Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.
Humans ; Male ; Female ; Receptor, trkA/genetics* ; Stomach Neoplasms/surgery* ; In Situ Hybridization, Fluorescence ; Biomarkers, Tumor/genetics* ; Translocation, Genetic ; Carcinoma ; Oncogene Proteins, Fusion/genetics* ; Chromosomal Proteins, Non-Histone/genetics*

Female ; Humans ; Vaginal Diseases ; Adenocarcinoma ; Stomach ; Hyperplasia ; Vaginal Neoplasms/surgery*

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Diaphragm/surgery* ; Retrospective Studies ; Feasibility Studies ; Esophagogastric Junction/surgery* ; Lymph Node Excision/methods* ; Stomach Neoplasms/pathology* ; Laparoscopy/methods* ; Gastrectomy/methods* ; Esophageal Neoplasms/pathology* ; Adenocarcinoma/pathology* ; Thoracoscopy

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm²), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.
Male ; Humans ; Gastrointestinal Stromal Tumors/surgery* ; Retrospective Studies ; Ki-67 Antigen ; Stomach Neoplasms/pathology* ; Prognosis ; Mutation ; Intestines/pathology* ; Proto-Oncogene Proteins c-kit/genetics* ; Receptor, Platelet-Derived Growth Factor alpha/genetics*

Objective: To investigate the feasibility of Cai tube-assisted natural orifice specimen extraction surgery (NOSES) in gastrointestinal surgery. Methods: This was a descriptive case-series study. Inclusion criteria: (1) colorectal or gastric cancer diagnosed by preoperative pathological examination or redundant sigmoid or transverse colon detected by barium enema; (2) indications for laparoscopic surgery; (3) body mass index <30 kg/m² (transanal surgery) and 35 kg/m² (transvaginal surgery); (4) no vaginal stenosis or adhesions in female patients undergoing transvaginal specimen extraction; and (5) patients with redundant colon aged 18-70 years and a history of intractable constipation for more than 10 years. Exclusion criteria: (1) colorectal cancer with intestinal perforation or obstruction, or gastric cancer with gastric perforation, gastric hemorrhage, or pyloric obstruction; (2) simultaneous resection of lung, bone, or liver metastases ; (3) history of major abdominal surgery or intestinal adhesions; and (4) incomplete clinical data. From January 2014 to October 2022, 209 patients with gastrointestinal tumors and 25 with redundant colons who met the above criteria were treated by NOSES utilizing a Cai tube (China invention patent number:ZL201410168748.2) in the Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University. The procedures included eversion and pull-out NOSES radical resection in 14 patients with middle and low rectal cancer, NOSES radical left hemicolectomy in 171 patients with left-sided colorectal cancer, NOSES radical right hemicolectomy in 12 patients with right-sided colon cancer, NOSES systematic mesogastric resection in 12 patients with gastric cancer, and NOSES subtotal colectomy in 25 patients with redundant colons. All specimens were collected by using an in-house-made anal cannula (Cai tube) with no auxiliary incisions. The primary outcomes included 1-year recurrence-free survival (RFS) and postoperative complications. Results: Among 234 patients, 116 were male and 118 were female. The mean age was (56.6±10.9) years. NOSES was successfully completed in all patients without conversion to open surgery or procedure-related death. The negative rate of circumferential resection margin was 98.8% (169/171) with both two positive cases having left-sided colorectal cancer. Postoperative complications occurred in 37 patients (15.8%), including 11 cases (4.7%) of anastomotic leakage, 3 cases(1.3%) of anastomotic bleeding, 2 cases (0.9%) of intraperitoneal bleeding, 4 cases (1.7%) of abdominal infection, and 8 cases (3.4%) of pulmonary infection. Reoperations were required in 7 patients (3.0%), all of whom consented to creation of an ileostomy after anastomotic leakage. The total readmission rate within 30 days after surgery was 0.9% (2/234). After a follow-up of (18.3±3.6) months, the 1-year RFS was 94.7%. Five of 209 patients (2.4%) with gastrointestinal tumors had local recurrence, all of which was anastomotic recurrence. Sixteen patients (7.7%) developed distant metastases, including liver metastases(n=8), lung metastases(n=6), and bone metastases (n=2). Conclusion: NOSES assisted by Cai tube is feasible and safe in radical resection of gastrointestinal tumors and subtotal colectomy for redundant colon.
Humans ; Male ; Female ; Middle Aged ; Aged ; Anastomotic Leak/surgery* ; Stomach Neoplasms/surgery* ; Retrospective Studies ; Laparoscopy ; Rectal Neoplasms/surgery* ; Colectomy ; Postoperative Complications ; Liver Neoplasms/surgery* ; Treatment Outcome

Objective: To analyze the risk factors for complications of endoscopic full-thickness resection (EFTR) of upper gastrointestinal submucosal tumors (SMTs). Methods: This was a retrospective observational study. The indications for EFTR included: (1) SMTs originating from the muscularis propria layer and growing out of the cavity or infiltrating the deep part of the muscularis propria layer; (2) SMTs diameter <5 cm; and (3) tumor identified as closely adherent to the serous layer during endoscopic submucosal dissection or endoscopic mucosal resection. This study included patients with SMTs originating from the muscularis propria layer in upper digestive tract, diagnosed preoperatively by endoscopic ultrasonography or computed tomography, who were successfully treated with EFTR. Those with incomplete clinical data were excluded. The clinical data of 154 patients with upper gastrointestinal SMTs who underwent EFTR at the Department of Gastroenterology, First Affiliated Hospital of Soochow University from January 2016 to January 2022 were retrospectively analyzed. Post-EFTR complications (such as delayed perforation, delayed bleeding, and postoperative infection, including electrocoagulation syndrome) were monitored and the risk factors for them were analyzed. Results: Among the 154 study patients, 33 (21.4%) developed complications, including delayed bleeding in three (1.9%), delayed perforation in two (1.3%), and postoperative infection in 28 (18.2%). One patient with bleeding was classified as having a major complication (hospitalized for more than 10 days because of complication). According to univariate analysis, complication was associated with tumor diameter >15 mm, operation time >90 minutes, defect closure method(purse string suture), and diameter of resected specimen ≥20 mm (all P<0.05). Multivariate logistic regression analysis showed that operation time >90 minutes (OR=6.252, 95%CI: 2.530-15.446, P<0.001) and tumor diameter >15 mm (OR=4.843, 95%CI: 1.985-11.817, P=0.001) were independent risk factors for complications after EFTR in patients with upper gastrointestinal SMTs. The independent risk factors for postoperative infection in these patients were operation time>90 minutes (OR=4.993, 95%CI:1.964-12.694, P=0.001) and purse string suture (OR=7.142, 95%CI: 1.953-26.123, P=0.003). Conclusion: Patients with upper gastrointestinal SMTs undergoing EFTR with tumor diameter >15 mm or operation time >90 minutes have a significantly increased risk of postoperative complications. Postoperative monitoring is important for these patients with SMTs.
Humans ; Stomach Neoplasms/surgery* ; Endoscopic Mucosal Resection/methods* ; Gastroscopy/methods* ; Retrospective Studies ; Endosonography/adverse effects* ; Postoperative Complications/etiology* ; Treatment Outcome ; Gastric Mucosa/surgery*

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.
Humans ; Stomach Neoplasms/surgery* ; Gastrectomy ; Gastroesophageal Reflux ; Esophagogastric Junction/surgery* ; Pylorus/pathology*

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).
Humans ; Stomach Neoplasms/pathology* ; Gastrectomy/methods* ; Laparoscopy/methods* ; Lymph Node Excision/methods* ; Mesentery/surgery*

This century has seen significant advances in the treatment and research of gastric cancer in China. Chinese scholars have made a series of key technological breakthroughs in minimally invasive surgery, perioperative treatment and artificial intelligence diagnosis. These world-leading clinical researches have improved treatment outcomes and reduced surgical trauma. Global surveillance of trends in cancer survival 2000-14 reported that survival of gastric cancer in China has significantly improved during the last 20 years. This paper reviews the research history of surgical oncology for gastric cancer in China, summarises the experience and attempts to explore the future direction.
Humans ; Stomach Neoplasms/surgery* ; Surgical Oncology ; Artificial Intelligence ; Gastrectomy ; China/epidemiology* ; Minimally Invasive Surgical Procedures