Lucas McCormack

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

Objective:To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. Background:Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. Methods:Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. Results:Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. Conclusion:PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.

How Should Transection of the Liver Be Performed?: A Prospective Randomized Study in 100 Consecutive Patients: Comparing Four Different Transection Strategies

Objective:To identify the most efficient parenchyma transection technique for liver resection using a prospective randomized protocol. Summary Background Data:Liver resection can be performed by different transection devices with or without inflow occlusion (Pringle maneuver). Only limited data are currently available on the best transection technique. Methods:A randomized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver (25 patients each group). Primary endpoints were intraoperative blood loss, resection time, and postoperative liver injury. Secondary end points included the use of inflow occlusion, postoperative complications, and costs. Results:The clamp crushing technique had the highest transection velocity (3.9 ± 0.3 cm2/min) and lowest blood loss (1.5 ± 0.3 mL/cm2) compared with CUSA (2.3 ± 0.2 cm2/min and 4 ± 0.7 mL/cm2), Hydrojet (2.4 ± 0.3 cm2/min and 3.5 ± 0.5 mL/cm2), and dissecting sealer (2.5 ± 0.3 cm2/min and 3.4 ± 0.4 mL/cm2) (velocity: P = 0.001; blood loss: P = 0.003). Clamp crushing technique was associated with the lowest need for postoperative blood transfusions. The degree of postoperative reperfusion injury and complications were not significantly different among the groups. The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 &U20AC; to 2400 &U20AC; per case. Conclusions:The clamp crushing technique was the most efficient device in terms of resection time, blood loss, and blood transfusion frequency compared with CUSA, Hydrojet, and dissecting sealer, and proved to be also the most cost-efficient device.

Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study.

Objective:To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS) on major hepatectomy. Summary Background Data:While steatosis of a liver graft is an established risk factor in transplantation, its impact on major hepatectomy remains unclear. Methods:Fifty-eight steatotic patients who underwent major hepatectomy were matched 1:1 with patients with normal liver according to age, gender, ASA score, diagnosis, extent of hepatectomy, and need of hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively. Primary endpoints were mortality and complications. Results:Pure MaS and MiS were present in only 10 and 3 patients, respectively, while mixed steatosis was noted in 45 patients. Forty-four patients had mild (10%–30%) and 14 moderate/severe (>30%) steatosis. Steatotic patients had significantly higher serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased in steatotic patients. Complications were higher in steatotic patients when considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P = 0.001) complications. Patients with pure MaS had increased mortality (MaS: 20% vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS: 50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis was a highly significant risk factor for mortality in patients with hepatic steatosis. Conclusion:Steatosis per se is a risk factor for postoperative complications after major hepatectomy and should be considered in the planning of surgery. Caution must be taken to perform major hepatectomy in steatotic patients with preexisting cholestasis.

A Prospective, Randomized, Controlled Trial Comparing Intermittent Portal Triad Clamping Versus Ischemic Preconditioning With Continuous Clamping for Major Liver Resection

Objective:To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery. Summary Background Data:IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection. Methods:Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality. Results:Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30–75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm2 (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups. Conclusions:Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection.

Use of severely steatotic grafts in liver transplantation: a matched case-control study.

Background:Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers. Methods:We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers. Results:During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%–100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (≥21 days) and hospital (≥40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient. Conclusion:Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.

Simultaneous colorectal and hepatic resections for colorectal cancer: postoperative and longterm outcomes

BACKGROUND Our goal was to analyze the results of resection of colorectal cancer and liver metastases in one procedure. STUDY DESIGN Between June 1982 and July 1998, 522 patients underwent liver resection for colorectal metastases. Liver resection was performed simultaneously with colorectal resection in 71 cases, representing the population in this study. Morbidity, mortality, overall survival, and disease-free survival times were analyzed. Median followup time was 29 months (range 6 to 162 months). Prognostic factors and their influence on outcomes were analyzed. RESULTS The median hospital stay was 8 days (range 5 to 23 days). Morbidity was 21% and included nine pleural effusions, seven wound abscesses, four instances of hepatic failure, three systemic infections, three intraabdominal abscesses, and one colonic anastomosis leakage. Operative mortality was 0%. Recurrence rate was 57.7% (41 or 71), and progression of disease was detected in 33.8%. Overall and disease-free survivals at 1, 3, and 5 years were 88%, 45%, and 38% and 67%, 17%, and 9%, respectively. Prognostic factors with notable influence on patient outcomes were nodal stage as per TNM classification, number of liver metastases, diameter (smaller or larger than 5 cm), liver resection specimen weight (lighter or heavier than 90 g), and liver resection margin (smaller or larger than 1 cm). CONCLUSIONS Simultaneous resection of colorectal cancer and liver metastases can be performed with low morbidity and mortality rates, avoiding a second surgical procedure.

Surgical therapy of hepatocellular carcinoma

There is no worldwide consensus of an algorithm for the radical treatment of hepatocellular carcinoma (HCC). Surgical resection, liver transplantation and, recently, local ablation therapies achieve high curative rates in selected patients. However, recurrence of HCC remains a major problem. This review provides an overview of the current surgical treatment options available for patients with HCC.

Understanding the meaning of fat in the liver

The most impor-tantdeterminantsinrecipientoutcomeafterLDLTarethe careful selection of living donor and recipient, andthe technical skill and experience of the surgical team.While the use of marginal cadaveric donor livers is anappropriatestrategytoincreasethenumberofavailablegrafts for transplantation, only perfect “or almost per-fect” livers can be used in LDLT, because a healthyliving donor is concomitantly placed at risk. The pres-ence of any kind of hepatitis, fibrosis, and moderate /severesteatosisareabsolutecontraindicationsforlivingdonation in most centers. However, whether potentialdonor with mild steatosis ( 30% steatosis) should bedenied from donation remains controversial.Steatosis is increasingly prevalent in most societies,and is mainly related to obesity.

Nitric oxide synthase activity in the splanchnic vasculature of patients with cirrhosis: relationship with hemodynamic disturbances.

BACKGROUND/AIMS It has been demonstrated that an overproduction of nitric oxide plays an important role in the pathogenesis of the hyperdynamic circulation exhibited by cirrhotic patients. Nevertheless, evidence is supported by studies performed in experimental models or by indirect measurements in humans. The purpose of this study has been to evaluate nitric oxide production in splanchnic vasculature of patients with cirrhosis and to investigate its possible relationship with systemic and splanchnic hemodynamics. METHODS Nitric oxide synthase (NOS) activity was measured in hepatic artery and portal vein tissues of nine cirrhotic patients. Samples were obtained during liver transplantation. Control samples were obtained simultaneously from the corresponding tissues of the liver donors. Hemodynamic parameters were determined with Doppler ultrasonography. RESULTS NOS activity was significantly higher in hepatic artery of cirrhotic patients than in controls (8.17 +/- 1.30 vs 4.57 +/- 0.61 pmoles/g of tissue/min, P < 0.05). Patients with ascites showed a higher hepatic artery NOS activity than patients without ascites. Highly significant correlation was observed between cardiac output and hepatic artery NOS activity as well as between portal blood flow and hepatic artery NOS activity. CONCLUSIONS The present study demonstrates an enhanced production of nitric oxide in the splanchnic vasculature of patients with cirrhosis.

Extremely Marginal Liver Grafts From Deceased Donors Have Outcome Similar to Ideal Grafts

BACKGROUND Although there is a worldwide need to expand the donor pool, many cadaveric marginal livers are usually discarded for transplantation. Herein, we report the outcome of a series of patients receiving marginal grafts. METHODS We analyzed all patients who underwent liver transplantation in our unit from August 2006 to March 2011 (n = 125) with the use of a prospectively collected database. Patients with ≥3 of donor (prolonged hypotensive episodes, donor age >55 years, high vasopressor drug requirement, hypernatremia, prolonged intensive care unit stay, elevated transaminases) and graft-related (cold ischemia >12 hours, warm ischemia time >40 minutes and steatosis >30%) extended criteria were defined as extremely marginal liver grafts (EMLG). The outcomes of patients receiving EMLG were compared with the recipients of grafts without any marginal criteria (ideal grafts). RESULTS The EMLG group (n = 36) showed higher operative transfusion requirement (66.6% vs 55.6%) as well as 30-day (11.1% vs 55%) and 1-year (22.2% vs 5.5%) mortality rates, compared with the ideal grafts group (n = 18) but without a significant difference. Other variables, such as major complications, postoperative hemodialysis, ICU and hospital stay, and 1-year survival also were not significantly different. CONCLUSIONS The liver pool can be safely expanded using EMLG from deceased donors for liver transplantation. These usually discarded liver grafts showed similar early and long-term outcomes compared with ideal organs.