EDIL3 regulates gastric cancer cell migration, invasion and epithelial-mesenchymal transition via TGF-ß1/XIST/miR-137 feedback loop.

BACKGROUND: Human gastric cancer is a serious disease with high mortality rate all over the world. The one of difficulties in effective therapy of gastric cancer is metastasis. It has been reported that lncRNAs and miRNAs are involved in cancer metastasis. So, exploration of new molecular mechanism underlying gastric cancer metastasis involving in network of lncRNAs/miRNAs/effector proteins is important and meaningful for guiding the treatment of gastric cancer. METHODS: MTT assay, flow cytometric analysis and colony formation assay were performed to evaluate AGS or MKN-45 cell proliferation, cycle distribution and colony formation, and RT-qPCR was used to examine the expressive abundances of EDIL3, XIST and miR-137. EDIL3 and epithelial-mesenchymal transition (EMT) related proteins were detected by western blot and migration and invasion were measured by transwell analysis. Meanwhile, Dual-luciferase reporter gene assay was used to confirm XIST binding to miR-137, and miR-137 binding to EDIL3. AGS cells were used to establish the xenograft tumor model to verify the role of EDIL3 in tumorigenesis in nude mice. RESULTS: Expression levels of EDIL3 was increased in gastric cancer tissues and cell lines. Downregulation of EDIL3 or XIST and overexpression of miR-137 inhibited proliferation, migration, invasion and EMT in AGS and MKN-45 cells. XIST could specifically bind to miR-137, and EDIL3 was a target gene of miR-137. Moreover, TGF-ß1 stimulated XIST expression, inhibited miR-137 expression and induced migration, invasion and EMT. We also found that overexpression of EDIL3 elevated levels of TGF-ß1 and induced migration, invasion and EMT, which were reversed by TGF-ß1 inhibition. EDIL3 knockdown suppressed migration, invasion and EMT, which were reversed by XIST. Overexpression of miR-137 inhibited proliferation, migration, invasion and EMT, which were reversed by EDIL3 overexpression. CONCLUSIONS: EDIL3 regulates gastric cancer cell migration, invasion and EMT, which is involved in the regulation of TGF-ß1/XIST/miR-137 feedback loop, and EDIL3 knockdown inhibits tumor growth in nude mice. These findings indicate that the EDIL3 mediated molecular feedback loop may be developed as drug targets for the gastric carcinoma treatment.

Prevention of Venous Thromboembolism After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Development of a Physiotherapy Program.

BACKGROUND: This study was to assess the risk of venous thromboembolism (VTE) in patients with peritoneal carcinomatosis (PC) and to evaluate the safety and feasibility of physiotherapy program to prevent VTE during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: For VTE prevention, we developed a systematic physiotherapy program consisting of active exercises of both arms and legs, and intermittent pneumatic compression device to massage both legs. This physiotherapy was applied to all patients, and the VTE-related events were recorded and analyzed. RESULTS: Cytoreductive surgery + HIPEC was performed on 466 patients with PC. All patients had highest VTE risk, with the median Caprini risk factor score being 11. During the 3-month observation period, 8 patients had 9 (1.9%) clinically symptomatic VTE events, including 8 (1.7%) deep vein thrombosis and 1 (0.2%) pulmonary embolism. Among those, 5 patients received pharmacological treatments with low-molecular-weight heparin, and the other 3 received physical exercises only. All these patients recovered well, and there was no mortality about VTE perioperatively. CONCLUSIONS: Patients with PC treated by CRS + HIPEC are at highest risk for VTE. The systematic physiotherapy program is safe and feasible to prevent VTE post CRS + HIPEC.

The intra-neuroendoscopic technique: A new method for rapid removal of acute severe intraventricular hematoma.

The mortality rate of acute severe intraventricular hematoma is extremely high, and the rate of disability in survivors is high. Intraventricular hematoma has always been a difficult problem for clinical treatment. Although minimally invasive endoscopic hematoma evacuation is widely used to treat this disease, the technique still has room for improvement. Equipment for the intra-neuroendoscopic technique (INET) consists of two of our patented inventions: a transparent sheath (Patent No. ZL 200820046232.0) and a hematoma aspirator (Patent No. ZL 201520248717.8). This study explored the safety and efficacy of INET by comparing it with extraventricular drainage in combination with urokinase thrombolytic therapy. This trial recruited 65 patients with severe intraventricular hemorrhage, including 35 (19 men and 16 women, aged 53.2 ± 8.7 years) in the INET group and 30 (17 men and 13 women, aged 51.5 ± 7.9 years) in the control group (extraventricular drainage plus urokinase thrombolytic therapy). Our results showed that compared with the control group, the INET group exhibited lower intraventricular hemorrhage volumes, shorter intensive care-unit monitoring and ventricular drainage-tube placement times, and fewer incidences of intracranial infection, secondary bleeding, and mortality. Thus, the prognosis of survivors had improved remarkably. These findings indicate that INET is a safe and efficient new method for treating severe intraventricular hematoma. This trial was registered with ClinicalTrials.gov (NCT02515903).

A new modified neuroendoscope technology to remove severe intraventricular haematoma.

BACKGROUND: Minimally invasive endoscopic haematoma evacuation is widely used in the treatment of intraventricular haemorrhage. However, its technique still has room for improvement. A new modified neuroendoscope technology (MNT) was used in this study and we explored its safety and efficacy in the treatment of severe acute intraventricular haemorrhage by comparing it with extraventricular drainage plus urokinase thrombolytic (EVD + UT) therapy. METHODS: The following parameters were compared between the MNT group and the control group: incision design, operation time, ICU monitoring time, ventricular drainage tube (VDT) placement time, post-operative drainage tube obstruction (PDTO) rate, post-operative complications rate, 6-month mortality and Glasgow Outcome Scale (GOS). RESULTS: A total of 85 patients were enrolled. The ICU monitoring times, VDT placement times, PDTO rate were shorter in the MNT group. Multivariable logistic regression identified that good medium-term outcome (GOS scores 4-5) was significantly associated with MNT applied (OR 1.017, 95% CI 1.005-1.029, p = 0.008), age under 65 years (OR 4.223, 95% CI, 1.322-17.109, p = 0.034) and pre-operation GCS scores more than 10 (OR 3.427, 95% CI 1.048-11.205, p = 0.040). CONCLUSION: MNT surgery for severe intraventricular haematoma evacuation is a safe and efficient new surgical option. This technique is minimally invasive and may be helpful to provide good outcomes for selected patients.

Treatment of hypermyoglobinemia after CRS + HIPEC for patients with peritoneal carcinomatosis: A retrospective comparative study.

This retrospective comparative study aims to explore the time courses of serum myoglobin (Mb) changes, and summarize our experience in treating patients with hypermyoglobinemia after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).This study covered 60 patients with peritoneal carcinomatosis treated with CRS + HIPEC as the study group, and another 25 cancer patients treated with conventional extensive surgery without HIPEC as the control group from February to October 2016. In the study group, patients with postoperative hypermyoglobinemia were on a comprehensive treatment regimen consisting intravenous injection of sodium bicarbonate solution according to the Mb level. In the control group, patients were recorded and treated with the same regimen except for special sodium bicarbonate solution. The preoperative and postoperative serum Mb, blood urine nitrogen (BUN), and creatinine (Cr) levels were evaluated.There were no significantly difference between the 2 groups in serum Mb, BUN, and Cr levels before surgery. Postoperative serum Mb levels were elevated in both groups and significantly higher on postoperative 0 to 2 days (P < .05) in the study group than the control group. The peak value of serum Mb levels (426.65 ±â€Š108.386 µg/L) occurred on the surgery day. The serum Mb change rate was much bigger in the study group than the control group. Serum BUN levels in both groups revealed a slow increase during the early postoperative period and were significantly lower in the study group than the control group on days 1 and 2. The serum Cr levels were similar and stable between the 2 groups after surgery. The serum Cr change rates changed synchronously with same tendency in both groups, and on postoperative day 1 the increase rate was bigger in the control group than the study group.Hypermyoglobinemia is a common and prominent lab abnormality after CRS + HIPEC, and serum Mb levels could be an early and sensitive indicator for dramatic disturbances in the internal milieu after CRS + HIPEC. Adequate treatment with sodium bicarbonate could accelerate the reduction in serum Mb levels and reduce the risk for major organ damages.

Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases.

PURPOSE: There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM. MATERIALS AND METHODS: The published clinical trials on CRS + HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised. RESULTS: The natural course of GC PM is <5 months. CRS + HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS + HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS + HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS + HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS + HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS + HIPEC. CONCLUSIONS: The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel improves survival for patients with peritoneal carcinomatosis from abdominal and pelvic malignancies.

BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for the treatment of primary peritoneal serous carcinoma: Results of a Chinese retrospective study.

Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC. Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n = 12) or recurrent PPSC (group B, n = 10) treated with 25 CRS + HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles. Results A total of 25 CRS + HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3-39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8-42.2) for group A vs. 38.5 months (95% CI 9.6-67.4) for group B (P = 0.832, log rank test); 51.5 months (95% CI 34.9-68.1) for peritoneal cancer index (PCI) ≤ 15 vs. 20.3 months (95% CI 12.6-28.0) for PCI > 15 (P = 0.000, log rank test); and 38.5 months (95% CI 22.5-54.5) for completeness of cytoreduction (CC) of 0-1 vs. 23.5 months (95% CI 15.3-31.7) for CC of 2-3 (P = 0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7-63.4, P = 0.001). Conclusions CRS + HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.

Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer.

Peritoneal carcinomatosis (PC) is one of the most common causes of death in gastric cancer patients. Intraperitoneal free cancer cells (IFCCs) play a very important role in forming PC, but the administration of intraperitoneal chemotherapy (IPC) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) could be an effective treatment for IFCCs. This review focuses on the origin of IFCCs, the mechanism of PC formatting, the rationale of IPC/HIPEC, and the current clinical trials on IPC/HIPEC to treat advanced gastric cancer patients.