Development of an artificial portal vein using bioabsorbable polymers.

PURPOSE: During surgical resection of malignant tumors in the hepatobiliary pancreatic region, portal vein resection and reconstruction may be needed. However, there is no alternative to the portal vein. We therefore developed an artificial portal vein that could be used in the abdominal cavity. METHODS: In the experiments, hybrid pigs (n = 8) were included. An artificial portal vein was created using a bioabsorbable polymer sheet (BAPS). Subsequently, the portal vein's anterior wall was excised into an elliptical shape. A BAPS in the form of a patch was implanted at the same site. At 2 weeks (n = 3) and 3 months (n = 5) after the implantation, the BAPS implantation site was resected and evaluated macroscopically and histopathologically. RESULTS: Immediately after the implantation, blood leakage was not detected. Two weeks after implantation, the BAPS remained, and endothelial cells were observed. Thrombus formation was not observed. Three months after implantation, the BAPS had been completely absorbed and was indistinguishable from the surrounding portal vein. Stenosis and aneurysms were not observed. CONCLUSIONS: BAPS can replace a defective portal vein from the early stage of implantation to BAPS absorption. These results suggest that it can be an alternative material to the portal vein in surgical reconstruction.

Laparoscopic liver resection using a monopolar soft-coagulation device to provide maximum intraoperative bleeding control for the treatment of hepatocellular carcinoma.

BACKGROUND: The popularity of laparoscopic liver resection (LLR) is spreading, worldwide, because the intraoperative blood loss is less than for open hepatectomy and it is associated with a shorter hospitalization period [1-6]. During LLR, intraoperative hemostasis is difficult to achieve, unlike during laparotomy where bleeding can be stopped instantly [7-10]. Our LLR method for the treatment of hepatocellular carcinoma (HCC) includes maximal control of intraoperative bleeding using a monopolar soft-coagulation device. Although we use a monopolar soft-coagulation device to control bleeding during LLR, while coagulating the thin blood vessels, we also developed a maneuver (the hepatocyte crush method: HeCM) to allow liver transection to progress while liver parenchymal cells are being crushed. METHOD: Between January 2008 and March 2016, we performed total LLR on 150 hepatocellular carcinoma patients (144 partial liver resections and six left lateral sectionectomies) using the maneuver shown in the video. RESULTS: The patients had Child-Pugh Scores of grade A (n = 100), B (42), or C (n = 8) and the localizations of tumor were segment (S) 1(n = 7), S2 (19), S3 (23), S4 (28), S5 (17), S6 (26), S8 (17), and S8 (29). The median blood loss was 30 (range 0-490) g during a median surgical time of 207 (range 127-468) min. One patient required conversion to a laparotomy due to the presence of severe adhesions; none of the patients required conversion due to intraoperative hemorrhage. The peak aspartate aminotransferase (AST) level was 320 (range 57-1964) IU/L. Although some patients showed high AST levels, none showed signs of hepatic failure. The median postoperative hospital stay duration was 6 (range 3-21) days. Postoperative complications occurred in seven cases (4.7%), including intraabdominal abscesses (n = 2), wound infections (2), intraabdominal hemorrhage (1), bile duct stricture (1), and umbilical hernia (1). The mortality was zero. CONCLUSION: HeCM, combined with the use of a monopolar soft-coagulation device, is a good technique for reducing bleeding during liver resection in patients with HCC.

In Vitro Regio- and Stereoselective Oxidation of ß-Ionone by Human Liver Microsomes.

The metabolism of the norisoprenoid ß-ionone was investigated in vitro using human liver microsomes and 11 different recombinant cytochrome P450 enzymes expressed in Trichoplusia ni cells. ß-Ionone was found to be oxidized via 4S-hydroxylation by CYP2B6 in human liver microsomes. CYP1A2 also regioselectively catalyzed the hydroxylation of ß-ionone to yield 4-hydroxylation; this conversion was not stereoselective. Further kinetic analysis revealed that CYP2B6 exhibited the highest activity for ß-ionone 4-hydroxylation. Kinetic analysis showed that Km and Vmax for oxidation of ß-ionone by CYP1A2 and CYP2B6 was 107.9 ± 36.0 µM and 3200.3 ± 323.0 nmol/min/nmol P450 and 5.6 ± 1.2 µM and 572.8 ± 29.8 nmol/min/nmol P450, respectively. The reaction rates observed using human liver microsomes and recombinant CYP2B6 were very high compared with those of other CYP2B6 substrates reported thus far. These results suggest that ß-ionone, a norisoprenoid present in nature, is one of the effective substrates for CYP2B enzymes in human liver microsomes. To the best of our knowledge, this is the first time that 4-hydroxy ß-ionone has been described as a human metabolite of ß-ionone.

A case of intraductal papillary neoplasm of the bile duct preoperatively diagnosed using contrast-enhanced endoscopic ultrasonography.

A 71-year-old man was referred to our hospital and was diagnosed with jaundice and a liver function disorder. Although we suspected an intraductal papillary neoplasm of the bile duct (IPNB)-derived caudate branches on the basis of contrast-enhanced CT, MRI, and endoscopic retrograde cholangiopancreatography, we could not clearly identify the tumor. Therefore, we examined the lesion using endoscopic ultrasonography (EUS). We could visualize an iso-hyperechoic elevated tumor in the caudate branches. The tumor was observed as a hypervascular lesion using contrast-enhanced EUS, which is useful in preoperatively diagnosing IPNB and detecting the presence of lesions.

Fibrin glue closure for intractable pancreatic fistulae after pancreaticoduodenectomy.

CONTEXT: Treatment of pancreatic fistulae after pancreaticoduodenectomy is extremely important because it determines the patient's postoperative course. In particular, treatment of grade B cases should be conducted in a timely manner to avoid deterioration to grade C. OBJECTIVE: We report the successful treatment of six cases of postoperative intractable, grade B pancreatic fistulae, in which fistula closure was achieved through the use of tissue adhesive. METHODS: Six subjects presented at our hospital with grade B pancreatic fistulae after pancreaticoduodenectomy. In all cases, the drain amylase values were high immediately after the operation, and the replacement of the drain was enforced. Closure of the fistula was performed by pouring tissue adhesive into the fistula from the drain, after the fistula had been straightened. RESULTS: Closure of the fistula was achieved in all six cases at the first attempt. The average fistula length was 13.2 cm, the average volume of pancreatic fluid discharge just before treatment was 63.3 mL, the average amylase value in the drainage was 40,338.5 IU/L, and the subjects were discharged from hospital an average of 8.8 days after treatment. There were no recurrences after treatment. CONCLUSION: Intractable pancreatic fistulae can be effectively treated using the tissue adhesive method.

Metabolism of (-)-cis- and (-)-trans-rose oxide by cytochrome P450 enzymes in human liver microsomes.

The in vitro metabolism of (-)-cis- and (-)-trans-rose oxide was investigated using human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes for the first time. Both isomers of rose oxide were incubated with human liver microsomes, and the formation of the respective 9-oxidized metabolite were determined using gas chromatography-mass spectrometry (GC-MS). Of 11 different recombinant human P450 enzymes used, CYP2B6 and CYP2C19 were the primary enzymes catalysing the metabolism of (-)-cis- and (-)-trans-rose oxide. CYP1A2 also efficiently oxidized (-)-cis-rose oxide at the 9-position but not (-)-trans-rose oxide. α-Naphthoflavone (a selective CYP1A2 inhibitor), thioTEPA (a CYP2B6 inhibitor) and anti-CYP2B6 antibody inhibited (-)-cis-rose oxide 9-hydroxylation catalysed by human liver microsomes. On the other hand, the metabolism of (-)-trans-rose oxide was suppressed by thioTEPA and anti-CYP2B6 at a significant level in human liver microsomes. However, omeprazole (a CYP2C19 inhibitor) had no significant effects on the metabolism of both isomers of rose oxide. Using microsomal preparations from nine different human liver samples, (-)-9-hydroxy-cis- and (-)-9-hydroxy-trans-rose oxide formations correlated with (S)-mephenytoin N-demethylase activity (CYP2B6 marker activity). These results suggest that CYP2B6 plays important roles in the metabolism of (-)-cis- and (-)-trans-rose oxide in human liver microsomes.

Chemical Composition and Character Impact Odorants in Volatile Oils from Edible Mushrooms.

The aim of this study was to investigate the chemical composition and the odor-active components of volatile oils from three edible mushrooms, Pleurotus ostreatus, Pleurotus eryngii, and Pleurotus abalonus, which are well-known edible mushrooms. The volatile components in these oils were extracted by hydrodistillation and identified by GC/MS, GC-olfactometry (GC-O), and aroma extract dilution analysis (AEDA). The oils contained 40, 20, and 53 components, representing 83.4, 86.0, and 90.8% of the total oils in P. ostreatus, P. eryngii, and P. abalonus, respectively. Odor evaluation of the volatile oils from the three edible mushrooms was also carried out using GC-O, AEDA, and odor activity values, by which 13, eight, and ten aroma-active components were identified in P. ostreatus, P. eryngii, and P. abalonus, respectively. The most aroma-active compounds were C8 -aliphatic compounds (oct-1-en-3-ol, octan-3-one, and octanal) and/or C9 -aliphatic aldehydes (nonanal and (2E)-non-2-enal).

Thoracoscopic hepatectomy for malignant liver tumor.

BACKGROUND: Anatomical position of the liver poses a difficulty in approaching the lesions using a laparoscopic approach. METHODS: The patient was a 79-year-old man with a surgical history of laparoscopic sigmoidectomy for colon cancer and posterior segmentectomy of the liver for metastatic liver tumor. On admission, he presented with another liver tumor (diameter, 1.5 cm) in the dome of segment VIII. Because of the high possibility of severe adhesion around the liver and difficulty of approaching the lesion from the abdomen, we selected the transthoracic approach rather than the abdominal approach; the patient consented to this procedure. The patient was placed in the left-lateral position under general anesthesia with single-lung ventilation. We placed three trocars into the right thoracic space. The intrathoracic space was observed using a flexible-tip rigid scope (Olympus, Tokyo, Japan). The tumor was detected by inserting a flexible laparoscopic ultrasound probe (Hitachi Aloka, Ltd., Tokyo, Japan) through the diaphragm; the diaphragm was dissected immediately above the tumor using a harmonic scalpel (Ethicon Endo-Surgery, Inc., Cornelia, GA). The liver surface was precoagulated using a low-voltage monopolar coagulator with a ball-shaped tip (Amco Inc., Tokyo, Japan) with the electrosurgical unit VIO300D (Erbe Elektromedizin, Tuebingen, Germany). The parenchyma was first sealed using BiClamp LAP forceps (Erbe Elektromedizin) and divided using the harmonic scalpel. The specimen was extracted using a retrieval bag. After complete hemostasis was achieved, the diaphragm was closed by continuous suturing. RESULTS: The operation lasted for 310 min and estimated blood loss was 10 mL. The patient was discharged on postoperative day 4. CONCLUSIONS: Although the duration of TH was long because of the narrow thoracic cavity space, TH was performed without any problems. As a rule, we should select TH for lesions located in the dorsal segment VII/VIII, with severe adhesion around the liver.

Chemical composition and aroma evaluation of essential oils from Evolvulus alsinoides L.

The aim of this study was to investigate the chemical composition and the odor-active compounds of the essential oils from Evolvulus alsinoides, which is a well-known edible and medicinal plant. The volatile compounds in the oils were identified by hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE) in combination with GC, GC/MS, GC/O (=olfactometry), aroma extract dilution analysis (AEDA), and relative flavor activities (RFA values). The most abundant compound in the HD oil was cis-α-necrodol (12.62%), an irregular monoterpene with a cyclopentane skeleton, which is very unusual in the plant kingdom. In the SAFE oil, the main components included 2-butoxyethanol (9.01%), benzyl alcohol (8.01%), and γ-butyrolactone (7.37%). Through sensory analysis, 21 aroma-active compounds were identified by GC/O. The most intense aroma-active compounds in the HD oil were hexan-1-ol and γ-nonalactone, both of which showed high RFA values. α-Methyl-γ-butyrolactone and dimethyl sulfone contributed more strongly to the aroma of the SAFE oil. These results imply that the essential oils of E. alsinoides deserve further investigation in the food industry.

Aroma evaluation of setonojigiku (Chrysanthemum japonense var. debile) by hydrodistillation and solvent-assisted flavour evaporation.

INTRODUCTION: The Chrysanthemum genus consisting of about 200 species is mainly distributed over the Northern Hemisphere. Despite the pleasant odour of C. japonense var. debile (setonojigiku), no detailed analysis of the aroma-active compounds has been reported using sensory evaluation. OBJECTIVES: Using a hydrodistillation (HD) and a solvent-assisted flavour evaporation (SAFE) method to obtain the volatile oil from the leaf parts. METHODS: To clarify odorants contributing to the characteristic aroma-active compounds, the aroma-extract dilution analysis (AEDA) method was performed through gas chromatography olfactometry (GC/O) analysis. In addition, the odour activity value (OAV) was calculated in order to determine the relative contribution of each compound to the aroma-active compounds. RESULTS: A total of 42 components by HD oil were identified by GC-MS, whereas 34 components were identified in SAFE oil. Thirteen compounds were identified by GC/O analysis in HD and SAFE oils respectively. CONCLUSION: Each extraction method has its own advantages and disadvantages, and they are generally complementary to each other. On the basis of AEDA, OAV and sensory evaluations, [2.2.1] bicyclic monoterpenes (borneol, bornyl acetate and camphor) and ß-caryophyllene are considered to be the main aroma-active compounds of both extraction methods.

New compounds, 6-hydroxykarahanaenone and 10-hydroxykarahanaenone, from biotransformation of karahanaenone by CYP2A6.

The in vitro biotransformation of karahanaenone was examined in cytochrome P450 (CYP) 2A6. The biotransformation of karahanaenone by CYP2A6 was investigated by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Karahanaenone was found to be oxidized to two metabolites by CYP2A6. In order to produce large quantity of metabolites by CYP2A6, the biotransformation of karahanaenone by Salmonella typhimurium OY1002/2A6 was investigated. Similarly, two metabolites were confirmed by GC and GC-MS. The structure of metabolites was determined by 1D NMR, 2D NMR, and infrared, as a result there were new compounds, (6R)-hydroxykarahanaenone and 10-hydroxykarahanaenone.

Novel pancreatoenteric reconstruction using a bioabsorbable polymer sheet and biocompatible bond.

BACKGROUND: Pancreatoenteric reconstruction often induces severe complications. Although many techniques have been developed to prevent these complications, no standard technique has yet emerged. We developed a novel technique, sutureless pancreatoenteric anastomosis, that uses a bioabsorbable polymer sheet (BAPS) and biocompatible bond (BCB) to prevent the complications associated with pancreatoenteric anastomosis. We used large animals to investigate whether this technique is suitable for clinical use. MATERIALS AND METHODS: Six pigs were laparotomized under general anesthesia. The body of the pancreas was divided, and the proximal stump was closed by suture. A BAPS coated with BCB was rolled and fixed around the distal pancreatic stump to form a cylinder that was anastomosed to the duodenum without suturing the pancreas. Twenty weeks after the initial operation the operated sites were extirpated and evaluated grossly and histologically. RESULTS: All operated pigs survived without pancreatic juice leakage until they were killed. At 20 wk, the BAPS could not be identified. The pancreatic stump was tightly affixed to the duodenum. Histologic study revealed that the pancreatic stump and duodenal wall were continuous and the main pancreatic duct opened into the lumen of the duodenum. CONCLUSIONS: Sutureless pancreatoenterostomy with BAPS and BCB may be clinically feasible.

Synthesis, antioxidant capacity, and structure-activity relationships of tri-O-methylnorbergenin analogues on tyrosinase inhibition.

A series of tri-O-methylnorbergenin analogues 1-9 were synthesized and their antioxidant activities and inhibitory effects on tyrosinase were evaluated. Among tested analogues, compound 4 bearing cathechol moiety exhibited greater antioxidant activity and excellent inhibition on tyrosinase with IC50 value of 9.1 µM, comparable to that of corresponding positive controls. The inhibition mechanism analysis of compound 4 demonstrated that it was a mixed-type inhibitor on tyrosinase. These results suggest that these compounds may serve as a useful clue for further designing and development of novel potential tyrosinase inhibitors.

Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model.

BACKGROUND: Stricture formation is one of the major complications after endoscopic removal of large superficial squamous cell neoplasms of the esophagus, and local steroid injections have been adopted to prevent it. However, fundamental pathological alterations related to them have not been well analyzed so far. The aim of this study was to analyze the time course of the healing process of esophageal large mucosal defects resulting in stricture formation and its modification by local steroid injection, using an animal model. METHODS: Esophageal circumferential mucosal defects were created by endoscopic mucosal dissection (ESD) for four pigs. One pig was sacrificed five minutes after the ESD, and other two pigs were followed-up on endoscopy and sacrificed at the time of one week and three weeks after the ESD, respectively. The remaining one pig was followed-up on endoscopy with five times of local steroid injection and sacrificed at the time of eight weeks after the ESD. The esophageal tissues of all pigs were subjected to pathological analyses. RESULTS: For the pigs without steroid injection, the esophageal stricture was completed around three weeks after the ESD on both endoscopy and esophagography. Histopathological examination of the esophageal tissues revealed that spindle-shaped α-smooth muscle actin (SMA)-positive myofibroblasts arranged in a parallel fashion and extending horizontally were identified at the ulcer bed one week after the ESD, and increased contributing to formation of the stenotic luminal ridge covered with the regenerated epithelium three weeks after the ESD. The proper muscle layer of the stricture site was thinned with some myocytes which seemingly showed transition to the myofibroblast layer. By contrast, for the pig with steroid injection, esophageal stricture formation was not evident with limited appearance of the spindle-shaped myofibroblasts, instead, appearance of stellate or polygocal SMA-positive stromal cells arranged haphazardly in the persistent granulation tissue of the ulcer site. CONCLUSIONS: Proliferation of spindle-shaped myofibroblasts arranged in a parallel fashion is likely to play an important role in stricture formation after circumferential mucosal defects by esophageal ESD, which may be related to the thinning of the proper muscle layer in the healing course of the defects. Local steroid injection seems to be effective to prevent the stricture through the modification of this process.

Structure-activity relationships of bergenin derivatives effect on α-glucosidase inhibition.

The α-glucosidase inhibitory activities of bergenin derivatives were evaluated. Bergenin derivatives were synthesized from bergenin which is a characteristic compound of B. ligulata. A new bergenin derivative, 11-O-(3',4'-dimethoxybenzoyl)-bergenin showed the highest potent inhibitory activity among those of bergenin derivatives. The presence of substituents at 3',4'-position in bergenin derivatives altered the α-glucosidase inhibitory activity. 11-O-(3',4'-dimethoxybenzoyl)-bergenin was noncompetitive inhibitor for α-glucosidase. The present study reveals that bergenin derivatives could be classified as a new group of α-glucosidase inhibitors.

Newly designed bioabsorbable substitute for the treatment of diaphragmatic defects.

PURPOSE: Earlier studies have investigated the suitability of various materials and autologous grafts for the repair of diaphragmatic defects. Our group investigated the feasibility of using an artificial diaphragm (AD) to repair wide diaphragmatic defects. METHODS: Twelve pigs were laparotomized and, in each pig, a defect was fashioned by resecting a round 8-cm diameter hole in the left diaphragm. Next, the defect was repaired by implanting an AD. The animals were relaparotomized 8 or 24 weeks after implantation for gross, histological and radiological observation of the implanted sites. RESULTS: All recipient animals survived until killing for evaluation. Chest X-ray examinations showed no differences between the preoperative diaphragms and the grafted diaphragms at 8 and 24 weeks after implantation. At 8 weeks after implantation, the implanted sites exhibited fibrous adhesions to the liver and lungs without deformities or penetrations. Parts of the surface tissue at the graft sites had a varnished appearance similar to those of the native diaphragm. Histology performed at 8 weeks detected no trace of the ADs in the graft sites; however, numerous inflammatory cells and profuse fibrous connective tissue were observed. At 24 weeks after implantation, no differences were found in the thorax between the areas with the grafts and the unaffected areas. Histology of the graft sites in the thorax confirmed growth of mesothelial cells similar to that observed in the native diaphragm. CONCLUSIONS: Artificial diaphragms can be a novel substitute for diaphragmatic repair.

N-Caffeoyl serotonin as selective COX-2 inhibitor.

The inhibitory effects of the synthetic serotonin analogues (1-8) on COX (1 and 2) were evaluated. Two serotonin derivatives (4 and 8) showed inhibitory effect of COX (1 and 2). Especially, 4 exhibited excellent inhibitions on COX-2 with extremely high potency (IC(50)=42.5 µM). The inhibitory activities of cinnamic acid derivatives and serotonin were evaluated to clarify whether inhibitory activities of compound 4 and 8 are due to cinnamic acid moiety or serotonin moiety. Caffeic acid and N-caffeoyl serotonin (4) exhibited selective inhibition of COX-2 compared to aspirin. Comparison caffeic acid with 4 suggested that the linkage of caffeic acid and serotonin enhance COX-2 inhibition. Comparison of structures of caffeic acid and sinapic acid implied that catechol moiety of cinnamic acid derivatives is a major contributing factor for selective inhibition of COX-2. The selective COX-2 inhibitory activity of compound 4 is significant and could be employed as drugs against inflammatory and allergy.

Structure-activity relationships for naturally occurring coumarins as ß-secretase inhibitor.

The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of ß-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC(50) value of 9.9 µM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5-methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC(50) values <25.0 µM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors.

Single-port laparoscopic hepatectomy: technique, safety, and feasibility in a clinical case series.

BACKGROUND: The recent use of single-port-access surgery in cholecystectomy and other abdominal surgeries has confirmed its safety and validity as a treatment option. However, few reports have described the use of complete single-port access surgeries in hepatectomy for neoplasms. METHODS: The authors performed single-port laparoscopic hepatectomy (SLH) for eight patients (5 patients with hepatocellular carcinoma, 1 patient with metastatic liver tumor, 1 patient with endocrine liver tumor, and 1 patient with hemangioma). Furthermore, in terms of Child-Pugh classification, five patients were in category A, two in category B, and one in category C. The patients were eligible for SLH if they had solitary tumors measuring 3 cm or smaller on the caudal surface of the liver. The lesion was approached through a 20-mm supraumbilical incision using a single-port access device. RESULTS: No patient experienced intraoperative complications that required additional port access and conversion to laparotomy. The operative time was 148 min (range, 141-235 min). The postoperative course of the patients was uneventful, and they were discharged an average of 6.2 days (range, 3-11 days) after the operation. Approximately 2 weeks after discharge, the patients experienced no wound pain or liver dysfunction. CONCLUSION: The SLH technique is a safe and feasible procedure for a specific group of candidates, including patients with high-grade liver dysfunction.

Regeneration of extrahepatic bile ducts by tissue engineering with a bioabsorbable polymer.

With the widespread adoption of laparoscopic cholecystectomy and living-donor liver transplantation in recent years, complications involving the biliary system, stenosis in particular, are increasing. Various invasive and non-invasive techniques are now available for the treatment of biliary stenosis, but all are compromised by a high risk of recurrence and other problems. As a potential solution, our group has developed a bioabsorbable polymer (BAP) tube for implantation as a bypass graft. In the study reported here, we implanted this BAP tube and confirmed bile duct regeneration at the graft site after the tube had been degraded and absorbed into the body. We briefly describe our findings on extrahepatic biliary tissue regeneration, focusing on the possibility of its clinical application. This artificial bile duct may promote the development of novel treatments for biliary disease.