William C. Chapman

Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma

Our goal was to evaluate fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging patients with biliary tract cancers. Fifty consecutive patients who underwent FDG-PET for suspected cholangiocarcinoma (n = 36) or gallbladder carcinoma (n = 14) were reviewed. Patients with cholangiocarcinoma were divided into two groups: group 1 had nodular type (mass > 1 cm) (n = 22) and group 2 had inflltrating type (n = 14) cholangiocarcinoma. Thirty-one of 36 patients evaluated for cholangiocarcinoma had cholangiocarcinoma and five did not. Sensitivity was 85% for nodular morphology but only 18% for inflltrating morphology. Sensitivity for metastases was 65% but false negative for carcinomatosis in three of three patients. One false positive result occurred in a patient with primary sclerosing cholangitis who had acute cholangitis. Seven (58%) of 12 patients had FDG uptake along the tract of a biliary stent. FDG-PET led to a change in surgical management in 30% (11 of 36) of patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases. Eleven of 14 patients with gallbladder carcinoma were newly diagnosed by cholecystectomy or another type of exploratory procedure, whereas three patients were undergoing follow-up. Nine had residual gallbladder carcinoma at the time of PET. Sensitivity for gallbladder carcinoma was 78%. Sensitivity for extrahepatic metastases was 50% in eight patients; six of them had carcinomatosis. These data suggest that PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass > 1cm) but was not helpful for the inflltrating type. PET was also helpful for detecting residual gallbladder carcinoma following cholecystectomy, but was not helpful in patients with carcinomatosis. Although FDG-PET led to a change in management in 30% of patients with cholangiocarcinoma, it must be interpreted with caution in patients with primary sclerosing cholangitis and with stents in place, as well as in those with known granulomatous disease.

Positron Emission Tomography to Stage Suspected Metastatic Colorectal Carcinoma to the Liver

BACKGROUND Accurate detection of recurrent colorectal carcinoma remains a clinical challenge. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) is an imaging technique that allows direct evaluation of cellular metabolism. 18F-fluorodeoxyglucose PET was compared to computed tomography (CT) and CT portography for staging metastatic colorectal carcinoma. PATIENTS AND METHODS Twenty-four patients previously treated for colorectal carcinoma who had suspected recurrence to the liver underwent an 18FDG PET scan of the entire body. All patients had either a CT scan of the abdomen (n = 17), a CT portogram (n = 18), or both (n = 11). The final diagnosis was obtained by tissue pathology in 19 patients and clinical follow-up in 5 patients. RESULTS A total of 60 suspicious lesions were identified. Of the 55 intrahepatic lesions, 39 were malignant and 16 were benign. Of the 5 extra-hepatic lesions, 4 were malignant. The 18FDG PET imaging had a higher accuracy (93%) than CT and CT portography (both 76%) in detecting metastatic disease to the liver, and detected unsuspected extrahepatic recurrence in 4 patients. Although the sensitivity of 18FDG PET (90%) was slightly lower than that of CT portography (97%), the specificity was much higher (100% versus 9%), including postsurgical sites. 18FDG PET altered surgical plans in 6 (25%) of 24 patients. CONCLUSIONS 18FDG PET is extremely useful in staging patients with suspected metastatic colorectal carcinoma to the liver.

Repeat hepatic surgery for colorectal cancer metastasis to the liver.

OBJECTIVE The authors addressed whether a repeat hepatic operation is warranted in patients with recurrent isolated hepatic metastases. Are the results as good after second operation as after first hepatic operation? SUMMARY BACKGROUND DATA Five-year survival after initial hepatic operation for colorectal metastases is approximately 33%. Because available alternative methods of treatment provide inferior results, hepatic resection for isolated colorectal metastasis currently is well accepted as the best treatment option. However, the main cause of death after liver resection for colorectal metastasis is tumor recurrence. METHODS Records of 95 patients undergoing initial hepatic operation and 10 patients undergoing repeat operation for isolated hepatic metastases were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. The literature on repeat hepatic resection for colorectal metastases was reviewed. RESULTS The mean interval between the initial colon operation and first hepatic resection was 14 months. The mean interval between the first and second hepatic operation was 17 months. Operative mortality was 0%. At a mean follow-up of 33 +/- 27 months, survival in these ten patients was 100% at 1 year and 88% +/- 12% at 2 years. Disease-free survival at 1 and 3 years was 60% +/- 16% and 45% +/- 17%, respectively. After second hepatic operation, recurrence has been identified in 60% of patients at a mean of 24 +/- 30 months (median 9 months). Two of these ten patients had a third hepatic resection. Survival and disease-free survival for the 10 patients compared favorably with the 95 patients who underwent initial hepatic resection. CONCLUSIONS Repeat hepatic operation for recurrent colorectal metastasis to the liver yields comparable results to first hepatic operations in terms of operative mortality and morbidity, survival, disease-free survival, and pattern of recurrence. This work helps to establish that repeat hepatic operation is the most successful form of treatment for isolated recurrent colorectal metastases.

Acute lung injury after hepatic cryoablation: Correlation with NF-κB activation and cytokine production

Background: Previous clinical reports have documented multisystem organ injury after hepatic cryoablation. We hypothesized that hepatic cryosurgery, but not partial hepatectomy, induces a systemic inflammatory response characterized by distant organ injury and overproduction of nuclear factor κB (NF-κB)–dependent, proinflammatory cytokines. Methods: In this study, rats underwent either cryoablation of 35% of liver parenchyma or a similar resection of left hepatic tissue. Serum tumor necrosis factor-α and macrophage inflammatory protein-2 levels and NF-κB activation were assessed by electrophoretic mobility shift assay at 30 minutes 1, 2, 6, and 24 hours after either procedure. Results: Cryoablation of 35% of liver (n = 22 rats) resulted in lung injury and a 45% mortality rate within 24 hours of surgery, whereas 7% treated with 35% hepatectomy (n = 15 rats) died during the 24 hours after surgery (P < .05, cryoablation vs hepatectomy). Serum tumor necrosis factor-α and macrophage inflammatory protein-2 levels were markedly increased in rats (n = 10 rats) 1 hour after hepatic cryoablation compared with rats that underwent partial hepatectomy (P < .005). We evaluated NF-κB activation by electrophoretic mobility shift assay in nuclear extracts of liver and lung after cryosurgery and found that NF-κB activation was strikingly increased in the liver but not the lung at 30 minutes and in both organs 1 hour after cryosurgery, and returned to baseline in both organs by 2 hours. In rats undergoing 35% hepatectomy, no increase in NF-κB activation was detected in nuclear extracts of either liver or lung at any time point. Conclusions: These data show that hepatic cryosurgery results in systemic inflammation with activation of NF-κB and increased production of NF-κB–dependent cytokines. Our data suggest that lung injury and death in this animal model is mediated by an exaggerated inflammatory response to cryosurgery. (Surgery 1999:126:518-26.)

Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. METHODS In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. RESULTS During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Childs classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. CONCLUSIONS TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Hepatic cryoablation-induced multisystem injury: Bioluminescent detection of NF-κB activation in a transgenic mouse model

Hepatic injury from cryoablation has been associated with multisystem injury, including adult respiratory distress syndrome, renal insufficiency, and coagulopathy; but the responsible mechanisms have not been well defined. In the present study we investigated the role of the transcription factor NF-kB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-kB activity. Using transgenic mice expressing photinus luciferase under the control of the 5′ HIV-LTR (an NF-KB-dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-kB activity. Luciferase production was determined by in vivo bioluminescence and by luciferase assays of tissue homogenates. After measurement of basal luciferase activity, mice were treated with 35% hepatic cryoablation or sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from the liver, lungs, and kidneys was measured at multiple time points. Hepatic cryoablation induced a significant increase in photon emission by the liver, lungs, and kidneys, which correlated with markedly increased luciferase activity measured from each organ after death. Lung lavage 4 hours after cryoablation showed neutrophilic lung inflammation with increased MIP-2 levels compared with sham surgery. These findings demonstrate that 35% hepatic cryoablation is associated with NF-kB activation in the remnant liver and multiple distant sites, and may be causally related to the multisystem injury that is seen after direct liver injury.

Water warming garment versus forced air warming system in prevention of intraoperative hypothermia during liver transplantation: a randomized controlled trial [ISRCTN32154832].

BackgroundThe authors compared two strategies for the maintenance of intraoperative normothermia during orthotopic liver transplantation (OLT): the routine forced-air warming system and the newly developed, whole body water garment.MethodsIn this prospective, randomized and open-labelled study, 24 adult patients were enrolled in one of two intraoperative temperature management groups during OLT. The water-garment group (N = 12) received warming with a body temperature (esophageal) set point of 36.8°C. The forced air-warmer group (N = 12) received routine warming therapy using upper- and lower-body forced-air warming system. Body core temperature (primary outcome) was recorded intraoperatively and during the two hours after surgery in both groups.ResultsThe mean core temperatures during incision, one hour after incision and during the skin closing were significantly higher (p < 0.05, t test with Bonferroni corrections for the individual tests) in the water warmer group compared to the control group (36.7 ± 0.1, 36.7 ± 0.2, 36.8 ± 0.1 vs 36.1 ± 0.4, 36.1 ± 0.4, 36.07 ± 0.4°C, respectively). Moreover, significantly higher core temperatures were observed in the water warmer group than in the control group during the placement of cold liver allograft (36.75 ± 0.17 vs 36.09 ± 0.38°C, respectively) and during the allograft reperfusion period (36.3 ± 0.26 vs 35.52 ± 0.42°C, respectively). In addition, the core temperatures immediately after admission to the SICU (36.75 ± 0.13 vs 36.22 ± 0.3°C, respectively) and at one hr (36.95 ± 0.13 vs 36.46 ± 0.2°C, respectively) were significantly higher in the water warmer group, compared to the control group, whereas the core temperature did not differ significantly afte two hours in ICU in both groups.ConclusionsThe investigated water warming system results in better maintenance of intraoperative normothermia than routine air forced warming applied to upper- and lower body.

Effects of hepatitis C virus infection and its recurrence after liver transplantation on functional performance and health-related quality of life

Our aim was to examine the effects of hepatitis C virus (HCV) infection, a leading cause of end-stage liver disease, and its recurrence after liver transplantation on functional performance and health-related quality of life. Functional performance, liver function, and HCV recurrence were assessed longitudinally in 75 adult transplant recipients (28 with HCV). Quality of life was reported once after transplantation. Functional performance improved through year 2 (P < 0.001) and then declined in those with HCV, whereas the others remained stable (P = 0.05). Time had a positive effect (β = 0.22, P = 0.05) and HCV infection had a negative effect (β = —0.28, P = 0.01) on post-transplant functional performance. Educational level (β = 0.24, P < 0.05) and recent functional performance (β = 0.31, P = 0.01) had positive effects on quality of life. HCV recurrence was associated with relatively poorer pretransplant functional performance, a greater rate of improvement through month 3 (P < 0.05), and abnormal transaminase values between years 1 and 2 (P < 0.001). Rehospitalization for recurrent HCV was associated with reduced functional performance (P < 0.05). Functional performance improves with time following liver transplantation, but HCV infection exerts an opposing and comparably strong effect. Post-transplant functional performance, in turn, directly affects post-transplant quality of life. Severe, recurrent HCV illness is associated with reduced functional performance.

Systemic nf-κB activation in a transgenic mouse model of acute pancreatitis

Abstract Background. Transcription factor NF-κB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-κB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model. Materials and methods. Using transgenic mice expressing photinus luciferase controlled by an NF-κB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-κB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid. Results. Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P Conclusion. In this model, NF-κB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.

Technical advances toward interactive image-guided laparoscopic surgery

AbstractBackground: Laparoscopic surgery uses real-time video to display the operative field. Interactive image-guided surgery (IIGS) is the real-time display of surgical instrument location on corresponding computed tomography (CT) scans or magnetic resonance images (MRI). We hypothesize that laparoscopic IIGS technologies can be combined to offer guidance for general surgery and, in particular, hepatic procedures. Tumor information determined from CT imaging can be overlayed onto laparoscopic video imaging to allow more precise resection or ablation. Methods: We mapped three-dimensional (3D) physical space to 2D laparoscopic video space using a common mathematical formula. Inherent distortions present in the video images were quantified and then corrected to determine their effect on this 3D to 2D mapping. Results: Errors in mapping 3D physical space to 2D video image space ranged from 0.65 to 2.75 mm. Conclusions: Laparoscopic IIGS allows accurate (<3.0 mm) confirmation of 3D physical space points on video images. This in combination with accurately tracked instruments and an appropriate display may facilitate enhanced image guidance during laparoscopy.