Vol 19 No 3 May-June 2022 100 Record and Appraisal of Endophytic Tumor Localization Techniques in Minimally Invasive Kidney-Sparing Procedures. A Systematic Review Spyridon Paparidis1,2*, Eleftherios Spartalis1,3, Eleftheria Mavrigiannaki4, Nikolaos Ferakis2, Konstantinos Stravodimos1,5, Gerasimos Tsourouflis1,3, Dimitrios Dimitroulis1,3, Nikolaos I. Nikiteas1,3 Purpose: Review and efficacy assessment of techniques used for intraprocedural endophytic renal mass localiza- tion. Materials and Methods: Advanced search was carried out on PubMed, Cochrane Library, Web of Science and Google Scholar databases up to August 2020. Eligibility criteria were set, according to PRISMA statement. OR (95 % CI) for identification or technical success, positive margins and recurrence, were calculated for completely endophytic tumors. Risk of Bias was evaluated using ROBVIS tool. Results: 77 studies were used for result synthesis, including 1,317 endophytic tumors, with 758 of them complete- ly endophytic. 356 endophytic tumors were treated laparoscopically and 598 robotically, using ultrasound-based methods, transarterial embolization, dual-source CT, invasive signage, 3D printing, and augmented reality varia- tions. Identification success was 97.8-100%, positive margins 0-12.5 % (completely endophytic: 95 % CI; 0.255- 1.971, OR 0.709 in laparoscopic, 95 % CI ; 0.379-3.109, OR 0.086 in robotic partial nephrectomy), recurrences 0-3.9 % (completely endophytic: 0 recurrences in laparoscopic, 95 % CI ; 0.0917-2.25, OR 0.454, in robotic partial nephrectomy), and complications 0-60 % . 363 were treated with ablation techniques using CT-based methods, thermal monitoring, transarterial embolization, ultrasound guidance and invasive signage. Technical success was 33.4-100 % (completely endophytic: 95 % CI ; 0.00157-2.060, OR 0.0569 for invasive and 95 % CI ; 0.598-13.152, OR 2.804 for non-invasive localization techniques) and recurrences were 0-20%. Conclusion: Ultrasound-based techniques showed acceptable identification success and oncologic outcomes in the laparoscopic or robotic setting. Augmented reality, showed no superiority over conventional techniques. Near infrared fluoroscopy with intravenous indocyanine green, was incapable of endophytic tumor tracking, although when administered angiographic, results were promising, along with other embolization techniques. Percutaneous hook-wire or embolization coil signage, aided in safe and successful tracking of parenchymal isoechoic masses, but data are inadequate to assess efficacy. CT-guidance, combined with ultrasound or thermal monitoring, showed increased technical success during thermal ablation, unlike ultrasound guidance that showed poor outcomes. Keywords: endophytic, kidney, laparoscopy, neoplasms, robotic surgical procedures, systematic review INTRODUCTION Kidney-sparing procedures overrun radical nephrec-tomy for treating small renal masses. European Association of Urology guidelines 2019, recommend partial nephrectomy for T1 renal cell tumors(1). Not only kidney preservation is important but also main- tenance of maximum parenchyma for better function- al outcomes, especially in patients with impaired renal function, comorbidities or bilateral tumors(2), indicating 1Hellenic Minimally Invasive and Robotic Surgery (MIRS) Study Group, National and Kapodistrian University of Athens, Medical School, Agiou Thoma 15b, Goudi, 11527Athens, Greece. 2Department of Urology, “Korgialenio-Benakio” Hellenic Red Cross Hospital, Athanasaki 2, 11526, Athens, Greece. 3Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Medical School, Mikras Asias75, 11527, Athens, Greece. 4Second Pediatric Surgery Department, General Children’s Hospital “Agia Sofia”, Thivon 1, 11527, Athens, Greece. 5First Department of Urology, National and Kapodistrian University of Athens, Medical School, Mikras Asias75, 11527, Athens, Greece. *Correspondence: Hellenic Minimally Invasive and Robotic Surgery (MIRS) Study Group, National and Kapodistrian University of Athens, Medical School, Agiou Thoma 15b, 11527, Athens, Greece, Tel: 00306974971280, E-mail: sppap1986@gmail.com. Received November 2021 & Accepted April 2022 a shift from kidney to nephron-sparing procedures. Minimally invasive nephron-sparing procedures were stratified by Gill 2003(3) into three categories: excision, probe ablation, and non-invasive ablation. Excision methods include surgeries such as laparoscopic or ro- botic-assisted partial nephrectomy(4). Probe ablation methods include RFA, Cryoablation, MWA and IRE (5,6). Finally, non-invasive ablation procedures include HIFU and stereotactic body radiation ablation(5). Urology Journal/Vol 19 No. 3/ May-June 2022/ pp. 161-178. [DOI: 10.22037/uj.v19i.7056] REVIEW Identification of endophytic renal masses, especial- ly completely endophytic that acquire 3 points in the “(E)-endophytic/exophytic” parameter of R.E.N.AL nephrometry score(7), can be challenging. Lack of haptic feedback in minimally invasive procedures and visual feedback when treating intraparenchymal masses, are obstacles in tumor localization. Our rationale is to concisely present and evaluate endo- phytic tumor identification techniques described during minimally invasive nephron-sparing procedures. We aim to comprise a decision-making guide for the clini- cian when treating endophytic and especially non-visi- ble completely endophytic renal tumors. MATERIALS AND METHODS Clinical question and Eligibility Criteria This review is based on a focused clinical question us- ing P.I.C.O (Population, Intervention, Comparison, and Outcome) Worksheet and Search Strategy Protocol (8) .(P) Endophytic renal masses, (I) Minimally Invasive Kidney-sparing procedures, (C) Tumor localization techniques, (O) Presentation of recorded techniques and evaluation of efficacy and oncologic outcomes. Inclu- sion criteria were: 1) English language 2) Population: Renal masses characterized as endophytic, complete- ly endophytic, intrarenal, totally intrarenal, intrapa- renchymal and parenchymal, 3) Study design: Rand- omized controlled trials and observational studies, as well as systematic reviews/meta-analyses, reviews and case reports 3) Intervention: minimally invasive kid- ney-sparing treatments (laparoscopic or robotic partial nephrectomy, ablative methods and hybrid techniques). 4) Outcomes: Report, assessment or comparison of dif- ferent invasive or non-invasive localization techniques used for signage of the aforementioned masses. Ex- clusion criteria were: 1) Animal, phantom, ex-vivo or cadaveric studies 2) Abstracts or conference announce- ments and electronic book publications. 3) Studies on upper tract urothelial masses. Information Sources and Search Strategy An advanced search was carried out on PubMed, Cochrane Library, Web of Science and Google Schol- ar databases up to August 2020, with the terms: kid- ney/renal/nephron sparing OR kidney/renal/nephron preserving OR laparoscopic/3D Laparoscopic/robotic/ robotic assisted partial nephrectomy OR ablation OR minimal invasive AND endophytic OR intraparenchy- mal OR intrarenal OR parenchymal AND renal tumor/ mass/lesion/cancer OR kidney tumor/mass/lesion/can- cer. Keyword search with the terms: “tumor marking” Table 1. Summary of results from studies regarding Laparoscopic-assisted Partial Nephrectomy (LPN) for endophytic tumors. Review 162 a=endophytic refers to totally intrarenal tumors with no exophytic component, b=not included 4 radical nephrectomy conversions and 1 open conversion, c=all endophytic tumors were hilar, d= endophytic tumors were totally intraparenchymal not visualized in the kidney surface, e=endophytic defined as >66% of tumor volume embedded in parenchyma, f=5 conversions to open surgery are included with 14 intraoperative and postoperative complications, g=endophytic defined as <40% of the lesion extending off the kidney surface, h=endo- phytic defined as <40% mass protruding, i= Clavien ≥II, j=postoperative only, k= lesion extending <40% from the kidney surface,l=the exact number of endophytic were not described, all the masses were characterized as endophytic and complex, m=no complications directly related to dye injection, 9 overall complications Overall mean Follow-up months. 39.2 NA 34 6.32 3 26 NA NA 16 27 NA NA NA 6 12 17 NA 18 NA 16 NA 1 Recurrence n.(%) 0 0 0 0 NA 0 NA NA 0 0 NA NA NA NA 0 0 NA 0 NA 0 0 0 Complications n.(%) 10(19.6) 7(15.2)b 2(18) NA 2(25) 68(18.7) 13(23.6)d 19(60)f 9(47.4) NA NA NA 0i NA 2(13,3)j 0 0 NA NA 0 0 0m Positive margins n.(%) 1(1.96) 0 1(9) 0 1(12.5) 2(5.4) 0 NA 2(10.5) 0 0 0 0 0 0 0 0 0 NA 0 0 0 Mean endophytic tumor size mm. 25 24.2 16 NA 37 26 23 NA 23.1 NA NA NA 27.8 NA 27 NA 38 NA NA 33 16 NA identification success n.(%) 51(100) 46(100) 11(100) 2(100) 8(100) 41(100) 55(100) NA NA 3(100) 6(100) 15(100) 5(100) 8(100) 15(100) 10(100) 10(100) 25(100) 1(100) 1(100) 1(100) NA identification method IOUS IOUS IOUS IOUS and Hydro-Jet excision IOUS IOUS IOUS IOUS IOUS IOUS and perc needle delineation AR: 3D reconstruc tion manual registratio n AR: 3D reconstruc tion manual registratio n 3D printing physical kidney model navigation AR: 3D reconstruction manual registration AR: 3D reconstructio n manual registration combined with ILUS aid AR: manual registration with CBCT and fiducials AR: Manual registration with CB imaging no fiducials DSCT angiograp hy ROLL Perc Hook- Wire Perc Hook- Wire Blue dye emboliz ation Laparoscopic technique LPN retroLPN retroLP N LPN Unclampe d hand- assisted LPN transLP N retroLPN and transLPN transLPN transLPN and retroLPN LPN transLPN or retroLPN LPN transLPN or retroLPN 3D-retroLPN retroLPN transLPN retroLPN retroLPN transLPN transLP N transLP N LPN Study arms RAPN VS LPN for complet ely endophy tic tumors TIT VS exophytic Single arm Single arm Single arm TIT VS any exophyti compon ent Intraparen chymal VS any other tumor Single arm Exophytic VS mesophytic VS Endophytic VS hilar LPN VS LRN VS lap Cryoablation 3D reconstruc tion VS no 3D reconstruc tion Single arm Single arm 3D-MIRGS VS no 3D MIRGS Single arm Single arm Single arm Single arm Single arm Single arm Single arm Single arm multivariate regression: Statistically significant covariates/outc ome R.E.N.A L. Score/ Pentafec ta. NA NA NA NA NA No covariates significant / complicati ons, surgical margins, warm ischemia and excision times, and blood loss NA NA NA Parenchy mal mass preserved/ renal function NA NA NA NA NA NA Tumor location and number of clamped branches/ glomerula r filtration rate and blood loss NA NA NA NA Endophytic tumors n./total tumors n. 61/112 46/583a 11/11c 2/35 8/8 41/402n 55/8000 32/184e 19/123g 3/50 6/49 15/91h 5/5 8/35 15/15 NA/10l 10/10 25/125k 1/3 1/1 1/1 7/50 Study type Retrospe ctive compara tive Retrospec tive case- control Retrospe ctive case- series Prospective case-series Retrospec tive case- series Retrospe ctive case- control Retrospec tive comparati ve Prospectiv e case- series Retrospecti ve comparativ e Retrospective comparative Retrospec tive case- control Retrospec tive case- series Retrospective case-series Retrospective case-control Retrospective case-series Retrospecti ve case- series Retrospective case-series Retrospect ive case- series Case report Case report Case report Prospect ive case -series Study Gu et al.2020 (12) Qin et al.2018(13) Di Pierro et al.2014 (16) Gao et al.2014 (17) Engel et al.2013 (18) Nadu et al.2013 (14) Chung et al.2011 (15) Shikanov et al.2009(21) Venkatesh et al.2006 (19) Fazio et al.2006 (20) Wang et al.2019 (42) Zhang et al.2018(43) Fan.et al 2018 (31) Wang et al.2015(44) Chen et al.2014 (17) Simpfendor fer et al .2016 (37) Teber et al.2009 (38) Shao et al.2012 (30) Hernande z et al.2017 (45) Kouriefs et al. 2019 (33) Mandoo rah et al 2018 (32) Bouvier et al 2020 (34) Endophytic renal mass localization techniques-Paparidis et al. Vol 19 No 3 May-June 2022 100 “endophytic renal tumor” “minimal invasive” “kid- ney sparing” was performed synchronously in Google Scholar database. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 2009(9). PubMed and Cochrane Library search resulted in 429, Web of Science in 29 and Google Scholar search in 977 studies. 97 originated from references manual cross-searching in relevant articles. 1,498 studies were screened for eligibility after duplicate extraction. 1,234 studies were initially excluded by title and abstract, 153 studies were secondarily excluded, after full reading, due to eligibility criteria mismatch. Finally, 111 studies were included in our systematic review for evaluation. 77 studies, 1 multi-institutional prospective single arm, 6 prospective case-series, 5 prospective comparative and 59 retrospective and 6 case-reports, were included for narrative results presentation or subgroup analysis. Search results are summarized in PRISMA flow-dia- gram(Figure 1). Data extraction and Risk of Bias assessment Data extraction was performed in duplicate and includ- ed study type and design, minimally invasive approach, identification method, identification and technical suc- cess for ablative techniques, number and size of tum- ors, marginal status, perioperative complications, recur- rence and follow-up. Risk of bias was assessed using ROBVIS tool(10) based on ROBINS-I tool for assessing non-randomized studies of interventions(11). Obser- vational studies with inconclusive information, case reports and reviews were evaluated, although a priori considered critically biased. Risk of bias was evaluated throughout seven domains: confounding, selection of participants, classification of interventions, deviations of intended interventions, missing data, measurement of outcomes, selection of the reported results. For each domain we used a judgment from low to serious. Re- sults are presented in a traffic-light plot (Figure 2). Result synthesis and Statistical Analysis Results presentation is mainly narrative. A meta-anal- ysis was not performed due to heterogeneity of overall study population. Therefore, percentages of the out- come values for each variable instead of effect meas- ures were calculated. Table 2. Summary of results from studies regarding Robotic Assisted Partial Nephrectomy (RAPN) for endophytic tumors. a=5 intraoperative complications (3 conversions, 1 ureteric injury, 1 transfusion), 12 postoperative complications (2 ≥III), b=1 local re- currence, 1 metastasis, c=1 intraoperative, 18 postoperative complications (4 III-IV), d=1 tumor positive frozen biopsy, 97,8% technical success, e= 1 tumor positive frozen biopsies, conversion, f=3 intraoperative (2 conversion, 1 ureteric injury) and 9 postoperative (4 I, 3 II, 2 III), g=2 intraoperative and 6 postoperative (1 III-IV), h=20 tumors >50% endophytic in the laparoscopic IOUS and 29 in robotic IOUS, i= 75 underwent RAPN with robotic IOUS and 75 with laparoscopic IOUS, j=25,7 months in the laparoscopic IOUS and 10,3 months in the robotic IOUS, k=endophytic: ≥50% endophytic component, l=32mm in LDU, 34mm in non LDU, m,n= detection with IOUS, no fluorescence of ICG, o=HA3D identified all endophytic masses before fat detachment allowing no kidney rotation. Ov era ll me an Fo llo w- up 27, 3 12 59 NA NA 15, 2 10, 6 33 NA 48 12, 6 18j 13 14 8 NA 3 15 12 18, 5 12 NA 5 3 NA 4 NA Re cur r enc e n.( %) 0 0 2(3 ,9) b NA NA 0 0 0 NA 1(2 ,2) 1(1 ,6) 0 0 0 0 NA 0 0 0 NA 0 NA NA 0 NA NA NA Co mp li cat ion s n.( %) 50( 82) 0 17( 32, 7 ) 14( 21, 9 ) 0 19( 21, 8 )c 2(6 ,67 ) NA 0 12( 26, 7 )f 8(1 2,3 )g NA NA NA NA 0 0 0 0 NA 0 NA NA NA NA 0 0 Po siti ve ma rgi n s n .(% ) 2(3 ,27 ) 0 5(9 ,6) 0 0 4(5 ,4) 0 NA 0 1(2 ,2) e 3(4 ,6) 3(6 ,1) 0 NA NA NA 0 0 0 NA 0 0 NA NA 0 0 0 Me an end op h yti c tum or siz e mm . 23 24 28 26 NA 28 23 NA NA 26 26 NA NA NA NA 33l 32, 5 NA NA NA 30 NA NA NA NA NA 25 Ide nti fi cat ion suc ces s n.( %) 61( 100 ) 1(1 00) NA 64( 100 ) 22( 100 ) NA NA NA NA 44( 97, 8 )d 65( 100 ) NA 21( 100 ) 9(1 00) 3(1 00) NA 4(1 00) NA 6(1 00) 5(1 00) 10( 100 ) 0m 0n 28( 100 ) 0 12( 100 ) 2(1 00) 1(1 00) Ide nti fi cat ion me tho d IO US IO US wit h Do ppl er IO US and Fro zen bio psi es IO US and Fro zen bio psi es Ro bIO US IO US ILU S o r rob IO US IO US IO US ILU S and fro zen bio psi es IO US Ro bIO US a nd lLU Si Ro bIO US Ro bIO US ILU S ILU S wit h Do ppl er ILU S lIL US lIL US rob IO U S and CE US TA E NI RF - ICG IV NI RF - ICG and lap IO U S IV NI RF - ICG and ILU S/r o bIO US AR : HA 3D nav iga ti on or IO US AR : HA 3D nav iga ti on and NI RF tra cki ng AR : rea l- tim e IO US and VS P 3 D rec ons tr uct ion Per cut a neo us em bol iz atio n coi ls and IO US Su rgi ca l ap pro a ch RA PN tra nsR A PN tra nsR A PN tra nsR A PN Ro bot ic enu cle at ion RA PN 3 o r 4 - arm tra nsR A PN tra nsR A PN Tra ns or ret roR A PN tra nsR A PN tra nsR A PN Tra ns and ret ro RA PN 3 -ar m tra nsR A PN Of f- cla mp Tra ns and ret roR A PN tra nsR A PN RA PN tra nsR A PN 4 -ar m tra nsR A PN 3-a rm tra nsR A PN 4-a rm tra nsR A PN Of f- cla mp tra nsR A PN tra nsR A PN 4-a rm RA PN tra nsR A PN tra nsR A PN RA PN ret roR A PN Stu dy arm s RA PN VS LP N for com ple t ely end oph yti c tum ors - RA PN VS OP N for com ple t ely end oph yti c tum ors RA PN VS OP N for com ple t ely end oph yti c tum ors Sin gle arm RA PN VS OP N for com ple t ely end oph yti c tum ors Int rar en al VS exo phy t ic tum ors RA PN RA PN VS OP N out com es lon g WI T VS Sh ort WI T En dop h yti c V S me sop h yti c V S Ex oph y tic RA PN En dop h yti c V S me sop h yti c V S Ex oph y tic RA PN Ro bot ic VS lap aro sc opi c U S pro be in RA PN Sin gle arm Co mp le x VS not com ple x tum ors in RA PN Sin gle arm LD U VS no - LD U in RA PN Sin gle arm Sin gle arm Sin gle arm Glo bal VS sel ect iv e V S n o isc hem i a R AP N Sin gle arm Sin gle arm NI RF - ICG V S no NI RF - ICG RA PN 3D A R VS U S gui dan c e HA 3D VS no HA 3D gui dan c e for sel ect iv e cla mp in g Sin gle arm - mu ltiv a ria te reg res si on : Sta tist i cal ly sig nif ic an t cov ari a tes /ou tc om e R.E .N. AL . Sco re/ Pen taf e cta . NA NA PA DU A s cor e/ TR IFE CT A ach iev e me nt and tum or dia me te r for exc iso n al vol um e los s NA NA NA NA Tu mo r- atta che d sur fac e are a/ WI T Ag e a nd R.E .N. A.L sco re/ pos top e rat ive ren al fun ctio n NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA En do p hy tic tum ors n./ tot al tum ors n. 61/ 112 1/1 52/ 89 64/ 140 NA /22 87/ 143 30/ 297 8/6 6 4/4 8 45/ 225 65/ 389 49/ 150 h 21/ 22k 9/6 5 3/6 7 12/ 53 4/1 4 12/ 32 6/2 0 5/6 1 10/ 10 2/7 9 5/4 7 28/ 91 12/ 52 2/1 0 1/1 Stu dy typ e Re tro sp ect ive com par ativ e Ca se rep ort Re tro sp ect ive com par ativ e Re tro sp ect ive com par ativ e Re tro sp ect ive cas e- ser ies Re tro sp ect ive com par ativ e Re tro sp ect ive com par ativ e Re tro sp ect ive com par ativ e Re tro sp ect ive com par ativ e Re tro sp ect ive com par ativ e Pro spe c tiv e com par ativ e Re tro sp ect ive com par ativ e Re tro sp ect ive cas e- ser ies Re tro ps ect ive cas e- con tro l Re tro sp ect ive cas e- ser ies Pro spe c tiv e com par ativ e Re tro sp ect ive cas e- ser ies Re tro sp ect ive cas e- ser ies Re tro sp ect ive cas e- ser ies Re tro sp ect ive com par ativ e Pro spe c tiv e cas e- ser ies Re tro sp ect ive cas e- ser ies Pro spe c tiv e com par ativ e Re tro sp ect ice com par ativ e Pro spe c tiv e com par ativ e Re tro sp ect ive cas e- ser ies Ca se rep ort Stu dy Gu et al.2 020 (12 ) Tir yak i et al.2 018 (66 ) Ab del Ra hee m et al.2 018 (63 ) Ha rke et al.2 018 (65 ) Gu nel li et al.2 016 (49 ) Ka ra et al.2 016 (50 ) Cu rtis s et al.2 015 (51 ) Bo ylu et al.2 015 ( 52) Sh iro ki et al.2 015 (62 ) Ko mn in os et al.2 014 (64 ) Au tor in o et al.2 014 (53 ) Ka czm a rek et al.2 013 (54 ) Ka czm a rek et al.2 012 (56 ) Kim e t al.2 012 ( 55) Wh ite et al.2 011 (57 ) Hy am s et al.2 011 (61 ) Ro ger s et al.2 008 ( 60) Go ng et al.2 009 (58 ) Ho et al.2 009 (59 ) Ale nez i et al.2 016 (68 ) Sim one et al.2 018 (70 ) An gel l et al.2 013 (81 ) Kr ane et al.2 012 (80 ) Po rpi gli a et al.2 019 (74 ) Po rpi gli a et al.2 018 (73 ) La sse r et al.2 012 ( 77) Re eve s et al.2 015 (79 ) Endophytic renal mass localization techniques-Paparidis et al. Vol 19 No 3 May-June 2022 163 Statistical analysis, was performed for the distinctive subgroup of completely endophytic tumors (intrapa- renchymal, parenchymal, totally intrarenal, endophytic non-visible during surgery), which showed low clinical and methodological heterogeneity. Pooled Odds Ratios (OR) under random effects, using Cochran-Mantel- Haenszel test, were calculated with MedCalc-version 19.7.1 software, and forest-plots were used for presenta- tion (Figures 3-7). Measured outcomes were, positive margins and recurrences for laparoscopic and robotic or technical success for ablation procedures, due to ad- equacy of data. We have not used adjusted ORs, since they were not provided in all relevant studies and if ap- plied, covariates were not the same in each study. All tumor localization techniques in laparoscopic and ro- botic procedures were non-invasive ultrasound-based, whereas in ablation procedures such techniques were heterogeneous (invasive and non-invasive) therefore separate analysis was performed respectively. Publica- tion bias was assessed using Egger’s linear regression test and Begg’s rank test, and presented in funnel-plots (Figures 3-7). Statistical heterogeneity was quantified, using Cochran’s Q test and I2 statistic index (P < .05 as statistically significant, I2 ≤ 50% for low hetero- geneity). The latter was used to assess if the amount of variance across studies was likely to be real and not due to sampling errors. Results were presented along with forest-plots(Figures 3-7). “R package meta” in R (programming language) was used to perform subgroup meta–regression analysis and determine sources of heterogeneity. Only confounding covariates present in all studies, either defined from authors of each study or determined according to our experience, were used for meta-regression. Results showed that positive margins in robotic approach were negatively related to patient B.M.I. Successful ablation was also negatively related to the number of thermal ablation needles used, as concluded from the negative meta-regression slope(Table 4). RESULTS Laparoscopic Assisted Partial Nephrectomy Data from 22 studies regarding 363 endophytic mass- es that underwent Laparoscopic Partial Nephrectomy (LPN), were collected (Table 1). Described techniques were, Intraoperative Ultrasound (IOUS) (n = 265), Intraoperative dual-source CT (DSCT) (n = 25), Three dimensional printing physical kidney model technique (3Dp k.m) (n = 5), Intraopera- tive ultrasound guidance combined with 22 Gauge nee- dles for tumor delineation (needle-IOUS) (n = 3), Intra- tumoral CT-guided percutaneous Hook-Wire insertion for tumor signage (Hook-Wire) (n = 2), selective in- tra-arterial blue dye embolization (blue dye TAE) (n = Table 3.Endophytic tumor localization techniques during ablation procedures. Endophytic renal mass localization techniques-Paparidis et al. Review 164 Vol 19 No 3 May-June 2022 100 7), Augmented Reality (A.R.) (n = 54), Radio-Guided Occult Lesion Localization (ROLL) (n = 1). Results on IOUS were extracted from retrospective comparative studies(12-15), retrospective single arm stud- ies(16-20) and a prospective case-series study(21). Identi- fication success rate was 100%, mean tumor size was 16-37 mm, positive margin rate was 1.96 % -12.5 % , recurrence rate was 0 % in a mean 3-39.2 months fol- low-up and complication rate was 15.2 % -60 % . Var- ious observational studies(22-25) and reviews(26-29) high- lighted the importance of IOUS for the identification of intrarenal masses, precise delineation of size and depth, and presence of satellite renal masses or collecting sys- tem infiltration. DSCT was used in a retrospective study(30) for retrop- eritoneal LPN. Overall accuracy of feeding artery ori- entation was 93.6 %, tumor identification success was 100 %, no positive margins or recurrences occurred in a mean 18-month follow-up. 3Dp k.m(31) used markers orientated by anatomical land- marks, labeled on a kidney-model surface. Navigation intraoperatively was performed using kidney-model’s distance measurements. Mean tumor size was 27.8 mm, treated with trans or retro peritoneal LPN. Identification rate was 100 % . No complications or positive margins were reported. Needle IOUS assisted de novo identification of an un- identified intraparenchymal lesion with IOUS-only guidance. Neither positive surgical margins nor recur- rences were reported in 27-month follow-up. Hook-Wire was applied in 2 intraparenchymal tumors (32,33). Identification success was 100 % , no complica- tions or positive surgical margins were reported, and a 16-month follow-up in one case showed no recurrence. Blue dye TAE, followed by super selective tumor em- bolization with glue or micro coils was presented in a prospective study(34). No complications related to dye injection occurred nor positive surgical margins were present. All tumors were successfully embolized. Data regarding identification success were inconclusive. Early Follow-up imaging showed no recurrences. A.R. summarizes a spectrum of techniques, all based on superimposing pre/intraoperative images, onto en- doscopic scene. Intraoperative imaging or preoperative 3D-reconstructions can be registered within surgical view in three ways: 1) surface-based registration using a stylus or a range scanner tool, 2) manual registration using fiducials and markers, 3) 3D to 3D registration using stereoscopic robotic camera ability(35,36). 10 mass- es were identified with Real-time imaging like cone- beam CT (CBCT) combined with fiducial aid technique (37-39). CBCT helps to resolve the tissue deformation issue, due to natural organ movement, that can cause imprecise image fusion(40). 44 tumors were identified with 3D reconstructed preoperative image fused with 2D or 3D laparoscopic view(41-44). Identification rate was 100% and no positive surgical margins were reported Table 4. Results of meta-regression subgroup analysis for the five individual meta-analysis scopes. The model slope is presented in separate columns for the binary variables depending on their value (YES or NO). Statistically significant p values are presented in bold. Tables’s abbreviationsCE-CT=Contrast enhanced CT, NA= Not Assessed, data absent or inconclusive, n. =number, OPN= Open partial nephrectomy, perc=percutaneous, RFA= Radiofrequency ablation RF-RCPN= Radiofrequency ablation –assisted robotic clampless par- tial nephrectomy, retro= retroperitoneal, TIT= Totally intraparenchymal tumors, trans= trans peritoneal, VSP= Virtual surgical planning, VS= Versus, WIT= Warm ischemia time Endophytic renal mass localization techniques-Paparidis et al. Vol 19 No 3 May-June 2022 165 for both techniques. CBCT showed no complications while 3D reconstruction technique had 0-13.3 % com- plication rate. ROLL successfully used gamma camera for one intra- parenchymal tumor in an experimental setting(45), this was the only case reported in English literature(46). Completely endophytic subgroup analysis for LPN Data were extracted from 12 studies (6 retrospective comparative, 3 retrospective single arm, 3 case-reports) (12,42,13,31,41,18,14,15,20,32,33,45). From 239 tumors, 17 were identified with A.R., 5 with 3Dp k.m, 211 with IOUS, 3 with needle IOUS, 2 with Hook-wire and 1 with ROLL. Intraparenchymal growth showed no correlation to identification success among methods. All techniques had 100 % successful identification rates both for in- tervention and control groups. Odds Ratio was 95 % CI ; 0.255-1.971, OR 0.709, P = .510, with low heteroge- neity (Q = 1.355, 95 % CI ; 0.00-41.36, I2 0.00 % , P = .8553) for positive margins with IOUS guidance or A.R. navigation in LPN(Figure 3). Positive margins with IOUS guidance had 95%CI; 0.0519-6.701, OR 0.590 in LPN compared to RAPN. Consecutive studies showed 95 % CI; 0.0201-5.756, OR 0.340 ; 95 % CI ; 0.179-3.589, OR 0.790 and 95 % CI ; 0.0251-7.191, OR 0.425 for an exophytic compared to an intrarenal mass to have positive margins. Posi- tive margins for 3D reconstruction A.R. techniques, such as 3D-medical image reconstructing and guiding system (MIRGS), over control group had 95 % CI ; 0.116-115.805, OR 3.667 for totally intraparenchymal tumors. Local recurrence rate using IOUS, was 0 % in 5 comparative studies(12-14,20,41) with a mean 12-39.2 months follow-up, but data were insufficient for statis- tical analysis. Robotic Assisted Laparoscopic Partial Nephrectomy Data from 27 studies regarding 598 endophytic mass- es that underwent Robotic Assisted Laparoscopic Par- tial Nephrectomy (RAPN), were collected(Table 2). IOUS was the cornerstone of identification methods during RAPN(47,48). 365 masses were identified with IOUS. Other sonography-based methods were, IOUS combined with frozen sample biopsies from tumor bed (frozen-sample IOUS) (n = 161), Intraoperative laparo- scopic Ultrasound enhanced with color Doppler modal- ity (LDU) (n = 7) and Intraoperative Contrast Enhanced Ultrasound (CEUS) (n = 5). Apart from ultrasonogra- phy, embolization techniques such as iodized oil Trans arterial embolization in tumor feeding-artery (iodized oil TAE), TAE with Near infrared Fluoroscopy imaging using indocyanine Green (TAE NIRF-ICG) (n = 10), Figure 1. Search strategy presented with PRISMA flow-chart Endophytic renal mass localization techniques-Paparidis et al. Review 166 Vol 19 No 3 May-June 2022 167 A.R. (n = 42) and percutaneous placement of emboliza- tion coils inside the mass for tumor signage (emboliza- tion coils) (n = 1) were used. Endophytic tumor size in IOUS techniques(12,49-62) was 23-32,5mm. Identification success rate was 100%, complication rate varied 0-21.8% and positive margin rate ranged 0 -6.1 % . Recurrence rate varied among studies 0-1.6 % , in 8-48 months follow-up. Frozen sample IOUS studies(63-65) included masses sized 26-28mm. Identification success rate was 97.8 % - 100 % . Positive margin rate was 0-9.6 % . Complication rate was 21.9 % -32.7 % , and distal or local recur- rence rate was 2.2 % -3.9 % in a mean 48-59 months follow-up. LDU(61,66), was used, not only to locate tumor but to identify the resection margin, and tumor distance from collecting system(67) and to track adjacent vessels(60). Identification success was 100 % , without complica- tions. CEUS was an alternative sonographic method to drop-in robotic ultrasound for in situ renal blood flow mapping after contrast agent injection(68). It allowed occlusion angiography after mapping vasculature and scanning the tumor along with its position and intrapa- renchymal depth assessment. Tumor identification rate was 100 %(69). Efficacy of embolization techniques, such as iodized oil TAE and TAE NIRF-ICG, in localizing endophytic tumors was specified in one study(70-72). Mean tumor size was 30mm, identification success rate was 100 % , with no positive margins or recurrences at 12-month follow-up and no need for ultrasonography assistance. A.R. techniques with real-time 3D to 3D registration were: Hyperaccuracy 3-dimensional reconstruction (HA3D)(73,74) and Inverse Realism technique using NVIDIA Quadro DVP hardware(75). Comparing HA3D to 2D IOUS techniques, both showed 100 % identifica- tion success rates, but with improved maneuverability, enhanced surgical movement and visualization of oth- er hidden structures such as vessels or calyces for the HA3D arm. HA3D aided in 90% successful selective clamping versus 39 % successful pedicle management in non-HA3D group without positive margins in both arms. 3D to 2D image fusion utilizing vascular pulsa- tion cues for guiding preoperative to intraoperative reg- istration(76) was used for occluded structures tracking such as endophytic tumors or vessels occluded by fat during RAPN. IOUS 2D images and 3D reconstructed images integrated in surgical console, but not overim- posed to endoscopic view were also described without further numerical data provided. VSP, used recon- structions created preoperatively, and IOUS real-time imaging both projected simultaneously within surgical view (77). Tumor identification rate was 100 % , showing no positive margins or complications. This technique could be helpful in cases with intraparenchymal or hilar tumors accompanying complicated renal vessels(78). IOUS-tracked embolization coils, were used in an en- Figure 2. Risk of Bias Traffic-light plot created with ROBVIS tool. Assessment of bias for each non-randomized study throughout seven domains of bias (D1-D7). Domains are stratified with a judgment from low to serious. Endophytic renal mass localization techniques-Paparidis et al. dophytic isoechoic tumor during retroperitoneal RAPN (79). Identification success 100 % , and negative mar- ginal status or complications, might suggest this as a method of choice when dealing with isoechoic intrapa- renchymal lesions. Completely endophytic subgroup analysis for RAPN Data were extracted from 13 studies (7 retrospective comparative, 3 retrospective single arm, 3 prospective studies)(51,63,65,12,50,62,64,57,70,80,77,73,81). In 366 tumors, identi- fication success rates were 100 % for A.R. (n = 1), 100 % for IOUS (n = 158), 99.08 % for frozen sample IOUS (n = 109), 100 % for TAE NIRF-ICG (n = 10), and 0 % for intravenous (I.V.) NIRF-ICG (n = 7), (t-test, P = .9730). Intraparenchymal growth showed no signif- icant correlation to warm ischemia time(62). Analysis for positive margins in IOUS guided RAPN and A.R. navigation for completely endophytic tumors with or without frozen biopsies had total 95 % CI ; 0.379-3.109, OR 1.086, P = .878, with moderate heterogeneity (I2 = 46.39 % , P = .0826) (Figure 4). Positive margins using IOUS RAPN for intrarenal ver- sus exophytic tumors had 95%CI; 0.00336-1.221, OR 0.0641. Positive margins with frozen sample IOUS had 95%CI; 1.209-15.835, OR 4.375, for completely endo- phytic versus mesophytic or exophytic masses in LPN compared to RAPN. Positive margins for A.R. tech- niques such as HA3D compared to IOUS control group, had 95 % CI ; 0.186-247.067, OR 6.778. Total 95 % CI ; 0.0917-2.251, OR 0.454, P = .0334 with low heterogeneity (I2 = 0.00 % , P = .07645) was es- timated for recurrence in frozen sample IOUS RAPN for intrarenal tumors, as other identification techniques showed insufficient data for further analysis. Frozen sample IOUS had 95 % CI ; 0.0299-3.932, OR 0.343 for recurrence after RAPN compared to OPN and 95 % CI ; 0.0673-4.686, OR 0.562 for recurrence after RAPN when comparing intrarenal to mesophytic or exophytic tumors(Figure 5). Radiofrequency Ablation Data from 14 studies, with 225 endophytic renal masses that underwent Radiofrequency Ablation (RFA), were collected(Table 3). 127 neoplasms underwent percuta- neous RFA (PRFA), 55 underwent Laparoscopic RFA (LRFA), and 26 underwent RFA assisted RAPN. Hy- brid laparoscopic and robotic RFA assisted partial ne- phrectomy was described in literature without specific data recorded. Localization methods described during PRFA were: CT guidance alone or combined with CT guidance un- der general anesthesia (G.A-CT) and Fiber optic ther- mal monitoring (FOTM)(82-85), Fluoroscopy CT (F-CT) guidance with embolization coil markers (n = 8)(86), Ul- trasound (US)-only guidance (n = 9)(87) and iodized oil TAE(88). RFA with GA-CT and FOTM (n = 43) was the only method with 93.48 % technical success rate and 8.7 % recurrence rate compared to 100 % success rate and 0 % recurrence rate of other modalities. Tumor size data were only provided for US RFA, showing mean Figure 3. Odds Ratio Forest-plot for positive surgical margins after Laparoscopic partial nephrectomy for completely endophytic tumors. OR calculated overall and separately for positive margins using different localization techniques. I2 shows low heterogeneity of data. Funnel-plot, Egger’s test and Begg’s test were used for publication bias evaluation. Endophytic renal mass localization techniques-Paparidis et al. Review 168 Vol 19 No 3 May-June 2022 169 size 26.9mm. Complication rate 0% was announced for US and F-CT embolization coil methods. TAE was used for difficult-to-detect endophytic tumors, but con- cise numerical data regarding success rate and surgical outcomes were not provided. LRFA was facilitated either by IOUS-alone(85,89-91) or combined with visual guidance and FOTM(92-93) or CEUS (94) for tumor localization. IOUS-alone techni- cal success rate was 80 % -100 % and recurrence rate was 0 % overall. RFA assisted robotic clamp-less par- tial nephrectomy for 26 endophytic tumors had 100 % technical success rate and 0 % recurrence rate using IOUS alone(95). Results were inconclusive for IOUS- FOTM and CEUS. Cryoablation Data from 10 studies including 187 endophytic tumors treated with Cryoablation were collected (Table 3). 159 masses underwent with percutaneous Cryoablation (PCA) and 28 were treated with Cryoablation during laparoscopy (LCA). 88 were completely endophytic. Identification techniques used in PCA were: F-CT only or combined with US (n = 112)(96-99) and TAE (n = 29) combined with CT guidance such as iodized oil and ab- solute ethanol TAE (100) , iodized oil and gelatin parti- cles TAE(101), or polyvinyl alcohol particles in iodinated contrast agent TAE(102). Combined US and intermittent CT imaging during ab- lation for 76 masses showed 100% technical success rate, complication rates were 10 % -32 % . Recurrence rate was 13 % in one retrospective single arm study with long term follow-up. F-CT only method, had 75 % technical success rate and 12.5 % recurrence rate in a retrospective study including 8 endophytic tumors with mean size 27mm. Iodized oil and absolute ethanol TAE showed inferior results compared to other TAE techniques, with techni- cal success rate 94.12 % , and 29.4 % recurrence rate, versus 100 % technical success rate and 0 % recurrence rate respectively. Outcomes were comparable despite small study samples. IOUS was the only identification method described dur- ing LCA. A retrospective single arm study(103) showed 33.4 % technical success rate, 0 % complication and recurrence rate in mid-term follow-up during LCA for 3 completely endophytic non-visible tumors. Limited data, indicated ultrasonography signage inexpediency for treating intrarenal tumors. Retrospective compar- ative studies analysis on CT guided PCA and IOUS guided LCA(104-105) showed 100 % technical success and 20 % recurrence rates for both arms, while limitations such as small sample size and restrictions in definitions of technical success, persistent enhancement and recur- rence, obscured safe statistical conclusions. Microwave Ablation Data regarding Microwave Ablation (MWA) were col- lected (Table 3). Yu et al. 2012(106) reviewed interme- diate-term outcomes after MWA with US and FOTM sensors for 44 endophytic masses, mean size 18mm. 26 had parenchymal and 18 had endophytic growth patterns with 17.9-19.8 months median-follow up. Pa- renchymal nodules showed 100 % technique efficacy and no recurrences. Endophytic masses showed 94.4 % technique efficacy, and 15 % showed recurrence. Retrospective comparative studies(107-109) on CT percu- taneous thermal ablation for 165 endophytic masses Figure 4. Odds Ratio Forest-plot for positive surgical margins after Robotic partial nephrectomy for completely endophytic tumors. OR calculated overall and separately for positive margins using different localization techniques. I2 shows moderate heterogeneity of data. Funnel-plot, Egger’s test and Begg’s test were used for publication bias evaluation. Endophytic renal mass localization techniques-Paparidis et al. showed overall 100 % technical success rate for all in- tervention types. In MWA group, no urothelial injury or Clavien-Dindo II-IV complications occurred. Irreversible Electroporation One study from Diehl et al. (110) reported the use of Ir- reversible Electroporation (IRE) in endophytic tumors, but data were inconclusive (Table 3). Completely endophytic subgroup analysis for thermal ablation Data were extracted from 11 studies (9 retrospective single arm, 1 retrospective comparative, 1 prospective) (83,84,87,86,93,96,100,101,99,103,106) including 153 completely en- dophytic tumors. Localization methods during PRFA were: CT guidance alone or combined with US (n = 18), US-alone (n = 9), and F-CT with embolization coil markers (n = 8). Deep endophytic tumors during LRFA were identified with FOTM IOUS. Identifica- tion techniques during PCA were: CT guidance alone or combined with US (n = 77) and iodized oil TAE (n = 12), while IOUS was the only localization modality used during LCA (n = 3). US with FOTM was used for 26 tumors during percutaneous MWA. Total OR for technical success after thermal ablation procedures was 95 % CI ; 0.137-5.167, OR 0.842, P = .853. We applied separate pooled OR reporting for invasive (Figure 6.) and non-invasive (Figure 7) localization techniques regarding technical success in ablation pro- cedures, in order to avoid heterogeneous data analysis. Invasive techniques: Iodized TAE in PCA, 95 % CI ; 0.0118-9.39), OR 0.333 and laparoscopic IOUS guid- ance in PCA, 95 % CI ; 0.000293-0.291, OR 0.00923 both showed less likelihood for technical success, total random effect 95 % CI ; 0.0157-2.060, OR 0.05690, fixed effect 95 % CI ; 0.00799-0.907, OR 0.0851, P = .041, with significant heterogeneity of data 95 % CI ; 0.00-89.13, I2 55.26 % . Non-invasive techniques: All non-invasive imaging techniques showed increased likelihood for success with total random effects 95 % CI ; 0.598-13.152, OR 2.804 and low heterogeneity of data 95 % CI ; 0.00- 25.11, I2 0.00 % . US guidance in percutaneous RFA, 95 % CI ; 0.262- 152.872, OR 6.333 and combined CT and US guidance, especially when performed under FOTM, in MWA : 95 % CI ; 0.137 -91.090, OR 3.533, in PCA: 95 % CI ; 0.118- 47.114, OR 2.361 and PRFA: 95 % CI ; 0.0696- 26.205, OR 1.35, showed increased likelihood for success. Comparison between thermal ablation methods showed that endophytic growth pattern attributed to hematoma formation with Mean Relative Risk (RR) 95 % CI ; 0.90-1.51, RR 1.15 and to residual disease with Mean 95 % CI ; 1.10-1.87, RR 1.30(107-109). Overall estimat- ed cumulative incidence of recurrence was 95 % CI ; 1-19, 5 % , at 3 years and 95 % CI ; 4-27, 10 % at 5 years for PCA using combined CT and US guidance for completely endophytic tumors(96). Wingo et. al.2008 (93), contrariwise, failed to predict increased risk for re- currence due to endophytic location (chi-square = .81 < 5.99) for CT-FOTM PRFA or IOUS LRFA. High Intensity Focused Ultrasound Ritchie et al.(111) evaluated 5 entirely endophytic tumors, mean size 20,4mm treated with High Intensity Focused Ultrasound (HIFU). US was used for tumor localiza- tion, surgical planning and real time evaluation. All were successfully identified. Technical success rate was Figure 5. Odds Ratio Forest-plot depicting likelihood for tumour recurrence using intraoperative ultrasound guidance with frozen sam- ples from tumor bed in Robotic Partial Nephrectomy for completely endophytic tumours. I2 shows low heterogeneity of data. Funnel-plot, Egger’s test and Begg’s test were used for publication bias evaluation. Endophytic renal mass localization techniques-Paparidis et al. Review 170 Vol 19 No 3 May-June 2022 100 20 %. No major complications occurred. Recurrence rate was 25 % in a mean 36-month follow-up. DISCUSSION Evidence on excision techniques showed that IOUS was widely applied identification method, with high identification rates, and recurrence rates up to 1.6 % in follow up period up to 60 months. Positive margin rates were 1.96-12.5 % in LPN and 0-6.1 % in RAPN, while complication rates varied from 0 % in LPN to 0-21.8 % in RAPN. Kaczmarek et al.2013(54) showed similar effi- cacy between Laparoscopic and Robotic IOUS probes, Robotic group though, excelled in autonomy, maneu- verability, cost effectiveness and practicality when depicting challenging tumor angles. Frozen sample IOUS during RAPN, showed increased complications, without improving positive margin or recurrence rates; making it questionable whether it should be performed. LDU or CEUS showed insufficient data regarding tu- mor tracking but aided in identifying hidden vascula- ture, defining safe excisional margins or contact with the collecting system. DSCT combined high identifi- cation success rate with efficient tumor feeding artery orientation. A.R. was useful in identification, especially within a ro- botic setting. Overlapped 3D onto real- time endoscopic image, enhanced anatomical structures(112). Despite high identification success rates, data were inconclusive to support superiority over conventional techniques. Find- ings are compatible with international literature (113,114). Only HA3D showed superiority compared to IOUS during RAPN regarding surgical autonomy, and selec- tive artery clamping. Isoechoic intraparenchymal mass tracking was achieved using embolization coils during RAPN. Further stud- ies are needed to confirm whether embolization coil or hook wire techniques could be the gold standard for such tumors. Unlike TAE NIRF-ICG, I.V. NIRF-ICG was con- traindicated for endophytic tumors(115,40). Studies(80,81) showed no identification success. The only utility for intraparenchymal lesions, was tumor delineation once surrounding normal parenchyma was first incised(116-119). Regarding excision methods for completely endophyt- ic tumors, identification success rates were high, re- gardless of identification technique, both for LPN and RAPN. Positive margins showed 40% less likelihood in IOUS guided LPN compared to RAPN and significant- ly decreased odds for IOUS guided LPN or RAPN for totally intraparenchymal tumors compared to masses with exophytic component. Odds for positive margins were increased in A.R. techniques compared to IOUS during laparoscopic or robotic procedures for intrare- nal masses. Chances for recurrence were in favor of IOUS LPN compared to RAPN, LCA or laparoscopic radical nephrectomy and increased odds for recurrence were found during laparoscopy for intraparenchymal versus exophytic masses. Frozen sample IOUS showed increased likelihood for positive margins in intrarenal compared to exophytic tumors and 45% less likelihood for recurrence of parenchymal masses compared to mesophytic or other exophytic lesions. Evidence on ablation procedures suggest that, CT was preferred to US during all thermal ablation procedures Figure 6. Invasive techniques in Ablation procedures. Forest-plot depicting odds ratios for technical success during thermal ablation procedures for completely endophytic tumors. Cochran’s Q test and I2 statistic are calculated for heterogeneity. Funnel-plot, Egger’s test and Begg’s test show publication bias. Endophytic renal mass localization techniques-Paparidis et al. Vol 19 No 3 May-June 2022 171 due to improved anatomic resolution, ancillary maneu- ver permeability and periprocedural complication eval- uation(109). CT guided PRFA had technical success rate 93.48 % -100 % and recurrence rate 0-8.7 % in 2-year follow-up. G.A aided in better targeting and minimiz- ing complications risk. Wingo et al.2008(93) showed that FOTM RFA, improved success rate. Gupta et al.2009 (82) showed that OR, an endophytic lesion compared to non-endophytic to be incompletely treated, was 95 % CI ; 0.65-24.8, OR 4.0. RR of developing any recurrence for endophytic lesions compared to non-endophytic was 95 % CI ; 0.6-11.7, RR 2.6, P = .20. Endophytic tumors were more resistant to ablation because of the “heat sink” effect caused by blood vessels surrounding the tumor. Endophytic central masses had the highest risk for re- currence (Hazard Ratio HR, 6.3; P = .016). Matsumoto et al.2005.(120) stated that, endophytic lesions, hardly lo- calized during open partial nephrectomy and technical- ly challenging for LPN, were easily targeted and ablat- ed with CT-guided RFA. Pietryga et al.2012(86) showed that use of marker coils in poorly visualized tumors, such as intraparenchymal and isoechoic lesions, facil- itated CT PRFA, by 58 % reduction in CT fluoroscopy time, showing equivalent technical outcomes with non- coil group. TAE as add-on to PRFA for difficult-to-de- tect endophytic tumors, reviewed by Sommer et al.2017 (88), showed that residual post ablation positive margins were more common for endophytic tumors. IOUS LRFA, showed technical success 80-100%. Yang et al.2014(94) showed that CEUS, improved tumor out- line visibility prior to ablation, allowed enhancement status evaluation after ablation, required no warm is- chemia and allowed increased parenchymal preserva- tion. CT PCA showed technical success 75 % , reaching 100 % when combined with US. Recurrence rate was approximately 13 % in short-term follow-up, and com- plication rate was 10-32 %. TAE PCA, technical suc- cess rate was comparable (94.12 % to 100 % ) but with higher percentage for recurrences (29.4 % ). Harmon et al.2018(102) showed that pre ablation adjuvant em- bolization allowed better tumor demarcation, reduced cryoneedles needed and minimized procedural cost and complications. The “poor visualization phenomenon" concerning intra- parenchymal or partly endophytic renal masses in un- enhanced CT was a factor compromising PCA success. Therefore, Kajiwara et al.2020(101) proposed a five-tier visualization score based on Hounsfield units. Mean visualization score, solely for endophytic and paren- chymal tumors, after TAE PCA was 4, representing a tumor margin visibility 75-90 % . Data on IOUS LCA, showed technical success 33.4 % , probably due to ul- trasonography signage inexpediency(103). Multivariate analysis revealed that only endophytic status is a predic- tor of failure. Derweesh et al.2008(105) compared LCA to PCA for endophytic tumors and showed that they had significant association with tumor persistence. Nisbet et al. 2009(121) proposed a decision tree on whether to perform IOUS LCA or LPN for small renal masses. En- dophytic tumors were predicted to have better results when treated with LCA. Results on completely endophytic subgroup for ab- Figure 7. Non-invasive techniques in Ablation procedures. Forest-plot depicting odds ratios for technical success during thermal ablation procedures for completely endophytic tumors. Cochran’s Q test and I2 statistic are calculated for heterogeneity. Funnel-plot, Egger’s test and Begg’s test show publication bias. Endophytic renal mass localization techniques-Paparidis et al. Review 172 Vol 19 No 3 May-June 2022 173 lation procedures, showed that non-invasive imaging techniques had increased likelihood of success. CT PRFA had slightly increased odds for technical success between totally intrarenal and endophytic tumors (95 % CI ; 0.0696- 26.205, OR 1.351). Technical success during US PRFA was also in favor of intraparenchymal masses. Combined CT and US PCA, favored success over completely endophytic lesions compared to other endophytic tumors. US MWA with FOTM, increased likelihood of success when applied to intrarenal masses compared to endophytic. Contrariwise, invasive tech- niques showed less likelihood for success. TAE PCA showed 33 % less likelihood of success for intrarenal masses compared to masses with exophytic compo- nents. Chances of success for completely endophytic tumors were significantly lower compared to masses with exophytic component during IOUS LCA (95 % CI ; 0.000293-0.291, OR 0.00923). Data on recurrence after ablation were contradictive and therefore incon- clusive. Our limitations were 1) Study selection bias from Eng- lish language restriction: Additional database search re- sulted in 6 studies eligible for further evaluation accord- ing to abstract, written in Russian, Spanish, French and Hebrew. As authors were incapable of translating, we avoided including non-English literature due to bias of misinterpretation. 2) Further databases could have been searched, such as Scopus, which was not searched due to limited access. 3) Serious uncontrolled confounding bias due to unmeasured confounders. 4) Sparse data bias: unrealistic huge pooled OR estimates and confi- dence limits, observed in subgroup analysis, suggest that sparse data is an important source of bias. 5) Bias deriving from study design: No randomized controlled studies and limited number of prospective studies were included (6 comparative, 5 single arm studies and 1 multi-institutional), the majority were retrospective, making data extraction strenuous due to ambiguous reporting quality. 6) Missing data within studies: Data were partially missing or inconclusive in 58 studies, while 19 had complete data for extraction. 7) Hetero- geneity in terminology: Variance in definitions of terms was a major drawback. The term endophytic described a variety of masses, ranging from totally intraparenchy- mal to masses protruding up to 50% from capsule. Oth- er definitions such as technical success rate, tumor re- sponse rate and recurrence, were diverse among studies resulting in bias during the interpretation of outcomes, although Goldberg et al.2003(122) proposed a protocol for Standardization of Terms and Reporting Criteria for image guided ablation. 8) Small study samples. Low level of evidence, inconsistent reporting of data, bias in study design or subgroup analysis, small samples and heterogeneity of definitions led us to perform a narra- tive systematic review instead of meta-analysis. CONCLUSIONS IOUS in LPN and RAPN was an adequately evaluat- ed method for tumor localization with high identifica- tion rates and acceptable oncologic outcomes. A.R., although showing increased surgical maneuverability and autonomy, showed no superiority regarding identi- fication success, positive margins and recurrences. I.V NIRF-ICG, was not an appropriate option for success- ful endophytic tumor tracking. CT alone or combined with FOTM and US, showed increased technical success for endophytic and intra- parenchymal tumors during thermal ablation. US alone during LCA, had discouraging results regarding techni- cal success. Limited evidence on isoechoic endophytic masses, suggest that more invasive localization meth- ods such as hook-wire or embolization coil techniques, might rise as method of choice for such tumors. CONFLICT OF INTEREST The authors report no conflict of interest. REFERENCES 1. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur. Urol. 2019; 75:799–810. 2. Husain FZ, Badani KK, Sfakianos JP, Mehrazin R. 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