Mesenchymal Stem Cell Therapy in Acute Intracerebral Hemorrhage: A Dose-Escalation Safety and Tolerability Trial.

BACKGROUND: We conducted a preliminary phase I, dose-escalating, safety, and tolerability trial in the population of patients with acute intracerebral hemorrhage (ICH) by using human allogeneic bone marrow-derived mesenchymal stem/stromal cells. METHODS: Eligibility criteria included nontraumatic supratentorial hematoma less than 60 mL and Glasgow Coma Scale score greater than 5. All patients were monitored in the neurosciences intensive care unit for safety and tolerability of mesenchymal stem/stromal cell infusion and adverse events. We also explored the use of cytokines as biomarkers to assess responsiveness to the cell therapy. We screened 140 patients, enrolling 9 who met eligibility criteria into three dose groups: 0.5 million cells/kg, 1 million cells/kg, and 2 million cells/kg. RESULTS: Intravenous administration of allogeneic bone marrow-derived mesenchymal stem/stromal cells to treat patients with acute ICH is feasible and safe. CONCLUSIONS: Future larger randomized, placebo-controlled ICH studies are necessary to validate this study and establish the effectiveness of this therapeutic approach in the treatment of patients with ICH.

Probiotic effects of mixture of Groenewaldozyma salmanticensis and Gluconacetobacter liquefaciens on growth and immune responses in Paralichthys olivaceus.

This study was performed to evaluate the effects of dietary probiotics on growth, non-specific immune responses and disease resistance in olive flounder, Paralichthys olivaceus. During 8 weeks, the fish were fed the five experimental diets such as a basal commercial diet (CON), oxytetracycline (OTC) and three basal diets containing Bacillus subtilis (BS), a commercial microbial product (CES) and a mixture of yeast and bacterium (PI), respectively. Fish fed all the probiotics diets and OTC showed a significantly higher growth than fish-fed CON (P < 0·05). Fish-fed PI had a significantly higher nitroblue tetrazolium activity, whereas fish-fed CES showed a higher lysozyme level (P < 0·05). A 7-day challenge test also showed that fish-fed PI had a cumulative survival rate equivalent to that of fish-fed OTC (P < 0·05). Moreover, the diet (PI) appeared to increase the diversity of microbial community in the fish. All these results suggest that the probiotics diet could function as a potential antibiotic replacer in the olive flounder. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is unique in revealing that a diet mixture of yeast, Groenewaldozyma salmanticensis and bacterium Gluconacetobacter liquefaciens can enhance growth, innate immunity and diversity of microbial community including dominant species in the olive flounder. All these indicate that the diet mixture could function as a potential antibiotic replacer in one of the most commercially important fisheries in South Korea.

Differential diagnosis of jaw pain using informatics technology.

This study aimed to deduce evidence-based clinical clues that differentiate temporomandibular disorders (TMD)-mimicking conditions from genuine TMD by text mining using natural language processing (NLP) and recursive partitioning. We compared the medical records of 29 patients diagnosed with TMD-mimicking conditions and 290 patients diagnosed with genuine TMD. Chief complaints and medical histories were preprocessed via NLP to compare the frequency of word usage. In addition, recursive partitioning was used to deduce the optimal size of mouth opening, which could differentiate TMD-mimicking from genuine TMD groups. The prevalence of TMD-mimicking conditions was more evenly distributed across all age groups and showed a nearly equal gender ratio, which was significantly different from genuine TMD. TMD-mimicking conditions were caused by inflammation, infection, hereditary disease and neoplasm. Patients with TMD-mimicking conditions frequently used "mouth opening limitation" (P < .001), but less commonly used words such as "noise" (P < .001) and "temporomandibular joint" (P < .001) than patients with genuine TMD. A diagnostic classification tree on the basis of recursive partitioning suggested that 12.0 mm of comfortable mouth opening and 26.5 mm of maximum mouth opening were deduced as the most optimal mouth-opening cutoff sizes. When the combined analyses were performed based on both the text mining and clinical examination data, the predictive performance of the model was 96.6% with 69.0% sensitivity and 99.3% specificity in predicting TMD-mimicking conditions. In conclusion, this study showed that AI technology-based methods could be applied in the field of differential diagnosis of orofacial pain disorders.

Comparison of image quality between conventional VIBE and radial VIBE in free-breathing paediatric abdominal MRI.

AIM: To compare the image quality between conventional volume interpolated breath-hold examination (VIBE) and radial VIBE in contrast-enhanced fat-suppressed T1-weighted images of paediatric abdominal magnetic resonance imaging (MRI) during free-breathing. MATERIALS AND METHODS: Images from paediatric patients who underwent contrast-enhanced abdominal MRI with a 3 T magnet using conventional VIBE (conventional group) and radial VIBE (radial group) while freely breathing were reviewed retrospectively. For objective analysis, the mean values of noise and signal-to-noise ratio (SNR) in the liver on contrast-enhanced fat-suppressed T1-weighted images were compared. For subjective analysis, overall image quality, respiratory motion, portal vein clarity, and hepatic margin sharpness were assessed using four-point scales. RESULTS: Nine patients (mean age of 2.8±2.3 years) in the conventional and 17 patients (mean age of 2.4±2.8 years) in the radial groups were included. According to the objective analysis, the noise was significantly lower and the SNR was significantly higher in the radial group than those in the conventional group (all, p<0.001). In the subjective analysis, overall image quality, respiratory motion, portal vein clarity, and hepatic margin sharpness were all significantly higher in the radial group (all, p<0.001). CONCLUSION: Paediatric abdominal MRI images with radial VIBE showed lower noise with higher SNR in objective analysis and higher image quality in subjective analysis, compared to conventional VIBE.

Bioavailability of the Nano-Unit 14C-Agrochemicals Under Various Water Potential.

The study was conducted to investigate the effects of water potential on bioavailability of the nano-unit 14C-cafenstrole, 14C-pretilachlor, 14C-benfuresate, 14C-simetryn and 14C-oxyfluorfen applied with or without dimepiperate or daimuron under various water potential conditions. The highest bioavailable concentration in soil solution (BCSS) was found at 60% soil moisture, while the lowest occurred at 50% soil moisture for soil-applied alone or in combination. All water potential conditions differed significantly from each other with variations in total bioavailable amount in soil solution (TBSS) when either dimepiperate or daimuron were added to the soil, and changes were directly proportional to variations in water potential. Across all treatments, TBSS at 80% soil moisture was three to four times greater than that at 50% soil moisture when applied alone or in combination with dimepiperate or daimuron. Cafenstrole and simetryn had distribution coefficient (Kd) values <64 ml g-1 and a TBSS ranging from 10 to 44 ng g-1 soil, regardless of water potential conditions applied alone or in combination. Pretilachlor and benfuresate had Kd values <15 ml g-1 and a TBSS range of 38 to 255 ng g-1 soil when applied with or without dimepiperate or daimuron.

Staging accuracy of endoscopic ultrasound performed by nonexpert endosonographers in patients with resectable esophageal squamous cell carcinoma: is it possible?

The accuracy of endoscopic ultrasound (EUS) is operator-dependent. According to learning curve study, the accuracy of EUS T-staging for esophageal cancer has been reported to be greater in an investigator who had performed at least 100 EUS examinations. We determined comparative study regarding T-staging accuracy of EUS for esophageal squamous cell carcinoma between expert and nonexpert endoscopic ultrasonographers. We retrospectively identified 73 consecutive patients with esophageal squamous cell carcinoma who underwent EUS and endoscopic mucosal resection, endoscopic submucosal dissection, or surgery. EUS was performed by expert (Group 1) and nonexpert (Group 2) endoscopic ultrasonographers in multitertiary hospitals. Groups 1 and 2 were 37 and 36 patients during 2005-2011, respectively. Forty-two patients (57.5%) of the overall patients underwent surgical exploration. Correct endoscopic ultrasonographic T-staging of Group 1 was observed in 34 (91.9%) patients, while that of Group 2 was observed in 26 (72.2%) patients. And there was significant difference in correct endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.035). The incorrect endoscopic ultrasonographic T-staging of Group 1 were three cases that were overstaging (8.1%), but in Group 2 there were seven overstaging (19.4%) and three understaging (8.3%). There was no significant difference in overstaging or understaging of incorrect endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.528). This study first provides evidence that endoscopic ultrasonographic T-staging of nonexpert endoscopic ultrasonographers was inferior to be correct, compared with that of expert endoscopic ultrasonographers. EUS staging for esophageal cancer should be performed by expert endoscopic ultrasonographers to provide appropriate management strategy.

High-resolution impedance manometry facilitates assessment of pharyngeal residue and oropharyngeal dysphagic mechanisms.

The utility of high-resolution impedance manometry (HRIM) for evaluating oropharyngeal dysphagia (OPD) has been investigated. These approaches are limited because of the sophisticated methodology. A method of transforming HRIM into a simple and useful diagnostic tool for evaluating OPD is needed. A videofluoroscopic swallowing study (VFSS) and HRIM were performed by independent blinded examiners in 26 consecutive healthy volunteers (12 men; median age, 56.5 years) and 10 OPD patients (five men; median age, 59.5 years). Upper esophageal sphincter (UES) relaxation parameters were measured using a standard HRIM protocol. Peristalsis and bolus transit of the pharyngoesophageal (PE) segment were assessed using an HRIM-modified protocol in which the catheter was pulled back 10 cm. PE bolus transits were evaluated with an impedance contour pattern (linear vs. stasis) method. A significant difference was observed between the manometric measures of healthy volunteers and OPD patients for only the duration of pharyngeal contraction (0.49 ± 0.19 vs. 0.76 ± 0.33 s, P = 0.04). The percentage agreement and kappa value for detecting pharyngeal residue between the VFSS and the impedance analysis were 100% and 1.00, respectively. HRIM allowed for comprehensive assessment of abnormal pharyngeal components that caused pharyngeal residue on VFSS in two patients; reduced base of the tongue versus weak pharyngeal contraction in one, and reduced relaxation of the UES versus reduced laryngeal elevation in the remaining patient. Our findings demonstrated that HRIM using a simple methodology (i.e., pull-back of the catheter) detected pharyngeal residue through a simple analysis of the impedance contour pattern (linear vs. stasis). Furthermore, HRIM facilitated a comprehensive assessment of OPD mechanisms and recognition of subtle abnormalities not yet visible to the naked eye on VFSS.

Walnuts (seeds of Juglandis sinensis L.) protect human epidermal keratinocytes against UVB-induced mitochondria-mediated apoptosis through upregulation of ROS elimination pathways.

PURPOSE: Ultraviolet (UV) light from sunlight is an important environmental factor causing hazardous health effects, including various skin disorders. UV irradiation downregulates reactive oxygen species (ROS) elimination pathways, thereby promoting the production of ROS, which are implicated in mitochondria-mediated apoptosis. Walnuts, the seeds of Juglandis sinensis L., are a highly nutritious food and have been shown to have a number of pharmacological activities. To our knowledge, no study on the protective effects of walnuts on human epidermal keratinocytes has been reported previously. Here, we investigated the protective effects of walnuts against UVB (50 mJ/cm(2)) -induced mitochondria-mediated apoptosis. PROCEDURES AND RESULTS: Walnuts significantly and dose-dependently reduced UVB-induced apoptotic toxicity by lactate dehydrogenase assay kit. Walnuts decreased mitochondrial dysfunction, B-cell lymphoma 2 (Bcl-2)-associated X (Bax) protein levels, and cytochrome c release from mitochondria, while increasing Bcl-2 protein levels using immunofluorescence, Western blot, or kit analysis. Moreover, walnuts inhibited caspase-3 activity, indicating an inhibition of the apoptotic cascade, and induced the expression of heme oxygenase and NAD(P)H dehydrogenase via NF-E2-related factor-2 activation using immunofluorescence or Western blot analysis. CONCLUSION: Together, these results demonstrate that walnuts can protect human epidermal keratinocytes against UVB-induced mitochondria-mediated apoptosis by regulating ROS elimination pathways.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.

BACKGROUND: This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS: Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS: Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER: NCT01164176.

Clinical outcomes and risk factors of post-polypectomy coagulation syndrome: a multicenter, retrospective, case-control study.

BACKGROUND AND STUDY AIMS: Post-polypectomy coagulation syndrome (PPCS) is a well known complication of colonoscopic polypectomy. However, no previous studies have reported on the clinical outcomes or risk factors of PPCS. The aim of the current study was to analyze the clinical outcomes and risk factors of PPCS developing after a colonoscopic polypectomy. PATIENTS AND METHODS: Data for all patients who underwent colonoscopic polypectomies and required hospitalization in nine university hospitals were analyzed retrospectively. The incidence, clinicopathological characteristics, and clinical outcomes of PPCS cases were examined. Additionally, patients who developed PPCS were compared with controls who were matched by age and sex, in order to assess for possible risk factors. RESULTS: The rate of PPCS that required hospitalization after colonoscopic polypectomy was 0.7/1000. All patients with PPCS were treated medically without the need for surgical interventions. The median durations of therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively. The rates of major PPCS and mortality were 2.9 % and 0 %, respectively. On multivariate analysis, hypertension (OR = 3.023, 95 %CI 1.034 - 8.832), large lesion size (OR = 2.855, 95 %CI 1.027 - 7.937), and non-polypoid configuration (OR = 3.332, 95 %CI 1.029 - 10.791) were found to be independent risk factors related to the development of PPCS. CONCLUSIONS: In this study, the rates of major PPCS and mortality were only 2.9 % and 0 %, respectively. Hypertension, large lesion size, and non-polypoid configuration of the lesion were independently associated with PPCS. Therefore, patients may be reassured by the excellent prognosis of PPCS, while endoscopists should be especially careful when performing colonoscopic polypectomies in patients with hypertension or large and non-polypoid lesions.

A retrospective study of clinical outcomes of α-blocker or finasteride monotherapy followed by combination therapy: determination of the period of combination therapy of α-blocker and finasteride.

AIMS: We investigated outcomes after discontinuing alpha-blockers or finasteride in patients who initially received combination therapy and compared differences by duration of combination therapy. METHODS: Patients with international prostate symptom score ≥ 8, serum prostatic-specific antigen (PSA) < 4 ng/ml, prostate volume > 25 cm(3) and combination therapy of alpha-blockers and finasteride for more than 6 months were classified into three groups. Group 1 continued combination therapy; group 2, alpha-blockers monotherapy; and group 3, finasteride monotherapy. All parameters were evaluated before and after changing to monotherapy. Patients who received combination therapy for 6-9 months and those who received combination therapy for longer were comparatively analysed. RESULTS: Mean age of the 106 patients was 66.9 ± 7.8 years. No significant differences in baseline symptom scores, PSA or prostate volume were found. Following combination therapy, symptom scores, and quality of life (QoL) decreased for all groups. Group 1 maintained decreased PSA and prostate volume, and improved uroflowmetric profiles. No differences in uroflowmetric parameters were found after 6 months. Group 2 maintained improved symptoms, QoL and uroflowmetric profiles, although PSA and prostate volume returned to baseline. Group 3 maintained lowered PSA and prostate volume, whereas Qmax returned to baseline. QoL scores showed no change. Patients who received combination therapy for ≥9 months improved more in symptoms and QoL than those who received shorter combination therapy. CONCLUSIONS: Discontinuation of alpha-blockers or finasteride after combination therapy for ≥ 6 months maintained improvements in symptoms. The appropriate period of combination therapy was ≥ 9 months.

A randomised, double-blind, parallel design, multi-institutional, non-inferiority phase IV trial of imidafenacin versus fesoterodine for overactive bladder.

AIMS: Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB). METHODS: This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients. RESULTS: The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups. CONCLUSIONS: Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety.

Pancreaticoduodenectomy for advanced gastric carcinoma patients.

OBJECTIVE: The prognosis for patients with gastric carcinoma that has invaded adjacent organs, especially the pancreas, is very poor. We evaluated the survival of patients following pancreaticoduodenectomy (PD) and the survival benefit of intravenous chemotherapy in these patients. METHODS: We reviewed the hospital records of 16 gastric carcinoma patients who underwent PD during the period from 2001 to 2005. RESULTS: Half of the patients undergoing PD had Borrmann type III gastric carcinoma (8/16; 50%). Using Cox's proportional hazards regression model, only one factor was identified as an independent, statistically significant prognosticator intravenous chemotherapy (risk ratio, 0.054; 95% confidence interval, 0.01-0.45; p < 0.01). The 5-year survival rate was higher for patients who had intravenous chemotherapy than for patients who did not (22.2% vs. 0%; p < 0.01). CONCLUSION: The results highlight the improved survivorship of gastric carcinoma patients with PD who received intravenous chemotherapy compared with those who did not. We recommend resection in these patients and the administration of intravenous chemotherapy to improve their survival.

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis.

BACKGROUND: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. PATIENTS AND METHODS: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. RESULTS: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4-12) in Group A and 8 cycles (range 8-16) in Group B. CONCLUSION: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.

Endoscopic submucosal dissection with sentinel node navigation surgery for early gastric cancer.

We combined endoscopic submucosal dissection (ESD) and sentinel node navigation surgery with the purpose of achieving complete resection of early gastric cancer while preserving the organ and assessing pathological nodal status. A total of 13 patients with cT1( ≤ 3 cm)N0 early gastric cancer underwent combined ESD and sentinel node navigation surgery (ESN) at a single tertiary referral center. Sentinel node navigation surgery using indocyanine green was performed during ESD and all suspected sentinel nodes were removed laparoscopically and examined intraoperatively. ESN was converted to gastrectomy with D2 dissection if there was evidence of metastasis on frozen section. ESN was completed in 12 patients and in 1 patient was converted to gastrectomy after sentinel node navigation surgery. En bloc tumor resection was achieved in all cases. Two patients underwent additional gastrectomy because they had tumor-positive vertical margins. In all cases ESN was conducted without intraoperative or postoperative adverse events. ESN is a feasible minimally invasive procedure that allows en bloc tumor resection to be achieved while assessing the pathological status of the lymph nodes.

Coriandrum sativum L. protects human keratinocytes from oxidative stress by regulating oxidative defense systems.

BACKGROUND: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. METHODS AND RESULTS: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. CONCLUSION: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects.

Screening of plant extracts for human tyrosinase inhibiting effects.

Screening for tyrosinase (TYR) inhibitors potentially useful for control of skin pigmentation has been hampered by the limited availability of human TYR. To overcome this hurdle, we have established human embryonic kidney (HEK293)-TYR cells that constitutively express human TYR. In the current study, we assayed human TYR inhibition activities of 50 plant extracts using the lysates of transformed HEK293-TYR cells. The strongest inhibition of human TYR was shown by the extract of Vaccinium bracteatum Thunberg, followed by the extract of Morus bombycis Koidzumi. The former extract did not inhibit mushroom TYR activity whereas significant inhibition was observed with the latter extract, demonstrating the importance of using human TYR in the screening for human TYR inhibitors. Upon liquid-liquid partitioning of the extract from V. bracteatum, the active constituents were enriched in the ethyl acetate fraction, and the subsequent preparatory thin-layer chromatography identified p-coumaric acid (PCA) as the main active constituent. The hypo-pigmentation of PCA was verified in the MelanoDerm™ Skin Model. This study demonstrates that transformed HEK293-TYR cells could expedite the discovery of human TYR-specific inhibitors from natural sources which might be useful in the control of skin pigmentation.

Clinicopathologic features and prognosis of synchronous multiple gastric carcinomas.

OBJECTIVE: The study of synchronous multiple gastric carcinoma is of the utmost importance in the management of carcinoma of the gastric remnant and in the epidemiology and histogenesis of gastric carcinoma. We compared the clinicopathologic features and outcome of patients with synchronous multiple gastric carcinoma (SMGC) to those of patients with single gastric carcinoma. METHODS: Of the 3,320 patients diagnosed with gastric carcinoma who underwent surgery in our hospital, 188 patients (5.7%) were diagnosed with SMGCs. RESULTS: Early carcinomas were more frequently observed in patients with SMGCs than in patients with single gastric carcinoma (p < 0.001). In addition, lymph node metastasis was less common in patients with SMGCs than in patients with single gastric carcinomas (p < 0.05). Regarding the operative procedures, total gastrectomy was more frequently performed in patients with SMGC (32.5 vs. 20.2% ; p < 0.001). The 5-year survival rate of patients with SMGCs was higher than that of patients with single gastric carcinoma (69.3% vs. 54.1%, p < 0.001). Multivariate analysis showed that lymph node metastasis, serosal invasion, and curative resection were significant prognostic factors for the survival of patients with SMGCs. CONCLUSION: More recently, endoscopic or laparoscopic resection for early gastric carcinoma has frequently been performed. Careful preoperative and intraoperative evaluation and postoperative follow-ups are essential to detect any missed lesions in the remnant stomach, particularly in elderly patients with early gastric carcinoma.

Hybrid natural orifice transluminal endoscopic surgery: endoscopic full-thickness resection of early gastric cancer and laparoscopic regional lymph node dissection--14 human cases.

BACKGROUND AND STUDY AIM: Minimally invasive treatment has become a mainstay management strategy for early gastric cancer (EGC). Full-thickness incision of the gastric wall using natural orifice transluminal endoscopic surgery (NOTES) has been reported but is not easily applicable in clinical settings at present. The aim of the current study was to assess the feasibility of hybrid NOTES, which consists of endoscopic full-thickness gastric resection and a laparoscopic lymphadenectomy. PATIENTS AND METHODS: This was a prospective, pilot study at a single tertiary care referral center. A total of 14 patients with EGC located above the lower third of the stomach underwent hybrid NOTES. Clinically, the patients had contraindications to exclusive treatment using endoscopic submucosal dissection (ESD). The main outcome measure was technical success of hybrid NOTES. RESULTS: All cases were resected en bloc with negative surgical margins. Histologically, four cases were mucosal cancers, and 10 cases were submucosal cancers. The median tumor size was 26 mm (range 12 - 90 mm). Lymphatic vessel invasion was found in four cases without lymph node metastasis (LNM). The median number of obtained lymph nodes was 18 (range 7 - 67). LNM was discovered in one case of undifferentiated submucosal cancer without lymphovascular invasion. Hybrid NOTES was conducted without intraoperative or postoperative adverse events in nine cases. The median operating time and estimated blood loss of successful cases were 143 minutes (range 110 - 253 minutes) and 16 mL (range 5 - 30 mL), respectively. The median hospital stay was 6 days (range 4 - 10 days). Five cases were converted to a subtotal gastrectomy for various reasons. CONCLUSIONS: Hybrid NOTES could be a bridge between endoscopic resection and laparoscopic surgery and may prevent extensive gastrectomy in patients with EGC.

Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model.

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.