Kuo-Hsin Chen

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.

Mechanisms for the magnolol-induced cell death of CGTH W-2 thyroid carcinoma cells.

Magnolol, a substance purified from the bark of Magnolia officialis, inhibits cell proliferation and induces apoptosis in a variety of cancer cells. The aim of this study was to study the effects of magnolol on CGTH W‐2 thyroid carcinoma cells. After 24 h treatment with 80 µM magnolol in serum‐containing medium, about 50% of the cells exhibited apoptotic features and 20% necrotic features. Cytochrome‐c staining was diffused in the cytoplasm of the apoptotic cells, but restricted to the mitochondria in control cells. Western blot analyses showed an increase in levels of activated caspases (caspase‐3 and ‐7) and of cleaved poly (ADP‐ribose) polymerase (PARP) by magnolol. Concomitantly, immunostaining for apoptosis inducing factor (AIF) showed a time‐dependent translocation from the mitochondria to the nucleus. Inhibition of either PARP or caspase activity blocked magnolol‐induced apoptosis, supporting the involvement of the caspases and PARP. In addition, magnolol activated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt. These data suggest that magnolol promoted apoptosis probably by alleviating the inhibitory effect of Akt on caspase 9. Furthermore, inhibition of PARP activity, but not of caspase activity, completely prevented magnolol‐induced necrosis, suggesting the notion that it might be caused by depletion of intracellular ATP levels due to PARP activation. These results show that magnolol initiates apoptosis via the cytochrome‐c/caspase 3/PARP/AIF and PTEN/Akt/caspase 9/PARP pathways and necrosis via PARP activation. J. Cell. Biochem. 101: 1011–1022, 2007.

Effects of Calcineurin Inhibitors on Sirolimus Pharmacokinetics During Staggered Administration in Renal Transplant Recipients

Study Objective. To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long‐term, staggered administration in kidney transplant recipients.

An acidic extracellular pH induces Src kinase-dependent loss of β-catenin from the adherens junction

Little attention has been paid to the role of adherens junctions (AJs) in acidic extracellular pH (pHe)-induced cell invasion. Incubation of HepG2 cells in acidic medium (pH 6.6) induced cell dispersion from tight cell clusters, and this change was accompanied by downregulation of beta-catenin at cell junctions and a rapid activation of c-Src. Pretreatment with PP2 prevented the acidic pH-induced downregulation of beta-catenin at AJ and in the membrane fractions. The acidic pHe-induced c-Src activation increased tyrosine phosphorylation of beta-catenin and decreased the amount of beta-catenin-associated E-cadherin. The depletion of membrane-bound beta-catenin coincided with enhanced cell migration and invasion, and this acidic pHe-increased cell migration and invasion was prevented by PP2. In conclusion, this study characterizes a novel signaling pathway responsible for acidic microenvironment-promoted migration and invasive behaviors of cancer cells.

Laparoscopic diagnosis and treatment of acute small bowel obstruction resulting from a congenital band.

Acute small bowel obstruction is a common problem, especially for those patients with previous abdominal surgery that can cause postoperative adhesions. Acute, non-postoperative small bowel obstruction is less common and has various etiologies. We report a case of acute small bowel obstruction without previous abdominal surgery. The patient underwent laparoscopic exploration, and a congenital band was found to cause direct compression of the ileum and entrapment of a segment of bowel loop. There was evidence of bowel strangulation. The color and peristalsis of the entrapped bowel loop recovered gradually after division of the band, and segmental bowel resection was avoided. He has remained asymptomatic since the procedure. We suggest early and aggressive surgical intervention for patients with acute, non-postoperative small bowel obstruction to avoid possible complications of bowel strangulation and gangrene. A laparoscopic approach may be a safe, feasible, and favorable option for correct diagnosis and appropriate treatment in this situation.

Acidic extracellular pH induces p120-catenin-mediated disruption of adherens junctions via the Src kinase-PKCδ pathway.

An acidic microenvironment induces disruption of adherens junctions (AJs) of hepatoma cells. This study investigated the impact of an acidic extracellular pH (pHe) on p120‐catenin (p120‐ctn) serine phosphorylation. pH 6.6 treatment increased intracellular calcium levels, activated protein kinase C (PKC)α and PKCδ, and decreased serine phosphorylation of p120‐ctn. Further knockdown of PKCα and δ by small interference RNA (siRNA) prevented the pH 6.6‐induced downregulation of p120‐ctn at AJ and the serine dephosphorylation of p120‐ctn. Moreover, PP2 pretreatment and siRNA of c‐Src abrogated the pH 6.6‐induced PKCδ activation. Together, the c‐Src‐PKCδ cascade and PKCα regulate the acidic pHe‐induced AJ disruption.

Impact of previous abdominal surgery on laparoscopic appendectomy for acute appendicitis

BackgroundLaparoscopic appendectomy is one of the most commonly performed laparoscopic procedures. Impact of previous abdominal surgery on laparoscopic appendectomy has not been previously reported.MethodsFrom January 2001 to December 2005, 2029 patients with clinically suspected acute appendicitis underwent laparoscopic surgery in our hospital. Of these, 234 patients (11.5%) were found to have other pathology by intraoperative or histologic findings and were excluded from the study. The 1795 patients who underwent laparoscopic appendectomy for acute appendicitis were divided into three groups: group 1, patients without a history of previous abdominal surgery (n = 1652, 92%); group 2, patients with a history of upper abdominal surgery (n = 20, 1.1%); group 3, patients with a history of lower abdominal surgery (n = 123, 6.8%). Data were collected retrospectively by chart review and analyzed for conversion rate, operative time, intraoperative and postoperative complications, and hospital stay.ResultsOf the 1795 patients, 13 (0.7%) were converted to open appendectomy because of technical difficulty. Overall mean operative time was 57.2 (range, 20–225) min. There was no mortality or intraoperative complications. Overall postoperative complication rate was 10.7% (n = 193): rate of surgical wound infection was 8.2 % (n = 147), surgical wound seroma 1.3% (n = 24), and intra-abdominal abscess 0.8% (n = 14). Overall postoperative hospital stay averaged 3.2 (range, 0–39) days. There were no significant differences between the three groups regarding the conversion rate (0.8% vs. 0% vs. 0%, p = 0.567), operative time (57.3 vs. 55.8 vs. 56.9 min, p = 0.962), postoperative complication rates (10.7 vs. 10 vs. 12.2%, p = 0.863), and hospital stay (3.2 vs. 3.6 vs. 3.1 days, p = 0.673).ConclusionsPrevious abdominal surgery, whether upper or lower abdominal, has no significant impact on laparoscopic appendectomy for acute appendicitis.

Totally laparoscopic living donor right hepatectomy in a donor with trifurcation of bile duct

Donor operation in adult living donor liver transplantation is associated with significant postoperative morbidity. To avoid laparotomy wound complications and shorten postoperative recovery, laparoscopic liver graft harvest has been developed recently. However, to determine the cut point of bile duct is challenging. Herein, we report the application of totally laparoscopic approach for right liver graft harvest in a donor with trifurcation of the bile duct. A19-year-old man volunteered for living donation to his father who suffered from hepatitis B virus-related cirrhosis of liver and hepatocellular carcinoma. The graft was 880 mL with a single right hepatic artery and portal vein. The graft to recipient weight ratio was 1.06. The middle hepatic vein was preserved for the donor and the liver remnant was 42.3%. Two branches of middle hepatic veins were > 5 mm in diameter and needed reconstruction with cryopreserved allograft. Ductoplasty using laparoscopic intracorporeal suture technique was done to achieve single orifice of the graft bile duct. The postoperative course was uneventful for the donor. This report adds evidence of the feasibility of pure laparoscopic right donor hepatectomy and describes the necessary steps for bile duct division in donors with trifurcation of bile duct.

Robotic left hepatectomy with revision of hepaticojejunostomy

Laparoscopic hepatectomy and hepaticojejunostomy remain a surgical challenge despite the recent advances in minimally invasive surgery. A robotic surgical system has been developed to overcome the inherent limitations of the traditional laparoscopic approach. However, techniques of robotic hepatectomy have not been well described, and a description of robotic major hepatectomy with bilioenteric anastomosis can be found only in two previous reports. Here, we report a 33-year-old man with a history of choledochocyst resection. The patient experienced repeat cholangitis with left hepatolithiasis during follow-up. Robotic left hepatectomy and revision of hepaticojejunostomy were performed smoothly. The patient recovered uneventfully and remained symptoms-free at a follow-up of 20 months. The robotic approach is beneficial in the fine dissection of the hepatic hilum and revision of hepaticojejunostomy in this particular patient.

Favorable Results of Concomitant Tacrolimus and Sirolimus Therapy in Taiwanese Renal Transplant Recipients at 12 Months

BACKGROUND/PURPOSE Combined therapy of sirolimus and cyclosporine has been found to exacerbate cyclosporine-related nephrotoxicity and to imperil graft renal function. We hypothesized that tacrolimus could bring about better renal function than cyclosporine when used in combination with sirolimus and corticosteroids for de novo renal transplantation. METHODS A two-arm randomized study was conducted to test the hypothesis. Patients who gave written informed consent and received renal transplantation were randomized to take sirolimus in combination with either tacrolimus or cyclosporine. The primary endpoint of this study was renal function, and the secondary endpoints were acute rejection, graft and patient survival, metabolic side effects and infectious complications. RESULTS A total of 41 Taiwanese renal transplant patients were randomized to receive cyclosporine (CsA group, n = 20) or tacrolimus (TAC group, n = 21) in combination with sirolimus and corticosteroids. The average estimated glomerular filtration rate (eGFR) was 52.77 +/- 3.86 mL per minute for the TAC group at 6 months, and 46.42 +/- 3.95 mL per minute for the CsA group (p > 0.05). At 12 months, the average eGFR was 52.04 +/- 4.38 mL per minute for the TAC group, and 46.79 +/- 4.38 mL per minute for the CsA group (p > 0.05). The biopsy-proven acute rejection rate of the TAC group was 4.76% (1/21), and that of the CsA group was 5.00% (1/20) at 12 months. The 12-month graft survival rates for the TAC and CsA groups were 100% and 90% (p = 0.142), respectively. CONCLUSION Our study demonstrated that concomitant tacrolimus and sirolimus therapy resulted in a favorable outcome in Taiwanese renal transplant patients at 12 months. Large-scale clinical trials will be needed to further address the issue of which calcineurin inhibitor, cyclosporine or tacrolimus, provides better renal function and graft survival for renal transplant patients.