This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 1111-040-385). A total of 216 consecutive patients who underwent HoLEP for symptomatic BPH between July 2008 and October 2011 were included. Patients with a history of genitourinary malignancy, genitourinary surgery or radiation, interstitial cystitis or bladder pain syndrome, urinary tract infection, or congenital genitourinary anomaly were excluded from the study. Additionally, the first 30 patients were also excluded because of the learning curve period associated with the procedure. The patients were divided into two groups, the HNRM group (n =29) and the non-HNRM group (n=187), based on the need for intraoperative interventions to remove HNRM.

All surgical procedures were performed by one surgeon (S.J.O.) according to the technique described previously [10]. In brief, anatomical enucleation was adopted using the three-lobe technique. A 26-Fr resectoscope (Karl Storz, Tuttlingen, Germany) was used for enucleation of the prostate. A 550-μm end-firing laser fiber (SlimLine, Lumenis Ltd., Yokneam, Israel) was engaged with an 80-W holmium neodymium:yttrium-aluminum-garnet laser (VersaPulse Power-Suite, Lumenis Ltd.). The energy power was usually set at 2 J and 40 Hz. Continuous irrigation was applied with normal saline during enucleation and morcellation. The mechanical morcellator used was a VersaCut morcellator (Lumenis Ltd.) through a 0-degree rectangular nephroscope (Karl Storz). If the lump was small, it was washed out through the resectoscope sheath naturally. After complete retrieval of the enucleated prostatic tissue from the bladder, usually a 22-Fr 3-way urethral catheter was inserted for continuous bladder irrigation with normal saline. At the end of the operation, the extracted tissues were weighed after removing the irrigation fluid and sent for pathological analysis.

HNRM was defined as an enucleated prostate lump that was resistant to morcellation and required alternative methods for extracting the tissue from the bladder. The time needed for the alternative method was included in the morcellation time. Some nodules were retrieved using special equipment such as an endoscopic grasper. In some cases, the HNRM were lodged in the morcellator blades and caused morcellator failure. In those cases, electronic transurethral resection was adopted for further fragmentation of the enucleated HNRM. Commonly, the morcellator blades were replaced after eight surgeries.

All patients were evaluated preoperatively by physical examination with digital rectal examination, scoring of subjective symptoms with the International Prostate Symptom Score (IPSS), quality of life (QoL) assessment, laboratory analysis with urinalysis, urine culture (in the presence of pyuria), total serum prostate-specific antigen (PSA), and transrectal prostate ultrasound. Multichannel video urodynamic study (MMS UD 2000, Medical Measurement System, Enschede, The Netherlands) was performed to help identify obstruction and overactivity of the bladder components of the LUTS if necessary. To facilitate the statistical analysis, age ( <65 years vs. ≥65 years), body mass index (<23 vs. kg/m² ≥23 kg/m²), subtotal voiding symptom score (<5 vs. ≥5), subtotal storage symptom score (<4 vs. ≥4), total prostate volume (TPV; <65 mL vs. ≥65 mL), transition zone volume (<35 mL vs. ≥35 mL), PSA (<10 ng/mL vs. ≥10 ng/mL), and functional urethral length (<70 mm vs. ≥70 mm) were dichotomized. The bladder outlet obstruction index, which is equal to the detrusor pressure at the maximal flow rate (PdetQmax)–2Qmax, was used to evaluate the bladder outlet obstruction [11]. According to the bladder contractility index, bladder contractility can be determined as strong (>150), normal (100–150), and weak (<100) [12]. The IPSS scores were defined as no or mild (0–7) and moderate or severe (≥8), and the QoL scores were defined as mild (0–1) or moderate or severe (≥2) [13]. Operative parameters were obtained from the operation records, and included the retrieved tissue weight, operative time, enucleation time, morcellation time, enucleation ratio (enucleation weight/transitional zone volume), enucleation efficacy (enucleated weight/enucleation time), morcellation efficacy (enucleated weight/morcellation time), enucleation ratio efficacy (enucleation ratio/enucleation time) [14], intraoperative complications, and perioperative outcomes. Complications were assessed according to the Clavien-Dindo classification [15].

The tissue slices from the prostatectomy specimens were fixed in 10% phosphate buffered formalin, embedded in paraffin, and sectioned and stained with hematoxylin and eosin. Masson trichrome staining was carried out for the HNRM group to distinguish the prostate smooth muscle cells (red) from collagen fibers (blue) and other stromal cell types. Sections were imaged using microscopy (Leica Microsystems, Wetzlar, Germany) at magnifications of ×100 and ×200.

The independent t-test or Mann-Whitney U-test was used for comparing the mean differences in continuous variables between the two groups. Pearson chi-square or Fisher exact test was used for binary variables. To identify the independent risk factors for HNRM, we performed univariate and multivariate analyses with logistic regression to estimate the strength of influence of each variable. The odds ratios and 95% confidence intervals were calculated. All P-values were two-sided, and P<0.05 was considered statistically significant. Data were analyzed using IBM SPSS Statistics ver. 21.0 (IBM Co., Armonk, NY, USA).

Twenty-nine patients (13.4%) were found to have HNRM during morcellation. The basic demographics of the study patients are listed in Table 1. The HNRM group had significantly higher proportions of older age (≥65 years), larger total volume (≥65 mL) and transition zone volume (≥35 mL) of the prostate, higher serum PSA levels (≥10 ng/mL), and longer functional urethral length (≥70 mm) than the non-HNRM group (P<0.05). In addition, the former group had significantly longer operation, enucleation, and morcellation times; larger enucleation weight; higher enucleation ratio and enucleation efficacy; and more energy consumption than the latter (P<0.05). There were no significant differences in the other urodynamic variables (P >0.05). Intraoperative complications occurred in 25 cases, including 5 case of bladder mucosal injury (Clavien-Dindo classification grade I) and 6 cases of prostatic capsular injury (grade I). The complication rates were similar between the two groups (P>0.05). All complications were mild and were managed properly. Additionally, there were no significant differences in the length of hospital stay between the two groups (P>0.05) or in the operative efficiency, including the morcellation efficacy and enucleation ratio efficacy (P>0.05).

The risk factors for HNRM are shown in Table 2. In the univariate logistic regression models, age≥65 years, PSA≥10 ng/mL, TPV≥65 mL, transition zone volume≥35 mL, and functional urethral length≥70 mm were significant risk factors. In the multivariate logistic regression model, age≥65 years and TPV≥65 mL were found to be significantly and independently associated with HNRM. Presence of longer functional urethral length≥70 mm was a borderline significant risk factor in multivariate regression analysis.

The shapes of the HNRM were irregular, with diameters ranging from 7 to 13 mm, as shown in Fig. 1. Each HNRM was grayish-white with a tough consistency. Microscopically, hematoxylin and eosin staining showed that most nodules were predominantly fibrous proliferations, with only scattered blood vessels and occasional inflammatory cells noted. No malignant cells were observed, and the glandular cells were found to have uniform and basally located, small nuclei. The stromal tissues around the glandular cells were highly proliferated and exhibited a high density of fibers (Fig. 2A). Little calcification was observed. Masson trichrome staining of the HNRM sections showed that the tissue was predominantly and intensely stained blue, containing very little red staining and a few black-stained nuclei (Fig. 2B).