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Background/Aims@#A catheter is inserted through the nasal cavity during high-resolution esophageal manometry (HRM), which may cause adverse events such as pain or epistaxis. Despite these possible safety considerations, studies on this subject are very limited. We aimed to investigate the usefulness of nasal cavity evaluation before HRM to reduce the risk of adverse events and test failure. @*Methods@#Patients who underwent HRM after consultation with the ear-nose-throat department for nasal evaluation were retrospectively enrolled between December 2021 and May 2022. The included patients had a previous history of sinonasal disease or surgery or had subjective nasal discomfort. All patients answered the Sino-Nasal Outcome Test (SNOT-22) questionnaire, and subjective nasal discomfort was scored using a visual analog scale. Nasal endoscopy and acoustic rhinometry were performed for disease evaluation and volumetric assessment. @*Results@#The analysis included 22 patients with a mean age of 58.9 years. The mean SNOT-22 score was 24.2, and 16 patients (72.7%) complained of subjective nasal obstruction. The HRM catheter was successfully inserted in 20 patients (90.9%), without any significant adverse events. The objective measurement outcomes of acoustic rhinometry and sinus endoscopy did not always correspond to subjective symptoms. Narrowed nasal airways unresponsive to decongestants were observed in two patients with failed catheter insertion. @*Conclusions@#To reduce the risk of adverse events and test failure during HRM, a site-specific questionnaire to evaluate nasal obstruction might be helpful. When nasal obstruction is suspected, objective nasal cavity evaluation could be recommended for the safe and successful performance of HRM.
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Background/Aims@#Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes. @*Methods@#We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis. @*Results@#We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems). @*Conclusions@#During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.
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Background/Aims@#Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. @*Methods@#This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. @*Results@#This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. @*Conclusion@#High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.
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Duodenal varices are uncommon complications of portal hypertension. Although duodenal variceal bleeding is infrequent, it is a life-threatening condition with a high mortality rate. Non-surgical methods for duodenal variceal bleeding include endoscopic band ligation, endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and retrograde transvenous obliteration. On the other hand, an optimal treatment strategy for this rare condition has not been established. A 38-year-old male with a history of alcoholic liver cirrhosis presented with hematemesis. An emergency esophagogastroduodenoscopy (EGD) revealed large, multiple varices in the second portion of the duodenum, and plug-assisted retrograde transvenous obliteration (PARTO) was performed accordingly. Gastrointestinal bleeding was resolved after the procedure. Follow-up EGD conducted after 11 weeks revealed complete obliteration of the previously observed duodenal varices. PARTO may be considered a viable option for treating duodenal variceal bleeding.
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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@#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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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@#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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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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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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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@#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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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@#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@#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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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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Recently, many studies have reported the potential association of Helicobacter pylori (H. pylori) with various extragastric diseases. H. pylori, a major component of the gastric microbiota, is in symbiosis with humans. It is, therefore, assumed to potentially influence immune homeostasis in humans to some extent. There are several reports highlighting the possible association of H. pylori with allergic diseases. However, these were mainly based on cross-sectional or epidemiological studies. With a greater emphasis on the effects of human microbiota on host immunity and disease development, studies have attempted to explain the association between H. pylori infection and allergic diseases. Nevertheless, no concrete evidence for a causal relationship has been clearly demonstrated yet. The association of H. pylori infection with autoimmune disorders has also been reported in the literature. It has been hypothesized that environmental triggers act on genetically vulnerable hosts, leading to autoimmune disorders. The role of H. pylori infection as one of the triggers in autoimmune diseases has been explored previously. However, the results were conflicting and indistinct with respect to most autoimmune diseases. Similar findings were also detected in skin disorders where H. pylori infection was deemed to be a causative factor. The role of H. pylori in majority of the immune-mediated disorders or skin disorders remains controversial. In this review, the association of H. pylori with various immune-mediated disorders and skin disorders is discussed. The epidemiological, serological, and experimental evidences relevant to the aforementioned association are also addressed.
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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.