Hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally advanced gastric cancer after D2 radical resection: a randomized-controlled study.

BACKGROUND: Currently, there is a lack of an effective strategy for the prevention of peritoneal metastasis (PM) from locally advanced gastric cancer (AGC). This randomized-controlled study aimed to evaluate the outcome of D2 radical resection with hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally AGC patients. METHODS: All enrolled patients were randomly assigned to receive HIPEC plus systemic chemotherapy (HIPEC group) or systemic chemotherapy alone (non-HIPEC group) after radical gastrectomy. HIPEC was performed intraperitoneally with cisplatin (40 mg/m2) within 72 h after surgery, while systemic chemotherapy based on the SOX regimen (S-1 combined with oxaliplatin) was administered 4-6 weeks after radical surgery. Patterns of recurrence, adverse events, 3-year disease-free survival (DFS), and overall survival (OS) were analyzed. RESULTS: A total of 134 patients were enrolled in the present study. The 3-year DFS rate was 73.8% in the HIPEC group, which was significantly higher than that in the non-HIPEC group (61.2%, P = 0.031). The 3-year OS rate was 73.9% in the HIPEC group and 77.6% in the non-HIPEC group, with no significant difference (P = 0.737). PM was the most common distant metastasis in both groups. The occurrence rate of PM in the HIPEC group was statistically lower than that in the non-HIPEC group (20.9% vs. 40.3%, P = 0.015). Grade 3 or 4 adverse events occurred in 19 (14.2%) patients, and there was no significant difference between the two groups. CONCLUSION: Radical surgery followed by HIPEC combined with systemic chemotherapy is a safe and feasible strategy for locally AGC patients and could effectively improve DFS and reduce the occurrence of PM. However, more prospective randomized studies with a large sample size are warranted. TRIAL REGISTRATION: This study was registered with www.medresman.org.cn as ChiCTR2200055966 on 10/12/2016.

Knockdown of carboxypeptidase A4 (CPA4) inhibits gastric cancer cell progression via cell cycle arrest and apoptosis.

Background: Gastric cancer is one of the most prevalent cancers, with a low survival rate at the later stages. Carboxypeptidase A4 (CPA4) is associated with the aggressiveness and growth in cancer. However, its regulatory role in gastric cancer remains unknown. Therefore, we investigated the role of CPA4 in gastric cancer progression in vitro. Methods: The human gastric adenocarcinoma cell line (AGS cell line) was used in the present study. CPA4 knockdown lentiviruses were constructed. Western blot analysis was performed to evaluate the protein expression levels of epithelial-mesenchymal transition (EMT) transcription factors, EMT biomarkers, and proteins involved in the Wnt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was carried out to evaluate the mRNA expression level of CPA4. The String database was employed for protein-protein interaction (PPI) network analysis. Cell colony formation, proliferation, migration, invasion, apoptosis, and cell cycle analyses were performed using corresponding kits. Results: CPA4 is highly expressed in gastric cancer cell lines. Overexpressed CPA4 was associated with the induction of EMT. Knockdown of CPA4 inhibited cell colony formation, proliferation, migration, and invasion of gastric cancer cells. Knockdown of CPA4 also promoted cell apoptosis of gastric cancer cells. Conclusions: Knockdown of CPA4 inhibited cell progression via arresting the cell cycle and inducing EMT in gastric cancer.

Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study.

BACKGROUND: There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. METHODS: Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1-14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). RESULTS: A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7-25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3-14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). CONCLUSION: Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.

Management Of Synchronous Krukenberg Tumors From Gastric Cancer: a Single-center Experience.

Background: Whether metastasectomy improves prognosis of gastric cancer patients with ovarian metastases (Krukenberg tumors) is not clear. In this study, we examined the survival benefit of metastasectomy combined with chemotherapy for treatment of synchronous Krukenberg tumors from gastric cancer and identified the prognostic factors. Methods: The subjects of this study were patients diagnosed as synchronous Krukenberg tumors of gastric origin in the period between December 2004 and December 2015. Patients were classified in accordance with treatment modality: metastasectomy group (metastasectomy combined with chemotherapy) and non-metastasectomy group (chemotherapy alone). Clinicopathological characteristics together with treatment records were investigated in detail and their relationship with survival outcomes was examined. Results: Out of a total of 103 patients, 54 (52.4%) underwent metastasectomy of Krukenberg tumors while 49 (47.6%) patients had chemotherapy alone. Overall survival (OS) in the metastasectomy group was significantly longer than that in the non-metastasectomy group (18.9 months vs. 12.4 months, respectively; P<0.001). Metastasectomy (hazard ratio [HR] 0.486; 95% confidence interval [CI] 0.323-0.729; P<0.001), signet ring cells (HR 1.938; 95% CI 1.182-3.175; P=0.009), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230-3.049; P=0.004), expression of estrogen receptor-ß (ER-ß) (HR 0.404; 95% CI 0.251-0.648; P<0.001), and progesterone receptor (PR) (HR 0.496; 95% CI 0.301-0.817; P<0.001) were independent predictors of OS. Conclusion: Metastasectomy combined with chemotherapy showed an association with survival benefit in patients with synchronous Krukenberg tumors from gastric cancer. Metastasectomy, expression of ER-ß and PR, peritoneal carcinomatosis, and signet ring cells were independent predictors of survival. Further prospective studies are warranted.

Treatment strategy and prognostic factors for Krukenberg tumors of gastric origin: report of a 10-year single-center experience from China.

BACKGROUND: Gastric cancer patient with ovarian metastasis is common in clinical practice, but it is still uncertain whether surgical resection of ovarian metastasis could improve the outcome. This study aimed to explore the survival benefit of metastasectomy plus chemotherapy over chemotherapy alone in the treatment of Krukenberg tumors arising from gastric cancer and to identify prognostic factors. RESULTS: A total of 152 patients were identified, including 93 patients with synchronous ovarian metastasis and 59 patients with metachronous ovarian metastasis. Overall survival (OS) was significantly better in metastasectomy group relative to the non-metastasectomy group for patients with synchronous ovarian metastasis (19.0 months vs. 11.8 months; P < 0.001) and those with metachronous ovarian metastasis (24.6 months vs. 14.3 months; P = 0.02), respectively. Metastasectomy (hazard ration [HR] 0.486; 95% confidence interval [CI] 0.323-0.729; P < 0.001), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230-3.049; P = 0.004), and expression status of ER-ß (HR 0.404; 95% CI 0.251-0.648; P < 0.001) and PR (HR 0.496; 95% CI 0.301-0.817; P < 0.001) were independent predictors of OS. METHODS: All patients who were diagnosed with gastric cancer and ovarian metastases between January 2005 and December 2014 were included in the current study. Patients were subdivided according to treatment modality: the metastasectomy group (metastasectomy plus chemotherapy) and the non-metastasectomy group (chemotherapy alone). The clinicopathological features and the treatment records were reviewed in detail and their association with survival were analyzed. CONCLUSION: Metastasectomy plus chemotherapy was associated with survival benefits in patients with Krukenberg tumors from gastric cancer. Metastasectomy, peritoneal carcinomatosis, and expression status of ER-ß and PR were independent prognostic factors for survival.

Solid pseudopapillary neoplasms of the pancreas: clinical analysis of 45 cases.

AIMS: This study investigated the clinicopathological features and surgical management of solid pseudopapillary neoplasms (SPNs) at a single institution in China. METHODS: We investigated 45 patients who underwent surgery for pathologically confirmed SPNs between 1996 and 2014. RESULTS: The 45 cases included 44 female and 1 male patients, and the average age was 32.2 years. The tumor was located in the body and/or tail in 33 patients, the head in 9 patients and the neck in 3 patients. The median tumor size was 6.3 cm (range 1.5 to 16). All 45 patients had curative resections including 29 distal pancreatectomies, 9 pancreaticoduodenectomy, 5 central pancreatectomy and 2 enucleation. 2 patients required superior mesenteric vein resection due to local tumor invasion. Eight patients had malignant tumors. Ki-67 was detected positive in 5 patients with malignant potential. After a median follow-up of 51.7 months, one patient with malignant SPN had evidence of tumor recurrence. CONCLUSION: SPN is an infrequent tumor, typically affect young women with low malignant potential. Surgical resection is warranted even in the presence of local invasion or metastases as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential and poor outcome of SPNs.

[Clinical research on microecologic treatment combined enteral nutrition for hepatic encephalopathy].

OBJECTIVE: To evaluate the effect of microecologic treatment combined enteral nutrition on serum endotoxin, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), blood ammonia levels and nutritional status in patients with hepatic encephalopathy. METHODS: 60 patients with hepatic encephalopathy were allocted randomly into 3 groups, on the basis of conventional liver protective therapy and uragogue with one group given probiotics plus enteral nutrition, one given probiotics only, and the 3rd group given intravenous nutrition. The whole course of treatment was four weeks. Serum levels of endotoxin, TNF-α, IL-18, ammonia and albumin were determined before and on the 7th and 14th day after treatment. RESULTS: The levels of serum endotoxin, TNF-α, IL-18 and blood ammonia in the combined treatment group decreased remarkably after treatment, while the level of serum albumin elevated markedly. The difference was significant at statistics as compared with the only probiotics group and intravenous nutrition group (P < 0.05). CONCLUSION: Microecologic treatment combined enteral nutrition could effectively reduce blood ammonia and serum endotoxin levels, protect intestinal mucosal barrier, as well as improve nutritional status of patients with hepatic encephalopathy, which was considered as a safe and efficient therapy.