Effectiveness of a new approach to minimally invasive surgery in palliative treatment of patients with distal malignant biliary obstruction.

BACKGROUND: Palliative endoscopic biliary drainage is the primary treatment option for the management of patients with jaundice which results from distal malignant biliary obstruction (DMBO). In this group of patients, decompression of the bile duct (BD) allows for pain reduction, symptom relief, chemotherapy administration, improved quality of life, and increased survival rate. To reduce the unfavorable effects of BD decompression, minimally invasive surgical techniques require continuous improvement. AIM: To develop a technique for internal-external biliary-jejunal drainage (IEBJD) and assess its effectiveness in comparison to other minimally invasive procedures in the palliative treatment of patients with DMBO. METHODS: A retrospective analysis of prospectively collected data was performed, which included 134 patients with DMBO who underwent palliative BD decompression. Biliary-jejunal drainage was developed to divert bile from the BD directly into the initial loops of the small intestine to prevent duodeno-biliary reflux. IEBJD was carried out using percutaneous transhepatic access. Percutaneous transhepatic biliary drainage (PTBD), endoscopic retrograde biliary stenting (ERBS), and internal-external transpapillary biliary drainage (IETBD) were used for the treatment of study patients. Endpoints of the study were the clinical success of the procedure, the frequency and nature of complications, and the cumulative survival rate. RESULTS: There were no significant differences in the frequency of minor complications between the study groups. Significant complications occurred in 5 (17.2%) patients in the IEBJD group, in 16 (64.0%) in the ERBS group, in 9 (47.4%) in the IETBD group, and in 12 (17.4%) in the PTBD group. Cholangitis was the most common severe complication. In the IEBJD group, the course of cholangitis was characterized by a delayed onset and shorter duration as compared to other study groups. The cumulative survival rate of patients who underwent IEBJD was 2.6 times higher in comparison to those of the PTBD and IETBD groups and 20% higher in comparison to that of the ERBS group. CONCLUSION: IEBJD has advantages over other minimally invasive BD decompression techniques and can be recommended for the palliative treatment of patients with DMBO.

Infectious Complications of Acute Pancreatitis Is Associated with Peripheral Blood Phagocyte Functional Exhaustion.

BACKGROUND: Infected pancreatic necrosis is one of the most severe complications of acute pancreatitis (AP). The development of secondary infection doubles the risk of death during the late stage of necrotizing pancreatitis. Phagocytes play a major role in AP pathogenesis, as well as in local and systemic complications of the disease. AIMS: We aimed to investigate the relationship between quantitative and functional indices of circulating phagocyte at the time of admission and onset of infectious complications in patients with AP afterward. METHODS: A post hoc analysis of 97 patients with AP was conducted. The metabolic state of peripheral blood neutrophils and monocytes was analyzed based on their phagocytic activity and generation of reactive oxygen species (ROS), which were determined by flow cytometry on admission. The clinical end point was marked by onset of infectious complications of AP. RESULTS: On admission, baseline values and reactivity reserve of monocyte and neutrophil phagocytic activity in AP patients, who developed septic complications, were substantially decreased, whereas monocyte ROS generation was dramatically increased as compared to the group without infectious processes. ROC curve was obtained both for neutrophil and monocyte phagocytosis reactivity reserve expressed as modulation coefficient values and categorized as the risk factor of infectious complications, showing an area under curve of 0.95 (P < 0.0001) and 0.84 (P < 0.0001), respectively. CONCLUSIONS: Early (at the time of admission) detection of quantitative and functional indices of circulating phagocytes can be useful for the prediction of septic complications in SAP patients.

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes.

BACKGROUND: C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro. METHODS: Analysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation. RESULTS: Cytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties. CONCLUSIONS: The antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

Sex-based differences in phagocyte metabolic profile in rats with monosodium glutamate-induced obesity.

The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.

Complex of C60 Fullerene with Doxorubicin as a Promising Agent in Antitumor Therapy.

The main aim of this work was to evaluate the effect of doxorubicin in complex with C60 fullerene (C60 + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C60 + Dox complex action. We found that volume of tumor from mice treated with the C60 + Dox complex was 1.4 times less than that in control untreated animals. The number of metastatic foci in lungs of animals treated with C60 + Dox complex was two times less than that in control untreated animals. Western blot analysis of tumor lysates revealed a significant decrease in the level of heat-shock protein 70 in animals treated with C60 + Dox complex. Moreover, the treatment of tumor-bearing mice was accompanied by the increase of cytotoxic activity of immune cells. Thus, the potential mechanisms of antitumor effect of C60 + Dox complex include both its direct action on tumor cells by inducing cell death and increasing of stress sensitivity and an immunomodulating effect. The obtained results provide a scientific basis for further application of C60 + Dox nanocomplexes as treatment agents in cancer chemotherapy.

Physical activity interferes with the immunomodulatory effect of the antineoplastic drug NSC631570.

OBJECTIVE: The aim of the work was to evaluate the effect of moderate physical exercise on the response of circulating phagocytes to the antineoplastic drug NSC 631570. METHODS: Eight healthy adult men aged 23 ± 2 years were recruited to participate in the study; NSC 631570 was administered i.v. in a single therapeutic dose; blood samples were collected before and after the drug administration; the moderate physical exercise programme included 50 slow squats; total leukocyte, neutrophil and lymphocyte counts were determined using the haematological analyser; intracellular ROS generation and phagocytic activity of circulating monocytes and granulocytes were analysed by flow cytometry; PPAR-γ protein expression was evaluated by Western blot. RESULTS: introduction of NSC 631570 in an inpatient setting was associated with a decrease in phagocyte endocytic activity along with an increase in ROS generation. Drug injection in an outpatient setting was accompanied by a significant increase in monocyte and granulocyte phagocytosis along with a decrease in the daily mean of ROS generation as well as by a decrease in monocyte reactivity reserve after stimulation in vitro. PPAR-γ expression in circulating monocytes was significantly decreased after the drug administration in an inpatient setting and was slightly increased in active participants after the drug injection. CONCLUSION: NSC 631570 causes M1 (N1) shift of phagocytes after in vivo introduction. Moderate physical exercise exerts a negative effect on the immunomodulatory action of NSC 631570 by abrogating M1 (N1) shift of circulating phagocytes. One of the reasons for such an effect could be an increase in PPAR-γ expression by phagocytes.

Paraneoplastic syndrome in mice bearing high-angiogenic variant of Lewis lung carcinoma: relations with tumor derived VEGF.

BACKGROUND: It is well-known that tumor exerts nonmetastatic systemic effect on organism caused the development of paraneoplastic syndrome (PNS). Recent findings point to relationships between development of PNS and tumor-derived vascular endothelial growth factor (VEGF). AIM: Comparative study of PNS manifestations in mice with transplanted two variants of Lewis lung carcinoma with different angiogenic potential. METHODS: Plasma VEGF level was determined by immunoenzyme method, hematological indices were estimated with the use of hematological analyzer, the weight and cellularity of spleen and thymus were registered and histological analysis of tissue section of these organs was performed. RESULTS: Manifestations of anemia, extramedullary hemopoiesis and tumor-associated inflammatory disease was observed in animals with high angiogenic LLC/R9 variant and was not registered in low angiogenic LLC. The emergence of PNS symptoms correlated with elevated level of circulating VEGF at the early stages of LLC/R9 growth. CONCLUSION: Manifestation of the paraneoplastic hematological syndrome most likely is conditioned on the ability of cancer cell to secrete VEGF in a high rate.