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@#The aim of this review was to document the recently reported prevalence and risk factors for chronic obstructive pulmonary disease (COPD) in the last ten years. A scoping review of studies released between 2011 and 2021 was done. The main findings on selected studies’ prevalence and risk factors were summarised. Thirty-seven studies in total were chosen. The overall data on COPD prevalence was 1.3-36.7%, and the average incidence rate was 9.1%. The risk factors of COPD prevalence were identified as unchangeable risk factors (gender, age, family history of respiratory and cardiovascular disease, high blood pressure, and environmental temperature and humidity) and changeable risk factors (outdoor and indoor air pollution, cigarette smoking, occupational exposure, low education, low household income, obesity, underweight, physical inactivity, and cooking method). The highest changeable risk factors were cigarette smoking, indoor air pollution, and occupational exposure. In contrast, the lowest changeable risk factors were physical inactivity and cooking methods. Changeable risk factors significantly increase COPD risks. The COPD caused by household emissions from biofuel cooking in low-income rural areas deserves attention. Emphasis on healthy lifestyle interventions and economic and educational policies to reduce environmental impacts may prevent COPD.
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The standardized treatment of malignant tumor has always been the direction of continuous improvement of major medical institutions. In recent years, the basic research, prevention, screening and diagnosis and treatment level of gastric, gastroesophageal junction and esophageal cancer have been greatly improved, resulting in a significant improvement in the 5 years′ survival rate of patients, but there are still great differences in the diagnosis and treatment level among different regions. Chinese gastric cancer, gastroesophageal junction cancer and esophageal cancer differ greatly from European and American countries in etiology, pathological types, high incidence sites, etc. Therefore, the relevant guidelines of European and American countries cannot fully meet Chinese clinical practice. In 2021, Elsevier Publishing Group launched the Chinese edition of Elsevier clinical pathway for gastric, gastroesophageal junction and esophageal cancer, and the first update edition was made in 2022, which aims to promote the quality control of tumor diagnosis and treatment, standardize tumor diagnosis and treatment behaviors, promote the homogenization and standardization of tumor diagnosis and treatment, and ultimately improve the survival rate and quality of life of patients with malignant tumor. This pathway refers to the National Comprehensive Cancer Network clinical practice guidelines, the Chinese Society of Clinical Oncology guidelines, combines evidence-based medicine and clinical experience, and follows the scientific, universal, standardized and operable principles. It has been promoted and applied in clinical practice, and is constantly updated according to the latest research results.
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Tetanus consists of neonatal tetanus and non-neonatal tetanus.Non-neonatal tetanus remains a serious public health problem,although neonatal tetanus has been eliminated in China since 2012.Non-neonatal tetanus is a potential fatal disease.In the absence of medical intervention,the mortality rate of severe cases is almost 100％.Even with vigorous treatment,the mortality rate remains 30％-50％ globally.These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China,in order to improve medical quality and safety.These specifications introduce the etiology,epidemiology,pathogenesis,clinical manifestations and laboratory tests,diagnosis,differential diagnosis,grading and treatment of non-neonatal tetanus.
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Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital′s translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.
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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.
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Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate remains 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.
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Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization′s position paper on rabies vaccine in 2018 and related research progress in recent.
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Objective@#This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer (EGC) to assess the feasibility of using endoscopic submucosal dissection (ESD).@*Methods@#The records of patients with poorly differentiated early gastric cancer undergoing gastric radical resection between January 2012 and December 2016 were reviewed in Ruijin hospital. Those with distant metastasis, two or more malignant tumors, remnant gastric cancer, neo adjuvant therapy, previous history of gastric surgery or clear history of perigastric lymphadenectomy, and mixed tumors were excluded. Age, sex, presence of ulcerous lesion, tumor size, tumor location, depth of invasion, type of differentiation, lymphatic vessel invasion, vascular invasion, nerve invasion and HER2 expression were collected. Univariate and multivariate stepwise logistic regression analyses were used to identify the independent risk factors of perigastric lymph node metastasis.According to the Guidelines for the Treatment of Gastric Cancer (2018 edition) of the Chinese Society of Clinical Oncology (CSCO), the expanded indications of ESD for EGC are as follows: (1)no ulcerative lesions, the maximum diameter of lesions >2 cm of differentiated intramucosal cancer; (2)ulcerative lesions, the maximum diameter of lesions ≤3 cm of differentiated intramucosal cancer; (3)no ulcerative lesions, undifferentiated intramucosal carcinoma with diameter ≤2 cm. The relationship between clinicopathological factors and lymph node metastasis was analyzed.@*Results@#A total of 517 patients, aged 21-83 (57.1±11.7), including 307 males and 210 females, were enrolled in the study. Among them, 114 (22.0%) patients had lymph node metastasis. Univariate analysis showed that ulcerative lesion (P=0.042), tumor diameter (P=0.048), depth of invasion (P<0.001), location of tumors (P<0.001), lymphatic vessel invasion (P=0.009), vascular invasion (P<0.001) and nerve invasion (P=0.028) were related to lymph node metastasis after radical resection of poorly differentiated early adenocarcinoma. Age, sex, type of differentiation and HER2 expression were not significantly correlated to lymph node metastasis (P>0.05). Multivariate analysis showed that tumor size (OR=1.61, 95% CI: 1.03-2.52, P=0.037), depth of invasion (OR=2.77, 95% CI:1.66-4.63, P<0.001), lymphatic duct invasion (OR=14.74, 95% CI:1.58-137.36, P=0.018) were independent risk factors for lymph node metastasis in poorly differentiated EGC, and ulcerative lesion was not a risk factor for lymph node metastasis (OR=0.82, 95% CI:0.56-1.18,P=0.285). A total of 119 patients with poorly differentiated EGC fully complied with the relative indications of ESD recommended by the Japanese Statute and the criteria for radical resection after ESD. Among them, 14 (11.8%) still had perigastric lymph node metastasis, while the gender, tumor diameter, location, differentiation and HER2 expression were not associated with lymph node metastasis (P>0.05).@*Conclusion@#For patients with poorly differentiated EGC, the application of ESD should be carefully weighed with precise assessment of tumor diameter, depth of invasion, and lymphatic duct invasion.
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Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.
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Objective@#To investigate the differences of clinicopathological features, diagnosis, treatment and prognosis between patients with extra-gastrointestinal stromal tumors (EGIST) and duodenal gastrointestinal stromal tumors (DGIST).@*Methods@#A retrospective case - control study was performed. Case inclusion criteria: (1) tumor confirmed by histology and pathology; (2) primary tumor locating in the extra - gastrointestinal tract or duodenum; (3) without other synchronous tumors; (4) complete clinical and pathological data. Clinical data of 20 EGIST patients and 32 DGIST patients from March 2011 to September 2016 at Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were retrospectively collected and analyzed. The observational parameters included clinicopathological characteristics, treatment and prognosis conditions. Continuous data of abnormal distribution were expressed as median (range) and compared using the Mann-Whitney U-test. Survival curves were drawn by the Kaplan-Meier method and compared with the Log-rank test.@*Results@#Of the 20 EGIST patients, 8 were males and 12 were females with age of 61.0 (30.0 to 86.0) years and of the 32 DGIST patients, 12 were males and 20 were females with age of 55.5 (27.0 to 70.0) years. Compared with DGIST patients, EGIST patients were older (U=188.000, P=0.012], had larger tumor size [10.0 (3.0 to 29.0) cm vs. 4.0 (1.5 to 10.0) cm, U=98.500, P<0.001] and higher ratio of high risk classification [85.0% (17/20) vs. 12.5% (4/32), χ2=26.870, P<0.001]. Among the 20 EGIST patients, 5 were diagnosed with distal metastasis and received imatinib (400 mg/d), and the other 15 patients underwent radical resection who were included in survival analysis. All the 32 DGIST patients underwent radical resection. The median follow-up of whole group was 43 (14 to 76) months. The 3-year recurrence/metastasis-free survival rate of 15 cases undergoing radical resection in the EGIST group was 85.6%, which was lower than that of the DGIST group (88.6%), and the difference was not statistically significant (P=0.745). There was no significant difference in the 3-year overall survival rate between the EGIST group (92.9%) and the DGIST group (100%) (P=0.271).@*Conclusions@#As compared to DGIST, EGIST mostly occurs in those with older age, larger tumor size and higher risk grade. The prognosis of EGIST patients after radical resection is similar to that of DGIST patients.
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Objective@#To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis.@*Methods@#From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient′s body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator′s position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient′s legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m2) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m2) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m-2·d-1 for 14 consecutive days followed by 7-days rest. To observe the patients′ intraoperative and postoperative conditions.@*Results@#All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy.@*Conclusion@#Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.
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Objective@#To investigate the early immune effects of rabies vaccine combined with human rabies immunoglobulin (HRIG).@*Methods@#Rapid fluorescent focus inhibition test (RFFIT) was used to test the titers of rabies virus neutralizing antibodies (RVNA). The titers of RVNA of persons who had exposed to rabies at degree III on day 0, day 1, day 7, day 14 and day 45 were compared. The dynamic curves and seroconversion rates (SCR) of RVNA in persons of different genders, age and vaccine regimens (Essen and Zagreb) groups were analyzed.@*Results@#No significant differences of SCR among different genders, age and vaccine regimens groups were observed on the same day. SCR could be 100% on day14 in different groups. The dynamic curves of RVNA within the first 14 days showed the models of gradual rise, rapid rise and rapid decline.@*Conclusions@#The dynamic curves of RVNA within the first 14 days varied when rabies vaccines were used in combination with HRIG, and not all subjects were proved to be protected based on the RVNA detection within this period.
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The 12th International Gastric Cancer Congress (12th IGCC ) was successfully held in Beijing, China on 20th-23rd April, 2017, which gave Chinese surgeons a great opportunity to share clinical progress and experience in the surgical treatment of gastric cancer with colleagues from different countries. At the end of 2017, this article hereby reviews briefly the achievements of surgical work of gastric cancer, which was done by our Chinese surgeons in this year. Some aspects will be reviewed, aiming at summarizing experience, affirming achievement, finding out the gap and promoting improvement in the future. These aspects include the conversion therapy for stageIIII( gastric cancer; the minimally invasive surgery for gastric cancer; the alimentary tract reconstruction after gastrectomy; enhanced recovery after radical gastrectomy and surgery quality control and patient's quality of life after surgery. In 2017, the gastric cancer surgery in China has made some new progress in many fields, and some achievements have reached or are close to international advanced level. However, looking ahead to the coming year and the future, there are still some important works to be done in the field of clinical surgery for gastric cancer in China, which include (1) strengthening big clinical data in gastric cancer collection and analysis platform construction for the promotion of scientific decision in therapeutic strategy; (2) further participating in international academic exchange and cooperation with taking advantages of our big number of gastric cancer cases, great amount of bio-tissue samples and big number of professional surgeons to actively join the international clinical research and expand our academic influence in the world;(3)developing more multicentre prospective randomized controlled trials in order to further improve the scientific significance in Chinese clinical guideline, norms and expert consensus in surgical treatment for gastric cancer; (4) further improving effectiveness of the multidisciplinary team (MDT) model in order to truly play the role of each subject in resolving some difficult cases; (5) in terms of surgical treatment for patients, it should be continue to keep going on minimally invasive operation, rational perioperative treatment, refinement technique, radical cure resection, and to further improve operation quality control system, aiming at realizing both goals simultaneously in prolonging survival time and improving quality of life for the patients with gastric cancer.
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OBJECTIVE@#To investigate the clinical characteristics and prognostic factors of reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor (GIST).@*METHODS@#A retrospective case-control study was performed on the clinical data of 31 patients with GIST who had recurrence or metastasis after the first surgery and underwent one or more operations again from February 2003 to January 2016 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The clinical characteristics of these patients were analyzed. Kaplan-Meier survival curve was used to calculate the survival rate, Cox univariate and multivariate regression model was applied to prognosis analysis.@*RESULTS@#Age of these 31 patients at the first operation was 35-78 (median 49) years, including 17 males (54.8%) and 14 females (45.2%). The tumors of 21 cases located in small intestines (67.7%), 2 cases in stomach (6.5%), 4 cases (12.9%) in colorectum and of 4 cases (12.9%) in other sites. According to NIH criteria, risk assessment indicated 26 cases were(83.8%) with high risk, 3 cases (9.7%) with moderate risk, and 2 cases (6.5%) with low risk. After the first operation, 15 cases received the IM (imatinib) therapy regularly based on NCCN guideline,10 cases received the therapy irregularly, and the other 6 cases did not receive the therapy. R0 resection was performed in 29 cases (93.5%) and R1/R2 resection was performed in 2 cases (6.5%). The median interval between the first operation to the recurrence was 32.3 (5.2-117.6) months and the median age of recurrence was 56 years old. Refer to the recurrent location, 28 cases (90.3%) were found in the same location or liver, 1 case in greater omentum, and 2 cases in pelvic cavity. The median diameter of the tumor in reoperation was 6.5 cm. Twenty-three cases(74.2%) received R0 excision and the other 8 cases(25.8%) received R1/R2 excision. At diagnosis of tumor recurrence, 20 cases (64.5%) received the second surgery immediately and the other 11 cases received surgery after imatinib or sunitinib treatment. Twenty-nine (93.5%) patients were followed up for 7.3 to 160.3 (median 49.5) months. After the second surgery, the relapse-free survival (RFS) of the whole group was 3.2 to 148.6(median: 29.7) months. Till the end of follow-up, 9 cases died of recurrence. Among 20 alive cases, 8 cases were living with the tumor, 1 case received the third surgery. The median overall survival (OS) time was 38.4(6.2-160.3) months. The 5-year RFS and the 5-year OS of 15 cases who received regular targeted therapy after the first operation were 73.4% and 81.7% respectively, significantly higher than those of the other 16 cases who received irregular or no targeted therapy(37.6%, P=0.015 and 38.9%,P=0.023,respectively). The 5-year RFS rate and the 5-year OS rate of the 11 patients who were diagnosed or complicated with liver metastasis were 29.8% and 32.2% respectively, which were significantly lower than those of the 20 patients without liver metastasis (79.1% and 88.1% respectively, both P<0.001). Cox model for OS, the results showed that regular targeted therapy after first surgery(HR=0.362, 95%CI:0.210-1.074, P=0.089) and the liver metastasis (HR=5.342, 95%CI: 0.902-12.580, P=0.057) were not the independent risk factors.@*CONCLUSIONS@#Regular targeted therapy according to the guideline after the first operation for GIST patients with recurrence or metastasis may improve the prognosis. Prognosis of GIST patients with postoperative liver metastasis is poor.
Subject(s)
Female , Humans , Male , Middle Aged , Case-Control Studies , China , Gastrointestinal Stromal Tumors , Diagnosis , General Surgery , Neoplasm Metastasis , Neoplasm Recurrence, Local , Prognosis , Reoperation , Retrospective StudiesABSTRACT
Gastric cancer is the second most common malignancy and the one of the leading causes of cancer-related death in China. In particular, the survival rate of patients with stage IV or unresectable gastric cancer is very poor. Conversion therapy for stage IV gastric cancer has been the main subject with much attention recently. It is defined to achieve an R0 surgical resection after chemotherapy for originally unresectable cancer due to technical and/or oncological reasons. However, the optimal indications for conversion surgery are still controversial, and how to select the most appropriate candidates for conversion therapy remains to be clarified. A new biological category for stage IV gastric cancer proposed by K Yoshida from Gifu University has been tested out in some trials, from which stage IV gastric cancer can be divided into two different classifications based on the absence (category 1: potentially resectable metastasis and category 2: marginally resectable metastasis) or presence (category 3:incurable and unresectable metastasis and category 4: non-curable metastasis) of macroscopic peritoneal dissemination. The optimal indications for conversion therapy mainly include the patients with category 2, and partially for patients with categories 3 and 4. A surgery-oriented classification proposed by Peking University Cancer Hospital tried to classify the stage IV gastric cancer for conversion therapy. It would be classified as resectable and unresectable categories, depending on uhether R0 resection is available by preoperative evaluation. In this classification, unresectable cancer can be further classified as conversed, partly conversed and non-conversed types based on extent of cancer metastasis. The resection of primary and metastatic lesion in unscreened stage IV gastric cancer was not testified to improve survival. REGATTA trial has identified no significant difference in survival rate between the chemotherapy only and palliative gastrectomy with postoperative chemotherapy for stage IV gastric cancer with a single non-curable factor. With development of conversion therapy, a consensus has been reached that the patients with unresectable gastric cancer initially exhibiting one non-curative factor, if having clinical response to chemotherapy, may obtain a survival benefit from subsequent R0 radical gastrectomy. Several novel combined chemotherapy regimens occasionally allow for conversion of an initially unresectable gastric cancer to resectable cancer in clinical practice. Conversion surgery may result in long-term survival in selected patients who respond to chemotherapy. Several previous studies have evaluated the positive prognostic role of surgery after chemotherapy in stage IV gastric cancer patients with one non-curative factor, such as peritoneal metastasis, para-aortic lymph node metastasis or liver metastasis. Gastric cancer is a highly heterogeneous tumor in nature, consisting of varying aggressive biological characteristics. Oncologically stage IV gastric cancer is a systemic disease, and the complete response to any therapy is really very rare, so that conversion therapy is a great clinical challenging problem for gastric cancer patients. Due to the multi-pathway metastasis, perioperative systemic chemotherapy is the most important in conversion therapy for stage IV gastric cancer, and a radical surgical resection is the key to improve prognosis. A good local control does not necessarily lead to prolonged survival in patients with stage IV gastric cancer, in which other sites metastases often emerge even after successful local-regional cancer-oriented treatment. To date, most reports of conversion therapy for gastric cancer were from single-center or retrospective study. If more reliable evidences are to be obtained, more multi-center and prospective RCT studies must be carried out.
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The incidence of gastric cancer is high in China. Most patients are advanced incurable and by surgery at diagnosis. At present, the treatment of advanced gastric cancer in China has been mainly based on multidisciplinary treatment including surgery, chemotherapy, radiotherapy, molecular targeted therapy, as well as immunotherapy. In the pursuit of the ultimate goal of prolonging survival, from the perspective of management throughout the patient journey, we should further optimize and arrange the strategies, methods, techniques and timing in perioperative treatment. There are still many unsolved problems to promote gastric cancer surgery from simple technical resection to biological resection. Treatment procedure based on evidence-based medicine and efficacy evaluation criteria may result in correct decision. In addition molecular markers based on gene sequencing may help select oppropriate agents and predict efficacy and prognosis. In clinical practice, how to achieve individualized treatment based on precise staging and goal orientation is the aim of continuous efforts to prolong the survival of advanced gastric cancer patients.
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Gastric cancer with peritoneal dissemination is usually considered to be oncologically unresectable and is known to have a very poor prognosis. Despite recent advances in systemic chemotherapy, peritoneal dissemination due to advanced gastric cancer (AGC) still remains the most life-threatening type of metastasis and recurrence, which usually causes ascites accumulation, intestinal obstruction, or hydronephrosis, and then seriously impairs the quality of life. In general, the median survival time of these cases is reported to be just only 6-9 months. Recently, conversion therapy for gastric cancer with peritoneal dissemination has been highly concerned. It is defined as a conversion surgery aiming at an R0 resection after chemotherapy for both primary gastric cancer and distant metastatic cancerous foci including peritoneal dissemination, which were originally unresectable due to technical and/or oncological reasons. In numerous clinical practices, the results of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) have been reported to be more satisfactory in comparison with traditional systemic chemotherapy alone. Some clinical trials have demonstrated the clinical efficacy of intravenous and intraperitoneal administration of paclitaxel (PTX) combined with oral S-1 for peritoneal dissemination of gastric cancer with or without malignant ascites. Particularly, a longer period of survival can be expected when conversion R0 gastrectomy is successfully performed after observing significant responses of NIPS. Some clinical practice key points of conversion therapy for AGC patients with peritoneal dissemination are reviewed, including the importance of intraperitoneal and systemic synchronous chemotherapy, the reasonable choice of intraperitoneal chemotherapy drugs, the evaluation of primary gastric cancer and metastatic foci before and after conversion therapy, some special complications of NIPS, the indications of conversion surgery and the adjuvant therapy after conversion surgery, ect.
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Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor. To set up PDX model, primary or metastatic tumor are achieved to translate into immune-deficiency mice. The tumor in immune-deficiency mouse is acquired to translate to other immune-deficiency mouse to generate stable PDX model, which usually is affected by the strain of mouse, translation method and translation location in mouse. PDX models recapitulate the same histology and gene expression as the original patients' carcinoma. PDX models can accurately predict the effectiveness of novel drugs, screen more predictive biomarker for drug resistance and optimize the use of classic drugs in clinic. However, sole source of surgical resection of tumor, long time of construction, high failure rate and hardly used in evaluating immune drugs would be the barriers to be overcome to improve PDX models. The methodological issues, salient features, practical applications, and future directions of PDX models will be illustrated.
Subject(s)
Animals , Humans , Mice , Heterografts , Neoplasm Transplantation , Methods , Neoplasms , General Surgery , Translational Research, Biomedical , MethodsABSTRACT
Objective:To explore the quality of inventory samples of a biobank stored in a deep freezer from 0 to over 10 years in Shanghai Ruijin Hospital. Methods:We extracted 24 pairs of stocked gastric cancer samples between 2003 and 2014. We used 1%aga-rose gel electrophoresis to analyze DNA and RNA purity and integrity while adding the RNA integrity number (RIN) for precise analysis. Bicinchonininc acid (BCA) assay was used for protein concentration evaluation. Coomassie brilliant blue method was used for protein integrity assay. Results: The samples were divided into four groups according to cryopreservation period (9 years). No significant difference in DNA integrity was found between the groups (P>0.05);however, DNA degradation in normal gastric mucosa was faster than that in gastric cancer tissue (P=0.023). The RIN significantly declined when the storage period was 6 years or longer (P=0.018). No significant difference in protein concentration was observed between different groups. Using Coo-massie brilliant blue method, we found significant differences in preserved proteins with different molecular weights. Proteins with varying molecular weights were detected in the groups with the following cryopreservation periods:>9 years, a small number of low-molecular-weight (average 36.5 KD) proteins;6-8 years, medium-molecular-weight (average 65.63KD) proteins;3-5 years, high-molecu-lar-weight (average 127.5 KD) proteins;<2 years, high-molecular-weight (average 160 KD) proteins. Conclusion:Cryopreservation does not exert an obvious effect on DNA. If the cryopreservation period is more than 5 years, serious degradation of RNA should occur;like-wise, degradation of proteins with higher molecular weight should occur.
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The aim of the preoperative staging of gastric cancer was to evaluate the depth of tumor infiltration (T-stage), the extent or number of metastasized lymph nodes (N-stage), and distant metastasis (M-stage) before surgery, to develop an optimal therapeutic scheme for the patients with gastric cancer. Traditional methods of preoperative staging for gastric cancer are usually imaging diagnostic techniques, such as endoscopic ultrasonography (EUS), CT scan, magnetic resonance imaging (MRI) and laparoscopic exploration. At present, the accuracy of preoperative TNM staging of gastric cancer can generally reach 70% to 85% with significant clinical benefit. The accurate preoperative staging for cancer patients can have a major role in determining the final clinical outcome and in predicting the prognosis. According to the concept of "precision medicine", to achieve "preoperative precision staging of gastric cancer", the application of imaging diagnostic techniques must be combined with the analysis of individual genetic information or tumor molecular pathological classification, which should be based on research of the disease genomics, proteomics and metabolomics. In this article, we provide a review of results on preoperative staging of gastric cancer in recent years, and we also discuss how to think about the "preoperative precision staging of gastric cancer", with special emphasis on the potential of molecular imaging techniques, circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA), molecular targets for tumor targeting therapy and molecular pathological classification, etc. in judging bio-molecular behavior of gastric cancer before surgery.