Regarding the quality of the published studies, there is nothing wrong with their design and methodology, but sample sizes are relatively small in most of them. The largest study (mentioned above) addresses a well-defined geographic area (Central Europe) known for the relatively high prevalence of TC and collates contributions from the groups pioneering in TC miRs. It is still unclear how the test will perform in other patient populations, when different sequencing techniques are used in other health care settings. Future validation studies will strengthen the diagnostic and predictive findings and address, or define, possible variations in outcomes. For all reasons mentioned above, and due to the lack of a well-designed cost-effectiveness analyses (only two simulations are available), at this moment in time it is still too early to recommend miR371a-3p in the EAU TC Guidelines. Two reviews, co-authored by the most prominent experts in the subject, conclude that “miR-371a-3p is a very suitable tumour marker for testicular germ cell
tumours, although further prospective studies should follow in order to identify advantages and limitations in the different clinical scenarios”. The EAU TC Panel concur with these limitations.
for CS I surveillance where tests for early diagnosis and a decrease of the imaging burden are urgently needed. References
A final consideration relates to the role of biomarker-triggered follow-up. In the current guidelines the minimal follow-up schedules present a combination of histopathology and clinical stage and include periodic physical examination, serum tumour markers determination and imaging, either by CT scan or MRI. The goal of a biomarkers will be to accurately predict the need for imaging and either replace or complement information on anatomical location and characteristics of the recurrence. Although still not ready for prime time, by introducing molecular profiling into clinical decision making miRs could have the greatest potential to become the future TC serum biomarker. In particular
Selleck MJ, Senthil M, Wall NR. Making meaningful clinical use of biomarkers. Biomark Insight, 2017; 12: 1-7. Regouc M, Belge G , Lorch A, Dieckmann KP, Pichler M. Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer. Cancers, 2020; 12: 749. Leao R , Albersen M, Looijenga LHJ, et al. Circulating MicroRNAs, the Next-Generation Serum Biomarkers in 4 Testicular Germ Cell Tumours: A Systematic Review. Eur Urol, 2021; 80: 456-466. Dieckmann KP, Radtke A, Geczi L et al. Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study. J Clin Oncol, 2019; 37:1412-1423. Sauerbrei W, Taube SE, McShane LM, Cavenagh MM, Altman DG. Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged
Explanation and Elaboration. J Nat Cancer Ins, 2018; 110: 803- 811. Murray MJ, Huddart RA, Coleman N. The present and future of serum diagnostic tests for testicular germ cell tumors. Nat Rev Uro, 2016; 1: 715-725. Nappi L, Thi M, Lum A, et al. Developing a Highly Specific Biomarker for Germ Cell Malignancies: Plasma miR371 Expression Across the Germ Cell Malignancy Spectrum. J Clin Oncol, 2019; 37:3090-3098 MicroRNA-371a-3p as a blood-based biomarker in testis cancer Hamed Ahmadi a, Thomas L. Jang b, Siamak Daneshmand, Saum Ghodoussipour. Asian J Urol, 2021; 8: 400-406. Leão R, van Agthoven T, Figueiredo A et al. Serum miRNA predicts viable disease post-chemotherapy in testicular nonseminoma germ cell tumor patients. J Uro, 2018; 200: 126-135.
Robotic vesico-vaginal fistula repair: Waste of money? Summary of the counter-point view on the EAU22 debate on “The Utility of Robotic VVF Repair” Ms. Tamsin Greenwell Consultant Urological Surgeon University College London Hospital London (GB) Tamsin.greenwell2@ nhs.net Fig. 2: Vaginal view of post hysterectomy VVF
Up to 3.5 million women worldwide have a vesicovaginal fistula (VVF), the majority of which occur as a consequence of obstructed second stage of labour in low resource health care setting. [1,2,3] VVF are extremely rare (and all iatrogenic – as a consequence of surgery and / or radiotherapy) in well-resourced health care settings – with only 74 VVF recorded in England (population 55 million) in 2018-2019. [4] (Fig. 1 and 2) The aims of VVF management are anatomical closure of the VVF with restoration of urinary continence and volitional voiding. Spontaneous closure can occur in up to 12% of women following 3 - 6 weeks management with an indwelling catheter and anti-cholinergic medication after their precipitating injury. [5,6,7] Diathermy fulguration or fibrin glue have also been used with occasional successful closure of small fistula (< 5mm) [8,9] however there is no long-term data on either technique. The majority (> 90%) of VVF obstetric and iatrogenic require formal surgical repair. There continues to be debate about the best surgical approach (vaginal versus abdominal) for VVF repair. It is possible to close VVF vaginally in at least 70% of cases [10,11], with vaginal closure rates in excess of 85% reported in some series. [12] Anatomical closure rates are similar for both routes of repair however vaginal closure is less costly, with mean cost per repair of £3524.64 compared with £4751.83 per abdominal repair [13] mainly due to faster operative time and shorter length of stay. However recently there has
Fig. 1: Pessary VVF
March/May 2022
been an increasing number of reports (the majority of which (29/42 since 2005) are either single case reports (N = 21) or small case series of 5 or less (N = 8) about robotic abdominal repair of VVF enthusiastically touting this as the best way for future VVF repair! [14,15,16] Transvaginal VVF repair was first reported by Sims in 1838. [17] VVF should be repaired vaginally unless there is an absolute indication for abdominal repair (i.e., ureteric injury requiring reimplantation +/- small capacity bladder requiring clam cystoplasty). Relative indications are previous failed abdominal repair.
Fig. 3: Vaginal repair of VVF in process – inferior margin mobilised
Vaginal repair avoids a laparotomy (or in the case of robotic repair a transabdominal procedure) and its associated morbidities. It also avoids the need to bivalve the bladder which has associated longerterm functional morbidities. Vaginal repair is also associated with reduced post-operative pain, more rapid recovery, a shorter hospital stays and an earlier return to normal activities [13,18,19,20,21] compared with open abdominal repair. Local paravaginal interposition flaps (e.g., Martius fat pad) are immediately adjacent and readily available and it is relatively simple to perform simultaneous antiincontinence or prolapse surgery if indicated. There may also be a putative reduction in medicolegal litigation costs in high resource settings because of these advantages. The complications that have been reported with transvaginal repair include vaginal shortening and potential dyspareunia. [13, 18,19,20,21] There have been no published studies comparing vaginal repair with robotic repair – however the expectation would be that postoperative pain and inpatient stay would be similar. (Fig. 3 and 4) Transabdominal VVF repair may be transvesical using the O'Connor technique [22] (where the fistula is approached via a long anterior wall and bladder dome cystostomy) or extra-peritoneal, with dissection along the back wall of the bladder minimizing bladder trauma. [23] Robotic abdominal repair attempts to replicate these techniques. [24,25]
Both techniques utilise omental flap interposition. [26,27] Absolute indications for abdominal VVF repair are simultaneous ureteric involvement (obstruction or fistula) requiring concomitant ureteric reimplantation and or small capacity bladder requiring simultaneous augmentation cystoplasty. Relative indications for abdominal VVF repair are high fistula in a deep narrow or a floppy capacious vagina making surgical access impossible (the former can generally be overcome with an episiotomy and the latter with a vaginal retractor), previously irradiated tissues, complex fistulae (these can also be repaired vaginally in non-irradiated tissue with excellent outcomes using a modified approach) [28] and previous failed transvaginal approach. [23, 26] Complex fistulae are defined as those that are greater than 2cm in diameter, radiation induced (rare in low resource settings), involving the trigone or the urethrovesical junction. [29,30]
“Being in possession of a robot with insufficient vaginal surgical skills to close a VVF vaginally is NOT an indication for robotic abdominal repair - the patient and society would be better served by referral to an expert vaginal surgeon for closure.” Abdominal VVF repair permits simultaneous reimplantation of ureter(s) and/or clam cystoplasty if required. Omentum is also easily harvested without additional morbidity or incision in open abdominal repair, whereas in the case of robotic repair this will require redocking. The complications associated with the transabdominal open repair include the morbidity associated with a laparotomy, greater post-operative pain, longer recovery time and hospital stay and a marginally higher risk of failure, all of which (except the failure rate) are less with a robotic approach. [31,32] (Fig. 5 and 6) Although there are no randomized controlled trials to compare outcomes of vaginal and abdominal repair, series have consistently reported lower primary closure rates for abdominal repair. [12, 33] A recent systematic review of VVF repair cites a success rate for a vaginal closure of 91% versus 84% for abdominal repairs. [34] Robotic abdominal closure rates are difficult to calculate as the majority are single case reports – rates reported in series of > 5 are limited, with the largest series to date being 33. [15]
Fig. 4: Vaginal repair of VVF – appearance after Completion of vaginal closure
Fig. 5: Abdominal repair of VVF – bladder open and fistula indicated by forceps
Introduction of a new technique should only occur if it is better for society i.e. it is cheaper, yields better outcomes, or a reduced length of stay OR it is better for the patient i.e. yields better outcomes, a reduced length of stay or better cosmesis. A Da Vinci robot costs in excess of €2,000,000 to purchase, €110,000 annual maintenance contract fee and €1000s in disposable equipment costs per procedure (one recent US study suggested a mean of $1866 per procedure). [35,36] This compares poorly with the cost of a reusable vaginal Buckwalter type retractor of €6000 and the costs of the reusable scissors, forceps, needle holders and clips utilised for vaginal VVF repair. On a societal level the most clinically and cost-effective way to repair the overwhelming majority of VVF is vaginally.
Fig. 6: Abdominal repair of VVF – final appearance after abdominal closure of neobladder Vaginal fistula in patient with neobladder and Mitrofanoff
For those that have absolute indications for abdominal repair (<< 15% of all VVF) then robotic abdominal repair may be an alternative to open abdominal repair however the cost advantages of reduced length of stay and earlier mobilisation must be carefully weighed against the huge purchase, maintenance, and disposable equipment costs of the robot. Robotic surgery may also not be as cosmetic as enthusiasts maintain! Finally being in possession of a robot with insufficient vaginal surgical skills to close a VVF vaginally is NOT an indication for robotic abdominal repair - the patient and society would be better served by referral to an expert vaginal surgeon for closure!! The complete reference list of this article is available from the EUT Editorial Office. Please send an e-mail to: EUT@uroweb.org with reference to the article “Robotic vesico-vaginal fistula repair: Waste of money!” by Ms. Greenwell, March/May issue 2022. European Urology Today
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