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Background@#Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. @*Methods@#We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. @*Results@#Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.
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Background/Aims@#We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC. @*Methods@#EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA. @*Results@#A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal). @*Conclusions@#A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.
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Background/Aims@#Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs. @*Methods@#Patients with TPE and MPE with pleural f luid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve. @*Results@#A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural f luid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965. @*Conclusions@#A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.
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Background/Aims@#Extracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs. @*Methods@#LpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance. @*Results@#The isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner. @*Conclusions@#EVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.
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Cancer organoids are three-dimensional mini-organ analogues derived from cancer tissues and have been proposed as models capable of simulating the structure and function of human organs and tissues in vitro. We sought to establish gastric cancer patient-derived organoids (PDOs) from tissues obtained by endoscopic biopsies. Gastric cancer-PDOs were successfully established and cultured from cancer tissues with gastric adenocarcinoma by endoscopic biopsies. To confirm that gastric cancer-PDOs were derived from cancer tissue, the consistency of the original cancer tissue was assessed by histopathological examination.As a result, it was confirmed that the shape and internal structure of gastric cancer-PDO were derived from the original gastric cancer cells, and the tumor specificity of gastric cancerPDO was confirmed through Periodic acid-Schiff (PAS) and polyclonal carcinoembryonic antigen antibody staining. These results demonstrate that gastric cancer-PDO models show the characteristics of primary tumors and have potential for drug screening and providing a personalized medicine platform.
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The posterior malleolar fracture is relatively common fracture of the foot and ankle, but several aspects of this are still controversial. If the posterior malleolus is involved in the ankle fracture, the prognosis is usually poor. A computed tomography scan is essential for accurate diagnosis and treatment planning. Although indirect reduction and the anterior to posterior screw fixation technique have the advantages of a small incision with the requirement of relatively simple skills, direct open reduction and fixation from the posterior side provide a more biomechanically stable and accurate reduction. The precise reduction of the posterior malleolar fragment helps to achieve congruency of the tibia and fibula in the incisura and contributes to syndesmotic stability. It is important to determine the indications for surgical treatment by comprehensively evaluating the three-dimensional structure of the posterior malleolar fracture and all related injuries to the ankle.
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Background/Aims@#Bacteria-derived outer membrane vesicles (OMVs) are commonly associated with various biological activities and functions. Helicobacter pylori-derived OMVs are thought to contribute to pathogenesis. This study aimed to investigate the effects of H. pylori-derived OMVs. @*Methods@#H. pylori strains were isolated from patients with gastritis, gastric ulcer, or gastric cancer using endoscopic biopsy. The U-937, AGS, and MKN-45 cell lines were exposed to H. pylori and H. pylori-derived OMVs. The expression of interleukin 8 (IL-8) messenger RNA (mRNA) was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR, and IL-8 secretion was analyzed using enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB) activation was evaluated by Western blotting. @*Results@#H. pylori and H. pylori-derived OMVs induced the expression of IL-8 mRNA and protein. Importantly, the bacteria induced higher IL-8 mRNA and protein expression than the OMVs. IL-8 expression was induced to different levels in response to H. pylori-derived OMVs from hosts with different gastric diseases. Western blotting revealed the increased phosphorylation and reduced degradation of inhibitor of NF-κB alpha in cells exposed to OMVs. @*Conclusions@#H. pylori-derived OMVs may aid the development of various gastric diseases by inducing IL-8 production and NF-κB activation.
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Background/Aims@#Endoscopic submucosal dissection (ESD) for gastric neoplasms is a widely performed procedure. Local recurrence is rare, but various post-ESD scars are encountered during follow-up endoscopy. Therefore, we investigated atypical scar patterns and evaluated the associated factors. @*Materials and Methods@#Clinicopathologic and endoscopic reviews of gastric neoplasms treated with ESD from January 2009 to December 2015 were conducted. Atypical scar patterns were classified as irregular erythema, nodularity, or mucosal defect. @*Results@#A total of 264 patients with 274 gastric neoplasms, including 201 adenomas and 73 early gastric cancers, were enrolled. The key endoscopic findings at the resection scar were defined on the basis of gross morphology as follows: irregular erythema, mucosal defect (erosion or ulcer), and nodularity. An irregular erythema scar pattern was associated with male sex, a nodularity scar pattern with smoking, and a mucosal defect scar pattern with infra-angle location (angle and antrum) and cancer. An irregular erythema with nodularity scar pattern was also associated with male sex. An irregular erythema with nodularity and mucosal defect scar pattern was associated with liver disease and chronic kidney disease. @*Conclusions@#The atypical scar patterns after gastric ESD are associated with various clinicopathologic factors.
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Purpose@#To explore whether panretinal photocoagulation (PRP) improved retinal blood circulation in patients with diabetic retinopathy of various levels of severity based on changes in the retinal circulation time as measured by video fluorescein fundus angiography. @*Methods@#We recruited patients with severe diabetic retinopathy indicated for PRP; we performed video fluorescein fundus angiography before and after PRP. We measured changes in the arterial circulation time (ACT), arteriovenous passage time (APT), and venous filling time (VFT) in patients with diabetic retinopathy of varying severity, and compared the findings. We recorded HbA1c levels and hypertension status. @*Results@#We enrolled 33 patients, 17 with severe nonproliferative diabetic retinopathy (NPDR) and 16 with early proliferative diabetic retinopathy (PDR). After PRP, neither the ACT nor the APT changed significantly in patients with severe NPDR (p = 0.927, p = 0.138) or early PDR (p = 0.137, p = 0.268). After PRP, the VFT was significantly reduced in patients with both severe NPDR (p = 0.000) and early PDR (p = 0.022). The VFT reductions were similar in both groups (p = 0.217). @*Conclusions@#In patients with severe NPDR and early PDR, improvements in retinal blood circulation after PRP are reflected by reductions in the VFT evident on video fluorescein fundus angiography. We speculate that the improvements are similar in patients with severe NPDR and early PDR.
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Background/Aims@#Bacteria-derived outer membrane vesicles (OMVs) are commonly associated with various biological activities and functions. Helicobacter pylori-derived OMVs are thought to contribute to pathogenesis. This study aimed to investigate the effects of H. pylori-derived OMVs. @*Methods@#H. pylori strains were isolated from patients with gastritis, gastric ulcer, or gastric cancer using endoscopic biopsy. The U-937, AGS, and MKN-45 cell lines were exposed to H. pylori and H. pylori-derived OMVs. The expression of interleukin 8 (IL-8) messenger RNA (mRNA) was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR, and IL-8 secretion was analyzed using enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB) activation was evaluated by Western blotting. @*Results@#H. pylori and H. pylori-derived OMVs induced the expression of IL-8 mRNA and protein. Importantly, the bacteria induced higher IL-8 mRNA and protein expression than the OMVs. IL-8 expression was induced to different levels in response to H. pylori-derived OMVs from hosts with different gastric diseases. Western blotting revealed the increased phosphorylation and reduced degradation of inhibitor of NF-κB alpha in cells exposed to OMVs. @*Conclusions@#H. pylori-derived OMVs may aid the development of various gastric diseases by inducing IL-8 production and NF-κB activation.
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Background/Aims@#Endoscopic submucosal dissection (ESD) for gastric neoplasms is a widely performed procedure. Local recurrence is rare, but various post-ESD scars are encountered during follow-up endoscopy. Therefore, we investigated atypical scar patterns and evaluated the associated factors. @*Materials and Methods@#Clinicopathologic and endoscopic reviews of gastric neoplasms treated with ESD from January 2009 to December 2015 were conducted. Atypical scar patterns were classified as irregular erythema, nodularity, or mucosal defect. @*Results@#A total of 264 patients with 274 gastric neoplasms, including 201 adenomas and 73 early gastric cancers, were enrolled. The key endoscopic findings at the resection scar were defined on the basis of gross morphology as follows: irregular erythema, mucosal defect (erosion or ulcer), and nodularity. An irregular erythema scar pattern was associated with male sex, a nodularity scar pattern with smoking, and a mucosal defect scar pattern with infra-angle location (angle and antrum) and cancer. An irregular erythema with nodularity scar pattern was also associated with male sex. An irregular erythema with nodularity and mucosal defect scar pattern was associated with liver disease and chronic kidney disease. @*Conclusions@#The atypical scar patterns after gastric ESD are associated with various clinicopathologic factors.
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Purpose@#To explore whether panretinal photocoagulation (PRP) improved retinal blood circulation in patients with diabetic retinopathy of various levels of severity based on changes in the retinal circulation time as measured by video fluorescein fundus angiography. @*Methods@#We recruited patients with severe diabetic retinopathy indicated for PRP; we performed video fluorescein fundus angiography before and after PRP. We measured changes in the arterial circulation time (ACT), arteriovenous passage time (APT), and venous filling time (VFT) in patients with diabetic retinopathy of varying severity, and compared the findings. We recorded HbA1c levels and hypertension status. @*Results@#We enrolled 33 patients, 17 with severe nonproliferative diabetic retinopathy (NPDR) and 16 with early proliferative diabetic retinopathy (PDR). After PRP, neither the ACT nor the APT changed significantly in patients with severe NPDR (p = 0.927, p = 0.138) or early PDR (p = 0.137, p = 0.268). After PRP, the VFT was significantly reduced in patients with both severe NPDR (p = 0.000) and early PDR (p = 0.022). The VFT reductions were similar in both groups (p = 0.217). @*Conclusions@#In patients with severe NPDR and early PDR, improvements in retinal blood circulation after PRP are reflected by reductions in the VFT evident on video fluorescein fundus angiography. We speculate that the improvements are similar in patients with severe NPDR and early PDR.
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The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TBP. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.
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Gastric mixed adenoneuroendocrine carcinoma (MANEC) is an entity defined by World Health Organization in 2010, which is composed of adenocarcinoma and neuroendocrine neoplasm. This is a very rare type of tumor in the stomach, which is estimated to be one to two per one million people per year on gastrointestinal track. In general, as MANEC often shows a poor prognosis, early diagnosis of the disease is important for achieving a favorable outcome. However, due to its rarity and histological heterogeneity, it is hard to suspect this disease initially, and sometimes this tumor is misdiagnosed as adenocarcinoma. The present case was a 76-year-old man who was initially diagnosed with gastric tubular adenocarcinoma without distant metastasis. Only 1 month after a curative surgery, multiple liver metastases were newly detected. Retrospective pathologic review resulted in a revised diagnosis as a gastric MANEC, and the patient underwent palliative systemic chemotherapy to achieve partial response.
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Purpose@#Minor foot amputations are performed for recurrent or infected ulcers or osteomyelitis of the diabetic feet. Patients may require a large amount of bone resection for wound closure. On the other hand, this results in more foot dysfunction and a longer time to heal. The authors describe fillet flap coverage to avoid more massive resection in selected cases. This study shows the results of fillet flap coverage for the closure of diabetic foot minor amputation. @*Materials and Methods@#This was a retrospective case series of patients who underwent forefoot and midfoot amputation and fillet flap for osteomyelitis or nonhealing ulcers between March 2013 to November 2017. In addition, the patient comorbidities, hospital days, complications, and duration to complete healing were evaluated. @*Results@#Fourteen fillet flap procedures were performed on 12 patients. Of those, two had toe necrosis, nine had forefoot necrosis, and three had midfoot necrosis. Eleven forefoot amputations and three midfoot amputations were performed. Among forefoot necrosis after a fillet flap, three patients had revision surgery for partial necrosis of the flap, and two patients had an additional amputation. Two patients had additional amputations among those with midfoot necrosis. By the fillet flap, the amputation size was reduced as much as possible. The mean initial healing days, complete healing days, and hospital stay was 70.6 days, 129.0 days, and 60.0 days, respectively. @*Conclusion@#The fillet flap facilitates restoration of the normal foot contour and allows salvage of the metatarsal or toe.
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PURPOSE: To investigate correlations between macular retinal ganglion cell (RGC) layer thickness and best-corrected visual acuity (BCVA) and visual field parameters in patients with bilateral temporal optic atrophy.METHODS: Thirty eyes of 15 patients with bilateral temporal optic atrophy and 30 eyes of 15 normal subjects that were age- and sex-matched were included in the study. We measured the thicknesses of the RGC layers of posterior poles using optical coherence tomography volume scanning. The RGC layer was divided into nine zones based on the Early Treatment of Diabetic Retinopathy Study baseline. Possible correlations of the RGC layer with the BCVA and visual field parameters were determined.RESULTS: The RGC layer thickness was significantly thinner in all patients compared to those in the control group (p = 0.001). The RGC layer thicknesses in the inner superior, inner temporal, inner inferior, and inner nasal areas were significantly correlated with the BCVA (r = −0.650, r = −0.626, r = −0.616, and r = −0.636, respectively; p = 0.000). The RGC layer thicknesses in the outer superior, outer temporal, outer inferior, and outer nasal areas were significantly correlated with the mean deviation of the visual field test (r = 0.470, r = 0.349, r = 0.496, and r = 0.469, respectively; p < 0.05).CONCLUSIONS: In patients with bilateral temporal optic atrophy, the RGC layer thickness in the medial region was correlated with the BCVA, and the RGC layer thickness in the lateral region was correlated with the mean deviation of the visual field test.
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Humanos , Retinopatía Diabética , Atrofia Óptica , Células Ganglionares de la Retina , Retinaldehído , Tomografía de Coherencia Óptica , Trastornos de la Visión , Agudeza Visual , Pruebas del Campo Visual , Campos VisualesRESUMEN
Although high-risk gastrointestinal stromal tumors (GISTs) frequently recur, even after a complete resection and imatinib therapy, local recurrence at the suture line after complete resection is rare. The present case was an 88-year-old woman who was initially diagnosed with high-risk GIST without a distant metastasis. She underwent a complete surgical resection of the lesion and received adjuvant imatinib therapy for 18 months, which was discontinued due to severe drug-induced anemia. During the follow-up, an endoscopic examination performed 40 months after the initial surgery revealed local recurrence at the anastomosis site. Although a complete surgical resection was performed, repeated local recurrence was detected 18 months later, which progressed rapidly to metastatic disease. This paper reports a case of a completely resected gastric GIST with repeated local recurrence, despite the complete surgical resections and adjuvant imatinib therapy.
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Background/Aims@#We aim to evaluate the efficacy and safety of phloroglucinol in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). @*Methods@#Seventy-two patients with IBS-D who met Rome III criteria were 1:1 randomized in a parallel, double-blind design to receive phloroglucinol or placebo for 2 weeks. Patients were followed for 1 week after the end of treatment. The primary outcome was the proportion of responders, defined as those who answered “moderate or more of improvement” to the subject global assessment for at least 1 week of the 2-week treatment period. Secondary outcomes included the proportion of these patients during the 3-week period including 1 week of follow-up, IBS symptoms (abdominal pain/discomfort, diarrhea, urgency, mucus in stool, bloating, and passage of gas), stool frequency and consistency, and IBS quality of life (IBS-QOL). @*Results@#The proportion of responders during 2-week treatment period tended to be higher in the phloroglucinol group than in the placebo group, although the difference did not reach statistical significance (55.6% vs 30.6%, P = 0.056). The proportion of responders during the 3-week period was significantly higher in the phloroglucinol group than in the placebo group (61.6% vs 30.6%, P = 0.013). Individual symptom scores, IBS-QOL, stool frequency and consistency tended to improve in the phloroglucinol group, but there were no statistical significances compared to those of the placebo group. No serious adverse events were reported in both groups. @*Conclusions@#Phloroglucinol could be a safe and beneficial option for the management of overall IBS symptoms in patients with IBS-D. Further large scaled studies are warranted.
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Background/Aims@#Patients treated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) are at risk of developing metachronous gastric cancer (MGC).The aim of this study was to evaluate the clinical outcomes of MGC after ESD for EGC between the re-ESD and surgery groups. @*Methods@#In total, data from 1,510 patients who underwent ESD for EGC from January 2005 to May 2014were retrospectively reviewed, and data from 112 patients with MGC were analyzed according to the type of treatment, namely, re-ESD and surgery. The clinicopathological factors affecting the subsequent treatment and outcomes of MGC were evaluated. @*Results@#The median duration to the development of MGC was 47 months. In multivariate analysis, lower body mass index (BMI) (p=0.037) and multiplicity (p=0.014) of index cases were significantly associated with subsequent surgery for MGC. In cases of MGC, a diffuse or mixed-type Lauren classification (p=0.009), the depth of tumor mucosal invasion (p=0.001), and an upper stomach location (p=0.049) were associated with surgery. Overall survival was significantly shorter in the surgery group than in the re-ESD group after treatment for MGC (log-rank test, p=0.01). @*Conclusions@#Lower BMI and multiplicity of index cancers were significantly associated with the surgical resection of MGC. Close follow-up is needed to minimize additional treatment for cases at high risk of advanced MGC after ESD for EGC.
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Purpose@#The aim of this study was to evaluate the diagnostic image quality of low dose abdominal digital radiography processed with a new post-processing technique. @*Materials and Methods@#Abdominal radiographs from phantom pilot studies were post-processed by the novel and conventional post-processing methods of our institution; the proper dose for the subsequent patient study of 49 subjects was determined by comparing image quality of the two preceding studies. Two radiographs of each patient were taken using the conventional and derived dose protocols with the proposed post-processing method. The image details and quality were evaluated by two radiologists. @*Results@#The radiation dose for the patient study was derived to be half of the conventional method. Overall half-dose image quality with the proposed method was significantly higher than that of the conventional method (p < 0.05) with moderate inter-rater agreement (κ = 0.60, 0.47). @*Conclusion@#By applying the new post-processing technique, half-dose abdominal digital radiography can demonstrate feasible image quality compared to the full-dose images.