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.

Routine laboratory parameters in patients with necrotizing pancreatitis by the time of operative pancreatic debridement: Food for thought.

BACKGROUND: Timing of invasive intervention such as operative pancreatic debridement (OPD) in patients with acute necrotizing pancreatitis (ANP) is linked to the degree of encapsulation in necrotic collections and controlled inflammation. Additional markers of these processes might assist decision-making on the timing of surgical intervention. In our opinion, it is logical to search for such markers among routine laboratory parameters traditionally used in ANP patients, considering simplicity and cost-efficacy of routine laboratory methodologies. AIM: To evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery. METHODS: A retrospective analysis of routine laboratory parameters in 53 ANP patients undergoing OPD between 2017 and 2020 was performed. Dynamic changes of routine hematological and biochemical indices were examined in the preoperative period. Patients were divided into survivors and non-survivors. Survivors were divided into subgroups with short and long post-surgery length of stay (LOS) in hospital. Correlation analysis was used to evaluate association of laboratory variables with LOS. Logistic regression was used to assess risk factors for patient mortality. RESULTS: Seven patients (15%) with severe acute pancreatitis (SAP) and 46 patients (85%) with moderately SAP (MSAP) were included in the study. Median age of participants was 43.2 years; 33 (62.3%) were male. Pancreatitis etiology included biliary (15%), alcohol (80%), and idiopathic/other (5%). Median time from diagnosis to OPD was ≥ 4 wk. Median postoperative LOS was at the average of 53 d. Mortality was 19%. Progressive increase of platelet count in preoperative period was associated with shortened LOS. Increased aspartate aminotransferase and direct bilirubin (DB) levels the day before the OPD along with weak progressive decrease of DB in preoperative period were reliable predictors for ANP patient mortality. CONCLUSION: Multifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients.

Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study.

BACKGROUND/OBJECTIVES: Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP. METHODS AND ANALYSIS: The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04647097.

THE ROLE OF LASER AND ULTRASONIC DOPPLER FLOWMETRY IN THE CORRECTION OF COSMETIC DEFECTS OF THE ANTERIOR ABDOMINAL WALL AND PREVENTION OF COMPLICATIONS.

OBJECTIVE: The aim: Of work is to determine changes in blood flow in the vessels of the anterior abdominal wall that occur after plastic surgeries in order to improve the results of operations and to develop new methods for the prevention of complications. PATIENTS AND METHODS: Materials and methods: The study was conducted in 132 patients. Patients were divided into 2 groups: main group 64 and control group 68 patients. Main group has patients who underwent abdominoplasty in combination with liposuction; control group has patients who underwent abdominoplasty without liposuction. In both groups we make different simultaneous operations. Laser Doppler Flowmetry and Ultrasonic Doppler Flowmetry were performed to determine the blood flow indices in the flaps. RESULTS: Results: Liposuction volumes averaged 3.57 ± 0.74 liters of lipoaspirate. In the main group there were totaly 4 complications, in the control group complications developed in 9 patients. Comparing daily indicators between the two groups, no statistically significant difference in the dynamics of MI changes was found during the entire study period (p = 0.767). Increase in caliber of vessels, on average, from 1.55 ± 0.8 mm in the preoperative period to 1.68 ± 0.75 mm on the 14th day of the postoperative period was statistically significant (p < 0.05). CONCLUSION: Conclusions: The combination of abdominoplasty with liposuction and simultaneous operations does not lead to greater development of complications and allows to achieve good aesthetic results.

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.

Immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells.

PURPOSE: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated. METHODS: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined. The expression of immunologically relevant genes was evaluated by RT-PCR. Tumor cell susceptibility to the macrophage contact tumoricidal activity and NK-mediated cytolysis was investigated in MTT test. TNF-α-mediated tumor cell apoptosis as well as macrophage phagocytosis, oxidative metabolism, and CD206 expression after the treatment with conditioned media from normoxic and hypoxic tumor cells were studied by flow cytometry. Flow cytometry was also used to characterize dendritic cell maturity. RESULTS: When growing in vitro, LLC/R9 were characterized by slightly increased immunosuppressive cytokine gene expression. Transition to in vivo growth was associated with the enhancement of transcription of these genes in tumor cells. LLC/R9 cells had lowered sensitivity to contact-dependent macrophage-mediated cytotoxicity and to the TNFα-mediated apoptosis in vitro. Conditioned media from hypoxic LLC/R9 cells stimulated reactive oxygen species generation and CD206 expression in non-sensitized macrophages. Acquisition of drug resistance by LLC/R9 cells was associated with their increased sensitivity to NK-cell-mediated cytolysis. Meanwhile, the treatment of LLCR/9-bearing animals with generated ex vivo and loaded with LLC/R9 cell-lysate dendritic cells (DCs) resulted in profoundly enhanced tumor metastasizing. CONCLUSION: Decreased sensitivity to macrophage cytolysis, polarizing effect on DCs maturation along with increased susceptibility to NK-cell cytotoxic action promote extensive local growth of chemoresistant LLC/R9 tumors in vivo, but hamper their metastasizing.

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.

Efficacy of ukrain in the treatment of pancreatic cancer.

BACKGROUND: This monocentric study evaluated the effect of ukrain in the treatment of pancreatic cancer. MATERIAL AND METHODS: Between January 1996 and December 1999 we treated 21 patients with 10 mg ukrain every second day x10. The control group received supportive treatment only. RESULTS: Ukrain treatment was well tolerated. Mean values on pain measure and Karnofsky index were significantly better in the ukrain group than in controls ( P<0.05). One-year survival was 76% in the ukrain group, compared to 9.5% in the control group. Median survival after treatment with ukrain was 574 days, compared to 197 days in the control group. CONCLUSIONS: Our data demonstrate that ukrain improves quality of life in patients suffering from advanced pancreatic cancer and significantly prolongs survival time in these patients.