Clinical efficacy of endoscopic ultrasonography for decision of treatment strategy of gastric cancer.

BACKGROUND: Accurate preoperative tumor staging of gastric cancer is indispensable with expansion of indications for laparoscopic surgery and endoscopic resection. It is important to distinguish mucosal cancer (T1a) in smaller lesion and differentiate early gastric cancer (EGC) in larger lesion considering endoscopic resection indication and laparoscopic surgery indication. We evaluated the clinical outcomes of endoscopic ultrasonography (EUS) for the decision of treatment strategy of gastric cancer compared with pathological staging. METHODS: The patients who underwent EUS and surgical or endoscopic resection for gastric cancer were retrospectively reviewed between September 2005 and February 2016. The depth of tumor invasion (T staging) by EUS was compared with the pathological staging after endoscopic or surgical resection. RESULTS: A total of 6084 patients were finally analyzed. The accuracy rates for T1a and EGC were 75.0 and 89.4%, respectively. The overall accuracy of T staging by EUS was 66.3% when divided by T1a, T1b, and over T2. The accuracy of EUS prior to endoscopic resection was 75.1% in absolute indication and 73.1% in expanded criteria, respectively. The accuracy rates for T1a with lesion ≤ 2 cm in miniprobe EUS and EGC with lesion > 2 cm in conventional EUS were 84.6 and 83.2%, respectively. In multivariate analysis, presence of ulcer, large tumor size, and radial EUS were associated with overestimation, and small tumor size and miniprobe were associated with underestimation in T staging. CONCLUSIONS: EUS showed the high accuracy of 84.6% for T1a in lesion ≤ 2 cm in miniprobe EUS and 83.2% for EGC in lesion > 2 cm in conventional EUS, respectively. EUS can be a complementary diagnostic method to determine endoscopic or surgical treatment modality.

Combined use of dexmedetomidine and propofol in monitored anesthesia care: a randomized controlled study.

BACKGROUD: Although propofol and dexmedetomidine have been widely used for monitored anesthesia care, their adverse effects necessitate the search for better methods. Therefore, we performed this randomized controlled trial to evaluate the combined use of propofol and dexmedetomidine. METHODS: Eighty-seven adult patients undergoing hand surgery under brachial plexus block were randomly allocated to receive 1.6 µg/ml of the target effect site concentration of propofol (P group) and infusion of 0.4 µg/kg/h dexmedetomidine following a loading dose of 1.0 µg/kg for 10 min (D group). The M group received a half-dose of both drugs simultaneously. The maintenance dose was adjusted to maintain an Observer Assessment of Alertness/Sedation score of 3. Cardiorespiratory variables, adverse effects, and drug efficacy were observed. RESULTS: The significantly higher mean arterial pressure (mmHg) in the D group [P group 86.9 (12.6), D group 96.0 (12.2), M group 85.6 (10.6), p = 0.004)] and a significantly higher heart rate (beat/min) in the P group were observed [P group 67.3 (9.0), D group 57.8 (6.9), M group 59.2 (7.4), p < 0.001)]. The M group had a significant lower incidence of airway obstruction (p < 0.001) and the D group had a higher incidence of bradycardia requiring atropine (p = 0.001). The P group had higher incidences of hypoxia (p = 0.001), spontaneous movement (p < 0.001) and agitation (p = 0.001). The satisfaction scores of the patients (p = 0.007) and surgeon (p < 0.001) were higher in the M group. Onset time was significantly longer in the D group (p < 0.001). CONCLUSIONS: The combined use of propofol and dexmedetomidine provided cardiovascular stability with decreased adverse effects. Additionally, it led to a similar onset time of propofol and achieved higher satisfaction scores. TRIAL REGISTRATION: KCT0001284 . Retrospectively registered 25 November 2014.

An apolipoprotein B100 mimotope prevents obesity in mice.

Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44-65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.

The influence of mild hypothermia on reversal of rocuronium-induced deep neuromuscular block with sugammadex.

BACKGROUND: Mild hypothermia may be frequently induced due to cool environments in the operating room. The study analyzed patient recovery time and response to sugammadex after a prolonged rocuronium-induced deep neuromuscular block (NMB) during mild hypothermia. METHODS: Sixty patients were randomly (1:1) allocated to the mild hypothermia and normothermia groups, defined as having core temperatures between 34.5-35°C and 36.5-37°C, respectively. Patients received 0.6 mg/kg of rocuronium, followed by 7-10 µg/kg/min to maintain a deep NMB [post-tetanic count (PTC) 1-2]. After surgery, the deep NMB was reversed with sugammadex 4.0 mg/kg. The primary end-point was the time until the train-of-four (TOF) ratio was 0.9. RESULTS: The appropriate neuromuscular function (TOF ratio ≥ 0.9) was restored after sugammadex was administered, even after hypothermia. The length of recovery in the hypothermia patients [mean (SD), 171.1 (62.1) seconds (s)] was significantly slower compared with the normothermia patients [124.9 (59.2) s] (p = 0.005). There were no adverse effects from sugammadex. CONCLUSIONS: Sugammadex safely and securely reversed deep rocuronium-induced NMB during mild hypothermia. An additional 46 s was required for recovery from a deep NMB in hypothermia patients. Based on the results, we think this prolonged recovery time is clinically acceptable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965067.

Feasibility test of utilizing Saccharophagus degradans 2-40(T) as the source of crude enzyme for the saccharification of lignocellulose.

In the conversion of lignocellulose into high-value products, including fuels and chemicals, the production of cellulase and the enzymatic hydrolysis for producing fermentable sugar are the largest contributors to the cost of production of the final products. The marine bacterium Saccharophagus degradans 2-40(T) can degrade more than ten different complex polysaccharides found in the ocean, including cellulose and xylan. Accordingly, S. degradans has been actively considered as a practical source of crude enzymes needed for the saccharification of lignocellulose to produce ethanol by others including a leading commercial company. However, the overall enzyme system of S. degradans for hydrolyzing cellulose and hemicellulose has not been quantitatively evaluated yet in comparison with commercial enzymes. In this study, the inductions and activities of cellulase and xylanase of cell-free lysate of S. degradans were investigated. The growth of S. degradans cells and the activities of cellulase and xylanase were promoted by adding 2 % of cellulose and xylan mixture (cellulose:xylan = 4:3 in mass ratio) to the aquarium salt medium supplemented with 0.2 % glucose. The specific cellulase activity of the cell-free lysate of S. degradans, as determined by the filter paper activity assay, was approximately 70 times lower than those of commercial cellulases, including Celluclast 1.5 L and Accellerase 1000. These results imply that significant improvement in the cellulase activity of S. degradans is needed for the industrial uses of S. degradans as the enzyme source.

Secondary skull reconstruction with autogenous split calvarial bone grafts versus nonautogenous materials.

BACKGROUND: Skull reconstructions, which can be required for various reasons, including decompressive craniectomy, trauma, and tumors, are challenging issues in plastic surgery. Moreover, obtaining a low complication ratio in secondary skull reconstructions is more difficult than in primary skull reconstructions. Because standardized protocols have not been established, we here compare cranioplasty performance using fresh autogenous split calvarial bone grafts and allogenic or alloplastic materials in secondary revisional cases. METHODS: Surgical correction of skull defects was performed in 25 patients in our center between 2005 and 2012. Only secondary cranioplasty cases were reviewed retrospectively. There were 17 men and 8 women, with ages ranging from 8 to 62 years at the time of surgery. The mean follow-up was 55.6 months. The surgical procedure in each case was a routine cranioplasty. In most of the cases, a 1-piece split calvarial bone graft was used while minimizing the separation of the bone flap into multiple pieces. RESULTS: In comparison with the skull reconstructional approach using nonautogenous materials, the functional and esthetic results of skull reconstruction using autogenous calvarial bone grafts were better and more consistent in secondary revisional cases. The group that received autogenous calvarial bone grafts showed a reconstruction success rate of 80% without esthetic and functional complications. In contrast, the group that received nonautogenous materials had a 30% success rate. CONCLUSIONS: Secondary cranial defect reconstructions with autogenous calvarial bone grafts showed better functional and esthetic results than skull reconstructions with nonautogenous materials.

Discovery of a peripheral 5HT2A antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

Genome-scale reconstruction and in silico analysis of Klebsiella oxytoca for 2,3-butanediol production.

BACKGROUND: Klebsiella oxytoca, a Gram-negative, rod-shaped, and facultative anaerobic bacterium, is one of the most promising 2,3-butanediol (2,3-BD) producers. In order to improve the metabolic performance of K. oxytoca as an efficient biofactory, it is necessary to assess its metabolic characteristics with a system-wide scope, and to optimize the metabolic pathways at a systems level. Provision of the complete genome sequence of K. oxytoca enabled the construction of genome-scale metabolic model of K. oxytoca and its in silico analyses. RESULTS: The genome-scale metabolic model of K. oxytoca was constructed using the annotated genome with biochemical and physiological information. The stoichiometric model, KoxGSC1457, is composed of 1,457 reactions and 1,099 metabolites. The model was further refined by applying biomass composition equations and comparing in silico results with experimental data based on constraints-based flux analyses. Then, the model was applied to in silico analyses to understand the properties of K. oxytoca and also to improve its capabilities for 2,3-BD production according to genetic and environmental perturbations. Firstly, in silico analysis, which tested the effect of augmenting the metabolic flux pool of 2,3-BD precursors, elucidated that increasing the pyruvate pool is primarily important for 2,3-BD synthesis. Secondly, we performed in silico single gene knockout simulation for 2,3-BD overproduction, and investigated the changes of the in silico flux solution space of a ldhA gene knockout mutant in comparison with that of the wild-type strain. Finally, the KoxGSC1457 model was used to optimize the oxygen levels during fermentation for 2,3-BD production. CONCLUSIONS: The genome-scale metabolic model, KoxGSC1457, constructed in this study successfully investigated metabolic characteristics of K. oxytoca at systems level. The KoxGSC1457 model could be employed as an useful tool to analyze its metabolic capabilities, to predict its physiological responses according to environmental and genetic perturbations, and to design metabolic engineering strategies to improve its metabolic performance.

In silico aided metabolic engineering of Klebsiella oxytoca and fermentation optimization for enhanced 2,3-butanediol production.

Klebsiella oxytoca naturally produces a large amount of 2,3-butanediol (2,3-BD), a promising bulk chemical with wide industrial applications, along with various byproducts. In this study, the in silico gene knockout simulation of K. oxytoca was carried out for 2,3-BD overproduction by inhibiting the formation of byproducts. The knockouts of ldhA and pflB genes were targeted with the criteria of maximization of 2,3-BD production and minimization of byproducts formation. The constructed K. oxytoca ΔldhA ΔpflB strain showed higher 2,3-BD yields and higher final concentrations than those obtained from the wild-type and ΔldhA strains. However, the simultaneous deletion of both genes caused about a 50 % reduction in 2,3-BD productivity compared with K. oxytoca ΔldhA strain. Based on previous studies and in silico investigation that the agitation speed during 2,3-BD fermentation strongly affected cell growth and 2,3-BD synthesis, the effect of agitation speed on 2,3-BD production was investigated from 150 to 450 rpm in 5-L bioreactors containing 3-L culture media. The highest 2,3-BD productivity (2.7 g/L/h) was obtained at 450 rpm in batch fermentation. Considering the inhibition of acetoin for 2,3-BD production, fed-batch fermentations were performed using K. oxytoca ΔldhA ΔpflB strain to enhance 2,3-BD production. Altering the agitation speed from 450 to 350 rpm at nearly 10 g/L of acetoin during the fed-batch fermentation allowed for the production of 113 g/L 2,3-BD, with a yield of 0.45 g/g, and for the production of 2.1 g/L/h of 2,3-BD.

Functional cell surface display and controlled secretion of diverse Agarolytic enzymes by Escherichia coli with a novel ligation-independent cloning vector based on the autotransporter YfaL.

Autotransporters have been employed as the anchoring scaffold for cell surface display by replacing their passenger domains with heterologous proteins to be displayed. We adopted an autotransporter (YfaL) of Escherichia coli for the cell surface display system. The critical regions in YfaL for surface display were identified for the construction of a ligation-independent cloning (LIC)-based display system. The designed system showed no detrimental effect on either the growth of the host cell or overexpressing heterologous proteins on the cell surface. We functionally displayed monomeric red fluorescent protein (mRFP1) as a reporter protein and diverse agarolytic enzymes from Saccharophagus degradans 2-40, including Aga86C and Aga86E, which previously had failed to be functional expressed. The system could display different sizes of proteins ranging from 25.3 to 143 kDa. We also attempted controlled release of the displayed proteins by incorporating a tobacco etch virus protease cleavage site into the C termini of the displayed proteins. The maximum level of the displayed protein was 6.1 × 10(4) molecules per a single cell, which corresponds to 5.6% of the entire cell surface of actively growing E. coli.

Fermentation and evaluation of Klebsiella pneumoniae and K. oxytoca on the production of 2,3-butanediol.

Klebsiella is one of the genera that has shown unbeatable production performance of 2,3-butanediol (2,3-BD), when compared to other microorganisms. In this study, two Klebsiella strains, K. pneumoniae (DSM 2026) and K. oxytoca (ATCC 43863), were selected and evaluated for 2,3-BD production by batch and fed-batch fermentations using glucose as a carbon source. Those strains' morphologies, particularly their capsular structures, were analyzed by scanning electron microscopy (SEM). The maximum titers of 2,3-BD by K. pneumoniae and K. oxytoca during 10 h batch fermentation were 17.6 and 10.9 g L(-1), respectively; in fed-batch cultivation, the strains showed the maximum titers of 50.9 and 34.1 g L(-1), respectively. Although K. pneumoniae showed higher productivity, SEM showed that it secreted large amounts of capsular polysaccharide, increasing pathogenicity and hindering the separation of cells from the fermentation broth during downstream processing.

Aqueous ammonia pretreatment, saccharification, and fermentation evaluation of oil palm fronds for ethanol production.

Oil palm fronds are the most abundant lignocellulosic biomass in Malaysia. In this study, fronds were tested as the potential renewable biomass for ethanol production. The soaking in aqueous ammonia pretreatment was applied, and the fermentability of pretreated fronds was evaluated using simultaneous saccharification and fermentation. The optimal pretreatment conditions were 7 % (w/w) ammonia, 80 °C, 20 h of pretreatment, and 1:12 S/L ratio, where the enzymatic digestibility was 41.4 % with cellulase of 60 FPU/g-glucan. When increasing the cellulase loading in the hydrolysis of pretreated fronds, the enzymatic digestibility increased until the enzyme loading reached 60 FPU/g-glucan. With 3 % glucan loading in the SSF of pretreated fronds, the ethanol concentration and yield based on the theoretical maximum after 12 and 48 h of the SSF were 7.5 and 9.7 g/L and 43.8 and 56.8 %, respectively. The ethanol productivities found at 12 and 24 h from pretreated fronds were 0.62 and 0.36 g/L/h, respectively.

Sex-Specific B Cell and Anti-Myelin Autoantibody Response After Peripheral Nerve Injury.

Immunotherapy holds promise as a non-addictive treatment of refractory chronic pain states. Increasingly, sex is recognized to impact immune regulation of pain states, including mechanical allodynia (pain from non-painful stimulation) that follows peripheral nerve trauma. This study aims to assess the role of B cells in sex-specific responses to peripheral nerve trauma. Using a rat model of sciatic nerve chronic constriction injury (CCI), we analyzed sex differences in (i) the release of the immunodominant neural epitopes of myelin basic protein (MBP); (ii) the levels of serum immunoglobulin M (IgM)/immunoglobulin G (IgG) autoantibodies against the MBP epitopes; (iii) endoneurial B cell/CD20 levels; and (iv) mechanical sensitivity behavior after B cell/CD20 targeting with intravenous (IV) Rituximab (RTX) and control, IV immunoglobulin (IVIG), therapy. The persistent MBP epitope release in CCI nerves of both sexes was accompanied by the serum anti-MBP IgM autoantibody in female CCI rats alone. IV RTX therapy during CD20-reactive cell infiltration of nerves of both sexes reduced mechanical allodynia in females but not in males. IVIG and vehicle treatments had no effect in either sex. These findings provide strong evidence for sexual dimorphism in B-cell function after peripheral nervous system (PNS) trauma and autoimmune pathogenesis of neuropathic pain, potentially amenable to immunotherapeutic intervention, particularly in females. A myelin-targeted serum autoantibody may serve as a biomarker of such painful states. This insight into the biological basis of sex-specific response to neuraxial injury will help personalize regenerative and analgesic therapies.

The effect of intrathecal mu, delta, kappa, and alpha-2 agonists on thermal hyperalgesia induced by mild burn on hind paw in rats.

PURPOSE: Mild cutaneous thermal injury, leading to a first-degree burn, induces a sensation of burning pain and enhances the pain sensitivity of the skin. Opioid and α(2) receptor agonists are commonly used to reduce such hyperalgesia. We investigated conditions that induced adequate thermal hyperalgesia in rats and compared the effects of µ, δ, κ, and α(2) receptors at the level of the spinal cord in this model. METHODS: A total of 149 male Sprague-Dawley rats were submitted to this study. A first-degree burn injury was induced in the hind paw by contact with a hot plate. The nociceptive threshold was determined by measuring the time from the application of a light beam to the hind paw to the withdrawal response (paw withdrawal latency, PWL). Various hot-plate exposure times and light beam intensities were tested to determine the conditions that induced adequate hyperalgesia. We also tested the effects of intrathecal morphine (µ agonist), DPDPE ([D-Pen2, D-Pen5] enkephalin, a δ agonist), U50488H (trans(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzacetamide methane sulfonate salt, a κ agonist), and ST-91 (2-[2,6-diethyl-phenylamino]-2-imidazoline, an α(2) agonist) on PWL. RESULTS: A first-degree burn was induced by contact with the hot plate for 45 s. Using current of 5.0 A, PWL was reduced by 40% from baseline. Intrathecally administered morphine, DPDPE, and ST-91, but not U50488H, showed dose-dependent antinociceptive effects in both injured and normal paws. CONCLUSIONS: Based on these findings, we could find adequate conditions for thermal hyperalgesia model. In this experimental model, µ, δ, and α(2) receptor agonists produced antinociceptive effects at the level of the spinal cord, but the κ receptor agonist did not.

Clinical outcomes of early gastric cancer with non-curative resection after pathological evaluation based on the expanded criteria.

Additional surgical resection should be considered for the patients with pathological findings beyond the expanded criteria with the risk for LN metastasis. However, close observation without additional surgery may be applied because of various reasons. We aimed to determine the clinical outcomes of early gastric cancer beyond the expanded criteria after endoscopic resection according to the pathological extent. A total of 288 patients with 289 lesions beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer were analyzed between 2005 and 2016, and classified into two groups according to additional treatment: observation (n = 175 patients, 175 lesions) and surgery (n = 113 patients, 114 lesions). The depth of tumor invasion was greater and the tumor-positive vertical margin and lymphatic and venous invasion were more common in the surgery group than in the observation group (P<0.001). Residual, synchronous, and metachronous tumors were more common in the observation group; however, the occurrence of regional lymph node and distant metastasis did not differ between the groups. Overall survival and 5-year disease-specific survival did not differ between the groups (observation vs surgery, 88.6 vs 93.8%; P = 0.259, 98.2 vs 100%; P = 0.484, respectively), but the 5-year disease-free survival was lower in the observation group (73.5 vs 97.9%; P<0.001). On multivariate analysis, tumor-positive lateral margin was a risk factor for residual tumor and lymphatic and venous invasion were risk factors for regional lymph node metastasis. In conclusion, the clinical course of beyond the expanded criteria of endoscopic submucosal dissection for early gastric cancer showed good prognosis over 98% in 5-year disease specific survival. If additional surgery cannot be performed, a close follow-up with endoscopy and abdominal computed tomography can be considered as an alternative for carefully selected patients without lymphatic and vascular invasion.

The genome sequence of the ethanologenic bacterium Zymomonas mobilis ZM4.

We report the complete genome sequence of Zymomonas mobilis ZM4 (ATCC31821), an ethanologenic microorganism of interest for the production of fuel ethanol. The genome consists of 2,056,416 base pairs forming a circular chromosome with 1,998 open reading frames (ORFs) and three ribosomal RNA transcription units. The genome lacks recognizable genes for 6-phosphofructokinase, an essential enzyme in the Embden-Meyerhof-Parnas pathway, and for two enzymes in the tricarboxylic acid cycle, the 2-oxoglutarate dehydrogenase complex and malate dehydrogenase, so glucose can be metabolized only by the Entner-Doudoroff pathway. Whole genome microarrays were used for genomic comparisons with the Z. mobilis type strain ZM1 (ATCC10988) revealing that 54 ORFs predicted to encode for transport and secretory proteins, transcriptional regulators and oxidoreductase in the ZM4 strain were absent from ZM1. Most of these ORFs were also found to be actively transcribed in association with ethanol production by ZM4.

Co-Expression of a Chimeric Protease Inhibitor Secreted by a Tumor-Targeted Salmonella Protects Therapeutic Proteins from Proteolytic Degradation.

Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

Clinical Implication and Risk Factors for Malignancy of Atypical Gastric Gland during Forceps Biopsy.

Background/Aims: Although forceps biopsy is performed for suspicious gastric tumors during endoscopy, it is difficult to determine treatment strategies for atypical gastric glands due to uncertainty of the diagnosis. The aim of this study was to investigate clinical implications and risk factors for predicting malignancy in atypical gastric glands during forceps biopsy. Methods: We retrospectively reviewed medical records of 252 patients with a diagnosis of atypical gastric gland during forceps biopsy. Predictors of malignancy were analyzed using initial endoscopic findings and clinical data. Results: The final diagnosis for 252 consecutive patients was gastric cancer in 189 (75%), adenoma in 26 (10.3%), and gastritis in 37 (14.7%). In the multivariate analysis, lesion sizes of more than 10 mm (odds ratio [OR], 3.021; 95% confidence interval [CI], 1.480 to 6.165; p=0.002), depressed morphology (OR, 3.181; 95% CI, 1.579 to 6.406, p=0.001), and surface nodularity (OR, 3.432; 95% CI, 1.667 to 7.064, p=0.001) were significant risk factors for malignancy. Conclusions: Further evaluation and treatment should be considered for atypical gastric gland during forceps biopsy if there is a large-sized (>10 mm) lesion, depressed morphology, or surface nodularity.

Successful transfusion-free pancreatectomy in Jehovah's Witness patients.

BACKGROUNDS/AIMS: Although perioperative therapies have improved greatly, pancreatectomies still often need blood transfusions. However, the morbidity from blood transfusions, the poor prognosis of blood transfused patients, high cost, and decreasing supply of blood products is accelerating transfusion-free (TF) surgery in the patients who have pacreatectomies. The aim of this study was to assess the feasibility of TF pancreatectomies for patients who are Jehovah's Witness. METHODS: We investigated the possibility of TF pancreatectomies for the Jehovah's Witness patients undergoing pancreatectomies between January 2007 and Februay 2014. There were 4 cases of Whipple's operation, 4 of pylorus-preserving pancreaticoduodenectomy, 2 of radical antegrade modular pancreatosplenectomy and 1 of laparoscopic distal pancreatectomy. All were performed by one surgeon. RESULTS: Most of the TF pancreatecomies patients received perioperative blood augmentation and intraoperative acute normovolemic hemodilution (ANH). They received no blood transfusions at any time during their hospitalization, and pre- and intra-operative data and outcomes were acceptably favorable. CONCLUSIONS: To the best of our knowledge, this report is the first successful consecutive pancreatectomy program for Jehovah's Witness not involving blood transfusion. TF pancreatectomy can be performed successfully in selected Jehovah's Witness. Postoperative prognosis and outcomes should be confirmed in follow up studies.

Airway management in patient with continuous bleeding lesion of the trachea: a case report.

Hemoptysis requires proper treatment to prevent blood aspiration and asphyxiation. If the patient loses consciousness or is anesthetized, the bleeding inside the trachea may continuously flow into the distal part, which may be fatal. Fatal damage resulting from hemoptysis is mainly caused by asphyxiation, and it is important to find the exact location of the bleeding in order to prevent it from spreading to both lungs. However, endotracheal intubation may increase the bleeding by stimulating the bleeding lesion in the respiratory track, and can make airway management more difficult. We report a successful case of airway management using the cuff and Murphy eye of the endotracheal tube in a patient with tracheal bleeding.