Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

Gastric cancer is a prevalent malignancy of the digestive system, and traditional laparoscopic radical gastrectomy remains a crucial treatment modality. However, the abdominal wound associated with specimen removal during this procedure conflicts with contemporary concept of minimally invasive surgery. Natural orifice specimen extraction surgery (NOSES) is an emerging minimally invasive surgical technique that has gained increasing utilization in patients with gastrointestinal tumors, owing to its benefits of reduced wound, accelerated postoperative recovery, and diminished postoperative pain. In recent years, the extensive application of NOSES technology for colorectal cancer in China has provided theoretical support for the minimally invasive treatment of gastric cancer. With the standardization of community health examinations in China, the incidence of early gastric cancer diagnoses is expected to rise, making NOSES surgery the likely future trend in the surgical treatment for early gastric cancer. However, this area remains under-explored both domestically and internationally. This paper aims to synthesize prior literature and review the historical development, current research status, advantages and disadvantages, technical challenges, and future directions of completely laparoscopic radical treatment of distal gastric cancer utilizing NOSES.

Gastric cancer is a prevalent malignancy of the digestive system, and traditional laparoscopic radical gastrectomy remains a crucial treatment modality. However, the abdominal wound associated with specimen removal during this procedure conflicts with contemporary concept of minimally invasive surgery. Natural orifice specimen extraction surgery (NOSES) is an emerging minimally invasive surgical technique that has gained increasing utilization in patients with gastrointestinal tumors, owing to its benefits of reduced wound, accelerated postoperative recovery, and diminished postoperative pain. In recent years, the extensive application of NOSES technology for colorectal cancer in China has provided theoretical support for the minimally invasive treatment of gastric cancer. With the standardization of community health examinations in China, the incidence of early gastric cancer diagnoses is expected to rise, making NOSES surgery the likely future trend in the surgical treatment for early gastric cancer. However, this area remains under-explored both domestically and internationally. This paper aims to synthesize prior literature and review the historical development, current research status, advantages and disadvantages, technical challenges, and future directions of completely laparoscopic radical treatment of distal gastric cancer utilizing NOSES.

Objective:To evaluate the safety and feasibility of the laparoscopic indocyanine green (ICG) fluorescence imaging during the sentinel node navigational surgery for the early gastric cancer.Methods:Patients with <4 cm early gastric cancer were chosen. 0.5 ml ICG (2.5 mg/ml) was preoperatively injected into submucosa around the lesion in four points by the endoscopy. The sentinel lymph node basin including the stained tissue and lymph node (LN) were completely resected guided by the fluorescence mapping under ICG laparoscopy. The specimen was inspected by frozen pathology section. The radical gastrectomy was dependent on the pathology result.Result:Between 2019 and 2021, a total of 18 patients were included in the final analysis. Most tumors (16/18) located in the middle or distal stomach. Median tumor size was 2.0 cm. Lymph vessel invasion was revealed in five cases and perineural invasion in three cases. According to AJCC tumor grading system, tumor depth was classified as Tis in 2 cases, T1a in 5 cases and T1b in 11 cases. Lymph node metastasis (LNM) was revealed in four patients (4/18, 22%). Median sentinel lymph node basins per patient were 2 (range, 1-5). An average 6 (range, 2-13) LNs were harvested in each case, including 6 (1-13) ICG stained LNs and 1 (0-5) non stained LNs. All of four LNM patients were detected by sentinel node navigational surgery. The rate of the sensitivity and accuracy were 100% and 100%, respectively. The median follow-up for the entire group was 58.3 months (0.3-59.9 months), with no recurrence or metastasis observed in any patient.Conclusion:The sensitivity and accuracy of the laparoscopic indocyanine green fluorescence imaging during the sentinel node navigational surgery were satisfactory.

Objective:To explore long-term outcome and risk factors of recurrence in stage Ⅲ gastric cancer patients who underwent radical gastrectomy and adjuvant chemotherapy.Methods:The clinical and pathological data of patients with stage Ⅲ (AJCC V8) gastric adenocarcinoma were analyzed retrospectively. All patients received radical gastrectomy and adjuvant chemotherapy consisting of oxaliplatin, fluoropyrimidines with or without docetaxel in our center during 2006 and 2011.Results:A total of 324 patients were enrolled into the study. With a median follow-up time of 108 months, 175 (54%) patients developed tumor recurrence. One hundred and eighty-three (56.5%) patients died, including 169 (52.2%) dying of gastric cancer recurrence. The median disease-free survival (DFS) was 35 months, and the median overall survival (OS) was 64 months. The 5-year OS rates were 58.2%, 51.5% and 25.6% in patients with stage ⅢA, ⅢB and ⅢC diseases, respectively ( P<0.01). Multivariate analysis revealed that T4b cancers ( P=0.02), higher lymph meta node ratio (LNR) ( P<0.01) and perineural invasion ( P=0.01) were independent negative prognostic factors, while more than 12 weeks of adjuvant chemotherapy may improve survival. Higher LNR was correlated with locoregional ( P<0.01), distant lymph node metastases ( P<0.01), and peritoneal metastases ( P=0.038). Perineural invasion ( P=0.047) was prone to peritoneal metastases. More than 12 weeks of adjuvant chemotherapy could reduce the risk of haematogenous metastases ( P=0.023). Conclusions:Outcomes were significantly different in subgroups of patients with stage Ⅲ gastric cancers after radical gastrectomy. Higher LNR and perineural invasion could predict poor prognosis and different recurrence patterns.

Objective:To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) model of" neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy (CNCT) followed by surgery" for locally advanced gastric cancer.Methods:From 2018 to 2020, 28 patients clinically diagnosed with locally advanced gastric adenocarcinoma or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer were prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45 Gy, 1.8 Gy/f. Concurrent chemotherapy was S-1 at a dose of 40-60 mg twice daily. Then, patients received four to six cycles of CNCT of SOX regimen at three weeks after neoadjuvant chemoradiotherapy. D 2 lymphadenectomy was performed at 4-6 weeks after CNCT. Results:A total of 28 patients completed the whole therapy. Grade 3 or above adverse events occurred in 3 cases (11%) during CCRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7%) developed leukopenia and 3 cases (11%) of thrombocytopenia during CNCT. Twenty patients (71%) completed the surgery. The proportion of patients with pathological complete remission (pCR) was 50%. Three patients experienced surgical complications including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. All were recovered after symptomatic treatment.Conclusion:Interim analysis results demonstrate that TNT can yield significant down-staging for patients with locally advanced gastric cancer, which causes tolerable adverse events and postoperative complications.

Objective:To evaluate salvage surgery in patients with early gastric cancer after noncurative endoscopic resection .Method:A total of 56 cases with early gastric cancer receiving salvage surgery after noncurative endoscopic resection were enrolled and the clinicopathological and follow-up information were analyzed to evaluate the necessity and safety of salvage surgery.Results:Among the 44(79%)patients with submucosal invasion, 38 (68%) were with SM2 (invasion submucosal invasion≥500 μm) according to the pathological results after endoscopic resection. 33 (59%)cases had positive margin. The rate of lymph node metastasis and positive residual tumor as found by salvage gastrectomy were 11% (6/56) and 25% (14/56) . In the multivariate analysis, deeper submucosal invasion resulted as independent risk factor for residual tumor( OR=1.001, 95% CI=1.000-1.002, P=0.036). Among the 12(21%)cases with postoperative complications, 3 (5%)underwent unplanned reoperations because of anastomotic or intra-abdominal bleeding. There was no difference in the number of retrieved lymph nodes and rate of postoperative complications between laparoscopic and open surgery(all P>0.05). Conclusion:For patients with the risk factors of lymph node metastasis after noncurative endoscopic resection, salvage surgery was necessary and laparoscopic approach was safe and feasible.

Despite the continuous development of medical devices and the standardization of gastrectomy plus D2 lymph node dissection, advanced gastric cancer still has high distant metastasis rate and local recurrence rate, and the prognosis is poor. Neoadjuvant chemotherapy can improve the long-term survival of patients with advanced gastric cancer by reducing tumor stage, increasing R0 resection rate and eliminating potential micrometastasis. However, it is still the focus of concern that whether the adverse reactions of preoperative chemotherapy will increase the incidence of postoperative complications. Postoperative complications can affect the oncological outcomes by activating minimal residual lesions and promoting metastasis through related inflammatory changes or delaying adjuvant therapy, so the premise of wide application of neoadjuvant chemotherapy should be the guarantee of surgical safety. This article reviews the incidence, severity and prognosis of operative complications in gastric cancer patients after neoadjuvant chemotherapy and further explores its influencing factors.

The standard treatment for advanced gastric cancer remains surgery-based comprehensive treatment. The D2 radical surgery has made outstanding contributions to the standarlization of gastric cancer surgery, which has improved patients' prognosis and quality of life. In recent years, neoadjuvant chemotherapy has achieved a certain effect on the treatment of advanced gastric cancer. With the continuous development of the concept of membrane anatomy in gastric cancer surgery, new surgical challenges have also been raised. For patients after neoadjuvant therapy, there is heated controversy in the possibility of completing radical gastrectomy with membrane anatomical concept for gastric cancer. We believe that if neoadjuvant therapy pushes mesenteric cancer cell back into the mesentery, theoretically membrane anatomy combined with neoadjuvant therapy is beneficial to the treatment efficacy of advanced gastric cancer. However, membrane anatomy has two important problems when combined with neoadjuvant therapy: (1) After neoadjuvant chemotherapy, there are varying degrees of edema around the stomach tissue, which will affect the visualization of anatomic planes. In addition, because the patients' coagulation function is damaged to a certain extent, it is difficult to avoid bleeding or minimize bleeding during the operation. Therefore, it is still controversial whether the patients with gastric cancer after neoadjuvant chemotherapy can undergo radical gastrectomy with membrane anatomy. (2) For patients with complete pathological remission, whether to obtain the maximum rate of pathological remission through intensive neoadjuvant therapy, or to obtain the survival benefit of patients with membrane anatomy surgery in clinic is still controversial. Faced with these confusions, multi-center clinical researches on the application of membrane anatomy surgery after neoadjuvant therapy is the only solution.

Objective:To analyze the long-term therapeutic effect of endoscopic submucosal dissection (ESD) on the treatment of early gastric cancer (EGC).Methods:We retrospectively reviewed EGC patients who underwent ESD at Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), from January 2009 to December 2016. The incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were analyzed. Kaplan-Meier method was used to analyze 5-years recurrence free survival (RFS) and 5-years disease special survival (DSS) of all patients.Results:A total of 255 EGC patients were enrolled in this study, included 175 differentiated early gastric cancer (D-EGC) patients and 80 undifferentiated early gastric cancer (UD-EGC) patients. Among them, 171 patients within the extended indication of ESD while 84 patients beyond the extended indication of ESD. Among the 225 patients, the incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were 2.0%, 2.0% and 2.4%, respectively. The local recurrence rates of D-EGC group and UD-EGC group was 1.7% and 2.5%, respectively, without significant difference ( χ2=0.176, P=0.675). The incidence rates of synchronous and heterogenous cancer in the D-EGC group were 2.3% and 3.4%, higher than 1.2% and 0 of UD-EGC group, although there was no significant difference ( χ2=0.306, P=0.580 vs χ2=2.809, P=0.094). There were no significant differences in 5-years RFS (91.3% vs 95.9%, P=0.236) and 5-years DSS (100% vs 98.6%, P=0.156) between D-EGC group and UD-EGC group. Conclusions:The long-term outcome of ESD in the treatment of EGS is good. More attention should be paid to the occurrence of local recurrence and heterogeneous cancer in EGC patients undergo ESD. These patients still have a good long-tern outcome even undergoing ESD for more than once.