Endoscopic resection for gastric submucosal tumors: A single-center experience in Japan.

Objectives: Endoscopic resection (ER) for gastric submucosal tumors (SMTs) has gained prominence in recent years, with studies emerging from various countries. However, there is a paucity of reports from Japan. We aimed to elucidate the efficacy and safety of ER for gastric SMT in Japan. Methods: In this retrospective observational study, we investigated the outcomes of consecutive patients who underwent ER for gastric SMT from January 2017 to May 2023. The outcome variables assessed included the complete resection rate, procedure time, closure-related outcomes, and the incidence of adverse events. Results: A total of 13 patients were included in the analysis. The median procedure time was 163 (55-283) min. Complete full-thickness resection was performed in seven cases, while in four cases, the serosa remained, and in two cases, the outer layer of the muscularis propria remained. In two cases where the SMT was located on the anterior side, conversion to laparoscopic surgery became necessary, resulting in a procedural success rate of 84.6% (11/13). Excluding these two cases, endoscopic closure of the defect was successfully accomplished in the remaining 11 cases. R0 resection was achieved in 12 out of 13 cases (92.3%). Although one patient had peritonitis, which was successfully treated conservatively, no other treatment-related adverse events were encountered. Conclusions: Although ER for SMT on the anterior side may be challenging, our experience revealed that ER is a safe and efficacious approach for gastric SMT.

Associations Among Changes in Body Composition, Activity, Muscle Recovery, and Obesity Following Total Knee Arthroplasty: A Retrospective Study.

PURPOSE: Total knee arthroplasty (TKA) is expected to improve knee pain and enable patients to regain the ability to walk, but the associations between preoperative and postoperative changes in body composition, muscle strength, and activity remain unclear. In this study, we investigated the association between changes in body composition before and after TKA surgery, the recovery process of muscle strength, and changes in activity, as well as the effects of obesity on TKA. METHODS: A total of 124 patients with unilateral knee osteoarthritis (OA) who underwent TKA were retrospectively evaluated. Body weight (BW) and body composition (body fat percentage (BFP) and diseased limb muscle mass (DLMM)), measured by bioelectrical impedance analysis, quadriceps muscle strength (QMS), measured using the isometric muscle strength meter, number of steps (NOS), and Japanese Orthopaedic Association (JOA) OA knee diseases treatment outcome criteria (JOA score) before the operation, at postoperative six months (PO6M), and at postoperative one year (PO1Y) after the operation were investigated and compared between the non-obese (BMI < 25 kg/m2) group, including underweight (<18.5 kg/m2) and normal weight patients (18.5 to 24.9 kg/m2), and obese (BMI ≥ 25 kg/m2) group, including overweight (25.0 to 29.9 kg/m2) or obese patients (≥30.0 kg/m2). RESULTS: In all patients, JOA scores significantly improved from 59.7 preoperatively to 81.2 at PO6M, and 82.7 at PO1Y (both p < 0.01). QMS significantly increased from 112.4 N preoperatively to 144.0 N at PO6M, and 151.0 N at PO1Y (both p < 0.01). On the other hand, there was no significant change in BW, BFP, NOS, and DLMM. A comparison between the obese (n = 76) and non-obese (n = 48) groups demonstrated that there was no significant difference in JOA scores preoperatively, but scores at PO1Y were significantly higher in the non-obese group (p < 0.01), and QMS increased significantly postoperatively in both groups, but the enlargement rate at PO1Y was 1.4% in the obese group versus 10.4% in the non-obese group (p = 0.04). CONCLUSION: In the body composition of TKA patients, BW, BFP, and DLMM/BW did not change significantly from preoperatively to PO1Y, but QMS and JOA scores showed significant improvement at PO6M and PO1Y compared to preoperatively. The obese patients showed less improvement in JOA scores than non-obese patients, and the rate of increase in QMS at PO1Y was smaller, suggesting that rehabilitation focusing on muscle-strengthening training is necessary even at PO6M, especially in obese patients.

Loop9 closure technique for mucosal defects after colorectal endoscopic submucosal dissection (with video).

Background and study aims Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) has the potential to reduce the occurrence of delayed adverse events (AEs) such as bleeding and perforation. This study aimed to assess the feasibility and effectiveness of the Loop9 method for closing mucosal defects following colorectal ESD. Patients and methods A retrospective single-center study was conducted using prospectively collected data from May 2020 to March 2023. Loop9 was deployed through a single instrument channel and anchored with clips at the defect site. Closure was accomplished by tightening the loop and deploying additional conventional clips as needed for complete closure. The primary outcome was complete closure rate, with secondary outcomes including the sustained closure rate at 4 to 5 days post-ESD, closed defect size, closure time, number of additional clips, and incidence of delayed AEs. Results This study included 118 cases. Complete closure was achieved in 96.6% of cases (114/118) with a sustained closure rate of 93.9% (107/114). The median size of the closed mucosal defects was 30 mm (interquartile range [IQR]: 25-38, range: 15-74). The median closure time was 14 minutes (IQR: 11.25-17), and the median number of additional clips deployed was six (IQR: 4-7). Stenosis requiring balloon dilatation was observed in one patient; however, there were no instances of post-ESD bleeding or delayed perforation. Conclusions The Loop9 method proved feasible and effective for closing mucosal defects following colorectal ESD, achieving high rates of complete and sustained closure.

Clinical outcomes of anti-reflux mucosal ablation for gastroesophageal reflux disease: An international bi-institutional study.

BACKGROUND AND AIM: Anti-reflux mucosal ablation (ARMA) is an emerging endoscopic treatment aimed at enhancing the gastroesophageal junction flap valve. This study aimed to evaluate its feasibility, effectiveness, and safety. METHODS: Between May 2018 and December 2022, patients with gastroesophageal reflux disease (GERD) symptoms refractory to acid suppression medications or those dependent on such medications were enrolled for ARMA. This retrospective analysis utilized prospectively collected data from an international bi-center study. GERD questionnaire, upper endoscopy, and 24-h pH monitoring were conducted at 2-6 months and 12 months post-ARMA. Clinical success was defined as a > 50% reduction in a validated GERD questionnaire. RESULTS: A total of 68 patients underwent ARMA. Definitive GERD was diagnosed in 44 (64.7%) patients, while 24 (35.3%) exhibited reflux hypersensitivity. Clinical success rates at 2-6 months and 1 year post-ARMA were 60% (39/65) and 70% (21/30), respectively. The median GERD-health-related quality of life score significantly improved from 26 to 11 at 2-6 months (P < 0.001). Among the 51 patients (71.8%) who underwent 24-h pH monitoring, the median acid exposure time decreased from 5.3% to 0.7% (P = 0.003), accompanied by a significant reduction in esophagitis rates (P < 0.001). Multivariate analysis did not identify predictors of short-term success. Nine (13.2%) patients experienced transient stenosis requiring balloon dilation. CONCLUSIONS: ARMA demonstrates both technical feasibility and reproducibility as a safe procedure that effectively ameliorates GERD symptoms in approximately two-thirds of patients during short-term follow up. Both reflux hypersensitivity and confirmed GERD patients, regardless of their response to acid suppression medication, may be suitable candidates.

Endoscopic carbon dioxide insufflation tolerance test on the anal sphincter for anorectal hypofunction: a pilot and feasibility study.

Background: Anorectal function deteriorates with age. The diagnostic performance of the endoscopic pressure study integrated system (EPSIS), an endoscopic carbon dioxide (CO2) insufflation stress test of the lower esophageal sphincter has been previously evaluated as a diagnostic tool for gastroesophageal reflux disease. We aimed to evaluate the applicability of EPSIS in improving anorectal function. We hypothesized that EPSIS can be applied to the diagnosis of lower gastrointestinal tract disorders. Methods: This was a pilot, single-center, retrospective study using prospectively collected data between December 2021 and March 2022. It was designed to evaluate the differences in EPSIS rectal pressure measurements between older (≥80 years) and younger (<80 years) patients. At the end of the screening colonoscopy, the colonoscope was fixed in a retroflex position. When bowel movement was observed, CO2 was insufflated to the point where gas leakage occurred through the anus. The measured maximum pressure was defined as EPSIS-rectal pressure max (EPSIS-RP max) and compared between the groups. Results: Overall, 30 patients were included and examined. The median ages of the <80 and ≥80 years' groups were 53 (range: 27-79) and 82 (range: 80-94) years, respectively, with corresponding median measured EPSIS-RP max of 18.7 (range: 8.5-30.2) and 9.8 (range: 5.4-22.3) mmHg (P<0.001). Conclusions: Measurement of maximum rectal pressure illustrates the age-related decline in physiological anorectal function. Future studies should consider a loading test using EPSIS to quantify the decline in anorectal function and use it as a routine tool for screening and adjunctive diagnosis of anorectal hypofunction.

Determination of esophageal squamous cell carcinoma and gastric adenocarcinoma on raw tissue using Raman spectroscopy.

BACKGROUND: Cancer detection is a global research focus, and novel, rapid, and label-free techniques are being developed for routine clinical practice. This has led to the development of new tools and techniques from the bench side to routine clinical practice. In this study, we present a method that uses Raman spectroscopy (RS) to detect cancer in unstained formalin-fixed, resected specimens of the esophagus and stomach. Our method can record a clear Raman-scattered light spectrum in these specimens, confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue. AIM: To evaluate the use of Raman-scattered light spectrum for detecting endoscop-ically resected specimens of esophageal squamous cell carcinoma (SCC) and gastric adenocarcinoma (AC). METHODS: We created a Raman device that is suitable for observing living tissues, and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues. We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility, ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions. Furthermore, a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed. RESULTS: We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens. After data capture, the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations. Based on data analysis of molecular-level substrates, we established cut-off values for the diagnosis of esophageal SCC and gastric AC. By analyzing specific Raman shifts, we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses. CONCLUSION: Our technique provides qualitative information for real-time morphological diagnosis. However, further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.

Learning curve for peroral endoscopic myotomy in therapeutic endoscopy experts and nonexperts: Large single-center experience.

OBJECTIVES: Reports on learning curve for peroral endoscopic myotomy (POEM) in therapeutic endoscopy nonexperts are limited. We aimed to assess the number of cases required to achieve POEM proficiency for endoscopic submucosal dissection (ESD) experts and nonexperts. METHODS: This is a retrospective study at the largest POEM referral center in Japan. POEM between April 2014 and December 2020 were included. Nonexperts and ESD experts were divided by training phases: A, 1-20; B, 21-40; C, 41-60; D, 61-80; and E, 81-100 cases. Primary outcome was operation time, and the phase to reach target time (83 min) was investigated. Secondary outcomes were clinical success rate, adverse events, and post-POEM gastroesophageal reflux disease (GERD). RESULTS: Five hundred and sixty-six cases were performed by 14 nonexperts, and 555 cases by 15 ESD experts. As the primary outcome, operation time in nonexperts was: A, 95 (79-115.8); B, 86.5 (71-105); C, 80 (70-100); D, 73 (64.5-100.5); and E, 73.5 (57.8-88.8) min, while in ESD experts: A, 90 (74-128); B, 77 (70-92); and C, 77 (70-93.5) min (median [interquartile range]). Operation time decreased significantly as experience increased in both groups (P < 0.001), and nonexperts required 41-60 cases to achieve proficiency, while experts required 21-40 cases. As secondary outcomes, in nonexperts, clinical success was 96.9-100%, adverse events were 5.0-9.2%, symptomatic GERD was 11.8-26.5%, and proton pump inhibitor (PPI) intake was 11.5-18.7% in each phase. While in experts, clinical success was 96.2-100%, adverse events were 3.0-5.8%, symptomatic GERD was 14.6-22.0%, and PPI intake was 12.6-17.9%. There were no significant differences among training phases. CONCLUSIONS: Non-ESD experts require more cases to achieve proficiency in POEM. These results are useful for establishing POEM training programs and institutional implementation of the procedure.

Adverse Tissue Reactions and Metal Ion Behavior After Small-Head Metasul Hip Arthroplasty: A Long-Term Follow-Up Study.

OBJECTIVE: To investigate the long-term survivorship, incidence of adverse reactions to metal debris (ARMD), and metal ion behavior in patients who underwent small-head Metasul metal-on-metal (MoM) total hip arthroplasty (THA). METHODS: Between February 1998 and September 2003, a retrospective study was performed on 43 consecutive patients (43 hips) who underwent unilateral cementless Metasul MoM THAs at our institution. Of them, 35 patients (nine males and 26 females) who were available for follow-up more than 15 years after THA were enrolled in this study and underwent metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) to identify ARMD. The mean age at surgery of the patients was 59.7 years old (range, 31-83). Clinical and radiographic outcomes were evaluated retrospectively. Clinical examinations were conducted using the Harris Hip Score (HHS). Serum cobalt (Co) and chromium (Cr) ion levels and Co/Cr ratio were assessed at different postoperative periods of <5, 5-10, 11-14, and ≥15 years. RESULTS: The mean follow-up period for the 35 patients included was 18.1 years (range, 15-22). The mean HHS significantly improved from 44.6 ± 11.3 points preoperatively to 89.4 ± 7.9 points at the final follow-up (P < 0.0001). ARMD was found in 20% of the patients using MARS-MRI. No signs of stem loosening were found clinically or radiographically, whereas cup loosening and ARMD were observed in three patients (9%), for whom revision THAs were performed. The Kaplan-Meier survival rates with revision for any reason as the endpoint were 90.9% at 5 years, 84.8% at 10 years, 84.8% at 15 years (95% CI, 67.1-93.6), and 70.3% at 20 years (95% CI, 43.6-87.0). The survival rates with revision for ARMD as the endpoint were 100% at 5 years, 96.6% at 10 years, 96.6% at 15 years (95% CI, 77.2-99.7), and 80.1% at 20 years (95% CI, 45.3-95.2). Serum Co ion level peaked at 5-10 years after THA, which was significantly higher than that <5 years; however, it decreased to the initial level after 15 years. In contrast, serum Cr ion level significantly increased at 5-10 years and then remained almost constant. Significant differences in Cr ion levels (1.0 vs 2.0 µg/L, P = 0.024) and Co/Cr ratio (1.3 vs 0.9, P = 0.037) were found between non-ARMD and ARMD patients at >11 years postoperatively. CONCLUSION: Our results suggest that increased Cr ion levels and decreased Co/Cr ratio may be signs of ARMD in patients who underwent small-head Metasul MoM THA.

Esophageal carcinoma in achalasia patients managed with endoscopic submucosal dissection and peroral endoscopic myotomy: Japan Achalasia Multicenter Study.

OBJECTIVES: Indications for peroral endoscopic myotomy (POEM) and endoscopic submucosal dissection (ESD) in patients with achalasia concomitant with esophageal carcinoma (EC) are unclear. This study aimed to clarify the role of POEM in cases of achalasia concomitant with EC and to elucidate the indications for ESD and efficient surveillance for EC. METHODS: We conducted a multicenter cohort study at 14 hospitals in Japan, including 3707 cases of achalasia-related esophageal motility disorders (EMDs). Factors contributing to EC risk, the characteristics of EC, and clinical outcomes of POEM/ESD were analyzed. RESULTS: In patients undergoing POEM, screening and surveillance endoscopy throughout a 1-year period resulted in diagnosis of 72.1% new EC cases. Of 62 patients with 123 ECs, 40.3% had multiple or metachronous lesions within 37.5 months. EC was predominantly observed in the middle thoracic esophagus (58.5%) and posteriorly (73.2%). POEM had comparable safety and efficacy in cases of concomitant EC even after ESD. Endoscopic en bloc resection was performed in 95.8% and 89.3% of ECs diagnosed before and after POEM, respectively (P = 0.351); however, ESD on the POEM-line was impaired by fibrosis. Multivariate analysis revealed risk factors for EC, including regular alcohol consumption, a history of smoking, advanced age, and extended disease duration. Alcohol intake and smoking had a synergistic effect on EC development. CONCLUSIONS: Screening and surveillance of POEM help in detecting EC. ESD is feasible in achalasia, although on the POEM-line is challenging. Surveillance endoscopy for EC is recommended for cases with specific risks and a history of ECs.

A novel endoscopic purse-string suture technique, "loop 9", for gastrointestinal defect closure: a pilot study.

BACKGROUND : This study aimed to assess the feasibility and efficacy of the novel loop 9 method of gastrointestinal (GI) defect closure. METHODS : 20 patients underwent a GI procedure that required defect closure. Loop 9 can be delivered through a single instrument channel (3.2 mm) and released at the defect site. After it has been anchored by two clips positioned on opposite sides of the defect edge, the loop 9 is tightened by pulling the end of the suture intraluminally using biopsy forceps. Additional clips are placed to achieve complete closure. The primary outcome was complete closure rate. The secondary outcomes were closure time, sustained closure rate, and adverse events. RESULTS : Complete closure was achieved in 100 % of cases. The mean size of the mucosal defects was 17.5 mm (range 10-55 mm). The median closure time was 14 minutes. The sustained closure rate was 90 %. No adverse events were noted. CONCLUSIONS : The loop 9 technique is feasible and effective in achieving complete and sustained closure of therapeutic endoscopy-related GI defects.

Unified magnifying endoscopic classification for esophageal, gastric and colonic lesions: a feasibility pilot study.

Background and study aims Image-enhanced magnifying endoscopy allows optimization of the detection and diagnosis of lesions found in the gastrointestinal tract. Current organ-specific classifications are well-accepted by specialized endoscopists but may pose confusion for general gastroenterologists. To address this, our group proposed the Unified Magnifying Endoscopic Classification (UMEC) which can be applied either in esophagus, stomach, or colon. The aim of this study was to evaluate the diagnostic performance and clinical applicability of UMEC. Patients and methods A single-center, feasibility pilot study was conducted. Two endoscopists with experience in magnifying narrow band imaging (NBI), blinded to white-light and non-magnifying NBI findings as well as histopathological diagnosis, independently reviewed and diagnosed all images based on UMEC. In brief, UMEC is divided into three categories: non-neoplasia, intramucosal neoplasia, and deep submucosal invasive cancer. The diagnostic performance of UMEC was assessed while using the gold standard histopathology as a reference. Results A total of 303 gastrointestinal lesions (88 esophageal squamous lesions, 90 gastric lesions, 125 colonic lesions) were assessed. The overall accuracy for both endoscopists in the diagnosis of esophageal squamous cell cancer, gastric cancer, and colorectal cancer were 84.7 %, 89.5 %, and 83.2 %, respectively. The interobserver agreement for each organ, Kappa statistics of 0.51, 0.73, and 0.63, was good. Conclusions UMEC appears to be a simple and practically acceptable classification, particularly to general gastroenterologists, due to its good diagnostic accuracy, and deserves further evaluation in future studies.

Importance of second-look endoscopy after per-oral endoscopic myotomy for safe postoperative management.

OBJECTIVES: Per-oral endoscopic myotomy (POEM) is a safe and effective treatment for achalasia and esophageal motility disorders. The role of second-look endoscopy (SE) on postoperative day 1 has not been examined. This study aimed to evaluate the findings and need of SE after POEM. METHODS: This is a single-center, retrospective study. All consecutive patients who underwent POEM and SE on postoperative day 1 between December 2017 and September 2019 were included. The primary endpoint was the rate of newly-detected adverse events (nAE) during SE that required endoscopic intervention or deviation from the normal postoperative course. Multivariate logistic regression was used to identify predictors of nAE. RESULTS: Four-hundred-ninety-seven patients (mean age, 50.3 years; female, 49.9%) were included. SE identified abnormal findings in a total of 71 patients (14.3%). nAE which required endoscopic intervention or deviation from the normal postoperative course were identified in 12 patients (2.4%): eight (1.6%) entry site dehiscence; two (0.4%) submucosal hemorrhage or hematoma; and two (0.4%) dehiscence of an intraoperative perforation site after endoclip closure. Other findings such as mucosal thermal damage without perforation and small submucosal hematoma were found in 54 patients (10.9%) and five patients (1.0%), respectively. Multivariate analysis showed that longer operation time and intraoperative adverse events (AE) were associated with clinically significant nAE during SE. CONCLUSIONS: Second-look endoscopy can detect and treat nAE that may lead to severe AE. Thus, SE should be highly considered before starting oral ingestion in all cases, and especially in those who present an intraoperative AE and longer operation time.

Endoscopic Classifications of Early Gastric Cancer: A Literature Review.

Endoscopic technologies have been continuously advancing throughout the years to facilitate improvement in the detection and diagnosis of gastric lesions. With the development of different endoscopic diagnostic modalities for EGC, several classifications have been advocated for the evaluation of gastric lesions, aiming for an early detection and diagnosis. Sufficient knowledge on the appearance of EGC on white light endoscopy is fundamental for early detection and management. On the other hand, those superficial EGC with subtle morphological changes that are challenging to be detected with white light endoscopy may now be clearly defined by means of image-enhanced endoscopy (IEE). By combining magnifying endoscopy and IEE, irregularities in the surface structures can be evaluated and highlighted, leading to improvements in EGC diagnostic accuracy. The main scope of this review article is to offer a closer look at the different classifications of EGC based on several endoscopic diagnostic modalities, as well as to introduce readers to newer and novel classifications, specifically developed for the stomach, for the assessment and diagnosis of gastric lesions.

Do Polyethylene Supra-Macroparticles Lead to Pseudotumor Formation in Metal-on-Polyethylene Total Hip Arthroplasty?

We describe 2 cases of pseudotumors induced by an unusual size of polyethylene wear particle after metal-on-polyethylene total hip arthroplasty (MoP THA). The supra-macroparticles of size >100 µm originated from a polyethylene liner with relatively small cup anteversion, potentially leading to excessive loading and increased wear of the anterior edge of the polyethylene liner. Histopathology showed a foreign-body reaction to the polyethylene particles without an adverse reaction to metal debris and with no severe signs of corrosion at the head-neck junction, which have been noted in past reports of pseudotumors in MoP THA. It has been suggested that the large polyethylene wear particles might be the cause of pseudotumor formation in MoP THA.

High-throughput identification of peptide agonists against GPCRs by co-culture of mammalian reporter cells and peptide-secreting yeast cells using droplet microfluidics.

Since G-protein coupled receptors (GPCRs) are linked to various diseases, screening of functional ligands against GPCRs is vital for drug discovery. In the present study, we developed a high-throughput functional cell-based assay by combining human culture cells producing a GPCR, yeast cells secreting randomized peptide ligands, and a droplet microfluidic device. We constructed a reporter human cell line that emits fluorescence in response to the activation of human glucagon-like peptide-1 receptor (hGLP1R). We then constructed a yeast library secreting an agonist of hGLP1R or randomized peptide ligands. We demonstrated that high-throughput identification of functional ligands against hGLP1R could be performed by co-culturing the reporter cells and the yeast cells in droplets. We identified functional ligands, one of which had higher activity than that of an original sequence. The result suggests that our system could facilitate the discovery of functional peptide ligands of GPCRs.

Massively parallel whole genome amplification for single-cell sequencing using droplet microfluidics.

Massively parallel single-cell genome sequencing is required to further understand genetic diversities in complex biological systems. Whole genome amplification (WGA) is the first step for single-cell sequencing, but its throughput and accuracy are insufficient in conventional reaction platforms. Here, we introduce single droplet multiple displacement amplification (sd-MDA), a method that enables massively parallel amplification of single cell genomes while maintaining sequence accuracy and specificity. Tens of thousands of single cells are compartmentalized in millions of picoliter droplets and then subjected to lysis and WGA by passive droplet fusion in microfluidic channels. Because single cells are isolated in compartments, their genomes are amplified to saturation without contamination. This enables the high-throughput acquisition of contamination-free and cell specific sequence reads from single cells (21,000 single-cells/h), resulting in enhancement of the sequence data quality compared to conventional methods. This method allowed WGA of both single bacterial cells and human cancer cells. The obtained sequencing coverage rivals those of conventional techniques with superior sequence quality. In addition, we also demonstrate de novo assembly of uncultured soil bacteria and obtain draft genomes from single cell sequencing. This sd-MDA is promising for flexible and scalable use in single-cell sequencing.

Characterization of retinoic acid-inducible gene-I (RIG-I) expression corresponding to viral infection and UVB in human keratinocytes.

BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic protein that recognizes viral double-stranded RNA to induce the type I interferon (IFN) response. In human keratinocytes, RIG-I is induced by IFN-γ and tumor necrosis factor-α stimulation, and is abundantly expressed in psoriatic keratinocytes of the spinous and basal layers. OBJECTIVE: This study investigated the effects of extraneous stimuli including viral infection and UVB exposure on RIG-I expression in human keratinocytes. METHODS: Human skin keratinocytes (HaCaT cells) were stimulated by polyinosinic-polycytidylic acid (poly(I:C)), which mimics viral infection, and UVB exposure. We assessed the expression of RIG-I and IFN-regulatory factor (IRF)-1 in HaCaT cells by RT-PCR and Western blot analysis. Moreover, we investigated the effect of IRF-1 binding site of RIG-I gene promoter on the regulation of RIG-I expression by luciferase promoter assay and electrophoretic mobility shift assay. RESULTS: Poly(I:C) induced RIG-I expression, while UVB inhibited basal RIG-I expression and the poly(I:C)-induced RIG-I overexpression in HaCaT cells. IRF-1, which binds to a regulatory element located on the RIG-I gene promoter, was required for both inductions of RIG-I expression. IRF-1 expression was enhanced three hours after the poly(I:C) stimulation, consistent with the RIG-I response to poly(I:C), and thereafter was suppressed. Moreover, UVB exposure promptly decreased IRF-1 expression, resulting in decreased IRF-1 protein binding to the RIG-I promoter, and consequently, decreased RIG-I expression. CONCLUSION: Thus, suppression of RIG-I and IRF-1 expression caused by UVB exposure may partly explain the inhibition of skin-based immune responses, leading to viral infection and recrudescence.

Dermoscopy of eccrine poroma with calcification.

BACKGROUND: Eccrine poromas are relatively common slow-growing benign solitary adnexal tumors originating from the intraepidermal portion of the eccrine sweat duct (acrosyringium). Dystrophic calcification is rarely found in lesions of eccrine poroma, and only 2 cases of eccrine poroma with calcification have been reported thus far. In the present report, we describe another case of eccrine poroma with calcification occurring in the palm of the hand. Also, we show dermoscopic features of this case. MAIN OBSERVATIONS: A 73-year-old man with hemiparesis, who had a 10-year history of tumor on his right palm, which was occasionally injured by a walking crutch, causing bleeding and ulceration. Physical examination revealed a pigmented dome-shaped tumor. Dermoscopic analysis revealed glomerular vessels, multiple pink-white structureless areas, and lacunae. Histological examination revealed that the tumor was composed of cords of tumor cells extending from the epidermis into the dermis. These were uniformly cuboidal cells with round, basophilic nuclei and dense vascular stromas with telangiectasia. The tumor showed cystic structures and calcification. The patient was diagnosed with Pinkus-type eccrine poroma on the basis of histological findings. CONCLUSIONS: Although cutaneous neoplasms commonly associated with calcification are of follicular origin, it is known that dystrophic calcification may be triggered also in tumors of eccrine origin by multiple factors, including mechanical injury. Dermoscopy may be helpful in establishing clinical diagnosis of calcified eccrine poromas.