Hamidreza Fonouni

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.

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.

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.

Surgical strategies for liver transplantation in the case of portal vein thrombosis – current role of cavoportal hemitransposition and renoportal anastomosis

Abstract:  Portal vein thrombosis (PVT), a common complication of end stage liver disease, is no longer considered a definite contraindication for liver transplantation (LTx). The clinical decision to perform an LTx in the case of PVT depends on the degree of PVT and the experience of the surgeon. Eversion thromboendovenectomy was suggested by most authors as the surgical technique of choice for PVT grade 1, 2, and 3. If PVT obstructs more extended parts of the porto‐mesenteric venous circulation, surgical options would include different types of venous jump graft reconstructions or arterialization of the portal vein. Combined liver and small bowel transplantation is another possible alternative. Cavoportal hemitransposition (CPHT) and renoportal anastomosis (RPA) were recently particularly advocated as creative surgical strategies in case of diffuse PVT. In this work, we focus on CPHT and RPA surgical techniques during LTx, which attempts to secure the portal flow to the liver graft in case of pre‐existent diffuse PVT. We provide a review of all reported clinical experience at international clinical centers using these techniques. According to our meta‐analysis a total of 15 studies were published on this topic between 1996 and 2005. In summary, a total of 56 orthotopic LTx have been performed in 53 patients (28 men, 25 women) combined with either CPHT or RPA, for the purpose of providing the donor graft with adequate inflow. Mean age was 44 yr including two patients who were infants, with the youngest recipient being two yr old. Main indications for LTx were liver cirrhosis caused by viral hepatitis, alcoholic cirrhosis and cryptogenic cirrhosis. CPHT was performed in 46 cases, and RPA in 10 cases. Thirty‐five of 53 patients (66%) had surgery previous to LTx. Of these, 13 (37%) patients presented with a history of other previous surgical procedures for decompression of portal hypertension or treatment of associated complications (portocaval shunts, splenectomy, etc). Ascites, renal dysfunction, lower extremity and torso edema and variceal bleeding were dominant post‐operative complications after CPHT or RPA noted in 22 cases (41.5%), 18 cases (34%), 17 cases (32%) and 13 cases (24.5%) respectively. Patients’ follow‐up ranged from two to 48 months. Patients survived [39 (74%)] and patients died [14 (26%)] during the course of observation. Based on the literature, we conclude that the ideal technique to overcome PVT during LTx is still controversial. Short‐term follow‐up results of both methods are promising, however, long‐term results are unknown at present. Furthermore, clinical follow‐up and basic experimental work is required to evaluate the influence of systemic venous inflow to the liver graft with respect to long‐term liver function and liver regeneration.

Surgical Treatment of Patients with Wandering Spleen: Report of Six Cases with a review of the literature

Wandering spleen, which is defined as a spleen without peritoneal attachments, is a rare disease and a delay in the clinical and/or radiological diagnosis may lead to splenic torsion, infarction, and necrosis. Owing to the physiologic importance of the spleen, especially in children, and the risk of postsplenectomy sepsis, early diagnosis and splenopexy are recommended. In the present article, we describe the results of our management of this rare problem on six patients, and we review all available literature from 1895 to 2005. Briefly, our technique includes flap creation from parietal peritoneum and settlement of spleen in the fossa splenica. Free edges of this flap are stitched to the stomach and the left end of transverse colon and the beginning of the descending colon. The body of the stomach was stitched to the abdominal wall to prevent gastric volvulus, while the fundus region was fixed to the diaphragm to support the spleen. Finally, an omental patch was stitched to the intact abdominal wall above the flap. In conclusion, the procedure of splenopexy without using mesh is considered to be a safe and curative modality for wandering spleen without imposing any undue risk of infection or foreign material reaction.

A systematic review of localization, surgical treatment options, and outcome of insulinoma.

Objective Insulinoma with an incidence of 0.4% is a rare pancreatic tumor. Preserving surgery is the treatment of choice. Exact localization is necessary to plan the appropriate approach. This article gives an overview on localization and surgical strategies for treatment of insulinoma. Methods In this systematic review, 114 articles with 6222 cases of insulinoma were reviewed with emphasis on localization techniques and surgical treatment. Results Insulinoma happens mostly in the fifth decade of life, with a higher incidence in men. They occur mostly sporadic (94%), benign (87%), and single (90%). Insulinomas are mostly smaller than 20 mm (84%). The tumors are distributed almost equally in the pancreas. Conclusions Computed tomography is routinely used as first choice preoperatively. Intraoperative inspection, palpation, and sonography were applied with high success rate. Intraoperative sonography is considered as the most reliable technique. Enucleation is the most administered type of surgery (56%). Different types of resection include distal pancreatectomy (32%), Whipple procedure (3%), and subtotal pancreatectomy (<3%). Despite the development of laparoscopy, open approach is the favorite method (90%). The most common surgical complication is fistula. The mortality rate of open approach was higher (4vs0%). Despite high cure rate, recurrence of insulinoma occurs in 7% after surgery.

Current concepts in transplant surgery: liver transplantation today

IntroductionThe discipline of liver transplantation (LTx) has been developed over the past decades, and LTx is now considered the gold standard for the treatment of patients with end-stage liver diseases and early liver tumors in cirrhotic livers. This procedure is now performed routinely in many transplant centers, and it has provided an enormous technical innovation to the field of hepatobiliary surgery. Allocation decision of liver organs is based on medical need and timing.Materials and methodsThe Mayo Model for End Stage Liver Disease based on patient-specific criteria was developed and applied to prioritize patients on the waiting list. From the donor aspects of LTx, sources of organ, excluding xenotransplantation, can be brain-dead donors, living donors, and non-heart-beating donors. Today, the majority of livers are procured from cadaveric donors. In addition to the conventional LTx, other types are living-donor LTx, reuse of grafts as domino transplantation, ex situ as well as in situ split LTx, and reduced-size LTx. The transplantation procedure consists of several steps including donor selection and management, liver procurement and preservation, back-table preparation, recipient operation with liver implantation, postoperative care, immunosuppression, and follow-up.ResultsThe postoperative complications are divided into surgical, non-surgical, and multifactorial complications. Surgical complications account about 34% of morbidities after LTx and are mainly categorized to vascular and biliary complications. The main medical ones are non-surgical bleeding and infections. The multifactorial complications include primary non- or poor function and small-for-size syndrome. The pretransplant outcome predictors of LTx can be divided into donor, recipient, operative, and postoperative factors.ConclusionLTx is now considered a safe and standardized procedure with a substantially improved graft and patient survival and acceptable morbidity rates. However, the new problems, including recurrence of hepatitis C or hepatocellular carcinoma, chronic biliary complications, opportunistic infections, and development of de-novo malignancies are the major problems affecting the long-term outcome of transplanted patients.

Mesohepatectomy as an Option for the Treatment of Central Liver Tumors

BACKGROUND Despite substantial improvements in intra- and postoperative management of extended hemihepatectomy as the curative option for treatment of central liver tumors, the high morbidity and mortality rates accompanying the procedure still represent major obstacles. Mesohepatectomy preserves up to 35% more functional liver tissue than extended hepatectomy, but it has not been widely applied, perhaps because of its complexity as a resection method. STUDY DESIGN Forty-eight consecutive patients (29 men and 19 women) with centrally located liver tumors underwent mesohepatectomy. Peri- and postoperative morbidity and mortality rates were prospectively evaluated and analyzed. Mean age of the patients was 60.7 years. Indications for mesohepatectomy were liver metastasis (n = 29), hepatocellular carcinoma (n = 5), gallbladder carcinoma (n = 4), cholangiocellular carcinoma (n = 4), hemangioma (n = 2), and other benign diseases (n = 4). RESULTS Mean operative time was 238 minutes (range 65 to 480 minutes) and mean intraoperative blood loss was 1,120 mL (range 100 to 5,000 mL). Mean amount of intraoperative red blood cells and fresh frozen plasma transfusion was 3.6 U (range 1 to 12 U) and 3.8 U (range 2 to 14 U), respectively. Mean postoperative hospitalization was 15.8 days (range 6 to 104 days). Postoperative surgical complications were seen in 18.8% of patients (n = 9) and included liver failure (n = 1), intraabdominal abscess (n = 1), bilioma or bile leakage (n = 4), hemorrhage and hematoma (n = 2), peritonitis because of intestinal perforation (n = 1), and wound infection (n = 1). One patient (2%) died in the early postoperative phase from portal vein bleeding and disseminated intravascular coagulation, followed by liver failure. CONCLUSIONS Compared with extended liver resection, mesohepatectomy clearly leads to less parenchymal loss. Although it is a technically difficult operation and requires special attention to prevent surgical complications, it is justified in selected patients with centrally located tumors and is a feasible and safe alternative to extended liver resection.

The need for venovenous bypass in liver transplantation.

Since introduction of the conventional liver transplantation (CLTx) by Starzl, which was based on the resection of recipient inferior vena cava (IVC) along the liver, the procedure has undergone several refinements. Successful use of venovenous bypass (VVB) was first introduced by Shaw et al., although in recent decades there has been controversy regarding the routine use of VVB during CLTx. With development of piggyback liver transplantation (PLTx), the use of caval clamping and VVB is avoided, leading to fewer complications related to VVB. However, some authors still advocate VVB in PLTx. The great diversity among centers in their use of VVB during CLTx, or even along the PLTx technique, has led to confusion regarding the indication setting for VVB. For this reason, we present an overview of the use of VVB in CLTx, the target of patients for whom VVB could be beneficial, and the needs assessment of VVB for patients undergoing PLTx. Recent studies have shown that with the advancement of surgical skills, refinement of surgical techniques, and improvements in anesthesiology, there are only limited indications for doing CLTx with VVB routinely. PLTx with preservation of IVC can be performed in almost all primary transplants and in the majority of re-transplantations without the need for VVB. Nevertheless, in a few selective cases with severe intra-operative hemodynamic instability, or with a failed test of transient IVC occlusion, the application of VVB is still justifiable. These indications should be judged intra-operatively and the decision is based on each centers preference.