Systemic lidocaine does not attenuate hepatic dysfunction after liver surgery in rats.

BACKGROUND: Lidocaine has been shown to attenuate ischemia-reperfusion (I/R) injury in the heart, lung, and brain, potentially due to modulation of inflammatory responses and apoptotic signaling pathways. Because hepatic I/R injury after liver surgery still poses a significant risk for postoperative liver dysfunction or even failure, we investigated whether systemic lidocaine would also positively affect hepatocellular damage and overall liver function after hepatic I/R injury. In addition the potential underlying mechanisms of action were studied. METHODS: A standardized rat model of 70% I/R injury was used to assess the effects of systemic lidocaine on hepatocellular damage after 60 minutes of ischemia and subsequent reperfusion. To better mimic the clinical situation, we combined 45 minutes of ischemia with partial hepatectomy in a second model. Systemic lidocaine was administered continuously, starting 30 minutes before the ischemic insult until 20 minutes of reperfusion. Hepatocellular function was assessed using different variables of liver synthesis, cellular integrity, and metabolism. Inflammation was evaluated by measuring leukocyte influx and apoptosis detected using TUNEL staining and a caspase-3 assay. RESULTS: In both models, I/R injury resulted in a significant increase in biochemical and histological hepatocellular damage with comparable values in control and lidocaine-treated animals. Postoperative liver function was significantly impaired secondary to ischemia, yet no significant differences between control and lidocaine groups could be observed. Likewise, there was no significant difference between control and lidocaine-treated animals with respect to I/R injury-induced leukocyte influx, as a marker for inflammatory response. CONCLUSION: Systemic lidocaine in therapeutic concentrations neither attenuated hepatocellular damage nor improved postoperative liver function after hepatic I/R injury.

Morbidity and mortality after liver resection for benign and malignant hepatobiliary lesions.

AIM: Although most partial liver resections are performed for malignant lesions, an increasing contingent of benign lesions is also considered for surgery. The aim was to assess post-operative morbidity and mortality after liver resection for benign hepatobiliary lesions in comparison with outcome after resection of malignant lesions. METHODS: A total of 286 liver resections were undertaken between January 1992 and December 2004. After exclusion of resection for bile duct tumours or hepatocellular carcinoma, 205 partial liver resections were retrospectively analysed. RESULTS: Patients with benign lesions comprised 34% of the group (n=70). Benign lesions mainly consisted of focal nodular hyperplasia (n=12; 17%) and liver haemangiomas (11; 15.7%). The malignant lesions consisted of colorectal tumour metastases (n=121; 89%). Patients with benign lesions predominantly underwent minor liver resections (66 vs. 47%; P=0.013). The overall post-operative morbidity occurred in 31% (64/205). Major morbidity occurred in 16% (22/135) in the malignant group compared with 9% (6/70) in the benign group (P=0.099). No differences were seen in major post-operative morbidity in the earlier period compared with the later period (14 vs. 14.3%, P=0.950). In multivariate analysis, only presence of comorbidity (P=0.017), prolonged surgical procedure (P=0.021) and surgical irradicality (P=0.039) maintained significance as independent risk factors for major morbidity. CONCLUSION: Limited liver resections for the treatment of a wide range of benign hepatobiliary lesions are associated with low morbidity and no mortality. However, the indications must be assessed with care. The presence of comorbidity, prolonged surgical time and incomplete resections were associated with major morbidity.

Liver adenomatosis: re-evaluation of aetiology and management.

BACKGROUND: Liver adenomatosis (LA) is a rare benign parenchymal liver disease with unknown aetiology. In recent reports, LA has been associated with hepatic steatosis, with potential implications for the management of this disease. The aim of this study was to determine prognosis and optimal management of patients with LA. METHODS: Clinical presentation, diagnostic studies and management of patients with LA were analysed in our centre. Furthermore, a Medline search of all published case reports and series of LA patients was performed. RESULTS: Ninety-four patients with LA have been reported in the literature. Fifty-two per cent of females had a history of oral contraceptive use. Eighteen per cent of patients had steatosis in nontumoral tissue. In our own series, five of six patients had histologically confirmed steatosis. Forty-three per cent of patients presented with acute pain, of whom 46% had a haemorrhagical complication, in contrast to 2% of nonsymptomatic patients. Tumours <5 cm tended to increase in size during follow-up and only in four patients tumour regression was observed. CONCLUSION: Liver adenomatosis is a progressive, benign parenchymal disease mainly occurring in females. There is a potential link with hepatic steatosis with implications for the management of patients with LA. Noninvasive diagnosis is difficult because of the variety of tumoral and nontumoral components. Management should primarily be conservative.

Differentiation of malignant and benign proximal bile duct strictures: the diagnostic dilemma.

AIM: To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These findings were analyzed to obtain the final diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group I) whereas 10 patients (15%, group II) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group I vs 60% group II, P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group I compared to group II. The various imaging modalities showed vascular involvement exclusively in the malignant group (36%, P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group I whereas none in group II showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.

Results of percutaneous sclerotherapy and surgical treatment in patients with symptomatic simple liver cysts and polycystic liver disease.

AIM: To evaluate the results of the treatment of simple liver cysts (solitary and multiple) and polycystic liver disease (PLD) using percutaneous sclerotherapy and/or surgical procedures in a single tertiary referral centre. METHODS: Retrospective analysis of 54 patients referred for evaluation and possible treatment of simple liver cysts (solitary and multiple) and PLD, from January 1997 to July 2006. RESULTS: Simple liver cysts were treated in 41 pts (76%) with a mean size of 12.6 cm. The most common reason for referral was abdominal pain or discomfort (85%). Percutaneous sclerotherapy was performed as initial treatment in 30 pts, showing cyst recurrence in 6 pts (20%). Surgical treatment was initially performed in 11 pts with cyst recurrence in 3 pts (27%). PLD was treated in 13 pts (24%) with a mean size of the dominant cyst of 13 cm. Percutaneous sclerotherapy for PLD was performed in 9 pts with recurrence in 7 pts (77.8%). Surgical treatment for PLD was undertaken in 4 pts (30.8%) with recurrence in all. Eventually, 2 pts with PLD in the presence of polycystic kidney disease underwent liver- and kidney transplantation because of deterioration of liver and kidney function. CONCLUSION: The majority of patients with simple liver cysts and PLD are referred for progressive abdominal pain. As initial treatment, percutaneous sclerotherapy is appropriate. Surgical deroofing is indicated in case of cyst recurrence after percutaneous sclerotherapy. However, the results of percutaneous sclerotherapy and surgical treatment for PLD are disappointing. Partial liver resection is indicated when there is suspicion of a pre-malignant lesion.

Obstructive jaundice due to hepatobiliary cystadenoma or cystadenocarcinoma.

Hepatobiliary cystadenomas (HBC) and cystadenocarcinomas are rare cystic lesions. Most patients with these lesions are asymptomatic, but presentation with obstructive jaundice may occur. The first patient presented with intermittent colicky pain and recurrent obstructive jaundice. Imaging studies revealed a polypoid lesion in the left hepatic duct. The second patient had recurrent jaundice and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a cystic lesion at the confluence of the hepatic duct. In the third patient with intermittent jaundice and cholangitis, cholangioscopy revealed a papillomatous structure protruding into the left bile duct system. In the fourth patient with obstructive jaundice, CT-scan showed slight dilatation of the intrahepatic bile ducts and dilatation of the common bile duct of 3 cm. ERCP showed filling of a cystic lesion. All patients underwent partial liver resection, revealing HBC in the specimen. In the fifth patient presenting with obstructive jaundice, ultrasound examination showed a hyperechogenic cystic lesion centrally in the liver. The resection specimen revealed a hepatobiliary cystadenocarcinoma. HBC and cystadenocarcinoma may give rise to obstructive jaundice. Evaluation with cross-sectional imaging techniques is useful. ERCP is a useful tool to differentiate extraductal from intraductal obstruction.

Preoperative assessment of postoperative remnant liver function using hepatobiliary scintigraphy.

UNLABELLED: Hepatic resection is the therapy of choice for malignant and symptomatic benign hepatobiliary tumors. The concept of remnant liver volume (RLV) has been introduced and can be assessed with CT. However, inhomogeneous liver function distribution and a lack of correlation between morphologic hypertrophy and functional recovery fuelled the enthusiasm for functional imaging. The aim of the present study was to assess liver function reserve (LFR) and remnant liver function (RLF) before and after major liver surgery with hepatobiliary scintigraphy (HBS) and to compare scintigraphic results with volumetric CT data and indocyanine-green (ICG) clearance test results. Furthermore, HBS was used to assess functional recovery of liver function, and results were compared with volumetric data. METHODS: Fifteen patients with a partial liver resection were included. HBS was performed before, 1 d after, and 3 mo after surgery. ICG clearance and CT were performed before and 3 mo after surgery. Liver function determined with HBS was compared with ICG and volumetric data. RESULTS: Liver function determination using HBS was highly reproducible. A strong positive association (r = 0.84) was found between LFR determined with HBS and ICG clearance. Little or no association (r = 0.27) was found between CT volumetric analysis and corresponding ICG clearance. A strong positive association (r = 0.95) was found between the RLF determined preoperatively on HBS and the actually measured value postoperatively. A weak positive association (r = 0.61) was found between functional liver regeneration and liver volume regeneration in the 3 mo after partial liver resection. CONCLUSION: HBS offers a unique combination of functional liver uptake and excretion with the ability to assess the preoperative LFR and to estimate the RLF preoperatively. Determination of the RLF instead of the RLV might clarify some of the discrepancies observed in the literature between RLV and clinical outcome in patients with an inhomogeneous liver function. Finally, liver function regeneration can be monitored using HBS.

Management of giant liver hemangiomas: an update.

Liver hemangiomas are the most common benign liver tumors and are usually incidental findings. Liver hemangiomas are readily demonstrated by abdominal ultrasonography, computed tomography or magnetic resonance imaging. Giant liver hemangiomas are defined by a diameter larger than 5 cm. In patients with a giant liver hemangioma, observation is justified in the absence of symptoms. Surgical resection is indicated in patients with abdominal (mechanical) complaints or complications, or when diagnosis remains inconclusive. Enucleation is the preferred surgical method, according to existing literature and our own experience. Spontaneous or traumatic rupture of a giant hepatic hemangioma is rare, however, the mortality rate is high (36-39%). An uncommon complication of a giant hemangioma is disseminated intravascular coagulation (Kasabach-Merritt syndrome); intervention is then required. Herein, the authors provide a literature update of the current evidence concerning the management of giant hepatic hemangiomas. In addition, the authors assessed treatment strategies and outcomes in a series of patients with giant liver hemangiomas managed in our department.

[Giant haemangioma of the liver: diagnosis and treatment]. / Het reuzenhemangioom in de lever: diagnostiek en behandeling.

A liver haemangioma is a benign, usually small tumour comprised of blood vessels, which is often discovered coincidentally; giant haemangiomas are defined as haemangiomas larger than 5 cm. The differential diagnosis includes other hypervascular tumours, such as hepatocellular adenoma, hepatocellular carcinoma, metastasis of a neuro-endocrine tumour or renal cell carcinoma.- The diagnosis is based on abdominal ultrasonography and can be confirmed by a CT or MR scan. A wait-and-see approach is justified in patients without symptoms or with minimal symptoms, even in the presence of a giant haemangioma. Surgical resection of a giant haemangioma is only necessary when the preoperative diagnosis is inconclusive, or when the haemangioma leads to mechanical symptoms or complications. Extirpation is the only effective form of treatment of the giant haemangioma; enucleation is preferred over partial liver resection. A known complication of a giant haemangioma is the occurrence of disseminated intravascular coagulation, the Kasabach-Merritt syndrome; intervention is then demanded.

A comparative study of intraductal papillary neoplasia of the biliary tract and pancreas.

Intraductal papillary mucinous neoplasm of the pancreas is a rare but well-established entity in contrast to intraductal papillary mucinous neoplasm of the biliary tract. The aim of this study was to compare the clinicopathologic features of intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas. Twenty patients who underwent resection for intraductal papillary mucinous neoplasm of the biliary tract were compared with 29 cases resected for intraductal papillary mucinous neoplasm of the pancreas. Clinicopathologic characteristics and resection specimens of all patients were reassessed and immunohistochemically screened for expression of a distinct set of tumor markers. Median ages of patients with intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas were 66 and 62 years, respectively (P < .05). Twelve patients with intraductal papillary mucinous neoplasm of the biliary tract (60%) had neoplasms with infiltrating carcinoma, compared with 6 patients with intraductal papillary mucinous neoplasm of the pancreas (21%, P < .05). Cytokeratin 7 and 20 expressions were equal in biliary and pancreatic intraductal papillary mucinous neoplasms. Cytokeratin 20 expression was mainly found in intestinal-type tumors. Gastric, pancreaticobiliary, and oncocytic subtypes were all observed in the intraductal papillary mucinous neoplasm of the biliary tract group. The distribution was significantly different from the intraductal papillary mucinous neoplasm of the pancreas group. The 3-year overall survival rate of malignant biliary and pancreatic intraductal papillary mucinous neoplasm was 63% and 65%, respectively (P = .798). Positive lymph nodes and a high expression of membranous mucin were associated with a significantly shorter overall survival in patients with malignant intraductal papillary mucinous neoplasm. Finally, p53 and Ki67 proliferation index were both associated with the carcinogenesis of intraductal papillary mucinous neoplasm, whereas DPC4 and CDX2 were not. Clinicopathologic features of intraductal papillary mucinous neoplasm of the biliary tract largely resemble those of intraductal papillary mucinous neoplasm of the pancreas, although intraductal papillary mucinous neoplasm of the biliary tract was associated with a higher malignancy rate at the time of surgical treatment. The level of membranous mucin expression and positive lymph nodes are significant prognosticators in patients with malignant intraductal papillary mucinous neoplasm.

Transit-time volume flow measurements in autogenous femorodistal bypass surgery for intraoperative quality control.

The aim of this study was to assess intraoperative transit-time volume flow measurements (VFMs) as a tool for intraoperative evaluation of lower extremity arterial bypass grafts and to predict their patency. We analyzed 273 consecutive patients who had an infrainguinal bypass procedure using the great saphenous vein from 1998 until 2008; 103 had an intraoperative VFM. All intraoperative revisions were recorded and analyzed. Patency and revision rates were compared between those receiving and those not receiving intraoperative VFM. Cox regression was used for analysis of predictors of patency. Primary patency at 1 and 2 years was 75 and 67%, respectively, in patients receiving intraoperative VFM versus 72 and 69% in those without VFM (p  =  .79). In the VFM group, 12% had an immediate revision versus 6% without VFM (p  =  .06). In the VFM group, 4% underwent revision to salvage the bypass within the first postoperative 30 days versus 6% without VFM (p  =  .32). Patency was not associated with the use of VFM. Receiver operating characteristic curve was significant for occlusion at 30 days postoperatively but with a low predictive value (p  =  .019,area under the curve 0.648). VFM may be helpful in selecting bypasses requiring immediate revision to prevent postoperative occlusion. The use of VFM is not significantly associated with patency.

Evolution of fibrinogen-coated collagen patch for use as a topical hemostatic agent.

Human fibrinogen and thrombin have been combined and coated onto a collagen patch for use as a topical hemostatic agent. These agents have now been used for many years to induce rapid hemostasis and tissue sealing after various indications including thoracic-, plastic-, pediatric-, liver-, and minimally invasive surgery. The only ready-to-use fibrinogen-coated collagen patch at this moment, the third-generation surgical patch (SP-3), contains no bovine aprotinin (antifibrinolytic protein) in contrast to its precursor SP-2, and is thus devoid of bovine-derived components. In vitro studies have shown equal bioequivalence between SP-2 and SP-3. Various experiments in animal models under normal, stressful, and hyperfibrinolytic conditions showed that SP-3 has comparable tissue sealing properties and also outperformed fibrin sealants alone in some studies. The results from these pre-clinical bridging studies showed that aprotinin is not essential for the therapeutic efficacy of SP-3. In conclusion, SP-3 has evolved into a rapid, ready-to-use adjunct to primary measures for tissue sealing and hemostasis, suitable in cardiovascular-, thoracic-, neuro-, spleen-, kidney-, and liver-surgery.

Prevention of biliary leakage after partial liver resection using topical hemostatic agents.

Liver resection is widely accepted as the only potentially curative treatment in malignant or benign hepatobiliary lesions. Although not frequent, biliary leakage is a postoperative complication which may have considerable consequences. The field of topical hemostatic agents is rapidly developing, with various products currently available. This article reviews the risk factors associated with biliary leakage and the methods used for testing or prevention of biliary leakage. A literature search was performed using key words related to experimental and clinical studies dealing with biliary leakage. Experimental studies assessed the potential bilio-static effect of different topical hemostatic agents after bile duct reconstruction. Clinical series show biliary leakage rates up to 12%. There is no evidence that flushing of the bile duct system after resection reduces the incidence of biliary leakage. Further controlled studies are needed to clarify the preventive effect of topical hemostatic agents on biliary leakage after liver resection.

Selective transcatheter arterial embolization for treatment of bleeding complications or reduction of tumor mass of hepatocellular adenomas.

Hepatocellular adenomas (HCAs) are benign liver lesions which may be complicated by spontaneous intratumoral bleeding, with or without rupture into the abdominal cavity, or malignant degeneration. Recent advances in radiological interventional techniques now offer selective transcatheter arterial embolization (TAE) as an alternative approach to surgery as the initial treatment to stop the bleeding or as an elective treatment to reduce the tumor mass of the HCA. Herein, we report our initial experience using TAE in the management of HCA. Five female patients and one male patient presented with spontaneous hemorrhage of HCA. Four patients were initially treated with selective TAE to stop the bleeding. In two patients in whom the bleeding stopped spontaneously, TAE was electively undertaken 1 year after presentation to reduce the tumor mass of HCAs >5 cm. Selective TAE as initial treatment in patients with spontaneous bleeding of HCA with or without rupture is effective and will change the need for urgent laparotomy to control bleeding. Selective TAE may also be used as an elective treatment to reduce the tumor mass of larger HCAs.

Management of liver hemangiomas according to size and symptoms.

BACKGROUND AND AIM: Liver hemangiomas are the most common benign liver tumors. These lesions are usually incidental findings during imaging studies of the abdomen performed for other reasons. The indication for surgical resection of these lesions remains controversial. METHODS: Records of patients referred for evaluation of radiologically and/or histopathologically proven liver hemangiomas, from June 1991 to February 2006, were retrospectively analyzed. Reason for referral, results of imaging studies, and surgical treatment and outcome were reviewed. RESULTS: There were 34 patients identified. The hemangioma size was <5 cm in 15 patients (44%) and >5 cm in 19 patients. The most common reason for referral was right upper abdominal pain in 59% (20/34) of patients. Abdominal ultrasound was conclusive in 66.7% (16/24) and four-phase computed tomography (CT) in 82.6% (19/23) of patients. Surgical resection was undertaken in 14 patients (41%) after a mean follow-up time of 36.5 months. The indication for treatment was progressive abdominal pain in 78.6% (11/14). Mean size of resected lesions was larger compared to non-resected lesions (10.3 vs 4.8 cm; P = 0.004). Postoperative morbidity occurred in three patients (21.4%). One patient had persisting abdominal pain after resection of an 8-cm hemangioma. Twenty patients were observed and showed no complications related to the liver hemangioma during follow-up. CONCLUSIONS: Liver hemangiomas can be readily diagnosed by ultrasound or multiphase contrast-enhanced helical CT. The indications for surgical resection are progressive abdominal pain in combination with size >5 cm. Observation is justified in patients with minimal or no symptoms, even in patients with giant hemangiomas.

Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A single centre experience.

BACKGROUND: Hepatocellular adenomas (HCA) may present with spontaneous haemorrhage and rupture. The aim of this study was to assess management in 22 patients treated for haemorrhage and/or rupture of HCA. PATIENTS AND METHODS: Between May 1990 and July 2005, 22 female patients were diagnosed with acute haemorrhage and/or rupture of lesions highly suspicious of HCA. Preoperative imaging diagnostics and pathologic specimens were reviewed. RESULTS: Twelve haemodynamically stable and four unstable patients could be treated conservatively. One patient underwent acute partial liver resection, whereas four patients underwent laparotomy with initial packing of the liver. In one patient, selective embolisation of the left hepatic artery was performed. Fifteen patients eventually underwent resection after a mean time of 8 months after initial treatment. Six patients did not undergo resection and showed no complications or rebleeding after a mean follow-up of 24.6 months. Only in seven patients, histopathological examination showed HCA, and in one patient, HCA with focal nodular hyperplasia. CONCLUSION: HCA with haemorrhage and/or rupture does not necessarily require immediate liver resection. Conservative treatment is justified in stable patients. In case of an instable patient with or without hemoperitoneum, laparotomy with packing or selective embolisation can stop the bleeding.

Preoperative assessment of liver function: a comparison of 99mTc-Mebrofenin scintigraphy with indocyanine green clearance test.

BACKGROUND/AIMS: The indocyanine green (ICG) clearance test is the most frequently used test for preoperative assessment of liver parenchymal function but has its limitations. The aim of this study was to investigate the correlation between ICG clearance test and the liver uptake of 99-Technetium-labelled (99mTc)-Mebrofenin (99mTc-Mebrofenin) as measured with hepatobiliary scintigraphy. METHODS: Fifty-four patients were diagnosed as hepatocellular carcinoma (n=9), hilar tumours (n=20) and 25 patients with non-parenchymal tumours including colorectal metastasis (n=15) and miscellaneous tumours (n=10). One day prior to operation, hepatobiliary 99mTc-Mebrofenin scintigraphy was performed after intravenous injection of 85 MBq and the 15-min clearance rate of ICG (ICG-C15) was measured. RESULTS: The mean ICG-C15 was 86.86+/-1.19% (SEM). The mean 99mTc-Mebrofenin uptake rate was 12.87+/-0.52%/min. A significant correlation was obtained between 99mTc-Mebrofenin uptake rate by scintigraphy and ICG-C15 (r=0.73, P<0.0001). The mean clearance capacity of the right liver segments (79.83+/-1.63, range 47.75-95.97%) was larger than that of the left segments (20.24+/-1.55, range 6.51-52.51%). CONCLUSION: 99mTc-Mebrofenin uptake rate as assessed by scintigraphy is an efficient method for determining liver function and correlates well with ICG clearance. At the same time, 99mTc-Mebrofenin scintigraphy provides information of segmental functional liver tissue, which is of additional use when planning liver resection.