Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Contains fulltext : 109282.pdf (publisher's version ) (Open Access)BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405

Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation

Laparoscopic versus open left lateral segmentectomy

<p>Abstract</p> <p>Background</p> <p>Laparoscopic liver surgery is becoming increasingly common. This cohort study was designed to directly compare perioperative outcomes of the left lateral segmentectomy via laparoscopic and open approach.</p> <p>Methods</p> <p>Between 2002 and 2006 43 left lateral segmentectomies were performed at King's College Hospital. Those excluded from analysis included previous liver resections, polycystic liver disease, liver cirrhosis and synchronous operations. Of 20 patients analysed, laparoscopic (n = 10) were compared with open left lateral segmentectomy (n = 10). Both groups had similar patient characteristics.</p> <p>Results</p> <p>Morbidity rates were similar with no wound or chest infection in either group. The conversion rate was 10% (1/10). There was no difference in operating time between the groups (median time 220 minutes versus 179 minutes, p = 0.315). Surgical margins for all lesions were clear. Less postoperative opiate analgesics were required in the laparoscopic group (median 2 days versus 5 days, p = 0.005). The median postoperative in-hospital stay was less in the laparoscopic group (6 days vs 9 days, p = 0.005). There was no mortality.</p> <p>Conclusion</p> <p>Laparoscopic left lateral segmentectomy is safe and feasible. Laparoscopic patients may benefit from requiring less postoperative opiate analgesia and a shorter post-operative in-hospital stay.</p

Perioperative outcome of laparoscopic left lateral liver resection is improved by using a bioabsorbable staple line reinforcement material in a porcine model

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model. Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test. Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p <0.05). There was no mortality. There was no morbidity in the 6-week follow-up period; however, two animals in group B had subphrenic bilomas (20%) at necropsy. At necropsy, methylene blue injection via the main bile duct revealed leakage from the biliary tree in four animals in group B and none in group A (p <0.05). Histopathological examination of the resection site revealed minor abnormalities in group A while animals in group B demonstrated marked fibrotic changes and damaged vascular and biliary endothelium. Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model

Deciduous Trees and the Application of Universal DNA Barcodes: A Case Study on the Circumpolar Fraxinus

The utility of DNA barcoding for identifying representative specimens of the circumpolar tree genus Fraxinus (56 species) was investigated. We examined the genetic variability of several loci suggested in chloroplast DNA barcode protocols such as matK, rpoB, rpoC1 and trnH-psbA in a large worldwide sample of Fraxinus species. The chloroplast intergenic spacer rpl32-trnL was further assessed in search for a potentially variable and useful locus. The results of the study suggest that the proposed cpDNA loci, alone or in combination, cannot fully discriminate among species because of the generally low rates of substitution in the chloroplast genome of Fraxinus. The intergenic spacer trnH-psbA was the best performing locus, but genetic distance-based discrimination was moderately successful and only resulted in the separation of the samples at the subgenus level. Use of the BLAST approach was better than the neighbor-joining tree reconstruction method with pairwise Kimura's two-parameter rates of substitution, but allowed for the correct identification of only less than half of the species sampled. Such rates are substantially lower than the success rate required for a standardised barcoding approach. Consequently, the current cpDNA barcodes are inadequate to fully discriminate Fraxinus species. Given that a low rate of substitution is common among the plastid genomes of trees, the use of the plant cpDNA “universal” barcode may not be suitable for the safe identification of tree species below a generic or sectional level. Supplementary barcoding loci of the nuclear genome and alternative solutions are proposed and discussed

Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria