Pancreas preservation by the 2-layer cold storage method before islet isolation protects isolated islets against apoptosis through the mitochondrial pathway

BACKGROUND: Apoptosis in isolated islets has been implicated in primary nonfunction or early graft failure after islet transplantation. Recently, pancreas preservation by the 2-layer method (TLM) before islet isolation has been proved to improve the islet yield, quality, and transplant results not only in experimental models, but also in clinical settings. We examined the influence of TLM on apoptosis of isolated islets. METHOD: Rat islets freshly isolated and after pancreas preservation by TLM or conventional cold storage in University of Wisconsin solution (UW) were examined and compared. Islet apoptosis was assessed by TUNEL and annexin V assays. The apoptosis pathways involved were investigated by measurement of caspase 3, 8, and 9 activities and by immunoblotting for total and phosphorylated c-Jun NH2-terminal kinase (JNK) and p38. RESULTS: Islet apoptosis in the UW group was significantly increased compared with the fresh and TLM groups. Both caspase 3 and 9 activities in the UW group were higher than in the fresh and TLM groups with an approximate increase of 2- to 3-fold. On the other hand, there was no significant difference in caspase 8 activity among these 3 groups. JNKs were strongly activated both in the TLM and UW groups; although they were not activated in the fresh group, p38 was activated to almost the same levels in these 3 groups. CONCLUSIONS: Pancreas preservation by TLM before islet isolation protects isolated islets against apoptosis mainly through the mitochondrial pathway. Pancreas storage before islet isolation even with TLM triggers activation of JNKs in isolated islets.     

Hydrodynamic evaluation of axillary artery perfusion for normal and diseased aorta

Axillary artery perfusion is an attractive alternative to reduce the frequency of atheroembolism in extensive atherosclerotic aorta and aortic aneurysms. This study was conducted to evaluate the flow dynamics of axillary artery perfusion. Transparent glass models of a normal aortic arch and an aortic arch aneurysm were used to evaluate hydrodynamic properties. Streamline analysis and distribution of the shear stress was evaluated using a particle image velocity method. In the normal aortic arch model, rapid flow of 80 cm/s from the right axillary artery ran out from the brachiocephalic artery and grazed the lesser curvature of the aortic arch. There was secondary reversed flow in the ascending aorta. Flow from left axillary perfusion went straight to the descending aorta. In the aortic arch aneurysm model, flow from both axillary arteries hit the lesser curvature of the aortic arch and went into the ascending aorta with vortical flow. Distribution of shear stress was high along the jet from the ostium of the brachiocephalic artery and left subclavian artery. Flow in the aortic arch and the ascending aorta was unexpectedly rapid. Special care must be taken when the patient has frail atheroma around arch vessels or the lesser curvature of the aortic arch during axillary artery perfusion.     

Modification of the Bentall operation using the proximal double sewing technique without excision of leaflets

We present a report on reinforcement of the proximal anastomosis during the Bentall operation. The aortic wall was excised with a 5-mm remnant, and aortic valve leaflets were preserved. Interrupted horizontal mattress sutures (2-0 Polyestel) reinforced with pledgets were placed. The composite graft was placed at the intraannular position inside of the preserved leaflets. The aortic valve leaflets were then pasted to the sewing cuff with fibrin glue. A running suture with 4-0 monofilament was placed between the remnant of the aortic wall and the peripheral side of the sewing cuff wrapped with native aortic valve leaflets.     

Liver transplantation for multiple liver metastases from solid pseudopapillary tumor of the pancreas

Solid pseudopapillary tumor (SPT) of the pancreas usually shows a benign clinical course. However, sometimes, distant metastasis may occur. Even in such case, the prognosis is good only if metastatic lesions are resected completely. We report the case of a 14-year-old girl with SPT of the pancreas and unresectable synchronous liver metastasis who underwent successful living donor liver transplantation. For 2 years, she has been disease free. This is the first report on transplantation to relieve liver metastasis of SPT.     

Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

Propofol Increases Pulmonary Artery Smooth Muscle Myofilament Calcium Sensitivity: Role of Protein Kinase C

Background: Vascular smooth muscle tone is regulated by changes in intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity. These cellular mechanisms could serve as targets for anesthetic agents that alter vasomotor tone. This study tested the hypothesis that propofol increases myofilament Ca2+ sensitivity in pulmonary artery smooth muscle (PASM) via the protein kinase C (PKC) signaling pathway.

Methods: Canine PASM strips were denuded of endothelium, loaded with fura-2/AM, and suspended in modified Krebs- Ringer's buffer at 37[degrees]C for simultaneous measurement of isometric tension and [Ca2+]i.

Results: The KCl (30 mm) induced monotonic increases in [Ca2+]i and tension. Verapamil, an L-type Ca2+ channel blocker, attenuated KCl-induced increases in [Ca2+]i and tension to an equal extent. In contrast, propofol attenuated KCl-induced increases in [Ca2+]i to a greater extent than concomitant changes in tension and caused an upward shift in the peak tension-[Ca2+]i relation. Increasing extracellular Ca2+ in the presence of 30 mm KCl resulted in similar increases in [Ca2+]i in control and propofol-pretreated strips, whereas concomitant increases in tension were greater during propofol administration. The Ca2+ ionophore, ionomycin (0.1 [mu]m), increased [Ca2+]i to approximately 50% of the value induced by 60 mm KCl. Under these conditions, propofol (10, 100 [mu]m) caused increases in tension equivalent to 11 +/- 2 and 28 +/- 3% of the increases in tension in response to 60 mm KCl, whereas [Ca2+]i was slightly decreased. Similar effects were observed in response to the PKC activator, phorbol 12-myristate 13-acetate (PMA, 1 [mu]m). Specific inhibition of PKC with bisindolylmaleimide I before ionomycin administration decreased the propofol- and PMA-induced increases in tension and abolished the propofol- and PMA-induced decreases in [Ca2+]i. Selective inhibition of Ca2+-dependent PKC isoforms with Go 6976 also attenuated propofol-induced increases in tension.     

Selection of pancreaticojejunostomy techniques according to pancreatic texture and duct size

HYPOTHESIS: Selection of proper pancreaticojejunostomy techniques according to pancreatic texture and the main duct size reduces the pancreatic fistula rate. DESIGN AND PATIENTS: Data from 50 consecutive patients undergoing pancreatoduodenectomy with 3 different anastomotic techniques prospectively used according to pancreatic texture and the main duct size were analyzed. Duct-invagination anastomosis was selected for pancreata with a small duct (n = 34 [29 with a soft texture and 5 with a hard texture]). Stitches between the stump parenchyma and the jejunal seromuscular layer were added to this anastomosis procedure only for the hard pancreata. Pancreata with a large duct were reconstructed with a conventional duct-to-mucosa anastomosis (n = 16). SETTING: A university hospital department of digestive surgery. RESULTS: The morbidity was 40% (20 of 50 patients) in this series. Four patients (8%) with a soft pancreas and a small duct developed a pancreatic stump leak after duct-invagination anastomosis, but all of them were removed without sequelae. No pancreatic anastomotic leak was seen in this series, which resulted in no mortality, no remnant pancreatectomy, and only 1 relaparotomy in the consecutive 50 patients. CONCLUSION: The proper selection of pancreatic reconstruction techniques according to our criteria may reduce the pancreatic fistula rate, eliminate risky pancreatic anastomotic leaks, and result in excellent outcomes for those undergoing pancreatoduodenectomy.     

Long-term survival and functional recovery after isolated coronary artery bypass grafting in patients with severe left ventricular dysfunction

Objective  Coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction has been considered to be a challenging operation. We assessed the early angiographic and long-term clinical and functional outcomes of patients with poor left ventricular function who underwent isolated CABG. Methods  We retrospectively reviewed the records of 78 patients with a poor left ventricular ejection fraction (35% or less) who underwent isolated CABG between January 1991 and November 2006. The mean age of the patients was 66.1 ± 9.4 years, and their mean New York Heart Association functional class was 3.1 ± 0.8. Their mean end-diastolic left ventricular diameter was 57.4 ± 8.1 mm, and their mean grade of mitral regurgitation was 0.7 ± 1.0. Early postoperative angiograms were performed at 32.5 ± 33.5 days after the operation. Interval echocardiographic data were analyzed, and the long-term survival rate was evaluated. Results  The average number of distal anastomoses per patient was 3.2 ± 1.1. The operative mortality rate was 7.7%. Stroke occurred in 1.3% of patients. The overall patency rates for arterial and venous grafts were 100% and 97.2%, respectively. The left ventricular ejection fraction significantly improved from 28.2% ± 5.1% to 34.4% ± 8.4%. Both the end-diastolic and end-systolic left ventricular dimensions significantly decreased from 57.4 ± 8.1 to 55.1 ± 8.8 mm and from 47.4 ± 8.4 to 45.1 ± 9.7 mm, respectively. The actuarial patient survival rate at 10 years was 73.1%. Conclusion  CABG in patients with left ventricular dysfunction was effective, with favorable early graft patency rates. The long-term outcome was also acceptable, with echocardiographic functional recovery.     

Surgical Resection of Hilar Cholangiocarcinoma: Analysis of Survival and Postoperative Complications

Background Surgery is the only potentially curative treatment for hilar bile duct cancer. This study sought to evaluate the efficacy and feasibility of surgical management of hilar bile duct carcinoma, including radical hepatectomy, at a single institution. Methods We performed a retrospective review of 49 consecutive patients who underwent surgery at our hospital between 1990 and 2003. Results Altogether, 44 of 49 patients underwent radical hepatectomy combined with caudate lobectomy and lymphadenectomy. One and four patients underwent partial hepatectomy or bile duct resection, respectively. No patients underwent preoperative portal vein embolization. The 5-year survival rate was 39.7%, with a median survival time of 3.75 years. The postoperative morbidity and mortality rates were 46.8% and 2.0%, respectively. Cox’s proportional hazard model revealed that lymph node status and the residual tumor factor were independent prognostic factors. Multivariate analysis revealed that preoperative hyperbilirubinemia, postoperative complications, and extended surgical procedures were independently associated with postoperative hyperbilirubinemia. After potentially curative resection, 39.4% of patients suffered from disease recurrence. In 60% of the total cases, the sites of recurrence were distant metastases. Conclusion Surgery, including radical hepatectomy combined with caudate lobectomy and lymph node dissection, is a feasible, effective treatment for hilar bile duct cancer.     

Value of Laparoscopic Appendectomy in Perforated Appendicitis

Background The purpose of this clinical study was to evaluate the efficacy of laparoscopic appendectomy in patients with perforated appendicitis. Methods This study involved a total of 73 consecutive patients who had undergone appendectomy for perforated appendicitis between January 1999 and December 2004. While 39 patients underwent open appendectomy (OA) during the first 3 years, the remaining 34 patients underwent laparoscopic appendectomy (LA) during the last 3 years. Results There was no case of LA converted to OA. No significant difference was found in the operating time between the two groups. Laparoscopic appendectomy was associated with less analgesic use, earlier oral intake restart (LA, 2.6 days; OA, 5.1 days), shorter median hospital stay (LA, 11.7 days; OA, 25.8 days), and lower rate of wound infections (LA, 8.8%; OA, 43.6%). Conclusions These results suggest that LA for perforated appendicitis is a safe procedure that may prove to have significant clinical advantages over conventional surgery.