Effect of Interstitial Laser Hyperthermia in a Murine Model of Colorectal Liver Metastases: Scanning Electron Microscopic Study

Interstitial laser hyperthermia (ILH) is an in situ ablative technique used to treat colorectal liver metastases. The relatively high recurrence of tumor after treatment by ILH may be related to incomplete destruction. Little is known about the effectiveness of ILH for destroying tumor microvasculature. The aim of this study was to define the changes to the microvascular architecture of tumors after treatment with ILH, specifically focusing on the completeness of tumor vasculature destruction. An intrasplenic induction model of liver metastases in 4- to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to liver and tumor tissue using a bare optical quartz fiber from a Medilas Fibertom 4100 Nd:YAG surgical laser generator. The animals underwent microvascular corrosion casting of the livers immediately after application of ILH. Microvascular casts were then prepared and studied by scanning electron microscopy. ILH produced complete, uniform destruction of the tumor microvasculature with compete hemostasis. Blood flow in vessels larger than 100 m diameter had a relatively protective effect, although ILH was able to overcome this barrier effectively by increasing the energy applied. ILH produces complete destruction of tumor microvasculature with hemostasis. The protective effect of blood flow in larger vessels can be overcome by the appropriate use of higher energy levels.     

Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine

1 Voltage-gated Na+ channels are transmembrane proteins that are essential for the propagation of action potentials in excitable cells. Nav1.7 and Nav1.8 dorsal root ganglion Na+ channels exhibit different kinetics and sensitivities to tetrodotoxin (TTX). We investigated the properties of both channels in the presence of lidocaine, a local anesthetic (LA) and class I anti-arrhythmic drug. 2 Nav1.7 and Nav1.8 Na+ channels were coexpressed with the beta1-subunit in Xenopus oocytes. Na+ currents were recorded using the two-microelectrode voltage-clamp technique. 3 Dose-response curves for both channels had different EC50 (dose producing 50% maximum current inhibition) (450 microm for Nav1.7 and 104 microm for Nav1.8). Lidocaine enhanced current decrease in a frequency-dependent manner. Steady-state inactivation of both channels was also affected by lidocaine, Nav1.7 being the most sensitive. Only the steady-state activation of Nav1.8 was affected while the entry of both channels into slow inactivation was affected by lidocaine, Nav1.8 being affected to a larger degree. 4 Although the channels share homology at DIV S6, the LA binding site, they differ in their sensitivity to lidocaine. Recent studies suggest that other residues on DI and DII known to influence lidocaine binding may explain the differences in affinities between Nav1.7 and Nav1.8 Na+ channels. 5 Understanding the properties of these channels and their pharmacology is of critical importance to developing drugs and finding effective therapies to treat chronic pain.     

Hyperbaric oxygen therapy for severe acute pancreatitis

Despite improvements in the supportive management of severe acute pancreatitis over the last decade, the morbidity and mortality rate remains high. The main feature of this condition is pancreatic necrosis leading to sepsis, with both localized and systemic inflammatory response syndromes. Early pathophysiological changes of the pancreas include alterations in microcirculation, ischemia reperfusion injury, and leukocyte and cytokine activation. The efficacy of hyperbaric oxygen (HBO) therapy in improving these pathophysiological disturbances is documented for various conditions. However, its effect in the treatment of severe acute pancreatitis is undetermined. This report documents the case of a 56-year-old woman presenting with severe acute pancreatitis treated by HBO therapy. The severity of disease was based on an Acute Physiology and Chronic Health Evaluation (APACHE II) illness grading score of 11 and a Baltazar based computed tomography severity index (CTSI) score of 9. Administration of 100% oxygen was commenced within 72 h of presentation at a pressure of 2.5 atmospheres for 90 min and given twice daily for a total of 5 days. Therapy was well tolerated with improvements in APACHE II and CTSI grading scores. HBO therapy for severe acute pancreatitis appeared to be safe and may have a role in improving treatment outcomes. Further study is required.     

Outcomes after identical and compatible orthotopic liver transplantation for fulminant hepatic failure: a single center experience in UK

To analyze the outcomes between identical and compatible liver transplantation (OLT) for fulminant hepatic failure (FHF) from September 1984 to November 2005. The patients were divided in three groups; group 1 (identical), group 2 (compatible) and group 3 (incompatible), according to the donor-recipient blood type matching. We analyzed several outcomes regarding mortality, patient and graft survival, incidence of acute graft rejection during the first postoperative month (30 days), incidence of biliary complications and indications of re-transplantation. We also analyzed the relationship of Coomb's positive test with postoperative hemolysis to all the above mentioned factors. During the study period, 168 males and 112 females underwent their first OLT for FHF, with 37.1% overall mortality and 42.1% overall graft failure rate. The results between group 1 (203 patients) and group 2 (73 patients) were comparable. A statistically significant difference was recorded in 1 year and overall graft survival between group 1 and group 2 (P = 0.049 and log-rank = 0.035 respectively). Coomb's positive test did not influence the outcomes. OLT in FHF can be safely carried out whether the donor organs are identical or compatible. Hemolysis (Coomb's positive test) after identical or compatible OLT does not influence the outcomes.     

The effect of hyperbaric oxygen on apoptosis and proliferation in severe acute pancreatitis

Objectives:

This paper investigates the significance of apoptosis in severe acute pancreatitis (SAP) and the possible modulating effects of hyperbaric oxygen (HBO).

Methods:

Wistar rats (250–350 g) were induced with SAP by biliopancreatic infusion of 4% sodium taurocholate. Rats were randomized for HBO treatment. Pancreatic tissue was stained for apoptosis with immunohistochemistry (anti-CASPASE-3 antibody and TUNEL), and histopathology haematoxylin and eosin (H&E). Acini were stained for proliferation with an anti-KI67 antibody. ImageProPlus was used to quantify apoptosis and proliferation in acinar cells. Statistical analysis was performed with two-independent-sample t-test or non-parametric Mann–Whitney test.

Results:

In normal acini there is a low rate of apoptosis (0.165 ± 0.157%, 0.181 ± 0.168%, 0.130 ± 0.298% in CASPASE-3, H&E and TUNEL, respectively) and proliferation (0.951 ± 0.926%) (mean ± standard deviation [SD]). When compared with normal, apoptosis (CASPASE-3: 1.28 ± 1.12%, P= 0.008; 2.40 ± 3.04%, P= 0.101; 1.23 ± 0.87%, P= 0.091; H&E: 0.47 ± 0.36%, P= 0.051; 0.69 ± 0.63%, P= 0.001; 0.68 ± 0.28%, P= 0; TUNEL: 1.08 ± 1.42%, P= 0; 1.96 ± 1.87%, P= 0; 2.36 ± 2.26%, P= 0) and proliferation (1.96 ± 1.89%, P= 0.187; 1.73 ± 1.76%, P= 0.165; 1.36 ± 1.40%, P= 0.571) were increased on days 1, 2 and 3 post-induction, respectively. In comparison with the untreated controls, HBO increased apoptosis on day 1 (CASPASE-3: 3.11 ± 1.97%, P= 0.04; H&E: 0.97 ± 0.76%, P= 0.005) and day 2 (TUNEL: 3.61 ± 3.05%, P= 0.034). Treatment with HBO increased proliferation (3.04 ± 3.14%, P= 0.519; 7.33 ± 7.55%, P= 0.153) on days 2 and 3, respectively, compared with the untreated controls.

Conclusions:

During SAP, acini apoptosis and proliferation were increased. Hyperbaric oxygen therapy may improve the condition of SAP by promoting apoptosis and proliferation.     

Effect of interstitial laser hyperthermia in a murine model of colorectal liver metastases

Interstitial laser hyperthermia (ILH) is an in situ ablative technique used for the treatment of colorectal liver metastases. At present, few data exist concerning the optimum power settings required to maximize tissue necrosis.The aim of this study was to establish the dose-response relationship between the laser power setting and the extent of tissue necrosis produced in liver and tumor tissue, as well as the pattern of necrosis in a murine model of liver metastases. An intrasplenic induction model of liver metastases in 4- to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to liver and tumor tissue using a bare optical quartz fiber from a Laserex SLY500 Nd:YAG surgical laser generator. Two-watt and 5-watt power settings were used at specific time intervals. The livers were then excised, fixed in formalin, and the extent and degree of necrosis were measured. Results were expressed as mean ? standard deviation and were normally distributed. Analysis of variance was performed, and the least significant difference was used for post hoc tests. A P value of less than 0.05 was considered significant. Interstitial laser hyperthermia at 5 watts of power produced larger diameters of necrosis than did 2 watts for specific exposure times in normal liver tissue. However, when the total energy applied was compared, there was no significant difference in the diameters of tissue necrosis produced by the two power settings. The diameter of tissue necrosis in the normal liver increased from 2 mm at 10 joules to 8 mm at 600 joules of energy. Within tumor tissue, ILH at 2 and 5 watts produced similar diameters of necrosis for specific exposure times. When amounts of total energy applied were compared, ILH at the lower power setting (2 watts) produced a significantly larger diameter of necrosis than the higher power setting (5 watts). The diameter of necrosis achieved in tumor tissue was significantly larger than that in normal liver tissue at both power settings, for an equivalent amount of applied energy. The difference was more pronounced when ILH was performed at the lower power setting. The maximum diameter of necrosis achieved was 6.8 ± 0.7 mm in normal liver tissue and 7.7 ± 0.8 mm in tumor tissue. Charring of the fiber tip was delayed when the lower power setting was used, occurring after 20 seconds of exposure, compared to 5 seconds at the higher power setting. Similarly, cavitation occurred initially at 50 seconds at 5 watts of power and was delayed until 90 seconds of exposure at 2 watts of power. Histopathologic findings revealed an elliptical area of homogeneous necrosis, with a central acellular coagulum surrounded by intact but nonviable tissue. ILH is capable of producing highly reproducible, uniform, and complete tissue necrosis. The diameter of necrosis is related to the total energy applied. At low-power settings at any given amount of applied energy, a significantly larger diameter of tissue necrosis was achieved in tumor tissue compared to normal liver tissue.