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OBJECTIVES: The M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers. METHODS: Immunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls. RESULTS: Epithelial quick scores of M1 (CD11c) in NOM, Stages 1-4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1-2 OSF. CONCLUSION: The interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation.

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PURPOSE: A step-based anastomotic urethroplasty is a standard technique for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). We aim to identify pre-operative factors, including results of conventional radiological imaging, for prediction of elaborated perineal or a combined abdominoperineal procedure. METHODS: Retrospective observational study on 114 consecutive patients undergoing urethroplasty for PFUI between January 2020 and December 2022 was conducted. Surgical procedures were categorized according to the Webster classification into two groups: steps 1-2 (group 1) and steps 3-4 or a combined abdominoperineal repair (group 2). Pre-operative pattern results of RGU/VCUG were categorized regarding the relation between the proximal urethral stump with the pubic symphysis: posterior urethral stump below (pattern 1) or above (pattern 2) the lower margin of the pubic symphysis. Patient demographics were assessed. Univariate and multivariate logistic regression analyses were utilized. RESULTS: Overall, 102 patients were enrolled in the study for data analysis. On the multivariate logistic regression analysis, the presence of erectile dysfunction (OR 4.5; p = 0.014), prior combined treatment (endoscopic and urethroplasty) (OR 6.4; p = 0.018) and RGU/VCUG pattern 2 (OR 66; p < 0.001) significantly increased the likelihood of the need of step 3 or higher. CONCLUSIONS: The need of step 3 or higher during urethroplasty for PFUI can be predicted pre-operatively with conventional imaging (RGU/VCUG). Patients with proximal urethral stump above the lower margin of pubic symphysis were about 66 times more likely to need step 3 or higher during urethroplasty.

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OBJECTIVE: We assessed the efficacy of anti-desmoglein 1 (anti-DSG1) and anti-DSG3 levels by enzyme-linked immunosorbent assay (ELISA) as a preliminary diagnostic test in the diagnosis of oral pemphigus vulgaris (OPV) with or without skin involvement compared to biopsy. STUDY DESIGN: We retrospectively analyzed data collected from 23 patients (mean age 45.13 years) who had presented with chronic oral ulcerations, desquamative gingivitis, and a positive Nikolsky's sign. We performed ELISA, histopathologic examination, and direct immunofluorescence (DIF) and then calculated the sensitivity and specificity of the results of ELISA, histopathology, DIF, and the presence of a positive Nikolsky's sign in diagnosis. RESULTS: The ELISA results showed that 18 patients had elevated anti-DSG3 levels, of whom 8 also had elevated anti-DSG1 levels. The histopathology results indicated that 18 patients had OPV, of whom 4 had oral lichen planus, and 1 had sub-epithelial blistering disease confirmed to be mucous membrane pemphigoid MMP by DIF. ELISA, histopathology, and DIF had a 100% sensitivity and specificity, and the presence of a positive Nikolsky's sign had a sensitivity and specificity of 100% and 78.26%, respectively. CONCLUSIONS: Measurement of anti-DSG1 and anti-DSG3 levels by ELISA warrants consideration as a first-line diagnostic test for early detection of OPV with or without skin involvement over biopsy.

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PURPOSE: To report the 12-month results of a novel urethroplasty technique relying on a spiral preputial graft for panurethral stricture disease. MATERIALS AND METHODS: Twenty consecutive patients were treated between May and October 2021 at our center. A spiral preputial mucocutaneous graft is a foreskin-based graft, developed from a 5-cm-wide preputial skin, which is harvested using a helicoidal shape and can reach up to 20 cm in length. Stricture characteristics were assessed through preoperative retrograde and voiding cystourethrogram and maximum uroflowmetry data (Qmax). Complications were collected up to 30 days after surgery and graded using the Clavien-Dindo (C-D) classification. The patients were followed up to 12 months. RESULTS: Preoperative median Qmax was 6.5 ml/s [interquartile range (IQR): 4.0-8.7]. After a median follow-up of 12 months (IQR 12-13), six patients experienced at least one complication. Of them, two patients had grade 2 C-D complications, while only one developed a grade 3a C-D complication. The median postoperative Qmax was 16 ml/s (IQR: 13-18). Only one patient had early urethral stricture recurrence treated with dilatation after catheter removal. At one-year follow-up, no other patients had urethral stricture recurrence with an overall median Qmax of 15.1 ml/s (IQR 13.5-16.4). CONCLUSIONS: Our novel single-stage spiral preputial graft urethroplasty for panurethral stricture treatment appears to be safe and could be used as a valid alternative to two-stage procedures or even to single-stage buccal mucosa graft augmentation.

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OBJECTIVE: Persistent buccopharyngeal membrane (PBM) is a rare anomaly associated with failure of ecto-endodermal resorption of the buccopharyngeal membrane on the 26th day of intrauterine life. The current literature has insufficient information about PBM. DESIGN: Systematic Review. PATIENTS, PARTICIPANTS: Online electronic databases such as PubMed-MEDLINE, Embase, and Scopus were searched using appropriate keywords from the earliest available data until 30th August 2022, with no language restriction. Additional sources such as Google Scholar, major journals, gray literature, conference proceedings, and cross-referencing were also explored. MAIN OUTCOME MEASURES: The present systematic review evaluated and analysed the data available on PBM along with its treatment options and clinicopathological findings, prevalence, and prognosis of the patient. RESULTS: Thirty-four publications with 37 reported cases were included in this systematic review. The majority of patients had dyspnea (n = 18), followed by dysphagia (n = 10). Approximately 16 patients suffering from PBM reported orofacial abnormalities. Seventeen patients reported complete PBM, and 18 patients had partial PBM. The treatment modality followed by most patients (n = 15) was surgical excision of the membrane, along with stent placement in four patients. Oropharyngeal reconstruction was performed in four cases. The overall prognosis and survival rate of this rare condition is good. CONCLUSION: This review suggests that PBM is poorly understood, and the diagnosis of partial PBM is confirmed only when the patient complains of difficulty in breathing or eating. In-depth analysis and follow-up of the reported cases should be performed to diagnose the disease early so that clinicians can provide adequate treatment to the patients.

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Webster described a step-based perineal approach for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). The higher the complexity of the step, the higher the morbidity for the patient and the lower the surgical outcomes. We evaluated the outcomes of anastomotic urethroplasty (especially Step 4 or higher) or substitution urethroplasty in patients with PFUI at our center. Between 2013 to 2021, we retrospectively collected data on patients with PFUI. Surgical procedures were categorized according to the Webster classification and rates of each step were reported. The success rate was defined as Qmax above 10 mL/s and no need for further treatment. In this period, 737 male patients with PFUI were surgically treated. Notably, 18.8%, 17.6%, 46%, 1.8%, and 5.6% of included patients received steps 1, 2, 3, and 4 and the abdominoperineal approach, respectively. In 68 (9.2%) patients, the substitution of urethroplasty with a pedicled preputial tube (PPT) was needed. The success rate was 69.2% in Step 4, 74.4% in the abdominoperineal approach, and 86.4% in PPT; however, recurrence-free survival was not significantly different between groups (p = 0.22). Step 4 perineal anastomotic urethroplasty represents a surgical option in the armamentarium of PFUI treatment. Indications should be carefully reviewed to improve patient selection and avoid surgical failure, stopping at the step which first gives a tension-free anastomosis.

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There has been rapid evolution in management of urethral strictures in the last 3 decades. From the era of dilatation, we have moved to urethral reconstruction. Reinvention of buccal grafts changed the outcomes of urethroplasty. Barbaglis dorsal onlay popularised stricture management across the globe. Kulkarni described a single stage surgery for panurethral stricture. Advances have taken place, and we have moved from transecting to the non-transecting approaches. We describe the various advances in urethral reconstruction in the last decade.

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Effective retraction and clear exposure of urethral tissue is essential in reconstructive penile surgery. The Joshi-Kulkarni retractor provides stable, bloodless operative exposure via non-traumatic tissue compression at the base of penis. The self-retaining design of this retractor also improves ergonomics thereby reducing surgeon fatigue. In this article, we describe how to do a penile urethroplasty by using the Joshi-Kulkarni penile retractor.

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Objective: Incidences of post-transurethral resection of the prostate (post-TURP) strictures are between 2.2% and 9.8%. Stricture commonly occurs within the first 6 months. Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty. Methods: This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020. We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention. We have excluded patients with bladder neck contracture. Primary outcome was treatment success, defined as the no need for further treatments. Secondary outcome was post-urethroplasty continent rate. Results: Seventeen patients were included in the study with median age of 66 (interquartile range 40-77) years; median time of follow-up was 24 (interquartile range 12-84) months; median stricture length was 4 (interquartile range 2-6) cm. Of the 17 patients, 15 (88.2%) were successful. All patients were continent after urethroplasty. Conclusion: With mid-term follow-up, treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure. Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

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Schaumann bodies are the inclusion bodies usually seen in sarcoidosis, but can also be found in other conditions like tuberculosis, chronic beryllium diseases and Crohn's diseases. Histopathologically, these bodies appear as round to oval shell-like basophilic calcifications usually considered to be as a residuum of lysosomal organelles activity.

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Although the optical properties of localized surface plasmon resonance and the relaxation processes of excited hot electrons in gold nanoparticles (AuNPs) have been well understood, the phenomena that occur when AuNPs relax on solid surfaces of semiconductors or insulators remain largely unknown. Thermal energy diffusion and electron transfer are relatively simple physical processes, but the phenomena they induce are interesting because of a variety of new application developments. In this Perspective, we introduce the fundamental aspects as well as advanced applications of several new physical phenomena induced by AuNPs-based hybrid materials with oxides or 2D materials. Localized heat can induce a great force on the surrounding medium to control mass transport, and plasmon-induced charge transfer reactions are expected to have applications in photocatalysis and solar cells. We also review increasing reports on the development of nano-optical sensors, transistors, and nano-light sources based on precisely controlled device structures utilizing AuNPs.

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Urethroplasty has evolved over time. The twentieth century saw management of urethral strictures and hypospadias with flaps. Things changed in the late 1990s with reintroduction of grafts. Buccal mucosa grafts gained popularity. There are failed urethroplasties and obliterative strictures, mostly iatrogenic, after urologic endosurgery. Such strictures need vascularized augmentation or substitution with flaps. Reconstructive urologists should be well versed in management of all types of complex cases. This article discusses the commonly used flaps in genitourinary reconstruction. Penile flaps are the commonest. Overall, the winner is the dartos. All penile flaps are based on the excellent vascularity of dartos.

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3D bioprinting is a major area of interest in health sciences for customized manufacturing, but lacks specific bioinks to enhance the shape fidelity of 3D bioprinting and efficiency of tissue repair for particular clinical purposes. A naringin derived bioink, which contains 1.5 mM methylacryloyl naringin and 0.15 mM methylacryloyl gelatin, improves the fidelity of 3D bioprinting due to 405 nm light absorption of methylacryloyl naringin. The naringin derived bioink promotes the growth of chondrocytes due to preserving bioactivities of naringin and functions as a medical ingredient from which it has been described as a medical bioink in this study. It facilitates cartilage regeneration by upregulating the transcription of chondrogenesis-related genes like SOX9 and genes against oxidative stress like SOD1 and SOD2 and maintains chondrocytes active resulting from the significantly enhanced COL II/COL I ratio. According to a rabbit cartilage defect model, the proposed naringin derived medical bioink significantly improves the efficiency and quality of cartilage defect repair, suggesting that the bioink is suitable for cartilage defect repair applications and a feasible strategy is provided for the formulation of medical bioinks for specific clinical purposes.

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Background: Urethral stricture is a well-known complication after transurethral prostate surgery (TPS) and it is usually considered an easy-to-treat condition. We aimed to examine characteristics of post-TPS urethral stricture cases that were referred for urethroplasty at our tertiary center. Methods: We identified 201 patients with TPS-induced stricture treated with urethroplasty at our institution from 2017 to 2021. First, stricture length and location were evaluated during preoperative assessment. Second, multiple sets of multivariable logistic regression (MLR) analyses were run to assess whether clinical variables were associated with the location of the stricture. Results: Median stricture length was 5 cm (4-7). One hundred forty-one (70.1%) patients received previous no-invasive treatments (dilatation and/or direct visual internal urethrotomy). Proximal bulbar urethra was the commonest site for stricture, whereas panurethral stricture (≥10 cm) was diagnosed in 41 (20.4%) patients. Lichen sclerosus was more common in patients with penile stricture location, compared with patients with other involved segments (26% vs 19%, p = 0.03), and it was the only predictor of penile and midbulbar urethra location at MLR. Surgical approaches were augmented urethroplasty in 94% of patients, especially for patients with previous treatment including urethroplasty (95.8% vs 82.5% for naive, p = 0.004). Dorsal onlay was the preferred approach for bulbar (53.4%) and penile urethra (90.7%), whereas ventral onlay (38.2%) and double face augmentation (20.6%) were the preferred approaches in membranous strictures. Conclusions: Most patients who were referred for TPS-induced stricture attempted previous noninvasive managements. Referred TPS-induced urethral strictures were long and frequently involving multiple segments of urethra. Augmentation urethroplasty was our preferred surgical approach because of the characteristics and complexity of these strictures. The presence of lichen may increase the risk of post-TPS stricture in a specific segment of urethra, namely the penile and midbulbar urethra.

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PURPOSE: Patients with devastated bulbar urethras have limited surgical options to restore normal upright voiding. We investigated the long-term feasibility of using two independently vascularized urethral hemi-plates lined with buccal mucosal graft (BMG) to treat these patients. METHODS: A multi-institutional retrospective review was conducted for patients that underwent this staged repair. In stage-1, the affected urethra is dissected and removed or prepared for a dorsal inlay augmentation. Two BMG segments are harvested; one graft is quilted on corpora cavernosa and urethra, creating an augmented perineal urethrostomy, and the other is quilted on the exposed distal gracilis muscle. Stage-2 utilizes the gracilis-BMG composite to recreate ventral bulbar urethra. The primary outcome measure was stricture recurrence. Secondary outcome measures included patient-reported outcome measures (PROMs). RESULTS: Five patients with mean age of 50 years (45-56) underwent staged repairs at two institutions between 7/2014 and 4/2016. All patients presented with suprapubic tubes and underwent at least one prior failed repair (1-9). Mean stricture length was 7.2 cm (5-9). Mean time between stage-1 and stage-2 repairs was 6.2 weeks (1-10). At a mean follow-up of 61 months (39-87), there were no recurrences. The mean uroflow was 20 cc/s (9-42) with a mean PVR of 59 cc (0-157). Four patients completed post-operative surveys; all reported at least a moderate improvement in their condition on Global Response Assessment (GRA), and a mean IPSS of 7.3 (0-26). CONCLUSIONS: Our bi-institutional case series demonstrates that this technique is a feasible option for devastated urethras with long-term durability.

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BACKGROUND: Non-traumatic obliterative bulbar urethral stricture with residual urethral lumen below 3 Fr is a challenging surgical scenario for reconstructive surgeons, because either anastomotic or single augmentation urethroplasty is not an option. OBJECTIVES: To describe our double-face buccal mucosa graft (BMG) urethroplasty with dorsal onlay and ventral inlay relying on the vessels and nerve-sparing technique of Kulkarni's one-side dissection. METHODS: We retrospectively reviewed a prospectively maintained database of patients with non-traumatic obliterative bulbar urethral strictures who underwent double-face bulbar urethroplasty with one-side dissection and dorsal onlay plus ventral inlay BMG. Patient demographics, clinical data, and follow-up were analyzed. RESULTS: A total of 59 patients underwent double-face urethroplasty with dorsal approach. The median age was 37 years (IQR 27-49) and the median stricture length was 5 cm (IQR 3.75-6). No patients had immediate post-operative complications. The overall success rate was 88% with a median follow-up of 30.9 months (IQR 16.9-44.2). Two patients were treated with DVIU, and two patients with open urethral surgery. One patient developed erectile dysfunction after surgery. Age, etiology, stenosis length and previous treatment were not factors related to surgical failure. CONCLUSION: Our preliminary albeit encouraging results showed that this approach was feasible in all patients and with negligible perioperative complications. Success rate was 88%. We did not find any factors related to surgical failure. Our dorsal double-face augmented urethroplasty may be a valid alternative to the Palminteri's ventral double-face urethroplasty, especially in those patients with mid-distal bulbar or peno-bulbar urethral strictures.

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BACKGROUND: Graft plus flap urethroplasty is gaining momentum in patients with nearly or completely obliterated urethral strictures, in whom staged procedures or perineal urethrostomy is the only possible alternative. However, graft plus flap urethroplasty is mainly adopted for strictures involving the penile urethra. OBJECTIVE: To report our experience on graft plus flap urethroplasty for bulbar and penobulbar reconstruction. DESIGN SETTING AND PARTICIPANTS: Between January 2014 and June 2020, patients with nearly or completely obliterated long (>4 cm) bulbar or penobulbar strictures, who required graft plus flap urethroplasty, were considered for this study. SURGICAL PROCEDURE: The bulbar and the penile urethra were accessed through a perineal incision and penile invagination when required. Grafts were harvested from cheek, lingual, or preputial skin and quilted over the corpora to reconstruct the dorsal plate of the neourethra. The fasciocutaneous penile flap recreated the ventral plate of the neourethra. The corpus spongiosum was flapped over the neourethra to prevent the formation of diverticula. MEASUREMENTS: Any need for instrumentation after surgery was defined as the primary failure. Obstructive symptoms or maximum flow rate (Qmax) below 10 ml/s, with or without a need for instrumentation, was defined as a secondary failure. RESULTS AND LIMITATIONS: We identified 15 patients who met the inclusion criteria. The median stricture length was 7 cm (interquartile range [IQR] 5-8 cm). The inner cheek was the preferred site for graft harvesting (53.3%). No perioperative complication of Clavien-Dindo grade ≥III were recorded in the first 30 postoperative days. The median Qmax at catheter removal was 23 ml/min (IQR 21.5-26 ml/min). The median follow-up was 25 mo (IQR 10-30 mo). The primary success rate was 86.7% (13/15) and the secondary success rate was 73.3% (11/15). Post-traumatic strictures represent a contraindication for this technique. CONCLUSIONS: In referral centers, graft plus flap urethroplasty represents a feasible option for patients with nearly or completely obliterated long (>4 cm) strictures. Our study demonstrated that this option is also feasible for strictures involving mainly the bulbar urethra. PATIENT SUMMARY: Perineal urethrostomy should be considered as the last option in patients with a nearly or completely obliterated bulbar urethral stricture. Nowadays, graft plus fasciocutaneous penile flap augmentation enriched our armamentarium of bulbar urethra reconstruction.