Influence of Pelvicaliceal Anatomy on Stone Clearance After Flexible Ureteroscopy and Holmium Laser Lithotripsy for Large Renal Stones.

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Journal of Endourology Influence of Pelvicaliceal Anatomy on Stone Clearance After Flexible Ureteroscopy and Holmium Laser Lithotripsy for Large Renal Stones (doi: 10.1089/end.2015.0071) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

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Influence of Pelvicaliceal Anatomy on Stone Clearance After Flexible Ureteroscopy

and Holmium Laser Lithotripsy for Large Renal Stones

Takaaki Inoue, MD1, Takashi Murota, MD1, Shinsuke Okada, MD3, Shuzo Hamamoto, MD, PhD4, Kouei Muguruma, MD, PhD1 , Hidefumi Kinoshita, MD, PhD2, Tadashi Matsuda, MD, PhD2* on behalf of the SMART Study Group

1

Department of Urology and Stone Center, Takii Hospital, Kansai Medical University

2

Department of Urology, Hirakata Hospital, Kansai Medical University

3

Department of Urology, Gyotoku General Hospital

4

Department of Urology, Toyota Kousei Hospital

*Complete List of All Authors Takaaki Inoue, MD1, Takashi Murota, MD1, Kouei Muguruma, MD, PhD1

: Department of Urology and Stone Center, Takii Hospital, Kansai Medical University,

Fumizono-tyo 10 chome 15, Moriguchi City, Osaka 570-8507, Japan 1

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Tel: +81-06-6992-1001

E-mail: Takaaki inoue: [email protected]

Takashi Murota: [email protected]

Kouei Muguruma: [email protected] Shinsuke Okada, MD3,

: Department of Urology, Gyotoku General Hospital,

Gyotokuekimae 1-12-6, Ichikawa City, Chiba 272-0133, Japan

Tel: +81-047-395-1151

E-mail: [email protected] Shuzo Hamamoto, MD, PhD4,

: Department of Urology, Toyota Kousei Hospital,

Ihobara Jyosui-tyo 500-1, Toyota City, Aichi 470-0396, Japan

Tel: +81-0565-43-5000

E-mail: [email protected] Hidefumi Kinoshita, MD, PhD2,

: Department of Urology, Hirakata Hospital, Kansai Medical University, Hirakata 2

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Shinmachi 2 chome 3-1, Hirakata City, Osaka 573-1191, Japan

Tel: +81-072-804-0101

E-mail: [email protected]

*Corresponding author: Tadashi Matsuda, MD, PhD

Department of Urology, Hirakata Hospital, Kansai Medical University, Hirakata

Shinmachi 2 chome 3-1, Hirakata City, Osaka 573-1191, Japan

Tel: +81-072-804-0101

Fax: +81-072-804-2068

E-mail: [email protected]

Word count for abstract: 244/300

Key words: pelvicaliceal anatomy, large renal stone, flexible ureteroscopy

Short running title: Pelvicaliceal anatomy and stone clearance 3

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Abstract Purpose: This study was performed to evaluate the impact of pelvicaliceal anatomy on

stone clearance in patients with remnant fragments in the lower pole after flexible

ureteroscopy and Holmium laser lithotripsy (fURSL) for renal stones of >15 mm.

Patients and Methods: This retrospective study included 67 patients with radio-opaque

residual fragments (>2 mm) in the lower pole after fURSL for large renal stones (>15

mm). The preoperative infundibular length

(IL),

infundibular

width

(IW),

infundibulopelvic angle (IPA), and caliceal pelvic height (CPH) were measured using

intravenous urography. Multivariate analysis was performed to determine whether any

of these measurements affected stone clearance.

Results: Of the 67 patients, 55 (82.1%) were stone-free 3 months after fURSL. The

anatomic factors significantly favorable for a stone-free status were a short IL, broad IW,

wide IPA, and low CPH. On multivariate analysis, the IPA had a significant influence on

a stone-free status after fURSL (p = 0.010). An IPA of 20 mm) with high stone clearance rates in some specialist institutions.8,9 Although the outcome of SWL for lower-pole stones is poor, Kumar et al.10 reported that the

clearance rate of fURSL for 10- to 20-mm lower-pole stones was higher than that of SWL (86.1% vs. 73.8%, respectively). Breda et al.11 reported that the stone-free rate of fURSL for multiple intrarenal stones was 92.2%. Similarly, Huang et al.12 reported that

the stone-free rate of bilateral multiple intrarenal stones was 92.0%. Thus, fURSL is a

beneficial procedure for all calyx stones. Following lithotripsy by fURSL for large renal

stones, however, some small disintegrated fragments may remain in the renal pelvis and

calices. Such fragments are particularly common in the lower pole because of the effects

of gravity. In these cases, the surgeon must decide whether these residual fragments

should be extracted by a second procedure or observed without additional procedures.

Nontreatment of these residual fragments may result in new stone events, stone

regrowth, and the need for retreatment. Which patients are expected to have 7

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spontaneous stone passage among those with residual fragments after fURSL is

controversial. This is an important clinical issue in the treatment of large renal stones

with fURSL.

In this study, we retrospectively evaluated the impact of the pelvicaliceal anatomy on

stone clearance in patients with remnant fragments in the lower pole after fURSL for

renal stones of >15 mm.

Patients and Methods In total, 473 fURSL procedures were performed from January 2011 to September 2014

at the Department of Urology and Stone Center, Kansai Medical Takii Hospital, Osaka,

Japan. We retrospectively collected the data of 67 patients with >2-mm radio-opaque

residual lower-pole fragments that could not be sufficiently extracted during treatment

of large renal stones of >15 mm, fURSL was selected according to patient preference.

Plain X-ray examination of the kidney, ureters, and bladder (KUB) and abdominal

ultrasonography were performed on postoperative day 1 to determine whether residual

fragments were present in the lower pole. All patients with congenital anomalies of the 8

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kidney, significant hydronephrosis, chronic kidney disease (stage 3A or higher; glomerular filtration rate of ≤45 ml/min), and a performance status of ≥2 were excluded

from this study. All patients underwent preoperative KUB, intravenous urography (IVU),

and abdominal ultrasonography. The stone size and location were reviewed on KUB. In

patients with multiple renal stones, the stone size was calculated by adding the length of

the longest axis of each stone.

All fURSL procedures were performed using a flexible ureteroscope (Flex-X2; Karl

Storz, Tuttlingen, Germany or URF-P6; Olympus, Tokyo, Japan) and a Holmium laser

lithotripsy system (Odyssey 30; Convergent Laser Technologies, Alameda, CA, USA)

under natural perfusion without a saline flush under general anesthesia. A ureteral

access sheath was placed in all patients (size of 9.5/11.5, 11/13, 12/14, or 13/15 F). Our

holmium laser settings used to disintegrate the target stones were an energy level of 0.8

to 1.2 J and a rate of 5 to 10 Hz. A 1.5- or 1.7-F tipless nitinol basket was routinely used

for stone removal, and as many large fragments as possible were extracted using this

basket. The lower-pole stones were repositioned to the greatest extent possible before

starting fragmentation. If the operative time exceeded 120 min, we discontinued the 9

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procedure to minimize perioperative complications. At the conclusion of the procedure,

an indwelling ureteral stent was placed in all patients.

KUB and ultrasonography were performed 1 day, 1 month, and 3 months

postoperatively to assess stone clearance and the need for additional interventions.

Treatment success was defined as complete stone clearance with no residual fragments

on KUB and abdominal ultrasonography at 3 months postoperatively; i.e., a stone-free

(SF) status. We compared the SF group with the non-SF group to evaluate the impact of

pelvicaliceal anatomy on stone clearance. We evaluated intraoperative and postoperative complications using the Clavien–Dindo classification system.13,14

We measured the infundibular length (IL), infundibular width (IW), and

infundibulopelvic angle (IPA) with preoperative IVU to evaluate the pelvicaliceal anatomy, as previously described by Elbahnasy et al.6 Furthermore, we measured the caliceal pelvic height (CPH) with preoperative IVU as described by Tuckey et al.15 The

IL was measured as the distance from the most distal point of the lower calyx to the

infundibulopelvic junction. The IW was measured at the narrowest point along the

lower infundibular axis. The IPA was measured as the inner angle formed at the 10

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intersection of the ureteropelvic axis defined by Elbahnasy et al.6 and central axis of the

lower pole of the infundibulum. The CPH was measured as the distance between a

horizontal line from the lowermost point of the calyx to the highest point of the lower

lip of the renal pelvis (Fig. 1).

SPSS Statistics for Windows, Version 21 (IBM Corp., Armonk, NY, USA) was used to

analyze the collected data. The statistical significance of differences in pelvicaliceal

anatomic variables between the SF and non-SF groups was calculated by the Mann–Whitney U test and Pearson’s chi-squared test, with statistical significance

defined as p < 0.05. Receiver operating characteristic analysis with the Youden index

was used to determine the most critical cut-off value for the IL, IW, IPA, and CPH. The

calculated cut-off points were as follows: IL, 27 mm (area under the receiver operating

characteristic curve [AUC], 0.787); IW, 8 mm (AUC, 0.698); IPA, 30°(AUC, 0.877);

and CPH, 25 mm (AUC, 0.840) (Fig. 2). These variables in addition to a stone size of

30 mm and stone computed tomography (CT) value of 1000 Hounsfield units (HU) with respect to stone clearance were calculated to compare the SF rate by Pearson’s

chi-squared test in the univariate analysis. Multivariate analysis using a logistic 11

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regression model was also performed to identify the most significant factor affecting an

SF status.

Results

Of all 67 patients, 55 (82.1%) had achieved an SF status at 3 months postoperatively.

The perioperative characteristics of the patients and stones in the SF and non-SF groups

are summarized in Table 1. The Karnofsky performance status score and prerenal

function were not different between the SF and non-SF groups. There was no significant

difference in stone location (p = 0.091). Among all 30 patients with lower-pole stones in

both groups, the success rate of moving the lower-pole stones was 93.3% (n = 28),

including 22 (100%) patients in the SF group and 6 (75%) in the non-SF group (p =

0.064). The mean CT value in the SF and non-SF groups was 977.5 ± 301.7 and 1163.0

± 196.3 HU, respectively (p = 0.033), indicating that the stones in the non-SF group

were significantly harder. The number of prestenting procedures was not significantly

different (p = 0.259); however, the mean stent removal day was significantly later in the

SF than non-SF group (p = 0.041). The stone composition was not significantly 12

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different between the SF and non-SF groups (p = 0.633).

The radiographic measurements, including the IL, IW, IPA, and CPH, are compared

between the SF and non-SF groups in Table 2. There were significant differences in

these parameters between the two groups. The significantly favorable anatomic factors

for an SF status were a short IL, broad IW, wide IPA, and low CPH. The performance of

logistic regression analysis to determine the most influential factor revealed that the IPA

had a significant influence on an SF status after fURSL (p = 0.010, OR = 1.167, 95% CI,

1.038–1.312) (Table 2). Table 3 shows the outcomes of the univariate analysis according

to the cut-off points related to stone clearance; i.e., IL (27 mm), IW (8 mm), IPA (30°),

CPH (25 mm), stone size (30 mm), and stone CT value (1000 HU). An IPA of 2 cm were historically managed with SWL, PCNL, or a combination

of both; in rare cases, they required an open or laparoscopic procedure. Recent technical

advancements in endoscopic procedures and devices as well as improved surgical skills

have led more urologists to attempt management of large renal stones by fURSL. Since Grasso et al.16 first published a report describing 51 cases of fURSL for renal stones of

>2 cm in 1998, other investigators have also described the outcomes of fURSL for large renal stones.17 In 2012, Aboumarzouk et al.9 summarized nine articles on fURSL and

reported that the stone clearance rate associated with fURSL was not inferior to that

associated with PCNL because when performed by very experienced surgeons, fURSL

had a high SF rate of 93.7% (77.0%–97.5%) in patients with renal stones of a mean size 14

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of 2.5 cm. However, it is often difficult to achieve a complete SF status during a single

fURSL procedure by repeating disintegration and extraction for large renal stones.

Consequently, most patients have some residual fragments. In such cases, we must

decide whether to expect spontaneous stone passage or require the additional procedures

such as fURSL, SWL, and PCNL in patients with residual fragments. Most commonly, the ultimate decision-making factor for the optimal retreatment strategy is the surgeon’s

experience level. Although these residual fragments after fURSL often stay in the renal

pelvis and middle pole calices, most move and stay in the lower pole calices because of

the effects of gravity. Residual fragments may increase the risk of new stone events, stone regrowth, and retreatment including SWL or fURSL.18

In the present study, we selected patients with postoperative residual fragments in the

lower-pole calices. However, the SF rate was quite high (82.1%) at 3 months

postoperatively. Few reports have evaluated the factors affecting spontaneous passage

of residual fragments after fURSL; thus, many investigators do not know in which types

of cases to expect spontaneous stone passage. We evaluated the predictive factors for

stone clearance in patients with residual fragments after fURSL in the present study. 15

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Typically, stone-related factors such as stone size, stone composition, stone location,

and pelvicaliceal anatomy have some effects on spontaneous stone clearance after SWL treatment.7 Aboumarzouk et al.9 reported that fURSL had high SF rates of 95.7%

and 84.6% for renal stones of 20 to 30 mm versus those of >30 mm, respectively. They

found that the larger the stone, the lower the SF rate. In the present study, however,

there was no significant difference in the SF status between renal stones of 30 mm (Table 3). Even if a renal stone is >30 mm, fURSL may be beneficial.

Stones composed of brushite, calcium oxalate monohydrate, or cystine are particularly hard.19 According to the literature, stone attenuation on noncontrast CT (NCCT) as

measured in HU reflects stone hardness and thus predicts SWL success. Stones with a medium density of >1000 HU on NCCT are less likely to benefit from SWL treatment.20

However, the stone composition and stone attenuation on NCCT do not significantly predict the achievement of an SF status after fURSL.21,22 In the present study, stone attenuation with a stone density of ≥1000 HU was significantly associated with stone

clearance in univariate analysis; however, it was not significantly associated with stone

clearance in multivariate analysis. 16

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The stone clearance rate after SWL is typically poorer for lower-pole stones than for

stones of other intrarenal locations because of the gravity-dependent position of the

former. Therefore, the 2014 European Association of Urology Guidelines recommend that PCNL and fURSL are the first-line treatments for lower-pole stones of >15 mm.8 Perlmutter et al.23 stated that stone location does not significantly affect the SF rates when performing fURSL for intrarenal calculi of

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