Crebanine N-oxide, a natural aporphine alkaloid isolated from Stephania hainanensis, induces apoptosis and autophagy in human gastric cancer SGC-7901 cells

Objective: To investigate the cytotoxic effects and the potential mechanisms of crebanine N-oxide in SGC-7901 gastric adenocarcinoma cells. Methods: The cytotoxicity of crebanine N-oxide was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cellular morphology was observed under a microscope. Cell apoptosis was determined by flow cytometry using propidium iodide staining. The expression levels of apoptotic-related proteins, cleaved caspase-3, cytochrome C, p53 and Bax, and autophagyrelated proteins p62, beclin1 and LC3 were detected by Western blotting assays. Results: Crebanine N-oxide treatment significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent and timedependent manner via induction of G2-phase cell cycle arrest, apoptosis, and autophagy in SGC-7901 cells.Conclusions: Crebanine N-oxide could inhibit the growth of gastric cancer cells by promoting apoptosis and autophagy and could be used as a potential agent for treating gastric cancer.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Laparoscopic vs open D2 gastrectomy for locally advanced gastric cancer: A meta-analysis

AIM:To conduct a meta-analysis comparing laparoscopic(LGD2)and open D2 gastrectomies(OGD2)for the treatment of advanced gastric cancer(AGC).METHODS:Randomized controlled trials(RCTs)and non-RCTs comparing LGD2 with OGD2 for AGC treatment,published between 1 January 2000 and 12January 2013,were identified in the Pub Med,Embase,and Cochrane Library databases.Primary endpoints included operative outcomes(operative time,intraoperative blood loss,and conversion rate),postoperative outcomes(postoperative analgesic consumption,time to first ambulation,time to first flatus,time to first oralintake,postoperative hospital stay length,postoperative morbidity,incidence of reoperation,and postoperative mortality),and oncologic outcomes(the number of lymph nodes harvested,tumor recurrence and metastasis,disease-free rates,and overall survival rates).The Cochrane Collaboration tools and the modified Newcastle-Ottawa scale were used to assess the quality and risk of bias of RCTs and non-RCTs in the study.Subgroup analyses were conducted to explore the incidence rate of various postoperative morbidities as well as recurrence and metastasis patterns.A Begg’s test was used to evaluate the publication bias.RESULTS:One RCT and 13 non-RCTs totaling 2596patients were included in the meta-analysis.LGD2 in comparison to OGD2 showed lower intraoperative blood loss[weighted mean difference(WMD)=-137.87 m L,95%CI:-164.41--111.33;P<0.01],lower analgesic consumption(WMD=-1.94,95%CI:-2.50--1.38;P<0.01),shorter times to first ambulation(WMD=-1.03d,95%CI:-1.90--0.16;P<0.05),flatus(WMD=-0.98d,95%CI:-1.30--0.66;P<0.01),and oral intake(WMD=-0.85 d,95%CI:-1.67--0.03;P<0.05),shorter hospitalization(WMD=-3.08 d,95%CI:-4.38--1.78;P<0.01),and lower postoperative morbidity(odds ratio=0.78,95%CI:0.61-0.99;P<0.05).No significant differences were observed between LGD2 and OGD2 for the following criteria:reoperation incidence,postoperative mortality,number of harvested lymph nodes,tumor recurrence/metastasis,or three-or five-year diseasefree and overall survival rates.However,LGD2 had longer operative times(WMD=57.06 min,95%CI:41.87-72.25;P<0.01).CONCLUSION:Although a technically demanding and time-consuming procedure,LGD2 may be safe and effective,and offer some advantages over OGD2 for treatment of locally AGC.

Staging laparoscopy improves treatment decision-makingfor advanced gastric cancer

AIM To evaluate the clinical value of staging laparoscopyin treatment decision-making for advancedgastric cancer （GC）.METHODS： Clinical data of 582 patients with advancedGC were retrospectively analyzed. All patientsunderwent staging laparoscopy. The strength ofagreement between computed tomography （CT） stage,endoscopic ultrasound （EUS） stage, laparoscopic stage,and final stage were determined by weighted Kappastatistic （Kw）. The number of patients with treatmentdecision-changes was counted. A χ 2 test was used toanalyze the correlation between peritoneal metastasisor positive cytology and clinical characteristics.RESULTS： Among the 582 patients, the distributions ofpathological T classifications were T2/3 （153, 26.3%）,T4a （262, 45.0%）, and T4b （167, 28.7%）. Treatmentplans for 211 （36.3%） patients were changed after staging laparoscopy was performed. Two （10.5%） of19 patients in M1 regained the opportunity for potentialradical resection by staging laparoscopy. Unnecessarylaparotomy was avoided in 71 （12.2%） patients. Thestrength of agreement between preoperative T stageand final T stage was in almost perfect agreement （Kw= 0.838; 95% confidence interval （CI）： 0.803-0.872;P 〈 0.05） for staging laparoscopy; compared with CTand EUS, which was in fair agreement. The strengthof agreement between preoperative M stage andfinal M stage was in almost perfect agreement （Kw= 0.990; 95% CI： 0.977-1.000; P 〈 0.05） for staginglaparoscopy; compared with CT, which was in slightagreement. Multivariate analysis revealed that tumorsize （≥ 40 mm）, depth of tumor invasion （T4b）, andBorrmann type （Ⅲ or Ⅳ） were significantly correlatedwith either peritoneal metastasis or positive cytology.The best performance in diagnosing P-positive wasobtained when two or three risk factors existed.CONCLUSION： Staging laparoscopy can improvetreatment decision-making for advanced GC anddecrease unnecessary exploratory laparotomy.

Laparoscopic splenic hilum lymph node dissection for advanced proximal gastric cancer:A modified approach for pancreasand spleen-preserving total gastrectomy

AIM:To investigate the feasibility and optimal approach for laparoscopic pancreasand spleen-preserving splenic hilum lymph node dissection in advanced proximal gastric cancer.METHODS:Between August 2009 and August 2012,12 patients with advanced proximal gastric cancer treated in Nanfang Hospital,Southern Medical University,Guangzhou,China were enrolled and subsequently underwent laparoscopic total gastrectomy with pancreasand spleen-preserving splenic hilum lymph node(LN)dissection.The clinicopathological characteristics,surgical outcomes,postoperative course and followup data of these patients were retrospectively collected and analyzed in the study.RESULTS:Based on our anatomical understanding of peripancreatic structures,we combined the characteristics of laparoscopic surgery and developed a modified approach(combined supraand infra-pancreatic approaches)for laparoscopic pancreasand spleenpreserving splenic hilum LN dissection.Surgery was completed in all 12 patients laparoscopically without conversion.Only one patient experienced intraoperative bleeding when dissecting LNs along the splenic artery and was handled with laparoscopic hemostasis.The mean operating time was 268.4 min and mean number of retrieved splenic hilum LNs was 4.8.One patient had splenic hilum LN metastasis(8.3%).Neither postoperative morbidity nor mortality was observed.Peritoneal metastasis occurred in one patient and none of the other patients died or experienced recurrent disease during the follow-up period.CONCLUSION:Laparoscopic total gastrectomy with pancreasand spleen-preserving splenic hilum LN dissection using the modified approach for advanced proximal gastric cancer could be safely achieved.

Laparoscopic management of gastric gastrointestinal stromal tumors: A retrospective 10-year single-center experience

AIM To determine the feasibility,safety,and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors(GISTs)based on favorable or unfavorable location.METHODS Our hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015.Patient demographics,clinical presentation,surgery,histopathology,postoperative course,and oncological outcomes were reviewed and analyzed.RESULTS Gastric GIST in favorable locations was present in81/207(39.1%)cases,and in unfavorable locations in 126/207(60.9%)cases.Overall mean tumor size was 3.28±1.82 cm.No conversions occurred,and complete R0 resection was achieved in 207(100%)cases.There were three incidences of iatrogenic tumor rupture.The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups,respectively:for operative time:83.86±44.41 vs 80.77±36.46 min,P=0.627;conversion rate:0%vs 0%;estimated blood loss:27.74±45.2vs 29.59±41.18 m L,P=0.780;tumor rupture during surgery:0.90%vs 2.82%,P=0.322;or postoperative complications:3.74%vs 7.04%,P=0.325.The follow-up period recurrence rate was 1.89%with no significant differences between the two groups(3.03%vs 0%,P=0.447).Overall 5-year survival rate was98.76%and survival rates were similar between the two groups:98.99%vs 98.39%,P=0.623(unfavorable vs favorable,respectively).CONCLUSION The laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes.Strategies for laparoscopic resection should be selected according to the location and size of the tumor.Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.

Laparoscopic vs open extended right hemicolectomy for colon cancer

AIM:To evaluate the feasibility,safety,and oncologic outcomes of laparoscopic extended right hemicolectomy(LERH)for colon cancer.METHODS:Since its establishment in 2009,the Southern Chinese Laparoscopic Colorectal Surgical Study(SCLCSS)group has been dedicated to promoting patients’quality of life through minimally invasive surgery.The multicenter database was launched by combining existing datasets from members of the SCLCSS group.The study enrolled 220 consecutive patients who were recorded in the multicenter retrospective database and underwent either LERH(n=119)or open extended right hemicolectomy(OERH)(n=101)for colon cancer.Clinical characteristics,surgical outcomes,and oncologic outcomes were compared between the two groups.RESULTS:There were no significant differences in terms of age,gender,body mass index(BMI),history of previous abdominal surgery,tumor location,and tumor stage between the two groups.The blood loss was lower in the LERH group than in the OERH group[100(100-200)mL vs 150(100-200)mL,P<0.0001].The LERH group was associated with earlier first flatus(2.7±1.0 d vs 3.2±0.9 d,P<0.0001)and resumption of liquid diet(3.6±1.0 d vs 4.2±1.0 d,P<0.0001)compared to the OERH group.The postoperative hospital stay was significantly shorter in the LERH group(11.4±4.7 d vs 12.8±5.6 d,P=0.009)than in the OERH group.The complication rate was 11.8%and17.6%in the LERH and OERH groups,respectively(P=0.215).Both 3-year overall survival[LERH(92.0%)vs OERH(84.4%),P=0.209]and 3-year disease-free survival[LERH(84.6%)vs OERH(76.6%),P=0.191]were comparable between the two groups.CONCLUSION:LERH with D3 lymphadenectomy for colon cancer is a technically feasible and safe procedure,yielding comparable short-term oncologic outcomes to those of open surgery.

Performance of risk stratification systems for gastrointestinal stromal tumors: A multicenter study

BACKGROUND Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumor type in the gastrointestinal system. Presently, various classification systems to prognosticate GISTs have been proposed.AIM To evaluate the application value of four different risk stratification systems for GISTs.METHODS Patients who were diagnosed with GISTs and underwent surgical resection at four hospitals from 1998 to 2015 were identified from a database. Risk of recurrence was stratified by the modified National Institute of Health(NIH)criteria, the Armed Forces Institute of Pathology(AFIP) criteria, the Memorial Sloan Kettering Cancer Center(MSKCC) prognostic nomogram, and the contour maps. Receiver operating characteristic(ROC) curves were established to compare the four abovementioned risk stratification systems based on the area under the curve(AUC).RESULTS A total of 1303 patients were included in the study. The mean age of the patients was 55.77 ± 13.70 yr; 52.3% of the patients were male. The mean follow-up period was 64.91 ± 35.79 mo. Approximately 67.0% the tumors were located in the stomach, and 59.5% were smaller than 5 cm; 67.3% of the patients had a mitotic count ≤ 5/50 high-power fields(HPFs). Thirty-four tumors ruptured before and during surgery. Univariate analysis demonstrated that tumor size > 5 cm(P <0.05), mitotic count > 5/50 HPFs(P < 0.05), non-gastric location(P < 0.05), and tumor rupture(P < 0.05) were significantly associated with increased recurrence rates. According to the ROC curve, the AFIP criteria showed the largest AUC(0.754).CONCLUSION According to our data, the AFIP criteria were associated with a larger AUC than the NIH modified criteria, the MSKCC nomogram, and the contour maps, which might indicate that the AFIP criteria have better accuracy to support therapeutic decision-making for patients with GISTs.

Using Materialise’s interactive medical image control system to reconstruct a model of a patient with rectal cancer and situs inversus totalis: A case report

BACKGROUND Situs inversus totalis(SIT)is a rare congenital anomaly that refers to a completely reversed location of abdominal and thoracic organs.An extremely small number of patients with this condition,especially those with rectal neoplasms,have been reported.Surgery in these patients is technically challenging.Therefore,we reconstructed a three-dimensional(3D)digital model with the Materialise’s interactive medical image control system(Mimics)as a guide for laparoscopic resection.CASE SUMMARY We report the case of a 68-year-old woman with rectal neoplasms and SIT diagnosed by electronic colonoscopy biopsy and enhanced computed tomography(CT),which showed that there was a soft tissue mass protruding into the lumen in the lower rectal segment,a lesion that involved the serosal layer,multiple enlarged peripheral lymph nodes,and visceral situs abnormalities.Based on the CT images,we reconstructed a 3D model with Mimics to assist with our surgical planning.Then,we performed laparoscopyassisted radical resection of the rectal neoplasms and total excision of the lesion.Adjuvant chemotherapy with the XELOX regimen(oxaliplatin 150 mg,D1+Xeloda 1.0 g,Bid,D1-14)was initiated 1 mo after the operation.The patient recovered well after surgery,and her physical condition remained stable.CONCLUSION Preoperative 3D reconstruction of the imaging results could help reduce the unknown risks during surgery caused by anatomical abnormalities and improvethe perioperative safety for patients.

对比经口置入砥钉座方法进行食管空肠吻合与使用圆形吻合器进行腔外吻合应用于Siewert 2型食管胃结合部腺癌全胃切除后消化道重建的安全性

背景:对于近端胃癌全胃切除后消化道重建,采用经口置入砥钉座方法进行腔内食管空肠吻合已被证明是安全可行的。但尚未见到该方法用于Siewert 2型食管胃结合部腺癌(AEG)的评估报道。方法:2008年1月至2016年12月间,428例连续胃癌患者在广州南方医院接受腹腔镜全胃切除术,其中98例被归为Siewert 2型AEG。在98例AEG患者中,27例采用经口置入砥钉座方法进行腔内食管空肠吻合(经口组),71例采用圆形吻合器进行腔外食管空肠吻合(腔外组)。在基于吻合口漏危险因素进行1:1的倾向评分匹配后,26对匹配患者纳入分析。比较两组患者术后30天的安全性。结果:两组患者基线资料均衡。手术时间、消化道重建耗时、淋巴结清扫数量、近切缘长度、术中失血量、术中并发症发生率和术后恢复时间两组差异均无统计学意义。经口组相较腔外组,砥钉座置入时间更短(平均数:9.7 vs 13.4 min,P<0.001),手术切口更短(中位数:5.5 vs 7.0 cm,P<0.001)。术后并发症发生率两组差异无统计学意义(26.9%vs 23.1%,P¼0.749),并发症严重程度亦无显著差异(P¼0.939)。结论:采用经口置入砥钉座方法进行腔内食管空肠吻合,用以简化并优化Siewert 2型AEG患者全胃切除术后的消化道重建,是潜在安全的。

腹腔镜辅助对比开腹远端胃切除术治疗老年进展期胃癌的并发症发生率和病死率:随机对照试验

Laparoscopy-assisted distal gastrectomy(LDG)combined with D2 lymphadenectomy may be safely performed in patients with advanced gastric cancer(AGC)by experienced surgeons at specialized high-volume institutions as shown in the Chinese Laparoscopic Gastrointestinal Surgery Study(CLASS)-01.However,studies focusing on the use of LDG in patients with gastric cancer older than 65 years are rare.This study was designed to investigate the morbidity and mortality of elderly patients with gastric cancer who underwent laparoscopic-assisted or open distal gastrectomy(ODG).In this prospective,randomized,open,parallel controlled trial,patients older than 65 years with tumor located at the middle or lower part of the stomach will be enrolled in this study.Patients will be randomly divided into a laparoscopic group and an open surgery group.The early post-operative complications,intra-operative complications and post-operative recovery will be compared between the two groups.This trial will provide valuable clinical evidence for the objective assessment of the feasibility,short-term safety,and potential benefits of LDG compared with ODG for gastric cancer in the elderly patients.This trial has been registered on ClinicalTrials.gov.(Identifier:NCT02246153.)in September 22,2014.