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Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced In Vitro reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an In Vitro model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis In Vitro. We also highlight recent progress in generating vascularized liver organoids In Vitro and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.
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Objectives@#Since the easiest way to identify pills and obtain information about them is to distinguish them visually, many studies on image processing technology exist. However, no automatic system for generating pill image data has yet been developed. Therefore, we propose a system for automatically generating image data by taking pictures of pills from various angles. This system is referred to as the pill filming system in this paper. @*Methods@#We designed the pill filming system to have three components: structure, controller, and a graphical user interface (GUI). This system was manufactured with black polylactic acid using a 3D printer for lightweight and easy manufacturing. The mainboard controls data storage, and the entire process is managed through the GUI. After one reciprocating movement of the seesaw, the web camera at the top shoots the target pill on the stage. This image is then saved in a specific directory on the mainboard. @*Results@#The pill filming system completes its workflow after generating 300 pill images. The total time to collect data per pill takes 21 minutes and 25 seconds. The generated image size is 1280 × 960 pixels, the horizontal and vertical resolutions are both 96 DPI (dot per inch), and the file extension is .jpg. @*Conclusions@#This paper proposes a system that can automatically generate pill image data from various angles. The pill observation data from various angles include many cases. In addition, the data collected in the same controlled environment have a uniform background, making it easy to process the images. Large quantities of high-quality data from the pill filming system can contribute to various studies using pill images.
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Purpose@#This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. @*Methods@#Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon’s decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. @*Results@#Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. @*Conclusion@#PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.
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Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex sets of secretory molecules, called secretomes, into host injured tissues. In recent years, extracellular vesicles (EVs) have gained much attention for their diverse and important roles in a wide range of pathophysiological processes. EVs are released from most types of cells and mediates cell–cell communication by activating receptors on target cells or by being taken up by recipient cells. EVs, including microvesicles and exosomes, encapsulate and carry proteins, nucleic acids, and lipids in the lumen and on the cell surface. Thus, EV-mediated intercellular communication has been extensively studied across various biological processes. While a number of investigations has been conducted in different tissues and body fluids, the field lacks a systematic review on stem cell-derived EVs, especially regarding their roles in stemness and differentiation. Here, we provide an overview of the pathophysiological roles of EVs and summarize recent findings focusing on EVs released from various types of stem cells. We also highlight emerging evidence for the potential implication of EVs in self-renewal, differentiation, and reprograming and discuss the benefits and limitations in translational approaches.
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Purpose@#This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs. @*Materials and Methods@#Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included. @*Results@#The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS. @*Conclusion@#The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.
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Purpose@#To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. @*Materials and Methods@#From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50–70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. @*Results@#The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3–5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. @*Conclusion@#HFRT with 50–70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.
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Objective@#Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. @*Materials and Methods@#We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017– 2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: ‘AND,’ if both showed CR; ‘OR,’ if any one showed CR; and ‘conditional OR,’ if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. @*Results@#Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. @*Conclusion@#AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.
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Purpose@#Despite the existence of Snoezelen method, there is no case of researching the effects on game addiction. Therefore, this study aims to investigate the effects of Snoezelen therapy on stress, depression, anxiety and quality of life of college students who overuse computer games or mobile phone games. @*Methods@#Eight students who responded to spend more than 30 hours of computer or mobile phone games in the selection questionnaire were recruited (The total respondents were 224 students). Students were randomly assigned to either the study group (4 students) or the control group (4 students). Stress (Korean version of Perceived Stress Scale, K-PSS), depression (Korean Screening Tool for Depression Disorders, K-DEP), Anxiety (Korean Beck Anxiety Inventory, K-BAI) and quality of life (Short Form Health Survey version 2 [SF-36]) were assessed three times (before intervention [pre], post-3 weeks [post 1], post-6 weeks [post 2]). @*Results@#First, the study group (-4.75±3.86) and control group (1.00±2.71) showed significant difference (p<0.05) in the analysis of score changes between pre-test and test at 6 weeks (post 2) for K-DEP. Next, pre-test and test at 3 weeks of intervention (post 1) for K-BAI showed significant difference (p<0.05) in the study group (-2.50±1.91) and control group (2.25±2.99). In addition, pre-test and test at 6 weeks (post 2) showed significant difference (p<0.05) for the study group (-3.00±1.51) and control group (4.75±6.24). @*Conclusion@#The study confirmed the possibility of Snoezelen therapy as a therapy method to induce effective responses in stress, depression, anxiety, and quality of life of college students with game addiction.
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Objective@#If the size of an intracranial aneurysm is below 3 mm, clinicians rarely treat them because of the low risk of rupture. But subarachnoid hemorrhage (SAH) due to the rupture of very small intracranial aneurysm (VSIA) (saccular aneurysm sized less than 3 mm) may lead to many critical neurological complications. So we analyzed the characteristics and differences between the ruptured VSIA group and the ruptured non-VSIA group. @*Methods@#421 saccular aneurysms from patients with SAH between January 2016 and December 2019 were included. Patient information including age, sex, and medical history and information about the aneurysm including location, size, aspect ratio, inflow angle, and height-width ratio were collected. And we compared the VSIA group with non-VSIA group about these characteristics @*Results@#12.1% (51/421) of the aneurysms were included in the VSIA group, while the non-VSIA group consisted of 87.9% of the aneurysms (370/421). The female predominance was significantly higher in the VSIA group than that in the non-VSIA group (p=0.011). No significant difference was observed in location, medical history, height-width ratio between the groups. The mean value of the inflow angle in the VSIA group was much lower than that in the non-VSIA group, but no statistically significant association between rupture risk and the inflow angle was observed. The average aspect ratio was significantly lower than that in the non-VSIA group. @*Conclusions@#Ruptured VSIA group has higher percentage of females and lower aspect ratio than ruptured non-VSIA group. Further studies regarding the characteristics of ruptured and unruptured VSIA patients is required for assistance in clinical decision related to treatment of VSIA group before the aneurysmal sac rupture.
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Purpose@#To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. @*Materials and Methods@#From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50–70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. @*Results@#The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3–5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. @*Conclusion@#HFRT with 50–70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.
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Objective@#Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. @*Materials and Methods@#We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017– 2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: ‘AND,’ if both showed CR; ‘OR,’ if any one showed CR; and ‘conditional OR,’ if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. @*Results@#Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. @*Conclusion@#AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.
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Purpose@#Despite the existence of Snoezelen method, there is no case of researching the effects on game addiction. Therefore, this study aims to investigate the effects of Snoezelen therapy on stress, depression, anxiety and quality of life of college students who overuse computer games or mobile phone games. @*Methods@#Eight students who responded to spend more than 30 hours of computer or mobile phone games in the selection questionnaire were recruited (The total respondents were 224 students). Students were randomly assigned to either the study group (4 students) or the control group (4 students). Stress (Korean version of Perceived Stress Scale, K-PSS), depression (Korean Screening Tool for Depression Disorders, K-DEP), Anxiety (Korean Beck Anxiety Inventory, K-BAI) and quality of life (Short Form Health Survey version 2 [SF-36]) were assessed three times (before intervention [pre], post-3 weeks [post 1], post-6 weeks [post 2]). @*Results@#First, the study group (-4.75±3.86) and control group (1.00±2.71) showed significant difference (p<0.05) in the analysis of score changes between pre-test and test at 6 weeks (post 2) for K-DEP. Next, pre-test and test at 3 weeks of intervention (post 1) for K-BAI showed significant difference (p<0.05) in the study group (-2.50±1.91) and control group (2.25±2.99). In addition, pre-test and test at 6 weeks (post 2) showed significant difference (p<0.05) for the study group (-3.00±1.51) and control group (4.75±6.24). @*Conclusion@#The study confirmed the possibility of Snoezelen therapy as a therapy method to induce effective responses in stress, depression, anxiety, and quality of life of college students with game addiction.
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Objective@#If the size of an intracranial aneurysm is below 3 mm, clinicians rarely treat them because of the low risk of rupture. But subarachnoid hemorrhage (SAH) due to the rupture of very small intracranial aneurysm (VSIA) (saccular aneurysm sized less than 3 mm) may lead to many critical neurological complications. So we analyzed the characteristics and differences between the ruptured VSIA group and the ruptured non-VSIA group. @*Methods@#421 saccular aneurysms from patients with SAH between January 2016 and December 2019 were included. Patient information including age, sex, and medical history and information about the aneurysm including location, size, aspect ratio, inflow angle, and height-width ratio were collected. And we compared the VSIA group with non-VSIA group about these characteristics @*Results@#12.1% (51/421) of the aneurysms were included in the VSIA group, while the non-VSIA group consisted of 87.9% of the aneurysms (370/421). The female predominance was significantly higher in the VSIA group than that in the non-VSIA group (p=0.011). No significant difference was observed in location, medical history, height-width ratio between the groups. The mean value of the inflow angle in the VSIA group was much lower than that in the non-VSIA group, but no statistically significant association between rupture risk and the inflow angle was observed. The average aspect ratio was significantly lower than that in the non-VSIA group. @*Conclusions@#Ruptured VSIA group has higher percentage of females and lower aspect ratio than ruptured non-VSIA group. Further studies regarding the characteristics of ruptured and unruptured VSIA patients is required for assistance in clinical decision related to treatment of VSIA group before the aneurysmal sac rupture.
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Background@#Acral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear. @*Objective@#To investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma. @*Methods@#A retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors. @*Results@#The heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT,/i> amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were ob-served in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p= 0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p＞0.05). @*Conclusion@#PTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients.
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Surgical resection is the mainstay of treatment for locally advanced esophageal cancer.Neoadjuvant therapy is recommended to improve survival, based on the results of severalrandomized trials and meta-analyses. However, controversy remains regarding howto combine surgery, radiotherapy, and chemotherapy. Moreover, in East Asia, the predominanthistological type is esophageal squamous cell carcinoma, which has a differentepidemiology and tumor biology from esophageal or gastroesophageal junctional adenocarcinoma.As such, the management of esophageal cancer in East Asia seems to bedifferent from that in Western countries. Thus, this article reviews the current evidence onneoadjuvant therapy and considers the optimal combinations and ongoing strategies ofmultimodal therapy for esophageal squamous cell carcinoma.
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Objective@#: Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. @*Methods@#: Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. @*Results@#: Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. @*Conclusion@#: Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.
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Background/Aims@#Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs. @*Methods@#A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria. @*Results@#Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events. @*Conclusions@#SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.
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BACKGROUND@#Mannitol increases blood–brain barrier permeability and can improve the efficiency of systemically administered stem cells by facilitating stem cell entry from the periphery into the injured brain. The aim of this study was to elucidate the neuroprotective effects of a combination of mannitol pretreatment and stem cell transplantation on strokeinduced neural injury. @*METHODS@#The experimental rats were randomly assigned to three groups 24 h after middle cerebral artery occlusion and reperfusion. One group received intravenous (IV) injections of phosphate-buffered saline (vehicle), another group received IV injections of human adipose-derived stem cells (hADSCs), and the last group received IV injections of hADSCs 10 min after IV mannitol injections. Neurobehavioral functions and infarct volume were compared. Immunohistochemistry (IHC) analyses were performed using antibodies against ionized calcium binding adapter-1 (IBA-1), rat endothelial antigen-1 (RECA-1), and bromodeoxyuridine/doublecortin (BrdU/DCX). @*RESULTS@#PKH-26 labeling revealed no difference in the number of stem cells that had migrated into the injured brain, and hADSC transplantation did not improve the infarct volume. However, neurobehavioral functions improved in the mannitol group. IHC showed higher numbers of RECA-1-positive cells in the peri-infarcted brain and BrdU-/DCXcolocalized cells in the subventricular zone in the mannitol group. IBA-1-positive cell number decreased in the hADSConly and mannitol-pretreatment groups compared with the vehicle group even though there was no difference between the former two groups. @*CONCLUSION@#Combinatorial treatment with mannitol and hADSC transplantation may have better therapeutic potential than hADSC monotherapy for ischemic stroke.
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Purpose@#We retrospectively evaluated the prognostic significance of lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma who underwent neoadjuvant concurrent chemoradiation therapy (NCRT) followed by surgery. @*Materials and Methods@#In total, 270 patients who underwent NCRT followed by surgery between August 2005 and December 2015 were included. They were divided into three groups: LNR 0 (n = 196), LNR low (0 0.1; n = 11). The primary endpoint was overall survival (OS), and the secondary endpoints were freedom from local recurrence (FFLR), distant metastasis-free survival (DMFS), and disease-free survival (DFS). @*Results@#The median number of retrieved lymph nodes per patient was 33. Pathologically, 74 patients had positive lymph nodes. The median follow-up duration was 36.1 months, and the median survival period was 68.4 months. There was a significant correlation between LNR and the number of positive lymph nodes (correlation coefficient = 0.763, p < 0.001). There was a substantial difference in the OS among the LNR groups, with 2-year survival rates of 79.0%, 54.0%, and 9.1% in the LNR 0, LNR low, and LNR high groups, respectively (p < 0.001). A marked decrease in FFLP, DMFS, and DFS was observed with the increasing LNR. In subgroup analysis, the survival results of patients with clinically positive lymph node were similar from those of entire cohort. @*Conclusion@#LNR is a significant prognostic factor in patients with esophageal squamous cell carcinoma who underwent NCRT followed by surgery. Additional treatment and closer follow-up would be necessary for patients with a high LNR.
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Neutrophilic urticarial dermatosis (NUD) clinically resembles urticaria but histopathologically represents a neutrophilic dermatoses. Affected patients develop erythematous macules, papules or slightly raised plaques lasting 24 to 48 hours. Histopathologic examination reveals an intense neutrophilic infiltration in the dermis with leukocytoclasia, but without fibrinoid necrosis of vessel walls. Clinical manifestations of NUD are similar to urticaria or Sweet’s syndrome, but it differs in that accompanying systemic symptoms like fever or arthralgia, and histologic features of dense neutrophilic infiltration in the dermis. A 69-year-old female patient presented with a one-day history of pruritic skin rashes and fever. Skin rashes appear erythematous patches and plaques on the whole body accompanied with multiple vesiculobullous lesions on both lower legs. Skin biopsy of lesion displayed interstitial neutrophilic infiltration in Indian file between collagen fiber, and leukocytoclasia. There were no clinical and laboratory findings that suspect of associated diseases. Herein, we report the first case of NUD developing vesiculobullous lesions.