Short-term efficacy of totally laparoscopic distal gastrectomy after endoscopic submucosal dissec-tion versus totally laparoscopic distal gastrectomy for early gastric cancer / 中华消化外科杂志

Objective:To investigate the short-term efficacy of totally laparoscopic distal gastrectomy (TLDG) after endoscopic submucosal dissection (ESD) versus direct TLDG for early gastric cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 623 patients with early gastric cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University from March 2014 to December 2019 were collected. There were 405 males and 218 females, aged from 26 to 86 years, with a median age of 62 years. Of 623 patients, 25 cases undergoing TLDG after ESD were divided into ESD+TLDG group and 598 cases undergoing TLDG directly were divided into TLDG group. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after propensity score matching; (2) intraoperative and postoperative situations of TLDG; (3) stratification analysis of the ESD+TLDG group. The propensity score matching was conducted by 1∶2 matching using the nearest neighbor method. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was done using the t test. Measurement data with skewed distribution were represented as M (range) and comparison between groups was done using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test. Results:(1) The propensity score matching conditions and comparison of general data between the two groups after propensity score matching: 75 of 623 patients had successful matching, including 25 in the ESD+TLDG group and 50 in the TLDG group. Before propensity score matching, the body mass index (BMI), cases with tumor diameter ≤20 mm, 21 to 30 mm or>30 mm, cases with tumor classified as stage Ⅰ, stage Ⅱ or stage Ⅲ of clinical staging were (22.3±3.6)kg/m 2, 16, 6, 3, 24, 1, 0 of the ESD+TLDG group, respectively, versus (24.3±2.7)kg/m 2, 238, 125, 235, 312, 126, 160 of the TLDG group, showing significant differences in the above indicators between the two groups ( t=2.744, Z=?2.834, ?4.209, P<0.05). After propensity score matching, the BMI, cases with tumor diameter ≤20 mm, 21 to 30 mm or >30 mm, cases with tumor classified as stage Ⅰ or stage Ⅱ of clinical staging were (22.3±3.6)kg/m 2, 16, 6, 3, 24, 1 of the ESD+TLDG group, versus (23.6±2.9)kg/m 2, 29, 12, 9, 48, 2 of the TLDG group, showing no significant difference between the two groups ( t=1.542, Z=?0.597, 0.000, P>0.05). (2) Intraoperative and postoperative situations of TLDG: after propensity score matching, the operation time and time to postoperative drainage tube removal were 180 minutes(range, 124 to 289 minutes) and 6 days(range, 4 to 13 days) of the ESD+TLDG group,respectively,versus 170 minutes(range, 106 to 250 minutes) and 6 days (range, 4 to 9 days) of the TLDG group, showing significant differences between the two groups ( Z=-2.396, -3.039, P<0.05). Cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL, the number of lymph node dissected, duration of postoperative hospital stay, cases with perioperative complications as incision fat liquefaction, delayed gastric emptying, anastomotic bleeding or pulmonary infection were 7, 9, 9,34(range, 16 to 58), 8 days(range, 6 to 31 days), 1, 1, 0, 0 of the ESD+TLDG group,respectively,versus 18, 26, 6, 39 (range, 22 to 68), 8 days (range, 6 to 29 days), 0, 0, 1, 1 of the TLDG group, showing no significant difference between the two groups ( Z=-1.703, -1.958, -1.139, χ2=0.033, P>0.05). Cases with anastomotic bleeding were recovered after hemostasis under endoscopy and cases with other perioperative complications were recovered after conservative treatment. (3) Stratification analysis of the ESD+TLDG group. ① For 5 cases undergoing TLDG ≤14 days after ESD and 20 cases undergoing TLDG >14 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 200 minutes(range, 170 to 289 minutes), 0, 3, 2, 36(range, 9 to 57), 7 days(range, 5 to 9 days), 8 days(range, 7 to 9 days), 1 and 180 minutes (range, 124 to 253 minutes), 8, 6, 6, 34(range, 8 to 78), 6 days(range, 4 to 13 days), 8 days(range, 6 to 31 days), 1, respectively, showing no significant difference in the operation time of TLDG, volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative tube removal and duration of postoperative hospital stay between the two groups ( Z=?1.536, ?1.993, ?0.238, ?0.932, ?0.589, P>0.05), and no significant difference in cases with perioperative complications between the two groups ( P>0.05). ② For 13 cases undergoing TLDG ≤21 days after ESD and cases undergoing TLDG >21 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss as <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 200 minutes(range, 145 to 289 minutes), 2, 6, 5, 34(range, 8 to 57), 6 days(range, 4 to 11 days), 8 days(range, 6 to 11 days), 1 and 179 minutes(range, 124 to 240 minutes), 6, 3, 3, 34(range, 16 to 78), 6 days(range, 5 to 13 days), 8 days(range, 6 to 31 days), 1, respectively, showing a significant difference in the operation time of TLDG between the two groups ( Z=?2.241, P<0.05), while showing no significant difference in the volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay between the two groups ( Z=?1.471, ?0.163, ?0.084, ?0.194, P>0.05) and no significant difference in cases with perioperative complications between the two groups ( P>0.05). ③ For 15 cases undergoing TLDG ≤28 days after ESD and 10 cases undergoing TLDG >28 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 190 minutes (range, 145 to 289 minutes), 2, 7, 6, 33(range, 8 to 57), 6 days(range, 4 to 11 days), 8 days(range, 6 to 31 days), 1 and 179 minutes(range, 124 to 240 minutes), 6, 2, 2, 37(range, 16 to 78), 6 days (range, 5 to 13 days), 8 days(range, 6 to 14 days), 1, respectively, showing no significant difference in the operation time of TLDG, volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative tube removal and duration of postoperative hospital stay between the two groups ( Z=?1.619, ?2.000, ?0.667, ?0.370, ?0.057, P>0.05), and no significant difference in cases with perioperative complications between the two groups ( P>0.05). Conclusions:Compared with cases undergoing TLDG directly, the operation time to TLDG and time to drainage tube removal after TLDG for cases undergoing ESD+TLDG are prolonged, but there is no difference in the short-term efficacy. For cases undergoing TLDG ≤21 days after ESD and cases undergoing TLDG >21 days after ESD, there is a significant difference in the operation time of TLDG.

Application value of the π-shaped esophagojejunostomy in totally laparoscopic total gastrectomy / 中华消化外科杂志

Objective To explore the safety and feasibility of the π-shaped esophagojeunostomy in totally laparoscopic total gastrectomy.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 6 patients with gastric cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University between May 2016 and August 2016 were collected.All the 6 patients underwent totally laparoscopic total gastrectomy,operation procedures included esophagus and stomach mobilization,lymph node dissection,π-shaped esophagojejunostomy,and then laparoscopic digestive tract reconstruction after jejunojejunal anastomosis.Observation indicators included:(1) surgical situations:conversion to open surgery,operation time,time of π-shaped esophagojejunostomy,volume of intraoperative blood loss,number of lymph node dissected;(2) postoperative situations:time for initial out-of-bed activity,time of initial anal exsufflation,time of initial liquid diet intake,time of abdominal drainage tube removal,postoperative complications and duration of postoperative hospital stay;(3) postoperative pathological examination;(4) follow-up and survival situations.Follow-up using outpatient examination was performed to detect the anastomotic stenosis,patients' survival and tumor metastasis and recurrence up to November 2016.The measurement data with normal distribution were represented as (x)±s.Results (1) Surgical situations:all the 6 patients underwent successful totally laparoscopic total gastrectomy using the π-shaped esophagojejunostomy,without conversion to open surgery and perioperative death.Operation time,time of π-shaped esophagojejunostomy,volume of intraoperative blood loss and number of lymph node dissected were respectively (282 ± 49) minutes,(37 ± 9) minutes,(37 ± 8) mL and 39 9.(2) Postoperative situations:time for initial out-of-bed activity,time of initial anal exsufflation,time of initial liquid-diet intake,time of abdominal drainage tube removal and duration of postoperative hospital stay of 6 patients were (44± 38)hours,(72±21)hours,(6.5±l.1)days,(11±7) days and (15±7) days,respectively.Six patients were not complicated with postoperative hemorrhage,duodenal stump fistula and death.One patient with anastomotic fistula was cured by abdominal puncture drainage under guidance of computed tomography (CT),enteral nutrition and antibiotic therapy,and then was discharged from hospital.(3) Postoperative pathological examination:pTNM staging showed that stage Ⅰ A,Ⅱ A,ⅡB and ⅢA were detected in 3,1,1 and 1 patients,respectively.(4) Follow-up and survival situations:6 patients were followed up for 3-6 months,with a median time of 4 months.During follow-up,results of compound meglumine diatrizoate gastrointestinal radiography showed that there were smooth anastomoses,and no tumor recurrence or metastasis and death.Conclusion The π-shaped esophagojejunostomy is safe and feasible in totally laparoscopic total gastrectomy.

Analysis of clinicopathologic factors affecting formation of lymphovascular invasion in 1 260 patients with gastric cancer / 中华消化外科杂志

Objective To analyze the clinicopathologic factors affecting the formation of lymphovascular invasion (LⅥ) in patients with gastric cancer.Methods The retrospective case-control study was conduted.The clinicopathologic data of 1 260 patients with gastric cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University between January 2014 and December 2015 were collected.All the surgical specimens of patients were detected by hematoxylin-eosin (HE) stain and diagnosed by pathological experts.Stages of patients were evaluated by the seventh TNM staging system for gastric cancer of American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC).Observation indicators:(1) pathologica features:histological differentiation,invasive depth,lymph node metastasis and TNM staging;(2) follow-up situations;(3) influenced factors of the positive LⅥ:sex,age,histological differentiation,invasive depth,number of lymph node metastasis and TNM staging affecting positive LⅥ were analyzed.Follow-up using outpatient examination and telephone interview were performed to detect survival of patients up to June 2016.Univariate analysis was done using the chi-square test,and multivariate analysis was done using the trend chi-square test,and binary Logistic regression model.Results (1) Pathological features:1 260 patients with gastric cancer were diagnosed by postoperative pathological examinations,including 355 with positive LⅥ and 905 with negative LⅥ.Histological differentiation:high-differentiated tumor was detected in 13 patients,moderate-differentiated tumor in 232 patients and low-differentiated tumor in 775 patients.There were 95 patients with mucinous adenocarcinoma and 145 with signet-ring cell carcinoma.Invasive depth:tumor invasion into mucosal layer or submucosal layer (T1 stage) was detected in 242 patients,muscular layer (T2 stage) in 160 patients,gastric wall layer and no invasion into serosal layer (T3 stage) in 37 patients and subserosal layer (T4 stage) in 821 patients.Lymph node metastasis:no regional lymph node metastasis (N0 stage) was detected in 461 patients,1-2 lymph nodes metastases (N1 stage)in 164 patients,3-6 lymph nodes metastases (N2 stage) in 245 patients and more than 7 lymph nodes metastases (N3 stage) in 390 patients.TNM staging:there were respectively 191 patients in Ⅰ A stage,114 in Ⅰ B stage,62 in ⅡA stage,202 in ⅡB stage,132 in ⅢA stage,80 in ⅢB stage,476 in ⅢC stage and 3 in Ⅳ stage.(2)Follow-up situations:1 142 patients (320 with positive LⅥ and 822 with negative LⅥ) were followed up for 4.0-24.0 months,with a meidan time of 11.0 months and a follow-up rate of 90.635％ (1 142/1 260).During the follow-up,154 patients died,including 41 with positive LⅥ and 113 with negative LⅥ.(3) Influenced factors of the positive LⅥ:① results of univariate analysis showed that histological differentiation,invasive depth,number of lymph node metastasis and TNM staging were factors affecting positive LⅥ of patients with gastric cancer (X2=16.930,29.190,64.463,46.539,P＜0.05).② Results of the trend chi-square test showed that histological differentiation,invasive depth,number of lymph node metastasis and TNM staging were factors affecting positive LⅥ of patients with gastric cancer,with a linear correlation (X2 =54.883,69.130,164.618,119.594,r=0.211,0.243,0.365,0.316,P＜0.05).There was a greater correlation between number of lymph node metastasis and formation of lymphovascular invasion.③ Results of the binary Logistic regression model showed that moderate-and low-differentiated tumor and N1-N3 stage of lymph node metastasis were independent risk factors affecting positive LⅥ of patients with gastric cancer (OR=2.572,1.782,95％ confidence interval:0.495-1.494,0.386-0.781,P＜0.05).Conclusion Patients with lower tumor differentiation and / or greater number of lymph node metastasis may have a higher risk of forming LⅥ.

The key points of prevention for special surgical complications after radical operation of gastric cancer / 中华胃肠外科杂志

Incidence of gastric cancer is high in China and standard radical operation is currently the main treatment for gastric cancer. Postoperative complications, especially some special complications, can directly affect the prognosis of patients, even result in the increase of mortality. But the incidences of these special complications are low, so these complications are often misdiagnosed and delayed in treatment owing to insufficient recognition of medical staff. These special complications include (1) Peterson hernia: It is an abdominal hernia developed in the space between Roux loop and transverse colon mesentery after Roux-Y reconstruction of digestive tract. Peterson hernia is rare and can quickly result in gangrenous ileus. Because of low incidence and without specific clinical symptoms, this hernia does not attract enough attention in clinical practice, so the outcome will be very serious. Once the diagnosis is made, an emergent operation must be performed immediately. Peterson space should be closed routinely in order to avoid the development of hernia. (2) Lymphatic leakage: It is also called chyle leakage. Cisterna chylus is formed by gradual concentration of extensive lymphatic net to diaphragm angle within abdominal cavity. Lymphadenectomy during operation may easily damage lymphatic net and result in leakage. The use of ultrasonic scalpel can decrease the risk of lymphatic leakage in certain degree. If lymphatic leakage is found during operation, transfixion should be performed in time. Treatment includes total parenteral nutrition, maintenance of internal environment, supplement of protein, and observation by clamp as an attempt. (3)Duodenal stump leakage: It is one of serious complications affecting the recovery and leading to death after subtotal gastrectomy. Correct management of duodenal stump during operation is one of key points of the prevention of duodenal stump leakage. Routine purse embedding of duodenal stump is recommend during operation. The key treatment of this complication is to promt diagnosis and effective hemostasis.(4) Blood supply disorder of Roux-Y intestinal loop: Main preventive principle of this complication is to pay attention to the blood supply of vascular arch in intestinal edge. (5) Anastomotic obstruction by big purse of jejunal stump: When Roux-en-Y anastomosis is performed after distal radical operation for gastric cancer, anvil is placed in the remnant stomach and anastomat from distal jejunal stump is placed to make gastrojejunal anastomosis, and the stump is closed with big purse embedding. The embedding jejunal stump may enter gastric cavity leading to internal hernia and anastomotic obstruction. We suggest that application of interruptable and interlocking suture and fixation of stump on the gastric wall can avoid the development of this complication.

A Chinese multi-center study on the significance of monitoring imatinib plasma concentration in patients with gastrointestinal stromal tumor before and after administration / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.</p><p><b>METHODS</b>A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.</p><p><b>RESULTS</b>Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).</p><p><b>CONCLUSIONS</b>The imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.</p>

Peripheral blood skin-homing CD8+ T cells in patients with atopic dermatitis / 中华皮肤科杂志

Objective To quantify the percentage of CD8+ T cells and their expressions of cytotoxic molecules and homing-related chemokine receptors in peripheral blood from patients with atopic dermatitis (AD).Methods Peripheral blood was obtained from 15 patients with AD and 14 healthy controls.Flow cytometric analysis was performed to determine the percentages of CD8+ T cells and CD8+CLA+ T cells in the peripheral blood samples,as well as the expression levels of cytotoxic molecules and homing-related chemokine receptors on these cells.Differences in these parameters were analyzed using t test,and relationship between these parameters was evaluated using Pearson correlation coefficient.Results No significant difference was observed between the patients with AD and healthy controls in the percentage of CD8+ T cells,the expressions of perforin,granzyme B,CCR10,CCR6 or FasL on CD8+ T cells,or the expressions of CCR4,CCR10,CXCR6 or FasL on CLA+CD8+ T cells (all P ＞ 0.05).A significant increase was noted in the percentage of CLA+CD8+ T cells (3.80％ ± 1.46％ vs.2.18％ ± 0.85％,t =3.636,P ＜ 0.01) and expression rates of CCR4 on CD8+ T cells (13.86％ ± 4.42％ vs.9.50％ ± 2.14％,t =3.738,P ＜ 0.01) as well as perforin and granzyme B on CLA+CD8+ T cells (74.27％ ± 15.94％ vs.57.20％ ± 14.64％,t =2.998,P ＜ 0.01; 70.90％ ± 13.85％ vs.56.41％ ± 11.00％,t =3.104,P ＜ 0.01) in the patients with AD compared with the healthy controls.Conclusions The proportion of CLA+CD8+ T cells is increased with enhanced expressions of cytotoxic molecules such as perforin and granzyme B in peripheral blood of patients with AD,which may contribute to the pathogenesis of AD.

Cholesterol nucleation-promoting potency of retinol binding protein / 中华消化外科杂志

Objective To detect the nucleation-promoting potency of retinol binding protein (RBP) in the simulated bile system,and observe the process of cholesterol nucleation and crystallization.Methods Small and synthetic bile systems were synthesized.RBP (RBP group),α1-acid glycoprotein (AAG,AAG group) and albumin ( Alb,Alb group) were added into the Small bile respectively.The derived indices of nucleation time,crystal growth rate and final concentration of crystal were studied by Busch method.Alb ( control group) and RBP (experimental group) were added into the Small and synthetic bile systems respectively.The nucleation time was detected by polarizing microscopy according to the Holan method and the nucleation-promoting potency was calculated according to the Holzbach method. The morphological dynamics of cholesterol nucleation and crystallization were observed under a light microscope.All data were analyzed by using the analysis of variance or the t test.Results The derived indices of nucleation time,crystal growth rate and final concentration of crystal were 0.66,1.29 and 1.01 in the AAG group,and 0.73,1.02,0.95 in the RBP group,respectively.In the Small bile system,the average nucleation time of cholesterol monohydrate crrystals were ( 12.2 ± 1.2 )days in the control group and (8.2 ± 1.5)days in the experimental group,respectively,with a significant difference between the 2 groups (t =2.97,P ＜ 0.05 ).The nucleation activity of RBP was 0.67 in the Small bile system.In the synthetic bile system,the average nucleation time of cholesterol monohydrate crystals were (9.5 ± 1.1 ) days in the control group and (7.5 ± 1.1 )days in the experimental group,respectively,with a significant difference between the 2 groups ( t =2.35,P ＜ 0.05 ).The nucleation activity of RBP was 0.79 in the synthetic bile system.The process of cholesterol nucleation and crystallization was divided into 4 stages,and the split phenomenon appeared in the bile system at day 21.Conclusion RBP is a pro-nucleation factor in simulated bile system.