AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studi...AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studies published from January 1, 1994 through January 31, 2015. The search terms included "laparoscopic," "total gastrectomy," and "gastric cancer." First, we selected 16 non-randomized controlled trials(RCTs) comparing LTG with open total gastrectomy(OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system(NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0%(30 of 984 patients) among LTG procedures and 2.1%(31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG(odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I2 = 0%). Anastomotic stenosis related to EJS was reported in 72(2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG(OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I2 = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar(1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the Or VilTM device was used(8.8%) compared with other procedures(1.0% to 3.6%).CONCLUSION:The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the Or VilTM device was used.展开更多
AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS: We analyze...AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS: We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection (17 curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30 fractions), with 11 receiving an ad- ditional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading. ILBT was performed using percu-taneous transhepatic biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into nonresected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.RESULTS: No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P = 0.0076). Cumu展开更多
Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant ...Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant comorbidities who have early-stage NSCLCThe safety of SBRT is being confirmed in internationalmulti-institutional PhaseⅡtrials for peripheral lungcancer in both inoperable and operable patients,bureports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer.Radiation pneumonitis(RP)is oneof the most common toxicities of SBRT.Although mospost-treatment RP is Grade 1 or 2 and either asymptomatic or manageable,a few cases are severe,symptomatic,and there is a risk for mortality.The reportedrates of symptomatic RP after SBRT range from 9%to28%.Being able to predict the risk of RP after SBRT isextremely useful in treatment planning.A dose-effecrelationship has been demonstrated,but suggesteddose-volume factors like mean lung dose,lung V20and/or lung V2.5 differed among the reports.We foundthat patients who present with an interstitial pneumo-nitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumo-nitis after SBRT.At our institution,lung cancer patients with these risk factors have not received SBRT since 2006,and our rate of severe RP after SBRT has de-creased significantly since then.展开更多
It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a co...It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a complex and heterogeneous tumor with several genomic mutations,it usually develops in the context of chronic liver damage and inflammation,suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC.Chronic liver damage induces a persistent cycle of necroinflammation and hepatocyte regeneration,resulting in genetic mutations in hepatocytes and expansion of initiated cells,eventually leading to HCC development.Recently,several inflammation-and stress-related signaling pathways have been identified as key players in these processes,which include the nuclear factor B,signal transducer and activator of transcription,and stress-activated mitogen-activated protein kinase pathways.Although these pathways may suggest potential therapeutic targets,they have a wide range of functions and complex crosstalk occurs among them.This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis.展开更多
Background Endovascular treatment of intracranial aneurysms usually involves stent-assisted coiling(SAC)and flow diverters.Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy(DAPT)are requ...Background Endovascular treatment of intracranial aneurysms usually involves stent-assisted coiling(SAC)and flow diverters.Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy(DAPT)are required to prevent thromboembolic complications afterwards.We sought to determine the safety of tirofiban and DAPT in these cases.Methods We conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion.The tirofiban-DAPT protocol used is described.Data regarding duration of infusion,placement of external ventricular devices(EVDs),complications,haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed.results One-hundred and forty-one patients with 148 aneurysms/procedures were included.110 aneurysms were treated acutely and 38 electively.Minor and major haemorrhagic events were recognised in 20%(30/148)aneurysms.Only 5(3.4%)intracerebral haemorrhages were symptomatic:3 cortical/SAH and 2 EVD-related.The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages(p=0.002).The rate of EVD-related haemorrhages was 15.7%(19/121)and only 2(1.7%)were symptomatic.Most haemorrhagic events occurred in ruptured aneurysms(90.1%,p=0.01).No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented.Concomitant administration of heparin did not increase haemorrhagic events.Conclusion The use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe.Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications.展开更多
Diffusion-weighted imaging (DWI) is an established diagnostic method of acute stroke. The latest advances in magnetic resonance imaging (MRI) technology have greatly expanded the utility of DWI in the examination of v...Diffusion-weighted imaging (DWI) is an established diagnostic method of acute stroke. The latest advances in magnetic resonance imaging (MRI) technology have greatly expanded the utility of DWI in the examination of various organs. Recent studies have revealed the usefulness of DWI for imaging of the liver, kidney, ovary, and breast. We report a patient with acute pancreatitis detected by DWI and discussed the efficacy of DWI in diagnosing acute pancreatitis. A 50-year old man presented with a primary complaint of abdominal pain. We performed both DWI and computed tomography (CT) for this patient. The signal intensity in a series of DWI was measured and the apparent diffusion coefficient (ADC) values were calculated to differentiate inflammation from normal tissue. Two experienced radiologists evaluated the grade of acute pancreatitis by comparing the CT findings. Initially, the pancreas and multiple ascites around the pancreas produced a bright signal and ADC values were reduced on DWI. As the inflammation decreased, the bright signal faded to an iso-signal and the ADC values returned to their normal level. There was no difference in the abilities of DWI and CT images to detect acute pancreatitis. However, our case indicates that DWI can evaluate the manifestations of acute pancreatitis using no enhancement material andhas the potential to replace CT as a primary diagnostic strategy for acute pancreatitis.展开更多
AIM: To darify bhe efficacy and safety of bhree-dimensional conformal radiotherapy (3-D CRT) for bhis disease and to specify patient subgroups suitable for this treatment. METHODS: Fifty-two patients with HCC rece...AIM: To darify bhe efficacy and safety of bhree-dimensional conformal radiotherapy (3-D CRT) for bhis disease and to specify patient subgroups suitable for this treatment. METHODS: Fifty-two patients with HCC received PVItargeted radiation therapy from .January 1995 through December 2003. Portal venous invasion (PVI) was found in the second or lower order branches of the portal vein in 6 patients, in the first branch in 24 patients and in the main trunk in 22 patients. Child classifications of liver function before radiation therapy were A, B, and C for 19, 24 and 2 patients, respectively. All patients received three-dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy (57.0 Gy in average). RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis revealed that Child status, the number of tumor foci, tumor type, transcatheter arterial embolization (TAE) after radiation therapy were statistically significant prognostic factors. Multivariate analysis showed that the number of tumor foci and TAE after radiation therapy were statistically significant. CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as treatment for PVI in HCC. 3-D CRT is recommended in combination with postradiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with Child A liver function.展开更多
Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid (DHA) on lipegen...Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid (DHA) on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet ( 1.5% DHA ethyl ester/kg diet) for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.展开更多
With the undetermined coefficient method, a new high order scheme for convection equation named as HAUC was worke d out. The accuracy of the new scheme was analyzed by comparing the computed res ults with the exact s...With the undetermined coefficient method, a new high order scheme for convection equation named as HAUC was worke d out. The accuracy of the new scheme was analyzed by comparing the computed res ults with the exact solutions of 1-D pure convection equation and nonlinear con vection equation. The effectiveness of the HAUC was also examined by comparing w ith the results obtained by other schemes. Finally, it was applied to simulate 1 -D dam break flow with differenct ratios of initial upstream water depth to do wnstream one. The results show that the scheme has the ability to simulate both undular bores and moving hydraulic jumps.展开更多
We report a successful endovascular technique using a snare with a suture for retrieving a migrated broken peripherally inserted central catheter(PICC)in a chemotherapy patient.A 62-year-old male received monthly chem...We report a successful endovascular technique using a snare with a suture for retrieving a migrated broken peripherally inserted central catheter(PICC)in a chemotherapy patient.A 62-year-old male received monthly chemotherapy through a central venous port implanted into his right subclavian area.The patient completed chemotherapy without complications 1 mo ago;however,he experienced pain in the right subclavian area during his last chemotherapy session.Computed tomography on that day showed migration of a broken PICC in his left pulmonary artery,for which the patient was admitted to our hospital.We attempted to retrieve the ectopic PICC through the right jugular vein using a gooseneck snare,but were unsuccessful because the catheter was lodged in the pulmonary artery wall.Therefore,a second attempt was made through the right femoral vein using a snare with triple loops,but we could not grasp the migrated PICC.Finally,a string was tied to thetop of the snare,allowing us to curve the snare toward the pulmonary artery by pulling the string.Finally,the catheter body was grasped and retrieved.The endovascular suture technique is occasionally extremely useful and should be considered by interventional cardiologists for retrieving migrated catheters.展开更多
High-pressure ultrafast dynamics,as a new crossed research direction,are sensitive to subtle non-equilibrium state changes that might be unresolved by equilibrium states measurements,providing crucial information for ...High-pressure ultrafast dynamics,as a new crossed research direction,are sensitive to subtle non-equilibrium state changes that might be unresolved by equilibrium states measurements,providing crucial information for studying delicate phase transitions caused by complex interactions in Mott insulators.With time-resolved transient reflectivity measurements,we identified the new phases in the spin–orbit Mott insulator Sr_(3)Ir_(2)O_7 at 300 K that was previously unidentified using conventional approaches such as x-ray diffraction.Significant pressure-dependent variation of the amplitude and lifetime obtained by fitting the reflectivity?R/R reveal the changes of electronic structure caused by lattice distortions,and reflect the critical phenomena of phase transitions.Our findings demonstrate the importance of ultrafast nonequilibrium dynamics under extreme conditions for understanding the phase transition of Mott insulators.展开更多
In recent years,there has been extensive utilization of actuators driven by artificial muscles in wearable devices.However,the muscle distribution configurations of most wearable devices have been specifically designe...In recent years,there has been extensive utilization of actuators driven by artificial muscles in wearable devices.However,the muscle distribution configurations of most wearable devices have been specifically designed and are difficult to generalize.Consequently,wearable devices that allow direct installation of actuators onto existing clothing are better suited for a wider range of application scenarios.This letter presents the development and evaluation of Funabot-Suit,a human muscle configuration inspired wearable assist device that employs McKibben artificial muscles to induce natural kinesthetic perception in the wearer’s torso.By integrating thin McKibben muscles into an existing motion capture suit,the Funabot-Suit is capable of generating four fundamental motions:forward and backward bending,and left and right twisting.The suit’s performance was assessed through experiments involving three subjects who wore the suit while standing and seated,with the subjects reporting the direction of their kinesthetic perception.The subjects also rated the perceived ease of kinesthetic perception direction on a five-point scale.Our results demonstrate that the Funabot-Suit successfully induces kinesthetic perceptions for the wearer,with a one hundred percent detection ratio for accurate responses in the command direction across all subjects and positions.We observed variations in the sensitivity of left–right and up-down sensations,which can be attributed to the positioning of artificial muscles and individual differences.展开更多
Amplified fragment length polymorphism (AFLP) analysis was used to evaluate the genetic diversity of four wild geographical populations of Japanese flounder (Paralichthys olivaceus). A total of 775 loci (58.32% o...Amplified fragment length polymorphism (AFLP) analysis was used to evaluate the genetic diversity of four wild geographical populations of Japanese flounder (Paralichthys olivaceus). A total of 775 loci (58.32% of which was polymorphic) in the range between 100 and 1 300 base pairs were detected from 110 individuals using seven primer combinations. The percentage of polymorphic loci detected by single primer combination for each population was calculated, ranging from 19.59% to 53.33%. Genetic similarities within and among the populations were calculated from the binary matrices of presence - absence. Phylogenetic tree of four populations was constructed by using the UPGMA method using PHYLIP Version 3.5. According to intrapopulation genetic similarities, CW population displayed the highest genetic diversity value and KY population had the lowest genetic diversity value. The distance between CW and CF populations was the farthest, which was possibly resulted from the farthest distance of Weihai of Shandong and Fujian of China compared with the geographical distance between other locations of populations. The subpopulation differentiation value (G.,) is 0. 356 5, showing a certain extent of differentiation among the four geographical populations. AFLP technology was confirmed to be an effective tool to assess within- and among-population genetic diversity of Japanese flounder. The present survey provided significant insights for research in the Japanese flounder breeding program.展开更多
We developed an apparatus for producing high-density hydrogen plasma. The atomic hydrogen density was 3.1 × 1021 m<sup>?3</sup> at a pressure of 30 Pa, a microwave power of 1000 W, and a hydrogen gas ...We developed an apparatus for producing high-density hydrogen plasma. The atomic hydrogen density was 3.1 × 1021 m<sup>?3</sup> at a pressure of 30 Pa, a microwave power of 1000 W, and a hydrogen gas flow rate of 10 sccm. We confirmed that the temperatures of transition-metal films increased to above 800<sup>。</sup>C within 5 s when they were exposed to hydrogen plasma formed using the apparatus. We applied this phenomenon to the selective heat treatment of nickel films deposited on silicon wafers and formed nickel silicide electrodes. We found that this heat phenomenon automatically stopped after the nickel slicidation reaction finished. To utilize this method, we can perform the nickel silicidation process without heating the other areas such as channel regions and improve the reliability of silicon ultralarge-scale integration devices.展开更多
BACKGROUND Accurate diagnosis and early resection of colorectal polyps are important to prevent the occurrence of colorectal cancer.However,technical factors and morphological factors of polyps itself can lead to miss...BACKGROUND Accurate diagnosis and early resection of colorectal polyps are important to prevent the occurrence of colorectal cancer.However,technical factors and morphological factors of polyps itself can lead to missed diagnoses.Imageenhanced endoscopy and chromoendoscopy(CE)have been developed to facilitate an accurate diagnosis.There have been no reports on visibility using a combination of texture and color enhancement imaging(TXI)and CE for colorectal tumors.AIM To investigate the visibility of margins and surfaces with the combination of TXI and CE for colorectal lesions.METHODS This retrospective study included patients who underwent lower gastrointestinal endoscopy at the Toyoshima Endoscopy Clinic.We extracted polyps that were resected and diagnosed as adenomas or serrated polyps(hyperplastic polyps and sessile serrated lesions)from our endoscopic database.An expert endoscopist performed the lower gastrointestinal endoscopies and observed the lesion using white light imaging(WLI),TXI,CE,and TXI+CE modalities.Indigo carmine dye was used for CE.Three expert endoscopists rated the visibility of the margin and surface patterns in four ranks,from 1 to 4.The primary outcomes were the average visibility scores for the margin and surface patterns based on the WLI,TXI,CE,and TXI+CE observations.Visibility scores between the four modalities were compared by the Kruskal-Wallis and Dunn tests.RESULTS A total of 48 patients with 81 polyps were assessed.The histological subtypes included 50 tubular adenomas,16 hyperplastic polyps,and 15 sessile serrated lesions.The visibility scores for the margins based on WLI,TXI,CE,and TXI+CE were 2.44±0.93,2.90±0.93,3.37±0.74,and 3.75±0.49,respectively.The visibility scores for the surface based on WLI,TXI,CE,and TXI+CE were 2.25±0.80,2.84±0.84,3.12±0.72,and 3.51±0.60,respectively.The visibility scores for the detection and surface on TXI were significantly lower than that on CE but higher than that on WLI(P<0.001).The visibility scores for the margin and surface on TXI+CE展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer, and obesity has been established as a risk factor for HCC development. Nonalcoholic steatohepatitis(NASH) is apparently the key link between obesity and h...Hepatocellular carcinoma(HCC) is the fifth most common cancer, and obesity has been established as a risk factor for HCC development. Nonalcoholic steatohepatitis(NASH) is apparently the key link between obesity and hepatocarcinogenesis, and obesity also accelerates HCC development synergistically with other risk factors, such as hepatitis virus infection and alcohol consumption. As an explanation for the pathogenesis of NASH, the so-called "two-hit" theory has been widely accepted, but recently, a better model, the so-called "multiple-hits hypothesis" was proposed, which states that many disease-promoting factors may occur in parallel, rather than consecutively. However, the overall mechanism remains largely unknown. Various cell-cell and organ-organ interactions are involved in the pathogenesis of NASH, and thus appropriate in vivo disease models are essential for a deeper understanding. However, replicating the full spectrum of human NASH has been difficult, as NASH involves obesity, insulin resistance, steatohepatitis, fibrosis, and ultimately HCC, and the lack of an appropriate mouse model has been a considerable barrier to determining the missing links among obesity, NASH, and HCC. In recent years, several innovative mouse models presenting obesity- and NASHassociated HCC have been established by modified diets, chemotoxic agents, genetic manipulation, or a combination of these factors, shedding some light on this complex network and providing new therapeutic strategies. Thus, in this paper, I review the mouse models of obesity- and NASH-associated HCC, especially focusing on recent advances and their clinical relevance.展开更多
Following the recent report by Dasenbrock-Gammon et al.[Nature 615,244–250(2023)]of near-ambient superconductivity in nitrogendoped lutetium trihydride(LuH_(3-δ)N_(ε)),significant debate has emerged surrounding the...Following the recent report by Dasenbrock-Gammon et al.[Nature 615,244–250(2023)]of near-ambient superconductivity in nitrogendoped lutetium trihydride(LuH_(3-δ)N_(ε)),significant debate has emerged surrounding the composition and interpretation of the observed sharp resistance drop.Here,we meticulously revisit these claims through comprehensive characterization and investigations.We definitively identify the reported material as lutetium dihydride(LuH_(2)),resolving the ambiguity surrounding its composition.Under similar conditions(270–295 K and 1–2 GPa),we replicate the reported sharp decrease in electrical resistance with a 30%success rate,aligning with the observations by Dasenbrock-Gammon et al.However,our extensive investigations reveal this phenomenon to be a novel pressure-induced metal-to-metal transition intrinsic to LuH_(2),distinct from superconductivity.Intriguingly,nitrogen doping exerts minimal impact on this transition.Our work not only elucidates the fundamental properties of LuH_(2)andLuH_(3),but also critically challenges the notion of superconductivity in these lutetium hydride systems.These findings pave the way for future research on lutetium hydride systems,while emphasizing the crucial importance of rigorous verification in claims of ambient-temperature superconductivity.展开更多
Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC).Alpha-fetoprotein,Lens culinaris agglutininreactive fraction of alpha-fetoprotein,and...Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC).Alpha-fetoprotein,Lens culinaris agglutininreactive fraction of alpha-fetoprotein,and des-c-carboxy prothrombin are well-known and useful tumor markers for HCC.The positive number status of these tumor markers has recently been demonstrated as beneficial for predicting outcome for HCC patients treated with local therapy.Although the normal ranges reported have differed by institution,the positivity of tumor markers is consistent and can easily be assessed.Kumamoto and Wakayama's group clearly demonstrated the following:1) Regardless of the degree of tumor stage,a triple-positive tumor marker profile can predict poor outcome in HCC patients undergoing HR;2) For RFA alone,HCC patients with double-and triple-positive status,having less than three lesions and lesions ≤3 cm in diameter show comparably insufficient outcomes;3) For HCC patients with lesions ≤5 cm in Child-Pugh grade A,HR is preferred over RFA;4) Microvascular invasion rates increased even in the double-positive patients,while poorly differentiated HCC was frequently observed only in the triple-positive patients;and 5) RFA with chemoembolization,anatomical liver resection,and postoperative adjuvant chemoembolization or hepatic arterial chemotherapy might improve the outcome for patients with highly malignant HCC with multiple positive tumor markers.However,the impacts of these therapies still need to be evaluated in prospective comparative studies.展开更多
文摘AIM: To investigate the anastomotic complications ofesophagojejunostomy(EJS) after laparoscopic total gastrectomy(LTG), we reviewed retrospective studies.METHODS: A literature search was conducted in Pub Med for studies published from January 1, 1994 through January 31, 2015. The search terms included "laparoscopic," "total gastrectomy," and "gastric cancer." First, we selected 16 non-randomized controlled trials(RCTs) comparing LTG with open total gastrectomy(OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system(NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0%(30 of 984 patients) among LTG procedures and 2.1%(31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG(odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I2 = 0%). Anastomotic stenosis related to EJS was reported in 72(2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG(OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I2 = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar(1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the Or VilTM device was used(8.8%) compared with other procedures(1.0% to 3.6%).CONCLUSION:The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the Or VilTM device was used.
文摘AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS: We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection (17 curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30 fractions), with 11 receiving an ad- ditional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading. ILBT was performed using percu-taneous transhepatic biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into nonresected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.RESULTS: No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P = 0.0076). Cumu
文摘Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant comorbidities who have early-stage NSCLCThe safety of SBRT is being confirmed in internationalmulti-institutional PhaseⅡtrials for peripheral lungcancer in both inoperable and operable patients,bureports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer.Radiation pneumonitis(RP)is oneof the most common toxicities of SBRT.Although mospost-treatment RP is Grade 1 or 2 and either asymptomatic or manageable,a few cases are severe,symptomatic,and there is a risk for mortality.The reportedrates of symptomatic RP after SBRT range from 9%to28%.Being able to predict the risk of RP after SBRT isextremely useful in treatment planning.A dose-effecrelationship has been demonstrated,but suggesteddose-volume factors like mean lung dose,lung V20and/or lung V2.5 differed among the reports.We foundthat patients who present with an interstitial pneumo-nitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumo-nitis after SBRT.At our institution,lung cancer patients with these risk factors have not received SBRT since 2006,and our rate of severe RP after SBRT has de-creased significantly since then.
基金Supported by A fellowship from the Daiichi Sankyo Foundation of Life Science,to Nakagawa H
文摘It has been established that cancer can be promoted and exacerbated by inflammation.Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide,and its long-term prognosis remains poor.Although HCC is a complex and heterogeneous tumor with several genomic mutations,it usually develops in the context of chronic liver damage and inflammation,suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC.Chronic liver damage induces a persistent cycle of necroinflammation and hepatocyte regeneration,resulting in genetic mutations in hepatocytes and expansion of initiated cells,eventually leading to HCC development.Recently,several inflammation-and stress-related signaling pathways have been identified as key players in these processes,which include the nuclear factor B,signal transducer and activator of transcription,and stress-activated mitogen-activated protein kinase pathways.Although these pathways may suggest potential therapeutic targets,they have a wide range of functions and complex crosstalk occurs among them.This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis.
基金This study was supported by an educational grant from Medicure.
文摘Background Endovascular treatment of intracranial aneurysms usually involves stent-assisted coiling(SAC)and flow diverters.Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy(DAPT)are required to prevent thromboembolic complications afterwards.We sought to determine the safety of tirofiban and DAPT in these cases.Methods We conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion.The tirofiban-DAPT protocol used is described.Data regarding duration of infusion,placement of external ventricular devices(EVDs),complications,haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed.results One-hundred and forty-one patients with 148 aneurysms/procedures were included.110 aneurysms were treated acutely and 38 electively.Minor and major haemorrhagic events were recognised in 20%(30/148)aneurysms.Only 5(3.4%)intracerebral haemorrhages were symptomatic:3 cortical/SAH and 2 EVD-related.The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages(p=0.002).The rate of EVD-related haemorrhages was 15.7%(19/121)and only 2(1.7%)were symptomatic.Most haemorrhagic events occurred in ruptured aneurysms(90.1%,p=0.01).No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented.Concomitant administration of heparin did not increase haemorrhagic events.Conclusion The use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe.Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications.
文摘Diffusion-weighted imaging (DWI) is an established diagnostic method of acute stroke. The latest advances in magnetic resonance imaging (MRI) technology have greatly expanded the utility of DWI in the examination of various organs. Recent studies have revealed the usefulness of DWI for imaging of the liver, kidney, ovary, and breast. We report a patient with acute pancreatitis detected by DWI and discussed the efficacy of DWI in diagnosing acute pancreatitis. A 50-year old man presented with a primary complaint of abdominal pain. We performed both DWI and computed tomography (CT) for this patient. The signal intensity in a series of DWI was measured and the apparent diffusion coefficient (ADC) values were calculated to differentiate inflammation from normal tissue. Two experienced radiologists evaluated the grade of acute pancreatitis by comparing the CT findings. Initially, the pancreas and multiple ascites around the pancreas produced a bright signal and ADC values were reduced on DWI. As the inflammation decreased, the bright signal faded to an iso-signal and the ADC values returned to their normal level. There was no difference in the abilities of DWI and CT images to detect acute pancreatitis. However, our case indicates that DWI can evaluate the manifestations of acute pancreatitis using no enhancement material andhas the potential to replace CT as a primary diagnostic strategy for acute pancreatitis.
文摘AIM: To darify bhe efficacy and safety of bhree-dimensional conformal radiotherapy (3-D CRT) for bhis disease and to specify patient subgroups suitable for this treatment. METHODS: Fifty-two patients with HCC received PVItargeted radiation therapy from .January 1995 through December 2003. Portal venous invasion (PVI) was found in the second or lower order branches of the portal vein in 6 patients, in the first branch in 24 patients and in the main trunk in 22 patients. Child classifications of liver function before radiation therapy were A, B, and C for 19, 24 and 2 patients, respectively. All patients received three-dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy (57.0 Gy in average). RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis revealed that Child status, the number of tumor foci, tumor type, transcatheter arterial embolization (TAE) after radiation therapy were statistically significant prognostic factors. Multivariate analysis showed that the number of tumor foci and TAE after radiation therapy were statistically significant. CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as treatment for PVI in HCC. 3-D CRT is recommended in combination with postradiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with Child A liver function.
文摘Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid (DHA) on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet ( 1.5% DHA ethyl ester/kg diet) for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.
文摘With the undetermined coefficient method, a new high order scheme for convection equation named as HAUC was worke d out. The accuracy of the new scheme was analyzed by comparing the computed res ults with the exact solutions of 1-D pure convection equation and nonlinear con vection equation. The effectiveness of the HAUC was also examined by comparing w ith the results obtained by other schemes. Finally, it was applied to simulate 1 -D dam break flow with differenct ratios of initial upstream water depth to do wnstream one. The results show that the scheme has the ability to simulate both undular bores and moving hydraulic jumps.
文摘We report a successful endovascular technique using a snare with a suture for retrieving a migrated broken peripherally inserted central catheter(PICC)in a chemotherapy patient.A 62-year-old male received monthly chemotherapy through a central venous port implanted into his right subclavian area.The patient completed chemotherapy without complications 1 mo ago;however,he experienced pain in the right subclavian area during his last chemotherapy session.Computed tomography on that day showed migration of a broken PICC in his left pulmonary artery,for which the patient was admitted to our hospital.We attempted to retrieve the ectopic PICC through the right jugular vein using a gooseneck snare,but were unsuccessful because the catheter was lodged in the pulmonary artery wall.Therefore,a second attempt was made through the right femoral vein using a snare with triple loops,but we could not grasp the migrated PICC.Finally,a string was tied to thetop of the snare,allowing us to curve the snare toward the pulmonary artery by pulling the string.Finally,the catheter body was grasped and retrieved.The endovascular suture technique is occasionally extremely useful and should be considered by interventional cardiologists for retrieving migrated catheters.
基金The project supported by the National Key Research and Development Program of China(Grant No.2018YFA0305703)Science Challenge Project(Grant No.TZ2016001)the National Natural Science Foundation of China(Grant Nos.U1930401 and 11874075)。
文摘High-pressure ultrafast dynamics,as a new crossed research direction,are sensitive to subtle non-equilibrium state changes that might be unresolved by equilibrium states measurements,providing crucial information for studying delicate phase transitions caused by complex interactions in Mott insulators.With time-resolved transient reflectivity measurements,we identified the new phases in the spin–orbit Mott insulator Sr_(3)Ir_(2)O_7 at 300 K that was previously unidentified using conventional approaches such as x-ray diffraction.Significant pressure-dependent variation of the amplitude and lifetime obtained by fitting the reflectivity?R/R reveal the changes of electronic structure caused by lattice distortions,and reflect the critical phenomena of phase transitions.Our findings demonstrate the importance of ultrafast nonequilibrium dynamics under extreme conditions for understanding the phase transition of Mott insulators.
基金supported by JST Fusion Oriented REsearch for disruptive Science and Technology(FOREST)Program(JPMJFR216T)JST Moonshot R&D Program,Japan(JPMJMS2214-08).
文摘In recent years,there has been extensive utilization of actuators driven by artificial muscles in wearable devices.However,the muscle distribution configurations of most wearable devices have been specifically designed and are difficult to generalize.Consequently,wearable devices that allow direct installation of actuators onto existing clothing are better suited for a wider range of application scenarios.This letter presents the development and evaluation of Funabot-Suit,a human muscle configuration inspired wearable assist device that employs McKibben artificial muscles to induce natural kinesthetic perception in the wearer’s torso.By integrating thin McKibben muscles into an existing motion capture suit,the Funabot-Suit is capable of generating four fundamental motions:forward and backward bending,and left and right twisting.The suit’s performance was assessed through experiments involving three subjects who wore the suit while standing and seated,with the subjects reporting the direction of their kinesthetic perception.The subjects also rated the perceived ease of kinesthetic perception direction on a five-point scale.Our results demonstrate that the Funabot-Suit successfully induces kinesthetic perceptions for the wearer,with a one hundred percent detection ratio for accurate responses in the command direction across all subjects and positions.We observed variations in the sensitivity of left–right and up-down sensations,which can be attributed to the positioning of artificial muscles and individual differences.
文摘Amplified fragment length polymorphism (AFLP) analysis was used to evaluate the genetic diversity of four wild geographical populations of Japanese flounder (Paralichthys olivaceus). A total of 775 loci (58.32% of which was polymorphic) in the range between 100 and 1 300 base pairs were detected from 110 individuals using seven primer combinations. The percentage of polymorphic loci detected by single primer combination for each population was calculated, ranging from 19.59% to 53.33%. Genetic similarities within and among the populations were calculated from the binary matrices of presence - absence. Phylogenetic tree of four populations was constructed by using the UPGMA method using PHYLIP Version 3.5. According to intrapopulation genetic similarities, CW population displayed the highest genetic diversity value and KY population had the lowest genetic diversity value. The distance between CW and CF populations was the farthest, which was possibly resulted from the farthest distance of Weihai of Shandong and Fujian of China compared with the geographical distance between other locations of populations. The subpopulation differentiation value (G.,) is 0. 356 5, showing a certain extent of differentiation among the four geographical populations. AFLP technology was confirmed to be an effective tool to assess within- and among-population genetic diversity of Japanese flounder. The present survey provided significant insights for research in the Japanese flounder breeding program.
文摘We developed an apparatus for producing high-density hydrogen plasma. The atomic hydrogen density was 3.1 × 1021 m<sup>?3</sup> at a pressure of 30 Pa, a microwave power of 1000 W, and a hydrogen gas flow rate of 10 sccm. We confirmed that the temperatures of transition-metal films increased to above 800<sup>。</sup>C within 5 s when they were exposed to hydrogen plasma formed using the apparatus. We applied this phenomenon to the selective heat treatment of nickel films deposited on silicon wafers and formed nickel silicide electrodes. We found that this heat phenomenon automatically stopped after the nickel slicidation reaction finished. To utilize this method, we can perform the nickel silicidation process without heating the other areas such as channel regions and improve the reliability of silicon ultralarge-scale integration devices.
基金Our study was approved by the ethics committee of the Certified Institutional Review Board of the Yoyogi Mental Clinic(certificate number.RKK227).
文摘BACKGROUND Accurate diagnosis and early resection of colorectal polyps are important to prevent the occurrence of colorectal cancer.However,technical factors and morphological factors of polyps itself can lead to missed diagnoses.Imageenhanced endoscopy and chromoendoscopy(CE)have been developed to facilitate an accurate diagnosis.There have been no reports on visibility using a combination of texture and color enhancement imaging(TXI)and CE for colorectal tumors.AIM To investigate the visibility of margins and surfaces with the combination of TXI and CE for colorectal lesions.METHODS This retrospective study included patients who underwent lower gastrointestinal endoscopy at the Toyoshima Endoscopy Clinic.We extracted polyps that were resected and diagnosed as adenomas or serrated polyps(hyperplastic polyps and sessile serrated lesions)from our endoscopic database.An expert endoscopist performed the lower gastrointestinal endoscopies and observed the lesion using white light imaging(WLI),TXI,CE,and TXI+CE modalities.Indigo carmine dye was used for CE.Three expert endoscopists rated the visibility of the margin and surface patterns in four ranks,from 1 to 4.The primary outcomes were the average visibility scores for the margin and surface patterns based on the WLI,TXI,CE,and TXI+CE observations.Visibility scores between the four modalities were compared by the Kruskal-Wallis and Dunn tests.RESULTS A total of 48 patients with 81 polyps were assessed.The histological subtypes included 50 tubular adenomas,16 hyperplastic polyps,and 15 sessile serrated lesions.The visibility scores for the margins based on WLI,TXI,CE,and TXI+CE were 2.44±0.93,2.90±0.93,3.37±0.74,and 3.75±0.49,respectively.The visibility scores for the surface based on WLI,TXI,CE,and TXI+CE were 2.25±0.80,2.84±0.84,3.12±0.72,and 3.51±0.60,respectively.The visibility scores for the detection and surface on TXI were significantly lower than that on CE but higher than that on WLI(P<0.001).The visibility scores for the margin and surface on TXI+CE
基金Supported by Grants from the Japanese Society of GastroenterologyThe Tokyo Society of Medical SciencesKanae Foundation for the Promotion of Medical Science
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer, and obesity has been established as a risk factor for HCC development. Nonalcoholic steatohepatitis(NASH) is apparently the key link between obesity and hepatocarcinogenesis, and obesity also accelerates HCC development synergistically with other risk factors, such as hepatitis virus infection and alcohol consumption. As an explanation for the pathogenesis of NASH, the so-called "two-hit" theory has been widely accepted, but recently, a better model, the so-called "multiple-hits hypothesis" was proposed, which states that many disease-promoting factors may occur in parallel, rather than consecutively. However, the overall mechanism remains largely unknown. Various cell-cell and organ-organ interactions are involved in the pathogenesis of NASH, and thus appropriate in vivo disease models are essential for a deeper understanding. However, replicating the full spectrum of human NASH has been difficult, as NASH involves obesity, insulin resistance, steatohepatitis, fibrosis, and ultimately HCC, and the lack of an appropriate mouse model has been a considerable barrier to determining the missing links among obesity, NASH, and HCC. In recent years, several innovative mouse models presenting obesity- and NASHassociated HCC have been established by modified diets, chemotoxic agents, genetic manipulation, or a combination of these factors, shedding some light on this complex network and providing new therapeutic strategies. Thus, in this paper, I review the mouse models of obesity- and NASH-associated HCC, especially focusing on recent advances and their clinical relevance.
基金the National Key Research and Development Program of China(Grant Nos.2022YFA1402301 and 2018YFA0305703)the National Natural Science Foundation of China(Grant No.U2230401)+2 种基金the National Key R&D Program of China(Grant No.2021YFA1400200),the National Natural Science Foundation of China(Grant Nos.12025408 and 11921004)the Strategic Priority Research Program of CAS(Grant No.XDB33000000).
文摘Following the recent report by Dasenbrock-Gammon et al.[Nature 615,244–250(2023)]of near-ambient superconductivity in nitrogendoped lutetium trihydride(LuH_(3-δ)N_(ε)),significant debate has emerged surrounding the composition and interpretation of the observed sharp resistance drop.Here,we meticulously revisit these claims through comprehensive characterization and investigations.We definitively identify the reported material as lutetium dihydride(LuH_(2)),resolving the ambiguity surrounding its composition.Under similar conditions(270–295 K and 1–2 GPa),we replicate the reported sharp decrease in electrical resistance with a 30%success rate,aligning with the observations by Dasenbrock-Gammon et al.However,our extensive investigations reveal this phenomenon to be a novel pressure-induced metal-to-metal transition intrinsic to LuH_(2),distinct from superconductivity.Intriguingly,nitrogen doping exerts minimal impact on this transition.Our work not only elucidates the fundamental properties of LuH_(2)andLuH_(3),but also critically challenges the notion of superconductivity in these lutetium hydride systems.These findings pave the way for future research on lutetium hydride systems,while emphasizing the crucial importance of rigorous verification in claims of ambient-temperature superconductivity.
文摘Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC).Alpha-fetoprotein,Lens culinaris agglutininreactive fraction of alpha-fetoprotein,and des-c-carboxy prothrombin are well-known and useful tumor markers for HCC.The positive number status of these tumor markers has recently been demonstrated as beneficial for predicting outcome for HCC patients treated with local therapy.Although the normal ranges reported have differed by institution,the positivity of tumor markers is consistent and can easily be assessed.Kumamoto and Wakayama's group clearly demonstrated the following:1) Regardless of the degree of tumor stage,a triple-positive tumor marker profile can predict poor outcome in HCC patients undergoing HR;2) For RFA alone,HCC patients with double-and triple-positive status,having less than three lesions and lesions ≤3 cm in diameter show comparably insufficient outcomes;3) For HCC patients with lesions ≤5 cm in Child-Pugh grade A,HR is preferred over RFA;4) Microvascular invasion rates increased even in the double-positive patients,while poorly differentiated HCC was frequently observed only in the triple-positive patients;and 5) RFA with chemoembolization,anatomical liver resection,and postoperative adjuvant chemoembolization or hepatic arterial chemotherapy might improve the outcome for patients with highly malignant HCC with multiple positive tumor markers.However,the impacts of these therapies still need to be evaluated in prospective comparative studies.
基金Supported by Grant support from Daiichi Sankyo Co.,Ltd.,Astra Zeneca Co.,Ltd.,and Otsuka Pharmaceutical Co.,Ltd(To Yokosuka O)the lecture fees from Daiichi Sankyo,AstraZeneca(To Arai M)
文摘AIM: To investigate the optimum period of treatment for post endoscopic submucosal dissection (ESD) ulcers.