I-Rue Lai

Randomized clinical trial of Ligasure™ versus conventional surgery for extended gastric cancer resection

The Ligasure™ Vessel Sealing System is a haemostatic device designed primarily for use in abdominal surgery. Randomized trials have demonstrated that it is safe and quick for haemorrhoidectomy, but there is no evidence that it confers any advantage in complicated gastrointestinal surgery. The aim of the present study was to examine the value of the Ligasure™ system in extended lymph node dissection (D2) during gastrectomy for cancer in a randomized clinical trial.

Transient limb ischemia induces remote preconditioning in liver among rats : The protective role of heme oxygenase-1

Background. We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats. Methods. The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured. Results. HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7±167.4 U L−1) when compared with controls (1297.7±729.3 U L−1) and RP+ ZnPP pretreated groups (1429.9±750.9 U L−1). The heme oxygenase activity in treated rats also correlated these results (286.8±34.3 pmol mg−1 protein hr−1 for the RP group, 156.3±27.5 pmol mg−1 protein hr−1 for the RP+ ZnPP pretreated group, and 170.6±19.4 pmol mg−1 protein hr−1 for the control group, 144.8±7.8 pmol mg−1 protein hr−1 for the control+ ZnPP pretreated group). Conclusion. Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.

Pharmacological Preconditioning With Simvastatin Protects Liver From Ischemia-Reperfusion Injury by Heme Oxygenase-1 Induction

Background. The protective role of heme oxygenase-1 (HO-1) against liver ischemia-reperfusion (I/R) injury in models of hypoxic and remote preconditioning has been proved. The feasible candidates who induce HO-1 and thorough which exert the protective effects are under investigation. The aim was to study the role of HO-1 in pharmacological preconditioning by simvastatin in a rat model. Methods. Pharmacological preconditioning by intraperitoneal injection of simvastatin (5 mg/kg) was tested on a partial liver I/R model on rats. The expression of HO-1 protein and enzyme activities in livers, serum alanine transaminase (ALT) levels, and TUNEL staining of liver after I/R injury were measured in rats with and without simvastatin preconditioning. Results. HO-1 was induced and persistently overexpressed in the hepatocytes 24 hr after simvastatin treatment. Simvastatin preconditioning diminished the elevation of serum ALT levels 4 hr after I/R injury (69.6±26.3 U/L) (P<0.05 vs. other groups) when compared with control (403.8±261.9 U/L) and zinc protoporphyrin (ZnPP)-pretreated (717.5±205.6 U/L) groups. Simvastatin preconditioning diminished the apoptosis after I/R injury as well (apoptosis index: 26.4±8 for Simvastatin, 78±7 for control, and 85.3±2 for ZnPP group; P<0.05). The addition of ZnPP negated the protective effects of simvastatin as evidenced in the ALT level (406.2±243.0 U/L) and apoptosis index (75.6±6). The heme oxygenase activity in treated rats correlated with these results. Conclusions. The induction of HO-1 by simvastatin preconditioning played a protective role against hepatic I/R injury.

Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method.

A new core-shell nanostructure consisting of inorganic hydroxyapatite (HAP) nanoparticles as the core and organic alginate as the shell (denoted as HAP@Alg) was successfully synthesized by a pre-gel method and applied to pH-responsive drug delivery systems (DDS). HAP@Alg nanoparticles have the advantages of hydroxyapatite and alginate, where hydroxyapatite provides pH-responsive degradability, and alginate provides excellent biocompatibility and COOH functionality. Through the subsequent addition of CaCl(2) and phosphate solutions to the alginate solution, HAP@Alg nanoparticles with controllable particle sizes (ranging from 160 to 650 nm) were obtained, and their core-shell structure was confirmed through transmission electron microscopy (TEM) observation. Rhodamine 6G (R6G), a positively charged dye, was selected as a model drug for pH-sensitive DDS. R6G was encapsulated in the HAP/Alg nanoparticles upon synthesis, and its loading efficiency could reach up to approximately 63.0%. The in vitro release behavior of the loaded R6G at different pH values was systematically studied, and the results indicated that more R6G molecules were released at lower pH conditions. For example, after releasing for 8 h, the release amount of R6G at pH 2.0 was 2.53-fold the amount at pH 7.4. We attributed this pH-sensitive release behavior to the dissolution of the HAP core in acidic conditions. The results of the MTT assay and confocal laser scanning microscopy indicated that the HAP@Alg were successfully uptaken by liver cancer cells (HepG2) without apparent cytotoxicity. The synthesized HAP@Alg nanoparticles show great potential as drug nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive features for future intracellular DDS.

Laparoscopic versus open appendectomy for perforated appendicitis

The role of laparoscopic appendectomy (LA) for perforated appendicitis is under investigation. A retrospective study was conducted to compare the outcomes of laparoscopic versus open appendectomy (OA) for perforated appendicitis. From January 2001 through December 2003, 229 patients with perforated appendicitis were treated at Far-Eastern Memorial Hospital. LA was successfully completed in 91 of 99 patients. OA was performed in 130 patients. Operation time was longer in the LA group (mean ± SD =96.1±43.1 vs. 67.8±32.2 minutes, P<0.01). Return of oral intake was faster in the LA group (3.2±2.4 vs. 5.0±7.0 days, P<0.01). The intravenous antibiotic usage period was shorter in the LA group (4.4±2.8 vs. 6.3±7.1 days, P<0.01). The postoperative wound infection rates were 15.2 % (LA group) and 30.7% (OA group). The overall infectious complication rates were 19% in the LA group and 37% in the OA group (P<0.01). Hospital stay days were shorter for the LA group (6.3±2.9 vs. 9.3±8.6 days, P<0.01). Our results indicated that laparoscopic appendectomy is a safe and effective procedure for treating patients with perforated appendicitis.

Minimally invasive surgery for gastric stromal cell tumors : Intermediate follow-up results

Laparoscopic wedge resection of the stomach (LWS) has become the treatment of choice for patients with benign gastric tumors. The technical consideration and long-term follow-up data of LWS for gastrointestinal stromal tumors (GISTs) of the stomach are limited. We present our experience of 28 LWSs for gastric GISTs with a mean follow-up of 43 months. From October 1995 to December 2002, we successfully performed 28 LWSs for 29 patients with GISTs of the stomach, and one patient needed conversion to laparotomy because of suspected bowel injury when establishing pneumoperitoneum. Patient demographics, perioperative parameters, and outcomes of the 28 patients were assessed retrospectively. The tumors were located in the upper third of the stomach in 13 patients, in the middle third, in eight patients, and in the lower third, in seven patients. The mean size of tumors was 3.4 ± 1.6 cm in diameter. The duration of operation ranged from 95 to 390 minutes: 189.6 ± 79.5 minutes with the stapler method and 194.3 ± 50.5 minutes with the hand-sewn method (P = 0.8870). No blood transfusion was given in the perioperative period in all cases. Cholecystectomy in three patients and repair of hiatal hernia in one patient were performed during the same operation. The oral intake was restored at the third to fourth postoperative days. The hospital stay ranged from 3 to 11 days (mean, 6.7 ± 1.8 days). The follow-up period ranged from 12 to 95 months (mean, 43.3 ± 23.5 months, median 42 months). There has been no evidence of tumor recurrence, including one patient with microscopic invasion of section margin. LWS can be performed safely with a satisfactory remission rate for patients with gastric stromal cell tumors.

In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

Background Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor. Methods The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections. Results VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice. Conclusion These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.

Minilaparoscopic (needlescopic) cholecystectomy: a study of 1,011 cases

Background:The safety and feasibility of minilaparoscopic cholecystectomy has not been documented with a large patient sample. This study reports the results of 1,011 minilaparoscopic cholecystectomies performed in a single institution.Methods:From November 1997 to May 2002, 1,023 consecutive patients underwent minilaparoscopic cholecystectomy at National Taiwan University Hospital, Taipei, Taiwan. Patients with clinical evidence of common bile duct stones (1 patient) and combined surgery for other purposes (11 patients) were excluded. The operative indication, total operative time, conversion rate, hospital stay, morbidity and mortality of 1,011 patients were reviewed and statistically analyzed.Results:Minilaparoscopic cholecystectomy was performed in 1,009 of 1,011 patients (375 males and 636 female; mean age, 54.8 years; range 13–92 years). The total operative time was 68.8 ± 31.9 min. The total hospital stay was 2.5 ± 2 days. One patient (0.10%) underwent conversion to open cholecystectomy because of common hepatic duct laceration. One patient (0.10%) underwent conversion to standard laparoscopic cholecystectomy for control of cystic artery bleeding. Ten patients (0.99%) experienced major complications including intraabdominal abscess (1 patient), bile leakage (5 patients), major bile duct injury (2 patients), bowel injury (1 patient), and postoperative hemorrhage (1 patient). Eleven patients (1.09%) had minor complications including wound infection, incisional herniation, postoperative ileus, and acute urine retention. One patient (0.10%) with bleeding tendency succumbed to postoperative hemorrhage.Conclusions:Minilaparoscopic cholecystectomy is a technically demanding approach. Our results indicate that this procedure could be performed successfully and safely by experienced surgical teams.

Isolated mitochondria infusion mitigates ischemia-reperfusion injury of the liver in rats.

ABSTRACT A recent study showed that the injection of mitochondria isolated from a nonischemic region mitigated myocardial injury. We tested the protective effects of infusing isolated mitochondria on the reperfusion injury in the liver of rats. A partial liver ischemia-reperfusion (I/R) model in male Wistar rats was used. At the 45th minute of liver ischemia, the recipient’s spleen was infused with vehicle (I/R-vehicle group) or vehicle containing isolated mitochondria (7.7 × 106 ± 1.5 × 106/mL, I/R-mito group). After a 240-min reperfusion, the serum and livers were collected to assess tissue injury. Our results show that the elevation of serum alanine aminotransferase (414.3 ± 67.1 vs. 208.8 ± 30.2 U/L), the necrosis of hepatocytes on hematoxylin-eosin staining, increase in positive counts in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (59.5% ± 4.4% vs. 24.6% ± 9.1%), the expression of cytosolic cytochrome c, cleaved caspase 9, and 4-hydroxynonenal were all reduced in the I/R-mito group, compared with the I/R-vehicle group. The membrane potential of the isolated mitochondria measured by JC-1 fluorescence remained high, and the infused mitochondria were distributed in the liver parenchyma at 240 min after reperfusion. These results demonstrate that an intrasplenic infusion of viable mitochondria isolated from the donor before reperfusion significantly reduced I/R injury in the liver.

Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance.

Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various cancers; however, it remains unclear how FAK participates in tumor malignancy in vivo. This study seeks to understand the role of FAK activation in gastric cancer progression. Using immunohistochemical staining and Western blotting, we found that pY397 FAK, an autophosphorylation site on FAK activation, was abundant in the cancerous tissues of 21 of 59 patients with gastric carcinomas. We attempted to correlate clinicopathological parameters, including histological types, TNM staging, and cancer recurrence, with the expression of FAK and pY397 FAK in cancerous tissues. Intriguingly, patients with higher levels of pY397 FAK displayed higher incidences of gastric cancer recurrence after surgery and poor 5-year recurrence-free survival. Furthermore, multivariate analyses showed that pY397 FAK was an independent predictor of gastric cancer recurrence. As a result, expression of pY397 FAK is a significant prognostic factor for the recurrence of gastric cancer. Additionally, in vitro studies showed that overexpression of Y397F, a dominant-negative mutant of FAK, in AGS human gastric carcinoma cells impaired cell migration, invasion, and proliferation compared with cells overexpressing wild-type FAK. Thus, activation of FAK through autophosphorylation at Tyr397 leads to the progression of gastric carcinomas by promoting cell migration, invasion, and proliferation. Collectively, our results have provided valuable insights for the development of novel diagnoses and therapeutic targets for gastric cancer treatments.