Complications in 2200 Consecutive Laparoscopic Radical Prostatectomies: Standardised Evaluation and Analysis of Learning Curves

EUROPEAN UROLOGY 58 (2010) 733–741

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Prostate Cancer

Complications in 2200 Consecutive Laparoscopic Radical Prostatectomies: Standardised Evaluation and Analysis of Learning Curves Marcel Hruza a, Hagen O. Weiß a, Giovannalberto Pini b, Ali S. Goezen a, Michael Schulze a, Dogu Teber c, Jens J. Rassweiler a,* a

Department of Urology, SLK-Kliniken Heilbronn, Heilbronn, Germany

b

Department of Urology, University of Modena and Reggio Emilia, Modena, Italy

c

Department of Urology, University of Heidelberg, Heidelberg, Germany

Article info

Abstract

Article history: Accepted August 11, 2010 Published online ahead of print on August 20, 2010

Background: Laparoscopic radical prostatectomy (LRP) represents an established treatment modality for localised prostate cancer. Objective: To report standardised complication rates for LRP, evaluate the development of complication rates over time, and show changes within the learning curves of laparoscopic surgeons. Design, setting, and participants: We conducted a standardised analysis of 2200 consecutive patients who underwent LRP between 1999 and 2008 at a single institution. Intervention: LRP was performed using a transperitoneal (n = 871) or extraperitoneal (n = 1329) retrograde Heilbronn technique. Five surgeons operated on 96% of the patients. Measurements: Complications were classified according to the modified Clavien system. Total complication rates and changes over time were analysed. Three generations of surgeons were defined for evaluation of learning curves. Results and limitations: Minor complications occurred in 21.7% of patients (Clavien 1: 6.8%; Clavien 2: 14.9%); anaemia requiring transfusion (10.4%) dominated. Early reinterventions were necessary in 6.7% of patients (Clavien 3a: 3.6%; Clavien 3b: 1.5%; Clavien 4a: 1.5%; Clavien 4b: 0.1%). Late Clavien 3b complications occurred in 4.7% of patients—most of them anastomotic strictures. Mortality was 0.1% (Clavien 5). There was a significant decrease in overall complication rates over time, resulting predominantly from decreasing Clavien 1–2 events. Learning curves of third-generation surgeons plateaued earlier compared to the first generation (250 vs 700 cases). The limitation of this study is that data concerning comorbidity were not included. Conclusions: LRP is a safe procedure characterised by an acceptable profile of complications. Specifically, few major complications are reported. According to the complication rates, the learning curve of third-generation surgeons is significantly shorter compared to first- and second-generation surgeons.

Keywords: Complications Laparoscopy Prostatectomy Prostate cancer Clavien classification

# 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, SLK-Kliniken Heilbronn, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany. Tel. +49 7131 492401; Fax: +49 7131 492429. E-mail address: [email protected] (J.J. Rassweiler). 0302-2838/$ – see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.eururo.2010.08.024

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1.

EUROPEAN UROLOGY 58 (2010) 733–741

Table 2 – Criteria of accurate and comprehensive reports of surgical complications according to Martin et al [21]

Introduction

The introduction of laparoscopic radical prostatectomy (LRP) at the end of the last century [1–3], its acceptance as an alternative during the recent decade [4], and its further development leading to robot-assisted laparoscopic radical prostatectomy (RALP) [5–7] influenced the management of localised prostate cancer. Morbidity and complications of LRP have been published frequently [8–16], but there is a lack of standardised reporting [17]. Clavien presented a systematic classification system rating complications according to the effort required to treat them [18]. Recent urologic studies [10–16,19] have applied a modified Clavien classification [20], and Martin et al defined further criteria for accurate and comprehensive reports of surgical complications, including parameters for data acquisition, processing, and analysis as important for correct interpretation [21]. High-quality analysis of complications and their management represents the basis for future reduction of complication rates. Such analyses are important for quality management at the respective institution but may also be relevant for other centres, offering possibilities to minimise complications. We conducted this study based on our large singeinstitution series of 2200 LRP cases, including >10 yr of experience. The purposes of the present study are a standardised reporting of complication rates of LRP using the modified Clavien system and the Martin criteria in a large cohort at a pioneering institution, showing the evaluation of the development of complications over time and demonstrating changes in the learning curves of laparoscopic surgeons. 2.

Materials and methods

2.1.

Patients, intervention, and pathologic examination

1. Definition of the method of data accrual 2. Indication of duration of follow-up 3. Inclusion of outpatient information 4. Definitions of complications 5. Listing of the mortality rate and causes of death 6. Indication of the morbidity rate and total complications 7. Inclusion of procedure-specific complications 8. Use of a severity grade 9. Inclusion of length-of-stay data 10. Inclusion of risk factors

trained by first- or second-generation surgeons using a special training program [22,23]. Our series consisted of one first-generation surgeon (n = 1209 cases), two second-generation surgeons (n = 197; n = 170), and two third-generation surgeons (n = 292; n = 241). In the first 100 patients, no nerve-sparing surgery (NSS) was performed. Extended pelvic lymph node dissection (PLND) became standard for high-risk tumours following 1200 cases. After 1059 cases, we changed from interrupted to single-knot sutures for vesicourethral anastomosis. The urethral catheter was removed at day 7 when no significant extravasation was documented and was left for another week in case of leakage. Cotrimoxazol was administered until catheter removal. After inking the specimen to delineate surgical margins and fixing it in 10% formalin, it was examined in whole-mount 3-mm serial sections using the Stanford technique.

2.2.

Follow-up schedule and recording of data

Pre- and postoperative data for all patients without exclusion criteria were recorded prospectively using a Microsoft Office Excel spreadsheet. Complications were noted with all details, including treatment and outcomes, as part of our internal quality management system, with undersigned consent for scientific use of data. All complications other than erectile dysfunction and urinary incontinence were included. Medical and surgical complications during the first 6 wk were evaluated at the end of this period using medical records of our institution and

LRP was performed in 2200 consecutive patients between March 1999

reports of the rehabilitation centre and of other physicians. Patients had

and October 2008 using the transperitoneal (first 871 patients) and

follow-up examinations every 3 mo for 3 yr after surgery and every 6 mo

extraperitoneal (n = 1329) retrograde Heilbronn technique [1,4,5],

afterwards. We used inpatient and outpatient medical records,

respectively. Five surgeons operated on 96% of the patients. Ninety-one

correspondence with other physicians, and data from follow-up

patients were operated on by different surgeons performing<20 cases.

questionnaires completed by the patients recording all complications

Three generations of surgeons were defined: first-generation surgeons

possibly related to LRP.

with a great deal of experience in open surgery but no laparoscopic

Two colleagues not involved in surgery (MH and HW) classified all

training, second-generation surgeons with experience in open surgery

complications according to the modified Clavien system [20], distin-

who were trained by first-generation surgeons, and third-generation

guishing between early and late Clavien 3b complications (Table 1). The

surgeons with no or limited experience in open surgery who were

Martin criteria [21], as listed in Table 2, were included.

Table 1 – Modified Clavien classification system for surgical complications Grade

Definition

Clavien 1 Clavien Clavien Clavien Clavien Clavien Clavien

2 3a 3b 4a 4b 5

ICU = intensive care unit.

Any deviation from the normal intraoperative or postoperative course, including the need for pharmacologic treatment other than antiemetics, antipyretics, analgesics, diuretics, electrolytes, or physiotherapy Complications needing only the use of intravenous medications, total intravenous nutrition, or blood transfusion Complications needing surgical, endoscopic, or radiologic intervention under local anaesthesia Complications needing surgical, endoscopic, or radiologic intervention under general anaesthesia Life-threatening complications requiring ICU management: single organ dysfunction Life-threatening complications requiring ICU management: multiorgan dysfunction Death of the patient

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EUROPEAN UROLOGY 58 (2010) 733–741

Table 3 – Demographics and characteristics of 2200 patients

Table 3 (Continued )

Age, yr: Mean (SD) Range

Lymph node status, no. (%): Negative lymph nodes/no lymph node dissection (pN0/pNx) Positive lymph nodes (pN1)

BMI, kg/m2 (%): >25 (normal weight) 26–30 (obesity I8) 31–40 (obesity II8) >40 (obesity III8) Mean (SD) Range PSA preoperatively, ng/ml (%): <4.0 4.0–9.9 10.0–19.9 >19.9 Median (IQR) Clinical stage, no. (%): Organ confined Non–organ confined Operating room time, min: Mean  SD Range Access, no. (%): Extraperitoneal Transperitoneal

63.8 (6.15) 40–84

772 (45.1) 789 (46.0) 148 (8.6) 5 (0.3) 26.8 (3.35) 15–58

224 (10.2) 1247 (56.8) 535 (24.4) 189 (8.6) 7.6 (5.3–11.5)

1486 (70.2) 630 (29.8)

SD = standard deviation; BMI = body mass index; PSA = prostate-specific antigen; IQR = interquartile range; NSS = nephron-sparing surgery; NSM = negative surgical margins; PSM = positive surgical margins; LND = lymph node dissection; PLND = pelvic lymph node dissection.

2.3.

Statistical analysis

Analysis of individual learning curves was performed by dividing the institutional learning curve was defined as the sum of the individual learning curves showing complication rates irrespective of the surgeon. For this purpose, we divided the cohort into subgroups of 200

217  52.6 97–600

consecutive patients. For statistical analysis, we used a commercially available software package (SPSS [SPSS, Chicago, IL, USA]), including Pearson x2 test and

867 (39.4) 1333 (60.6)

Fisher exact test to check for statistical significance in univariable analysis. A logistic regression model was used for multivariable analysis, including the following parameters: age, body mass index (BMI),

1181 (53.8) 261 (11.9) 752 (34.3)

Suture of vesicourethral anastomosis, no. (%): Interrupted Running

1159 (49.1) 1141 (51.9)

Length of hospital stay, d Median (IQR)

41 (1.9)

patients of each surgeon into subgroups of 50 consecutive patients. The

NSS, no. (%): Non–nerve sparing Unilateral nerve sparing Bilateral nerve sparing

Blood loss during surgery, ml Median (IQR)

2159 (98.1)

preoperative prostate-specific antigen (PSA), prostate volume, clinical stage, access (transperitoneal, extraperitoneal), PLND, nerve sparing, type of anastomosis, operating room time, and surgeon experience. All complications were considered in this model; we compared patients

800 (600–1100)

11 (9–15)

Weight of specimen, g (%): 30 31–60 >60 Median (IQR)

457 (21.0) 1454 (66.8) 265 (12.2) 40.0 (32.0–50.0)

Volume of tumour, cm3 (%): 0.01–1.00 1.01–5.00 5.01–10.00 >10.00 Median (IQR)

550 (26.6) 1228 (59.3) 221 (10.7) 72 (3.4) 2.0 (1.0–3.5)

Pathologic T stage (pT stage), no. (%): pT2 pT3a pT3b pT4

1261 (57.4) 588 (26.8) 260 (11.8) 89 (4.0)

Gleason score, no. (%): 4–5 6 7 8–10

229 (10.8) 676 (31.8) 1020 (48.1) 197 (9.3)

Surgical margins, no. (%): NSM (R0) PSM (R1)

1683 (76.6) 513 (23.4)

LND, no. (%): No LND PLND Extended LND

761 (34.6) 1400 (63.7) 38 (1.7)

without any complications to patients with complications (Clavien grade 1–5). P < 0.05 was considered statistically significant.

3.

Results

3.1.

Patient characteristics and distribution of complications

Demographics as well as clinical and pathologic data are given in detail in Table 3. Median follow-up was 50 mo (interquartile range [IQR]: 26–72). Minor complications requiring no or noninterventional treatment occurred in 21.7% of patients (Clavien 1: 6.8%; Clavien 2: 14.9%; Table 4). Major complications requiring reinterventions within 6 wk

Table 4 – Total complication rates in 2200 consecutive cases of laparoscopic radical prostatectomy performed at a single centre Reintervention status

No reinterventions necessary Reinterventions necessary

Grade

Clavien Clavien Clavien Clavien early Clavien late Clavien Clavien Clavien

Complication rate by grade

1 2 3a 3b

6.8% 14.9% 3.6% 1.5%

3b

4.7%

4a 4b 5

1.5% 0.1% 0.1%

Complication rate by grade and reintervention status 21.7% 9.8%

1.6% 0.1%

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Table 5 – Detailed analysis of Clavien grade 1 complications (n = 150 of 2200; 6.8%) Complication

Treatment

Urinary retention after catheter removal Recatheterisation without cystoscopy Prolonged secretion of lymph Prolonged retention of the drain Superficial wound dehiscence Local disinfection, wound dressing Prolonged pain Oral analgesics Minor bladder tapenade Bladder irrigation through catheter Allergic exanthema Ointment Major haematoma No special therapy Incomplete intestinal obstruction No special therapy Minor extravasation of urine after removal of the Recatheterisation without cystoscopy catheter—small volume of fluid detected with ultrasound Others: Diarrhoea caused by antibiotics, superficial wound after collapse, shoulder–hand syndrome, hyposensibility of the penis/scrotum, transient minor faecal incontinence, gouty arthritis, prolonged amentia after anaesthesia

n

%

54 48 10 8 5 5 4 3 3

2.4 2.2 0.45 0.36 0.23 0.23 0.18 0.14 0.14

10

0.45

Table 6 – Detailed analysis of Clavien grade 2 complications (n = 328 of 2200; 14.9%) Complication Anaemia without additional complications Acute cystitis Superficial injury to rectal serosa Rectovesical fistula Phlebothrombosis of the leg Infected lymphocoele Ileus Other infections Amaurosis fugax Tachyarrhythmia

Treatment

n

%

Transfusion Parenteral antibiotics Intraoperative suture, gradual return to solid food Prolonged catheterisation, parenteral nutrition Anticoagulation, local compression Parenteral antibiotics Gradual return to solid food Parenteral antibiotics No special treatment Parenteral antiarrhythmics

229 47 26 7 6 4 4 3 1 1

10.40 2.10 1.12 0.31 0.28 0.18 0.18 0.13 0.05 0.05

Table 7 – Detailed analysis of Clavien grade 3a complications (n = 80 of 2200; 3.6%) Complication Major urine extravasation during catheterisation time Urinary retention after catheter removal Lymphocoele (in extraperitoneal cases only) Dislocation of the catheter with extravasation Hydronephrosis Haematoma Clip migration into the urethra without stricture formation Major urine extravasation after removal of the catheter Major bladder tapenade Abscess

were necessary in 6.7% of patients (Clavien 3a: 3.6%; Clavien 3b: 1.5%; Clavien 4a: 1.5%; Clavien 4b: 0.1%). Mortality was 0.1% (Clavien 5), and 4.7% of patients underwent late reinterventions (11.4% early and late reinterventions).

Treatment

n

%

Ureteral stent (mono-J stent) Cystoscopic recatheterisation Percutaneous drainage Cystoscopic recatheterisation Ureteral stent (double-J stent) Percutaneous drainage Cystoscopy and removal of the clip Cystoscopy and recatheterisation Cystoscopy with clot removal Percutaneous drainage

24 14 12 10 7 4 3 3 2 1

1.10 0.63 0.55 0.45 0.31 0.17 0.14 0.14 0.09 0.05

Major bleeding was the most important factor for lifethreatening complications (47% of Clavien 4–5). Detailed information on all complications and treatment modalities are provided in Tables 5–13.

Table 8 – Detailed analysis of early Clavien grade 3b complications (n = 32 of 2200; 1.5%) Complication Hydronephrosis, urinary extravasation (JJ-stenting failed) Early anastomotic stricture Major intraoperative bleeding Intraoperative visceral injury Intraoperative injury of the ureter Intraoperative respiratory insufficiency Epididymitis with abscess formation Embolism of the external iliac artery Major dehiscence of the anastomosis after catheter removal Intra-abdominal dislocation of the drain Injury of the external iliac artery Stenosis of the distal ureter

Treatment

n

%

Percutaneous nephrostomy Transurethral laser incision Conversion Conversion, surgical repair Laparoscopic reimplantation Conversion Parenteral antibiotics, epididymectomy Embolectomy Open revision of the anastomosis and recatheterisation Laparoscopic removal of the drain Laparoscopic suture of the external iliac artery Ureteroscopy and laser incision of the ureter

10 5 4 4 2 1 1 1 1 1 1 1

0.45 0.23 0.18 0.18 0.1 0.05 0.05 0.05 0.05 0.05 0.05 0.05

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Table 9 – Detailed analysis of late Clavien grade 3b complications (n = 103 of 2200; 4.68%) Complication Anastomotic stricture Incisional hernia Bladder stone formation after clip migration Bladder stone formation without visual clip Local recurrence of the carcinoma causing stricture of the bladder neck

Treatment

n

%

Transurethral laser incision Hernioplasty with mesh Cystoscopy and lithotripsy Cystoscopy and lithotripsy Transurethral resection

96 3 2 1 1

4.4 0.14 0.09 0.05 0.05

Table 10 – Detailed analysis of Clavien grade 4a complications (n = 32 of 2200; 1.5%) Complication

Treatment

n

%

Open revision, transfusions, treatment in ICU Temporary colostomy, treatment in ICU Artificial respiration, treatment in ICU Thrombolysis, treatment in ICU Cardiac catheterisation and stent treatment in ICU Laparoscopic revision, transfusions, treatment in ICU Medical treatment in ICU Resection of caecum, treatment in ICU Treatment in ICU, speech therapy Treatment in ICU

12 4 3 4 2 2 2 1 1 1

0.54 0.18 0.14 0.18 0.09 0.09 0.09 0.05 0.05 0.05

n

%

Open revision, artificial respiration, treatment in ICU

1

0.05

Open revision, transfusions, artificial respiration, treatment in ICU

2

0.09

Major postoperative bleeding Rectovesical fistula/major rectal injury Acute respiratory insufficiency Thromboembolism MI postoperatively Major postoperative bleeding Cardiac arrhythmia postoperatively Sepsis after unnoticed injury to caecum during trocar insertion Stroke during surgery, aphasia Allergic shock caused by analgesics ICU = intensive care unit; MI = myocardial infarction.

Table 11 – Detailed analysis of Clavien grade 4b complications (n = 3 of 2200; 0.14%) Complication Circulatory insufficiency caused by major bleeding and incomplete intestinal obstruction Major bleeding and respiratory insufficiency

Treatment

ICU = intensive care unit.

Table 12 – Detailed analysis of Clavien grade 5 complications (n = 3 of 2200; 0.14%) Complication Major bleeding, lethal respiratory and acute renal insufficiency 21 d after LRP MI, death caused by postischaemic rupture of the left ventricle 40 d after LRP Sudden cardiac death after unapparent cardiac arrhythmia 7 d after LRP

Treatment

n

%

Transfusions, artificial respiration, treatment in ICU Treatment in ICU, cardiac catheterisation and stent Failed cardiopulmonary resuscitation

1 1 1

0.05 0.05 0.05

LRP = laparoscopic radical prostatectomy; ICU = intensive care unit; MI = myocardial infarction.

3.2.

Analysis of the learning curves

We compared the complications of first-, second-, and third-generation surgeons within their first 250 cases (Fig. 1). The second- and third-generation surgeons started with lower overall complication rates compared to the firstgeneration surgeons, but this trend showed no statistical significance. The higher gradient of the curve of the thirdgeneration surgeons correlates to a shorter learning curve: 250 versus 700 cases to reach a similar plateau. The analysis of individual learning curves suffers from a bias because of technical changes: The first- and second-generation surgeons performed their first 250 cases using transperitoneal access, less NSS, and interrupted sutures for vesicourethral anastomosis, whereas the third-generation surgeons performed their cases using extraperitoneal access, more NSS, and the single-knot anastomosis. There were no significant differences in BMI, preoperative PSA, weight of the prostate,

and pT stage between the first 250 patients of each generation of surgeons; however, the third-generation surgeons treated significantly more patients over the age of 65 yr ( p = 0.001). There is a significant decrease in overall complication rates over time, reflecting the learning curve of the institution (38% within the first 200 cases vs 22% within the last 200 cases; p < 0.001; Fig. 2). Predominantly, this change results from decreasing Clavien 1–2 events (29.6% vs 15.0%; p < 0.001). The change in Clavien 3–4 (8.6% vs 6.6%) was less relevant ( p = 0.235). We observed a decrease in transfusion rate (19.5% vs 6.5%), rectal injury (3% vs 0.5%), postoperative revisions (2% vs 1%), and conversion rate (2.5% vs 0%) but no changes with respect to urinary tract infection (UTI), prolonged lymphatic secretion, and medical complications. The institutional learning curve is also influenced by technical modifications over time. Patient age, BMI, weight of the prostate, and pathologic T stage did

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Table 13 – Definitions of complications Complication Acute cystitis Acute renal insufficiency Acute respiratory insufficiency Acute circulatory insufficiency Anaemia Anastomotic stricture Cardiac arrhythmia Hydronephrosis Ileus Lymphocoele Major bleeding Major haematoma Major rectal injury Prolonged secretion of lymph Superficial injury of the rectum Urinary retention Urinoma/urinary leakage

Definition Included when parenteral antibiotics had to be administered and/or when catheter removal was delayed Serum creatinine >1.5 mg/dl in patients with normal serum creatinine preoperatively Included when medical treatment or treatment in the ICU was necessary Included when medical treatment or treatment in the ICU was necessary Haemoglobin <8 ng/ml and/or symptoms resulting from anaemia with or without the need for any transfusions Narrowing of vesicourethral anastomosis or bladder neck causing voiding problems or the inability to void; usually verified during cystoscopy Includes new-onset atrial fibrillation, atrial flutter, or premature ventricular contractions Included when causing symptoms (pain, increase of serum creatinine); verified during ultrasound examination Abdominal distension and/or hypoactivity of the bowel causing deviations from normal postoperative course (special diet and/or medical/surgical interventions) Included when <5 cm in diameter in routine ultrasound examination done in every patient or when symptoms (eg, pain, infection of lymphocoele) occurred Haemoglobin <8 ng/ml and/or symptoms resulting from anaemia with the need for more than five transfusions and/or further medical or surgical treatment, including conversion or revision Included when they caused symptoms to the patients and in cases of large haematoma without symptoms Rectal injury, including disruption of the rectal mucosa Included when the drain could not be removed until day 7 postoperatively Injury of the rectum serosa without complete opening of the rectum (mucosa and muscular layers intact) Defined as total inability to void or >150 ml urine within the bladder after voiding Symptomatic extravasation of urine detected by any imaging modality

ICU = intensive care unit.

not differ significantly between the first and last 200 patients, but there were significantly more patients with high preoperative PSA (>10 ng/ml) within the first 200 cases. 3.3.

suture (OR: 1.59) were independent predictors of lower complication rates (Table 14). 4.

Discussion

4.1.

Comparison with other series

Predictive factors

Total complication rates are significantly lower in patients with a specimen of < 50 g ( p = 0.002) and a preoperative PSA < 10 ng/ml ( p = 0.003). Extraperitoneal access ( p = 0.005), NSS ( p < 0.001), single-knot suture for vesicourethral anastomosis ( p < 0.001), and operating room time <4 h ( p = 0.023) were associated with significantly lower complication rates. Other factors, such as patient age, BMI, clinical stage, the surgeon, and lymph node dissection (LND), did not have a significant impact. In multivariable analysis, only operating room time <4 h (odds ratio [OR]: 0.46), NSS (OR: 1.51), and single-knot

In our present study, complication rates were 21.7% (Clavien 1 + 2) and 11.5% (Clavien 3–5). There was a significant decrease in complication rates over time, mainly because of a decrease in minor complications. Rabbani [19] presented an [(Fig._2)TD$IG]

[(Fig._1)TD$IG]

Fig. 1 – Individual learning curves of first-, second-, and third-generation surgeons, including the first 250 cases respectively.

Fig. 2 – A significant decrease in complication-free rates (p < 0.001) and rates of Clavien 1–2 complications (p < 0.001) between the first and last 200 patients shows the institutional learning curve. There was no significant change in Clavien 3–4 complications. Arrows mark the following events: (A) start of second-generation surgeon 1, (B) start of second-generation surgeon 2, (C) start of third-generation surgeon 1, (D) running anastomosis replaces interrupted anastomosis, (E) start of third-generation surgeon 2, (F) extraperitoneal access replaces transperitoneal access.

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Table 14 – Predictive factors associated with lower complication rates (multivariable analysis) Factor

OR

Operating room time NSS (non–nerve sparing/unilateral plus bilateral nerve sparing) Suture (single knot/running) Patient age BMI Preoperative PSA Volume of the prostate Clinical stage (organ confined/non–organ confined) Surgeon Access (transperitoneal, extraperitoneal) PLND

95% CI

0.463 1.513 1.595 0.991 0.895 0.841 0.825 1.115 1.009 1.246 1.077

p

Lower

Upper

0.301 1.156 1.176 0.796 0.721 0.650 0.645 0.866 0.805 0.922 0.834

0.713 1.981 2.164 1.234 1.110 1.086 1.055 1.437 1.265 1.682 1.390

0.023 <0.001 <0.001 0.937 0.312 0.184 0.125 0.397 0.937 0.152 0.570

OR = odds ratio; CI = confidence interval; NSS = nerve-sparing surgery; BMI = body mass index; PSA = prostate-specific antigen; PLND = pelvic lymph node dissection.

Table 15 – Comparison of our complication rates with other series Complication

Urinoma/urinary leak Bladder neck contracture Urinary retention Hydronephrosis Ureteral injury Bladder calculus/suture/clip Lymphocoele Abscess Rectal/bowel injury Wound infection Cardiac ischemia Cardiac arrhythmia Respiratory distress Pneumonia Ileus Acute renal insufficiency Venous thromboembolism UTI Anaemia needing transfusions Total complications

Present series LRP, %

Rabbani et al [19], RRP, %

Rabbani et al [19], LRP, %

1.4 4.6 3.0 0.8 0.1 0.15 0.7 0.1 2.1* 0.5 0.15 0.2 0.3 0 0.3 0.05 0.5 2.1 14.8 33.1**

2.9 5.5 3.6 0.9 0.5 0.6 3.0 0.7 0.7 2.3 0.2 0.9 0.6 0.3 0.3 0.7 1.9 2.8 55.0 27.5***

8.7 0.7 3.0 1.9 0.2 0.2 5.4 1.7 0.4 3.8 0.4 0.7 0.6 0.4 2.1 1.0 2.0 7.8 4.0 39.02

Literature RRP, % [19] 0.2–6.7 1.0–17.9 0.6–2.0 0.2–1.0 0.1–0.8 N/A 0.1–6.9 0.4–1.7 0.4–4.9 0.6–13.8 0.0–1.0 0.2–4.8 0.5–1.2 0.2–1.4 0.3–3.0 0.2–0.4 0.4–1.3 0.1–3.0 NA NA

Literature LRP, % [19] 1.0–13.6 0.2–5.3 0.8–5.9 0.0–0.4 0.2–0.5 0.8 0.0–1.1 0.0–0.7 0.0–1.4 0.0–1.0 0.0–0.7 N/A 0.2–0.7 0.0–0.3 0.3–5.3 0.0–0.3 0.0–2.4 1.0–2.4 NA NA

LRP = laparoscopic radical nephrectomy; RRP = retropubic radical prostatectomy; NA = not available; UTI = urinary tract infection. 1.4% of cases were managed conservatively (intraoperative suture of superficial bowel/rectal injury followed by parental nutrition for several days and prolonged catheterisation time). ** Including blood transfusions, excluding patients with anaemia as only complication; total complication rate amounts to 22.7%. *** Excluding blood transfusions. *

excellent study using the modified Clavien system in 3458 patients treated with retropubic radical prostatectomy (RRP) and in 1134 LRP patients with a median follow-up of 37 mo. The study summarised grade 1–2 (minor) and grade 3–5 (major) complications, reporting 19.9% Clavien 1–2 following RRP compared to 37.3% after LRP. Separately, the study listed transfusion rates of 55% after RRP and 4% after LRP. Apparently, many patients receiving transfusions were not registered as Clavien 2. Table 15 shows that our results are comparable to the data discussed by Rabbani et al [19], although all cases of blood transfusions were included. Novara et al [16] observed 19% Clavien 1–2 (5.3% transfusions), corresponding to our series (21.7%, including 10.4% transfusions) as well as to the meta-analysis of Ficarra et al [7]. Rabbani et al [19] reported Clavien 3–5 in 6.4% after RRP and 8.9% after LRP versus 11.4% in our series.

Novara et al [16] identified prostate volume >50 ml as a univariate predictor of complications. However, on multivariate analysis, only the number of cases by surgeon remained a prognostic factor. Zorn et al [24] did not find any impact from prostate volume. However, Zorn’s study, with <400 patients subdivided into 4 groups, might be underpowered to detect any difference. In our series, operating room time <4 h, NSS, and anastomotic technique were independent predictors on multivariate analysis. However, many factors can influence the institutional learning curve. As marked with arrows in Fig. 2, we encountered major changes in operative technique with the introduction of extraperitoneal access or single-knot anastomosis as well as new surgeons starting with the procedure. The informative power of an institutional learning curve might be limited. Our curve shows a clear trend towards

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reduction of complications, mainly because of a reduction in Clavien 1 + 2 complications. Predominantly, we observed a decrease in transfusion rate (19.5% vs 6.5%), rectal injury (3% vs 0.5%), postoperative revisions (2% vs 1%), and conversion rate (2.5% vs 0%). Major medical complications such as thrombosis, embolism, or arrhythmia were already few, indicating that there are no inherent limits to laparoscopy. Detailed analyses, however, help identify possibilities for future reduction of major complications. Based on the Heilbronn Laparoscopic Training Program [22,23] we could shorten the individual learning curve of the third generation significantly. This applies also to fellows transferring the technique to other departments [25] and shows that a proper mentored training program, as developed and used in many centres throughout the world today, is important. Several studies on complications after RALP have been published recently, showing complication rates between 4.4% and 26% [26,27]. A standardised classification system, together with the Martin criteria used in large studies on RRP, LRP, and RALP, would allow a more powerful comparison because of the higher methodologic quality. However, it may be difficult to apply these standardised methods in series with long follow-up periods. In 1999, neither the modified Clavien system nor the Martin criteria had been published. There are some disadvantages to the Clavien system. Complications with different morbidity may be classified similarly. For example, Clavien 3b includes stenting for hydronephrosis, repair of ureteral injury, or conversion for bleeding. The only thing these complications have in common is that the repair is performed under general anaesthesia. Furthermore, treatment modalities of the same complications may differ: Reinterventions under general anaesthesia in one hospital may be performed under local anaesthesia in another. The same applies to indications for intensive care unit treatment, thus diminishing validity when comparing different series. Also, the Clavien system does not distinguish between early and late postoperative complications as being relevant when comparing series with different follow-up periods. Therefore, we stratified early from late Clavien 3 complications. In our eyes, excluding major complications recognised and managed intraoperatively is another limitation of the Clavien system. A major deviation from the operative course, such as the repair of ureteral or rectal injury, causes prolonged operating room time, increasing the risk of complications—particularly concerning the repaired organ. This is comparable to the risk of a secondary surgical procedure defined as Clavien 3. Therefore, we advocate its inclusion (see Tables 5–13). 4.2.

Limitations of the study

Prospective recording of complications over a long period of time may lead to a bias mainly concerning Clavien 1 + 2 events. Minor events classified as complications at the end may have been considered normal at the beginning. A major limitation of our study is that we are not able to provide data on comorbidity.

We defined medical problems occurring later than 6 wk as not related to surgery. This decision was reasonable, because most patients stayed at rehabilitation centres until 6 wk after surgery. Together with the hospitalisation for at least 1 wk after LRP that is common in the German health care system, this leads to a close observation of patients, with recognition of all minor complications during this 6-wk interval. It is questionable whether all small events can really be observed in systems that discharge the patient 1–2 d after surgery. Nevertheless, it may be discussed whether 30 d, 6 wk, or 90 d represents an appropriate interval. 4.3.

Lessons learned

To minimise or avoid errors, understanding of the error itself and determining factors are important [28]. A detailed analysis of technical modifications leading to a reduction in complications is useful for other surgeons. The rate of rectal lesions could be reduced by introduction of a rectal balloon. Rectal fistulae were eliminated by reducing the power of bipolar coagulation (maximum 50 W) and avoiding Hem-olok clips close to the rectum or urethra, which also reduced bladder neck stricture resulting from clip migration. Extravasation requiring retrograde stenting or percutaneous nephrostomy could be minimised through posterior bladder neck reconstruction if the ureteral orifices are close to the resection line. According to our low rate of UTI, we recommend antibiotic prophylaxis. There is little room for improvement concerning medical complications and wound healing problems. Perhaps patient selection could help to diminish major medical complications. We can still reduce our transfusion rate, however. Because the need for intraoperative transfusion is minimal, measures to avoid postoperative bleeding (ie, control of prostatic pedicles and neurovascular bundles) are important. 5.

Conclusions

Based on the Clavien system, complications of LRP were prospectively recorded, classified, reported, and analysed adequately in our large collective after LRP. However, no comorbidity status was available. Our complication rates are comparable to those published in other studies on radical prostatectomy, indicating that LRP is as safe as RRP, which is still the gold standard. We could demonstrate a decrease in total complication rates in time, mainly based on a decrease in Clavien 1 + 2 complications. The individual learning curve of the third-generation surgeons was shorter compared to first- and second-generation surgeons: This may be the result of a dedicated learning program. A standardised and critical analysis of complications is an important step for future reduction of complication rates. Author contributions: Jens J. Rassweiler had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hruza, Rassweiler. Acquisition of data: Hruza, Weiß, Goezen, Schulze. Analysis and interpretation of data: Hruza, Weiß, Rassweiler.

EUROPEAN UROLOGY 58 (2010) 733–741

Drafting of the manuscript: Hruza. Critical revision of the manuscript for important intellectual content: Teber, Schulze, Pini, Rassweiler. Statistical analysis: Hruza, Schulze, Weiß. Obtaining funding: None. Administrative, technical, or material support: None.

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[12] Badani KK, Kaul S, Menon M. Evolution of robotic radical prostatectomy: assessment after 2766 procedures. Cancer 2007;110:1951–8. [13] Stolzenburg JU, Rabenalt R, Do M, Kallidonis P, Liatsikos EN. Endoscopic extraperitoneal radical prostatectomy: the University of Leipzig experience of 2000 cases. J Endourol 2008;22:2319–25. [14] Constantinides CA, Tyritzis SI, Skolarikos A, Liatsikos E, Zervas A,

Supervision: Rassweiler.

Deliveliotis C. Short- and long-term complications of open radical

Other (specify): None.

prostatectomy according to the Clavien classification system. BJU Int 2008;103:336–40.

Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

[15] Hakimi AA, Blitstein J, Feder M, Shapiro E, Ghavamian R. Direct comparison of surgical and functional outcomes of robotic-assisted versus pure laparoscopic prostatectomy: single-surgeon experience. Urology 2009;73:119–23. [16] Novara G, Ficarra V, D’Elia C, Secco S, Cavalleri S, Artibani W. Prospective evaluation with standardised criteria for postoperative complications after robotic-assisted laparoscopic radical prostatectomy. Eur Urol 2010;57:363–70. [17] Graefen M. The modified Clavien system: a plea for a standardized

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