A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Phase II Study of Preoperative IntraArterial Epirubicin, Etoposide, and Oxaliplatin Combined with Oral S-1 Chemotherapy for the Treatment of Borrmann Type 4 Gastric Cancer

Purpose@#A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer. @*Materials and Methods@#A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality. @*Results@#All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%–72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%–85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%–89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%–82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24–31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%–66.1%). @*Conclusions@#Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.Trial Registration: ClinicalTrials.gov Identifier: NCT02949258

Phase II Study of Preoperative IntraArterial Epirubicin, Etoposide, and Oxaliplatin Combined with Oral S-1 Chemotherapy for the Treatment of Borrmann Type 4 Gastric Cancer

Purpose@#A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer. @*Materials and Methods@#A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality. @*Results@#All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%–72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%–85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%–89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%–82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24–31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%–66.1%). @*Conclusions@#Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.Trial Registration: ClinicalTrials.gov Identifier: NCT02949258

Prospects for gastric cancer treatment based on the revisions of Japanese Gastric Cancer Classification / 中国实用外科杂志

Japanese gastric cancer classification marks the lymph nodes associated with gastric cancer metastasis in groups, which allows the surgeons and pathologists to operate as per a uniform specification to obtain the distribution of metastatic lymph nodes in every case. Through a substantial number of cases, the rules and pathways of lymph node metastasis are summarized, thus laying a theoretical foundation for radical gastrectomy. From the simple to the complex, and then to the refined and expansive, the classification categorizes subgroup studies to better rationalize the lymph node dissection; and expands the researches on marker range to investigate the role of enlarged surgery.Researches over decades have explored the law of lymph node metastasis to the extreme, and the surgical efficacy of gastric cancer near limit. Thus, shortly after the mature treatment model was established as the Gastric Cancer Treatment Guidelines by Japanese experts, the revised classification in2010 altered the criterion for staging gastric cancer from the location of metastatic lymph nodes to the number of metastases. This indicates that the exploration of surgical approaches to gastric cancer is basically completed, and the`future efficacy improvement of gastric cancer depends on comprehensive therapy. The formation of radical gastrectomy is the result of multidisciplinary collaborative research.Surgery should still be performed in strict accordance with the specification. Postoperative grouped inspection of lymph nodes has great significance for determining the surgical outcome and prognosis.

Essence of early gastric cancer and confusion in clinical practic / 中国实用外科杂志

Staging is a subjective assessment of objective progress of gastric cancer by doctors.However, the progress of gastric cancer is the result of tumor breaking through the limitation of immunity according to its inherent characteristics.The subjective evaluation methods are difficult to fully reflect the progress of gastric cancer. From the beginning of the concept of early gastric cancer to the wide application of endoscopic submucosal dissection(ESD) in clinic, the biggest puzzle is how to exclude lymph node metastasis. So far, it has not been satisfactorily solved. Therefore, in all previous Japanese Gastric Cancer Treatment Guidelines, the indications of ESD must be accompanied by the evaluation and treatment after endoscopic resection for possible residual cancer. Comprehending the essence of early gastric cancer and the related factors affecting its progress will help us to improve the quality of treatment for early gastric cancer and benefit patients.

Effect of Saropenia on Clinical Prognosis of Gastric Cancer Patients: A Prospective Cohort Study / 肠外与肠内营养

Objective: To investigate the effects of preoperative sarcopenia on postoperative clinical outcome in patients with gastric cancer. Methods: A prospective study was performed in 93 patients with gastric cancer and the skeletal muscle mass was examined by bioelectrical impedance. The primary outcome was postoperative complications. The secondary outcomes were postoperative length of stay, overall hospital costs, 60 days re-admission and mortality rate. Results: A significant difference (sarcopenia group vs. non-sarcopenia group) was observed in the rates of overall postoperative complications, incidence of pleural effusion and intra-abdominal infection, overall hospital stay and postoperative hospital stay (P ＜ 0. 05). The rates of 60 days readmission, 60 days mortality and hospital costs in sarcopenia group were not different between the two groups (P ＞ 0. 05). By univariate and multivariate analysis, preoperative sarcopenia and preoperative nutritional risk are the risk factors of postoperative complications. Conclusion: Sarcopenia is an independent risk factor for postoperative complications in patients with gastric cancer; preoperative patients with sarcopenia have a worse prognosis and should be screened and optimized before surgery.

Effects of monosulfuron-ester on metabolic processes of nitrogen-fixing cyanobacteria Anabaena flos-aquae and Anabaena azotica

Abstract Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300 nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3 nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300 nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.

Diagnostic Performance of the GenoType MTBDRand MTBDRAssays to Identify Tuberculosis Drug Resistance in Eastern China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The WHO recently has recommended the GenoType MTBDRplus version 1.0 and MTBDRsl version 1.0 assays for widespread use in countries endemic with drug-resistant tuberculosis. Despite this, these assays have rarely been evaluated in China, where the burden of drug-resistant tuberculosis is among the highest globally.</p><p><b>METHODS</b>Mycobacterium tuberculosis clinical isolates were obtained between January 2008 and December 2008. Isolates were tested for drug resistance against rifampicin (RFP) and isoniazid (INH) using the GenoType MTBDRplus assay and drug resistance against ethambutol (EMB), ofloxacin (OFX), and kanamycin (KM) using the Genotype MTBDRsl assay. These results were compared with conventional drug-susceptibility testing (DST).</p><p><b>RESULTS</b>Readable results were obtained from 235 strains by GenoType MTBDRplus assay. Compared to DST, the sensitivity of GenoType MTBDRplus assay to detect RFP, INH, and multidrug resistance was 97.7%, 69.9%, and 69.8%, respectively, whereas the specificity for detecting RFP, INH, and multidrug resistance was 66.7%, 69.2%, and 76.8%, respectively. The sensitivity and specificity of the GenoType MTBDRsl assay were 90.9% and 95.2% for OFX, 77.8% and 99.5% for KM, 63.7% and 86.4% for EMB, respectively. Mutations in codon S531L of the rpoB gene and codon S315T1 of KatG gene were dominated in multidrug-resistant tuberculosis (MDR-TB) strains.</p><p><b>CONCLUSIONS</b>In combination with DST, application of the GenoType MTBDRplus and MTBDRsl assays may be a useful supplementary tool to allow a rapid and safe diagnosis of multidrug resistance and extensively drug-resistant tuberculosis.</p>

Effects of different anesthesia methods on perioperative hemodynamics and ECG in old CHD patients / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore an optimal anesthesia method with less impact on hemodynamics and electrocardiogram (ECG) of old patients with coronary artery disease (CHD) during abdominal operation.</p><p><b>METHODS</b>The 133 CHD patients waiting for abdominal operation were randomly divided into continuous epidural anesthesia (EA) group, general anesthesia group (GA) and combined spinal-epidural anesthesia (CSEA) group. Continuous monitoring was carried out during operation and mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SaO2), abnormal ECG were measured respectively at different time for comparison and the differences of the above hemodynamic parameters and abnormal ECG features were compared among the 3 groups.</p><p><b>RESULTS</b>At the 15 min and 30 min point after anesthesia, SaO2 in GA group was significantly increased compared to that in the EA group (P < 0.05). At 15 min, 30 min and 60 min point after anesthesia, MAP in CSEA group was significantly increased compared to that in the EA group (P < 0.05). At 30 min point after anesthesia, HR in CSEA group was increased significantly compared to the EA group (P < 0.05). At 15 min and 30 min point after anesthesia, SaO2 in the CSEA group was increased significantly compare to the EA group (P < 0.05). Compared with preanesthesia (T0) in EA group, MAP, HR and SaO2 decreased significantly at 15, 30 and 60 min after anesthesia (P < 0.05). The fluctuation of the three parameters in GA and CSEA groups were relatively small (P > 0.05). As well as the comparison of abnormal ECG among the 3 groups was concerned, the incidence of ST-T changes in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min, 30 min and 60 min after anesthesia and at the time of surgery termination (P < 0.05, P < 0.01). The incidence of arrhythmia in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min, 30 min and 60 min after anesthesia (P < 0.05, P < 0.01). Compared with T0 in the same group, the incidences of ST-T changes and arrhythmia in GA or CSEA group at the time of 15, 30 and 60 min after anesthesia and at the time of surgery termination were significantly lower than that before anesthesia (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>GA and CSEA have less impact on hemodynamics and have smaller incidence of abnormal ECG of old CHD patients with abdominal operation.</p>

Perioperative cardiovascular abnormality in elder patients with silent coronary heart disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the perioperative cardiovascular dysfunction and its relevance to age in patients with silent coronary heart disease (or silent myocardial ischemia), and explore the clinical treatment and recovery of perioperative arrhythmias.</p><p><b>METHODS</b>One hundred and eighty cases were selected from selective surgery patients with silent myocardial ischemia (SMI). Among the cases, 130 patients older than 51 years old were divided into 51 - 60 year-old group, 61- 70 year-old group and 71 - 80 year-old group. Control group was set up by other 50 patients younger than 51 years old. Electrocardiogram data of 24 h before the operation, 24 h after the operation and 48 h after the operation were continuously monitored by dynamic electrocardiogram (DCG). The electrocardiogram data of ST shifting, arrhythmia incidences of different type and at different time were analyzed by professional doctors. At the same time, the treatment and recovery of perioperative arrhythmia were recorded.</p><p><b>RESULTS</b>As the age increase, the magnitude and duration of ST shifting appeared upward trend compared to the control group (P < 0.05, P < 0.01). The incidence of ST elevation in 71 - 80 year-old group was higher than the control group (P < 0.05). The ST depression duration in 61 - 70 and 71 - 80 year-old group and ST elevation magnitude in 71 - 80 year-old group were higher than 51 - 60 year-old group (P < 0.05). Compared to the control group, the incidence of accelerated idioventricular rhythm (AIR) in 61 - 70 year-old group and the incidence of sinus bradycardia (SB), ventricular premature beat (VPB), ventricular tachycardia (VT) in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). Compared to the 51 - 60 year-old group, the incidence of atrial fibrillation (AF) in 61 - 70 year-old group and the incidence of VP, VT, AF in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). The arrhythmia incidences in 24 h after operation were higher than 48 h after operation and 24 h before operation (P < 0.01). As the age increase, the recovery incidence by removing inducement was decreased, but the recovery incidences by drug and electric-shock treatment were increased (P < 0.05).</p><p><b>CONCLUSION</b>Old SMI patients have high levels of perioperative myocardial ischemia and arrhythmia, and 24 h after operation is the period of high incidence.</p>