Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Iatrogenic Lesions of the Extrahepatic Bile Ducts during Laparoscopic Cholecystectomy

Introduction: Laparoscopic cholecystectomy is the gold standard in the treatment of gallstones. However, this surgical approach is also associated with potential complications. The most frequent of them, related to a very serious prognosis, are lesions of the extrahepatic bile ducts. Their understanding is a prerequisite for preventing them. Aim: The aim of this paper is to present in a concentrated form the iatrogenic lesions of the biliary tract as a major group of complications during laparoscopic cholecystectomy and the methods for their treatment. Materials and Methods: Information from the specialized surgical literature was used and, for comparison and illustration, we presented data about 30 patients with complications after laparoscopic cholecystectomy, treated in the Department of General and Hepato-Pancreatic Surgery at the University Hospital `Aleksandrovska` - Sofia for the period 2000- 2015. 11 (36.7%) of them are men and 19 (63.3%) - women, aged 38 to 65 years, with an average age of 50. Results: The clinical material from the Department of General and Hepato-Pancreatic Surgery is an illustration of some of the possible iatrogenic lesions of the extrahepatic bile ducts during laparoscopic cholecystectomy reported in the world literature. Their managing fit the generally accepted rules and priority was given to the open surgical methods. Conclusions: Minimally invasive methods, in particular laparoscopic cholecystectomy, are rarely associated with complications. The injuries of extrahepatic bile ducts are of great significance and often thorough knowledge and multidisciplinary approach in their treatment are required to achieve the best results

Prevention and Management of Leakage After Rectal Resection with Extraperitonization of Drainage and Anastomosis

Background: The aim of surgical treatment in cases of carcinoma of the distal rectum is to save the anal sphincter, decrease the number of postoperative complications and limit the risk of reoperation. Therefore, mechanical /stapler/ anastomosis is currently widely used. In our study we discussed the complications and the preconditions leading to them, when manual and mechanical anastomosis are performed. We clarified the role of extraperitonization of anastomosis and drainage. Aim: To analyze the early postoperative results - the leakage rate when performing manual and mechanical anastomosis following resection of the lower rectum. We aimed to estimate the significance of extraperitonization of the anastomosis and the drainage in the postoperative period. Materials and Methods: In the period January 1, 1995 - December 31, 2015, in the Clinic of General and Liver-Pancreatic Surgery, 389 patients with rectal carcinoma, who suffered frontal rectal resection, were operated on.Results: Out of the 389 patients, 216 /55.52%/ were male and 173 /44.48%/ - females. Mechanical suture anastomosis was performed on 183 /47.04%/, and a handmade one - on 206 /52.96%/. Anastomosis leakage was registered in 58 cases /14.91%/. From those, with mechanical suturing were 34 /18.57%/, and with handmade anastomosis - 14 /6.79%/. There were two cases of relaparotomy and no deceased patients with this complication for the researched period.Conclusions: Mechanical staplers give the opportunity to keep anastomosis at the possible lower limit, almost impossible for manual suturing. But even with mechanical suturing, we face the risk of anastomosis leakage. This is why we think that the extraperitonization of anastomosis is a reliable prevention of reoperation and fecal peritonitis

Short-Term Results after Surgical Treatment of Pancreatic Cancer - Prognostic Factors and Prerequisites for Their Improvement

Introduction: Over the past few decades there have been a significant improvement in the results of radical surgery for pancreatic cancer as the early postoperative mortality is minimized in the major centers. However, the rate of postoperative morbidity remains relatively high. The most common surgical complications are: insufficiency of pancreatic or biliary anastomosis, the occurrence of bleeding or delayed gastric emptying. Aim: The aim of this paper is to analyze the short-term results after left and right pancreatic resections for pancreatic cancer and to determine the factors influencing their appearance, the prerequisites for reducing the complications and possibilities for preventing them. Materials and Methods: A retrospective study was performed. Between 1999 and 2015, 365 patients underwent different pancreatic resections for pancreatic cancer in the Department of General and Hepato-pancreatic Surgery of the University Hospital `Alexandrovska`. Clinicopathological material was analyzed by different statistical methods using SPSS-19. Results: 244 duodenohemipancreatectomies, 40 left subtotal pancreatectomies and 81 left hemipancreatectomies were performed. Observed mortality rate was 6.85%. Applying own modification of the prosthesis of the anastomoses with drainage type `perdue` leads to decreased rates of pancreatic anastomotic leaks - 3.28%. With regard to the early postoperative results, prognostic factors are blood loss, the values of T-Bil, D-Bil and ALP. Conclusion: Optimizing surgical technique according to the existing changes of the pancreas in the specific case is the basis of reducing of the postoperative morbidity rate. On the other hand, the implementation of adequate intensive care leads to reduction in early postoperative mortality and improvement of survival

Gastrointestinal Stromal Tumors of Pancreas and Duodenum - Challenges in Their Diagnosis and Surgical Treatment

Introduction: Although gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, they constitute less than 1% of all cancers of the digestive tube. Only 4-5% of these are located in the duodenum and GISTs in the pancreas, omentum and retroperitoneum are extremely rare. Diagnosis of pancreatic or duodenal GIST is often difficult because formation resembles pancreatic cancer clinically or on the imaging tests.Aim: The aim of this paper is to make a detailed review of the literature regarding the surgical treatment of duodenal and pancreatic GISTs and to present the observed cases in our practice comparing them with the patients with other locations of the process. Materials and Methods: A retrospective study covering the period 2005 - 2015 was carried out in the University Hospital `Alexandrovska`. It included 50 patients who underwent surgery for GIST. Two of patients were diagnosed with duodenal GIST, and in one case - GIST arising from the left pancreas was found. In cases with a pancreatic tumor location, a distal pancreatectomy with splenectomy was performed. A partial resection of the duodenum and a pancreatoduodenectomy were carried out respectively, in the cases of duodenal GIST. Literature review was made on the basis of recent publications referenced in Medline, PubMed and Google scholar. Results and Conclusions: GISTs, and in particular those with pancreatic and duodenal localization, may have varying malignant potential. Surgical removal of the tumor in clear resection margins is the only method providing a cure. Sometimes, this can be achieved through a relatively limited resection in tight. In most cases, however, a pancreatoduodenectomy needs to be done given the mistaken interpretation of the tumor as pancreatic cancer and due to the anatomical connection between the pancreas, the duodenum, and the bile ducts

Doppler-guided transanal hemorrhoidal dearterilization versus conventional hemorrhoidectomy for treatment of hemorrhoids – early and long-term postoperative results

Abstract Background A variety of effective methods for treatment of hemorrhoids has been proposed. In recent years, there has been an increasing number of studies comparing transanal hemorrhoidal dearterilization (THD) and conventional hemorrhoidectomy (CH), but the focus of most studies has been about the early postoperative results. The data about long-term outcomes is still limited. We aimed to compare Doppler-guided THD and CH with regard to early and long-term postoperative results. Methods The conducted prospective research included 287 patients who underwent CH (167 cases) or Doppler-guided THD with mycopexy (120 patients) between November 2010 and December 2015. Information on hemorrhoidal stage, demographic data, presenting symptoms, complications, duration of hospital stay, postoperative pain, patients’ satisfaction and follow-up were obtained. Statistical tests were performed by SPSS 19.0. Results There was no significant difference between the studied groups according to gender, mean age, preoperative prolapse, pain and pruritus, hemorrhoidal stage and postoperative complications. Preoperative bleeding was more frequent in THD group (p = 0,002). The mean visual analog scale (VAS) pain scores in CH and THD groups on days 1, 2 and 7 were 7.01 vs 5.03, 5.07 vs 2.98, 2.39 vs 0,57 (p = 0,000). Practically, there was no difference in VAS on day 30 and patients’ satisfaction at the 18th month. Mean hospital stay was 5,13 (CH) and 3,38 days (THD), p = 0,000. The postoperative follow-up was between 18 and 78 months (mean 46 ± 16 months). During this stage, 5 patients (2,99%) in CH group required surgery for recurrence. In THD group, 3 patients (2,5%), all with 4th-degree hemorrhoids underwent additional procedures (p 0,802). Conclusions Doppler-guided THD seems to be an efficient and safe option for treatment of hemorrhoids, related to lower postoperative pain and excellent, similar long-term outcomes compared to CH. For advanced grades of hemorrhoids, Doppler-guided THD could be a valuable alternative, but there is a need for patients’ selection. Trial registration (retrospectively registered) researchregistry3090

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society