Comparative Evaluation in Pharyngo-oesophageal Reconstruction: Radial Forearm Flap compared with Jejunal Flap. A 10-year experience

We reviewed 109 consecutive patients with cancer of the hypopharynx or cervical oesophagus who underwent free flap transfer for immediate reconstruction after total pharyngolaryngo-oesophag-ectomy. The free flaps used were either free jejunal (n = 70) or radial forearm flaps (n = 39). Significantly more fistulas (3/70 compared with 15/39, p < 0.0001) and strictures (6/64 compared with 13/33, p = 0.0008) developed in the radial forearm than the jejunal flap group. However, functional donor site morbidity was minimal and there were no cases of total flap necrosis in the forearm flap group. We consider that the free jejunal flap should be the first choice for total reconstruction of pharyngo-oesophageal defects. However, the forearm flap is suitable for elderly, high risk patients, because it is less invasive and has minimal donor site morbidity, which facilitates early recovery.     

Safety of donor right hepatectomy for adult-to-adult living donor liver transplantation

The purpose of this study was to ascertain the usefulness of preoperative evaluations of donors by computed tomography (CT) volumetry and CT cholangiography for prevention of unexpected liver failure and biliary complications after donor right hepatectomy for adult-to-adult living donor liver transplantation. Fifty-two donors who underwent right hepatectomy without the middle hepatic vein were enrolled in this study. The values of graft weight (GW) were significantly correlated with those of estimated graft volume (GV; P < 0.0001). GW was predicted by the following formula: GW = 155.25 + 0.658 x GV; r(2) = 0.489. CT cholangiography revealed anatomical variants of biliary structure in one-third of the donors and also clearly showed one or two small biliary branches from the caudate lobe to the right hepatic ducts or the confluence in 58% of the donors. Biliary leakage, which was treated by conservative therapy, occurred in only one donor (1.9%). No donors received homologous blood transfusion. Hyperbilirubinemia (serum total bilirubin >5 mg/dl) occurred in 5.8% of the donors during their early postoperative periods. Precise evaluations of liver remnant volume by CT volumetry and biliary variation by CT cholangiography are essential for performing safe donor hepatectomy, preventing hepatic insufficiency and minimizing the risk of biliary tract complications.     

Myocardial tissue pCO2 and calcium content during ventricular fibrillation and reperfusion periods

Forty-one patients who underwent cardiac surgery under conditions of systemic hypothermia and intermittent cold crystalloid potassium cardioplegia were studied, in order to elucidate the effects of ventricular fibrillation and reperfusion on the myocardium, by using the intramyocardial pCO2 and temperature sensor. All patients were assigned to 2 groups, namely; group A (21 cases), in which the time between the aorta declamping and defibrillation was under 10 minutes, and group B (20 cases) in which the time was over 10 minutes. In both groups A and B, myocardial pCO2 increased at the rate of 3.58 +/- 1.70 and 2.16 +/- 0.62 mmHg/min (p less than 0.05) after aorta declamping, respectively and the myocardial pCO2 decreased at the rate of 5.59 +/- 0.60 and 4.18 +/- 0.76 mmHg/min (p less than 0.05) after defibrillation, respectively. In group A, the myocardial calcium content, pre-CPB (cardio pulmonary bypass) was 10.98 +/- 1.62 nmol/mg/dry weight and at the time of aorta declamping it was 15.90 +/- 1.81 nmol/mg/dry weight (p less than 0.05). In group B, the myocardial calcium content, pre-CPB, was 14.62 +/- 2.15 nmol/mg/dry weight and at the time of aorta declamping it was 18.23 +/- 4.36 nmol/mg/dry weight (p less than 0.05). At both three and six hours after the operation, the left ventricular work index per minute (LVWI) in group A showed better cardiac pump function than that in group B. We therefore conclude that when reperfusion is encountered, acidosis can be minimized by prompt defibrillation.     

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.     

Mitogenic and protein synthetic activity of tissue repair cells: control by the postsurgical macrophage

It is well known that fibroblasts are a main source of extracellular matrix synthesis necessary for tissue repair. In addition, macrophages secrete products that are known to modulate synthesis of extracellular matrix. Accordingly, we studied the incorporation of [3H]thymidine, [3H]proline, and [35S]sulfate into macromolecules produced by fibroblasts recovered from the site of peritoneal tissue repair cultured with and without spent media from postsurgical peritoneal macrophages. Rabbits underwent resection and reanastomosis of their small intestines. Peritoneal exudative cells (PEC) were then collected on postsurgical day 5 and day 10 as well as from nonsurgical controls, separated by discontinuous Percoll gradient centrifugation, and cultured for 48 h. A second group of rabbits underwent peritoneal wall abrasion from which fibroblast tissue repair cells (TRC) were collected from the site of injury at postsurgical day 7 and maintained in culture for varying times. Incorporation of radiolabeled precursors into DNA, collagen, and sulfated proteoglycans was determined. Incorporation of [3H]thymidine and [3H]proline into untreated TRC gradually decreased with culture duration. Conversely, [35S]sulfate incorporation gradually increased during prolonged culture. Macrophage spent media increased the levels of [3H]thymidine incorporation by the TRC. [3H]Proline and [35S]sulfate incorporation into TRC were also stimulated by macrophage spent media. However, this stimulation may be due to the enhanced proliferation of TRC by macrophage spent media. In conclusion, tissue repair fibroblasts are activated for postsurgical repair at the site of injury by many factors including secretory products from postsurgical macrophages.     

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.     

Efficacy and Safety of GPR119 Agonist DS-8500a in Japanese Patients with Type 2 Diabetes: a Randomized,Double-Blind,Placebo-Controlled, 12-Week Study

Introduction

G protein-coupled receptor 119 (GPR119) is a promising target for the treatment of type 2 diabetes mellitus (T2DM), as both insulin and glucagon-like peptide-1 secretion can be promoted with a single drug. We compared the efficacy and safety of the GPR119 agonist DS-8500a with placebo and sitagliptin 50 mg in Japanese patients with T2DM.

Methods

This randomized, double-blind, parallel-group comparison study was conducted in Japan (trial registration NCT02628392, JapicCTI-153068). Eligible patients aged ≥ 20 years with T2DM and hemoglobin A1c (HbA1c) ≥ 7.0% and < 10.0% were randomized to receive placebo, DS-8500a (25, 50, or 75 mg), or sitagliptin 50 mg once daily for 12 weeks. The primary efficacy endpoint was change in HbA1c from baseline to week 12. Secondary endpoints included change in fasting plasma glucose (FPG), glucose AUC_0–3h during a meal tolerance test, 2-hour postprandial glucose (2hr-PPG), and changes in lipid parameters (total, low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) cholesterol, and triglycerides) at week 12. Safety endpoints included adverse events, hypoglycemia, and clinical/laboratory variables.

Results

DS-8500a demonstrated dose-dependent HbA1c lowering compared with placebo at week 12: change from baseline ? 0.23% (p = 0.0173), ? 0.37% (p = 0.0001), and ? 0.44% (p < 0.0001) in the 25-mg, 50-mg, and 75-mg groups, respectively. At 50- and 75-mg doses, DS-8500a significantly lowered FPG, glucose AUC_0–3h, and 2hr-PPG compared with placebo. The glucose-lowering effect was maintained up to 12 weeks. DS-8500a did not lower any of the above parameters to a greater extent than sitagliptin. Compared with placebo and sitagliptin, DS-8500a 50 and 75 mg significantly reduced total cholesterol, LDL-cholesterol, and triglycerides, and significantly increased HDL-cholesterol. All DS-8500a doses were well tolerated. Two cases of clinically relevant drug-related hypoglycemia occurred in the DS-8500a 50-mg group.

Conclusion

DS-8500a was well tolerated and demonstrated significant glucose-lowering effects and favorable changes in lipid profiles up to 12 weeks in Japanese patients with T2DM.

Funding

Daiichi Sankyo Co. Ltd.

     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.