Strengths and limitations

The strength of our study is the long follow-up period (median follow-up: 7 years) with the largest cohort reported in the literature. Moreover, we used long-term treatment with hypertensive medications to define new-onset hypertension. Earlier retrospective registry studies also addressed the association between new-onset hypertension and SWL; however, whether the new-onset hypertension is transient, borderline, or long-term needing medication was unclear. Our study confirmed the association

between SWL and hypertension and showed that the risk of new-onset hypertension consistently increased even up to 14 years with a need for medication. Moreover, our studies proved that SWL will not increase the risk of diabetes. Furthermore, we evaluated the full medical records of patients undergoing SWL, including the number of SWL treatment sessions, and a comparable group–URSL patients–was used because the indications for stone treatment and patient characteristics were similar between these groups. Additionally, we used a time-varying Cox model to estimate the risk in a dose-responsive manner and corroborated our results with those of a nested case-control study. We also chose a group of patients with severe stone disease (treated with PCNL or open surgery) for sensitivity analysis and COPD for a negative outcome. Since this was a national population-based study, there was no selection bias and generalizability was warranted.

However, this study has three limitations. First, the NHID lacks laboratory and physical examination data, such as body mass index, which is correlated with hypertension. Other surrogates, such as hyperlipidemia and diabetes, were used to adjust the risk. Second, we did not differentiate kidney and ureter stones in the SWL group. The treatment was mixed as the number of SWL treatment sessions increased;

only 38% of treatment was in the kidney in the first session, and 62% of all treatments were SWL of the kidney. Furthermore, SWL of proximal ureter stones may cause renal injury. Hence, it is difficult to differentiate whether kidney injury developed in a single patient. However, the unmeasured confounder would nullify the results. Third, we lack data on stone severity (stone size, numbers) for adjustment. Hence, we used patients

with severe stone disease who received PCNL or open stone surgery for the sensitivity analysis.

5.2 Comparative Efficacy and Safety of Surgical Treatments for Benign Prostate Hyperplasia - an Application of Network Meta-Analysis

5.2.1 Main findings

In our study, enucleation methods, including bipolar EP, holmium, thulium, and diode LEP, yielded greater Qmax values at 6-12-months after treatment than did the resection and vaporization methods, and the difference could still be observed at 24-36 months after treatment. However, the advantages of the enucleation over vaporization methods were mainly observed in large prostates. Enucleation methods also achieved better IPSS than resection and vaporization methods, although the difference was not statistically significant. The new methods were generally safer than monopolar TURP.

They were less likely to require patient transfusion, cause blood clot tamponade, lead to postoperative hemoglobin decline, or cause TUR syndrome. Our findings support changes in the surgical treatment for BPH from monopolar TURP to new surgical methods.

5.2.2 Results in relation to other studies and reviews

Surgical treatment is usually reserved for patients in whom medications fail to achieve satisfactory outcomes. Consequently, patients are older at the time when surgical interventions are considered, leading to more comorbidities.^{73 74} The new

methods are therefore more suitable for these patients. Besides, the treatment goals for BPH are not only to relieve lower urinary tract symptoms, but also to prevent BPH-related adverse events, such as acute urinary retention, renal function deterioration, or bladder dysfunction. However, with the widespread use of medications, the prevalence of adverse BPH-related events had increased from 1998 to 2008.^{75 76} Besides, Flanigan and colleagues (1998) found that patients who underwent immediate TURP had greater improvements in Qmax and IPSS than men who were followed with an extended period of watchful waiting.⁷⁷ This seems to be a consequence of the delay in effective treatment. As new surgical methods showed fewer complications but achieved similar or even better effects compared to monopolar TURP, early surgical treatments may be considered, to avoid BPH-related adverse events.

Enucleation methods using fiberoptic lasers or bipolar loops mimic open prostatectomy.⁷⁸ It is not surprising that enucleation methods achieve the best Qmax values compared to resection and vaporization methods since enucleation removes more tissue and results in greater PSA reduction than resection and vaporization.⁷⁹ Our analysis showed that vaporization methods seemed to yield a higher BPH recurrence rate than enucleation or resection methods did.

A previous meta-analysis of 6 RCTs with 541 patients found that the holmium LEP achieved better Qmax values at 12 months after surgery than monopolar TURP, although there were no differences in IPSS.⁴⁴ Another meta-analysis that compared KTP LVP and monopolar TURP comprised 6 RCTs and 5 case-control studies with in total 889 patients.⁷⁹ That report found no difference in Qmax and IPSS when the prostate size

was <70 ml, but the Qmax and IPSS in the KTP LVP group were lower when the prostate size was >70. Our results confirmed that the enucleation method was better than resection when either bipolar or laser energy were used, although the vaporization method was not suitable for large prostates.

Both TUR syndrome and bleeding are the major complications of monopolar TURP. No cases of TUR syndrome associated with the 8 new methods was reported since all the new techniques used normal saline instead of distilled water for intraoperative irrigation.

Regarding bleeding, our study demonstrated that the 8 new methods yielded better outcomes than monopolar TURP, both intraoperatively and postoperatively. Enucleation and vaporization methods were better than resection methods regardless of the energy system used. Vaporization also produced coagulation effects, thereby leading to less bleeding. Only once during an enucleation procedure was a feeding vessel encountered in the capsule region, compared to several times during resection procedures. This may have contributed to the decrease in blood loss associated with enucleation. With respect to postoperative bleeding, shorter catheterization durations and fewer blood clot tamponade events were associated with less postoperative bleeding and better hemostatic effects. Laser energy, especially diodes and KTP, showed advantages over bipolar and monopolar energy in postoperative bleeding.

Regarding the re-catheterization rate, the enucleation method was also better than

resection, and vaporization was the worst. Enucleation methods remove more apical prostate tissue, while vaporization methods remove less of the apical prostate tissue because of the risk of sphincter injury. Hence, some surgeon resect the apex of the prostate after vaporization, to overcome the drawbacks of vaporization.⁷⁹