[Establishment and validation of a predictive nomogram model for advanced gastric cancer with perineural invasion].

Objective: Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan. Methods: Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results: A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 µg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 µg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results (P=0.415). Conclusion: A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

[Key points of perioperative whole-process management for patients with advanced gastric cancer].

Perioperative whole-process management (WPM) for patients with advanced gastric cancer (AGC) mainly focuses on some clinical issues which are easily neglected or underappreciated. WPM is helpful in making a scientific and rational therapeutic plan, and avoiding inadequate communication in multi-disciplinary participation, so that the diagnosis, treatment and rehabilitation for AGC patients can be integrated organically. Based on the current clinical practice for AGC patients, eight key issues in WPM should be emphasized.(1) Preoperative clinical staging. An accurate preoperative staging by endoscopy and imaging technique is helpful in setting up a rational therapeutic plan, and is also a prerequisite to start WPM. (2) Indications and value of diagnostic laparoscopy. Laparoscopic exploration is beneficial to find intraperitoneal micro-metastases so as to avoid unnecessary laparotomy. For cases of AGC infiltrating serosal layer or suspected of peritoneal metastasis, preoperative laparoscopic exploration should be routinely performed. (3) Neoadjuvant therapy. Multiple RCT studies have shown that neoadjuvant chemotherapy can benefit a majority of patients with AGC, improving prognosis and prolonging their overall survival. Therefore, neoadjuvant therapy should be considered first for stage III and IVA AGC patients. (4) Prediction of efficacy in neoadjuvant chemotherapy. Endoscopy, MDCT scan, PET-CT and liquid biopsy have certain predictive value individually, which can be used together or separately to improve the accuracy of prediction. (5) Effective prevention of postoperative peritoneal metastasis. Extensive intraoperative peritoneal lavage (EIPL), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) have been shown to be of various efficacy in preventing peritoneal metastases. (6) Prediction of postoperative prognosis of AGC patients. The key pathological indicators are tumor regression grade (TRG) and ypTNM staging, especially if there is lymph node metastasis. Usually for AGC patients who received neoajuvant chemotherapy with TRG 0 or ypN0, their prognosis was comparable to that of patients with cTNM stage I.(7) Postoperative adjuvant chemotherapy. Postoperative adjuvant therapy is always an important part of the WPM management of AGC patients. Several recent RCT studies have shown that duplet chemotherapy can significantly reduce the risk of death after D2 radical gastrectomy compared to singlet chemotherapy, especially for stage III patients. (8) Perioperative nutritional support. Due to different degrees of malnutrition in AGC patients, enhanced nutritional treatment in the perioperative period can not only reduce surgical complications, but also enable patients to complete necessary course of chemotherapy, and ultimately further improve their survival rate.

Key points of perioperative whole-process management for patients with advanced gastric cancer / 中华胃肠外科杂志

Perioperative whole-process management (WPM) for patients with advanced gastric cancer (AGC) mainly focuses on some clinical issues which are easily neglected or underappreciated. WPM is helpful in making a scientific and rational therapeutic plan, and avoiding inadequate communication in multi-disciplinary participation, so that the diagnosis, treatment and rehabilitation for AGC patients can be integrated organically. Based on the current clinical practice for AGC patients, eight key issues in WPM should be emphasized.(1) Preoperative clinical staging. An accurate preoperative staging by endoscopy and imaging technique is helpful in setting up a rational therapeutic plan, and is also a prerequisite to start WPM. (2) Indications and value of diagnostic laparoscopy. Laparoscopic exploration is beneficial to find intraperitoneal micro-metastases so as to avoid unnecessary laparotomy. For cases of AGC infiltrating serosal layer or suspected of peritoneal metastasis, preoperative laparoscopic exploration should be routinely performed. (3) Neoadjuvant therapy. Multiple RCT studies have shown that neoadjuvant chemotherapy can benefit a majority of patients with AGC, improving prognosis and prolonging their overall survival. Therefore, neoadjuvant therapy should be considered first for stage III and IVA AGC patients. (4) Prediction of efficacy in neoadjuvant chemotherapy. Endoscopy, MDCT scan, PET-CT and liquid biopsy have certain predictive value individually, which can be used together or separately to improve the accuracy of prediction. (5) Effective prevention of postoperative peritoneal metastasis. Extensive intraoperative peritoneal lavage (EIPL), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) have been shown to be of various efficacy in preventing peritoneal metastases. (6) Prediction of postoperative prognosis of AGC patients. The key pathological indicators are tumor regression grade (TRG) and ypTNM staging, especially if there is lymph node metastasis. Usually for AGC patients who received neoajuvant chemotherapy with TRG 0 or ypN0, their prognosis was comparable to that of patients with cTNM stage I.(7) Postoperative adjuvant chemotherapy. Postoperative adjuvant therapy is always an important part of the WPM management of AGC patients. Several recent RCT studies have shown that duplet chemotherapy can significantly reduce the risk of death after D2 radical gastrectomy compared to singlet chemotherapy, especially for stage III patients. (8) Perioperative nutritional support. Due to different degrees of malnutrition in AGC patients, enhanced nutritional treatment in the perioperative period can not only reduce surgical complications, but also enable patients to complete necessary course of chemotherapy, and ultimately further improve their survival rate.

[Problems for the conversion therapy in advanced gastric cancer].

Patients with advanced gastric cancer have a poor prognosis, which remains the clinical concerned hot topic. The main previous treatments for advanced gastric cancer were adjuvant chemotherapy and palliative surgery, however, the application of conversion therapy has improved the survival in recent years. There are still many problems and challenges for conversion therapy because of its initial stage, such as the definition of advanced gastric cancer and conversion therapy, the selection of suitable population for conversion therapy, and the role of surgery in conversion therapy. Precision medicine will be applied to conversion therapy for advanced gastric cancer in the future, which would benefit more patients.

Problems for the conversion therapy in advanced gastric cancer / 中华肿瘤杂志

Patients with advanced gastric cancer have a poor prognosis, which remains the clinical concerned hot topic. The main previous treatments for advanced gastric cancer were adjuvant chemotherapy and palliative surgery, however, the application of conversion therapy has improved the survival in recent years. There are still many problems and challenges for conversion therapy because of its initial stage, such as the definition of advanced gastric cancer and conversion therapy, the selection of suitable population for conversion therapy, and the role of surgery in conversion therapy. Precision medicine will be applied to conversion therapy for advanced gastric cancer in the future, which would benefit more patients.

Application value of programmed D2 radical gastrectomy for advanced gastric cancer / 中华消化外科杂志

Gastric cancer is one of the high incidence of malignant tumors in China,the incidence of which is in the second among the world and is only inferior to Japan.But the mortality of gastric cancer in China is 2 times of world's average level,which is often associated with low early diagnostic rate,big regional differentials in the surgical quantity of gastric cancer (especially D2 radical gastrectomy) and prognosis of patients influenced by surgical quantity.Therefore,a standardized treatment of gastric cancer is the current development trend and hotspot.The correct and programmed staging,evaluation,operation methods,approaches,lymph node dissection and digestive tract reconstruction are selected,thus improving the long-term survival of patients with advanced gastric cancer and reducing mortality in China.

Comparison of the efficacy between laparoscopic and open gastrectomy for the treatment of advanced gastric cancer: a Meta analysis / 中华消化外科杂志

Objective To compare the perioperative efficacy berween laparoscopic and open gastrectomy for the treatment of advanced gastric cancer.Methods Literatures on the comparison of the efficacy between laparoscopic and open gastrectomy were searched in the PubMed,EMBASE,the Cochrane Library,CNKI and CMCC.Articles were selected according to the inclusion criteria,and data were extracted from these trials by 2 reviewers independently and analyzed by Review Manager 5.0 software.The heterogeneity of the literatures was analyzed using the I2 test.Data were integrated by fixed or random effect model.The count data were presented by odds ratio (OR) and 95％ confidence interval (95％ CI).Results Twelve literatures were retrieved,including 1 published in Chinese and 11 in English,1 randomized controlled study and 11 retrospective non-randomized controlled studies.A total of 2 079 cases of advanced gastric cancer were included in this study,including 882 in the laparoscopic gastrectomy group and 1 197 in the open gastrectomy group.There were significant differences in the operation time,intraoperative blood loss,time to first flatus,time to first diet and duration of hospital stay between the 2 groups (WMD =41.33,-106.00,-0.55,-0.76,-2.62,95％ CI:25.44-57.21,-120.71--91.29,-0.80--0.29,-1.29--0.23,-4.05--1.18,P ＜ 0.05).There were no significant difference in the number of lymph nodes harvested and incidence of complications between the 2 groups (WMD =0.22,OR =0.82,95％CI:-1.48-1.93,0.62-1.08,P ＞ 0.05).Conclusion Laparoscopic gastrectomy can be safely performed for the treatment of advanced gastric cancer,and it brings benefits to patients in perioperative period than open gastrectomy.

Surgical techniques of para-aortic nodal dissection for advanced gastric cancer / 中华消化外科杂志

Gastric cancer is the second most common malignancy in the world.Surgical resection with lymph node dissection remains the only potentially curative therapy for gastric cancer.In a very long time,the appropriate extent of lymph node dissection accompanied by gastrectomy for cancer remained uncertian. Now gastrectomy with D2 lymphadeneotomy is the standard treatment for curable gastric cancer,but the addition of para-aortic nodal dissection is controversial and there is no worldwide consensus.In this article,we present a discussion on the surgicaltechniques of para-aorticnodaldissection for advanced gastric cancer.

Laparoscopic D3 radical gastrectomy for advanced gastric cancer / 中华消化外科杂志

Advanced gastric cancer is usually dealt with D2 radical dissection. There are different opinions as to whether it is necessary to perform D3 radical lymphadenectomy.Some scholars thought that properly enlarged radical dissection can improve long-term outcomes for the treatment of advanced gastric cancer.In recent years,laparoscopic D1 and D2 radical dissection of gastric cancer could be carried out in many hospitals.However,the technique and related skills for performing D3 radical lymphadeneetomy through laparoscope remains to be explored.Based on our previous experiences,D3 radical lymphadeneetomy using artery suspension method and medial-to-lateral approach for advanced gastric cancer is proved to be safe and feasihle.