Georgi Atanasov

Short-term TNF-alpha inhibition reduces short-term and long-term inflammatory changes post-ischemia/reperfusion in rat intestinal transplantation.

Background Tumor necrosis factor (TNF)-&agr; inhibition was shown to reduce ischemia/reperfusion injury (IRI) after intestinal transplantation (ITX). We studied the effects of different TNF&agr; inhibitors on acute IRI and long-term inflammatory responses in experimental ITX. Methods Orthotopic ITX was performed in an isogenic ischemia/reperfusion model in Lewis rats. The TNF&agr; inhibition groups received infliximab post-reperfusion; etanercept pre-reperfusion and at postoperative days (POD) 1, 3, 5, and 7; or pentoxifylline pre-reperfusion and at POD 1 to 5. Tissue samples were taken from proximal and distal graft sections and mesenteric lymph nodes at 20 min, 12 hr, 7 day, and 6 months post-reperfusion for histopathology, immunohistology, terminal deoxyribosyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and real-time RT-PCR. Lung sections were stained for the myeloperoxidase assay. Results TNF&agr; inhibitors decreased inflammatory changes after IRI in all treatment groups. Infliximab significantly improved 7-day survival and reduced the histological and immunohistochemical signs of IRI, the numbers of graft-infiltrating T cells and ED1+ monocytes and macrophages, and pulmonary neutrophil infiltration, and also enhanced the accumulation of cytoprotective markers. Graft injury was more prominent in the distal graft than in the proximal graft in all groups, regardless of TNF&agr; inhibition. Conclusion Infliximab significantly reduced both acute IRI and, as with other TNF&agr; inhibitors, long-term inflammatory responses after rat ITX. TNF&agr; inhibition may help diminish chronic inflammatory long-term effects and avoid chronic allograft enteropathy.

Alveolar echinococcosis-spreading disease challenging clinicians: a case report and literature review.

Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging.

Alternative treatment of symptomatic pancreatic fistula

BACKGROUND The management of symptomatic pancreatic fistula after pancreaticoduodenectomy is complex and associated with increased morbidity and mortality. We here report continuous irrigation and drainage of the pancreatic remnant to be a feasible and safe alternative to total pancreatectomy. MATERIALS AND METHODS Between 2005 and 2011, patients were analyzed, in which pancreaticojejunal anastomosis was disconnected because of grade C fistula, and catheters for continuous irrigation and drainage were placed close to the pancreatic remnant. Clinical data were monitored and quality of life was evaluated. RESULTS A total of 13 of 202 patients undergoing pancreaticoduodenectomy required reoperation due to symptomatic pancreatic fistula. Ninety-day mortality of these patients was 15.3%. Median length of stay on the intensive care unit and total length of stay was 18 d (range 3-45) and 46 d (range 33-96), respectively. Patients with early reoperation (<10 d) had significantly decreased length of stay on the intensive care unit and operation time (P < 0.05). Global health status after a median time of 22 mo (range 6-66) was nearly identical, when compared with that of a healthy control group. Mean follow-up was 44.4 mo (±27.2). Four patients (36.6 %) died during the follow-up period; two patients from tumor recurrence, one patient from pneumonia, and one patient for unknown reasons. CONCLUSIONS Treatment of pancreatic fistula by continuous irrigation and drainage of the preserved pancreatic remnant is a simple and feasible alternative to total pancreatectomy. This technique maintains a sufficient endocrine function and is associated with low mortality and reasonable quality of life.

Single incision laparoscopic liver resection (SILL) – a systematic review

Background: Today, minimally invasive liver resections for both benign and malignant tumors are routinely performed. Recently, some authors have described single incision laparoscopic liver resection (SILL) procedures. Since SILL is a relatively young branch of laparoscopy, we performed a systematic review of the current literature to collect data on feasibility, perioperative results and oncological outcome. Methods: A literature research was performed on Medline for all studies that met the eligibility criteria. Titles and abstracts were screened by two authors independently. A study was included for review if consensus was obtained by discussion between the authors on the basis of predefined inclusion criteria. A thorough quality assessment of all included studies was performed. Data were analyzed and tabulated according to predefined outcome measures. Synthesis of the results was achieved by narrative review. Results: A total of 15 eligible studies were identified among which there was one prospective cohort study and one randomized controlled trial comparing SILL to multi incision laparoscopic liver resection (MILL). The rest were retrospective case series with a maximum of 24 patients. All studies demonstrated convincing results with regards to feasibility, morbidity and mortality. The rate of wound complications and incisional hernia was low. The cosmetic results were good. Conclusions: This is the first systematic review on SILL including prospective trials. The results of the existing studies reporting on SILL are favorable. However, a large body of scientific evidence on the field of SILL is missing, further randomized controlled studies are urgently needed.

Diverticulitis in immunosuppressed patients: A fatal outcome requiring a new approach?

BACKGROUND Diagnosis and treatment of diverticulitis in immunosuppressed patients are more challenging than in immunocompetent patients, as maintenance immunosuppressive therapies may mask symptoms or impair the patients ability to counteract the local and systemic infective sequelae of diverticulitis. The purpose of this study was to compare the in-hospital mortality and morbidity due to diverticulitis in immunosuppressed and immunocompetent patients and identify risk factors for lethal outcomes. METHODS This retrospective study included consecutive in-patients who received treatment for colonic diverticulitis at our institution between April 2008 and April 2014. Patients were divided into immunocompetent and immunosuppressed groups. Primary end points were mortality and morbidity during treatment. Risk factors for death were evaluated. RESULTS Of the 227 patients included, 15 (6.6%) were on immunosuppressive therapy for solid organ transplantation, autoimmune disease, or cerebral metastasis. Thirteen of them experienced colonic perforation and showed higher morbidity (p = 0.039). Immunosuppressed patients showed longer stays in hospital (27.6 v. 14.5 d, p = 0.016) and in the intensive care unit (9.8 v. 1.1 d, p < 0.001), a higher rate of emergency operations (66% v. 29.2%, p = 0.004), and higher in-hospital mortality (20% v. 4.7%, p = 0.045). Age, perforated diverticulitis with diffuse peritonitis, emergency operation, C-reactive protein > 20 mg/dL, and immunosuppressive therapy were significant predictors of death. Age (hazard ratio [HR] 2.57, p = 0.008) and emergency operation (HR 3.03, p = 0.003) remained significant after multivariate analysis. CONCLUSION Morbidity and mortality due to sigmoid diverticulitis is significantly higher in immunosuppressed patients. Early diagnosis and treatment considering elective sigmoid resection for patients with former episodes of diverticulitis who are wait-listed for transplant is crucial to prevent death.

Impact of different immunosuppressive regimens on the health‐related quality of life following orthotopic liver transplantation

The influence of immunosuppression on the recipients’ quality of life (QoL) is of major importance after OLT and has not yet been evaluated.

Immunosuppressive protocol with delayed use of low-dose tacrolimus after aortic transplantation suppresses donor-specific anti-MHC class I and class II antibody production in rats.

BACKGROUND Arterial allografts are used as vascular conduits in the treatment of prosthetic graft infection. Immunosuppression decreases their rupture risk rate. However, immunosuppression can be unprofitable in florid infection. Previously, we confirmed inhibition of cell-mediated destruction of rat aortic grafts by delayed use of tacrolimus. In this work, we studied the influence of this protocol on the antibody-mediated rejection. MATERIAL AND METHODS Flow cytometry was used for the retrospective analysis of day 0, 14, and 30 sera obtained from Lewis rat recipients of isogeneic fresh infrarenal aortic grafts (group A) or Brown-Norway rat aortic grafts (group B,C,D) for the presence of donor-specific anti-MHC class I and II antibodies. Tacrolimus in daily dose of 0.2 mg/kg was administered from day 1 to day 30 (group C) or from day 7 to day 30 (group D). RESULTS Inhibition of fluorescence-labeled anti-BN MHC class I and MHC class II antibodies binding to BN-splenocytes was observed only by day 14 and day 30 sera of allogeneic non-immunosuppressed Lewis rats (group B). The day 30 sera significantly decreased anti-MHC I (42±3%) and anti-MHC II antibody binding (56±3%) compared to day 0 (76±9%, p=0.005 and 79±5%, p=0.003, respectively). Deposition of immunoglobulins G into the tunica media was observed only in non-immunosuppressed aortic allografts on day 30. CONCLUSIONS Fresh aortic allografts induce donor-specific anti-MHC class I and anti-MHC class II antibody production. Delayed administration of tacrolimus completely suppressed antibody production and antibody-mediated destruction of aortic allografts.

Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma.

Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang‐receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2‐expressing monocytes (TEMs) in cholangiocarcinoma.

The role of biologicals in intestinal transplantation.

Purpose of reviewThis article reviews the role of biologicals in intestinal transplantation. Recent findingsSeveral biologicals have been used in intestinal and multivisceral transplantation for various indications, such as induction therapy, prevention and treatment of antibody-mediated rejection, desensitization, anti-inflammatory treatment, as well as treatment of Epstein–Barr virus-associated posttransplant lymphoproliferative disease. Particularly, the administration of biologicals in induction therapy such as T-cell depleting antibodies and interleukin-2 receptor antagonists have significantly contributed to the great improvement of patient and allograft outcome. Novel biologicals, such as B-cell, plasma-cell, and complement-directed agents have been successfully applied to treat antibody and complement-driven alloimmune processes to stabilize long-term outcome. Several other inflammatory allotransplant conditions have been addressed with anti-TNF-&agr; antibodies, such as infliximab. SummaryBiologicals have contributed significantly to the recent success of intestinal transplantation. Novel developments in this field are supposed to aid in addressing various urgent needs in intestinal transplantation, such as preimmunization, antibody and complement-induced graft injury, as well as pathologies originating from innate immune responses.

Validity of the Iwate criteria for patients with hepatocellular carcinoma undergoing minimally invasive liver resection

Recently proposed by the International Consensus Conference on Laparoscopic Liver Resection, the Iwate criteria (IC) can be used by surgeons to predict the operative difficulty of laparoscopic liver resection (LLR) and were validated in patients with hepatocellular carcinoma (HCC), the most common indication for LLR.