Differential Effects of Etomidate and Midazolam on Vascular Adenosine Triphosphate-sensitive Potassium Channels: Isometric Tension and Patch Clamp Studies

Background: The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity.

Methods: In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2[DELTA]C36 channels), and (4) mutant Kir6.2[DELTA]C36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2[DELTA]C36-K185Q channels).

Results: Etomidate (>= 10-6 m), but not midazolam (up to 10-6 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10-8 m; maximum inhibitory concentration: 1.22 x 10-4 m). Etomidate (>= 3 x 10-6 m), but not midazolam (up to 10-4 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10-5 m and 1.52 x 10-5 m, respectively. Etomidate (10-5 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2[DELTA]C36 channels, and Kir6.2[DELTA]C36-K185Q channels with equivalent potency.     

成人活体肝移植

活体肝移植（LDLT）最初作为一种降低等待做肝移植患者死亡率的方法。日本京都大学LDLT开始于1990年6月,移植例数逐年增加,临床应用范围从小儿扩展到成人。肝脏右叶移植物的应用在LDLT具有重要临床意义,已经成为成人间LDLT标准方法。由于肝脏右叶移植物在LDLT移植后成功应用,近年来成人LDLT例数显著增加,自1990年6月至2005年12月,京都大学附属病院已完成了1140例LDLT手术,其中包括477例成人LDLT手术（年龄大于18岁）。HBV和HCV相关性肝硬化和肝癌是LDLT最常见的适应证,截至2005年12月,随访统计结果表明成人LDLT术后总的5年生存率为69．1％。     

Long-Term Characteristics of 5-Year Survivors After Liver Resection for Colorectal Metastases

Background We investigated factors affecting 5-year survival in patients undergoing hepatic resection for colorectal cancer metastases, including events long after initial hepatectomy. Although retrospective studies have demonstrated survival benefit of hepatectomy for metastatic colorectal cancer, few have included sufficient 5-year survivors to identify survival-related factors throughout the clinical course. Methods We divided 156 patients with hepatectomy for colorectal cancer metastases into 5-year survivors (n = 64) and patients dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were compared retrospectively with respect to long-term outcome. Results By multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P = .011), short tumor doubling time (1.809; P = .026), and origin from poorly differentiated primary adenocarcinoma (12.632; P = .001) compromised survival, whereas initial treatment-related variables did not. Although no difference was seen in initial treatment-related variables between 5-year survivors with recurrence after hepatectomy and patients dying before 5 years, repeat surgery was used more frequently in survivors (P < .001), typically with adjuvant chemotherapy. Conclusions Reoperations for each recurrence of metastases, followed by additional chemotherapy, frequently resulted in long survival.     

Novel technique of overlaying a poly-l-lactic acid nanosheet for adhesion prophylaxis and fixation of intraperitoneal onlay polypropylene mesh in a rabbit model

Background

One problem with polypropylene mesh (PPM) used to repair abdominal wall hernias is dense adhesions to the visceral surface. The authors developed the biocompatible poly-l-lactic acid (PLLA) nanosheet (thickness?Methods The PLLA nanosheet was fabricated by the spin-coating method and peeling technique with polyvinyl alcohol (PVA) as a supporting film. Two 1.5-cm-square pieces of mesh were implanted on each peritoneal side of the midline incision. The mesh was fixed to the peritoneum with a suture and then overlaid with a 4-cm-square piece of Seprafilm or nanosheet. To examine the fixative property, mesh was overlaid with Seprafilm or nanosheet without a fixed suture. After 4?weeks, mesh adhesion, inflammatory reaction, fixation, and dislocation of mesh were evaluated.

Results

Nanosheet-overlaid meshes were flexible and fit over the peritoneum. Adhesion was observed in 10% of the nanosheet-overlaid meshes and in 50% of the Seprafilm-overlaid meshes. The adhesion tenacity grade was significantly lower with the nanosheet-overlaid meshes (0.1?±?0.1) than with the Seprafilm-overlaid meshes (1.0?±?0.4) (p?=?0.029), and the percentage of the adhesion area also was lower with the nanosheet-overlaid meshes (1.0?±?1.0% vs 8.5?±?3.2%; p?=?0.037). The mean inflammatory cell counts were lower with the nanosheet-overlaid meshes (p?=?0.0023). Regarding the fixative property, 37.5% of the nanosheet-overlaid meshes were fixated on the peritoneum, but no Seprafilm-overlaid mesh was fixated.

Conclusion

Overlaying of a PLLA nanosheet was effective for adhesion prophylaxis of intraperitoneal mesh. It also may have a possible beneficial effect on fixation of mesh.     

Human herpesvirus 6 infection in adult living related liver transplant recipients.

To analyze human herpesvirus 6 (HHV-6) infection in adult living related liver transplantation, we performed a virological analysis, including viral isolation, serological assay, and real-time polymerase chain reaction, of serially collected blood samples from 67 recipients. In addition, cytokine levels were measured to determine their role in viral reactivation. HHV-6 was isolated from only 4 recipients (6.0%), and viral DNA was detected in 15 (22.4%) of the 67 recipients. A significant increase in HHV-6 immunoglobulin G antibody titers was observed in 19 (28.4%) of the 67 recipients. Finally, 26 recipients (38.8%) had HHV-6 reactivation 2-6 weeks after transplantation. HHV-6 associated clinical features were analyzed in the 17 recipients presenting with either viremia or DNAemia. Two recipients with viremia and 3 recipients with DNAemia had unexplained fever at the time of viral infection. An increase in aminotransferase levels was observed in 2 recipients with viremia and 3 recipients with DNAemia. Recipients with liver cirrhosis caused by hepatitis B virus or hepatitis C virus infection as the underlying disease were more likely to have HHV-6 infection (P = 0.025). Mortality at the last follow-up in recipients with HHV-6 reactivation was significantly higher than in those without viral reactivation (P = 0.0118). Plasma interleukin-6 levels were significantly higher in the recipients with HHV-6 viremia than in the recipients without viremia at 4 weeks post-transplant (P = 0.0411). Moreover, tumor necrosis factor alpha levels were also higher in recipients with HHV-6 viremia (P < 0.0001) or reactivation (P = 0.0011) than in recipients without viremia or reactivation 4 weeks post-transplant.     

Surgical resection of primary liposarcoma of the anterior mediastinum.

We report on the rare and surgical treatment of a case of primary mediastinal liposarcoma. A 64-year-old male complained of hoarseness for one month and was admitted to our hospital because of an abnormal shadow, which was postulated to be an anterior mediastinal tumor on a chest computed tomography (CT) scan. Horizontal T1-weighted magnetic resonance imaging (MRI) showed an anterior mediastinal round mass with a signal intensity similar to that of subcutaneous fat, which was 6.5 cm in diameter. An operation similar to extended thymectomy was perfomed through a median sternotomy. Histological examination of the resected specimen revealed that the tumor was composed of well-differentiated liposarcoma and pleomorphic malignant fibrous histiocytoma and the tumor was diagnosed as a de-differentiated liposarcoma. We discuss it with reference to a collective review of the Japanese literature for surgical cases of primary liposarcoma of the mediastinum.     

Long-term control or possible cure? Treatment of stage D2 prostate cancer under chemotherapy using cisplatin and estramustine phosphate followed by maximal androgen blockade

Metastatic prostate cancer (PC) is incurable by androgen deprivation therapy alone, due to the presence of androgen-independent/supersensitive cells in hormone-naive PC. A 67-year-old man was diagnosed with PC (Gleason score, 5 + 4) with multiple bone metastases. He was treated by chemohormonal therapy with cisplatin and estramustine phosphate (EMP) followed by maximal androgen blockade, and showed a complete response. As of the time of writing, no clinical or prostate-specific antigen recurrence has been observed for over 15 years, despite cessation of the treatment. This is the first report to indicate a possible cure of metastatic PC by chemohormonal therapy combined with appropriate anti-tumor drugs targeted to both androgen-independent and -dependent clones before the hormone-refractory state.     

Retroportal Hepaticojejunostomy for Extended Resection of Hilar Bile Ducts

High hepatic duct resection sometimes is unavoidable in achieving curative resection of hilar cholangiocarcinoma, as tumor cells can extend further than expected along the bile ducts from the macroscopically evident cancer. In patients undergoing left hemihepatectomy with caudate lobectomy whose bile duct must be severed at the subsegmental bile duct levels, the orifices of the posterior bile ducts would lie behind the right portal vein. Conventional hepaticojejunostomy would be risky in such cases because an anastomosis performed in the usual manner would be subjected to strain. Instead, between 2002 and 2004, three patients underwent retroportal hepaticojejunostomy using a jejunal limb mobilized and positioned behind the hepatoduodenal ligament. Primary tumors were classified as type IV in the Bismuth–Corlette classification. Tension-free hepaticojejunal anastomosis was performed successfully in all three patients; insufficiency of the hepaticojejunostomy did not develop. Neither early nor late complications directly related to this method occurred. Retroportal hepaticojejunostomy, thus, permits more peripheral resection of the hepatic duct while providing a sufficient operative field for safe, tension-free anastomosis. This technique is very useful for patients undergoing left hemihepatectomy requiring high hilar resection of the bile duct.     

Roles of Carbon Monoxide in Leukocyte and Platelet Dynamics in Rat Mesentery during Sevoflurane Anesthesia

Background: Heme oxygenase 1 (HO-1), induced by a variety of stressors, provides endogenous carbon monoxide (CO) and bilirubin, both of which play consequential roles in organs. The current study aimed to examine whether induction of HO-1 and its by-products modulated endothelial interaction with circulating leukocytes and platelets evoked by sevoflurane anesthesia in vivo.

Methods: Rats, pretreated with or without hemin, were anesthetized with sevoflurane in 100% O2, and lungs were mechanically ventilated. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized during sevoflurane anesthesia at 1,000 frames/s using intravital ultrahigh-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on leukocyte and platelet behavior, these studies were repeated with superfusion of either CO, bilirubin, or N[omega]-nitro-l-arginine methyl ester (l-NAME).

Results: As reported previously, the elevation of sevoflurane concentration evoked adhesive responses of leukocytes, concurrent with platelet margination and rolling. Pretreatment with hemin, a HO-1 inducer, prevented such sevoflurane-elicited changes in the microvessels. These changes were restored by zinc protoporphyrin IX, a HO inhibitor, and repressed by CO but not by bilirubin. During sevoflurane anesthesia, however, nitric oxide suppression by l-NAME deteriorated microvascular flows irrespective of the presence or absence of the HO-1 induction.     

Ultrasound-guided radiofrequency thermal ablation of liver tumors: Percutaneous, laparoscopic, and open surgical approaches

Only 10% to 20% of patients with primary and colorectal metastatic liver tumors are candidates for curative surgical resection. Even after curative treatment, tumors recur commonly in the liver. As a less invasive therapy, radiofrequency thermal ablation (RFA) of primary, metastatic, and recurrent liver tumors was performed under percutaneous, laparoscopic, or open intraoperative ultrasound guidance. The safety and local control efficacy of RFA were investigated. RFA was performed mostly in patients with unresectable hepatomas or metastatic liver tumors. Patients with large tumors, major vessel or bile duct invasion, limited extrahepatic metastases, or liver dysfunction were not excluded. An RFA system with a 15-gauge electrode-cannula with four-pronged retractable needles was used. All patients were followed for more than 8 months to assess morbidity and mortality, and to determine tumor recurrence. Sixty RFA operations were performed in 46 patients: 11 patients underwent repeat RFA once or twice. A total of 204 tumors were treated: 70 hepatomas and 134 metastatic tumors. Tumor size ranged from 5 mm to 180 mm (mean 36 mm). RFA was performed in 29 operations for 81 tumors percutaneously, in seven operations for 14 tumors laparoscopically, and in 24 operations for 109 tumors by open surgery. Combined colorectal resection was carried out in five operations and combined hepatic resection was carried out in three operations. There was one death (1.7%) from liver failure, and there were three major complications (5%): one case of bile leakage and two biliary strictures due to thermal injury. There were no intra-abdominal infectious or bleeding complications. The length of hospital stay ranged from 0 to 2, 1 to 3, and 4 to 7 days for percutaneous, laparoscopic, and open surgical RFA, respectively. During a mean follow-up period of 20.5 months, local tumor recurrence at the RFA site was diagnosed in 18 (8.8%) of 204 tumors. The risk factors for local recurrence included large tumor size and major vessel invasion: recurrence rates for tumors less than 4 cm, 4 to 10 cm, and greater than 10 cm, and for those with vessel invasion were 3.3%, 14.7%) 50%) and 47.8%) respectively. Ten of 18 tumors recurring locally were retreated by RFA, and eight of them showed no further recurrence. Ultrasound-guided RFA is a relatively safe, well-tolerated, and versatile treatment option that offers excellent local control of primary and metastatic liver tumors. The appropriate use of percutaneous, laparoscopic, and open surgical RFA is beneficial in the management of patients with liver tumors in a variety of situations.