OBJECTIVE To establish HPLC methods with different separation principles to analyze the relevant impurities in the APIs of bivalirudin from seven enterprises, to provide a basis for the comprehensive control of related substances of bivalirudin. METHODS Reversed-phase high performance liquid chromatography(RP-HPLC) was used to separate and analyze 11 kinds of impurities. Hydrophilic chromatography(HILIC)-HPLC was used to control four process impurities. Polymers were determined by size exclusion chromatography(SEC)-HPLC. RESULTS The established RP-HPLC could effectively separate the principal component and 11 impurities, the correction factors of 11 impurities were between 0.8−1.2, the detection concentration of bivalirudin was 0.1 μg·mL−1, and the detection limit was 0.004%. The established HILIC-HPLC could effectively separate the principal components and four process impurities, and the detection concentration of bivalirudin was 0.3 μg·mL−1, and the detection limit was 0.01%. Under SEC-HPLC conditions, the polymer and bivalirudin peaked sequentially, the resolution of the two was 2.9, the detection concentration of bivalirudin was 6 ng·mL−1, and the detection limit was 0.000 6%. Fifteen kinds of known impurities and polymers in 15 batches of samples from 7 enterprises were calculated by the self-control method of principal components, and the impurity contents from different enterprises had a certain correlation with their production processes. CONCLUSION The three different principles of the method have good specificity, high sensitivity, good durability, and reliable results, and can be used for quality control of substances related to bivalirudin.

Objective:To investigate the correlation between Lauren classification and pathological response after preoperative chemoradiotherapy in patients with locally advanced gastric cancer.Methods:From 2013 to 2019, 98 patients with definite Lauren classification who were enrolled in Sun Yat-sen University Cancer Center 5010 Phase Ⅲ clinical trials. Among them, 46 patients received preoperative chemoradiotherapy (CRT), and the remaining 52 cases received preoperative chemotherapy (ChT) and radical surgery. After preoperative therapy, the correlation between pathological response including the tumor regression grade (NCCN-TRG 0-3) and the lymph node stage (ypN 0-3) and Lauren classification was analyzed. A favorable pathological response (FPR) was defined as TRG 0-2 and ypN 0. Results:In the CRT group, patients with intestinal type (IT) tumors had a higher rate of ypN 0( OR=6.8, 95% CI: 1.8-25.0, P=0.004) and FPR ( OR=8.0, 95% CI: 2.2-29.9, P=0.002) than their counterparts with diffuse or mixed type tumors. However, Lauren classification was not significantly correlated with pathological response in the ChT group ( P>0.05). For patients with IT tumors, those receiving CRT had a higher likelihood of achieving a TRG 0-2 response ( P=0.033), an ypN 0 nodal regression ( P<0.001), and a FPR ( P<0.001) than their counterparts receiving ChT, whereas pathological response was not significantly associated with preoperative therapeutic method in patients with diffuse or mixed tumors ( P>0.05). Conclusion:Lauren classification may be a reliable predictor of the clinical efficacy of preoperative chemoradiotherapy for locally advanced gastric cancer, which can be utilized to select and optimize preoperative treatment.

OBJECTIVETo assess the clinical value of the diagnostic laparoscopy in choosing treatment strategies for patients with gastric cancer.

METHODSRetrospective analysis was performed on clinical and pathological data collected from 2 023 patients undergoing gastric cancer surgery in the Zhongshan Hospital of Fudan University from 2009 to 2014. All the patients were diagnosed as gastric cancer by endoscopic biopsy and staged by imaging examination before surgery. During the diagnostic laparoscopy procedure, a small periumbilical incision was made and a pneumoperitoneum with COunder 10-15 mmHg was established through a port. A 10 mm trocar was put in, and the camera was inserted. Two 5 mm trocars were put in two ports which located in midclavicular line two fingers under the left and right costal margin and then the instruments were inserted. A thorough inspection included ascites, the abdominal cavity, liver, diaphragm, spleen, greater omentum, colon, small intestine, mesentery, adnexa (female) and pelvic floor. If the tumor located at the posterior part of the stomach, the gastrocolic ligament was opened in order to look for carcinomatosis in the omental bursa. The accuracy rate of diagnostic laparoscopy in diagnosing adjacent organ invasion and intra-abdominal metastasis was calculated, and the rate of adjusting treatment plans after diagnostic laparoscopy was also calculated.

RESULTSThere were 52.7%(1 067/2 023) of patients underwent diagnostic laparoscopy. The accuracy rate of diagnostic laparoscopy in evaluating adjacent organ invasion and intra-abdominal metastasis were 98.3%(1 049/1 067) and 98.1%(1 047/1 067) respectively. Besides, 14 patients with stage T4b and 32 with intra-abdominal metastasis, which were missed by imaging examination, were diagnosed by diagnostic laparoscopy. The treatment plans of 9.3% (99/1 067) of patients were changed after diagnostic laparoscopy, and 65 (6.1%) cases of non-therapeutic laparotomy were avoided. However, 18 cases of adjacent organ invasion and 20 cases of intra-abdominal metastasis were still missed by diagnostic laparoscopy, and 12 cases received non-therapeutic laparotomy.

CONCLUSIONDiagnostic laparoscopy has considerable value in assessing adjacent organ invasion and intra-abdominal metastasis and has great clinical significance in making precise treatment plans.

Abdominal Neoplasms ; diagnostic imaging ; secondary ; Digestive System ; pathology ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopes ; Laparoscopy ; instrumentation ; methods ; statistics & numerical data ; Laparotomy ; statistics & numerical data ; Male ; Neoplasm Invasiveness ; diagnostic imaging ; Patient Care Planning ; statistics & numerical data ; Retrospective Studies ; Stomach Neoplasms ; diagnostic imaging ; surgery ; Surgical Instruments ; Unnecessary Procedures ; statistics & numerical data

OBJECTIVETo investigate the efficacy of targeted therapy combined with surgery in the treatment of recurrent and metastatic gastrointestinal stromal tumor(GIST).

METHODSClinicopathological and followed-up data of 318 patients with recurrent and metastatic GIST admitted in Zhongshan Hospital between January 2000 and December 2015 were analyzed retrospectively. According to different treatment methods, the patients were divided into four groups: surgery group (operation alone, 44 cases), target therapy group (imatinib alone, 108 cases), target therapy combined with surgery group (imatinib plus operation, 139 cases), other therapy group (chemotherapy, Chinese medicine and others, 27 cases). The progression-free survival (PFS) and overall survival (OS) of four groups were compared.

RESULTSThe baseline informations, such as age, gender, primary site, et al, were not significantly different (all P>0.05), but the recurrent and metastatic site was significantly different among 4 groups (P=0.000). The medial PFS of surgery group, target therapy group, target therapy combined with surgery was 16(95%CI: 4.9 to 27.0) months, 44 (95%CI: 30.9 to 57.1) months, 35 (95%CI: 26.5 to 43.5) months, respectively, and the latter 2 groups had significantly longer PFS than surgery group(P=0.000), while no significant difference was found between target therapy group and target combined with surgery group (P=0.251). The median OS of surgery group, target therapy group, target therapy combined with surgery, and other therapy group was 24 (95%CI: 9.0 to 39.0) months, 69(95%CI: 40.8 to 97.2) months, 92(95%CI: 78.0 to 106.0) months, 12(95%CI: 9.5 to 14.5) months. Target therapy group and target therapy combined with surgery group had significantly longer OS than surgery and other therapy groups (P=0.000), while the target therapy combined with surgery group had significantly longer OS than target therapy group(P=0.028).

CONCLUSIONTarget therapy combined with surgery can prolong the survival of recurrent and metastatic GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Retrospective Studies

OBJECTIVETo explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with duodenum gastrointestinal stromal tumor(GIST).

METHODSClinicopathological and follow-up data of 80 patients with duodenum GIST in the Zhongshan Hospital from January 2000 to December 2013 were analyzed retrospectively.

RESULTSThere were 38 male and 42 female patients with a median age of 54 years. The major symptoms were upper alimentary tract hemorrhage and abdominal pain. Thirty-nine patients received local tumor excision, 18 patients underwent segmental duodenectomy, 23 patients were subjected to pancreaticoduodenectomy, all these operations were R0 resection. Thirty patients received imatinib treatment after operation, and 11 among them had metastasis relapse. Recurrence-free survival rates of 1-, 3-, and 5-years were 96.2%, 90.6%and 78.6% retrospectively. Overall survival rates of 1-, 3-, and 5-years were 100%, 98.3% and 96.1%. Multivariate Cox analysis showed tumor size >5 cm, mitotic count >5 mitosis/50 HPF and intermediate/high NIH risk classification were associated with an increased risk of recurrence. The significant difference was not detected between the limited resection group and pancreaticoduodenectomy group in OS and RFS.

CONCLUSIONSSurgery is still the main treatment for duodenum GIST. The surgical program is mainly determined by the location and size of tumor. Imatinib therapy should be used if necessary.

Abdominal Pain ; Benzamides ; Duodenal Neoplasms ; Female ; Gastrointestinal Hemorrhage ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Pancreaticoduodenectomy ; Piperazines ; Prognosis ; Pyrimidines ; Retrospective Studies ; Survival Rate

OBJECTIVETo investigate the clinicopathological features of small gastrointestinal stromal tumors(GISTs) and to evaluate the efficacy of endoscopic therapy for GISTs.

METHODSClinicopathological and follow-up data of 418 patients with GISTs undergoing endoscopic therapy in the Zhongshan Hospital between January 2009 and July 2014 were analyzed retrospectively. All the cases were evaluated by the NIH risk classification and AIFP classification, and were grouped according to the tumor size and location. Nuclear atypia and mitotic count were used to evaluate the biological behavior of small GIST. Efficacy of endoscopic therapy was analyzed with follow-up data.

RESULTSOut of 418 patients, GISTs located in the esophagus was 14(3.3%), in the stomach 389(93.1%), in the duodenum 5(1.2%), in the rectum 10(2.4%). A total of 412(98.6%) patients were mainly spindle cells, and mitosis was not found in 320(76.5%) patients. In 389 small stomach GIST, 245(58.6%) were in fundic region. Cases were divided into four groups according to the size and the result revealed the bigger the size, the more the mitotic count. Nuclear atypia in the 1.5-1.9 cm group was significantly higher compared to other groups. Cases were divided into four groups according to the location and the result revealed the mitotic count was not associated to the location. While the nuclear atypia of stomach GIST was significantly higher than that of esophageal GIST and the nuclear atypia of rectum GIST was significantly higher than that of other positions. The median follow-up was 32(4-69) months. One case(gastric fundus GIST, >1.5 cm) presented local recurrence 23 months after operation and underwent endoscopic resection again. No recurrence or metastasis was found in other patients.

CONCLUSIONSEndoscopic resection technique is effective for small GISTs patients. The small GISTs with 0.4 cm diameter or less are often benign and should be followed up for long time. The small GISTs with 0.5 cm diameter or more possess the risk of malignancy, then surgical resection should be performed. Rectum small GISTs (except for 0.4 cm diameter or less) have worse biological behavior and should be removed.

Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies

Objective To analyze the different spreading patterns and the prognostic factors of nasopharyngeal adenocarcinoma (NPAC).Methods The clinical and radiological data of 39 pathologically confirmed consecutive cases of NPAC were retrospectively reviewed.Results In the 1 1 patients with CT/MRI-detected cranial nerve (CN)involvement,there were ACC (n=7),CAC (n=2)and MEC (n=2)(P <0.05).Lymph node metastasis occurred in 40% of CAC,7.7% of ACC and 1 6.7% of MEC (P =0.035). Significant differences were observed in 5 year OS and DFS rates between patients with and without CT/MRI-detected CN involve-ment (P <0.001;P =0.001).In 1 9 patients with early stage disease (stageⅠ-Ⅱ),significant difference was observed in 5 year OS rate between the surgical treatment group and non-surgical treatment group (P =0.038),and the difference was not significant in DFS (P =0.056).Conclusion CT and MRI are valuable tools not only for discovering the different spreading patterns of NPAC, but also for its prognosis.

Objective To explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with duodenum gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of 80 patients with duodenum GIST in the Zhongshan Hospital from January 2000 to December 2013 were analyzed retrospectively. Results There were 38 male and 42 female patients with a median age of 54 years. The major symptoms were upper alimentary tract hemorrhage and abdominal pain. Thirty-nine patients received local tumor excision , 18 patients underwent segmental duodenectomy, 23 patients were subjected to pancreaticoduodenectomy, all these operations were R0 resection. Thirty patients received imatinib treatment after operation , and 11 among them had metastasis relapse. Recurrence-free survival rates of 1-, 3-, and 5-years were 96.2% , 90.6%and 78.6%retrospectively. Overall survival rates of 1-, 3-, and 5-years were 100%, 98.3%and 96.1%. Multivariate Cox analysis showed tumor size >5 cm, mitotic count > 5 mitosis/50 HPF and intermediate/high NIH risk classification were associated with an increased risk of recurrence. The significant difference was not detected between the limited resection group and pancreaticoduodenectomy group in OS and RFS. Conclusions Surgery is still the main treatment for duodenum GIST. The surgical program is mainly determined by the location and size of tumor. Imatinib therapy should be used if necessary.

Objective To investigate the clinicopathological features of small gastrointestinal stromal tumors (GISTs) and to evaluate the efficacy of endoscopic therapy for GISTs. Methods Clinicopathological and follow-up data of 418 patients with GISTs undergoing endoscopic therapy in the Zhongshan Hospital between January 2009 and July 2014 were analyzed retrospectively. All the cases were evaluated by the NIH risk classification and AIFP classification , and were grouped according to the tumor size and location. Nuclear atypia and mitotic count were used to evaluate the biological behavior of small GIST. Efficacy of endoscopic therapy was analyzed with follow-up data. Results Out of 418 patients, GISTs located in the esophagus was 14 (3.3%), in the stomach 389 (93.1%), in the duodenum 5(1.2%), in the rectum 10(2.4%). A total of 412(98.6%) patients were mainly spindle cells, and mitosis was not found in 320(76.5%) patients. In 389 small stomach GIST, 245(58.6%) were in fundic region. Cases were divided into four groups according to the size and the result revealed the bigger the size, the more the mitotic count. Nuclear atypia in the 1.5-1.9 cm group was significantlyhigher compared to other groups. Cases were divided into four groups according to the location and the result revealed the mitotic count was not associated to the location. While the nuclear atypia of stomach GIST was significantly higher than that of esophageal GIST and the nuclear atypia of rectum GIST was significantly higher than that of other positions. The median follow-up was 32(4-69) months. One case (gastric fundus GIST, >1.5 cm) presented local recurrence 23 months after operation and underwent endoscopic resection again. No recurrence or metastasis was found in other patients. Conclusions Endoscopic resection technique is effective for small GISTs patients. The small GISTs with 0.4 cm diameter or less are often benign and should be followed up for long time. The small GISTs with 0.5 cm diameter or more possess the risk of malignancy, then surgical resection should be performed. Rectum small GISTs (except for 0.4 cm diameter or less) have worse biological behavior and should be removed.

Objective To explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with duodenum gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of 80 patients with duodenum GIST in the Zhongshan Hospital from January 2000 to December 2013 were analyzed retrospectively. Results There were 38 male and 42 female patients with a median age of 54 years. The major symptoms were upper alimentary tract hemorrhage and abdominal pain. Thirty-nine patients received local tumor excision , 18 patients underwent segmental duodenectomy, 23 patients were subjected to pancreaticoduodenectomy, all these operations were R0 resection. Thirty patients received imatinib treatment after operation , and 11 among them had metastasis relapse. Recurrence-free survival rates of 1-, 3-, and 5-years were 96.2% , 90.6%and 78.6%retrospectively. Overall survival rates of 1-, 3-, and 5-years were 100%, 98.3%and 96.1%. Multivariate Cox analysis showed tumor size >5 cm, mitotic count > 5 mitosis/50 HPF and intermediate/high NIH risk classification were associated with an increased risk of recurrence. The significant difference was not detected between the limited resection group and pancreaticoduodenectomy group in OS and RFS. Conclusions Surgery is still the main treatment for duodenum GIST. The surgical program is mainly determined by the location and size of tumor. Imatinib therapy should be used if necessary.