key techniques in MALDI mass spectrometry imaging / 药学学报

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a new imaging technique with label-free, rapid, and high throughput features. It has bloomed in the analysis on the spatial distribution of biomolecules such as drugs, metabolites, peptides and proteins on the tissue surface in virtue of providing high data throughput from non-targeted full analysis and high accuracy from targeted analysis. The acquisition of MSI signal response with high sensitivity, high spatial resolution, and good stability is directly depended on the appropriate sample preparation approaches, and flexible and various data processing tools will help the non-target data mining to meet the demands of visualization, spatial distribution and multiple index applications so as to reveal the scientific rules beneath the data. This review briefly summarizes the key advances in MALDI-MSI from aspects of sample preparation procedures, data processing and visualization. It also illustrates the characteristics, difficulties and probable solutions derived from these key techniques.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer / 中华胃肠外科杂志

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

Effect of Preoperative Tumor Under-Staging on the Long-term Survival of Patients Undergoing Radical Gastrectomy for Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effect of preoperative tumor staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC). @*Materials and Methods@#Clinicopathological data of 2,346 patients who underwent RGGC were retrospectively analyzed. The preoperative tumor-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients. @*Results@#There were 1,031 uTNM (44.0%) and 1,315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). The patients less than 65 years old, with lower American Society of Anaesthesiologists score, 2-5 cm tumor located at the lower stomach, and cT1 or cN0 preoperative staging would more likely undergo D1+ lymph node dissection (LND) in uTNM (p 2 cm and body mass index ≤ 22.72 kg/m2 were independent risk factors of preoperative TNM tumor under-staging in patients with cT1N0M0 staging (p < 0.05). @*Conclusion@#Underestimated tumor staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

Identification of Unknown Toxicants in Food Poisoning by High Resolution Mass Spectrometry-Data Independent Acquisition-Post Targeted Screening Strategy / 分析化学

Based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF MS/MS),a post targeted screening strategy using high resolution mass spectrometry under data independent acquisition was established,and successfully applied to screen and identify unknown toxicants in food poisoning patients' vomit and feces.After solvent extraction,the samples were separated and analyzed on a reversed-phase C18column using a gradient elution program of 5 mmol/L ammonium formate and 0.1% formic acid aqueous solution(A) and 0.1% formic acid in acetonitrile solution (B).All-ions MS/MS information of samples was obtained using Q-TOF MS(ESI+) in MSE mode,followed by peak recognition and library searching using the UNIFI Scientific Information System,as a result,suspected toxic compound α-solanine was primarily detected.Furthermore,the related chemicals including hydrolysates and metabolites were identified in both samples based on post-targeted screening strategy,such as α-chaconine,β-chaconine,γ-solanine/chaconine and solanidine.The concentration of α-solanine in both samples was approximately 0.1 mg/kg by one-point calibration method,the total amount of solanine analogues in two samples was about 0.5 mg/kg and 0.6 mg/kg respectively through normalization of peak area.The high resolution mass spectrometry screening strategy established here could provide efficient screening method for rapid detection and identification of toxicants in unknown food poisoning.

Expression tumor stem cell surface marker CD44 in gastric cancer and its significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of tumor stem cell surface marker CD44 in gastric cancer and its clinical value.</p><p><b>METHODS</b>Expressions of CD44 protein family, including CD44s, CD44v5 and CD44v6, in gastric cancer and peritumoral tissues specimens were detected by immunohistochemistry in 156 patients with gastric cancer from December 2006 to December 2007. Associations of CD44 family expressions with of clinicopathological parameters and prognosis in gastric cancer patients were examined.</p><p><b>RESULTS</b>The positive rates of CD44s expression in gastric cancer and peritumoral tissues were 50.0%(78/156) and 40.3%(63/156) respectively(P>0.05). The positive rates of CD44v5 and CD44v6 expression in gastric cancer were 49.3% and 63.4%, significantly higher than those in peritumoral tissues(7.6% and 0 respectively, all P<0.05). There were no positive correlations among the expression levels of CD44s, CD44v5 and CD44v6(all P>0.05). High expression rate of CD44s was associated with depth of invasion, lymph node metastasis and TNM stages. CD44v5 expression was only associated with depth of invasion. CD44v6 expression was associated with depth of invasion, lymph node metastasis, TNM stages and Lauren classification. The 5-year survival rates in the positive and negative groups of CD44s, CD44v5 and CD44v6 expressions were 35.8% and 52.5%(P<0.05), 38.9% and 49.3%(P>0.05), 26.2% and 75.4%(P<0.05) respectively. Only the CD44v6 expression was an independent prognostic factor for gastric cancer(RR=1.931, 95%CI:1.183-3.152).</p><p><b>CONCLUSION</b>CD44 plays an important role in invasion and lymph node metastasis, and may serve as potential predictors of prognosis in gastric cancer.</p>

Clinicopathologic features and prognosis of gastric cancer in young patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and prognosis of gastric cancer in young patients (YGC) in order to improve the treatment outcome of YGC.</p><p><b>METHODS</b>Clinical data of 63 YGC patients (40 years of age and less) who underwent surgery from January 2004 to December 2006 were analyzed retrospectively. A total of 654 older gastric cancer patients (OGC, above 40 years) during the same period patients were selected and compared to the YGC patients.</p><p><b>RESULTS</b>The proportions of female patients, patients with a family history or with undifferentiated tumor in YGC were significantly higher than OGC (all P<0.05). The curative resection rate of YGC patients was 61.9% (39/63), significantly lower than that of OGC (93.1%, 595/654, P<0.01). A total of 653 (91.1%) patients were followed up, with a period of time of 1 to 84 months. The 5-year survival rates for YGC and OGC patients were 40.5% and 55.6% respectively, and the difference was statistically significant (P<0.05). Cox proportional hazards model showed that the depth of invasion, lymph node metastasis, and radical surgery were the independent factors associated with the prognosis of YGC (all P<0.05). The stratified analysis showed that the 5-year survival rates for YGC and OGC patients undergoing radical surgery were 63.2% and 56.7% respectively and the difference was not statistically significant (P>0.05). The 5-year survival rates for YGC and OGC patients undergoing palliative surgery were 4.2% and 22.2% respectively and the difference was statistically significan t(P<0.05).</p><p><b>CONCLUSION</b>Gastric cancer in young patients is highly malignant, with lower rate of curative resection and poorer prognosis. The long-term outcome of YGC is similar to that of OGC if radical resection is possible.</p>

Application of delta-shaped anastomosis in totally laparoscopic distal gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the technical feasibility, safety, and clinical efficacy of delta-shaped anastomosis in totally laparoscopic distal gastrectomy (TLDG).</p><p><b>METHODS</b>Clinical data of 18 patients with gastric cancer who received TLDG with delta-shaped anastomosis from November 2012 to December 2012 were retrospectively analyzed. The delta-shaped anastomosis is a new method of intraabdominal Billroth I anastomosis using only linear stapler. The posterior wall of the stomach and that of the duodenum were put together using linear stapler, and the common stab incision was also closed with linear stapler. The anastomosis was finished with a delta-shaped.</p><p><b>RESULTS</b>TLDG with delta-shaped anastomosis was successfully carried out in all the patients. The mean operation time and mean time for anastomosis were (156.3 ± 38.5) minutes and (24.6 ± 11.2) minutes. The lengths of upper and lower segment of resection form gastric cancer were (5.8 ± 2.4) cm and (4.1 ± 2.7) cm. Blood loss was (70.7 ± 43.8) ml and number of dissected lymph nodes was 32.4 ± 12.0 per patient. The average time to ground activities, time to flatus, time to fluid diet and length of hospital stay were (1.8 ± 0.9) days, (3.1 ± 1.2) days, (3.6 ± 1.7) days, and (9.6 ± 2.5) days, respectively. Only one patient developed chylus leak with intraabdominal infection. There was no mobility related to the anastomosis in all the patients.</p><p><b>CONCLUSION</b>The delta-shaped anastomosis is a safe and feasible procedure for totally laparoscopic distal gastrectomy and provides satisfactory short-term efficacy.</p>

Impact of the extent of gastric resection on the prognosis of patients with middle one-third gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of the extent of gastric resection on the prognosis of patients with middle one-third gastric cancer.</p><p><b>METHODS</b>From January 1998 to December 2005, 222 patients with middle one-third gastric cancer underwent D2 radical resection in the Affiliated Union Hospital, Fujian Medical University. Among them, 66 underwent distal gastrectomy (DG group), while 156 underwent total gastrectomy (TG group). The 5-year survival rates were compared between two groups. The prognostic factors were evaluated by univariate and multivariate analyses.</p><p><b>RESULTS</b>The 5-year survival rates of DG group and TG group were 63.9% and 49.8% respectively, with significant difference (P<0.05). Nevertheless, compared to DG group, the tumors in TG group had bigger size, later TNM stage, and higher proportion of locating lesser curvature of stomach (all P<0.01). Multivariate analysis revealed that invasion depth, lymph node metastasis and TNM classification were independent prognostic factors (all P<0.05), but the extent of gastric resection was not (P>0.05).</p><p><b>CONCLUSION</b>If curative resection can be performed, the long-term prognosis of patients with middle one-third gastric cancer is not affected by the extent of gastric resection, and distal gastrectomy is feasible.</p>

Laparoscopy-assisted radical gastrectomy with D2 lymph node dissection for gastric cancer in the elderly / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and efficacy of laparoscopy-assisted radical gastrectomy with D2 lymph node (LN) dissection for elderly patients with gastric cancer.</p><p><b>METHODS</b>From January 2007 to December 2009, 255 gastric cancer patients aged over 65 years underwent D2 LN dissection. Of these, 116 patients underwent laparoscopy-assisted radical gastrectomy (LAG group), while 139 patients underwent conventional open gastrectomy (OG group). The recovery and complication rate were compared between the two groups. Risk factors associated with postoperative complications were investigated by univariate and multivariate analyses.</p><p><b>RESULTS</b>Compared to the OG group, the mean blood loss and number of patients who required blood transfusion were less, and the time to first flatus, the time to resume soft diet, and postoperative hospital stay were shorter in the LAG group (all P<0.01). However, the operation time and the mean number of LN retrieval were not significantly different between the two groups (both P>0.05). The postoperative morbidity in the LAG group was 15.5% (18/116), lower than that in OG group [28.1% (39/139), P<0.05]. Logistic regression analysis revealed that there were three significant factors associated with postoperative complications such as laparoscopy-assisted gastrectomy (P<0.05), operation time (P<0.01), and preoperative comorbidity (P<0.01). Operation time (P<0.05) and preoperative comorbidity (P<0.01) were independent risk factors for complication in laparoscopy-assisted radical gastrectomy of elderly patients. The mean survival time of LAG and OG were 23.0 months and 22.5 months, respectively, and the difference was not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>Laparoscopy-assisted radical gastrectomy with D2 LN dissection is oncologically compatible with open gastrectomy in elderly patients with gastric cancer less invasive. Operation time and preoperative comorbidity are independent risk factors for complication in laparoscopy-assisted radical gastrectomy of elderly patients.</p>

Clinicopathologic features and prognostic factors of gastric gastrointestinal stromal tumor with synchronous gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluated the clinicopathologic features and prognostic factors of gastric gastrointestinal stromal tumor(GIST) with synchronous gastric cancer.</p><p><b>METHODS</b>The clinicopathologic records of 122 patients with gastric GIST who underwent surgical treatment from April 2000 to June 2010 were analyzed retrospectively. Twenty-six patients presented synchronous gastric cancer(group A), while 96 patients did not(group B). The clinicopathologic features of gastric GIST were compared between the two groups. Potential prognostic factors were evaluated by univariate and multivariate analyses.</p><p><b>RESULTS</b>Gastric GIST in group A were associated with smaller tumor diameter (P<0.01), lower mitotic count(P<0.05), lower Fletcher classification(P<0.01), and lower rate of pre-operative diagnosis(23.1% vs. 97.9%, P<0.01). On univariate analysis, maximum tumor diameter (P<0.01), mitotic count (P<0.01), Fletcher classification (P<0.01) and synchronous gastric cancer(P<0.05) were the predictive factors of survival. Multivariate analysis showed that Fletcher classification(P<0.05) and synchronous gastric cancer (P<0.01) were independent prognostic factors.</p><p><b>CONCLUSIONS</b>In patients with synchronous gastric GIST and gastric cancer, Fletcher classification of GIST is usually very low or low invasion risk and has minimal impact on the prognosis. Survival depends primarily on the gastric cancer.</p>

Impact of previous abdominal operations on the outcome of laparoscopy-assisted radical total gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the impact of previous abdominal operations on the outcome of laparoscopy-assisted radical total gastrectomy (LATG).</p><p><b>METHODS</b>Clinical data of 328 patients with gastric cancer who underwent LATG from January 2008 to December 2010 were analyzed retrospectively. Among the patients, 57 cases had previous abdominal surgeries (PAS group) and 271 cases had no previous abdominal surgeries (NPAS group). The intraoperative and postoperative parameters were compared, and risk factors associated with postoperative complications were analyzed using univariate and multivariate analysis.</p><p><b>RESULTS</b>There was no significant difference between the two groups in the mean number of lymph nodes harvested (30.2±10.5 vs. 31.1±9.4, P>0.05). The operative time [(247.0±60.5) min vs. (214.7±57.0) min, P<0.01] and the postoperative complication rate [21.1%(12/57) vs. 11.1%(30/271), P<0.05] were significantly different between the two groups. However, there were no differences in intraoperative blood loss, transfused patients, conversion, postoperative ambulation time, postoperative flatus passage time, resumption of liquid diet, removal of gastric tube, and postoperative hospital stay (all P>0.05). Multivariate logistic regression analysis showed that previous abdominal surgeries was not an independent risk factor associated with postoperative complication morbidity (P>0.05).</p><p><b>CONCLUSIONS</b>LATG is feasible for gastric cancer patients who has previous abdominal surgeries. Previous abdominal surgery may prolong operative time but is not an independent risk factor associated with postoperative complication.</p>

Gastric carcinoma in a 12-year-old girl: a case report and literature review / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To report the diagnosis and treatment experience of pediatric gastric cancer.</p><p><b>METHODS</b>Clinicopathological data of a girl with gastric carcinoma in December 2011 was analyzed retrospectively. The literatures were reviewed. The disease onset, clinical manifestations, treatment, and prognosis of the patient with gastric carcinoma were studied.</p><p><b>RESULTS</b>The patient was a 12-year-old girl, and the tumor was located in greater curvature. The girl underwent laparoscopy-assisted radical total gastrectomy (D2). Pathological examination showed gastric ulcerative signet-ring cell cancer (pT4N0M0, stage II b). The outcome at the recent follow up was satisfactory. Literature review demonstrated 15 cases of pediatric gastric carcinoma, of whom 7 were boys and 8 girls. Their average age was 12.7 years (2.5-17.8 years). Tumor locations included cardia (n=5), gastric body (n=1), gastric antrum or stomach corner (n=4), gastric antrum and gastric body (n=1), and unknown (n=4). Histology showed signet-ring cell cancer in 4 patients, poorly differentiated in 6, moderate to poorly differentiated and moderate differentiated adenocarcinoma in 2. Operation was performed in 11 cases and perioperative chemotherapy in 8 cases. Nine patients had follow-up. Four patients died within 6 months and other 4 patients survived for 6 months to one year. The survival time of one patient who underwent radical surgery and perioperative chemotherapy was 102 months.</p><p><b>CONCLUSIONS</b>Pediatric gastric carcinoma is extremely rare. It is highly malignant and associated with poor prognosis. Radical surgery is the most important treatment. Perioperative chemotherapy may improve the prognosis.</p>

Clinical efficacy analysis of laparoscopy-assisted radical gastrectomy for 1380 patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the technical feasibility, safety, and clinical efficacy of laparoscopy assisted radical gastrectomy(LAG) for patients with gastric cancer.</p><p><b>METHODS</b>Clinical data of 1380 patients with gastric cancer who received LAG from May 2007 to April 2012 were analyzed retrospectively.</p><p><b>RESULTS</b>LAG was successfully carried out in 1363 patients, and 17 patients(1.2%) were converted to open surgery. The mean operation time, blood loss, number of dissected lymph nodes were(196.2±59.2) minutes, (79.7±115.8) ml, and 30.1±11.0, respectively. The average time to ground activities, time to flatus, time to fluid diet, and length of hospital stay were(2.4±1.0) days, (3.3±1.2) days, (4.2±1.6) days, and (12.4±8.5) days, respectively. The postoperative morbidity was 12.1% and the mortality was 0.4%. According to Simple Scatter analysis, the number of surgical cases(surgeons' experience) was negatively related with the rate of converted to open surgery and operation time, but positively with number of dissected lymph nodes. A total of 1332 patients were followed up for 2-51 months(median 19 months), and the 3-year survival rate was 71.0%, the 3-year survival rates in stage I(, stage II(, and stage III( were 94.5%, 83.9%, and 56.7%, respectively.</p><p><b>CONCLUSION</b>Laparoscopy assisted radical gastrectomy is a safe and feasible procedure with better clinical efficacy for gastric cancer. With improvement in the surgical technology, the conversion rate and operation time decrease, and the number of dissected lymph nodes will increase.</p>

Expression of microRNA-183 in stage II ( gastric cancer and its association with Ezrin protein / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of microRNA-183 (miR-183) and Ezrin protein in stage II( gastric cancer (GC).</p><p><b>METHODS</b>Specimens of stage II( GC and paracancer tissues (5 cm away from the tumor tissues) were collected from 72 patients. Real-time PCR was used to detect the miR-183 expression. Immunohistochemistry was used to examine the Ezrin protein expression in the tumor tissue. The associations of miR-183 expression with the clinicopathologic features of stage II( GC and Ezrin expression were analyzed.</p><p><b>RESULTS</b>miR-183 expression was lower in stage II( gastric cancer tissues compared with the paracancer tissues samples(median relative expression, 0.676 vs. 1.000, P<0.05). Low expression of miR-183 was significantly associated with histological differentiation(0.429 vs. 0.907, P<0.05), lymph node metastasis(0.507 vs. 0.908, P<0.05). The survival was shorter in patient with low expression of miR-183(63.0±4.0) as compared to those with high expression of miR-183(75.2±3.8)(P<0.05). There was a negative correlation between the expression of miR-183 and Ezrin(r=-0.272, P<0.05).</p><p><b>CONCLUSIONS</b>miR-183 is down-regulated in stage II( GC, and associated with the differentiation, metastasis, and prognosis. Ezrin is a potential regulatory protein of miR-183.</p>

Extraluminal laparoscopic wedge resection for gastric stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility and safety of extraluminal laparoscopic wedge resection(ELWR) surgery for gastrointestinal stromal tumors (GIST) in the stomach.</p><p><b>METHODS</b>The clinical data of 31 patients with gastric GIST undergoing ELWR from July 2007 to June 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>There were 19 males and 12 females with a mean age of 65.5 years old. Locations of the tumor included fundus of the stomach (n=22) and anterior wall (n=9). The mean diameter was (3.3±1.5) cm (range 1.5 to 5 cm). All the procedures were performed successfully without conversion to open operation. The mean operative time of ELWR was (54.1±6.2) min (range 45 to 65 min), the mean intraoperative blood loss was (35.2±10.5) ml (range 15 to 55 ml), the mean recovery time was (1.5±0.2) d (range 3 to 6 d) and the mean postoperative hospital stay was (4.5±1.0) d. No patient experienced complications postoperatively. The entire cohort were followed up for 4 to 48 months (mean 18.8 months) and no recurrence or metastasis was found.</p><p><b>CONCLUSION</b>ELWR for gastric GIST is technically feasible and safe.</p>

Impact of operative time on patients undergoing laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of operative time on laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection and the influencing factors of operative time.</p><p><b>METHODS</b>Clinical data of 332 patients with gastric cancer undergoing LADG with D2 lymph node dissection from January 2007 to December 2010 were analyzed retrospectively. The average operative time was (205±56) minutes. Operative indices and postoperative recovery were compared between patients with operative time≥205 min (long-time group) and operative time<205 min (short-time group).</p><p><b>RESULTS</b>The mean blood loss [(81.0±65.7) ml vs. (65.8±55.0) ml], time to ambulation [(3.1±1.7) d vs. (2.3±1.2) d], time to first flatus [(3.8±1.1) d vs. (3.2±1.3) d], postoperative hospital stay [(14.2±6.3) d vs. (12.5±7.0) d], and postoperative complication [16.0% (19/119) vs. 8.5% (18/213)] between long-time group and short-time group were significantly different (all P<0.05), while there were no significant differences in transfused patients, time to resume soft diet, and mortality (all P>0.05). Multivariate logistic regression analysis revealed that BMI (P<0.01), lymph node metastasis (P<0.05), and surgeon experience (P<0.01) were independent risk factors for operation time.</p><p><b>CONCLUSION</b>Surgeons who have limited experience in LADG with D2 lymph node dissection should operate on patients with low BMI and less lymph node metastasis in order to reduce postoperative complications.</p>

Metabolite profiling of two anti-HIV lead compounds in rat liver microsomes / 药学学报

The metabolite profiling of DAPA-7012 and DAAN-4442, the lead compounds from two new kinds of non-nucleoside reverse transcriptase inhibitors (NNRTIs), was performed using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), with the assistance of a metabolite data processing software. By utilizing the mass defect filter (MDF) technique, the data acquired from the 0 h-incubation and the 2 h-incubation were compared and analyzed with the MetaboLynx software. After incubation, 14 metabolites of DAPA-7012 and 14 metabolites of DAAN-4442 were found in rat liver microsome. The MS2 spectra for some metabolites were obtained using the MS(E) technique to get fragment ions for structural elucidation. The results indicated that both compounds could undergo extensive metabolism in rat liver microsomes. The major phase I reaction was oxidation/hydroxylation. The major phase II reaction was S-glutathione conjugation. The metabolic pathways were similar between the two lead compounds, though they have different backbone structures. Besides, the 4-NO2 of ring B in DAAN-4442 was susceptible to reduction, the benzyl of ring C in DAPA-7012 was tend to be oxidized. The common metabolic soft spots were primary amine of ring B and two methyl groups of ring C. Early SAR results showed that the primary amine and methyl were necessary substituent groups. The stability of these active groups needs to be improved and optimized. The approach of combining metabolites information and structure-activity analysis can provide a reference for further structural optimization.

Prognostic significance of tumor size in T3 gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of tumor size on the prognosis of patients with T3 gastric cancer.</p><p><b>METHODS</b>D2 curative resection was performed on 408 patients with T3 gastric cancer. Cox proportional hazards model was used to identify the optimal cut-off of tumor size. Potential prognostic factors were evaluated by univariate and multivariate analysis. Multivariate analysis was performed to evaluate the prognostic factors stratified by tumor size.</p><p><b>RESULTS</b>Among 408 patients with T3 gastric cancer, Cox proportional hazards model showed that 8 cm was the optimal cut-off of tumor size. There were 85 patients with tumor size ≥8 cm(large size group), and 323 patients with tumor size <8 cm(small size group). The 5-year survival rate was significantly lower for patients with small size tumor(33.8% vs. 52.2%, P<0.05). Cox proportional hazards model showed that lymph node metastasis, tumor size, and Borrmann type were independent prognostic factors for the entire cohort. Borrmann type IIII( and N2-3 nodal metastasis were independent prognostic factors for the large size group. Lymph node metastasis was independent prognostic factor for the small size group.</p><p><b>CONCLUSIONS</b>Tumor size is an independent prognostic factor in patients with T3 gastric cancer. Lymph node metastasis is a significant predictor for the prognosis regardless of tumor size. Furthermore, Borrmann classification is associated with the prognosis in patients with tumor size ≥8 cm.</p>