Arianeb Mehrabi

Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis

Transient elastography (FibroScan [FS]) is a novel non‐invasive tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if other liver diseases such as extrahepatic cholestasis interfere with fibrosis assessment because liver stiffness is indirectly measured by the propagation velocity of an ultrasound wave within the liver. In this study, we measured liver stiffness immediately before endoscopic retrograde cholangiopancreatography and 3 to 12 days after successful biliary drainage in patients with extrahepatic cholestasis mostly due to neoplastic invasion of the biliary tree. Initially elevated liver stiffness decreased in 13 of 15 patients after intervention, in 10 of them markedly. In three patients, liver stiffness was elevated to a degree that suggested advanced liver cirrhosis (mean, 15.2 kPa). Successful drainage led to a drop of bilirubin by 2.8 to 9.8 mg/dL whereas liver stiffness almost normalized (mean, 7.1 kPa). In all patients with successful biliary drainage, the decrease of liver stiffness highly correlated with decreasing bilirubin (Spearmans ρ = 0.67, P < 0.05) with a mean decrease of liver stiffness of 1.2 ± 0.56 kPa per 1 g/dL bilirubin. Two patients, in whom liver stiffness did not decrease despite successful biliary drainage, had advanced liver cirrhosis and multiple liver metastases, respectively. The relationship between extrahepatic cholestasis and liver stiffness was reproduced in an animal model of bile duct ligation in landrace pigs where liver stiffness increased from 4.6 kPa to 8.8 kPa during 120 minutes of bile duct ligation and decreased to 6.1 kPa within 30 minutes after decompression. Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Once extrahepatic cholestasis is excluded (e.g., by liver imaging and laboratory parameters) transient elastography is a valuable tool to assess liver fibrosis in chronic liver diseases. (HEPATOLOGY 2008.)

Liver stiffness is directly influenced by central venous pressure

BACKGROUND & AIMS Liver stiffness (LS) as measured by transient elastography [Fibroscan] offers a novel non-invasive approach to assess liver cirrhosis. Since Fibroscan seems to be unreliable in patients with congestive heart failure, it remains to be determined whether hemodynamic changes affect LS irrespective of fibrosis. METHODS & RESULTS Using landrace pigs, we studied the direct relationship between the central venous pressure and LS measured by Fibroscan. Clamping of the inferior caval vein increased LS from 3.1 to 27.8kPa while reopening reversed LS within 5min to almost normal values of 5.1kPa. We then studied LS as a function of venous pressure in the isolated pig liver by clamping the upper and lower caval, portal vein and hepatic artery. The stepwise increase of intravenous pressure to 36cm of water column (3.5kPa) linearly and reversibly increased LS to the upper detection limit of 75kPa. We finally measured LS in 10 patients with decompensated congestive heart failure before and after recompensation. Initial LS was elevated in all patients, in 8 of them to a degree that suggested liver cirrhosis (median 40.7kPa). Upon recompensation with a median weight loss of 3.0kg, LS decreased in all 10 patients down to a median LS of 17.8kPa. Inflammation could not account for increased LS since initial liver enzyme counts were only slightly elevated and did not change significantly. CONCLUSION LS is a direct function of central venous pressure which should be considered when assessing the degree of fibrosis.

Fewer adhesions induced by laparoscopic surgery

BackgroundLaparoscopic surgery has potential theoretical advantages over open surgery in reducing the rate of adhesion formation, but very few comparative studies are available to prove this.MethodsA literature search was performed within Medline and Cochrane databases using the key words: adhesion*, adhesiolysis, laparoscop*, laparotomy, open surgery. Further articles were identified from the reference lists of retrieved literature. Both clinical and experimental studies comparing laparoscopy and laparotomy with regard to adhesion formation were retained. In each article, the rates of adhesion formation were identified or deduced for the operative site, access wound site, and distant sites.ResultsFifteen studies from 1987 to 2001 were identified. Most studies assessed the operative site. Thus, three clinical studies and six experimental ones found fewer adhesions following laparoscopy than laparotomy, while other five experimental studies found similar adhesion rates for the two surgical methods. There were fewer adhesions to trocar wounds than to the laparotomy wounds in seven studies and equal rates of adhesion in one study. The problem of distant adhesions is poorly represented in literature; three studies favored laparoscopy as being followed by fewer adhesions. Because of the important differences between studies with regard to the design, end points, and statistical calculations, a metaanalysis could not be achieved. The conclusion is based on the prevalence of evidence.ConclusionsAll clinical studies and most of the experimental studies found a reduction of adhesion formation after laparoscopic surgery compared to open surgery.

Primary malignant hepatic epithelioid hemangioendothelioma : A comprehensive review of the literature with emphasis on the surgical therapy

Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant tumor of vascular origin with unknown etiology and a variable natural course. The authors present a comprehensive review of the literature on HEH with a focus on clinical outcome after different therapeutic strategies. All published series on patients with HEH (n = 434 patients) were analyzed from the first description in 1984 to the current literature. The reviewed parameters included demographic data, clinical manifestations, therapeutic modalities, and clinical outcome. The mean age of patients with HEH was 41.7 years, and the male‐to‐female ratio was 2:3. The most common clinical manifestations were right upper quadrant pain, hepatomegaly, and weight loss. Most patients presented with multifocal tumor that involved both lobes of the liver. Lung, peritoneum, lymph nodes, and bone were the most common sites of extrahepatic involvement at the time of diagnosis. The most common management has been liver transplantation (LTx) (44.8% of patients), followed by no treatment (24.8% of patients), chemotherapy or radiotherapy (21% of patients), and liver resection (LRx) (9.4% of patients). The 1‐year and 5‐year patient survival rates were 96% and 54.5%, respectively, after LTx; 39.3% and 4.5%, respectively, after no treatment, 73.3% and 30%, respectively, after chemotherapy or radiotherapy; and 100% and 75%, respectively, after LRx. LRx has been the treatment of choice in patients with resectable HEH. However, LTx has been proposed as the treatment of choice because of the hepatic multicentricity of HEH. In addition, LTx is an acceptable option for patients who have HEH with extrahepatic manifestation. Highly selected patients may be able to undergo living‐donor LTx, preserving the donor pool. The role of different adjuvant therapies for patients with HEH remains to be determined. Cancer 2006.

Circulatory and Respiratory Complications of Carbon Dioxide Insufflation

Background: Although providing excellent outcome results, laparoscopy also induces particular pathophysiological changes in response to pneumoperitoneum. Knowledge of the pathophysiology of a CO2 pneumoperitoneum can help minimize complications while profiting from the benefits of laparoscopic surgery without concerns about its safety. Methods: A review of articles on the pathophysiological changes and complications of carbon dioxide pneumoperitoneum as well as prevention and treatment of these complications was performed using the Medline database. Results: The main pathophysiological changes during CO2 pneumoperitoneum refer to the cardiovascular system and are mainly correlated with the amount of intra-abdominal pressure in combination with the patient’s position on the operating table. These changes are well tolerated even in older and more debilitated patients, and except for a slight increase in the incidence of cardiac arrhythmias, no other significant cardiovascular complications occur. Although there are important pulmonary pathophysiological changes, hypercarbia, hypoxemia and barotraumas, they would develop rarely since effective ventilation monitoring and techniques are applied. The alteration in splanchnic perfusion is proportional with the increase in intra-abdominal pressure and duration of pneumoperitoneum. Conclusion: A moderate-to-low intra-abdominal pressure (<12 mm Hg) can help limit the extent of the pathophysiological changes since consecutive organ dysfunctions are minimal, transient and do not influence the outcome.

Robot‐assisted abdominal surgery

Robotic assistance or telemanipulation is the latest technological advance in minimally invasive surgery. Its future implementation will depend on the advantages that it can provide over standard laparoscopy or open surgery.

Etiology‐dependent molecular mechanisms in human hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is characterized by aggressive tumor behavior coupled with poor prognosis. Various etiologies have been linked to HCC development, most prominently chronic hepatitis B and C virus infections as well as chronic alcohol consumption. In approximately 10% of HCCs, the etiology remains cryptic; however, recent epidemiological data suggest that most of these cryptogenic HCCs develop due to nonalcoholic steatohepatitis. To identify etiology‐dependent DNA copy number aberrations and genes relevant to hepatocarcinogenesis, we performed array‐based comparative genomic hybridization of 63 HCCs of well‐defined etiology and 4 HCC cell lines followed by gene expression profiling and functional analyses of candidate genes. For a 10‐megabase chromosome region on 8q24, we observed etiology‐dependent copy number gains and MYC overexpression in viral and alcohol‐related HCCs, resulting in up‐regulation of MYC target genes. Cryptogenic HCCs showed neither 8q24 gains, nor MYC overexpression, nor target gene activation, suggesting that tumors of this etiology develop by way of a distinct MYC‐independent pathomechanism. Furthermore, we detected several etiology‐independent small chromosome aberrations, including amplification of MDM4 on 1q32.1 and frequent gains of EEF1A2 on 20q13.33. Both genes were overexpressed in approximately half the HCCs examined, and gene silencing reduced cell viability as well as proliferation and increased apoptosis rates in HCC cell lines. Conclusion: Our findings suggest that MDM4 and EEF1A2 act as etiology‐independent oncogenes in a significant percentage of HCCs. (HEPATOLOGY 2008.)

Stapler Hepatectomy is a Safe Dissection Technique: Analysis of 300 Patients

BackgroundIn many surgical procedures, stapling devices have been introduced for safety and to reduce the overall operative time. Their use for transection of hepatic parenchyma is not well established. Thus, the feasibility of stapler hepatectomy and a risk analysis of surgical morbidity based on intraoperative data have been prospectively assessed on a routine clinical basis.Materials and MethodsFrom October 1, 2001, to January 31, 2005, a total of 416 patients underwent liver resection in our department. During this period endo GIA vascular staplers were used for parenchymal transection in 300 cases of primary (22%) and metastatic (57%) liver cancer, benign diseases (adenoma, focal nodular hyperplasia [FNH], cysts) (14%), gallbladder carcinoma (2%), and other tumors (5%). There were 193 (64%) major resections (i.e., removal of three segments or more) and 107 minor hepatic resections. Additional extrahepatic resections were performed in 44 (15%) patients.ResultsMedian values for operative time and intraoperative hemorrhage were 210 minutes and 700 ml, respectively. Further, transfusion of RBC and FFP was needed in 17% and 11% of patients, respectively. A postoperative ICU stay for >2 days was required in 18% of patients. The median postoperative hospital stay was 10 days (IQR 8–14 days). The most frequent surgical complications were bile leak (8%), wound infection (3%), and pneumothorax (2%). In 7% of cases after stapler hepatectomy a relaparotomy was necessary. Treated medical complications were pleural effusion (7%), renal insufficiency (5%), and cardiac insufficiency (3%). Risk assessment revealed that both operative time and indication for resection had significant impact on surgical morbidity. Mortality (4%) and morbidity (33%) were comparable to other high-volume centers performing conventional liver resection techniques.ConclusionIn conclusion, stapler hepatectomy can be used in a routine clinical setting with a low incidence of surgical complications.

A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: it's time to randomize.

BACKGROUND Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas. METHODS A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals. RESULTS A total of 4,148 citations were retrieved initially; available data of 29 observational studies (3,701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited. CONCLUSION Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more nonrandomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined end points, and cost-effectiveness.

Wound complications following kidney and liver transplantation.

Abstract:  Advances in surgical techniques and immunosuppression (IS) have led to an appreciable reduction in postoperative complications following transplantation. However, wound complications as probably the most common type of post‐transplantation surgical complication can still limit these improved outcomes and result in prolonged hospitalization, hospital readmission, and reoperation, consequently increasing overall transplant cost. Our aim was to review the literature to delineate the evidence‐based risk factors for wound complications following kidney and liver transplantation (KTx, LTx), and to present the preventive and therapeutic modalities for this bothersome morbidity. Generally, wound complications are categorized as superficial and deep wound dehiscences, perigraft fluid collections and seroma, superficial and deep wound infections, cellulitis, lymphocele and wound drainage. The results of several studies showed that the most important risk factors for wound complications are IS and obesity. Additionally, there are surgical and/or technical factors, including type of incision, reoperation, and surgeons expertise, as well as comorbidities such as advanced age, diabetes mellitus, malnutrition, and uremia. Preventive management of wound complications necessitates defining their etiological factors so that their detrimental effects on healing processes can be addressed and reduced. IS modalities and agents, especially sirolimus (SRL), and steroids (ST) should be adjusted according to the patients co‐existing risk factors. SRL should be administered three months after transplantation and ST should be tapered as soon as possible. A body mass index (BMI) lower than 30 kg/m2 is advisable for inclusion in a transplantation program, but higher BMIs do not exclude recipients. Surgical risk factors can be prevented by applying precise surgical techniques. Therapeutic modalities must focus on the most efficient and cost‐effective medications and/or interventions to facilitate and improve wound healing.