Cell Line ; Humans ; MicroRNAs ; metabolism ; Stomach Neoplasms ; metabolism

Objective To investigate the clinical efficacy of laparoscopic vagus nerve and pylorus-preserring gastrectomy (LVNPPG) for early gastric cancer.Methods The retrospective descriptive study was conducted.The clinical data of 5 patients who underwent LVNPPG for early gastric cancer at the Peking University Cancer Hospital between May 2016 and September 2016 were collected.Patients underwent laparoscope-assisted or total laparoscopic vagus nerve (hepatic branch and celiac branch) and pylorus-preserving gastrectomy.Observation indicators:(1) surgical situations;(2) postoperative situations;(3) postoperative pathological examination;(4) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and tumor metastasis and recurrence up to December 2016.Measurement data with normal distribution was represented as average (range).Results (1) Surgical situations:of 5 patients undergoing successful LVNPPG,digestive tract reconstruction using auxiliary incision was conducted in 3 patients and total laparoscopic surgery in 2 patients.Three patients received appliance side-to-side anastomosis and 2 received manual end-to-end anastomosis.Hepatic branch and celiac branch of vagus nerve in 5 patients were preserved.Average operation time and volume of intraoperative blood loss were 220 minutes (range,180-305 minutes) and 108 mL (range,30-216 mL).(2) Postoperative situations:average time to initial bowel exsufflation,average times for fluid diet intake and for semifluid diet intake were 3 days (range,2-4 days),3 days (range,1-5 days)and 10 days (range,5-25 days),respectively.One patient complicated with delayed gastric emptying was improved by conservative treatment.Duration of hospital stay of 5 patients was 13 days (range,7-32 days).(3)Postoperative pathological examination:number of lymph node dissected,average lengths of proximal margin and distal margin were 22 (range,15-35),3.5 cm (range,2.2-5.0 cm) and 3.7 cm (range,2.0-5.5 cm),respectively.Pathological T stage:pT0 stage was detected in 1 patient,pT1a stage in 1 patient,pT1b stage in 2 patients and pT2 stage in 1 patient.Pathological N stage:pN0 stage was detected in 3 patients and pN2 in 2 patients.Pathological TNM stage:0 stage was detected in 1 patient,Ⅰ a stage in 2 patients,Ⅱ a stage in 1 patient and Ⅱb stage in 1 patient.Two patients had stage migration,including from cT1N0 to pT2N2 and from cT0N0 to pTlbN2.(4) Follow-up situations:5 patients were followed up for 2.8-7.0 months,with a median time of 5.6 months.During follow-up,there were no death and occurrence of tumor metastasis and recurrence.Conclusion LVNPPG is safe and feasible for early gastric cancer.

Objective To explore the impact of neoadjuvant therapy on the number of harvested lymph nodes in D2 radical resection of the proximal locally advanced gastric cancer (GC).Methods The retrospective cohort study was conducted.The clinicopathological data of 319 patients with proximal locally advanced GC who were admitted to the Beijing Cancer Hospital from January 2013 to September 2016 were collected.Of 319 patients,200 underwent D2 radical resection of GC and didn't undergo neoadjuvant therapy who were divided into the surgery group,88 underwent neoadjuvant chemotherapy into the chemotherapy group,and 31 underwent neoadjuvant chemoradiotherapy into the chemoradiotherapy group.Observation indicators and evaluation criteria:comparison of postoperative pathological results among 3 groups,according to tumor staging guideline of American Joint Committee on Cancer (AJCC) (8th version) Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA.Measurement data with skewed distribution were described as M (range),comparisons among groups were analyzed using the ANOVA,and pairwise comparisons were analyzed using nonparametric test.Comparisons of count data among groups were analyzed using the exact chisquare test,and pairwise comparisons were analyzed using the chi-square partition method.Results Comparison of postoperative pathological results among 3 groups:stage T0,Tla,Tlb,T2,T3,T4a and T4b of T staging were respectively detected in 0,2,10,24,99,58,7 patients in the surgery group and 5,1,2,11,41,26,2 patients in the chemotherapy group and 5,1,2,8,10,4,1 patients in the chemoradiotherapy group.Stage N0,N1,N2,N3a and N3b of N staging 56,41,34,47,22 patients in the surgery group and 29,17,27,10,5 patients in the chemotherapy group and 18,10,2,1,0 in the chemoradiotherapy group.Cases with and without lymphovascular invasion were respectively 124,76 in the surgery group and 43,45 in the chemotherapy group and 6,25 in the chemoradiotherapy group.Total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis in the surgery,chemotherapy and chemoradiotherapy groups were respectively 31 (range,15-87),30 (range,15-62),21 (range,15-36) and 3 (range,0-39),2 (range,0-37),0 (range,0-7) and 9.2％ (range,0-91.3％),7.7％ (range,0-78.7％),0 (range,0-30.4％).There were statistically significant differences in the T staging,N staging,with and without lymphovascular invasion,total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis among groups (x2 =35.799,32.489,21.076,Z =27.120,22.088,16.947,P ＜ 0.05).There were statistically significant differences in the above indicators between surgery group and chemoradiotherapy group (x2 =28.500,20.124,19.570,P＜0.05),and no statistically significant difference in the above indicators between surgery group and chemotherapy group (x2 =11.436,12.343,4.295,P＞ 0.05).There were statistically significant differences in the N staging,with and without lymphovascular invasion,total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis between chemotherapy group and chemoradiotherapy group (x2 =14.027,8.313,P＜ 0.05),and no statistically significant difference in the T staging between chemotherapy group and chemoradiotherapy group (x2=11.742,P＞ 0.05).Conclusion Neoadjuvant chemoradiotherapy could reduce the total number of harvested lymph nodes and number of lymph node metastases after radical resection of proximal locally advanced GC.

OBJECTIVETo compare the short-term safety and costs between laparoscopic assisted or totally laparoscopic uncut Roux-en-Y and Billroth II((BII() + Braun reconstruction after radical gastrectomy of distal gastric cancer.

METHODSClinical data from our prospective database of radical gastrectomy were systematically analyzed. The patients who underwent laparoscopic gastrectomy with uncut Roux-en-Y or BII(+ Braun reconstruction between March 1st, 2015 and June 30th, 2017 were screened out for further analysis. Both the reconstructions were completed by linear staplers. Uncut Roux-en-Y reconstruction was performed with a 45 mm no-knife linear stapler (ATS45NK) on the afferent loop below the gastrojejunostomy. Continuous variables were compared using independent samples t test or Mann-Whitney U. The frequencies of categorical variables were compared using Chi-squared or Fisher exact test.

RESULTSEighty-one patients were in uncut Roux-en-Y group and 58 patients were in BII(+Braun group. There were no significant differences between uncut Roux-en-Y group and BII(+Braun group in median age (56.0 years vs. 56.5 years, P=0.757), gender (male/female, 52/29 vs. 46/12, P=0.054), history of abdominal surgery (yes/no, 10/71 vs. 4/54, P=0.293), neoadjuvant chemotherapy (yes/no, 21/60 vs. 11/47, P=0.336), BMI (thin/normal/overweight/obesity, 2/49/26/3 vs. 3/39/14/2, P=0.591), NRS 2002 score (1/2/3/4, 58/15/5/3 vs. 47/5/3/3, P=0.403), pathological stage (0/I(/II(/III(, 3/41/20/17 vs. 1/28/13/16, P=0.755), median tumor diameter in long axis (2.5 cm vs. 3.0 cm, P=0.278), median tumor diameter in short axis (2.0 cm vs. 2.0 cm, P=0.126) and some other clinical and pathological characteristics. There were no significant differences between uncut Roux-en-Y group and BII(+Braun group in morbidity of postoperative complication more severe than grade I([12.3% (10/81) vs. 17.2% (10/58), P=0.417], morbidity of anastomotic complication [1.2%(1/81) vs. 0, P=1.000] or hospitalization costs [(94000±14000) yuan vs.(95000±16000) yuan, P=0.895]. The median first time to liquid diet (57.1 hours vs. 70.8 hours, P=0.017) and median postoperative hospital stay (9 days vs. 11 days, P=0.003) of the patients in uncut Roux-en-Y group were shorter than those in BII(+Braun group.

CONCLUSIONLaparoscopic assisted or totally laparoscopic uncut Roux-en-Y reconstruction after radical gastrectomy of distal gastric cancer is safe and feasible with better recovery than BII(+Braun reconstruction.

Anastomosis, Roux-en-Y ; Databases, Factual ; Female ; Gastrectomy ; Gastroenterostomy ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Prospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

Objective To explore the application value of carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy.Methods The retrospective cohort study was conducted.The clinicopathological data of 56 patients with adenocarcinoma of esophagogastric junction who underwent preoperative chemoradiotherapy in the Peking University Cancer Hospital from January 2014 to November 2017 were collected.There were 52 males and 4 females,aged from 22 to 76 years,with an average age of 62 years.Among 56 patients undergoing total gastrectomy and D2 lymphadenectomy,17 using carbon nanoparticle lymph node staining and 39 using traditional lymph node sorting were respectively allocated into observation group and control group.Observation indicators:(1) treatment situations;(2) detection of lymph nodes;(3) perioperative complications;(4) follow-up.Followup using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis up to May 2019.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated by the independent sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was evaluated by the Mann-Whitney U test.Count data were described as absolute numbers,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data was analyzed using the nonparametric rank sum test.Results (1) Treatment situations:patients in both groups were successfully treated with concurrent chemoradiotherapy based on intensity modulated radiotherapy before operation.Radical gastrectomy with D2 lymphadenectomy was successfully performed after chemoradiotherapy,and Roux-en-Y esophagojejunostomy was used to reconstruct the digestive tract during operation.The operation time and volume of intraoperative blood loss were respectively (217± 58)minutes and (112±60)mL in the observation group,and (235±65) minutes and (119±77)mL in the control group,with no statistically significant difference between the two groups (t =1.017,0.341,P＞0.05).(2) Detection of lymph nodes:the average number of harvested lymph nodes,average number of radiation target lymph nodes,and average number of peritarget lymph nodes were respectively 32± 10,21±8,and 7±4 in the observation group,and 22±7,16±5,5±3 in the control group,with statistically significant differences between the two groups (t=4.138,2.881,2.401,P＜0.05).The median number of positive lymph nodes harvested,median number of positive radiation target lymph nodes,and median number of positive peritarget lymph nodes were respectively 0 (range,0-2),0 (range,0-2),and 0 (range,0-0) in the observation group,and 0 (range,0-7),0 (range,0-3),and 0 (range,0-1) in the control group,showing no statistically significant difference between the two groups (Z=1.305,1.101,0.660,P ＞ 0.05).(3) Perioperative complications:6 and 18 patients in the observation group and the control group had complications,respectively,with no statistically significant difference between the two groups (x2=0.570,P＞0.05).Patients with complications were improved after drug treatment and local treatment without second operation.No local or systemic adverse reactions caused by carbon nanoparticles was observed during and after operation in the observation group.(4) Follow-up:56 patients were followed up for 5-65 months,with a median follow-up time of 32 months.There were 14 and 6 patients in the observation group and the control group with tumor recurrence or metastasis,respectively,showing no significant difference between the two groups (x2 =0.002,P＞0.05).Conclusion Carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy can increase the number of harvested lymph nodes.

Since the outbreak of Corona Virus Disease 2019 occurred in December 2019, the reduction of population mobility has curbed the spread of the epidemic to some extent but also prolonged the waiting time for the treatment of patients with gastric cancer. Based on fully understanding the different staging characteristics of gastric cancer, clinical departments should develop reasonable out-of-hospital management strategies. On one hand, reasonable communication channels should be established to allow patients to receive adequate guidance out of the hospital. On the other hand, shared decisions with patients should be made to adjust treatment strategies, and education on viral prevention should be implemented to minimize the impact of the epidemic on tumor treatment.

OBJECTIVETo investigate the regulation of α-Tocopherol on NFκB and Nrf2 signaling pathway at early stage of N-nitrosomethylbenzylamine (NMBzA)-induced human esophageal carcinogenesis.

METHODSHuman normal esophageal HET-1A cells were treated with NMBzA at 50 µmol/L, 100 µmol/L for 24 h to intimate the initiation of esophageal carcinogenesis. For intervention groups, HET-1A cells were pre-treated with α-T at 25, 50, 100 µmol/L for 3 h and then co-treated with NMBzA (100 µmol/L) for 24 h. In comparison with HET-1A cells, human esophageal cancer EC109 cells were treated with α-T at corresponding concentrations. Cells treated with 0.1% DMSO were used as negative control. Immunofluorence staining was used for the determination of distribution and activation of NFκB p65 and Nrf2 in the cell. Real time PCR and Western blot were used to determine the expression levels of target genes including cyclinD1, KI67, proliferating cell nuclear antigen (PCNA), cyclo-oxygen-ase 2 (COX2), 5LOX, HO-1, NQO1 and GCLC. Flow cytometry was utilized to analyze the reactive oxygen species contents in the cells.

RESULTSAs compared to the control group (1.00 ± 0.08), the expression of CyclinD1 (2.99 ± 0.15), KI67 (2.35 ± 0.38) and PCNA (2.46 ± 0.25) in HET-1A were all markedly increased by NMBzA treatment (F values were 97.23, 65.28, 34.62, P < 0.001). Also, the proportion of cells with nucleus translocation of NFκB p65 (71.0%, 98/138) or Nrf2 (36.3%, 49/135) were significantly increased (χ² values were 194.71, 133.72, P < 0.001), and the expression of COX2 (3.22 ± 0.17), 5LOX (2.87 ± 0.12) as well as HO-1 (1.87 ± 0.22), NQO1 (2.14 ± 0.08), GCLC (2.63 ± 0.41) at protein levels were elevated (F values were 72.35, 43.87, 69.23, 71.34, 85.79, P values were 0.013, 0.015, 0.010, 0.011, 0.002). Under the treatment with 50 µmol/L α-T, comparing with the control group(59.1%,65/110),the nuclear translocation of NFκB p65 (77.7%, 8/104) was clearly inhibited (χ² = 148.1, P < 0.001), and protein expression levels of COX2 (0.74 ± 0.19) and 5LOX (0.42 ± 0.13) were decreased (F values were 56.31, 73.25, P values were 0.003, 0.001). However, no changes on Nrf2 signaling pathway were observed; α-T showed little impact on NFκB or Nrf2 pathway in EC109 cells.

CONCLUSIONSAt the early stage of NMBz-induced esophageal cancer, α-T could block the initiation of carcinogenesis through suppressing the activation of NFκB signaling pathway. It might be the major mechanism by which α-T is potentially chemopreventive to esophageal cancer. During the progression of esophageal cancer, the cells may acquire the adaptive functions to accommodate oxidative stress via activating Nrf2 pathway.

Carcinogenesis ; Cyclooxygenase 2 ; Dimethylnitrosamine ; analogs & derivatives ; Esophageal Neoplasms ; Heme Oxygenase-1 ; Humans ; NAD(P)H Dehydrogenase (Quinone) ; NF-E2-Related Factor 2 ; NF-kappa B ; Oxidative Stress ; Reactive Oxygen Species ; Signal Transduction ; alpha-Tocopherol

Sennoside A (SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota-GLP1 axis to improve glucose metabolism in the obese mice.