Phase II Study of Preoperative Intra-Arterial Epirubicin, Etoposide, and Oxaliplatin Combined with Oral S-1 Chemotherapy for the Treatment of Borrmann Type 4 Gastric Cancer.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer. MATERIALS AND METHODS: A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality. RESULTS: All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%-72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%-85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%-89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%-82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24-31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%-66.1%). CONCLUSIONS: Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02949258.

Laparoscopic management of cholecystoenteric fistula: A single-center experience.

Aim To report our experience regarding management of cholecystoenteric fistula (CEF) and identify the most effective diagnostic methods and surgical treatment. Methods In total, 10,588 patients underwent laparoscopic cholecystectomy for cholecystolithiasis from January 2000 to December 2014 at the Research Institute of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively collected on demographics, preoperative diagnostics, intraoperative findings, laparoscopic procedures, complications, and follow-up. Results Twenty-nine patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated. Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four (13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients obtained a preoperative diagnosis. All patients initially underwent laparoscopic treatment, but five (17.2%) underwent conversion to open surgery; three of these five developed postoperative morbidity or mortality, and the other two had an uneventful postoperative course. Among patients managed successfully by laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All patients were asymptomatic at a mean follow-up of 13 months (range, 3-21 months). Conclusion Ultrasound and computed tomography can provide valuable diagnostic clues for CEF. Laparoscopic management of CEF in experienced hands is safe, feasible, and associated with rapid postoperative recovery.

Combination therapy with thymosin alpha1 and dexamethasone helps mice survive sepsis.

Immune dysfunction is a major cause of mortality in septic patients. Current evidence indicates an important role for dendritic cells (DCs) in the pathophysiology of immune dysfunction, and these cells are potential targets of immunomodulation therapies. In the present study, our aim was to enhance the resistance of endotoxemic mice to bacterial translocation and secondary infection and to improve the outcome of these infections using a combination therapy consisting of thymosin alpha1 and dexamethasone in a timely manner according to the changes of DCs' number. The effect of treatment with dexamethasone (DXM) and thymosin alpha1 (Tα1) on DCs was investigated by examining their number, MHCII and CD86 expression and their capacity to induce T cell activation. Endotoxemic mice were randomly divided into five treatment groups. The survival rates, the levels of TNF-α and IL-10, the occurrence of bacterial translocation, and the ability to clear secondary infections were determined. Additionally, the behavior of DCs over time was also evaluated. Tα1 induced significant increases in DC numbers in vivo, whereas DXM reduced cell numbers both in vitro and in vivo. However, neither drug induced significant changes in the capacity of DCs to induce T cell activation or their expression of MHCII or CD86. Among the five treatment groups, the mice treated with a combination of DXM and Tα1 had the highest survival rate; this increased survival was associated with a decrease in bacterial translocation to extra-intestinal organs and an enhanced ability to eradicate secondary infections by reversing the change in DC numbers during endotoxemia. Immunomodulatory therapy that combines Tα1 and DXM in a timely manner and was based on changes in DCs enhanced the resistance of endotoxemic mice to bacterial translocation and secondary infections, improving the outcome of the infection.

Accumulation of DC in lamina propria induced by FMS-like tyrosine kinase 3 ligand aggravates the intestinal inflammatory response during endotoxemia.

It is known that the loss of DC plays an important role for immune suppression during endotoxemia or sepsis. To verify our hypothesis that pre-enrichment of the lamina propria (LP) DC pool may improve protective immunity to bacterial translocation and outcome in endotoxemic mice, we pre-treated mice with Flt3L or normal saline, and then challenged them with or without LPS. Twelve hours later the population size and maturity of DC in the LP and circulation were analyzed by flow cytometry. Bacterial translocation to distant organs, inflammatory responses in the intestine and the survival rate of mice were evaluated. We observed that pretreatment of Flt3L significantly expanded DC in the LP and blood, but did not alter their maturation. However, exacerbation of DC growth induced by Flt3L-pretreatment aggravated intestinal inflammation and increased the mortality of endotoxemic mice rather than enhancing their resistance to bacterial translocation.