Total gastrectomy-induced reductions in food intake and weight are counteracted by rikkunshito by attenuating glucagon-like peptide-1 elevation in rats.

BACKGROUND: Decrease in appetite and weight after total gastrectomy in patients with gastric cancer leads to a decrease in quality of life, increased mortality, and may necessitate discontinuation of adjuvant chemotherapy. The aim of this study is to determine whether rikkunshito, a Japanese herbal medicine, increases food intake and weight after gastrectomy in rats. METHODS: Male rats underwent gastrectomy followed by roux-en-Y reconstruction or sham operation and were then treated with rikkunshito for 14 days starting on postoperative day 3. Daily food intake, weight, plasma glucagon-like peptide-1 (GLP-1), and ghrelin levels were measured. A pilot study to measure pre- and postoperative plasma GLP-1 levels was conducted in patients who underwent total gastrectomy for gastric cancer. RESULTS: Administration of rikkunshito after gastrectomy in rats significantly increased food intake and weight, which continued for at least 2 weeks after treatment. Both fasting and postprandial plasma GLP-1 levels were increased markedly after gastrectomy compared with sham-operated animals. Increased GLP-1 levels in rats after gastrectomy were suppressed markedly by rikkunshito. rikkunshito had no significant effect on plasma ghrelin levels after gastrectomy. Treatment with a GLP-1 receptor antagonist significantly improved food intake and weight after gastrectomy. Plasma fasting GLP-1 levels in patients with gastric cancer were increased greatly after gastrectomy on postoperative day 1. CONCLUSION: Administration of rikkunshito suppresses plasma GLP-1 levels after total gastrectomy, which is associated with recovery from reduced food intake and weight in rats.

The ß-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin.

Gastric hormone ghrelin regulates insulin secretion, as well as growth hormone release, feeding behavior and adiposity. Ghrelin is known to exert its biological actions by interacting with the growth hormone secretagogue-receptor (GHSR) coupled to G(q/11)-protein signaling. By contrast, ghrelin acts on pancreatic islet ß-cells via Gi-protein-mediated signaling. These observations raise a question whether the ghrelin action on islet ß-cells involves atypical GHSR and/or distinct signal transduction. Furthermore, the role of the ß-cell GHSR in the systemic glycemic effect of ghrelin still remains to be defined. To address these issues, the present study employed the global GHSR-null mice and those re-expressing GHSR selectively in ß-cells. We here report that ghrelin attenuates glucose-induced insulin release via direct interaction with ordinary GHSR that is uniquely coupled to novel cAMP/TRPM2 signaling in ß-cells, and that this ß-cell GHSR with unique insulinostatic signaling largely accounts for the systemic effects of ghrelin on circulating glucose and insulin levels. The novel ß-cell specific GHSR-cAMP/TRPM2 signaling provides a potential therapeutic target for the treatment of type 2 diabetes.

Complete pathological response to transcatheter arterial infusion despite a rapidly progressing recurrent hepatocellular carcinoma with portal vein tumor thrombus: A case report.

INTRODUCTION: We report a patient with a rapidly progressing recurrence of hepatocellular carcinoma (HCC) with a portal vein tumor thrombus after radiofrequency ablation of the original lesion, then treated with transcatheter arterial infusion. Radical hepatic resection demonstrated a complete pathological response. PRESENTATION OF CASE: A 60-year old male with alcoholic cirrhosis and gastric varices was diagnosed with HCC measuring 12mm in segment 8. He underwent laparoscopic radiofrequency ablation, but recurred three months later. The lesion progressed rapidly and the right portal vein was occluded. He then underwent transcatheter arterial infusion with miriplatin and iodized oil, which was effective in reducing the size of the main lesion and portal vein tumor thrombus. Right anterior sectionectomy was then performed. Pathologically, there were no viable HCC cells in either the main lesion or the portal vein thrombus. He is alive two years and nine months after surgery without recurrence. DISCUSSION: A rapidly progressing HCC recurrence with portal vein tumor thrombus is usually associated with a poor prognosis. No effective treatments have been reported in this situation except hepatic resection. In this patient the tumor was effectively reduced after three courses of transarterial miriplatin and subsequent radical hepatic resection. This is the first report to achieve a complete pathological response for such an aggressive recurrence after initial radiofrequency ablation. CONCLUSION: This strategy may result in long-term survival of patients with rapidly progressing recurrent HCC with portal vein thrombus, and further study is warranted.

Preoperative segmental embolization of the proper hepatic artery prior to pylorus-preserving pancreaticoduodenectomy: A case report.

INTRODUCTION: Radical resection of bile duct carcinoma may require resection of hepatic arteries. Preoperative segmental embolization of the hepatic artery for resection of hilar cholangiocarcinoma has been reported. We report a patient with bile duct carcinoma infiltrating the proper hepatic artery. PRESENTATION OF CASE: A 66-year old male with jaundice was diagnosed with mid-distal bile duct carcinoma. A replaced left hepatic artery originated from the left gastric artery. Pylorus-preserving pancreaticoduodenectomy (PPPD) with combined resection of hepatic artery was planned. To promote the development of collateral blood flow after excision of the hepatic artery, preoperative segmental embolization of the proper hepatic artery was performed. The patient underwent PPPD with concurrent resection of the common hepatic, right hepatic, and middle hepatic arteries without arterial reconstruction. He received adjuvant chemotherapy with gemcitabine for six months and is alive three years after surgery without tumor recurrence. DISCUSSION: The growth of collateral vessels after selective embolization of the proper hepatic artery has been used for hilar lesions and bile duct lesions. Resection of the hepatic artery without the need for complex arterial reconstruction, allowing a radical resection, may have contributed to this patient's relatively unremarkable recovery and long-term survival. Retroperitoneal mobilization of the pancreatic head and duodenum must be limited as important collaterals may originate in that area. CONCLUSION: Preoperative segmental embolization of the hepatic artery before PPPD for a patient with a replaced left hepatic artery encouraged the growth of collateral blood supply, allowing radical resection including the vessels and obviated the need for arterial reconstruction.

Recurrent cholangitis by biliary stasis due to non-obstructive afferent loop syndrome after pylorus-preserving pancreatoduodenectomy: report of a case.

We report a 71-year-old man who had undergone pylorus-preserving pancreatoduodenectomy (PPPD) using PPPD-IV reconstruction for cholangiocarcinoma. For 6 years thereafter, he had suffered recurrent cholangitis, and also a right liver abscess (S5/8), which required percutaneous drainage at 9 years after PPPD. At 16 years after PPPD, he had been admitted to the other hospital because of acute purulent cholangitis. Although medical treatment resolved the cholangitis, the patient was referred to our hospital because of dilatation of the intrahepatic biliary duct (B2). Peroral double-balloon enteroscopy revealed that the diameter of the hepaticojejunostomy anastomosis was 12 mm, and cholangiography detected intrahepatic stones. Lithotripsy was performed using a basket catheter. At 1 year after lithotripsy procedure, the patient is doing well. Hepatobiliary scintigraphy at 60 minutes after intravenous injection demonstrated that deposit of the tracer still remained in the upper afferent loop jejunum. Therefore, we considered that the recurrent cholangitis, liver abscess, and intrahepatic lithiasis have been caused by biliary stasis due to nonobstructive afferent loop syndrome. Biliary retention due to nonobstructive afferent loop syndrome may cause recurrent cholangitis or liver abscess after hepaticojejunostomy, and double-balloon enteroscopy and hepatobiliary scintigraphy are useful for the diagnosis of nonobstructive afferent loop syndrome.

Participation of surgical residents does not adversely affect the outcome of inguinal hernia repair in an integrated teaching program.

OBJECTIVE: The Lichtenstein inguinal hernia repair is commonly performed and suitable for teaching basic surgical skills. The objective of this study is to evaluate the feasibility of this procedure for surgical training, particularly in regard to patient outcomes. DESIGN: Retrospective case review after introduction of an integrated teaching program. SETTING: University teaching hospital. PARTICIPANTS: The Lichtenstein inguinal hernia repair is the standard procedure for adult primary unilateral inguinal hernia since 2003 at Jichi Medical University. We introduced an integrated teaching system of lectures, skill training. and videos to teach the skills for Lichtenstein inguinal hernia repair to residents and junior faculty in 2003. Cases were retrospectively divided into 4 groups based on the experience of the operating surgeon; junior residents (PGY 1-2, group A), senior residents (PGY 3-5, group B), junior faculty (PGY 6-10, group C), and senior faculty (PGY 11 or more, group D). Background, perioperative factors, and outcomes were evaluated among the groups. RESULTS: A total of 246 elective inguinal hernia repairs (group A: 136, group B: 49, group C: 42, group D: 19) were performed. There was a significant difference in the frequency of concomitant diseases (p = 0.012) and anticoagulant therapy (p = 0.031). Average operating time was 80.7 ± 24.9, 72.6 ± 20.8, 63.5 ± 22.0, and 54.7 ± 27.9 (min ± SD) in groups A, B, C, and D, respectively, with a significant difference between groups A and D (p < 0.001). No significant differences were observed in estimated blood loss (p = 0.216) or morbidity (p = 0.294). CONCLUSIONS: The Lichtenstein inguinal hernia repair can be safely performed by residents and junior faculty with the appropriate supervision of senior faculty without any disadvantage to patients. This integrated teaching program for Lichtenstein inguinal hernia repair is effective and feasible for training residents and junior faculty.

Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats.

BACKGROUND: Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD. RESULTS: In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B. CONCLUSIONS: The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.

Thoracoscopic findings of a small posterior mediastinal parathyroid adenoma.

We report herein the rare case of a posterior mediastinal parathyroid adenoma 8 mm in diameter, that was identified by both 99m-technetium-methoxyisobutylisonitrile scintigraphy (Tc-MIBI) and high-resolution chest computed tomography (HRCT). Thoracoscopy clearly showed a mediastinal parathyroid adenoma which was successfully removed.

[Cardiac papillary fibroelastomas: report of 2 cases].

We report 2 cases of cardiac papillary fibroelastomas in adults. Case 1: A 61-year-old man was admitted because echocardiography showed a 1 cm pedunculated papillary tumor in the left atrium. In an operation, it was located in the left atrium near the mitral valve and was resected along with a 5 mm margin of endocardium. Case 2: A 60-year-old woman had a 1 cm mobile tumor in the right ventricle near the tricuspid valve located by echocardiography in a preoperative examination of a ventricular septal defect. In an operation, a pedunculated tumor located in the right ventricle was resected. In these 2 cases, histopathology showed the tumor to be a papillary fibroelastoma. Almost all cardiac papillary fibroelastoma are closely related to the cardiac valve, but in these cases, the tumors were located in the left atrium, and the right ventricle, respectively, which is quite rare.

Clinical features of third open-heart valve surgery at the same valve position.

OBJECTIVE: Recently, there has been an increase in case of repeated open-heart valve surgery and the clinical results of the second surgery are only slightly worse than those of the first surgery. However, clinical results of the third open-heart valve surgery at the same position are rarely reported. Clinical features of third open-heart valve surgery at the same position are discussed in this study. METHODS: Between 1995 and 2004, 16 patients underwent third open-heart valve surgery at the same valve position under cardiopulmonary bypass. The average age of the 16 patients, 12 females and 4 males, was 56 +/- 15 years. Clinical features of the 16 cases were retrospectively analyzed. RESULTS: Mechanical valve nonstructural dysfunction was the most common valve malady, followed by bioprosthetic valve dysfunction. The duration of surgery from skin incision to establishment of the cardiopulmonary bypass was 94 +/- 42 minutes. Myocardial ischemia time was 137 +/- 38 minutes and extracorporeal circulation time was 212 +/- 82 minutes. Early mortality was seen in 1 patient (6.25%) and late mortality was seen in 1 patient. CONCLUSION: Mechanical valve nonstructural valve dysfunction leads to repeated valve surgery. The clinical results of the third open-heart valve surgery at the same valve position are acceptable, and the mid-term survival is excellent.

Twenty-two year experience with the omniscience prosthetic heart valve.

This study was designed to evaluate the long-term clinical results of the Omniscience tilting disc valve. Omniscience valves were implanted in 51 patients (mean age, 50 +/- 10 years); 18 had aortic valve, 24 had mitral valve, and 9 had both aortic and mitral valve replacements. Oral warfarin potassium and dipyridamole were prescribed as our anticoagulant therapy. Preoperatively, 42 patients were in New York Heart Association class III or IV, and 23 of 25 surviving patients were in class I or II after operation. There were 2 (3.9%) early deaths and 23 late deaths (3.5 +/- 0.7% per patient-year). Cardiac related mortality including congestive heart failure, sudden death, and thromboembolism, and hemorrhagic complications were seen in 16 patients. Overall survival at 10, 15, and 20 years was 77 +/- 6%, 62 +/- 7%, and 46 +/- 7%, respectively. Thromboembolic complications were seen in 5 patients, for a rate of 0.8 +/- 0.3% per patient-year; similarly, hemorrhagic complications were also seen in 5 patients. Nonstructural prosthetic valve dysfunction was seen in 4 patients, for a rate of 0.6 +/- 0.3% per patient-year, and sudden death was seen in 2, a rate of 0.3 +/- 0.2% per patient-year. The Omniscience prosthesis demonstrated excellent postoperative clinical status with low rates of valve related complications.