Proximal gastrectomy may be a reasonable choice for patients with selected proximal advanced gastric cancer: A propensity score-matched analysis.

BACKGROUND: Whether proximal gastrectomy (PG) can be applied to patients with proximal advanced gastric cancer (AGC) remains controversial. We aimed to explore the oncological safety of PG for proximal AGC in this study. METHODS: 452 patients undergoing surgery for proximal AGC in the Affiliated Cancer Hospital of Nanjing Medical University were enrolled in this study. 329 patients with AGC were finally analyzed, of which 254 patients underwent total gastrectomy (TG) and 75 patients underwent PG. We used propensity score-matched (PSM) analysis to reduce biases. RESULTS: After PSM, 67 patients with proximal AGC were included in the PG group and TG group, respectively. The estimated 5-year OS rates for TG and PG group after PSM were 64.3% and 74.9%, respectively, and no significant difference in OS existed between the two groups (p = 0.275). Multivariate analysis showed that PG was not an independent prognostic factor. Incidence of metastasis in No.5 or 6 lymph node (LN) station was significantly higher in the patients with pathological T4 and Borrmann III tumors (9.9% and 10.6%) than those with pathological T2/3 and Borrmann I/II tumors (2.2% and 3.3%). No metastasis was observed in No.5 or 6 LN station in patients with pathological T2/3 tumors or Borrmann I/II tumors when tumor size was ≤4 cm. CONCLUSIONS: PG is a reasonable choice for patients with selected proximal AGC, especially for those with tumors of size ≤4 cm, Borrmann type I/II, and pathological T2/3. Future prospective randomized trials should be conducted first in patients with these specific proximal tumors.

Clinicopathological features and risk factors analysis of lymph node metastasis and long-term prognosis in patients with synchronous multiple gastric cancer.

BACKGROUND: As a common malignancy, gastric cancer (GC) remains an important threat to human's health. The incidence of synchronous multiple gastric cancer (SMGC) has increased obviously with technical advances of endoscopic and pathological examinations. Several studies have investigated the relationship between SMGC and solitary gastric cancer (SGC). However, little is known about the relationship between early and advanced SMGCs, and the independent risk factors of lymph node metastasis and prognosis in SMGC patients remain unclear. METHODS: We retrospectively collected 57 patients diagnosed as SMGC and underwent radical gastrectomies from December 2011 to September 2019. Epidemiological data and clinicopathological characteristics of all patients were recorded. Postoperative follow-up was performed by telephone or outpatient service. Chi-squared test or Fisher's exact test was adopted in analysis of categorical data. Continuous data were analyzed by using unpaired t test. Univariate and multivariate analyses were performed to investigate the independent risk factors of lymph node metastasis and tumor recurrence of SMGC. RESULTS: There were 45 males and 12 females. The average age was 62.1 years old. There were 20 patients with early SMGC and 37 patients with advanced SMGC. Most of patients (91.2%) had two malignant lesions. Tumor recurrence occurred in 8 patients, among which 7 patients died from recurrence. The rates of total gastrectomy, tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer and nerve invasion, and preoperative CEA level were significantly higher in advanced SMGC patients compared to those with early SMGC. Lymphovascular cancer plug and preoperative CA125 were the independent risk factors of lymph node metastasis in patients with SMGC. Lymph node metastasis, nerve invasion, and preoperative AFP might be the risk factors of tumor recurrence of SMGC, but need further validation. CONCLUSIONS: In patients with SMGC, the presence of tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer, nerve invasion, and relatively high preoperative CEA level might indicate the advanced SMGC. More attention should be paid to lymph node metastasis in SMGC patients with lymphovascular cancer plug and high preoperative CA125. Lymph node metastasis, nerve invasion, and preoperative AFP might be associated with recurrence of SMGC, needing further validation.

Comparison on the Efficacy of Double Tract Gastric Interposition Reconstruction Versus Jejunal Interposition Reconstruction After Proximal Gastrectomy.

BACKGROUND This study aimed to compare the efficacy of antrum-preserving double tract gastric interposition reconstruction (ADGR) versus antrum-preserving double tract jejunal interposition reconstruction (ADJR) after proximal gastrectomy (PG). MATERIAL AND METHODS In a retrospective study, 62 cases of proximal gastric cancer undergoing proximal gastrectomy were divided into an ADJR group (n=32) and an ADGR group (n=30) according to reconstruction methods. Perioperative outcomes and postoperative complications were compared between the 2 groups, and the changes in hemoglobin (Hb), total protein (TP), body weight, and quality of life (QOL) were observed at 1, 3, 6, and 12 months postoperatively. Endoscopy was given at 12 months postoperatively for assessing reflux esophagitis and residual food. RESULTS Differences were indistinct in the 2 groups regarding the operation time, intraoperative blood loss, postoperative length of stay (LOS), first flatus time, and postoperative complications (P>0.05). At 1, 3, 6, and 12 months after operation, no evident differences were shown between the 2 groups regarding weight loss and Visick scores (P>0.05). Compared with the ADJR group, the Hb level at 6 and 12 months after operation and TP level at 12 months after operation were increased markedly in the ADGR group (P<0.05). No apparent difference was detected between the 2 groups in reflux esophagitis (P=0.467). The incidence of residual food in the ADGR group was significantly lower than that in the ADJR group (6.67% versus 31.25%, P=0.014). CONCLUSIONS ADGR was superior to ADJR in improving nutritional status and preventing residual food of patients with proximal gastric cancer after proximal gastrectomy.

Treatment experience of delayed massive gastrointestinal bleeding caused by intra-abdominal arteriointestinal fistula in gastric cancer patients after radical gastrectomy.

BACKGROUND: Gastric cancer (GC) remains one of the leading causes of cancer-related death. Arteriointestinal fistula is a very rare but lethal postoperative complication in GC patients after gastrectomy. However, very few reports associated with arteriointestinal fistula have been published, and there is no matured diagnosis and treatment consensus for arteriointestinal fistula. Herein, we will investigate the etiology, clinical feature, diagnostic method, treatment, and prognosis by summarizing two patients we treated and consulting related cases reported in recent years. CASE PRESENTATION: A 61-year-old male and 75-year-old female with advanced gastric cancer of gastric antrum underwent radical distal gastrectomy and D2 regional lymphadenectomy. Residual gastrojejunostomies by the Roux-en-Y method were performed. The two patients recovered well after gastrectomy, and they received postoperative adjuvant chemotherapy. However, both of them suffered sudden hematemesis and melena about 2 months after surgery, resulting in unstable vital signs. Emergency exploratory laparotomy and interventional embolotherapy by digital subtraction angiography were immediately respectively performed. During this process, arteriointestinal fistulas were found in both of them. Pseudoaneurysms of gastroduodenal artery and common hepatic artery were respectively ruptured and bleeding into the duodenum. Finally, the male patient recovered, while the female patient died because of rebleeding and hemorrhagic shock. CONCLUSIONS: Arteriointestinal fistula, with low morbidity but high mortality, is an acute and fatal postoperative complication for GC patients after radical gastrectomy. DSA is the preferred method to diagnose arteriointestinal fistula. Embolotherapy by DSA should be performed immediately once arteriointestinal fistula is confirmed. Emergency laparotomy is another selection if the embolotherapy failed. We should pay more attention to perioperative preventive measures for formation of pseudoaneurysm, which is the leading cause of arteriointestinal fistula.

Her3 is associated with poor survival of gastric adenocarcinoma: Her3 promotes proliferation, survival and migration of human gastric cancer mediated by PI3K/AKT signaling pathway.

ErbB3 (Her3) is a membrane-bound protein which can form heterodimers with other EGF receptor family members with kinase activity. Previous reports identified Her3 as a significant predictor of poor survival in human gastric cancer (GC), but its mechanism has remained unclear. We sought to investigate the mechanism of Her3 in GC and its association with clinical characteristics. Her3 was detected by both real-time PCR and immunohistochemistry (IHC) in 161 GC patients, and its related downstream signaling PI3K/AKT activity and clinical characteristics were accessed by statistical analysis. Her3 siRNA was used in both in vitro and in vivo assay to investigate the mechanism. Her3 expression was significantly increased in human GC compared with adjacent normal gastric tissues as observed by both real-time PCR and IHC. Her3 expression was associated with downstream AKT activation and increased tumor size, metastasis and poor survival in GC patients. Knockdown of Her3 in human GC cell line can inhibit cell proliferation and tumor growth both in vitro and in vivo by inactivation of AKT. Her3 knockdown had no observed impact on Her2 expression or activity. G2/M arrest was investigated due to decreased CyclinB1 and p27(kip1) at T157. Increased apoptosis occurred in Her3 silenced GC cell treated with cisplatin due to decreased BAD at S112. Moreover, Her3 silence can inhibit cell migration in vitro and metastasis in vivo by down-regulating MMPs via PI3K/AKT signaling. Her3 is a new prognostic factor associated with tumor growth and metastasis via PI3K/AKT signaling.

[Clinical significance of human epidermal growth factor receptor family molecules expression in gastric cancer].

OBJECTIVE: To study the association of human epidermal growth factor receptor family molecules expression in gastric cancer tissues with the prognosis of patients with gastric cancer. METHODS: Clinical data of 161 patients with gastric cancer undergoing gastrectomy in Jiangsu Cancer Hospital between January 2006 and January 2007 were analyzed retrospectively. The expression of HER1, HER2, HER3 and HER4 was detected by immunohistochemistry. Association of the expression of HER family with the prognosis of patients was examined. Kaplan-Meier method was used to analyze the survival. RESULTS: High expression rates of HER1, HER2, HER3 and HER4 were 46.0% (74/161), 10.6% (17/161),55.9% (90/161) and 68.3% (110/161) respectively. Univariate analysis revealed that high expression of HER3 was associated with tumor invasion depth, lymph node metastasis, stage, neurovascular invasion, and overall 4-year survival. High expression of HER4 was associated with tumor distant metastasis and stage. High co-expression of HER2 and HER3 was associated with overall 4-year survival (P=0.023). Multivariate analysis revealed that high expression of HER3 and stage were prognostic independent factors. CONCLUSION: Up-regulated expression of HER3 is associated with the poor prognosis in gastric cancer patients.

[Effect of intraoperative intraperitoneal chemotherapy and postoperative nutritional support on intestinal permeability and cellular immune function in patients with advanced gastric cancer].

OBJECTIVE: To investigate the effect of hyperthermic intraoperative intraperitoneal chemotherapy(HIIC) and postoperative nutritional support on the intestinal permeability and the cellular immunity function in patients with advanced gastric cancer. METHODS: All the patients diagnosed as advanced gastric cancer in the Gastric Tumor Diagnosis and Treatment Center of Jiangsu Cancer Hospital were randomly divided into three groups using random digit table:(1)EN group treated with enteral nutrition during postoperative period; (2)HIIC+EN group treated with HIIC combined with postoperative enteral nutrition;(3)HIIC+PN group treated with HIIC combined with postoperative parenteral nutrition. Index of lactulose/mannitol(L/M) ratio was used to evaluate the permeability of intestinal mucosa. The percentage of CD4(+), CD8(+) and NK cell, the ratio of CD4/CD8 T cell in peripheral blood were tested by flow cytometry. The time points of these measurements were the day before surgery, postoperative days (POD) 3, 7, and 12. RESULTS: Compared with the day before surgery(POD-1), the ratio of L/M on POD+3 increased significantly in all the three groups(0.1235±0.0611 vs. 0.0280±0.0183, 0.1648±0.0571 vs. 0.0305±0.0208, 0.1702±0.0628 vs. 0.0298±0.0229)(P<0.05) and then decreased gradually. The L/M ratio of EN(0.0278±0.0217) and HIIC+EN(0.0336±0.0235) groups recovered to the baseline on POD+12, however HIIC+PN group still had elevated L/M ratio(0.0616±0.0430). The percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and HIIC+PN group were significantly lower than those in EN group(P=0.033, P=0.002, respectively). Compared with the POD-1,the percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and EN group on POD+12 were increased significantly(P<0.05). CONCLUSIONS: HIIC may cause significant increase in intestinal permeability and inhibit cellular immunity in patients undergoing radical resection for advanced gastric cancer. Mucosal permeability can be reversed by enteral nutrition.

The effect of early enteral nutrition on hyperthermic intraoperative intraperitoneal chemotherapy-induced mucosal permeability following gastrectomy.

AIM: To investigate (1) the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on intestinal permeability of patients with advanced gastric cancer and (2) the protective effect of postoperative enteral nutrition (EN) on patients. METHODS: All patients were divided randomly into 3 groups: the EN group, treated with EN during postoperative period; the EN+HIIC group, treated with HIIC and postoperative EN; and the PN+HIIC group, treated with HIIC and postoperative parenteral nutrition. The lactulose/mannitol (L/M) ratio was used to evaluate the permeability of intestinal mucous. RESULTS: Compared with the ratio of L/M on the day before operation (POD-1), the ratio of L/M on POD+3 increased significantly in all 3 groups (P < .0001) and then decreased gradually. The L/M ratio of the EN and EN+HIIC groups recovered to the baseline on POD+12. In contrast, the PN+HIIC group still had an elevated L/M ratio until POD+12. The ratios of L/M in the EN+HIIC group on POD+7 and POD+12 were significantly different from those of the PN+HIIC group (0.0855 ± 0.0462 vs 0.1298 ± 0.063, P = .007; 0.0336 ± 0.0235 vs 0.0616 ± 0.0430, P = .038, respectively). CONCLUSION: Gastric cancer radical resection resulted in a significant increase in intestinal permeability. HIIC aggravated the injury of intestinal mucous permeability, which could be reversed by EN.