Vol 13 No 01 January-February 2016 2471 REVIEW Effect of Obesity on Prone Percutaneous Nephrolithotomy Outcomes: A Systemic Review Faruk Ozgor,* Burak Ucpinar, Murat Binbay Purpose: With decreased physical activity, growing sedentary lifestyle, and high fat diet, obesity has become a pandemic disease all over the world. In this review, we aim to assess the effect of obesity on prone percutaneous nephrolithotomy. (PNL) outcomes. Materials and Methods: We performed a comprehensive review of the published articles in PubMed®, Medline, Scopus, Cochrane database from January 1, 2004 through June 31, 2015, using the key words; body mass index, obesity, morbid obesity, super obese, urolithiasis, nephrolithiasis, percutaneous nephrolithotomy and percutaneous lithotripsy. Original research articles published in English language with accessibility to the full text article were analyzed for our review. Results: At the end of the evaluation, we found 12 articles in English language, analyzing the effect of obesity on prone PNL outcomes. Except one study, eleven studies were evaluated in this review had a retrospective nature without randomization. Stone free status of patients was in a wide range between 49%-90% in obese patients and 41%-90% in morbid obese patients. Conclusion: PNL is a safe and effective treatment modality for renal stone(s) in obese and morbid obese patients. However, effect of body mass index on PNL outcomes including operation time, fluoroscopy screening time, hos- pitalization time, complications and stone free status are still debatable. Keywords: kidney calculi; complications; surgery; length of stay; nephrostomy; percutaneous; adverse effects; obesity; morbid; operative time; overweight; prospective studies. INTRODUCTION According to World Health Organization.(WHO), obesity is described as a body mass index. (BMI) greater than or equal to 30 kg/m2.(1) With decreased physical activity, growing sedentary lifestyle and high fat diet, prevalence of obesity has doubled over last decades and obesity has become a pandemic disease, not only in developed countries, but also all over the world.(2,3) Its well known that, obesity is associated with comorbid conditions such as diabetes mellitus, hyper- tension and nephrolithiasis.(4,5) Additionally, anesthetic and surgical complications are higher in obese patients when compared with normal weight patients.(6) Percutaneous nephrolithotomy (PNL) is a preferred treatment option for renal stone(s) larger than 2 cm and staghorn calculi.(7,8) Although its' minimally invasive nature, PNL procedure has potential serious complica- tions including; bleeding, adjacent organ injuries and urosepsis.(9,10) Moreover, in obese patients, PNL has some technical difficulties.(11) Excessive fat tissue de- crease image quality of fluoroscopy screening and re- duce the accuracy of defining the appropriate calyx or stone during access. Besides, identifying a landmark at the beginning of the operation is complicated in obese patients. Also, accessing to the pelvicaliceal system and dilating the tract is more challenging. Additionally, in- adequate length of working sheath and working instru- ments in obese patients affects adversely on PNL out- comes.(12-14) In this review, we aim to assess the effect of obesity on prone PNL outcomes and try to lead the way for urologists who are planning to perform PNL on obese patients. MATERIALS AND METHODS Before writing this review, we performed a compre- hensive PubMed®, Medline, Scopus, Cochrane data- base investigation of articles published from January 1, 2004 through June 31, 2015, using the key words; BMI, obesity, morbid obesity, super obese, urolithiasis, nephrolithiasis, percutaneous nephrolithotomy and per- cutaneous lithotripsy. All terms are in acordance with Department of Urology, Haseki Research and Training Hospital, Fatih, Istanbul, Turkey. *Correspondence: Department of Urology, Haseki Training and Research Hospital, Fatih, Istanbul, Turkey. Tel: +90 212 5294400. Fax: +90 212 5896229. E-mail: md.farukozgor@yahoo.com. Received: June 2015 & Accepted: September 2015 Table 1. Preoperative Characteristics in different study. Studies Body Mass Index Patients Mean BMI Age, years Male ASA ≥ 3 Stone size(cm) Single stone Multiple Stones Previous Surgery Alyami et al.(29) Normal (< 25) 39 NA 55 23 NA 2.3 NA NA 17 Overweight 24 NA 60 10 NA 2.3 NA NA 9 Obese (30-39) 41 NA 60 15 NA 2.2 NA NA 19 Morbid obese 10 NA 53 5 NA 2.4 NA NA 4 P value .1* .2** .9* .5** Bagrodia et al.(21) Normal (< 25) 26 NA 58 NA 8 1.7 13 13 10 Overweight 44 NA 54 NA 13 1.6 14 30 33 Obese (30-39) 51 NA 53 NA 19 1.8 19 32 31 morbid obese 29 NA 45 NA 12 2.3 11 18 18 P value .06 .7 .61 .51 .03 Fuller et al.(22) Normal (< 25) 1394 NA Na 755 98 NA 581 813 NA Overweight 1568 NA Na 970 108 NA 683 885 NA Obese (30-39) 650 NA Na 335 123 NA 260 390 NA Super (≥ 40) 97 NA Na 32 60 NA 37 60 NA P value < .001 < .001 .591 El-Assym et al.(30) Normal (< 25) 270 NA 46.5 ± 10.9 176 Na 2.5 ± 0.8 98 172 NA Overweight 235 NA 47 ± 10.9 220 Na 2.5 ± 0.7 121 204 NA Obese (30-39) 468 NA 46.9 ± 10.5 302 Na 2.4 ± 0.8 172 296 NA Morbid obese 92 NA 46.5 ± 10 43 Na 2.5 ± 0.8 44 48 NA P value .75 .003 .76 .43 Keheila et al.(15) Super (≥ 50) 17 57.2 54.8 6 2.7 3.3 Na Na Na P value Koo et al.(23) Normal (< 25) 65 22.1 50 35 7 NA NA NA NA Overweight 79 27.5 56 54 13 NA NA NA NA Obese (30-39) 67 33.8 56 55 7 NA NA NA NA Morbid obese 12 43.9 51 6 4 NA NA NA NA P value Kuntz et al.(14) Normal (< 25) 55 22.40 58 22 21 NA 18 26 NA Overweight 74 27.40 51 37 19 NA 23 27 NA Obese(30-35) 67 32 52 35 28 NA 26 31 NA Morbid obese 72 40.5 29 31 34 NA 23 43 NA P value < .001 .123 0.47 < .001 0.01 Ortiz et al. (28) Normal (< 25) 77 22.70 51.9 ± 15.8 40 NA NA 70 7 10 Overweight 93 27.30 56.2 ± 13.3 56 NA NA 84 9 10 Obese (30-39) 75 33.7 54.7 ± 12.1 40 NA NA 64 11 7 Morbid obese 10 44.1 58.4 ± 11.2 3 NA NA 7 3 2 P value < .01 .24 .24 .72 .1 Sergeyev et al.(16) Normal (< 25) 15 22.65 57.93 NA NA NA NA NA NA Overweight 33 27.60 52.82 NA NA NA NA NA NA Obese (≥ 30) 37 36.28 52.46 NA NA NA NA NA NA P value .41 Shohab et al. Normal (< 24) 47 NA 43.29 ± 1.69 NA NA 2.546 ± 0.89 NA NA NA Overweight (24-30) 56 NA 47.08 ± 1.29 NA NA 2.801 ± 0.84 NA NA NA Obese (≥ 30) 26 NA 43.61±1.25 NA NA 2.684 ± 0.74 NA NA NA P value Simsek et al. Normal (< 25) 849 NA 38.19 ± 14.1 490 215 NA 375 474 NA Overweight 883 NA 46.39 ± 12.9 510 205 NA 392 491 NA Obese (30-39) 334 NA 49.52 ± 12.8 217 83 NA 121 213 NA Morbid obese 36 NA 50.22 ± 11.1 20 10 NA 15 21 NA P value .001 .102 .896 .059 Tomaszewski et al. Normal (< 25) 61 NA 52.6 NA NA 3.6 NA NA NA Overweight 45 NA 57.4 NA NA 3.1 NA NA NA Obese (30-34.9) 43 NA 53 NA NA 3.7 NA NA NA Morbid obese 38 NA 53 NA NA 3.9 NA NA NA P value .34 .70 *ANOVA, **Logistics Regression Analysis Review 2472 Obesti and PCNL outcome-Ozgor et al. Vol 13 No 01 January-February 2016 2473 Table 2. Operative characteristics in different studies. Obesti and PCNL outcome-Ozgor et al. Studies Body Mass Index Patients Operation time Complications, % Multiple Accesses Alyami et al. Normal (< 25) 39 44.6 7 NA Overweight 24 43.4 8 NA Obese (30-39) 41 47 2 NA Morbid Obese 10 55 0 NA P value .3 .55 Bagrodia et al. Normal (< 25) 26 NA 26 4 Overweight 44 NA 11 7 Obese(30-39) 51 NA 19 5 Morbid obese 29 NA 17 5 P value .42 .76 Fuller et al. Normal (< 25) 1394 NA 5 112 Overweight 1568 NA 7 112 Obese (30-39) 650 NA 5 44 Super (≥ 40) 97 NA 4% 6 p value 2/0, /5.8* < .001 El-Assym et al. Normal (<25) 270 69.8 ± 32.4 NA NA Overweight 235 71.4 ± 28.7 NA NA Obese (30-39) 468 68.5 ± 29.6 NA NA Morbid obese 92 77.2 ± 32.4 NA NA P value .45 Keheila et al. Super (≥ 50) 17 106 Na 7 p value Koo et al Normal (< 25) 65 75.2 7 NA Overweight 79 68.8 8 NA Obese (30-39) 67 68.5 14 NA Morbid obese 12 81.4 16 NA P value .35 Kuntz et al. Normal (< 25) 55 NA NA 5 overweight 74 NA NA 6 Obese (30-35) 67 NA NA 3 Morbid Obese 72 NA NA 3 P value .664 Ortiz et al. Normal (< 25) 77 101.7 ± 48.1 0 NA Overweight 93 96.6 ± 41.1 3% NA Obese (30-39) 75 110.2±46.2 4% NA Morbid obese 10 116.0 ± 49.8 0% NA P value .2 .34** Sergeyev et al. Normal (< 25) 15 NA NA NA Overweight 33 NA NA NA Obese (≥ 30) 37 NA NA NA P value Shohab et al. Normal (< 24) 47 128.4 ± 48.61 NA NA Overweight (24-30) 56 126.62 ± 59.75 NA NA Obese 26 129.42 ± 48.61 NA NA P value Simsek et al. Normal (< 25) 849 66.44 ± 26.93 3 184 Overweight 883 65.74 ± 28.69 4 147 Obese (30-39) 334 66.13 ± 28.42 5 56 Morbid obese 36 68.20 ± 24.66 5 7 P value .638 .313 Tomaszewski et al. Normal (< 25) 61 NA NA NA Overweight 45 NA NA NA Obese (30-34.9) 43 NA NA NA Morbid obese 38 NA NA NA P value * Failed access/perforation/hydrothorax, respectively. ** Failure to get access. Table 3. Postoperative Characteristics in different studies. Studies Body Mass Index Patients Stone Free Rate, % Complications Hospital Stay Second Procedure Hb Drop Alyami et al.(29) Normal (< 25) 39 90.0 5 1.6 (0.3) 0 1 Overweight 24 87.0 2 1.9 (0.3) 1 1.8 Obese (30-39) 41 90.0 9 1.5 (0.2) 3 1.2 Morbid obese 10 80.0 20 1.7 (0.3) 1 1.5 P value .8 .1 .59 .3 .13 Bagrodia et al.(21) Normal (< 25) 26 46.0 NA 3 11 NA Overweight 44 50.0 NA 2 19 NA Obese (30-39) 51 53.0 NA 3 18 NA Morbid obese 29 41.0 NA 2 11 NA P value .21 .86 Fuller et al.(22) Normal (< 25) 1394 77.5 1 NA 12 NA Overweight 1568 79.7 2 NA 9 NA Obese (30-39) 650 78.9 18 NA 98 NA Super (≥ 40) 97 65.6 21 NA 27 NA P value .009 .707 < .001 El-Assym et al.(30) Normal (< 25) 270 83.70 6 3.4 ± 2.6 70 1.3 ± 1.4 Overweight 235 86.70 9 3.3 ± 3 75 1.1 ± 1.3 Obese (30-39) 468 84.80 5 3.3 ± 2.5 114 1.3 ± 1.4 Morbid obese 92 84.70 7 3.1 ± 2 16 1.1 ± 1.4 P value .38 .66 .38 .6 .13 Keheila et al.(15) Super (≥ 50) 17 76.0 23 4.5 4 1.2 P value Koo et al.(23) Normal (< 25) 65 79.0 10 5.4 NA 1.1 Overweight 79 76.0 13 6.5 NA 1.4 Obese (30-39) 67 79.0 8 6.1 NA 1.1 Morbid obese 12 83.0 8 5.1 NA 1.5 P value .93 .91 .17 Kuntz et al.(14) Normal (< 25) 55 45.0 18 NA NA NA Overweight 74 36.0 21 NA NA NA Obese (30-39) 67 49.0 19 NA NA NA Morbid obese 72 41.0 16 NA NA NA P value .864 .89 Ortiz et al.(28) Normal (< 25) 77 76.60 31 5.2 ± 3.4 9 1.9 ± 1.9 Overweight 93 68.80 35 5.7 ± 4.1 16 2.2 ± 2.0 Obese (30-39) 75 78.70 29 5.2 ± 4.6 15 1.4 ± 1.4 Morbid obese 10 90.0 10 5.3 ± 3.1 2 1.0 ± 1.4 P value .29 .39 .84 .59 .02 Sergeyev et al.(16) Normal (< 25) 15 93.0 NA 5.40 1 2.31 Overweight 33 100.0 NA 3.64 0 2.25 Obese (≥ 30) 37 89.0 NA 3.70 4 2.29 P value .01 .98 Shohab et al. Normal (< 24) 47 91.18 6 3.00 ± 1.04 NA NA Overweight (24-30) 56 89.62 8 3.00 ± 1.17 NA NA Obese 26 90.23 23 3.03 ± 1.82 NA NA P value Simsek et al. Normal (< 25) 849 83.0 1 2.86 ± 1.56 NA NA Overweight 883 80.9 1 2.90 ± 1.93 NA NA Obese (30-39) 334 80.2 1 1.70 ± 1.58 NA NA Morbid Obese 36 86.1 2 2.81 ± 0.98 NA NA P value Tomaszewski et al. Normal (< 25) 61 80.6 NA 3.4 NA 6.2 (Htc) Overweight 45 76.9 NA 2.4 NA 7.3 (Htc) Obese (30-34.9) 43 77.0 NA 3 NA 6.5 (Htc) Morbid obese 38 78.9 NA 2.6 NA 5.3 (Htc) P value .82 .53 .22 Review 2474 Obesti and PCNL outcome-Ozgor et al. Abbreviations: Hb, hemoglobin; Htc, hematocrit; NA, not applicable. Vol 13 No 01 January-February 2016 2471Vol 13 No 01 January-February 2016 2475 the definitions reported in the PRISMA Statement for reviewers (Figure). Two collaborators (FO and BU) independently reviewed all of the articles and data dis- agreement was resolved by a third reviewer or by con- sensus. Original research articles published in English language with accessibility to the full text article were analyzed for our review. Studies evaluating only the adult population were enrolled to our review. Addition- ally, we excluded expert opinions, editorials comments, studies evaluating the effect of supine PNL on obese patients, letters to the editor and case reports from our review. Additional citations were identified cautiously by reviewing reference lists of pertinent articles. At the end of the evaluation, we found 12 articles in English language, analyzing the effect of obesity on prone PNL outcomes. Parameters like; total number of patients, BMI, age, male: female ratio, maximum stone diameter or stone burden, American Society of Anesthesiologists (ASA) score and history of previous renal stone surgery were taken into account. Perioper- ative parameters including operation time, fluoroscopy screening time, requirement of multiple access and per- operative complications were evaluated. Also, length of hospital stay, stone free rates, requirement of additional procedures and complications were collected. RESULTS All studies were evaluated in this review had a retro- spective nature without randomization except Clinical Research Office of Endourology Society (CROES) study which had a prospective data collecting design. Additionally, reviewed original articles had different study designs which made it difficult to obtain a cer- tain conclusion about the effect of obesity on PNL out- comes. Nine of the twelve articles were divided patients into four groups; normal weight, overweight, obese and morbid obese. Kuntz and colleagues and Tomaszewski and colleagues accepted obesity range BMI between 30 and 35 kg/m2.(14,15) However, remaining seven articles defined obesity as BMI in the range of 30-39 kg/m2. One study was interested with only results of PNL in super obese patients and super obese was defined as BMI > 50 kg/m2.(16) Another two studies categorized patients who underwent PNL into three groups (normal weight, overweight, obese) and did not analyze morbid obese patients.(17,18) Additionally, the mean BMI of each groups were cal- culated in only five of these studies and as expected, the mean BMI was significantly higher in morbid obese patients. The ASA score of the patients was mentioned in five comparative studies and in two articles the ASA score was significantly higher in obese and morbid obese patients. The mean operation times and means fluoroscopy screening times were given in six and in one comparative studies, respectively, without any stat- ically significant difference (Tables 1 and 2). Stone free status of patients was in wide range between 49%-90% in obese patients and 41%-90% in morbid obese patients. However, when each study evaluated in their own study groups, there was no statistically signif- icant difference in stone free rates. Similarly, post-op- erative complications were not significantly different in morbid obese and obese patients when compared with normal weight and over weight patients. The results of the included studies from the literature for our review are summarized in Table 3. DISCUSSION With increasing BMI, metabolic disorders such as hy- percalciuria, hyperoxaluria, hyperinsulinemia and low urine volume are more commonly seen and these condi- tions are also strong risk factors for stone formation.(19) Because of all these, obese and morbid obese patients are more likely to face with renal stone disease. Al- though, extracorporeal shock wave lithotripsy (SWL) is accepted as one of the first line treatment modalities for kidney stones < 20 mm, according to the guidelines, Obesti and PCNL outcome-Ozgor et al. Figure. PRISMA Chart. longer skin to stone distance (SSD) and difficulties in focusing the stone under ultrasonography or fluorosco- py guidance reduces SWL success rates in obese pa- tients.(20) On the other hand, several studies mentioned that effectiveness of Flexible ureterorenoscopy (f-URS) was decreased and requirement of second intervention is increased with the increase in stone size.(21,22) Mul- tiple interventions may lead to more anesthetic usage and surgical complications in obese patients. Recently, PNL still remains one of the most important treatment options for renal stone treatment. In obese patients, anesthetic and pre-surgical problems can be challenging for urologists. Five studies evaluat- ed the ASA score of patients who underwent PNL and two of them had demonstrated patients with > 3 ASA score were more common in obese and morbid obese patients.(14,23-26) Also, complications including atelec- tasis, venous thromboembolism and longer recovery period may be associated with higher ASA scores.(27) Conversely, other two studies failed to show significant difference between groups according to their BMI's. Additionally, changing patients from lithotomy po- sition to prone position requires special attention and more trained personnel, especially in obese patients. Being a center with high stone patients volume, may have resulted in increased experience of surgeons, anes- thetists and personnel that prevent unfortunate pre-op- erative events. Complete clearance of the stone after PNL operation is the most pleasing condition for urologist and also for the patient. Stone free status after PNL in obese pa- tients was surprisingly in a wide range (49%-90% in obese patients and 41%-90% in morbid obese patients) according to the studies in the literature. These differ- ences may due to different defining criteria for the term ‘success’ among different articles. Stone free status ac- cepted as complete clearance of stone and presence of residual fragments by some authors. Other studies ne- glect the presence of residual stone fragments < 5 mm and define these conditions as stone free. Moreover, some authors evaluated stone free status by abdominal computerized tomography and others used intravenous urography (IVU) or ultrasonography.(14,23) It is clear that imaging modalities have different sensitivities in detecting stone(s) and this difference may lead to mis- interpretation of the results.(28,29) However, when each study is evaluated on its own, no difference was detect- ed in groups with different BMI's. The mean operation time was given in four compara- tive studies and all of them demonstrated significantly longer operation time in morbid obese patients. Howev- er, the differences were not statically significant. More- over, none of these studies had given an exact defini- tion of operative time. To our knowledge, some authors accepted operation time from beginning of anesthesia to nephrostomy tube placement but others accepted op- erative time from access attempt to nephrostomy tube placement.(30) This difference in calculations can lead to confusion when assessing the effect of BMI on PNL op- eration time. We believe that, calculating the operation time from anesthesia induction to the end of the opera- tion is a more reliable approach to identify the effect of high BMI on PNL operation time. Deterioration of image quality of stone and target calyx due to extensive fat tissue in obese patients was men- tioned above. In the light of this information, fluoros- copy screening time is expected to be influenced by BMI. However, only Ortiz and colleagues. discussed fluoroscopy screening time and found that the fluor- oscopy screening time became longer with increasing BMI but their findings were not statistically significant. (31) Radiation exposure to the surgical team and patients is an important issue. Because of high recurrence risk of nephrolithiasis and technical difficulties of PNL in obese patients, longer fluoroscopy screening times are expected and this issue must be assessed carefully in further studies. The mean hospitalization time was similar in six com- parative studies. Only Sergeyev and colleagues had demonstrated a significant difference in between groups according to their BMI's.(17) Surprisingly, patients with normal weight had longer hospitalization times when compared with overweight and obese patients. We believe that longer hospitalization time is associated with operative or post operative complications such as bleeding, fever, adjacent organ injuries instead of tech- nical difficulties. Sergeyev and colleagues and and col- leagues did not mention about their complications after PNL in details. The hospitalization time was longer in Koo and colleagues and Ortiz and colleagues studies and as expected, their complication rates were higher when compared with other studies.(25,31) Requirement of additional procedures was discussed in five studies. Alyami and colleagues reported 8% and 10% re-admission rates in obese and morbid obese pa- tients, respectively, but they did not mention about the additional procedures in detail.(32) Sergeyev and col- leagues only mentioned about second-look PNL after initial procedure and they performed it only in five of their patients (1/15 in normal weight patients and 4/37 in morbid obese patients).(17) In Bagrodia's study, need for a second look PNL rates were 35% and 38% in Review 2476 Obesti and PCNL outcome-Ozgor et al. Vol 13 No 01 January-February 2016 2477 obese and morbid obese patients, respectively, much higher when compared with Sergeyev and colleagues study.(23) However, there was no statistically significant difference in between groups. Similarly, requirement of second procedures including PNL, URS and SWL, were similar between groups in both El-Assmy and col- leagues and Ortiz and colleagues studies.(31,33) Bleeding is one of the most serious complications of PNL procedure, 2%-45% and 0.8% of patients required blood transfusion and angioembolization, respective- ly.(34) All studies analyzed the hemoglobin drop after PNL procedure and there was no association between bleeding rates and BMI values of the patients. Obesity seems to be a technical challenge for urologists while performing access into the calyceal system. We believe that bleeding complication rates are associated with the experience of the surgeon, applying multiple accesses into the system and history of previous surgeries, in- stead of technical difficulties during PNL surgery. It is quite complicated to assess the effect of obesity and morbid obesity on prone PNL complications due to different classification systems in different studies. Or- tiz and colleagues used Clavien complication classifica- tion to categorize complications.(31) However, Koo and colleagues classified their complications as minor and major complications.(25) Differently, El-Assmy did not categories the complications under subgroups, instead, they listed all the complications separately.(33) Due to this different classification system, it is quite difficult to assess all the studies and come up with a certain re- sult. However, when we assess all the studies separate- ly, complication rates were not statistically significant between different BMI groups. CONCLUSIONS PNL is a safe and effective treatment modality for renal stone(s) in obese and morbid obese patients. However, effect of body mass index on PNL outcomes including operation time, fluoroscopy screening time, hospitali- zation time, complications and stone free status are still debatable. 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