Stesura Seveso 69Archivio Italiano di Urologia e Andrologia 2019; 91, 2 ORIGINAL PAPER Running suture hemostatic technique versus standard reconstruction of the surgical bed in Zero - Ischemia Time mini-flank Open Partial Nephrectomies. Retrospective, Match-Paired Case-Control Study Petar Kavaric, Aleksandar Magdelinic, Marko Vukovic Faculty of Medicine, University of Montenegro, Podgorica, Montenegro. Objective: To estimate the efficacy of our technique of zero ischemia time partial nephrectomy (ZTPN) with hemostatic running suture and com- pare it to the standard technique, in terms of perioperative complications, operative time (OT) and estimated blood loss (EBL). Materials and methods: We retrospectively analysed 180 con- secutive patients who underwent ZTPN using a supra 11th or supra 12th rib mini flank approach. First group numbered 90 patients treated with running suture hemostatic technique (RSHT), while the control group enrolled 90 patients in whom we performed standard reconstruction technique (SRT). According the propensity score, both groups were similar in terms of tumor size, age and PADUA score. Patients with soli- tary tumour limited to the kidney (T1-T2a) were included. Our technique included a running suture of surgical bed edges and closure of the renal cortex by the positioning of peri-renal fat within the cortical bed and fixation with interrupted sutures. Results: PADUA score and tumor size were comparable between groups (7.12 ± 1.33 vs 7.1 ± 2.11, p = 0.4 and 52.9 ± 14.8 vs 50.0 ± 13.2, p = 0.3). The mean operative time (OT) was significantly longer in first group (165.2 vs 95, p = 0.04), while median estimated blood loss (EBL) was significantly reduced (250 vs 460 ml, p = 0.02). Surgical resection margins were negative in 100% of cases and no patient developed a local or distant recurrence during follow up. There was signifi- cant difference in postoperative GFR value between groups (p < 0.05). Conclusions: Our technique could be safely performed in local, low volume facilities, thus reducing the need for expensive and more challenging minimal invasive surgical techniques.. KEY WORDS: Nephrectomy; Ischemia time; Hemostatic technique. Submitted 12 February 2019; Accepted 13 February 2019 Summary No conflict of interest declared. oped - the supra 11th rib mini flank approach and supra 12th rib approach (2, 3). These techniques provide opti- mum anatomical exposure and better aesthetic outcomes with a low risk of long-term complications (2). Typically, for a lower pole tumor, a supra 12th rib inci- sion is more appropriate, while for mid and upper pole tumors a supra 11th incision ispreferred (3). Clamping of the hilar vessels during partial nephrectomy may cause ischemic damage to the kidney and subsequent chronic renal impairment, which implies the necessity for improving zero-ischemia time techniques, especially for long lasting procedures, where ischemia time can be more than 25-30 minutes (4, 5). This led to the devel- opment of techniques such as zero ischemia time partial nephrectomy (ZTPN) (6). There are however difficulties with this approach, which include increased intraopera- tive blood loss compared with on-clamp procedure, hence requiring new, technically less demanding haemo- static techniques with comparable blood loss. The aim of this study was to present our approach – open ZTPN using a running suture hemostatic technique for surgical bed – in order to reduce intraoperative blood loss and maintain stable renal function (RF), comparing to standard reconstruction technique. PATIENTS AND METHODS From 543 patients who underwent tumour nephrectomy in our clinic between January 1997 and March 2017, we retrospectively analysed 186 consecutive patients who underwent PN using supra 11th or supra 12th rib mini flank approach (2, 3). First group numbered 96 patients with running suture hemostatic technique (RSHT), while the control group enrolled 90 patients in whom we per- formed standard reconstruction technique (SRT). The patients who underwent RSHT were matched to control group according to the following variables: tumor size, age and anatomic classification of renal tumors (PADUA) score. Finally, 90 patients from the first group were matched to 90 patients from the control group. The indication for surgery was solitary renal tumor limited to the kidney (cT1-cT2a). We used pre- operative CT or MRI tumor staging according to the DOI: 10.4081/aiua.2019.2.69 INTRODUCTION Partial nephrectomy (PN) for localized kidney tumor has oncological outcomes similar to that of radical surgery (1). According to current guidelines, patients with low grade renal cell carcinoma (RCC) should undergo nephron-sparing surgery rather than radical nephrecto- my whenever possible (EAU guidelines). Utilizing mini- mally invasive surgical approaches to open nephrecto- my, two mini-flank open techniques have been devel- Archivio Italiano di Urologia e Andrologia 2019; 91, 2 P. Kavaric, A. Magdelinic, M. Vukovic 70 2004 World health organization (WHO) classification of renal epithelial tumors (7). Patients with the following criteria were excluded: those with blood disorders; evi- dence of locally advanced or systemic disease; regional adenopathy or previous kidney surgery. The presence of hereditary renal cancers was no contraindication for sur- gery. The variables we examined when reviewing our database were demographics (age, gender, body mass index), lesion characteristics (location, centrality and size), pathological stage and histological subtype, peri- operative variables operative time (OT), estimated blood loss (EBL), postoperative glomerular filtration rate (pGFR), length of hospital stay and intraoperative and postopera- tive complications (POC) (3). POC were classified accord- ing to the modified Clavian system (8). • The primary end points evaluated included EBL, post- operative creatinine and pGFR, POC and hospital stay. • The secondary end points evaluated included OT, transfusion rate and surgical margin status. Tumour histology was evaluated using modified Heidelberg histopathological classifications of renal tumors (9). Surgical approach and hemostatic technique After positioning a patient in a standard flank position, we then perform a supra 11th or supra 12th skin and sub- cutaneous incision, using the mini-flank technique as described by Diblasio et al. (2). After the transection of abdominal wall muscle layers and division of the trans- verses abdominis fibers, we use a combination of blunt and sharp dissection (finger and Metzenbaum scissors) to divide the transversalis and lumbodorsal fascia, with displacement of the pleura using a sponge stick. We use a self-retaining retractor with an additional bladder blade or Morris retractor to retract the 10th or 11th rib superi- orly. Typically, we do not perform resection of the 12th rib. After accessing the retroperitoneal space using blunt- dissection and reflecting the kidney with surrounding fat tissue medially, we create the plane between the quadrates lumborum and psoas muscle. In the case of upper pole tumours, after medial and lateral mobilisa- tion of the kidney we isolate the ureter from the lower pole and place it in a yellow vessel loop. When operat- ing upper pole tumors, the adrenal gland would be inspected & palpated, and if there is no indication for adrenalectomy we proceed with mobilization of the upper pole of the kidney using LigaSure bipolar current (LigaSuretm, Covidien, Minneapolis, USA). After mobiliza- tion of surrounding fat, the kidney is carefully inspected to determine the depth and proximity of the tumour to the renal vessels and collecting system (2). For centrally located tumors and for endophitic ones, we use intraop- erative ultrasonography in order to accurately identify tumour borders. Upon demarcation of tumor contours with monopolar current (Figure 1A), we use sharp dis- section of tumour tissue together with resection of an approximately 0.5 cm thick rim of tissue from the tumour bed (Figure 1B-C ). We do not perform tumour margins frozen section routinely, even for deep renal tumour specimen. Prominent arterial branches within the tumor bed are ligated with 2/0 Vicryl ligature or clipped using surgical microclips, in order to selectively devascularize the tumour without interruption of normal renal perfusion (6). With incidental break (what do you mean) within the collecting system, the calyces are sutured with 4/0 PDS suture (Figure 1D). After the exci- sion of tumour tissue, we utilize running 4/0 PDS suture of surgical bed edges, with additional hemostatic sutures in case of minor bleeding within the surgical bed (Figure 1E). At the end, we close the renal cortex by placing peri- renal fat within the cortical bed and placing size 0 chromic liver interrupted sutures (Figire 1F). Standard reconstruction technique consists of tumor resection and reconstruction of the surgical bed with sin- gle, interrupted sutures, followed by application of hemo- static agents within resection cavity (Surgicel; Johnson and Johnson, New Brunswick, New Jersey). The renal capsule is reaproximated using 0 - Vicryl sutures pledged with Surgicel to prevent tearing of the renal cortical capsule and further bleeding (10). The surgical incision is closed using 3/0 absorbable sutures in a subcuticular fashion (2). During the early post- operative period (48h), blood pressure is tightly controlled (e.g. mean arterial pressure (MAP) between 60 - 100 mmHg) in order to avoid addi- tional bleeding from renal parenchyma, but also to maintain safe tissue perfusion and oxygena- tion, preserving normal postoperative RF. Figure 1. Surgical technique of ZTPN using running suture technique for surgical bed with fat tissue tamponade: demarcation of tumor with monopolar current (A); sharp dissection of tumor tissue with approximately 0.5 cm thick rim of renal tissue (B); tumor appearance after C); suturing of ruptured calyces and tumor bed (D); hemostatic running suture of wound edges (E); Fat tamponade (F). A. B. C. D. E. F. Statistical analysis For statistical analysis we used SPPS v16.0, SPPS, Chicago, IL, USA. Methods of statistical description and significance included the Student T test and Mann Whitney U test. Descriptive analyses were also generated and some data are reported as median, interquartile range (IQR), or number (%). The difference of the obtained values was considered to be significant when p < 0.05, and highly significant when p < 0.01. RESULTS Following exclusion criteria and score matching, 180 patients were eligible for this study. According the propensity score, both groups were similar in terms of tumor size, age and PADUA score (52.9 ± 14.8 vs 50.0 ± 13.2 mm, p = 0.3; 57 ± 17.26 vs 55 ± 12.19 years, p = 0.5 and 7.12 ± 1.33 vs 7.1 ± 2.11, p = 0.4, respectively) (Table 1). Median follow up time was 52.75 months in first group and 59.25 within control group (p = 0.3). Additionally, hospital stay and surgical margin status did not differ between the groups. The mean PADUA score in first group was 7.12 ± 1.33 where 14.7% of patients had a score > 8 and 5 patients (5.25%) had a score > 10. The majority of masses (55.5%) were malignant with pre- dominance of the clear cell subtype (67.7%) and exophitic growth (78.9%). The demographic data are given in Table 2. Intraoperatively, three patients (3.3%) from the first group and 7 from the control group (7.77%) required radical nephrectomy due to hilar or deeply penetrating endophytic tumours. Concomitant radical tumor nephrectomy of the other kidney was required in 9 and 7 patients (10% vs 7.77%), with no clinical confirmation of hereditary cancer occurence. No other complications were recorded during surgery. There were 11.2 % and 23.3% POC during follow-up, which were predominantly Clavien grade II (Table 1). Postoperative transfusion rate was 1.1% and 2.2% with a maximum of 1 blood unit required; mean EBL was 250 and 460 ml, while average OT was 165.2 and 95 min. Intraoperative ultrasound was used in 26 patients (28.8%). Surgical resection margins were negative in 100% of all cases (Table 1) and no patient developed a local or distant recurrence during follow up. Table 3 shows pre and postoperative parameters between groups. There was no significant difference in preoperative creati- nine value, GFR or haemoglobin (Hgb) between groups (p = 0.43; p = 0.51 and p = 0.6). Nevertheless, GFR was significantly increased in first group during the early postoperative period (98.86 ± 8.4 vs 77 ± 6.8, p = 0.01). DISCUSSION The primary goal of this study was to determine whether RSHT could substantially decrease the morbidity associat- ed with SRT, regarding EBL, postoperative creatinine and pGFR. Our results showed that EBL and POC were sig- 71Archivio Italiano di Urologia e Andrologia 2019; 91, 2 Open partial nephrectomy with specific hemostatic technique Table 1. Comparison of perioperative outcomes between two groups. Table 2. Demographic data within first group. Mean (SD)/Median (IQR) N Group I Control group 90 patients 90 patients Age (years) 57 (17.26) 55 (12.19) PADUA score 7.12 (1.33) 7.1 (2.11) Tumor size (mm) 52.9 (14.8) 50 (13.2) Operative time 165.2 (47.31) 95 (32.1) * Estimated blood loss (ml) 250 (100-350) 460 (170-530)* Hospital stay (days) 5 (2.5) 7 (1.5) Number (%) Surgical margin 0 (100) 0 (100) Transfusion rate 1 (1.1) 2 (2.2) Complications 11 (12.22) 21 (23.3)* Clavien I 3 7 Clavien II 5 8 Clavien III 2 4 Clavien IV 1 2 * Statistically significant difference between corresponding groups (p < 0.05). Mean (SD)/Median (IQR) N 90 patients Male, n (%) 60 (66.6) Female, n (%) 30 (33.3) Median body mass index, kg/m2 30.75 (7.45) ASA class 3 (1-4) Indication for PN Number (%) Elective 80 (88.2) Solitary kidney 4 (4.4) Bilateral tumors 6 (6.6) Tumor location Number (%) Upper pole 45 (50) Mid pole 9 (10) Lower pole 31 (34.4) Renal hilus 5 (5.6) Tumor histology Number (%) Clear cell 61 (67.7) Papillary 15 (16.7) Oncocytoma 7 (7.8) Chromophobe 3 (3.4) Multilocular cystic 4 (4.4) Table 3. Comparison of several parameters before and after surgical treatment between groups. Mean (SD)/Median (IQR) First group Before treatment 72 h after the treatment Creatinine (mg/dl) 1.16 (0.5) 1.10 (0.46) GFR (ml/min) 91.66 (9.5) 95.86 (8.4)** Control group Before treatment 72 h after the treatment Creatinine (mg/dl) 1.10 (0.3) 1.55 (0.76) GFR (ml/min) 88.25 (8.7) 77 (6.8) * Statistically significant difference comparing preoperativeand postoperative values within first group (p < 0.05). ** Statistically significant difference comparing postoperative values between first and control group (p < 0.05). Archivio Italiano di Urologia e Andrologia 2019; 91, 2 P. Kavaric, A. Magdelinic, M. Vukovic 72 nificantly reduced within first group, while postoperative GFR increased, compared to control group of patients. Nevertheless, OT was significantly prolonged using RSHT. The main goal in PN is to achieve negative tumor mar- gins with a minimal decrease in renal function (RF) and minimal blood loss. Since warm ischemia may be detri- mental to RF and cold ischemia may be difficult to achieve during minimally invasive PN, several tech- niques have been developed in order to avoid clamping of the renal artery (6). Anatomical zero-ischemia PN, introduced by Gill et al. (11) was based on clipping of tumor-specific arterial branches, in order to devascular- ize the tumor without interruption of normal renal per- fusion. This technique led to low EBL (206 ml) with 100% negative surgical margins and a transfusion rate of 21% with POC grade > 3 of 3.5%. We used a similar concept during excision of tumour tissue and after final hemostasis of the surgical bed, mean EBL was 250 ml in first and 460 ml in control group, with a transfusion rate of 1.1% and 2.2% and a 100% negative surgical margin. Although we performed open PN in both groups, mean EBL was significantly lower in group treated with RSHT, which could be associated with meticulous surgical tech- nique and suturing of surgical bed edges with additional fat tissue tamponade. The importance of the improving outcomes of RF through technical modification of resec- tion techniques has already been emphasized (12), with an emphasis on minimization of resection margins and amount of tissue incorporated into renorrhaphy. Desai et al. (13) shares our attitudes on ‘tissue-sparing’ technique using running suture for wound edges through their reporting of point-specific hemostasis of the parenchy- mal defect. However, it is worth noting limitations in comparing these techniques with simple interrupted ren- orrhaphy, as our study describes open technique of PN, while majority of other studies outline a laparoscopic or robotic assisted minimal invasive approach. One of the few papers comparing perioperative and func- tional outcomes for patients treated with open, off-clamp PN, is research made by Smith et al. (14), where authors retrospectively evaluated 192 patients and reported long operative times (226.5 min), significant EBL (500 ml) and a high transfusion rate (42%). Our study however, found a significantly better outcome in all above mentioned peri- operative parameters, which reinforces the importance of the applied surgical technique. Moreover, lack of stan- dardization in off-clamp surgical approach requires more comprehensive studies in order to establish proper tech- nique with adequate hemostasis and preservation of sur- rounding parenchyma (15). This concept is strongly emphasized by Maurice MJ et al. (16), where volume loss of renal parenchyma was recognized to be the most important modifiable determinant of long term renal func- tion. Tissue sparing technique with simple hemostatic principles could assist in achieving this goal. Kreigmar MC et al. (17) identified 40 cases of open partial nephrec- tomies, performed without clamping of the renal artery. The mean operative time was shorter compared to our study (106 vs 162.5 min), but EBL was significantly high- er (521 vs 250 ml); nevertheless, their study included patients with PADUA scores > 8 and more complexity of tumour localization. This indicates that our surgical technique could be improved, since more favourable PADUA scores and tumour positions should lead to shorter operative time. However, complication rate and surgical margin status were comparable between studies. The most common tumour location in our study was upper pole and the majority of patients were elective, with a normal contralateral kidney. This is an important prerequisite for normal postoperative kidney function. Serum creatinine is the easiest and most commonly used tool to assess RF after PN; however, it is not reliable since its value is significantly affected by age, sex, and muscle mass, especially in the presence of a healthy contralater- al kidney (18). Nevertheless, determination of GFR has been shown to reflect RF more accurately than serum creatinine. Our study showed significant improvement in RF in the early postoperative period after using RSHT, comparing GFR values between groups. This confirms effectiveness of our technique, even in patients with soli- tary or bilateral kidney tumours. The impact of different resection and renorrhaphy tech- niques on postoperative RF and perioperative blood loss has not been sufficiently investigated, and standardized reporting of these techniques for future PN series is war- ranted (19). Our technique consisted of nephron sparing PN with running suture of the surgical edges and fat tis- sue tamponade of the surgical bed and showed promis- ing results. Operative time and EBL were at least compa- rable to other studies using open or minimal invasive ZTPN, with preservation of renal function, negative sur- gical margins and no signs of tumour recurrence during a median of three years follow up time, with additional low transfusion rate and relatively short hospital stay. Our research could be a starting point for future, so that more comprehensive studies comparing different surgi- cal approaches could be developed. This research, however, has its limitations. First of all, our study concerned only patients treated with an open approach, a single technique and performed by one sur- geon. Additionally, our study included only one patient with T2 stage RCC with a relatively low PADUA score. Only few patients had a solitary kidney tumour, so post- operative RF could not be accurately estimated without renal scintigraphy. Finally, the majority of tumours had polar localization (84.4%) and exophitic growth (78.9%), therefore, the risk of complications in our study population may have been inherently lower. During PN surgery, the most important considerations in preserving RF are efforts at minimizing blood loss and reducing operative time, while maximizing renal parenchyma volume. Our surgical technique showed satisfactory results regarding all perioperative outcomes, with no additional technical requirements. It could be safely performed in local, low volume facilities, thus reducing the need for expensive and more challenging minimal invasive surgical techniques. Statement of ethics Each subject signed the acceptance of the study protocol, in which the Ethical Principles for Medical Research Involving Human Subjects (The Helsinki Declaration) were clearly stated. 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ZIRK -Technique: Zero ischemia resection in the kidney for high-risk renal masses: Perioperative outcome. Urol Int. 2015; 95:216-222. 18. Volpe A, Blute ML, Ficarra V, et al. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol. 2015; 68:61-74. 19. Minervini A, Carini M, Uzzo RG, et al. Standardized reporting of resection technique during nephron sparing surgery: the surface- intermediate-base margin score. Eur Urol. 2014; 66:803-5. 73Archivio Italiano di Urologia e Andrologia 2019; 91, 2 Open partial nephrectomy with specific hemostatic technique Correspondence Petar Kavaric, MD, PhD petar.kavaric@kccg.me Aleksandar Magdelinic, MD acomgd@yahoo.com Marko Vukovic, MD (Corresponding Author) marko.vukovic09@gmail.com Department of Urology, Clinical centre of Montenegro Ljubljanska bb, 81000 Podgorica, Montenegro