META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Update on liver transplantation for cholangiocarcinoma : a review of the recent literature.

Cholangiocarcinoma (CC) represent 3% of all gastrointestinal tumours and can be classified anatomically in 3 types: intrahepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinomas. Resection is the treatment of choice but is only achieved in a few cases (<20%) because of invasion of the biliary tract and/or vascular structures. The outcome of advanced CC is poor with an overall survival (OS) of maximum 15 months with chemotherapy. In the 1990s, CC was regarded as a contraindication for liver transplantation (LT). LT has recently been proposed as potentially curative option for ICC and PCC. Careful patient selection has changed OS. This article provides an update on current status of LT for patients with unresectable CC.

EHS clinical guidelines on the management of the abdominal wall in the context of the open or burst abdomen.

PURPOSE: To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers of the abdominal wall, and regarding possible materials to be used. METHODS: The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument. RESULTS: For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE. RECOMMENDATIONS: When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.

EHS clinical guidelines on the management of the abdominal wall in the context of the open or burst abdomen

To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers of the abdominal wall, and regarding possible materials to be used. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument. For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE. When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.

Correction to: Clinical and genetic aspects of defects in the mitochondrial iron-sulfur cluster synthesis pathway.

The article "Clinical and genetic aspects of defects in the mitochondrial iron-sulfur cluster synthesis pathway", written by A. V. Vanlander, R. Van Coster was originally published.

Clinical and genetic aspects of defects in the mitochondrial iron-sulfur cluster synthesis pathway.

Iron-sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron-sulfur clusters are located in the mitochondria and in the cytosol. The mitochondrial iron-sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich's ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron-sulfur cluster biosynthesis.

Tigecycline-induced inhibition of mitochondrial DNA translation may cause lethal mitochondrial dysfunction in humans.

BACKGROUND: A 65-year-old patient developed an unexplained and ultimately lethal metabolic acidosis under prolonged treatment with tigecycline. Tigecycline is known to have a selective inhibitory effect on eukaryotic mitochondrial translation. The underlying molecular mechanisms of the metabolic acidosis in this patient were explored. METHODS: Oxidative phosphorylation system (OXPHOS) analysis, blue native polyacrylamide gel electrophoresis followed by in-gel activity staining in mitochondria, molecular analysis of mitochondrial DNA (mtDNA) for genomic rearrangements and sequencing of the rRNA genes was performed on the subject's skeletal muscle. RESULTS: OXPHOS analysis revealed a combined deficiency of the complexes I, III, IV and V, with a preserved function of complex II (encoded by nuclear DNA), thus demonstrating a defective mtDNA translation. There were no known underlying mitochondrial genetic defects. The patient had a (m.1391T>A) variant within the 12SrRNA gene in heteroplasmy (50-60%). CONCLUSIONS: This patient developed an ultimately lethal mitochondrial toxicity while receiving prolonged treatment with tigecycline, which was caused by a defective translation of the mtDNA. Tigecycline is known to suppress eukaryotic mitochondrial DNA translation, but until now this effect has been considered to be clinically insignificant. The observations in this patient suggest a clinically significant mitochondrial toxicity of tigecycline in this patient, and warrant further investigation.

Mitochondrial Neurogastrointestinal Encephalopathy: Clinical, Biochemical and Molecular Study in Three Egyptian Patients.

Background: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy sundrome from two different pedigrees. Subjects and Methods: The three patients were subjected to thorough neurologic examination. Brain Magtnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis. Results: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of themuscle biopsy revealed deficient cytochrome C oxidase and mitochrondrial respiratory chain enzyme assay revealed isolated complex 1 deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371 A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings. Conclusions: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagmosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.

Laparoscopic cholecystectomy in acute cholecystitis: support for an early interval surgery.

BACKGROUND AND STUDY AIMS: Although laparoscopic cholecystectomy is advocated for acute cholecystitis, debate still exists about its optimal timing. This retrospective study compares the outcome of laparoscopic cholecystectomy within versus later than 5 days of onset of symptoms in patients with acute cholecystitis. PATIENTS AND METHODS: One hundred thirty six patients with acute cholecystitis grade I or II were included in the study and divided in two groups. Group 1 received surgery within 5 days of symptoms and group 2 received conservative therapy and delayed surgery after 6 weeks. RESULTS: Group 1 and 2 consisted of 100 and 36 patients respec- tively. Because of failure of conservative therapy 5 patients of group 2 had surgery before 6 weeks. The remaining 31 patients underwent surgery after 6 weeks. Preoperative ERCP was indicated in 2 and 11 patients in groups 1 and 2 respectively (p < 0.001). The median total hospital stay was 3.0 days for group 1 and 11.0 days for group 2 (p < 0.001). In terms of operation time, conversion rates, intraoperative cholangiography, postoperative ERCP, morbidity or mortality both groups were comparable (p > 0.05). CONCLUSION: Laparoscopic cholecystectomy can be performed safely within 5 days after the onset of symptoms in patients with acute cholecystitis. Because of shortened total hospital stay and risk of failure of conservative therapy, early laparoscopic cholecystectomy should be favored.

Pure laparoscopic full-left living donor hepatectomy for calculated small-for-size LDLT in adults: proof of concept.

Adult-to-adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end-stage liver disease. Right-lobe grafts have usually been preferred in view of the higher graft volume, which lowers the risk of a small-for-size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left-liver graft procurement for calculated small-for-size A2ALDLT in four donors are presented. The graft-to-recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux-en-Y loop 4 months later in one donor. We show that LDH of the full-left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.

Open preperitoneal mesh repair of inguinal hernias using a mesh with nitinol memory frame.

PURPOSE: To prospectively evaluate the use of a continuous Nitinol containing memory frame patch during a TIPP-technique in the open repair of inguinal and femoral hernias. METHODS: Over a 3-year period all consecutive adult patients that needed treatment for an inguinal or femoral hernia were treated by the TIPP repair using the Rebound Shield mesh. Intra-operatively the type and size of the hernia were evaluated according to the EHS classification, as well as the size of the mesh used. Baseline characteristics for all patients were evaluated considering age, gender, BMI and American society of Anesthesiologists score. Standard X-ray was performed to evaluate mesh position. All patients were evaluated for post-operative pain using the visual analogue scale (VAS 0-10 scale). RESULTS: In total 289 groin hernias were operated using a nitinol containing patch in 235 patients. The mean operating time was 38 min for unilateral hernias and 59 min for bilateral hernias. The median follow-up is 21.2 months (14-33 months) during which three patients died, unrelated to the groin hernia repair. At the time of re-evaluation 12 patients (5.0 %) complained of chronic pain, with a VAS score higher than 3 after 3 months (range 3-10). Two of these patients already had severe pain pre-operatively. A total of 3 recurrences (2.9 %) were noted with strong correlation with X-ray findings. CONCLUSION: A nitinol memory frame containing mesh is a valuable tool to achieve complete deployment of a large pore mesh in a TIPP repair for inguinal hernias with acceptable morbidity and a low recurrence rate.

Infected large pore meshes may be salvaged by topical negative pressure therapy.

PURPOSE: To evaluate the efficacy of negative pressure therapy for superficial and deep mesh infections after ventral and incisional hernia repair by a prospective monocentric observational study. METHODS: During a 6-year period, 724 consecutive open ventral and incisional hernia repairs were performed. Pre- and intraoperative data as well as postoperative complications were prospectively recorded. In case of wound infection, negative pressure therapy (NPT) was our primary treatment. RESULTS: Sixty-three patients (8.7 %) were treated using negative pressure therapy after primary ventral and incisional hernia repair. Infectious complications needing NPT occurred in 54 patients in the retromuscular group (54/523; 10.3 %), none when laparoscopically treated and in 9 patients (9/143; 6.3 %) treated by an open intraperitoneal mesh technique. Considering outcome, all meshes were completely salvaged in the retromuscular mesh group after a median of 5 dressing changes (range, 2-9), while in the intraperitoneal mesh, group 3 meshes needed complete (n = 2) or partial (n = 1) excision. Mean duration to complete wound closure was 44 days (range, 26-63 days). CONCLUSION: NPT is a useful adjunct for salvage of deep infected meshes, particularly when large pore monofilament mesh is used.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome.

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.