Clinical efficacy of neoadjuvant chemotherapy combined with radical surgery for elderly patients with locally advanced gastric cancer / 中华普通外科杂志

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.

Clinical imaging and prognostic analysis of rectal neuroendocrine tumors with lymphatic metastasis / 国际外科学杂志

Objective:To explore the clinical features, diagnosis, treatment and prognosis of rectal neuroendocrine tumor with lymphatic metastasis.Method:There were 153 case who were diagnosed with RNET, among them, there were 10 patients(6.5%) with lymphatic metastasis in Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from January 2012 to December 2020, including 4 males and 6 females, aged from 32 to 71 years old, and the median age was 56.5 years.Results:Of the 10 patients, 3 had tumors < 1 cm in diameter, 4 had 1 to 2 cm, and 3 had > 2 cm. Preoperative CT examination was performed in 10 patients, of which 9 suggested lymphatic metastasis; preoperative MRI examination was performed in 7 patients, of which 6 suggested lymphatic metastasis. All patients were received radical resection, in which Miles operation was performed in 2 cases, Dixon operation in 6 cases, and additional Dixon operation after endoscopic submucosal dissection in 2 cases.All patients were followed up for 51 months (ranged from 14 to 118 months). Nine patients had no recurrence or metastasis, and one patient had abdominal metastasis 40 months after surgery and died after 31 months of comprehensive treatment.Conclusions:Lymphatic metastasis is rare in rectal neuroendocrine tumor. Imaging examination has important reference value for judging the status of lymphatic metastasis. For rectal neuroendocrine tumor with lymphatic metastasis, radical resection is effective.

Analysis of therapeutic strategy after non-curative endoscopic submucosal dissection for early gastric cancer / 中华消化内镜杂志

Objective:To evaluate the clinical outcomes of additional surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Sixty-nine patients with early gastric cancer who underwent ESD and were diagnosed as having non-curative resection by postoperative pathology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were included in the retrospective observation. Patients were divided into the additional surgery group ( n=12) and the follow-up group ( n=57). The differences in clinical and pathological data of the two groups, the surgical outcomes of the additional surgery group, three-year recurrence-free survival and tumor-specific survival of the two groups, and the independent risk factors affecting three-year recurrence-free survival in the follow-up group were analyzed. Results:Compared with the follow-up group, the rates of submucosal infiltration [66.7% (8/12) VS 21.1% (12/57), χ 2=7.927, P=0.005], vascular invasion [33.3% (4/12) VS 1.8% (1/57), P=0.003] and nerve invasion [16.7% (2/12) VS 0.0% (0/57), P=0.028] in the additional surgery group were significantly higher. In the additional surgery group, the interval between the additional surgery and ESD was 18.5 d (7-55 d), the surgical time was 286.4±85.9 min, and the number of dissected lymph nodes was 25.6±7.4. Four patients (33.3%) had residual tumor. Postoperative complications occurred in 4 patients (33.3%) (all were discharged after conservative treatment), and there was no perioperative death. One patient developed liver metastases 17 months after the surgery, and died 22 months after surgery due to liver metastases. One patient died 22 months after surgery due to non-tumor causes. The three-year recurrence-free survival and three-year tumor-specific survival in additional surgery group were 91.7% (11/12) and 91.7% (11/12), respectively, and those in the follow-up group were 87.7% (50/57) and 100.0% (57/57), respectively. Multivariate Cox regression analysis showed that tumor size ≥2 cm was an independent risk factor for three-year recurrence-free survival in the follow-up group ( P=0.037, HR=15.595, 95% CI: 1.181-205.952). Conclusion:Additional surgery and close follow-up are safe and feasible therapeutic strategies for early gastric cancer patients who underwent non-curative ESD. Clinicians should make reasonable choice based on the pathological results, patients' physical condition and surgery intention. But for patients with primary tumor size ≥2 cm, additional surgery is recommended.

Management and risk factors of anemia in patients with gastric cancer / 中华普通外科杂志

Objective:To review the incidence and treatment status of perioperative anemia in patients with gastric cancer.Methods:The clinicopathological data of gastric cancer patients who underwent surgery at Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Jan to Dec 2019 were collected. Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors of preoperative anemia in gastric cancer.Results:A total of 879 patients were included in this study. The incidence of preoperative anemia in patients with gastric cancer was 35.6%. The incidence of postoperative anemia was 63.5%. The proportion of patients with preoperative anemia receiving treatment was 17.3%, and the proportion of patients with postoperative anemia receiving treatment was 17.4%. Univariate analysis showed that age, nutritional risk screening 2002, T stage, M stage, tumor stage and lymph node metastasis were associated with preoperative anemia (all P<0.05). Multivariate Logistic regression analysis showed that age >60 years , nutritional risk screening 2002 ≥3, T 3-4 stage and M 1 stage were independent risk factors for preoperative anemia in patients with gastric cancer (all P<0.05). Conclusions:The incidence of perioperative anemia in patients with gastric cancer is high. At present, the proportion of patients with perioperative anemia receiving treatment is low. High nutritional risk, advanced age, late tumor T stage and distant metastasis are independent risk factors for preoperative anemia in patients with gastric cancer.

Clinicopathological features and prognosis analysis of patients with gastric gastrointestinal stromal tumor combined with digestive tract cancer / 中华消化外科杂志

Objective:To investigate the clinicopathological features and prognosis of patients with gastric gastrointestinal stromal tumor (GIST) combined with digestive tract cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 163 patients with gastric GIST who were admitted to the Union Hospital admitted to Tongji Medical College of Huazhong University of Science and Technology from January 2002 to December 2021 were collected. There were 606 males and 557 females, aged 59(range,20?94)years. Of the 1 163 patients, 129 cases with gastric GIST combined with other digestive tract cancer were divided into the combined group, and 1 034 cases with only gastric GIST were divided into the non-combined group. Observation indicators: (1) clinicopathological features of patients; (2) surgical situations and postoperative complications; (3) follow-up and survival of patients; (4) analysis of prognosis associated affecting factors. Follow-up was conducted using outpatient examination, telephone and online interview to detect survival of patients up to January 2022. The overall survival time was defined as the time from surgery to the last tine of follow-up or the outcome events, such as death of patient, loss of follow-up, etc. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Com-parison of ordinal data was conducted using the non-parameter Mann-Whitney U test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) Clinicopathological features of patients. Of the 129 patients in the combined group, there were 81 cases combined with gastric cancer, 39 cases combined with esophageal cancer, 8 cases combined with colon cancer and 1 case combined with rectal cancer. Gender (male, female), cases with age ≤60 years or>60 years, cases without or with clinical symp-toms before surgery, cases with tumor diameter of gastric GIST as<2 cm, 2?5 cm, 5?10 cm,>10 cm, cases with mitotic index as <5/50× high power field, 5?10/50× high power field, >10/50× high power field, cases with cell proliferation index of Ki-67 as ≤5% or >5%, cases classified as extremely low risk, low risk, medium risk and high risk of the modified national institutes of health (NIH) risk classification, cases with or without tumor necrosis of the gastric GIST, cases without or with adjuvant imatinib therapy, cases with the expression of DOG-1 detected by immunohistochemical staining as positive or negative, cases with the expression of CD34 as positive or negative were 92, 37, 30, 99, 9, 120, 114, 10, 3, 2, 126, 1, 2, 122, 2, 112, 8, 5, 4, 129, 0, 121, 8, 118, 3, 117, 12 in the combined group, versus 514, 520, 585, 449, 194, 840, 383, 360,201, 90, 799, 155, 80, 851, 143, 337, 308, 192, 197, 960, 74, 769, 265, 850, 80, 990, 44 in the non-combined group, showing significant differences in the above indicators between the two groups ( χ2=21.46, 51.11, 11.06, Z=?10.27, ?5.34, χ2=15.94, Z=?10.61, χ2=9.86, 24.10, 5.52, 6.37, P<0.05). Of the 1 163 patients, there were 12 cases of the combined group suspected diagnosed as gastric GIST before surgery and 1 case of the combined group dia-gnosed as gastric GIST by gastroscopy and pathological examination before surgery. The rest of 1 150 patients were diagnosed as gastric GIST by intraoperative exploration or postoperative pathological examination. (2) Surgical situations and postoperative complications. Of the 129 patients in the combined group, 72 cases underwent open surgery and 57 cases underwent laparoscopic or thoracoscopic surgery including 3 cases converted to open surgery. Of the 1 034 patients in the non-combined group,207 cases underwent endoscopic surgery, 371 cases underwent open surgery, and 456 cases underwent laparoscopic or thoracoscopic surgery including 8 cases converted to open surgery. Incidence of postoperative complications was 10.078%(13/129) in the combined group, versus 2.321%(24/1 034) in the non-combined group, showing a significant difference between the two groups ( χ2=22.40, P<0.05). (3) Follow-up and survival of patients. Of the 1 163 patients, 1 046 cases were followed up for 44(range, 1?220)months, with the postoperative 5-year overall survival rate as 87.2%. The postoperative 5-year overall survival rate was 51.2% in the combined group, versus 91.4% in the non-combined group, showing a significant difference between the two groups ( χ2=169.07, P<0.05). (4) Analysis of prognosis associated affecting factors. Results of univariate analysis showed that gender, age, tumor diameter of gastric GIST as 2?5 cm, 5?10 cm and >10 cm, combined with other digestive tract cancer, mitotic index as >10/50× high power field and tumor necrosis of the gastric GIST were related factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=2.16, 2.27, 0.46, 0.57, 1.75, 7.58, 2.70, 1.80, 95% confidence intervals as 1.52?3.07, 1.60?3.22, 0.29?0.71, 0.34?0.94, 1.11?2.77, 5.29?10.85, 1.67?4.38, 1.08?2.98, P<0.05). Results of multivariate analysis showed that gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index were independent factors affecting the post-operative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=1.91, 1.82, 2.10, 7.11, 2.75, 95% confidence intervals as 1.33?2.75, 1.27?2.62, 1.14?3.87, 4.58?11.04, 1.50?5.03, P<0.05). Conclusions:The tumor diameter of gastric GIST is short in patients combined with other digestive tract cancer, and the risk grade of modified NIH risk classification is lower. Gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index are independent factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST.

Short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy for locally advanced rectal cancer: a prospective study / 中华消化外科杂志

Objective:To investigate the short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-programmed death-1 (PD-1) antibody therapy for locally advanced rectal cancer.Methods:The prospective study was conducted. The clinicopathological data of 30 locally advanced rectal cancer patients who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from November 2019 to September 2020 were selected. Patients underwent laparos-copic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Observation indicators: (1) situations of the enrolled patients; (2) situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events; (3) preoperative evaluation and surgical situations; (4) postoperative situations and pathological examinations; (5) postoperative adjuvant chemo-therapy and follow-up. Follow-up was conducted using outpatient examination and telephone interview up to March 2022. Patients were followed up once every 3 weeks during the period of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy to detect the adverse events and patients were followed up once every 3 months during the first postoperative 2 years and once every 6 months thereafter to detect tumor recurrence and survival of patients. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Situations of the enrolled patients. A total of 30 patients were selected for eligibility. There were 17 males and 13 females, aged (57±16)years. Cases with preoperative primary tumor in stage cT3 and cT4 were 22 and 8, respectively. Cases with preoperative clinical lymph node metastasis in stage cN0, cN1, cN2 were 4, 16, 10, respectively. Cases in preoperative clinical stage Ⅱ and Ⅲ were 4 and 26, respectively. Of the 30 patients, there were 21 cases with positive circumferential margin and 12 cases with vascular invasion in extramural of rectum in the preoperative imaging evaluation. Distance from the distal margin of tumor to anal margin and tumor diameter of the 30 patients were 4.7(range, 1.9?9.0)cm and 5.4(range, 2.1?10.0)cm, respectively. There were 28 cases with mismatch repair proficient and 1 case with mismatch repair deficiency in tumor tissues. There was 1 case missing the data of mismatch repair in tumor tissues as failed in biopsy of pathological examination before the treatment. (2) Situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events. All the 30 patients completed preoperative short-course radiotherapy successfully. Of the 30 patients, there were 3 cases not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy and there were 24 cases undergoing 2 courses of the sequential chemotherapy combined with anti-PD-1 antibody therapy and 3 cases undergoing 1 course of the sequential chemotherapy combined with anti-PD-1 antibody therapy. The time interval between ending of radiotherapy and starting of chemotherapy combined with anti-PD-1 antibody therapy of the 27 patients was 12(range, 4?18) days. Cases with leukopenia, cases with endothelial hyperplasia of skin capillaries, cases with radiation proctitis, cases with anemia, cases with peripheral neurotoxicity, cases with neutropenia, cases with thrombocytopenia, cases with fatigue, cases with anorexia, cases with abnormal liver function, cases with hypothyroidism were 24, 22, 21,20, 18, 16, 16, 13, 10, 9, 2 in the 30 patients during the preoperative short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Cases with the above adverse events were improved after symptomatic treatment. (3) Preoperative evaluation and surgical situations. Seven of the 30 patients were in clinical complete remission after preoperative multidisciplinary evaluation and the other 23 patients were not in clinical complete remission. Twenty-seven of the 30 patients underwent laparoscopic radical resection of rectal cancer and 3 patients not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy did not undergo surgery. The time interval between ending of chemotherapy combined with anti-PD-1 antibody therapy and the surgery of the 27 patients were 14(range, 5?141)days. Of the 27 cases, there were 13 cases and 14 cases with 0 and 1 of the preoperative Eastern Cooperative Oncology Group score, respectively, and there were 24 cases undergoing low anterior proctectomy and 3 cases undergoing abdominoperineal excision. The operation time and volume of intra-operative blood loss of the 27 cases were (182±36)minutes and 30(range, 10?150)mL, respectively. Of the 27 cases, there were 16 cases with protective ileostomy and 24 cases with anal preservation. (4) Postoperative situations and pathological examinations. The time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 27 patients undergoing surgery were 2(range, 1?4)days, 3(range, 2?5)days and 8(range, 7?16)days, respectively. Five of the 27 patients had postoperative grade Ⅰ?Ⅱ complications, including 2 cases with incision infection, 1 case with abdominal infection, 1 case with incision hemorrhage and 1 case with venous thrombosis in left lower limb intermuscular. Cases with postoperative complica-tions were improved after symptomatic treatment. Results of postoperative pathological examina-tion showed that the rate of pathologic complete response in 27 patients was 48.1%(13/27). Of the 27 cases, cases in grade 0, grade 1, grade 2, grade 3 of the tumor regression grading were 13, 5, 7, 2, respectively, cases in stage T0, stage Tis, stage T2, stage T3 of the tumor T staging were 13, 1, 5, 8, respectively, cases in stage N0, stage N1, stage N2 of the tumor N staging were 19, 6, 2, respectively, cases in stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ of the tumor TNM staging were 14, 0, 5, 8, respectively. The number of lymph node dissected of the 27 patients was 15(range, 3?29). Of the 27 patients, there was 1 case with positive circumferential margin and 26 cases achieving R 0 resection. None of the 27 patients underwent secondary operation or perioperative death. (5) Postoperative adjuvant chemotherapy and follow-up. Of the 27 patients undergoing surgery, 21 cases underwent post-operative adjuvant chemotherapy, with the cycles of 4(range, 1?6). All the 27 patients were followed up for 20(range, 20?29)months. During the follow-up, 3 cases not achieving pathological complete response had tumor recurrence and no patient died. The disease free survival rate of the 27 patients was 88.9%. Conclusion:Laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with immunotherapy for locally advanced rectal cancer is safe and feasible, with satisfied short-term efficacy.

Clinical characteristics and prognosis of primary gastrointestinal stromal tumors with PDGFRα mutation / 中华普通外科杂志

Objective:To investigate the clinicopathological characteristics of primary gastrointestinal stromal tumors (GIST) with PDGFRα mutation and analyze the prognosis of different subtypes.Methods:From Jun 2010 to Jun 2019, the clinicopathological data of 35 patients with primary PDGFRα mutation GIST, who underwent surgical therapy in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively.Results:The main symptoms was abdominal pain (28 cases, 80%), followed by abdominal mass (6 cases, 17%), and hemafecia (1 case, 3%). 31 primary lesions (89%) were located in the stomach and 4 (11%) in other than stomach. 13 cases (37%) were of epithelioid cells, 14 cases (40%) were of spindle cells and 8 cases (23%) were of mixed cells. 27 cases (77%) were CD117 positive , 28 cases (80%) CD34 positive , and 30 cases (86%) were DOG-1 positive. 19 cases (54%) had D842V mutation and 16 cases (46%) had non-D842V mutation. Complete surgical resection was performed in all patients, with no perioperative death. The 3-year recurrence-free survival rate of the D842V mutation group was lower than that of the non-D842V mutation group (84% vs. 100%, P=0.045). Conclusions:The mutation rate of PDGFRα gene was low, mostly derived from the stomach. PDGFRα mutation GIST presents inert biological behavior and the overall prognosis was good.

Risk factors of postoperative pathological upgrading in gastric high-grade intraepithelial neoplasia / 国际外科学杂志

Objective To analyze the consistency of gastroscopic biopsy in the diagnosis of high grade intraepithelial neoplasia (HGIN) and postoperative pathological diagnosis,and explore the risk factors associated with missed diagnosis of HGIN.Methods From January 2012 to December 2018,the clinical data of 63 patients who were diagnosed with HGIN by gastroscopic biopsy prior to operation and underwent complete resection in the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology were retrospectively analyzed.There were 55 males and 8 females,with a median age of 60 (35 to 76) years old.The gender,age,endoscopic lesion shape,longest diameter,CT image and inflammatory markers were analyzed,to investigate the correlation between them and pathological upgrading after operation.Receiver operating characteristic (ROC) curve was drawn to analyze the cut off value of measurement data,and the comparison of count data was performed by chisquare test or Fisher exact probability method.Univariate analysis was used to screen potential risk factors,and multivariate logistic regression analysis was futher utilized to analyze the independent risk factors of postoperative pathological upgrading.Results A total of 63 patients were enrolled,including 47 cases underwent surgical resection and 16 cases underwent endoscopic submucosal dissection(ESD).Among them,19 patients(30.2％) were pathologically diagnosed with HGIN,while 44 patients(69.8％) were pathologically diagnosed with invasive cancer after resection.Preoperative contrast-enhanced CT showed that 11 patients (17.5％) with perigastric fat spiculation around the lesion,all of which were confirmed as invasive carcinoma after operation.Univariate analysis showed that the longest diameter of the lesion ≥2 cm (P =0.002),ulcer lesions under gastroscopy (P =0.013),platelet to lymphocyte ratio (PLR) ≥ 103 (P =0.030),lymph node enlargement (P =0.046) and spiculation of the perigastric fat (P =0.025) were significant differences between the groups.Logistic regression analysis showed that the longest diameter of the lesion ≥2 cm (P =0.033) and ulcer lesions under gastroscopy (P =0.007) were independent risk factors for predicting postoperative pathological upgrading.Conclusions Gastroscopy biopsy in the diagnosis of high-grade intraepithelial neoplasia of the stomach has poor consistency with pathological diagnosis after operation.Clinicians should take active surgical intervention,especially for cases with the longest diameter of the lesions ≥2 cm,ulcer or perigastric fat spiculation on CT.

Risk factors of postoperative pathological upgrading in gastric high-grade intraepithelial neoplasia / 国际外科学杂志

Objective@#To analyze the consistency of gastroscopic biopsy in the diagnosis of high grade intraepithelial neoplasia(HGIN) and postoperative pathological diagnosis, and explore the risk factors associated with missed diagnosis of HGIN.@*Methods@#From January 2012 to December 2018, the clinical data of 63 patients who were diagnosed with HGIN by gastroscopic biopsy prior to operation and underwent complete resection in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. There were 55 males and 8 females, with a median age of 60 (35 to 76) years old. The gender, age, endoscopic lesion shape, longest diameter, CT image and inflammatory markers were analyzed, to investigate the correlation between them and pathological upgrading after operation. Receiver operating characteristic (ROC) curve was drawn to analyze the cut off value of measurement data, and the comparison of count data was performed by chi-square test or Fisher exact probability method. Univariate analysis was used to screen potential risk factors, and multivariate logistic regression analysis was futher utilized to analyze the independent risk factors of postoperative pathological upgrading.@*Results@#A total of 63 patients were enrolled, including 47 cases underwent surgical resection and 16 cases underwent endoscopic submucosal dissection(ESD). Among them, 19 patients(30.2%) were pathologically diagnosed with HGIN, while 44 patients(69.8%) were pathologically diagnosed with invasive cancer after resection. Preoperative contrast-enhanced CT showed that 11 patients(17.5%) with perigastric fat spiculation around the lesion, all of which were confirmed as invasive carcinoma after operation. Univariate analysis showed that the longest diameter of the lesion ≥2 cm (P=0.002), ulcer lesions under gastroscopy (P=0.013), platelet to lymphocyte ratio (PLR) ≥103 (P=0.030), lymph node enlargement (P=0.046) and spiculation of the perigastric fat (P=0.025) were significant differences between the groups. Logistic regression analysis showed that the longest diameter of the lesion ≥2 cm (P=0.033) and ulcer lesions under gastroscopy (P=0.007) were independent risk factors for predicting postoperative pathological upgrading.@*Conclusions@#Gastroscopy biopsy in the diagnosis of high-grade intraepithelial neoplasia of the stomach has poor consistency with pathological diagnosis after operation. Clinicians should take active surgical intervention, especially for cases with the longest diameter of the lesions ≥2 cm, ulcer or perigastric fat spiculation on CT.

Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor / 中华胃肠外科杂志

Objective@#To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 μg/L influences the efficacy of adjuvant therapy.@*Methods@#A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis.@*Results@#Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration <1100 μg/L and 53 patients with plasma concentration ≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration ≥1100 μg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242).@*Conclusions@#IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.

Clinical characteristics and prognosis analysis of 119 cases with giant gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, diagnosis and treatment as well as prognostic factors of the giant gastrointestinal stromal tumor (GIST).</p><p><b>METHODS</b>Clinical data of 235 patients with high risk GIST treated in the Union Hospital, Tongi Medical College, Huazhong University of Science and Technology between January 2005 and July 2015 were retrospectively analyzed. Patients were divided into giant GIST group (diameter equal to or larger than 10 cm, 119 cases) and high risk group (diameter less than 10 cm, 116 cases) according to tumor size. Clinical characteristics and prognosis of two groups were compared and the clinical features of giant GIST were summarized. Multivariate analysis was performed to evaluate the prognostic factors of giant GIST with Cox regression model.</p><p><b>RESULTS</b>Of the 119 patients with giant GIST, which accounted for 50.6%(119/235) of all the high risk patients, there were 63 male and 56 female patients with a median age of 53(20-82) years. Primary giant GIST of 43(36.1%) located in the stomach, of 39(32.8%) in the small intestine, 5(4.2%) in the colon and rectum, and of 32 (26.9%) outside the gastrointestinal tract (mesentery, retroperitoneum, abdominal cavity, etc) and pelvic. Compared to high risk group, age of onset was younger [ratio of ≤50 years, 44.5%(53/119) vs. 31.9%(37/116), P = 0.046] and incidence of outside the gastrointestinal tract was significantly higher [26.9%(32/119) vs. 9.5%(11/116), P=0.000] in giant GIST group. All the giant GIST patients underwent surgical resection, including 115 cases(96.6%) of R0 resection, 3 cases(2.5%) of R1 resection and 1 case(0.9%) of R2 resection, besides, 32 cases(26.9%) underwent expanded resection (namely, underwent lymphadenectomy or combined organ resection simultaneously). Thirty-nine giant GIST cases(32.8%)accepted imatinib 400 mg/d for targeted therapy after operations, which was not significantly different with high risk group (46 cases, 39.6%, P=0.232). Relapse and metastasis occurred in 8 cases in giant GIST group. The 1-, 3-, 5-year overall survival rates of giant GIST group were 94.5%, 89.3%, 79.4% respectively and of high risk group were 99.1%, 92.9%, 85.1% respectively, and no significant difference was found (P=0.788). The 1-, 3-, 5-year recurrence-free survival rates of giant GIST group were 93.6%, 85.1%, 72.8% respectively and of high risk group were 99.1%, 91.7%, 84.2% respectively, and no significant difference was found as well (P=0.932). Multivariate analysis revealed that gender (P=0.047, RR=0.383, 95%CI:0.149-0.987), mitotic count (P=0.001, RR=0.216, 95%CI:0.087-0.538) and targeted therapy(P=0.019, RR=5.719, 95%CI:1.324-24.695) were prognostic risk factors of overall survival (OS), moreover, tumor size (P=0.024, RR=0.368, 95%CI:0.155-0.875) and mitotic count(P=0.007, RR=0.357, 95%CI:0.169-0.755) were prognostic risk factors of RFS.</p><p><b>CONCLUSIONS</b>Giant GIST is not unusual in GIST and more likely occurs outside gastrointestinal tract. Complete surgical excision combined with targeted therapy can improve the prognosis significantly. The prognosis of giant GIST and common high risk GIST is similar. Mitotic count is the most important prognostic factor.</p>

An in vitro mineralization study of hydrogen existence form and surface bioactivity of titanium / 实用口腔医学杂志

Objective:To investigate the relationship between surface hydrogen form and the bioactivity of titanium.Methods:Sandblast titanium was etched with the combination of sulfuric and hydrochloric acids(SLA group,n=3 ).Then etched titanium was heat at 450 ℃in air(SLA+HT group,n=3).Surface topography,roughness,hydrophility,surface chemical texture were observed. Finally,the titanium samples were soaked in body simulate fluid for 3 days,the mineral deposition properties were observed by X-ray diffraction.Results:Titanium hydride was formed on the titanium surface after etching.After heat treatment,surface texture and roughness were not changed,titanium hydride decomposed and hydrophility increased.More hydroxyapatite was found on the surface of the samples treated by SLA+HT and followed by SBF.Conclusion:Titanium hydride can not improve the bioactivity of titanium, heat treatment may increase the mineralization.

Effects of (Val8)GLP-1-Glu-PAL on motor ability and dopaminergic neurons of Parkison's disease mice / 中华行为医学与脑科学杂志

Objective To investigate the protective effects of (Val8)GLP-1-Glu-PAL to dopaminergic neurons on PD mice induced by MPTP.Methods 56 male C57BL/6 mice which are 10-12 weeks old were randomly divided into Control,model (MPTP),muti-injection (Val8) and therapy (MPTP + Val8) groups by random number table method.Mice in MPTP group were received MPTP IP.treatment (30mg/kg · d),the control group were treated with 0.9％ saline with the same volume,Val8 group were injected with (Val8) GLP-1-Glu-PAL (25 nmol/kg),and MPTP+Val8 group were going to received (Val8)GLP-1-Glu-PAL 1 h after treatment of MPTP,all the groups were treated for 8 consecutive days.Behavior test were processed 2h after drug IP injection,including swimming test and rotarod test.Mice were sacrificed immediately 1h after the final trail of behavior test in 8th day,brains were withdraw for IHC assay which tested the number TH positive neurons in SNpc area.Results The classical PD behavior symptom were induced by MPTP,from 1 st to 8th,the swimming score(1.715±0.143 and dropping latency(68.048±7.823) were both decreasing compared with control.The differences were statistically significant (P＜0.05).The positive dopaminergic neurons were significantly lower in SNpc area (P＜0.01).Compared with MPTP group,(Val8) GLP-1-Glu-PAL could statistically improved the behavior deficit,the swimming score (1.120±0.143) and dropping latency(20.546±7.823) in the MPTP+Val8 group,and differences were statistically significant (P＜0.05).Meanwhile,the TH positive neurons were significantly elevated (P＜0.01).Conclusion The results suggest that (Val8)GLP-1-Glu-PAL has protective effects for MPTP induced mice PD dopaminergic neurons.

The effect of octreotide on lung injury after ischemia-reperfusion in the rabbit liver / 中国医师杂志

Objective To research the effect of octreotide on the lung injury of far place organ after ischemia-reperfusion in rabbit liver.Methods Prings maneuver rabbit hepatic ischemia-reperfusion models were established. 24 adult New Zealand rabbits were random divided into three groups: group Ⅰ (sham operative group) , group Ⅱ (ischemia-reperfusion by physiological saline group) and group Ⅲ (octreotide preconditioning group). To group Ⅲ, we injected octreotide of 20μg/kg to abdominal cavity and octreotide of 30(μg/kg to skin following, and octreotide was dissolved into 2ml with 0. 9% physiological saline. To group Ⅰ and Ⅱ, octreotide were replaced with the same amount of physiological saline. The changes of MAP, HR in every group were recorded at the time before ischemia (T1 ) , 30min (T2) after ischemia, 30min(T3) , 60min(T4) , 120min(T5) , 240min(T6) after reperfusion. The tumor necrosis factor-alpha (TNF-a) and interleukin-lbeta (IL-1β) in the plasma in every group at T1, T2, T3, T4 , T5, T6 were detected. These rabbits were killed 240 min after reperfusion, then the lung's hepatocellular ultrastructures of every group were observed under electromicroscope, and the apoptosis of lung was detected by TUNEL. Results The MAP, HR of group Ⅱ and group Ⅲ were lower than that of group Ⅰ at T2 to T4. Moreover, group Ⅱ were lower than that of group Ⅲ (P <0.05). The TNF-a, IL-1β of group Ⅱ (fromT2) and group Ⅲ ( from T3) were higher than that of group Ⅰ ( P < 0.05) , and group Ⅲ were lower than group Ⅱ after ischemia (P <0. 01). Through electromicroscope, we found that the injury of the lungs hepatocellular ultrastructure in group Ⅲ was slighter than that in group Ⅱ . We detected the apoptosis of the lung organizes by TUNEL under 5 fields of light microscopes, and found that the apoptosis counts of group Ⅱ (55. 82 ±4. 19) and group Ⅲ (32. 17 ±3. 10) were more than that of group Ⅰ (3. 96 ±0. 87), and group Ⅲ were less than thatof group Ⅱ (P < 0. 01). Conclusion Octreotide can protect the lung injury of far place organ after ische-mia-reperfusion in rabbit liver.

The protective effect of octreotide on myocardial injury after hepatic ischemia-reperfusion injury in rabbit / 中国医师杂志

Objective To study the protective effect of octreotide on myocardial injury after hepatic ischemia-reperfusion in rabbit. Methods Pringle's maneuver rabbit hepatic ischemia-reperfusion model was established. 24 adult New Zealand rabbits were random divided into equal 3 groups: sham operative group ( group A) , ischemia-reperfusion group( group B) and octreotide preconditioning group ( group C ). The levels of CK-MB( MB isoenzyme of creatine kinase) and LDH ( 1actate dehydrogenase), superoxide dismutase (SOD) and malondialdehyde (MDA) of each group were measured at the time before ischemia (T1) , after ischemia for 30 mins ( T2 ) and after reperfusion for 60 mins ( T3 ), 120mins ( T4 ), 240 mins ( T5 ). The SOD and MDA in myocardial tissue of each group were measured after reperfusion for 240 mins. The changes of ultrastructure in the myocardial cell were observed by transmission electron microscopy after reperfusion for 240 mins. Results There was no significant difference in the levels of CK-MB and LDH in serum of each group before ischemia ( P ＞0. 05). The CK-MB and LDH of group B and C were higher than that of group A ( P ＜0.05) after ischemia for30 mins. The CK-MB and LDH of group C were lower than that of group B in this period( P ＜0. 05 ). The highest time point of LDH and CK-MB were after reperfusion for 120 mins and 240 mins. The contents of MDA in group B and group C were higher than that in group A from after ischemia for 30 mins in plasma and after reperfusion for 240 mins in myocardial tissue ( P ＜ 0. 05 ),and it in group C were lower than that in group B( P ＜0.05) .The contents of SOD in group B and group C were lower than that in group A from after ischemia for 30 mins in blood plasma and after reperfusion for 240 mins in myocardial tissue ( P ＜0. 05), and in group C were higher than that in group B( P ＜0. 05).The electromicroscope showed that the pathological change of myocardial ultrastructure of group C was slighter than that of group B. Conclusion Octreotide can stabilize myocardial cell membrane and reduce release of oxygen free radical and significantly relieve the injury of myocardial ultrastructure after hepatic ischemiareperfusion in rabbit. Octreotide preconditioning can relieve myocardial injury after hepatic ischemia-reperfusion in rabbit.