1.Related risk factors analysis of pancreatic fistula after radical resection of gastric cancer and establishment of risk prediction scoring model
Ping'an DING ; Zhidong ZHANG ; Peigang YANG ; Yuan TIAN ; Shixin ZHAN ; Honghai GUO ; Yang LIU ; Dong WANG ; Yong LI ; Qun ZHAO
Cancer Research and Clinic 2021;33(2):104-108
Objective:To investigate the risk factors of pancreatic fistula after radical resection of gastric cancer, and to establish a risk prediction scoring model for pancreatic fistula.Methods:The clinico-pathological data of 312 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from January 2019 to January 2020 were retrospectively analyzed. Multiple factor logistic regression model was used to analyze the risk factors of pancreatic fistula after radical resection of gastric cancer, and a risk prediction scoring model based on the risk factors was established. Hosmer-Lemeshow test was used to detect the goodness of fit of regression equation, and receiver operating characteristics (ROC) curve was used to evaluate the distinction degree of regression equation.Results:Among 312 patients with gastric cancer, 27 cases (8.65%) had pancreatic fistula after radical resection of gastric cancer. Multiple factor logistic regression analysis showed that male patients ( OR = 5.312, 95% CI 1.532-18.420, P = 0.008), age ≥ 60 years old ( OR = 4.928, 95% CI 1.493-16.250, P = 0.009), preoperative diabetes mellitus ( OR = 3.062, 95% CI 1.091-8.589, P = 0.034), lesion location in the gastric body-gastric antrum ( OR = 3.121, 95% CI 1.052-9.251, P = 0.040), intraoperative omental bursa resection ( OR = 6.209, 95% CI 2.084-18.478, P = 0.001), intraoperative lymph node dissection at D2+ station ( OR = 3.114, 95% CI 1.044-9.281, P = 0.042), intraoperative combined organ resection ( OR = 5.063, 95% CI 1.473-17.400, P = 0.010), preoperative TNM stage Ⅲ ( OR = 4.973, 95% CI 1.189-20.792, P = 0.028) were independent risk factors for pancreatic fistula after radical resection of gastric cancer. A risk prediction equation of pancreatic fistula after radical resection of patients with gastric cancer was established: P = -8.619+1.670X 1+1.595X 2+1.119X 3+1.138X 4+1.826X 5+1.136X 6+1.622X 7+1.604X 8; factor X was set as a binomial assignment (0 or 1); X1-X8 were listed as follows respectively: gender (the male was 1), age (≥60 years old was 1), preoperative diabetes history (yes was 1), lesion location (gastric body-gastric antrum was 1), intraoperative resection of omental bursa or not (yes was 1), intraoperative lymph node dissection at D2+ station or not (yes was 1), intraoperative combined organ resection or not (yes was 1), preoperative TNM stage (stage Ⅲ was 1). The goodness of fit of regression equation was high ( P = 0.395). The area under the curve of ROC by using risk prediction scoring model to judge pancreatic fistula was 0.916 (95% CI 0.872-0.960, P<0.01). The probability of pancreatic fistula in patients with score ≥ 5 was 40.90%, and the probability of pancreatic fistula in patients with score < 5 was 3.35%. Conclusions:The occurrence of pancreatic fistula after radical resection of gastric cancer is closely related to a variety of risk factors. By establishing a risk prediction scoring model for pancreatic fistula after radical resection of gastric cancer, it is helpful to effectively identify patients with high risk of pancreatic fistula after radical surgery during the perioperative period.
2.Analysis of clinico-pathological features and risk factors affecting prognosis in elderly patients with gastric cancer
Ping'an DING ; Peigang YANG ; Yuan TIAN ; Yiyang HU ; Yang LIU ; Honghai GUO ; Zhidong ZHANG ; Dong WANG ; Yong LI ; Qun ZHAO
Chinese Journal of Geriatrics 2021;40(1):96-101
Objective:To explore the clinico-pathological characteristics and risk factors affecting prognosis in elderly patients with gastric cancer.Methods:A retrospective study was used to retrospectively analyze 2386 patients with gastric cancer undergoing radical surgery in Surgery Department of the Fourth Hospital of Hebei Medical University from 1 January 2012 to 1 January 2015.Patients aged 70 years and older were screened so as to analyze clinical characteristics and influencing factors for the prognosis.Results:A total of 2386 patients with gastric cancer were divided into the elderly group aged 70 years and older(342 of 2386 cases, 14.3%). There were statistically significant differences between the two groups in gender, number of concomitant diseases, NRS2002 score, PG-SGA score, tumor location, tumor diameter, histological type, Borrmann classification, tumor invasion depth staging(pT), lymph node metastasis staging(pN), the anatomic extent of tumor staging(TNM, pTNM), and Lauren classifications( P<0.05). The 981 of 2386 cases(41.4%)had postoperative complications, accompanied by 413 cases(17.3%)of surgery-related complications and 568 cases(24.0%)of non-surgery-related complications.A multivariate logistic analysis showed that the number of preoperative co-existing diseases ≥ 2 was an independent influencing factor for postoperative complications in elderly gastric cancer patients( HR=4.478, 95% CI: 1.121-7.918, P=0.006). The 5-year OS and DSS was 21.10% and 62.73% in the ≥70 years gastric cancer group, and was 54.1% and 70.0% in the <70 years gastric cancer group, respectively.The difference in the 5-year OS between the two groups was statistically significant( P<0.05), while the difference in the 5-year DSS between the two groups was not statistically significant( P>0.05). Multivariate analysis by the Cox proportional hazard model showed that the independent risk factors for the prognosis of elderly patients with gastric cancer included the low-undifferentiated histological type of the tumor( P=0.004), the depth of tumor invasion pT stage of pT4a-pT4b( P=0.007), lymph node metastasis( P=0.034), tumor pTNM stage ⅢA-ⅢC( P=0.002)and vascular tumor thrombus( P=0.034). Conclusions:Elderly patients with gastric cancer have many preoperative co-existing diseases, which increases the risk of postoperative non-surgical complications.Therefore, we should focus on the peri-operative management of their comorbid diseases so as to improve the safety and efficacy of surgery.The advanced age is not the independent risk factors for the prognosis.
3.Risk factors relating to lymphatic leakage and prediction scoring model after radical gastrectomy for gastric carcinoma
Ping'an DING ; Zhidong ZHANG ; Peigang YANG ; Yuan TIAN ; Honghai GUO ; Yang LIU ; Tao ZHENG ; Dong WANG ; Yong LI ; Qun ZHAO
Chinese Journal of General Surgery 2021;36(7):530-534
Objective:To explore the risk factors of lymphatic fistula after radical gastric cancer operation.Methods:We retrospectively analyze the clinicopathological data of gastric cancer patients who underwent radical surgery from May, 2019 to May, 2020 at the Third Department of Surgery, Fourth Hospital of Hebei Medical University, and analyze the risk factors impacting postoperative lymphatic leakage,for the establishment of the risk prediction scoring model.Results:A total of 487 patients with gastric cancer underwent radical gastrectomy, of which 32 patients (6.6%) had lymphatic leakage . Multivariate logistic regression analysis showed that hypoproteinemia before surgery (95% CI: 1.222-7.357, P=0.016), the lesion is located in the cardia-fundus of the stomach (95% CI: 1.117-6.788, P=0.028),stage T3-T4 (95% CI: 1.149-25.676, P=0.033), operation time ≥4 h (95% CI: 1.469-11.480, P=0.007), combined organ resection (95% CI: 1.106-12.886, P=0.034), D2+ lymph node dissection (95% CI: 1.969-11.510, P=0.001), anemia (95% CI: 1.271-9.392, P=0.015) were an independent risk factors. Equation based on multi-factor Logistic regression: logit( P)=-9.624+1.098×X 1+1.013×X 2+1.692×X 3+1.413×X 4+1.328×X 5+1.560×X 6+1.240×X 7 was estaslished, using Hosmer. Lemeshow test detects the goodness of fit of the regression equation ( P=0.348). The area under the ROC curve was 0.856 (95% CI: 0.787-0.926, P<0.001); the probability of lymphatic leakage when scores ≥4 points was 14.1%, when scores <4 points ,the probability of leakage was 2.5%. Conclusion:A risk prediction scoring model for lymphatic leakage after radical gastrectomy, can identify patients with high risk after surgery
4.Application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction
Honghai GUO ; Xiayu DU ; Qi XIE ; Jun WANG ; Bibo TAN ; Peigang YANG ; Yuan TIAN ; Ping'an DING ; Liqiao FAN ; Yong LI ; Qun ZHAO
Chinese Journal of Digestive Surgery 2021;20(6):665-674
Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.
5.Laparoscopic or robotic serosa muscular layer circumferential incision combined with mucosal layer cutting and closure for gastrointestinal mesenchymal tumors at difficult sites of the stomach
Honghai GUO ; Yiyang HU ; Peigang YANG ; Yuan TIAN ; Dong WANG ; Zhidong ZHANG ; Xuefeng ZHAO ; Ping'an DING ; Yang LIU ; Yong LI ; Qun ZHAO
Chinese Journal of General Surgery 2022;37(11):817-820
Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.
6.Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5.
Rong LI ; Wenqiang ZHU ; Piaopiao HUANG ; Chen DING ; Yaxin TANG ; Ping'an LIAN ; Xiansheng HUANG
Journal of Central South University(Medical Sciences) 2022;47(6):730-738
OBJECTIVES:
Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD.
METHODS:
This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively.
RESULTS:
After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced.
CONCLUSIONS
The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.
Animals
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Apolipoprotein A-V/genetics*
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Body Weight
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Dimethyl Sulfoxide/metabolism*
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Liver/metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Non-alcoholic Fatty Liver Disease/chemically induced*
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Olanzapine/metabolism*
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RNA, Messenger/metabolism*
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RNA, Small Interfering
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Triglycerides