Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Objective:To investigate the application value of manual anastomosis of gastro-duodenum in totally laparoscopic distal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 55 patients with gastric cancer who underwent totally laparoscopic distal gastrectomy combined with gastrointestinal anastomosis in the Tianjin Medical University Cancer Institute & Hospital from January 2020 to October 2022 were collected. There were 34 males and 21 females, aged 61(range, 29?75)years. Of 55 patients, 25 patients undergoing manual anastomosis of gastroduodenum were divided into the manual anastomosis group, 30 patients undergoing modified Delta anastomosis of gastroduodenum were divided into the modified Delta anastomosis group. Observation indicators: (1) surgical situations; (2) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using chi-square test or Fisher exact probility. Results:(1) Surgical situations. All 55 patients underwent surgery successfully, without conversion to laparotomy. The distance from the superior margin of tumor to the upper margin, anastomosis time, number of bookings used were (48±4)mm, (22.6±2.3)minutes, 3.2±0.5 in the manual anastomosis group, versus (41±4)mm, (14.0±1.4)minutes, 5.2±0.4 in the modified Delta anastomosis group, showing significant differences in the above indicators between the two groups ( t=5.04, 16.38, ?17.13, P<0.05). The location of tumor (antrum, gastric angle) was 18, 7 in the manual anastomosis group, versus 29, 1 in the modified Delta anastomosis group, showing a significant difference between the two groups ( P<0.05). (2) Postoperative complications. There was no patient undergoing anastomotic fistula in both of manual anastomosis group and modified Delta anastomosis group, and there was 1 patient undergoing anastomotic stenosis in the modified Delta anastomosis group. Conclusion:Compared with modi-fied Delta anastomosis of gastroduodenum,totally laparoscopic distal gastrectomy with manual anas-tomosis of gastroduodenum can remove more gastric tissue, and decrease the number of bookings used.

Objective:To investigate the clinical efficacy of radical proximal gastrectomy with esophagogastrostomy and double-tract anastomosis for upper gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 172 patients who underwent radical proximal gastrectomy for upper gastric cancer in Tianjin Medical University Cancer Institute and Hospital from January 2018 to December 2020 were collected. There were 147 males and 25 females, aged from 25 to 81 years, with a median age of 62 years. All the 172 patients underwent digestive reconstruction. Of the 172 patients, 83 cases undergoing esophagogastrostomy were allocated into esophagogastrostomy group, 89 cases undergoing double-tract anastomosis were allocated into double-tract anastomosis group. Patients were performed radical proximal gastrectomy combined with D 1+ lymph node dissection by attending surgeons from department of gastric cancer. The operator decided to adopt esophagogastrostomy or double-tract anastomosis for digestive reconstruction. Observation indicators: (1) surgical situations; (2) follow-up. Follow-up using outpatient examination, telephone interview, and online APP was conducted at postoperative 1 month, once three months within postoperative 2 years, and once six months within postoperative 2-5 years. The questionnaires of reflux esophagitis, gastroscopy and upper gastrointestinal angio-graphy were conducted to evaluate gastroesophageal reflux and anastomotic stenosis up to February 1, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Surgical situations: cases with open, laparoscopic or Da Vinci robotic surgery (surgical method), the number of metastatic lymph node, duration of postoperative hospital stay were 74, 9, 0, 2(range, 0-15), (12±4)days for the esophagogastrostomy group, versus 65, 15, 9, 3(range, 0-28), (11±3)days for the double-tract anastomosis group, respectively, showing significant differences in the above indicators between the two groups ( χ2=10.887, Z=-1.058, t=3.284, P<0.05). (2) Follow-up: 172 patients were followed up for 2-38 months, with a median follow-up time of 13 months. Cases with gastroesophageal reflux and anastomotic stenosis were 58 and 10 for the esophagogastrostomy group, versus 14 and 1 for the double-tract anastomosis group, respectively, showing significant differences in the above indicators between the two groups ( χ2=51.743, 7.219, P<0.05). Conclusions:For upper gastric cancer patients undergoing proximal radical gastrectomy, double-tract anastomosis is more suitable for Siewert type Ⅱ adenocarcinoma of esophagogastric junction in large curvature or lower located tumor. Compared with esophago-gastrostomy, double-tract anastomosis has lower incidence of postoperative gastroesophageal reflux and anastomotic stenosis, without increasing complications.

Two new SAM-dependent methyltransferase encoding genes (fvsmt1 and fvsmt2) were identified from the genome of Flammulina velutipes. In order to make a comprehensive characterization of both genes, we performed in silico analysis of both genes and used qRT-PCR to reveal their expression patterns during the development of F. velutipes. There are 4 and 6 exons with total length of 693 and 978 bp in fvsmt2 and fvsmt1, respectively. The deduced proteins, i.e., FVSMT1 and FVSMT2 contained 325 and 230 amino acids with molecular weight 36297 and 24894 Da, respectively. Both proteins contained a SAM-dependent catalytic domain with signature motifs (I, p-I, II, and III) defining the SAM fold. SAM-dependent catalytic domain is located either in the middle or at the N-terminal of FVSMT2 and FVSMT1, respectively. Alignment and phylogenic analysis showed that FVSMT1 is a homolog to a protein–arginine omega-N-methyltransferase, while FVSMT2 is of cinnamoyl CoA O-methyltransferase type and predicted subcellular locations of these proteins are mitochondria and cytoplasm, respectively. qRT-PCR showed that fvsmt1 and fvsmt2 expression was regulated in different developmental stages. The maximum expression levels of fvsmt1 and fvsmt2 were observed in stipe elongation, while no difference was found in mycelium and pileus. These results positively demonstrate that both the methyltransferase encoding genes are involved in the stipe elongation of F. velutipes.

OBJECTIVETo evaluate the value of D2+ lymph node dissection for patients with distal advanced gastric cancer.

METHODSClinicopathological data of 305 cases with distal advanced gastric cancer receiving D2+(n=68) or D2(n=237) lymph node dissection in the Tianjin Cancer Hospital from January 2003 to December 2007 were analyzed retrospectively. The overall 5-year survival rate between the 2 groups.

RESULTSThe median survival was 36 months and the 5-year overall survival rate was 40.3% in all patients. The 5-year overall survival rates in the D2+ and D2 groups were 50.4% and 37.4% respectively, and the difference was statistically significant(P=0.049). In multivariate prognostic analysis however, the extent of lymph node dissection was not identified as an independent prognostic factor(P=0.174). Subgroup analysis showed that 5-year survival rate of D2+ group was significantly higher as compared to D2 group for the following subgroups: maximum diameter of tumor larger than 4 cm(43.9% vs. 27.0%), Borrmann type III(-IIII((55.5% vs. 30.1%), poorly differentiated and undifferentiated tumor (49.8% vs. 37.0%), T4 stage (47.8% vs. 31.0%), N2 stage (53.3% vs. 13.9%), N3 stage (20.0% vs. 9.6%) and positive No.6 lymph nodes (33.1% vs. 16.0%).

CONCLUSIONCompared with D2 lymph node dissection, D2+ lymph node dissection may benefit some patients with large, poorly differentiated, or late-stage tumor.

Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; Survival Rate

Objective To evaluate the value of D2+ lymph node dissection for patients with distal advanced gastric cancer. Methods Clinicopathological data of 305 cases with distal advanced gastric cancer receiving D2+(n=68) or D2 (n=237) lymph node dissection in the Tianjin Cancer Hospital from January 2003 to December 2007 were analyzed retrospectively. The overall 5-year survival rate between the 2 groups. Results The median survival was 36 months and the 5-year overall survival rate was 40.3% in all patients. The 5-year overall survival rates in the D2+ and D2 groups were 50.4% and 37.4% respectively, and the difference was statistically significant (P =0.049). In multivariate prognostic analysis however, the extent of lymph node dissection was not identified as an independent prognostic factor(P=0.174). Subgroup analysis showed that 5-year survival rate of D2+group was significantly higher as compared to D2 group for the following subgroups: maximum diameter of tumor larger than 4 cm (43.9% vs. 27.0%), Borrmann type Ⅲ-Ⅳ (55.5% vs. 30.1%), poorly differentiated and undifferentiated tumor (49.8% vs. 37.0%), T4 stage (47.8% vs. 31.0%), N2 stage (53.3% vs. 13.9%), N3 stage (20.0% vs. 9.6%) and positive No.6 lymph nodes (33.1% vs. 16.0%). Conclusion Compared with D2 lymph node dissection, D2+ lymph node dissection may benefit some patients with large, poorly differentiated, or late-stage tumor.

Objective To evaluate the value of D2+ lymph node dissection for patients with distal advanced gastric cancer. Methods Clinicopathological data of 305 cases with distal advanced gastric cancer receiving D2+(n=68) or D2 (n=237) lymph node dissection in the Tianjin Cancer Hospital from January 2003 to December 2007 were analyzed retrospectively. The overall 5-year survival rate between the 2 groups. Results The median survival was 36 months and the 5-year overall survival rate was 40.3% in all patients. The 5-year overall survival rates in the D2+ and D2 groups were 50.4% and 37.4% respectively, and the difference was statistically significant (P =0.049). In multivariate prognostic analysis however, the extent of lymph node dissection was not identified as an independent prognostic factor(P=0.174). Subgroup analysis showed that 5-year survival rate of D2+group was significantly higher as compared to D2 group for the following subgroups: maximum diameter of tumor larger than 4 cm (43.9% vs. 27.0%), Borrmann type Ⅲ-Ⅳ (55.5% vs. 30.1%), poorly differentiated and undifferentiated tumor (49.8% vs. 37.0%), T4 stage (47.8% vs. 31.0%), N2 stage (53.3% vs. 13.9%), N3 stage (20.0% vs. 9.6%) and positive No.6 lymph nodes (33.1% vs. 16.0%). Conclusion Compared with D2 lymph node dissection, D2+ lymph node dissection may benefit some patients with large, poorly differentiated, or late-stage tumor.

OBJECTIVETo evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors(GIST).

METHODSClinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site, different NIH risk and different treatment was compared respectively.

RESULTSImatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56(median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97% in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69% in 2-year, and 52% in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy, none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases(83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year.

CONCLUSIONSThe prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Combined Modality Therapy ; Follow-Up Studies ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Survival Rate

Aim To provide an electrophysiological basis for hippocampus involved emotional changes caused by tinnitus, the effects of salicylate on electro-physiological characteristics of the voltage-gated calci-um channels in hippocampal neurons were performed. Method The effects of salicylate on voltage-gated cal-cium channels in rat hippocampal neurons were stud-ied, using the whole-cell voltage clamp method. Re-sults Salicylate blocked the voltage-gated calcium channels ( ICa ) in a concentration-dependent manner (0.1~10 mmol · L-1 ) . The half-inhibition concen-tration ( IC50 ) values for the blocking action of salicy-late on ICa were 1.64 mmol·L-1 . With 1 mmol·L-1 salicylate applicalted into bath solution, the steady-state activation curve of calcium channel was shifted by about 9 mV in the hyperpolarizing direction, and its steady-state inactivation curve was not changed. Con-clusion Salicylate inhibits ICa in rat hippocampal neu-rons and significantly affects the activation kinetics of ICa ,which could be related to emotional changes caused by tinnitus.

Objective To evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors (GIST). Methods Clinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site , different NIH risk and different treatment was compared respectively. Results Imatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56 (median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97%in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69%in 2-year, and 52%in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy , none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases (83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year. Conclusions The prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.