Repair Of Anterior Urethral Strictures Research Articles

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty: A Trauma and Urologic Reconstructive Network of Surgeons Analysis.

Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDIs, 0-100), which quantify the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox proportional hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and BMI. Median age was 46.0 years with a median follow-up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution-only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Multi-stage surgery for anterior urethral strictures: assessment of immediate and long-term surgical outcomes

BACKGROUND: The progress made in reconstructive urethral surgery over the past 20 years has shown the effectiveness of one-stage repair of anterior urethral strictures. Nevertheless, multi-stage urethroplasty retains its primary role in the treatment of patients with the most complex urethral narrowing and obliterations.
 AIM: To evaluate the immediate and long-term surgical results of multi-stage urethroplasty for penile and bulbar urethral strictures.
 MATERIALS AND METHODS: The study included 110 men aged 1884 years who underwent multi-stage urethroplasty for the anterior urethral structures in 20102019. The techniques of buccal and skin augmentation or urethral replacement plastics were applied. Before surgery, all patients underwent a standard urological examination. Early surgical complications were evaluated from medical records. Late surgical complications were determined according to examinations that included symptomatic assessment with specialized questionnaires, laboratory tests of serum and urine, physical examination, uroflowmetry, and retrograde urethrography and ureteroscopy (if urinary disorders were detected). The median follow-up was 5 years and 2 months.
 RESULTS: Early surgical complications were detected in 27 (24.5%) patients. Surgical interventions to resolve them were required in 7 (31.8%) cases: urethrocutaneous fistulas (5), acute urinary retention (1), scrotal hematoma (1). Late surgical complications were detected in 33 (30.0%) patients, including 29 (26.7%) cases of recurrent urethral strictures. All late complications cases were classified as Clavien-Dindo IIIb, and a total of 49 additional operations were performed to eliminate them. The primary success rate for multi-stage urethroplasty was 67.3 % with a median follow-up of 62 months. Only 73 (66.4%) completed all stages of the planned surgery. Urethral integrity throughout its entire length was restored in 67 (60.9%) cases, spontaneous urination in 106 (96.4%) cases.
 CONCLUSIONS: Multi-stage surgery for anterior urethral strictures is associated with relatively high risks of surgical complications at each stage of treatment. The probability of surgical revision of complications can reach 31.8%. Patients should be informed about the risks of developing surgical complications and the potential for more than two surgeries to achieve treatment goals when planning multi-stage urethroplasty.

Dorsal onlay versus dorsal inlay buccal mucosal graft urethroplasty for anterior urethral stricture: a single centre retrospective study

Background: Urethral stricture is a relatively common disease. The choice of surgery is based on the stricture location, length of the stricture and etiology. Buccal mucosal graft (BMG) urethroplasty with Asopa and Kulkarni techniques, revolutionized the approach to anterior urethral stricture repair. Objective of the study was to compare both the dorsal onlay BMG urethroplasty technique of Kulkarni and the dorsal inlay BMG urethroplasty technique of Asopa for the management of long anterior urethral stricture. Methods: From January 2015 to October 2019, a total of 90 patients with long anterior urethral strictures were randomized into two groups. Group A (42 patients) managed by Kulkarni technique. Group B (48 patients) managed by Asopa technique. BMG urethroplasty was considered successful if no further procedure required postoperatively with maximum flow rate >15 ml/s during the follow-up period.Results: The success rate in group A and B were 80.9% and 87.5%, respectively. The mean operative time was significantly longer in group A (175±22.6 min) than in group B (102±18.14 min, p-value <0.001). The average blood loss was significantly higher in group A (154±15.65 ml) than in group B (112.76±12.62 ml, p-value <0.012).Conclusions: The dorsal onlay technique of Kulkarni and the dorsal inlay technique of Asopa buccal mucosal graft urethroplasty are reliable and satisfactory procedures with good success rates and minimum complications.

Substitution urethroplasty for anterior urethral stricture repair: comparison between lingual mucosa graft and pedicled skin flap

Objectives: The aim of this study was to compare the effectiveness and outcomes of lingual mucosa graft (LMG) urethroplasty versus pedicled skin flap (PSF) urethroplasty in the repair of anterior urethral strictures.Materials and methods: A retrospective study in one urological center examined 293 male patients with anterior urethral strictures who received substitution urethroplasty from 2006 to 2015. Of these, 199 patients received PSF urethroplasty and 94 received LMG urethroplasty. The causes of stricture included catheter damage, transurethral instrumentation, trauma, infection, tumor and radiotherapy. Strictures caused by lichen sclerosus, hypospadias repair or failed urethroplasty were excluded. The success rate of PSF versus LMG in different urethra positions was analyzed.Results: Overall, PSF and LMG had similar success rates (83.4% vs 85.1%, p = 0.713). In distal penile urethra, penile skin flaps and LMG achieved similar success rates (87.7% vs 82.1%, p = 0.297), but in proximal penile urethra, scrotal flaps had relatively low success rates (69.0% vs LMG 83.3%, p = 0.345) and in bulbar urethra, perineal skin flaps had significantly lower success rates than LMG (66.7% vs 92.3%, p = 0.036).Conclusion: Lingual mucosa is a good material for the repair of urethral defects and achieves results similar to or even better than those of PSF. Scrotal skin and perineal skin had lower success rates.

1158 Kulkarni technique of perineal approach with penile inversion for surgical repair of anterior urethral strictures: Functional and cosmetic outcomes

1158 Kulkarni technique of perineal approach with penile inversion for surgical repair of anterior urethral strictures: Functional and cosmetic outcomes

Primary dorsal buccal mucosa graft urethroplasty for anterior urethral strictures in patients with lichen sclerosus.

To report our ongoing experience with dorsal buccal mucosa graft (BMG) urethroplasty for the primary repair of anterior urethral strictures in patients with lichen sclerosus (LS). A total of 32 men with LS underwent BMG urethroplasty from January 2010 to September 2012. In 27 patients, stricture was limited to the penile urethra, while in five patients, both bulbar and penile urethra were involved. In these five patients, the entire anterior urethra was replaced with BMG. In nine (28.1%) younger patients (mean age 38.2 years, range 33-45), with adverse local conditions and significant scarring, two-stage repair was done. The paired t test was performed on preoperative and postoperative Qmax as well as on preoperative and postoperative post-void residual urine volume, and the Fisher exact test was used to assess success between treatment groups. The chi-squared test was used to compare categorical data. The overall success rate was 90.6%. Complications occurred in 9.4% of the patients (3 of 32) including hematoma in two patients and fistula in one patient. In this cohort of patients, mean preoperative Qmax was 6.2 ml per second (range 2.6-10.2) versus 18.2 (range 15.8-21.2) postoperatively (at 9 months), which was statistically significant (p < 0.002). Also, mean preoperative post-void residual urine volume was 110 ml (range 75-180) versus 19 ml (range 10-40) postoperatively at 9 months, which was statistically significant (p < 0.004). Buccal mucosa is the most reliable graft for repairing anterior urethral strictures in patients with LS. Minimal complications are observed, even in cases of long stenosis completely afflicting anterior urethra.

Urethroplasty with circular fasciocutaneous flap in the treatment of complex anterior urethral strictures

To summarize the experience of urethral reconstruction using circular fasciocutaneous flap for the treatment of complex anterior urethral strictures. The circular fasciocutaneous flap was harvested from the distal penile shaft or foreskin. Then the circular configuration was converted into longitudinal strip of skin which was rotated to ventral side to repair the exposured urethral strictures using the ventral onlay method. The surveillance protocol after urethroplasty was urination observation, regularly uroflowmetry and urethrography examination. From Nov. 2006 to Oct. 2012, 15 cases were treated. The mean age was 45 years (20-76 years) and mean follow-up period was 18 months(3 months-3 years). Stricture was caused by chronic urethritis in 4 cases, long-term urethral catheterization in 3 cases, transurethral perfusion chem other aphy in 3 cases, transurethral prostatectomy in 3 cases and hypospadias after surgery in 2 patients. The mean stricture length was 7.0 cm (3.5-12.0 cm). The overall success rate was 80.0% (12/15). Recurrence stenosis was noted in 2 cases and diverticulum formation in 1 case. The penile circular fasciocutaneous flap can be used for anterior urethral stricture in nearly any length. The flap has the characteristics of hairless, adequate mobile and length, well-vascularized pedicle and easy to harvest. The onlay reconstruction provides excellent cosmetic results, less trauma, higher success rate. Therefore it should be one of the preferred techniques for complex anterior urethral stricture repair.

Dorsal onlay (Barbagli technique) versus dorsal inlay (Asopa technique) buccal mucosal graft urethroplasty for anterior urethral stricture: A prospective randomized study

To compare both the dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa for the management of long anterior urethral stricture. From January 2010 to May 2012, a total of 47 patients with long anterior urethral strictures were randomized into two groups. The first group included 25 patients who were managed by dorsal onlay buccal mucosal graft urethroplasty. The second group included 22 patients who were managed by dorsal inlay buccal mucosal graft urethroplasty. Different clinical parameters, postoperative complications and success rates were compared between both groups. The overall success rate in the dorsal onlay group was 88%, whereas in the dorsal inlay group the success rate was 86.4% during the follow-up period. The mean operative time was significantly longer in the dorsal onlay urethroplasty group (205 ± 19.63 min) than in the dorsal inlay urethroplasty group (128 ± 4.9 min, P-value <0.0001). The average blood loss was significantly higher in the dorsal onlay urethroplasty group (228 ± 5.32 mL) than in the dorsal inlay urethroplasty group (105 ± 12.05 mL, P-value <0.0001). The dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa buccal mucosal graft urethroplasty provide similar success rates. The Asopa technique is easy to carry out, provides shorter operative time and less blood loss, and it is associated with fewer complications for anterior urethral stricture repair.

Early Aggressive Treatment of Lichen Sclerosus May Prevent Disease Progression

When not recognized and treated aggressively, lichen sclerosus may progress and cause debilitating symptoms. It also may result in significant morbidity in patients undergoing treatment for urethral strictures because unrecognized, it may result in rapid and severe recurrence after surgical treatment. We present our experience treating patients with lichen sclerosus in an equal access health care system. We performed an institutional review board approved retrospective review of all adult men with lichen sclerosus treated at our institution during a 10-year period. We analyzed all patients diagnosed with lichen sclerosus, and recorded patient demographics and therapies. We recorded characteristics of the disease process including external and internal manifestations. We also recorded the various treatments, and whether the patients experienced recurrence. A total of 43 patients were diagnosed with lichen sclerosus during the review period. Of those patients presenting with more severe (urethral) involvement and undergoing 1 or 2-stage urethroplasties, we noted 7 with recurrence. In the remainder of patients presenting with less severe disease who were treated aggressively with clobetasol and/or minor procedures, no recurrences were noted on followup examination, and all of these patients had documented normal flow patterns on noninvasive urodynamics. Our data suggest that early aggressive topical therapy plus minimally invasive surgical therapy to relieve high pressure voiding may prevent the progression of lichen sclerosus in patients who present with limited disease involving the skin and meatus.

V1537 ONE-SIDED ANTERIOR URETHROPLASTY: A NEW DORSAL ONLAY GRAFT TECHNIQUE

You have accessJournal of UrologyReconstruction1 Apr 2010V1537 ONE-SIDED ANTERIOR URETHROPLASTY: A NEW DORSAL ONLAY GRAFT TECHNIQUE Sanjay Kulkarni and Guido Barbagli Sanjay KulkarniSanjay Kulkarni Pune, India More articles by this author and Guido BarbagliGuido Barbagli Arezzo, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1289AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES This video demonstrates our new surgical technique for the repair of anterior urethral strictures in order to preserve vascular supply to the urethra and its entire muscular and neurogenic support. METHODS Twenty four patients (mean age 46 years) underwent a new one-sided anterior dorsal oral mucosal graft urethroplasty. A midline perineal incision is made. The bulbar urethra is dissected from the corpora cavernosa only along the left side.Along the right side, the urethra remains attached to the corpora cavernosa preserving its lateral blood supply.On the left side, the urethra is partially rotated and the stricture is incised dorsally along its entire length.The oral mucosal graft is spread and fixed over the corpora cavernosa.The right urethral margin is sutured to the dorsally placed BMG on the right side.A 16F silicone Foley catheter is inserted. The bulbar urethra, with the intact bulbospongiosum muscle, is rotated to its original position over the graft.4-zero polyglactin sutures are used to suture the urethral margin onto the corpora cavernosa and the graft on the left side. In patients with panurethral strictures a midline perineal incision is made. By invaginating the penis into the perineal incision, the penile and bulbar urethra is similarly dissected, only along the left side,opened dorsally.A wide meatotomy is performed dorsally from the meatus through the urethra inside the glans. The first oral mucosa graft is sutured to the dorsal edge of the meatus and pushed inside the opened penile urethra and fixed to the corpora cavernosa. Another oral mucosa graft is applied to the corpora cavernosa opposite the bulbar urethra.The ventral urethral plate is sutured to the dorsally spread and fixed BMGs.There is no penile incision.Hypospadiac meatus is avoided.The catheter is left in place for three weeks. RESULTS Clinical outcome was considered a failure when any postoperative instrumentation was needed. Mean follow-up was 22 months (range 12 to 55 months). Out of the 24 patients, 22 (91.6%)had a successful outcome and 2 (8.4%) were failures. One failure was treated using definitive perineal urethrostomy and second underwent successful internal urethrotomy. CONCLUSIONS While performing dorsal placement of the graft the full circumferential dissection of the urethra is unnecessary.Preservation of the one-sided vascular supply to the urethra and its muscular and neurogenic support represents a significant step toward perfecting the surgical technique of urethral reconstruction using a minimally invasive approach. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byKulkarni S, Joshi P and Venkatesan K (2012) Management of Panurethral Stricture Disease in IndiaJournal of Urology, VOL. 188, NO. 3, (824-830), Online publication date: 1-Sep-2012. Volume 183Issue 4SApril 2010Page: e593 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sanjay Kulkarni Pune, India More articles by this author Guido Barbagli Arezzo, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

One‐sided anterior urethroplasty: a new dorsal onlay graft technique

To investigate the feasibility, tolerability, safety and efficacy of using a new surgical technique for the repair of anterior urethral strictures to preserve vascular supply to the urethra and its entire muscular and neurogenic support. In all, 24 patients (mean age 46 years) underwent a new one-sided anterior dorsal oral mucosal graft urethroplasty while preserving the lateral vascular supply to the urethra, the central tendon of the perineum, the bulbospongiosum muscle and its perineal innervation. The cause of stricture was instrumentation in three cases (12%), unknown in five (21%), infection in four (17%), and lichen sclerosus in 12 (50%). The stricture site was bulbar in 12 cases (50%) and panurethral in 12 (50%). The mean stricture length was 4.2 cm in patients with bulbar strictures and 10 cm in patients with panurethral strictures. Of 24 patients, 20 patients (83%) had received previous treatments. Clinical outcome was considered a failure when any postoperative instrumentation was needed, including dilatation. The overall mean (range) follow-up was 22 (12-55) months. Of the 24 patients, 22 (92%) had a successful outcome and two (8%) were failures. One failure was treated using definitive perineal urethrostomy and another failure underwent successful internal urethrotomy. The preservation of the one-sided vascular supply to the urethra and its entire muscular and neurogenic support should represent a slight but significant step toward perfecting the surgical technique of urethral reconstruction using a minimally invasive approach.

Buccal Mucosa Graft Urethroplasty for Anterior Urethral Stricture Repair: Evaluation of the Impact of Stricture Location and Lichen Sclerosus on Surgical Outcome

We report our experience with buccal mucosa grafts for anterior urethral strictures. We compared outcomes in the pendulous and bulbar urethra as well as the impact of lichen sclerosus on success. A total of 53 men underwent buccal mucosa graft urethroplasty from 1997 to 2004 for strictures of all etiologies, including lichen sclerosis in 13. Of the patients 46 underwent 1-stage repair and 7 with full-thickness circumferential disease underwent multistage repair. For 1-stage repair strictures were limited to the bulb in 33 cases and they involved the pendulous urethra in 13. A dorsal onlay was used in 24 cases and a ventral onlay was used in 22. For multistage urethroplasty 2 strictures were in the bulbar urethra and 5 were in the pendulous urethra. Success was defined as no postoperative procedures or complications. The success rate of all urethroplasties was 81% (43 of 53 cases) at a mean followup of 52 months. For bulbar vs pendulous urethroplasty the success rate was 86% (30 of 35 cases) vs 72% (13 of 18, p = 0.23). For 1-stage urethroplasty by graft location success was achieved in 20 of 24 cases (83%) for dorsal onlay vs 17 of 22 (77%) for ventral onlay (p = 0.61), in 18 of 21 (86%) for bulbar-dorsal onlay, in 10 of 12 (83%) for bulbar-ventral onlay, in 2 of 3 (66%) for pendulous-dorsal onlay and in 7 of 10 (70%) for pendulous-ventral onlay. For multistage urethroplasty success was achieved in 2 of 2 cases (100%) for bulbar repair vs 4 of 5 (80%) for pendulous repair. In the 13 patients with lichen sclerosus success was achieved in 4 of 8 (50%) with 1-stage repair vs 4 of 5 (80%) with multistage repair (p = 0.28). Complications developed in 10 of 53 cases (19%), including fistula in 1, urinary tract infection in 1 and stricture in 8 that required treatment, including dilation in 3, internal urethrotomy in 4 and perineal urethrostomy in 1. Five of these 8 recurrent strictures (63%) developed in patients with lichen sclerosus, including 4 in urethras in which 1-stage repair was done for lichen sclerosus. There were no donor site complications, postoperative erectile dysfunction or chordee. A buccal mucosa graft placed dorsally or ventrally remains an excellent graft material in the bulbar and pendulous urethra. When lichen sclerosus is present, careful consideration should be given to complete excision of the diseased urethra with multistage repair vs accepting a higher rate of stricture recurrence with 1-stage repair.

V-05.08: The use of buccal mucosal grafts in reconstructive urethral surgery

Buccal mucosa has become an increasingly popular graft tissue for anterior urethroplasty because is readily available from all patients and is easily harvested from the inner cheek or lower lip with a concealed donor site scar. In the video the authors present a wide view of the one stage or multistage procedures for the repair of anterior urethral strictures using buccal mucosal grafts.

BULBAR URETHROPLASTY USING BUCCAL MUCOSA GRAFTS PLACED ON THE VENTRAL, DORSAL OR LATERAL SURFACE OF THE URETHRA: ARE RESULTS AFFECTED BY THE SURGICAL TECHNIQUE?

The use of buccal mucosa graft onlay urethroplasty represents the most widespread method of bulbar urethral stricture repair. The graft may be placed on the ventral or dorsal urethral surface according to surgeon experience and preference. We investigated whether the results are affected by the surgical technique by comparing the outcome of 3 types of bulbar urethroplasty using buccal mucosa graft. We repaired 50 bulbar urethral strictures with buccal mucosa grafts from 1997 to 2002. Mean patient age was 42 years. The etiology of stricture was ischemia in 12 cases, trauma in 6, instrumentation in 4 and unknown in 28. Patients with lichen sclerosus, failed hypospadias or urethroplasty and stricture extending into the penile urethra were not included. A total of 47 patients (94%) had undergone previous urethrotomy or dilation. The buccal mucosa graft was always harvested from the cheek using a 2 team approach. Mean graft length was 4.2 cm. The graft was placed on the ventral, dorsal and lateral bulbar urethral surface in 17, 27 and 6 cases, respectively. Clinical outcome was considered a success or failure at the time that any postoperative procedure was needed, including dilation. Mean followup was 42 months (range 12 to 76). Of 50 cases 42 (84%) were successful and 8 (16%) failed. The 17 ventral grafts provided success in 14 cases (83%) and failure in 3 (17%). The 27 dorsal grafts provided success in 23 cases (85%) and failure in 4 (15%). The 6 lateral grafts provided success in 5 cases (83%) and failure in 1 (17%). No surgical complications were observed. Failures involved the anastomotic site (distal in 2 and proximal in 3) and the whole grafted area in 3 cases. They were treated with urethrotomy in 5 cases and 2-stage urethroplasty in 3. In our experience the placement of buccal mucosa grafts into the ventral, dorsal or lateral surface of the bulbar urethra showed the same success rates (83% to 85%) and the outcome was not affected by the surgical technique. Moreover, stricture recurrence was uniformly distributed in all patients.

URETHROPLASTY FOR REFRACTORY ANTERIOR URETHRAL STRICTURE

We present our results managing anterior urethral strictures previously treated with urethroplasty and/or urethrotomy. During a 32-month period 69 males 10 to 76 years old (mean age 36) underwent treatment for anterior urethral stricture, including 32 (46%) and 26 (38%) previously treated with urethroplasty and urethrotomy, respectively. In 11 patients (16%) no previous procedures had been done. Anastomotic and dorsal patch urethroplasty was performed for bulbar stricture in 13 and 14 cases, respectively, while in 4 a penile skin flap was placed for penile stricture and in 38 a 2-stage procedure was done with urethral substitution using buccal mucosa or post-auricular skin grafts. Patients were followed with ascending urethrography at 3 weeks, and 12 and 18 months as well as with uroflowmetry. Symptoms were assessed for 6 months to 4 years. Only 1 stricture recurred in patients treated with anastomotic or patch urethroplasty, or a skin flap. Of the patients scheduled for a 2-stage procedure stage 1 revision was required due to graft scarring or stenosis at the urethrostomy site in 21% and stage 2 revision was required in 23%. Other complications in this series included fistula in 3% of cases, wound infection in 3% and post-void dribbling in 12%. Overall early results are good in our urethroplasty series in patients with a previously instrumented urethra. Patients should be advised of the possible need for multiple revisions of planned staged procedures. The increased rate of revision in these staged procedures compared with the excellent outcome of 1-stage procedures appears to be inherent in this operation in patients with multiple previous procedures rather than due to surgeon experience.

Current controversies in anterior urethral stricture repair: free-graft versus pedicled skin-flap reconstruction.

Reconstruction of long anterior urethral strictures that cannot be excised and reanastomosed remains controversial. We critically reviewed the literature on free-graft and pedicled skin-flap urethroplasty to determine the optimal method of repair. Overall, free grafts were successful in 84.3% of cases and flaps, in 85.9%. Buccal mucosa grafts are the most successful method for reconstruction of bulbar urethral strictures. For strictures in the penile urethral or a compromised graft bed a distal penile skin flap is the most reliable and tested approach. Dorsal free-graft urethroplasty may be considered when penile skin deficiency prevents use of a flap. For the most complex strictures, in which a flap is not possible and the graft bed is of poor quality, a mesh graft in two stages may be the only option. Thus, for reconstruction of complex anterior urethral strictures, both free-graft and flap procedures remain indispensable.