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International Urology and
Nephrology
ISSN 0301-1623
Volume 43
Number 4
Int Urol Nephrol (2011) 43:1025-1031
DOI 10.1007/s11255-011-9957-2
Chronic pulmonary diseases are
independent risk factors for complications
after radical nephrectomy
Hüsnü Tokgöz, Bülent Akduman, İlker
Ünal, Bülent Erol, Ersöz Akyürek &
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U R O L O G Y – O R I G I N A L P A P E R
Chronic pulmonary diseases are independent risk factors
for complications after radical nephrectomy
Hu¨snu¨ Tokgo¨z•Bu¨lent Akduman•
I˙lker U¨ nal•Bu¨lent Erol• Erso¨z Akyu¨rek•
Necmettin Aydin Mungan
Received: 23 November 2010 / Accepted: 29 March 2011 / Published online: 24 April 2011 Ó Springer Science+Business Media, B.V. 2011
Abstract
Aim We aimed to identify the prognostic factors and the new parameters such as Charlson’s comor-bidity index (CCI) that might predict postoperative complication rates in a radical nephrectomy cohort. We also evaluated the correlation of CCI with the Clavien postoperative complication scale (CPCS). Materials and methods Perioperative characteristics of 47 patients undergoing radical nephrectomy were recorded. Following items were assessed: preoperative patient characteristics including age, gender, CCI, American Society of Anesthesiologists (ASA) phys-ical status classification system category, renal and hepatic functions, type of nephrectomy incision, operative time, clinical stage and histopathological subtype of the tumor, and preoperative co-morbid conditions including diabetes mellitus, hypertension, chronic pulmonary disease, peptic ulcers, renal and hepatic dysfunction. Postoperative complications were defined as death, wound infection, pneumonia, atelectasis, pulmonary emboli, anemia, sepsis, cardiac
arrhythmia, myocardial infarction, and deep vein thrombosis. In addition, postoperative complications were also graded according to the CPCS and accepted as those occurring within 30 days.
Results Preoperative chronic pulmonary diseases were found to be significant risk factors for the development of postoperative complications. Age adjusted odds ratio was 7.112 for chronic pulmonary disease. The mean CCI in patients who did not develop any postoperative complication was 4.49 ± 1.95, whereas it was 5.75 ± 2.60 for patients who developed postoperative complications (P = 0.138). In Spearman correlation analysis, CCI value was found to be significantly correlated with CPCS grade (P = 0.011, rho value = 0.366).
Conclusion Presence of chronic pulmonary disease is a strong predictor of postoperative complications after radical nephrectomy. Patients with higher preoperative CCI scores may have higher postoper-ative CPCS grades. Additional studies are warranted. Keywords Complications Early
Radical nephrectomy Risk factors
Introduction
The estimated new cases of renal cancer in 2008 in USA were about 54,390 cases and there will be an estimated 13,010 deaths from renal cancer. Renal cell
H. Tokgo¨z (&) B. Akduman B. Erol E. Akyu¨rek N. A. Mungan
Department of Urology, Karaelmas University School of Medicine, ZKU Tıp Fak. Hastanesi S-Blok Kat:4, 67600 Kozlu, Zonguldak, Turkey
e-mail: h_tokgoz@hotmail.com
I˙. U¨ nal
Department of Biostatistics, C¸ ukurova University School of Medicine, Adana, Turkey
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Int Urol Nephrol (2011) 43:1025–1031 DOI 10.1007/s11255-011-9957-2
carcinoma (RCC) is one of the most lethal genitouri-nary malignancies, with approximately 40% of patients dying after diagnosis [1]. Depending on the location and size of the primary tumor, either radical or nephron sparing open/laparoscopic surgery remains the main treatment for clinically localized disease. However, tumor nephrectomy is still a major operative procedure with the potential for significant postoperative compli-cations. In order to evaluate early postoperative complications (within 30 days), various systems/index were used. But, Clavien postoperative complication scale (CPCS) was the most accepted standardized complication reporting system among surgeons.
Recognition of specific prognostic factors may lead to an increase in postoperative surveillance and improve outcome in radical nephrectomy (RN) patients. Hakimi et al. [2]. was the first who aimed to identify and describe certain preoperative patient characteristics that would be related to early postop-erative complications after partial nephrectomy (PN). They defined preoperative renal insufficiency as a predictor of complications after PN. Nevertheless, to the best of our knowledge, no study evaluating the predictive value of various factors like preoperative patient characteristics, comorbid conditions, and analyzing the possible correlation of Charlson’s comorbidity index (CCI) with CPCS in a RN cohort has been published.
In our study, we aimed to identify the prognostic factors and the new parameters that might predict postoperative complication rates in RN performed for RCC.
Patients and methods
The approval of the hospital ethic committee was obtained, and a database of patients who underwent radical tumor nephrectomy in the last 5 years was retrospectively evaluated. The clinical and pathologic data of all patients treated by radical nephrectomy were reviewed. Patients whose surgery was done in an outside hospital were excluded Patients who underwent laparoscopic or other minimally invasive radical nephrectomy operations were also excluded from the study. Finally, a total of 47 patients treated with RN in our clinic were enrolled in the study.
Following items were assessed: preoperative patient characteristics including age, gender, CCI,
American Society of Anesthesiologists (ASA) phys-ical status classification system category, renal and hepatic functions, type of nephrectomy incision (subcostal/flank/thoracoabdominal/midline), operative time (minutes), clinical stage and histopathological subtype of the tumor and preoperative co-morbid conditions including diabetes mellitus, hypertension, chronic pulmonary disease, peptic ulcers, renal and hepatic dysfunction. Clinical staging was performed based on the International Union Against Cancer and American Joint Committee on Cancer TNM staging 2009 version.
Comorbidities were abstracted from the inpatient databases, and the CCI was calculated using 19 weighted indicators of coexisting conditions [3].
Postoperative complications were defined as those occurring within 30 days including readmission to the hospital. They were recorded as death, wound infec-tion, pneumonia, atelectasis, pulmonary embolus, ane-mia, sepsis, cardiac arrhythane-mia, myocardial infarction, and deep vein thrombosis. In addition, postoperative complications were also graded according to the CPCS. The system allows the surgeon to rank a complication in an objective and reproducible manner. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb, and V) [4].
For statistical analyses, SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) was used. Variables were compared using Student t test, Mann–Whitney U test or Chi-Square tests depending on the data type. Correlations between variables were measured using Spearman Rank Correlation coefficient. Univariate and multivariate logistic regression analysis were performed to evaluate the relationship between preoperative patient characteristics and postoperative complication status. A two-tailed P value of \0.05 was accepted as statistically significant.
Results
Clinical and demographic data, comorbidity admis-sion parameters, CCI, and ASA scores of 47 patients undergoing radical nephrectomy were reported in Table 1. Postoperative complications and CPCS grades were given in Table2. None of the cases had a solitary kidney at radical nephrectomy and none of them had bilateral tumors. For the whole group, mean preoperative hematocrit (%), white blood cell count (total/mm39 1,000), and platelet
count (/mm3) values were 38.62 ± 5.09; 1,677.30 ± 1,092.77; and 279.26 ± 86.71, respectively. Mean preoperative serum sodium (mmol/l), potassium (mmol/l), chloride (mmol/l), blood urea nitrogen (mg/dl), creatinine (mg/dl), fasting blood glucose (mg/dl), aspartate aminotransferase (IU/l), and ala-nine aminotransferase (IU/l) levels for the entire group were 140.89 ± 3.00; 4.52 ± 0.41; 104.28 ± 3.09; 35.08 ± 26.23; 1.13 ± 0.55; 106.79 ± 26.37; 21.35 ± 11.34; and 19.38 ± 12.10, respectively. In both univariable and multivariable models, none of
Table 1 Clinical and demographic data, comorbidity admis-sion parameters
Mean age (years) (range) 61.57 ± 12.10 (35–84) Gender
Male 32 Female 15
Mean CCI (Median) 4.80 ± 2.17 (4) ASA category 1 6 2 30 3 11 Clinical stage T1a 6 T1b 20 T2a 4 T2b 5 T3a 9 T3b 1 M1 2 Pathology Clear cell 31 Papillary 6 Chromofob 5 Sarcomatoid 2 Squamous 1 Transitional cell carcinoma 2 Diabetes mellitus Yes 8 No 39 Hypertension Yes 27 No 20
Chronic pulmonary disease
Yes 9
No 38
Peptic ulcers
Yes 0
No 47
Chronic renal failure
Yes 4
No 43
Hepatic dysfunction
Yes 1
No 46
Table 2 Postoperative complications
Parameters n(% total) Death 1 (2.1%) Wound infection 4 (8.5%) Pneumonia 0 (0%) Atelectasis 4 (8.5%) Pulmonary emboli 0 (0%) Anemia 5 (10.6%) Sepsis 0 (0%) Cardiac arrhythmia 2 (4.3%) Myocardial infarction 0 (0%) Deep vein thrombosis 0 (0%) Total 12 (25.5%) CPCS grade I 32 (68.1%) II 10 (21.3%) III 4 (8.5%) IV 0 (0%) V 1 (2.1%) CPCS Clavien postoperative complication scale
Table 1 continued
Mean age (years) (range) 61.57 ± 12.10 (35–84) Type of incision
Subcostal 22 Flank 12 Thoracoabdominal 11 Midline 2
Mean operative time (min) 241.38 ± 71.94 CCI Charlson comorbidity index, ASA American Society of Anesthesiologists
Int Urol Nephrol (2011) 43:1025–1031 1027
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those parameters were found to be a predictor of postoperative complications or CPCS grade after tumor nephrectomy.
Postoperative complication rate was 18.4% in patients who did not have chronic pulmonary disease, whereas it was 55.6% in patients who had chronic pulmonary disease (P = 0.035, chi-square test). Age adjusted odds ratio (OR) was 7.112 (95% confidence interval: 1.035–48.885) for chronic pulmonary dis-ease (Table3).
Chronic pulmonary disease was preoperatively diagnosed in 60% of cases with postoperative CPCS grade C3, whereas it was diagnosed in 30% of cases with CPCS grade 2 and 9.4% of cases with postop-erative CPCS grade 1. In multivariate analysis, preoperative chronic pulmonary diseases were found to be significant risk factors for the development of postoperative complications and higher CPCS grades. An important point we need to mention is that our hospital is located in a city where coal mining
Table 3 Multivariate analysis
Statistically significant P values were written as bold
CCI Charlson comorbidity index, ASA American Society of
Anesthesiologists, Ref Reference, NA Not available, OR Odds ratio
a Age adjusted
Parameters P value Univariate OR (CI)
P value Multivariate ORa(CI) Age 0.292 1.03 (0.97–1.09) 0.312 1.04 (0.96–1.12) Gender (ref. female) 0.302 0.49 (0.12–1.92) – –
CCI 0.095 1.30 (0.96–1.77) – – ASA category – – I ref 0.174 1.00 II 0.357 0.40 (0.06–2.81) III 0.629 1.67 (0.21–13.23) Clinical stage – – T1b ref 0.988 1.00 T1a 0.999 0.00 (0.00–NA) T2a 0.841 0.78 (0.07–9.08) T2b 0.999 0.00 (0.00–NA) T3a 0.452 1.87 (0.37–9.49) T3b 1.00 0.00 (0.00–NA) M1 0.571 2.33 (0.12–43.79) Pathology – – Clearcell ref 0.931 1.00 Papillary 0.453 2.08 (0.31–14.17) Chromofob 0.973 1.04 (0.10–11.09) Sarcomatoid 0.999 6.73 (0.00–NA) Squamous 1.000 0.00 (0.00–NA) Transitional cell carcinoma 0.337 4.17 (0.23–76.60)
Diabetes mellitus (ref yes) 0.970 0.97 (0.17–5.59) – – Hypertension (ref yes) 0.457 1.68 (0.43–6.64) – – Chronic pulmonary disease
(ref yes)
0.030 5.54 (1.175–26.072) 0.046 7.11 (1.04–48.89)
Chronic renal
Failure (ref yes) 0.261 3.30 (0.41–26.51) – – Type of incision – – Subcostal ref 0.984 1.00 Flank 0.881 1.13 (0.22–5.86) Thoracoabdominal 0.764 0.76 (0.12–4.70) Midline 0.999 5.49 (0.00–NA) Operative time 0.411 1.01 (0.99–1.013) – –
remains a major industry. So, some of our RN patients were active working or retired coal workers. We all know that increased coal dust exposure and smoking have been associated with increased risk of COPD. We observed that 11 out of 47 cases were coal workers (23.4%). Regarding tobacco consump-tion, we noticed that 24 out of 47 cases (51%) were cigarette smokers. For those 24 cases, mean duration of smoking was 26.63 ± 18.17 pack years (median value was 25 pack years). On statistical evaluation, we found that none of these 2 parameters were significantly correlated with any of the postoperative complications and the CPCS. Postoperative compli-cation rates were 18.2% for coal workers and 27.8% for non-coal workers (P = 0.703, chi-square test). The complication rates for smokers and non-smokers were also comparable (21.7 and 29.2%, respectively) (P = 0.740, chi-square test). Among 9 cases who had the diagnosis of COPD preoperatively, 4 (44%) were coal workers and 6 (67%) were cigarette smokers. Although coal workers and smokers had a higher rate of COPD disease when compared to non-coal work-ers and non-smokwork-ers, no statistically significant difference was observed. COPD was diagnosed in 36.4% of coal workers (13.9% for non-coal workers) and 26.1% of smokers (12.5% for non-smokers) (P = 0.183 for coal mining history and P = 0.286 for tobacco consumption, chi-square test).
The mean CCI in patients who did not develop any postoperative complication was 4.49 ± 1.95, whereas it was 5.75 ± 2.60 for patients who devel-oped postoperative complications (P = 0.138, Mann–Whitney U test). However, CCI value was found to be significantly correlated with CPCS grade (P = 0.011, rho value = 0.366) (Spearman correla-tion analysis) (Fig.1).
Discussion
Currently, in localized renal cell carcinomas, partial nephrectomy for small tumors and radical nephrec-tomy for large tumors continue to be the gold-standard treatments. In addition, cytoreductive nephrectomy is often indicated before the start of systemic treatment in patients with metastatic dis-ease. In a retrospective study, Lau et al. [5] reported the long-term follow-up of a matched comparison of radical and partial nephrectomy surgeries. In this
study, early complications in patients with RCC after RN were observed in 10 out of 164 (6.1%) cases. Postoperative complications were defined as postop-erative bleeding (1 case), pulmonary embolus (1), myocardial infarction (1), acute renal failure (1), ileus (4), and wound infection (2) in a selected study population. In our cohort, the rate of postoperative complications was 25% including the cases with anemia and cardiac arrhythmia. In series by Nazemi et al. [6], the overall complication rate was reported as 17%. For high risk patients, postoperative com-plication rate was reported as 53% [7]. So, periop-erative complications after a RN operation are not uncommon. Thus, for urooncologists, identification of certain predictive factors would be very informa-tive in order to suspect possible complicated cases.
In 2004, Han et al. [7] from California University performed a retrospective analysis to determine the impact of ASA classification on risk of perioperative complications. On univariate analysis, adjacent organ resection, inferior vena cava involvement, and 15-min increases in operative time were found to increase the risk of overall complications after tumor nephrectomy surgery. However, on multivariate analysis, only 15-min increases in operative time carried a statisti-cally significant risk of complications (relative risk = 1.12). In this study, PN cases were also included. ASA category, metastatic presentation of the tumor, gender, tumor stage, patient age, preoper-ative hemoglobin value, type (partial or radical), and side of the tumor were not found as predictors of
Fig. 1 Correlation between preoperative CCI scores and postoperative CPCS grades
Int Urol Nephrol (2011) 43:1025–1031 1029
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postoperative complications. In our study, operative time was not a predictor of any complication, but chronic pulmonary disease was found to be a risk factor for postoperative complications. During preop-erative evaluation, 9 out of 47 cases had chronic pulmonary disease which were diagnosed as chronic obstructive pulmonary disease (COPD) after Chest Diseases Department consultation. Kroenke et al. [8] proposed that noncardiac surgery could safely be performed in patients with severe COPD. More recently, Sakai et al. [9] established that female sex, age over 70, smoking, and COPD were independent risk factors for intra and postoperative pulmonary events in upper abdominal surgical operations. Con-sistent with our study, in other studies which were done for upper abdominal operations other than renal surgeries, chronic pulmonary disease was reported to be an important risk factor for postoperative compli-cations [10, 11, 12, 13]. It is expected that upper abdominal surgeries including renal operations should increase risk of especially pulmonary complications during postoperative period. So, better lung capacity leads to better postoperative outcome in upper abdominal surgeries. Interestingly, all the patients with COPD were under medication for this disease. So, we think that COPD still remains a risk factor independent of chronic medication.
CCI index is based on 19 categories of comorbid-ity [3]. Ather and Nazim [14] evaluated the impact of CCI on overall survival following tumor nephrec-tomy, and identified that CCI had a significant predictive value on overall survival. However, when we searched Medline, we could not reach published data investigating the association between CCI and CPCS in RN cases. When using the CPCS system, most of the patients experience complications rang-ing from analgesic/antiemetic requirement (grade I) to acute renal failure requiring hemodialysis (grade IV) or death (grade V). On univariate analysis, although the P value was not significant (0.09, OR = 1.3), we noticed that patients with higher CCI scores tend to develop postoperative complica-tions. A significant P value was reached when the correlation between CCI and CPCS was evaluated (Fig.1) (P = 0.011, rho value = 0.366, Spearman correlation analysis). However, our sample size is relatively small to give a discrete conclusion.
In our series, death was observed in a 68-year-old man on the postoperative 1st day. DIC was suspected
to be the reason for death with unknown etiology. CPCS system does not necessarily consider pulmon-ary complications. So, any kind and degree of postoperative complications were included and graded in CPCS system. In current study, half of the cases (2 out of 4), who developed postoperative atelectasis, have already had the diagnosis of COPD preoperatively. However, the other 2 cases did not bear any preoperative pulmonary disease or problem. In our opinion, with this series, we cannot conclude that the presence of preoperative pulmonary disease is a significant risk factor for the development of postoperative pulmonary complications.
Potential limitations to this study should be con-sidered. First of all, our cohorts were not performed by a single surgeon. Although complication rates in our study population were not found to be associated with operative time, experience of different surgeons may affect the outcome of surgery. Secondly, the study was retrospective, with the attendant biases routinely introduced in such studies. Prospective trials from large centers should further evaluate especially the correlation of CCI with the complications that would possibly be observed after RN operations. It would also be interesting to investigate CCI as an indepen-dent risk factor for adverse events in other surgical or non-surgical urological procedures. We already tried to identify the prognostic factors that might predict a worse outcome in nonsurvivors compared with survi-vors of Fournier’s gangrene and observed that a high CCI was associated with high mortality [15]. In addition, we noticed that increased respiratory rate, an important sign of pulmonary pathology, was found to be related to worse prognosis in those patients.
In conclusion, presence of chronic (obstructive) pulmonary disease is a strong predictor of postoper-ative complications after radical nephrectomy. Pres-ence of chronic pulmonary disease in a renal tumor patient may increase the risk up to sevenfold. In addition, patients with higher preoperative CCI scores may have higher postoperative complication rates and CPCS grades. Thus, after a RN operation, urooncologists must be alert to the symptoms and signs of postoperative complications in patients with chronic pulmonary diseases and high preoperative CCI scores. Additional studies with larger series may give more conclusive data.
References
1. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96
2. Hakimi AA, Rajpathak S, Chery L, Shapiro E, Ghavamian R (2010) Renal insufficiency is an independent risk factor for complications after partial nephrectomy. J Urol 183: 43–47
3. Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitu-dinal studies: development and validation. J Chron Dis 40:373–383
4. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213
5. Lau WK, Blute ML, Weaver AL, Torres VE, Zincke H (2000) Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 75:1236–1242
6. Nazemi T, Galich A, Sterrett S, Klingler D, Smith L, Balaji KC (2006) Radical nephrectomy performed by open, lap-aroscopy with or without hand-assistance or robotic methods by the same surgeon produces comparable peri-operative results. Int Braz J Urol 32:15–22
7. Han KR, Kim HL, Pantuck AJ, Dorey FJ, Figlin RA, Belldegrun AS (2004) Use of American Society of Anes-thesiologists physical status classification to assess
perioperative risk in patients undergoing radical nephrec-tomy for renal cell carcinoma. Urology 63:841–847 8. Kroenke K, Lawrence VA, Theroux JF, Tuley MR (1992)
Operative risk in patients with severe obstructive pul-monary disease. Arch Intern Med 152:967–971
9. Sakai RL, Abra˜o GM, Ayres JF, Vianna PT, Carvalho LR, Castiglia YM (2007) Prognostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery. Sao Paulo Med J 125:315–321 10. Tisi GM (1979) Preoperative evaluation of pulmonary
function. Validity, indications, and benefits. Am Rev Respir Dis 119:293–310
11. Mohr DN, Jett JR (1988) Preoperative evaluation of pul-monary risk factors. J Gen Intern Med 3:277–287 12. Jackson CV (1988) Preoperative pulmonary evaluation.
Arch Intern Med 148:2120–2127
13. Kroenke K, Lawrence VA, Theroux JF, Tuley MR, Hil-senbeck S (1993) Postoperative complications after tho-racic and major abdominal surgery in patients with and without obstructive lung disease. Chest 104:1445–1451 14. Ather MH, Nazim SM (2010) Impact of Charlson’s
comorbidity index on overall survival following tumor nephrectomy for renal cell carcinoma. Int Urol Nephrol 42:299–303
15. Erol B, Tuncel A, Hanci V, Tokgoz H, Yildiz A, Akduman B, Kargi E, Mungan A (2010) Fournier’s gangrene: over-view of prognostic factors and definition of new prognostic parameter. Urology 75:1193–1198
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