Cytoreductive surgery and HIPEC for malignant ascites from colorectal cancer - a randomized study.

INTRODUCTION: The efficacy of different timings of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites caused by peritoneal carcinomatosis of colorectal cancer (CRC) is not well defined. The study aims to investigate the clinical efficacy and safety of different timings of CRS with HIPEC for malignant ascites caused by peritoneal carcinomatosis from CRC. MATERIALS AND METHODS: This was a preliminary randomized controlled study performed at the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University (China) from December 2008 to December 2016. The patients were randomized to: CRS, followed by HIPEC (CRS+HIPEC; n = 14), and ultrasound-guided HIPEC, followed by CRS 1 to 2 weeks later (HIPEC+ delayed cytoreductive surgery (dCRS) group, n = 14). The endpoints were complete remission rate of ascites, successful complete CRS rate, and overall survival. RESULTS: Malignant ascites in all patients showed complete remission; the total effective rate was 100%. Complete CRS was not feasible in any patient. The median follow-up of the 2 groups was 41.9 and 42.3 months in the CRS+HIPEC and HIPEC+dCRS groups, respectively. Overall survival was 14.5 (95%CI: 7-19 months) and 14.3 months (95%CI: 4-21 months) (P > .05). The adverse effects of HIPEC were manageable. CONCLUSIONS: CRS+HIPEC and HIPEC+dCRS have the same efficacy in controlling malignant ascites caused by CRC and peritoneal carcinomatosis. The timing of CRS and HIPEC does not prolong the survival of patients with peritoneal carcinomatosis from CRC, even when a complete CRS is not feasible.

Combined effects of guanidinoacetic acid, coenzyme Q10 and taurine on growth performance, gene expression and ascites mortality in broiler chickens.

High levels of guanidinoacetate acid (GAA) deteriorate growth response in broiler chickens. We propose using coenzyme Q10 , an antioxidant, and taurine (TAU), a methyl donor, to cope with the situation when high level of GAA included in diet. GAA was supplemented at 0 (control), 0.75, 1.5 and 2.25 g/kg in isoenergetic and isonitrogenous diets and fed to broilers (Cobb 500) from 1 to 40 days post-hatch. Three additional diets were prepared by adding CoQ10 (40 mg/kg), TAU (40 mg/kg) or their combination (both CoQ10 and TAU at 40 mg/kg) to the 2.25 g/kg GAA group. The experimental design used was a completely randomized design. While weight gain (p = 0.038) and feed conversion ratio (p = 0.024) improved when GAA added at 1.5 g/kg, higher supplementation (2.25 g/kg) deteriorated these responses. These responses, however, were significantly restored by using CoQ10 , TAU or their combination. Abdominal fat deposition was significantly decreased when TAU added to broiler diets by virtue of upregulating peroxisome proliferator-activated receptor alpha. Supplementing broiler diets with CoQ10 and TAU or their combination significantly decrease ascites mortality. In conclusion, CoQ10 and TAU have shown beneficial effects when high level of GAA included in broiler diets.

Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer.

BACKGROUND: To compare the efficacy of three chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS: From January 2010 to December 2013, 38 GC patients were randomly divided into three groups and treated by laparoscopic HIPPC with one of the three following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin [trans-(±)-diaminocyclohexane oxalatoplatinum (l-OHP)], Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the three groups. RESULTS: The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months, and the median survival was 7.5 months for all patients. Patients in the Ra/l-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/l-OHP group and Ra/MMC group was significantly longer than in the Ra/DDP group (P < .05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky Performance Scale, and incidence rate of port-site metastases among the three groups. CONCLUSIONS: Laparoscopy-assisted HIPPC provides modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutic combination of Ra/l-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.

An Approach to Diagnosis and Endovascular Treatment of Refractory Ascites in Liver Transplant: A Pictorial Essay and Clinical Practice Algorithm.

OBJECTIVES: Recipients of liver transplant are surviving longer as both the surgical procedure and postsurgical care have improved. Despite improvements, serious complications from the procedure remain that significantly affect patient outcome and may result in retransplant. Refractory ascites is one complication, occurring in about 5.6% of transplant recipients. Management of refractory ascites after liver transplant presents a challenge to the multidisciplinary team caring for these patients. MATERIALS AND METHODS: We discuss approaches to the diagnosis and treatment of refractory ascites after liver transplant, based on a literature review, with a primary focus on vascular causes. These approaches are illustrated by case examples highlighting our experiences at an academic tertiary medical center. We propose a clinical practice algorithm for optimal endovascular treatment of refractory ascites after liver transplant. RESULTS: The cornerstone of refractory ascites care is diagnosis and treatment of the cause. Vascular causes are not infrequently encountered and, if not treated early, are associated with graft loss and high morbidity and mortality and are major indications for retransplant. For patients with recurrent disease or graft rejection needing large volume paracentesis, the use of a transjugular intrahepatic portosystemic shunt may serve as a bridge to more definitive treatment (retransplant), although it may not be as effective for managing ascites as splenic artery embolization, arguably underused, which is emerging as a potential alternative treatment option. CONCLUSIONS: A multidisciplinary strategy for the diagnosis and care of patients with refractory ascites after liver transplant is crucial, with endovascular treatment playing an important role. The aim is for this document to serve as a concise and informative reference to be used by those who may care for patients with this rare yet serious diagnosis.

Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites.

BACKGROUND: In peritoneal surface disease, accumulation of malignant ascites represents a difficult problem to treat, with adverse impact on quality of life. The role of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites is not well defined. METHODS: A retrospective analysis of a prospectively maintained database of 1,000 procedures was performed. Type of malignancy, resolution of ascites, duration and agent of chemoperfusion, performance status, resection status, morbidity, mortality, and survival were reviewed. RESULTS: Ascites was found in 299 patients (310 procedures) either before or during exploration. A total of 142 (46 %) procedures were performed for appendiceal primary disease, 53 (17 %) colorectal, 20 (6 %) gastric, 45 (15 %) mesothelioma, and 26 (8 %) ovarian. A total of 288 (93 %) patients had resolution of ascites by 3 months' follow-up. In patients with ascites, complete cytoreduction was obtained in 15 versus 59 % when ascites was not present (p < 0.001). In the group of patients who had their ascites controlled, 243 of 288 (84 %) had resection with residual macroscopic disease (R2 status). Twenty-two patients (7 %) had persistent ascites at 3 months' follow-up, 19 (86 %) of whom had an R2 resection. Univariate analysis revealed that type of primary disease, resection status, duration or agent of chemoperfusion, and performance status did not predict failure. CONCLUSIONS: CRS-HIPEC is effective in controlling ascites in 93 % of patients with malignant ascites, even when a complete cytoreduction is not feasible. Ascites is predictive of incomplete cytoreduction and worse overall survival. Although complete cytoreduction remains the goal of this procedure, HIPEC can provide palliative value in selected patients with malignant ascites.

Supplemental arginine administered in ovo or in the feed reduces the susceptibility of broilers to pulmonary hypertension syndrome.

1. Two experiments were conducted to determine if in ovo and in-feed arginine (ARG) supplementation is effective in the prevention of pulmonary hypertension syndrome (PHS) in broiler chickens reared at high altitude. 2. In Experiment I, a total of 300 fertile eggs were divided into two equal groups. On d 5 of incubation, one group was injected with 0.5 ml of ARG (20 mg/ml) and the other remained untreated and served as controls. After hatching, male chicks (64 chickens per treatment) were selected and given a commercial maize-soyabean meal diet up to 48 d of age. 3. In Experiment II, a total of 128 male broiler chickens (Ross 308) were randomly assigned to two treatments, a control group that were fed on a basal diet that met ARG requirements and the second was fed on the basal diet supplemented with 1.5 g ARG per kg of diet. 4. Cumulative mortality from ascites was recorded in both experiments. Results from Experiment I indicated that in ovo injection of ARG significantly decreased ascites mortality of broilers (18.8 vs. 43.8%). Results from Experiment II showed a similar effect so that ascites mortality in the group that were given Arg supplement was significantly lower than the control (28.1 vs. 43.8%).

Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a, iNOS, COX-2, IL-1ß, IL-6, IFN-γ, IL-2, GM-CSF) and pro-angiogenic growth factor- VEGF.

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/ kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in animals with DLA induced solid tumours. Increase in CD4+ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

Genistein attenuates low temperature induced pulmonary hypertension in broiler chicks by modulating endothelial function.

Pulmonary arterial hypertension is characterized by high pulmonary blood pressure, vascular remodeling and right ventricular hypertrophy. In the present study, we investigated whether genistein would prevent the development of low temperature-induced pulmonary hypertension in broilers. Hemodynamic parameters, vascular remodeling, the expression of endothelial nitric oxide and endothelin-1 content in lung tissue were evaluated. The results demonstrated that genistein significantly reduced pulmonary arterial hypertension and suppressed pulmonary arterial vascular remodeling without affecting broilers' performance. The beneficial effects appeared to be mediated by restoring endothelial function especially endothelial nitric oxide and endothelin-1, two critical vasoactive molecules that associated with the development of hypertension. Genistein supplementation might be a potential therapeutic strategy for the treatment of pulmonary hypertension.

Reduction of ascites mortality in broilers by coenzyme Q10.

Effects of coenzyme Q10 (CoQ10) supplementation on growth performance and ascites were studied in broilers. One hundred eighty 1-d-old Arbor Acre male broiler chicks were randomly allocated into 3 groups with 6 replicates each. From d 8, the diets were supplemented with CoQ10 at levels of 0, 20, and 40 mg/kg, respectively. From d 15 to 21, all the chicks were exposed to low ambient temperature (15 to 18 degrees C) to induce ascites. Average feed intake, BW gain, and feed conversion ratio of the broilers during 0 to 3 wk, 3 to 6 wk, and 0 to 6 wk were measured. The results showed that there were no influences observed on broilers' growth performance, but the mortality due to ascites was reduced by CoQ10 supplementation (P < or = 0.05). Erythrocyte osmotic fragility (EOF) was significantly decreased by 40 mg/kg CoQ10 compared with the control, but no significant changes were observed on blood packed cell volume (PCV) among the treatments. Pulmonary arterial diastolic pressure was significantly decreased on d 36, but no significant changes were observed on right ventricular pressure (RVP), pulmonary arterial systolic pressure, and the maximum change ratio of right intraventricular pressure (+/- dp/ dtmax). Ascites heart index (AHI) was significantly decreased by 40 mg/kg CoQ10 supplementation (P < or = 0.05). The results of this study suggested that CoQ10 has a beneficial effect in reducing ascites mortality in broilers, and 40 mg/kg CoQ10 seems to be more effective than 20 mg/ kg CoQ10.

Effects of dietary L-carnitine and coenzyme Q10 supplementation on performance and ascites mortality of broilers.

The study was conducted to determine the effects of dietary L-carnitine and coenzyme Q10 (CoQ10) supplementation on growth performance and ascites mortality of broilers. A 3 x 3 factorial arrangement was employed with three levels (0, 75 and 150 mg/kg) of L-carnitine and three levels of CoQ10 (0, 20 and 40 mg/kg) supplementation during the experiment. Five hundred and forty one-day-old Arbor Acre male broiler chicks were randomly allocated into nine groups with six replicates each. All birds were fed with the basal diets from day 1 to 7 and changed to the experimental diets from day 8. During day 15 to 21 all the birds were exposed to low ambient temperature (15-18 degrees C) to induce ascites. The results showed that under this condition, growth performance of broilers were not significantly affected by CoQ10 or L-carnitine + CoQ10 supplementation during week 0-3 and 0-6, but body weight gain (BWG) of broilers was significantly reduced by 150 mg/ kg L-carnitine during week 0-6. Packed cell volume (PCV) of broilers was significantly decreased by L-carnitine and L-carnitine + CoQ10 supplementation (P < 0.05). Erythrocyte osmotic fragility (EOF), ascites heart index (AHI) and ascites mortality of broilers were significantly decreased by L-carnitine, CoQ10 and L-carnitine + CoQ10 supplementation. Though no significant changes were observed in total antioxidative capability (T-AOC), total superoxide dismutase (T-SOD) was increased by L-carnitine, CoQ10 and L-carnitine + CoQ10 supplementation (P < 0.05). Malonaldehyde (MDA) content was significantly decreased by CoQ10 and L-carnitine + CoQ10 supplementation. The results indicate that dietary L-carnitine and CoQ10 supplementation reduce ascites mortality of broilers; the reason may be partially associated with their antioxidative effects.

Effect of dietary dl-alpha-tocopherol on tissue alpha- and gamma-tocopherol and pulmonary hypertension syndrome (ascites) in broilers.

The objectives of this experiment were to determine the effects of high dietary levels of vitamin E on growth performance and pulmonary hypertension syndrome (PHS) mortality. Male broiler chicks (Cobb 500) were randomly assigned to one of four dietary treatments consisting of standard starter and grower diets supplemented with 0, 17, 46, and 87 mg dl-alpha-tocopherol acetate/kg. To encourage the development of PHS, air temperature in the house was 32 and 28 C for Weeks 1 and 2, dropped to 18 C during Week 3, and kept between 10 and 15 C during Weeks 4 through 7. Also, chicks were placed in floor pens on litter used for five previous flocks and ventilation reduced to increase dust and ammonia in the house. Ammonia levels increased from an initial 18 to 36 ppm on Day 42 with the increase in ammonia corresponding to an obvious increase in dust in the air. Lung and liver tissue obtained at 2, 5, and 7 wk of age were analyzed for tissue alpha- and gamma-tocopherol by liquid chromatography. Dietary vitamin E had no effect on body weight, feed intake, or feed efficiency. Cumulative PHS mortality through 7 wk of age was 21% and was also unaffected by dietary treatment. Liver and lung alpha-tocopherol concentrations exhibited a dose-response increase to dietary tocopherol and there was a high correlation between lung and liver tissue alpha-tocopherol (r = 0.72, P < 0.05). Whereas gamma-tocopherol concentrations in lung and liver were unaffected by dietary treatment, liver and lung exhibited age-dependent increases in both alpha- and gamma-tocopherol. Despite dose-dependent increases in tissue alpha-tocopherol, supplementation of diets with up to 87 mg dl-alpha-tocopherol acetate had no effect on growth performance or PHS mortality in broilers under the conditions used in this study.

Effect of a urease inhibitor and ceiling fans on ascites in broilers. 1. Environmental variability and incidence of ascites.

A low ventilation model to induce ascites was introduced and characterized. In addition, the effect of supplemental air mixing via ceiling fans (CF) and the feeding of a urease inhibitor (0, 125, and 250 ppm) on incidence of ascites were investigated. Twelve environmental chambers were utilized in the trial; six were fitted with CF. Each dietary treatment was replicated twice per CF treatment. One hundred and twenty day-old male commercial broilers were reared per chamber. Atmospheric O2, CO2, and NH3, temperature, and humidity, as well as weekly litter moisture and pH, were monitored. Chamber CO2 levels increased immediately then stabilized. Chamber NH3 levels increased between 2 to 4 wk of age and rapidly declined when ventilation rates were increased to 1 cfm per bird. The CF and dietary treatments had little effect on air or litter variables except for NH3. Supplementing the diet with urease inhibitor resulted in a greater than 50% reduction in cumulative mortality due to ascites and a slight reduction in weekly BW gains. The CF treatment had no effect on production variables such as weekly feed intake, gain, and feed to gain ratio, or survivability due to ascites.

Changes in hematological, blood gas, and serum biochemical variables in broilers during exposure to simulated high altitude.

One-day-old broilers were reared until 35 days of age at both natural low (100 m) and simulated high altitude (2133 m) to assess the incidence and development of ascites syndrome. Clinical measurements were conducted at 7, 14, 21, 28, and 35 days of age. Birds reared at 2133 meters exhibited significantly (P less than or equal to 0.05) reduced body weights at 7 through 28 days of age. Total serum calcium and biochemical enzyme activities were found to be altered at 35 days of age. In addition, the high-altitude group had significantly (P less than or equal to 0.05) higher erythrocyte counts, hematocrits, and hemoglobin at 14, 21, 28, and 35 days of age and higher serum inorganic phosphorus at each weekly sample time than birds at the low altitude. Total mortality was 20.3% at 2133 meters and 4.6% at 100 meters. The incidence of ascites syndrome in the high-altitude group ranged from 16.6% to 61.1% during the 5-week experimental period.

Complications of diuresis in the alcoholic patient with ascites: a controlled trial.

Forty-three patients with decompensated alcoholic liver disease and ascites of recent onset were randomized to salt and water restriction alone (control group) or to salt and water restriction plus diuretics (diuresis group). The two treatment groups were comparable in clinical findings and laboratory results. Seven patients in the control group and 5 patients in the diuresis group died during the acute illness. Weight loss was more marked and the disappearance of ascites more common in those given diuretics. A modest decrease in serum sodium and increase in serum potassium, and readily reversible elevations of blood urea nitrogen were noted in the diuresis group. Eight patients in each treatment group developed either the hepatorenal syndrome, marked electrolyte abnormalities, or encephalopathy. Diuresis can be accomplished in these critically ill patients without serious complications that can be attributed to the diuretic treatment.