1 2 3 4 5 6 7 8 9 10 11 Q4 Q1 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
Surgery for Obesity and Related Diseases ] (2014) 00–00
Original article
Laparoscopic gastric plication in morbidly obese adolescents: a prospective study Atefeh Zeinoddini, Reza Heidari, Mohammad Talebpour* Laparoscopic Ward, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Received October 18, 2013; accepted February 24, 2014
Abstract
Background: The prevalence of obesity has increased rapidly among adolescents. Bariatric surgery is associated with significant weight loss and improvement in obesity related co-morbidities, but may be associated with serious complications. Therefore, attempts on finding a safe and effective bariatric procedure for adolescents are ongoing. The objective of this study was to evaluate safety and efficacy of laparoscopic gastric plication (LGP) on adolescents. Method: A prospective study was performed on adolescents who underwent LGP from 2007– 2013. Measured parameters included the percentage of excess weight (%EWL), percentage of body mass index loss (%BMIL), obesity related co-morbidities, operative time, and length of hospitalization and complications. Results: LGP was performed in 12 adolescents (9 female and 3 male). Mean (SD) age of the patients was 13.8 ⫾ 1 year. Mean preoperative weight and BMI were 112.4 ⫾ 19.7 kg and 46.0 ⫾ 4 kg/m2, respectively. Mean (SD) %EWL and %EBMIL were 68.2 ⫾ 9.9% and 79.0 ⫾ 9.0%, respectively after 2 years. All medical co-morbidities were improved after LGP. There were no deaths. One patient required replication 4 days postoperatively due to obstruction at the site of the last knot. No other major complications were observed. No patient required rehospitalization. Conclusion: LGP has the potential of being an ideal weight loss surgery for adolescents, resulting in excellent weight loss and minimal psychological disruption. It is associated with a minimal risk of leakage, bleeding, and nutritional deficiency. However, large well-designed studies with long-term follow-up are needed. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
Keywords:
Laparoscopy; Adolescent; Morbid obesity; Gastric placation
The prevalence of obesity has increased rapidly both in adults and adolescents, making it a significantly alarming disease. It is estimated that 18.4% of 12- to 19-year-old individuals in the United Stated are obese [1]. Obesity is associated with both physical and psychological health consequences including diabetes mellitus (DM), hypertension, dyslipidemia, social marginalization, reduced quality * Correspondence: Mohammad Talebpour, M.D., Tehran University of Medical Science, Laparoscopic Ward, Sina Hospital, Imam Khomeini St, Tehran, Iran. E-mail: [email protected]
of life, and depression [2–6]. According to a recent prospective study, 60 of 79 (70.5%) severely obese adolescents in 1996 were still severely obese as adults in 2009, indicating that the majority of obese adolescents carry the risk to their adulthood [7]. Obesity in children and adolescents is often managed through nonsurgical multidisciplinary approaches, including dietary modification, behavioral therapy, physical activity, and pharmacotherapy. These treatments may provide clinically significant weight loss. However, they are associated with unsatisfactory longterm weight loss and high rates of drop out [8,9]. Data has shown that obese adolescents, especially those with severe
http://dx.doi.org/10.1016/j.soard.2014.02.039 1550-7289/r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71
2
72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126
A. Zeinoddini et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
co-morbidities, might benefit from weight loss surgery. Laparoscopic Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), and laparoscopic sleeve gastrectomy (LSG) have resulted in promising sustainable weight loss and significant improvement in obesity-related co-morbidities in morbidly obese adolescents [10,11]. Laparoscopic gastric plication (LGP), a new restrictive procedure, which has been shown to be a safe and effective bariatric operation in a few early studies, is increasing in popularity in the treatment of morbid obesity [12,13]. In a recent randomized controlled trial study, LGP and laparoscopic mini gastric bypass provided similar weight loss at 1-year follow-up [13]. LGP is relatively similar to LSG; in both procedures, a narrow gastric tube is generated. However, in LGP procedure, the gastric capacity is preserved by folding the stomach into itself through sutures, resulting in minimal risk for nutritional deficiency, leakage, and bleeding. Therefore, we hypothesized that LGP could be an appropriate bariatric procedure for adolescents without gastric resection or the use of a foreign body as with LAGB. In this study, we evaluated the safety and efficacy of LGP for morbidly obese adolescents. Methods This prospective study was performed between 2007 and 2013 by 1 surgeon in Sina Hospital (a University Hospital of Tehran University of Medical Sciences) and Laleh Hospital (a private hospital). Approval was obtained from the ethical committee of the university before conducting the study. All patients and their parents were provided with enough information regarding the management of morbid obesity in adolescents, different types of bariatric surgical procedures, potential complications, the success rate of each procedure, the investigational nature of the LGP, possibility of weight regain, and the scarcity of information on the outcomes of LGP in adolescents. Informed consent was obtained from all patients and their parents. All adolescents underwent a multidisciplinary evaluation by the health professional group, consisting of a psychologist, nutritionist, endocrinologist, surgeon, and health educator. Inclusion criteria were age under 18, body mass index (BMI) 4 40 kg/m2 or BMI 4 35 kg/m2 with co-morbidity, history of unsuccessful weight loss attempts (failure to lose 10% of baseline weight despite a minimum of 6 months participation in a formal weight loss program), gaining 4 20% of their excess weight during the last preoperative year (indicating a high risk of incremental progression in excess weight), confirmation by a psychologist regarding the patient’s decisional capacity, adequate motivation and cooperation with postoperative diet, lifestyle change, follow-up visits, and family support. Patients with previous history of bariatric or antireflux surgery were excluded. Demographic characteristics included their preoperative
age, gender, weight, BMI and obesity related comorbidities. The criteria for the diagnosis and treatment of comorbidities were as follows: Hypertension was defined as systolic blood pressure (SBP) Z 140 mm Hg, diastolic blood pressure (DBP) Z 90 mm Hg or being under hypertensive drugs. Prehypertension was diagnosed if 120 r SBP o 139 mm Hg or 80 r DBP o 89 mm Hg. Remission was defined as SBP o 120 mm Hg and DBP o 80 mm Hg without any medication. Diabetes (DM) was diagnosed if fasting blood glucose (FBG) Z 126 mg/dL, 2-hour postload glucose (2 HPLG) Z 200 mg/dL or medical treatment was received. Prediabetes was diagnosed if 100 r FBG o 126 or 140 r 2 HPLG o 200. Remission was defined as FBG o 100 mg/dL, 2-hour postload glucose o 140 mg/dL. Dyslipidemia was diagnosed if the cholesterol (chol) Z 200 mg/dL, triglyceride Z 130 mg/dL, LDL-C 4 130 mg/dL, HDLC o 35 mg/dL or being under medication. Remission was defined as chol, triglyceride and LDL-C levels below the cut-off point, and HDL-C level higher than the cut-off point with no medications. Symptoms of gastroesophageal reflux disease were diagnosed in the presence of heartburn and symptoms of acid reflux or the use of acid reduction medications. Remission was defined as complete absence of symptoms without medication. Symptoms of sleep apnea were diagnosed by a positive response to enquiry about frequent breathing pauses during sleep and daytime sleepiness. Remission of symptoms was established when breathing pauses during sleep were no longer experienced. Depression was diagnosed as a children inventory score Z 20, and remission was defined as children inventory score less than the cut-off point. Irregular menstruation was diagnosed if menstrual cycles were o21 days or 435 days. Remission was defined as normal menstrual cycle length (21–35 days) under no oral contraceptive or hormonal medication. Eligible patients underwent LGP and were included in the study consecutively. Intervention All procedures were performed by a single surgeon. All patients underwent 2-row gastric plication as previously described. In brief, dissection was started at the greater curvature of the stomach in contact to the gastric wall from prepyloric area to 2-cm proximal to the Hiss angle preserving the anatomy of Hiss angle. All vessels along the greater curvature were separated using LigaSure (Covidien, Mansfield, MA, USA). The greater curvature (from the perimeter) was invaginated using 2 rows of 00 prolene or 00 nylon sutures. Two layers of plication were performed with continuous sutures with 1 surgical sting in all patients to prevent any displacement of inverted folds such as eversion outside or intussusception into esophagus or pylorus. All sutures were extramucusal to avoid their absorption by
127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181
Laparoscopic Gastric Plication in Adolescents / Surgery for Obesity and Related Diseases ] (2014) 00–00
Q3
182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236
gastric acid. Finally, a tube shaped stomach was achieved in which the greater curvature was inverted in to the stomach [13,14]. Postoperative care and follow-up Patients were discharged once liquid food was tolerated. Patients were advised to use soft liquids during the first 6 postoperative weeks. During the first postoperative year, clinical visits were made every 2 weeks in the first 6 months and monthly thereafter. Patients were visited and assessed every 2 months during the second postoperative year and annually afterwards. At each follow-up visit, patients were carefully monitored regarding possible postoperative complications, weight and height status, and obesity comorbidities. Weight-related calculation Weight loss was assessed by calculating: BMI (weight [kg]/height2[m2]), excess BMI (EBMI) (preoperative BMI – ideal BMI [BMI for 85th percentile for age- and genderspecific healthy weight]) and its percentage (%EBMIL) (preoperative BMI-BMI in each visit / EBMI), excess weight (preoperative weight – ideal weight [weight specifying for 85th percentile of BMI for the patient’s gender, age, and height]), percent of excess weight loss (%EWL) (preoperative weight – weight at each visit /excess weight 100%). %EWL o 25% was considered as treatment failure while success was defined as %EWL Z 25%. Statistical analysis Statistical Package of Social Science software (SPSS version 16, IBM Company, USA) was used for statistical analysis. Mean ⫾ SD of continuous variable and frequency of categorical variables are reported. Paired t test and independent t test were used for comparison. A P o .05 was considered statistically significant. Results LGP was performed in 12 adolescents (9 female and 3 male). Mean (SD) age of patients was 13.8 ⫾ 1 year (median: 13, range: 11–17). Mean preoperative weight and BMI were 112.4 ⫾ 19.7 kg (range 89–148 kg) and 46.0 ⫾ 4 kg/m2 (range: 39.3–56.9), respectively. Eight patients suffered from 1 or more preoperative comorbidity. Preoperative co-morbidities included prehypertension in 1 adolescent, DM in 2, prediabetes in 2, dyslipidemia in 1, irregular menstrual cycles in 2, depression in 3, and symptoms of obstructive sleep apnea in 2. Operative time and hospital stay were 61 ⫾ 14 min (range 41–88 min), and hospital stay ranged between 2 and 5 days. All procedures were successfully completed in all patients. No mortality was observed. After the surgery, 1 patient
3
Table 1 Weight loss and clinical outcomes of the procedures %EWL at 6 ⫾ .5 mo follow-up, n (12) %EWL at 12 ⫾ 1 mo follow up, N (10) %EWL at 24 ⫾ 1 mo follow up, N (9) %EWL at 36 ⫾ 2 mo follow up, N (9) %EWL at 48 ⫾ 2 mo follow up, N (4) %EBMIL at 6 ⫾ .5 mo follow up, N (12) %EBMIL at 12 ⫾ 1 mo follow up , N (10) %EBMIL at 24 ⫾ 1 mo follow up, N (9) %EBMIL at 36 ⫾ 2 mo follow up, N (9) %EBMIL at 48 ⫾ 2 mo follow up, N (4) Failure (%EWL o 30% at 12 mo postup)
55.2 ⫾ 10.5 [%] (range 37–72%) 63.6 ⫾ 9.5 [%] (range 42–83%) 68.2 ⫾ 9.9 [%] (range 57–88%) 68.5 ⫾ 11.9 [%] (range 56–97%) 62.1 ⫾ 10.7 [%] (range 51–74%) 60.1 ⫾ 10.0 [%] (range 41–77%) 70.5 ⫾ 9.5 [%] (range 60–90%) 79.0 ⫾ 9.0 [%] (range 68–98%) 80.6 ⫾ 13.5 [%] (range 57–106%) 76.7% ⫾ 18.4 [%] (range 53–98%) 0
%EBMIL ¼ percent of excess body mass index loss; %EWL ¼ percent of excess weight loss; n ¼ number of patients
experienced severe vomiting and reflux, in whom obstruction at the distal part of LGP was confirmed with a gastrografin upper gastrointestinal radiography. At the 4th postoperative day, all sutures were undone and replication was performed using guide bougie no. 32 at the same session, to prevent future obstruction, and vomiting and reflux were relieved immediately afterwards. Temporary vomiting was observed in 1 patient, and epigastric pain was manifested in 1 individual. However, both conditions resolved spontaneously after few days. One patient experienced gastroesophageal reflux disease 1 month postoperatively, which resolved spontaneously 3 months after surgery; all patients experienced %EWL Z 50% after 6 months. Values for %EWL and %EBMIL at 6 months and 1, 2, 3, and 4 years postoperatively are summarized in Table 1. No patient was lost to follow-up. Some adolescents had recently undergone LGP with o2 years of follow-up visits available. Nine patients (out of the 12) had 2 years of follow up visits. Mean (SD) %EWL and %EBMIL at 2 years postoperatively were 68.2 ⫾ 9.9% and 79.0 ⫾ 9.0, respectively. Remission of all medical co-morbidities was observed during the follow-up period. Discussion Obesity has increased considerably in children and adolescents. Conservative management usually does not provide sustainable sufficient weight loss and is associated with high rate of drop out [8,9]. Bariatric surgery, which is associated with considerable weight loss, is gaining popularity for the treatment of morbid obesity in adolescents.
237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 T1 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291
4
292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346
A. Zeinoddini et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
The application of bariatric surgery in adolescents has tripled between 2000 and 2003 [15]. This is the first report of LGP in adolescents. Although bariatric procedures usually provide considerable and sustainable weight loss in adolescents, concern regarding their potential serious complications remains. RYGB and LAGB are the 2 most commonly weight loss procedures that have been performed in adolescents. However, according to a systematic review and meta-analysis of bariatric surgery in pediatric patients, 8% (28/352) of patients who underwent LAGB needed reoperation to correct complications, including band slippage, intragastric band migration, gastric dilation, psychological intolerance of the band, tubing crack, and hiatal hernia. In their review of 140 patients who underwent RYGB, there was 1 death and 8 life-threatening complications, including shock, pulmonary embolism, severe malnutrition, immediate postoperative bleeding, and gastrointestinal obstruction. Three additional patients died, which were not directly related to RYGB. Finally, they concluded that bariatric surgeries are associated with sustained and clinically significant weight loss in pediatrics. However, they may lead to severe complications [10]. Therefore, attempts on finding a bariatric procedure, which provides significant weight loss with a minimal risk of complications, is ongoing. LGP is a recently developed restrictive bariatric operation, which limits the gastric volume by invaginating the greater curvature of the stomach rather than gastric resection. The present study found LGB to be safe and effective in the medium term treatment of morbid obesity and obesity related co-morbidities in adolescents. We reported % EBMIL for weight loss, as adolescent height increased % EWL is believed not be to be an ideal predictor of weight loss in adolescents [16]. To provide an easier comparison between our findings with other reports, % EWL is also reported here. %EBMIL at 2 and 4 years postoperatively were 79.0% and 76.7%, respectively, and mean %EWL were 63%, 68%, 68%, and 62% at 1, 2, 3, and 4 years follow-up visit, respectively. No failure (%EWL o 50%) occurred during the follow-up period, and all cases experienced %EWL 450%. LGP provided weight loss comparable to other bariatric procedures in adolescents [17–19]. Furthermore, in the present study, there were no deaths or the need for rehospitalization. Considering the less-invasive nature of LGP compared to other bariatric procedures, postoperative complications in this study were minimal. In a systematic review of 307 adults who underwent LGP, no deaths were reported and with complications occurring in 8% of patients [20]. Herein, all obesity related comorbidities improved after LGP, and did not reappear during the follow-up period. The authors believe that LGP might be an ideal weight loss procedure for adolescents. Despite its safety and efficacy, some other concerns should be considered while choosing an appropriate bariatric procedure for adolescents. Informed consent taken from
an adolescent remains a challenging issue; even with good decision making capacity confirmed by a psychologist, some patients who undergo bariatric surgery may later come to regret it [10]. Therefore, an ideal bariatric procedure for adolescents should be reversible [10]. Although LAGB could be easily removed, it is associated with some drawbacks. Possible foreign device-related complications include device-related infection and band slippage. Furthermore, considering the limited lifetime of mechanical devices, adolescents may need to undergo device replacement several times during their lifetime. Some studies reported high reoperation rates after LAGB. O’Brien et al. [21] in a randomized controlled trial comparing LAGB with a supervised lifestyle intervention in 50 adolescents, reported that revisional procedures were needed in 8 (33%) during a 2-year follow-up period, which were mostly due to proximal pouch dilation and tubing injury [21]. Furthermore, it should be mentioned that all patients undergoing LAGB remain at risk for eventual failure. LGP is a potentially reversible procedure; however, it does not need foreign body placement nor adjustment. One of the important characteristics of an optimal weight loss surgery includes minimal risk of nutritional deficiency, especially in children and adolescents, and not interfere with physical growth [10]. Children and adolescents may have lower compliance to postoperative regimes compared to adults. In 1 study, only 13% of pediatric patients continued using nutritional supplements as instructed [22]. According to a systematic review on weight loss operations in adolescents, protein-calorie malnutrition and micronutrient deficiency were the most frequent complications after RYGB [10]. Remarkably, there were no nutritional deficiencies seen in this small group of adolescents after LGP, since no section of the gastrointestinal system was bypassed or resected. LSG, a restrictive bariatric procedure, has shown promising shortterm results in adolescents. However, a portion of the stomach is permanently removed during LSG; it is accompanied with the risk of leakage or bleeding along the stomach stapling edges. Furthermore, as a portion of stomach is removed, it is irreversible. The advantages of the present study include its prospective nature, as well as the consecutive inclusion of all eligible patients and no loss to follow-up. Contrariwise, some limitations are encountered in this study including its small sample size and uncertain reproducibility. Finally, due to the small sample size, we remained within the limits of drawing a more comprehensive conclusion. Conclusion The present study provided evidence that LGP could be an ideal conservative weight loss surgical procedure for adolescents, providing optimal weight loss. Nonetheless,
347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401
Laparoscopic Gastric Plication in Adolescents / Surgery for Obesity and Related Diseases ] (2014) 00–00
Q3
402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 Q5 431 432 433
larger well-designed studies with long follow-up periods are warranted to draw a comprehensive conclusion. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. References [1] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA 2012;307:483–90. [2] Choudhary AK, Donnelly LF, Racadio JM, Strife JL. Diseases associated with childhood obesity. Am J Roentgenol 2007;188: 1118–30. [3] Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350: 2362–74. [4] Strauss RS, Pollack HA. Social marginalization of overweight children. Arch Pediatr Adolesc Med 2003;157:746–52. [5] Schwimmer JB, Burwinkle TM, Varni JW. Health-related quality of life of severely obese children and adolescents. JAMA 2003;289: 1813–9. [6] Goldfield GS, Moore C, Henderson K, Buchholz A, Obeid N, Flament MF. Body dissatisfaction, dietary restraint, depression, and weight status in adolescents. J Sch Health 2010;80:186–92. [7] The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P. Association of adolescent obesity with risk of severe obesity in adulthood. JAMA 2010;304:2042–7. [8] Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005;293:2873–83. [9] Whitlock EP, O’Conner EA, Williams SB, Beil TL, Lutz KW. 2010. [10] Treadwell JR, Sun F, Schoelles K. Systematic review and metaanalysis of bariatric surgery for pediatric obesity. Ann Surg 2008;248: 763–76.
5
[11] Alqahtani AR, Antonisamy B, Alamri H, Elahmedi M, Zimmerman VA. Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years. Ann Surg 2012;256:266–73. [12] Talebpour M, Amoli BS. Laparoscopic total gastric vertical plication in morbid obesity. J Laparoendosc Adv Surg Tech A 2007;17:793–8. [13] Darabi S, Talebpour M, Zeinoddini A, Heydari R. Laparoscopic gastric plication versus mini-gastric bypass surgery in the treatment of morbid obesity: a randomized clinical trial. Surg Obes Relat Dis 2013;9:914–9. [14] Talebpour M, Motamedi SM, Talebpour A, Vahidi H. Twelve year experience of laparoscopic gastric plication in morbid obesity: development of the technique and patient outcomes. Ann Surg Innov Res 2012;6:7. [15] Tsai WS, Inge TH, Burd RS. Bariatric surgery in adolescents: recent national trends in use and in-hospital outcome. Arch Pediatr Adolesc Med 2007;161:217–21. [16] Cole TJ, Faith MS, Pietrobelli A, Heo M. What is the best measure of adiposity change in growing children: BMI, BMI %, BMI z-score or BMI centile? Eur J Clin Nutr 2005;59:419–25. [17] Inge TH, Miyano G, Bean J, et al. Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk factors after surgical weight loss in adolescents. Pediatrics 2009;123:214–22. [18] Scheimann AO, Nadler EE, Driscoll DJ, et al. Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years by Alqahtani AR, Antonisamy B, Alamri H, Elahmedi M, Zimmerman VA. Ann Surg. Epub 2013 Sep 16. [19] Al-Qahtani AR. Laparoscopic adjustable gastric banding in adolescent: safety and efficacy. J Pediatr Surg 2007;42:894–7. [20] Abdelbaki TN, Huang CK, Ramos A, Neto MG, Talebpour M, Saber AA. Gastric plication for morbid obesity: a systematic review. Obes Surg 2012;22:1633–9. [21] O'Brien PE, Sawyer SM, Laurie C, et al. Laparoscopic adjustable gastric banding in severely obese adolescents: a randomized trial. JAMA 2010;303:519–26. [22] Rand CS, Macgregor AM. Adolescents having obesity surgery: a 6-year follow-up. South Med J 1994;87:1208–13.
434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465
Surgery for Obesity and Related Diseases ] (2014) 00–00
Original article
Laparoscopic gastric plication in morbidly obese adolescents: a prospective study Atefeh Zeinoddini, Reza Heidari, Mohammad Talebpour* Laparoscopic Ward, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Received October 18, 2013; accepted February 24, 2014
Abstract
Background: The prevalence of obesity has increased rapidly among adolescents. Bariatric surgery is associated with significant weight loss and improvement in obesity related co-morbidities, but may be associated with serious complications. Therefore, attempts on finding a safe and effective bariatric procedure for adolescents are ongoing. The objective of this study was to evaluate safety and efficacy of laparoscopic gastric plication (LGP) on adolescents. Method: A prospective study was performed on adolescents who underwent LGP from 2007– 2013. Measured parameters included the percentage of excess weight (%EWL), percentage of body mass index loss (%BMIL), obesity related co-morbidities, operative time, and length of hospitalization and complications. Results: LGP was performed in 12 adolescents (9 female and 3 male). Mean (SD) age of the patients was 13.8 ⫾ 1 year. Mean preoperative weight and BMI were 112.4 ⫾ 19.7 kg and 46.0 ⫾ 4 kg/m2, respectively. Mean (SD) %EWL and %EBMIL were 68.2 ⫾ 9.9% and 79.0 ⫾ 9.0%, respectively after 2 years. All medical co-morbidities were improved after LGP. There were no deaths. One patient required replication 4 days postoperatively due to obstruction at the site of the last knot. No other major complications were observed. No patient required rehospitalization. Conclusion: LGP has the potential of being an ideal weight loss surgery for adolescents, resulting in excellent weight loss and minimal psychological disruption. It is associated with a minimal risk of leakage, bleeding, and nutritional deficiency. However, large well-designed studies with long-term follow-up are needed. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
Keywords:
Laparoscopy; Adolescent; Morbid obesity; Gastric placation
The prevalence of obesity has increased rapidly both in adults and adolescents, making it a significantly alarming disease. It is estimated that 18.4% of 12- to 19-year-old individuals in the United Stated are obese [1]. Obesity is associated with both physical and psychological health consequences including diabetes mellitus (DM), hypertension, dyslipidemia, social marginalization, reduced quality * Correspondence: Mohammad Talebpour, M.D., Tehran University of Medical Science, Laparoscopic Ward, Sina Hospital, Imam Khomeini St, Tehran, Iran. E-mail: [email protected]
of life, and depression [2–6]. According to a recent prospective study, 60 of 79 (70.5%) severely obese adolescents in 1996 were still severely obese as adults in 2009, indicating that the majority of obese adolescents carry the risk to their adulthood [7]. Obesity in children and adolescents is often managed through nonsurgical multidisciplinary approaches, including dietary modification, behavioral therapy, physical activity, and pharmacotherapy. These treatments may provide clinically significant weight loss. However, they are associated with unsatisfactory longterm weight loss and high rates of drop out [8,9]. Data has shown that obese adolescents, especially those with severe
http://dx.doi.org/10.1016/j.soard.2014.02.039 1550-7289/r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71
2
72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126
A. Zeinoddini et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
co-morbidities, might benefit from weight loss surgery. Laparoscopic Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), and laparoscopic sleeve gastrectomy (LSG) have resulted in promising sustainable weight loss and significant improvement in obesity-related co-morbidities in morbidly obese adolescents [10,11]. Laparoscopic gastric plication (LGP), a new restrictive procedure, which has been shown to be a safe and effective bariatric operation in a few early studies, is increasing in popularity in the treatment of morbid obesity [12,13]. In a recent randomized controlled trial study, LGP and laparoscopic mini gastric bypass provided similar weight loss at 1-year follow-up [13]. LGP is relatively similar to LSG; in both procedures, a narrow gastric tube is generated. However, in LGP procedure, the gastric capacity is preserved by folding the stomach into itself through sutures, resulting in minimal risk for nutritional deficiency, leakage, and bleeding. Therefore, we hypothesized that LGP could be an appropriate bariatric procedure for adolescents without gastric resection or the use of a foreign body as with LAGB. In this study, we evaluated the safety and efficacy of LGP for morbidly obese adolescents. Methods This prospective study was performed between 2007 and 2013 by 1 surgeon in Sina Hospital (a University Hospital of Tehran University of Medical Sciences) and Laleh Hospital (a private hospital). Approval was obtained from the ethical committee of the university before conducting the study. All patients and their parents were provided with enough information regarding the management of morbid obesity in adolescents, different types of bariatric surgical procedures, potential complications, the success rate of each procedure, the investigational nature of the LGP, possibility of weight regain, and the scarcity of information on the outcomes of LGP in adolescents. Informed consent was obtained from all patients and their parents. All adolescents underwent a multidisciplinary evaluation by the health professional group, consisting of a psychologist, nutritionist, endocrinologist, surgeon, and health educator. Inclusion criteria were age under 18, body mass index (BMI) 4 40 kg/m2 or BMI 4 35 kg/m2 with co-morbidity, history of unsuccessful weight loss attempts (failure to lose 10% of baseline weight despite a minimum of 6 months participation in a formal weight loss program), gaining 4 20% of their excess weight during the last preoperative year (indicating a high risk of incremental progression in excess weight), confirmation by a psychologist regarding the patient’s decisional capacity, adequate motivation and cooperation with postoperative diet, lifestyle change, follow-up visits, and family support. Patients with previous history of bariatric or antireflux surgery were excluded. Demographic characteristics included their preoperative
age, gender, weight, BMI and obesity related comorbidities. The criteria for the diagnosis and treatment of comorbidities were as follows: Hypertension was defined as systolic blood pressure (SBP) Z 140 mm Hg, diastolic blood pressure (DBP) Z 90 mm Hg or being under hypertensive drugs. Prehypertension was diagnosed if 120 r SBP o 139 mm Hg or 80 r DBP o 89 mm Hg. Remission was defined as SBP o 120 mm Hg and DBP o 80 mm Hg without any medication. Diabetes (DM) was diagnosed if fasting blood glucose (FBG) Z 126 mg/dL, 2-hour postload glucose (2 HPLG) Z 200 mg/dL or medical treatment was received. Prediabetes was diagnosed if 100 r FBG o 126 or 140 r 2 HPLG o 200. Remission was defined as FBG o 100 mg/dL, 2-hour postload glucose o 140 mg/dL. Dyslipidemia was diagnosed if the cholesterol (chol) Z 200 mg/dL, triglyceride Z 130 mg/dL, LDL-C 4 130 mg/dL, HDLC o 35 mg/dL or being under medication. Remission was defined as chol, triglyceride and LDL-C levels below the cut-off point, and HDL-C level higher than the cut-off point with no medications. Symptoms of gastroesophageal reflux disease were diagnosed in the presence of heartburn and symptoms of acid reflux or the use of acid reduction medications. Remission was defined as complete absence of symptoms without medication. Symptoms of sleep apnea were diagnosed by a positive response to enquiry about frequent breathing pauses during sleep and daytime sleepiness. Remission of symptoms was established when breathing pauses during sleep were no longer experienced. Depression was diagnosed as a children inventory score Z 20, and remission was defined as children inventory score less than the cut-off point. Irregular menstruation was diagnosed if menstrual cycles were o21 days or 435 days. Remission was defined as normal menstrual cycle length (21–35 days) under no oral contraceptive or hormonal medication. Eligible patients underwent LGP and were included in the study consecutively. Intervention All procedures were performed by a single surgeon. All patients underwent 2-row gastric plication as previously described. In brief, dissection was started at the greater curvature of the stomach in contact to the gastric wall from prepyloric area to 2-cm proximal to the Hiss angle preserving the anatomy of Hiss angle. All vessels along the greater curvature were separated using LigaSure (Covidien, Mansfield, MA, USA). The greater curvature (from the perimeter) was invaginated using 2 rows of 00 prolene or 00 nylon sutures. Two layers of plication were performed with continuous sutures with 1 surgical sting in all patients to prevent any displacement of inverted folds such as eversion outside or intussusception into esophagus or pylorus. All sutures were extramucusal to avoid their absorption by
127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181
Laparoscopic Gastric Plication in Adolescents / Surgery for Obesity and Related Diseases ] (2014) 00–00
Q3
182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236
gastric acid. Finally, a tube shaped stomach was achieved in which the greater curvature was inverted in to the stomach [13,14]. Postoperative care and follow-up Patients were discharged once liquid food was tolerated. Patients were advised to use soft liquids during the first 6 postoperative weeks. During the first postoperative year, clinical visits were made every 2 weeks in the first 6 months and monthly thereafter. Patients were visited and assessed every 2 months during the second postoperative year and annually afterwards. At each follow-up visit, patients were carefully monitored regarding possible postoperative complications, weight and height status, and obesity comorbidities. Weight-related calculation Weight loss was assessed by calculating: BMI (weight [kg]/height2[m2]), excess BMI (EBMI) (preoperative BMI – ideal BMI [BMI for 85th percentile for age- and genderspecific healthy weight]) and its percentage (%EBMIL) (preoperative BMI-BMI in each visit / EBMI), excess weight (preoperative weight – ideal weight [weight specifying for 85th percentile of BMI for the patient’s gender, age, and height]), percent of excess weight loss (%EWL) (preoperative weight – weight at each visit /excess weight 100%). %EWL o 25% was considered as treatment failure while success was defined as %EWL Z 25%. Statistical analysis Statistical Package of Social Science software (SPSS version 16, IBM Company, USA) was used for statistical analysis. Mean ⫾ SD of continuous variable and frequency of categorical variables are reported. Paired t test and independent t test were used for comparison. A P o .05 was considered statistically significant. Results LGP was performed in 12 adolescents (9 female and 3 male). Mean (SD) age of patients was 13.8 ⫾ 1 year (median: 13, range: 11–17). Mean preoperative weight and BMI were 112.4 ⫾ 19.7 kg (range 89–148 kg) and 46.0 ⫾ 4 kg/m2 (range: 39.3–56.9), respectively. Eight patients suffered from 1 or more preoperative comorbidity. Preoperative co-morbidities included prehypertension in 1 adolescent, DM in 2, prediabetes in 2, dyslipidemia in 1, irregular menstrual cycles in 2, depression in 3, and symptoms of obstructive sleep apnea in 2. Operative time and hospital stay were 61 ⫾ 14 min (range 41–88 min), and hospital stay ranged between 2 and 5 days. All procedures were successfully completed in all patients. No mortality was observed. After the surgery, 1 patient
3
Table 1 Weight loss and clinical outcomes of the procedures %EWL at 6 ⫾ .5 mo follow-up, n (12) %EWL at 12 ⫾ 1 mo follow up, N (10) %EWL at 24 ⫾ 1 mo follow up, N (9) %EWL at 36 ⫾ 2 mo follow up, N (9) %EWL at 48 ⫾ 2 mo follow up, N (4) %EBMIL at 6 ⫾ .5 mo follow up, N (12) %EBMIL at 12 ⫾ 1 mo follow up , N (10) %EBMIL at 24 ⫾ 1 mo follow up, N (9) %EBMIL at 36 ⫾ 2 mo follow up, N (9) %EBMIL at 48 ⫾ 2 mo follow up, N (4) Failure (%EWL o 30% at 12 mo postup)
55.2 ⫾ 10.5 [%] (range 37–72%) 63.6 ⫾ 9.5 [%] (range 42–83%) 68.2 ⫾ 9.9 [%] (range 57–88%) 68.5 ⫾ 11.9 [%] (range 56–97%) 62.1 ⫾ 10.7 [%] (range 51–74%) 60.1 ⫾ 10.0 [%] (range 41–77%) 70.5 ⫾ 9.5 [%] (range 60–90%) 79.0 ⫾ 9.0 [%] (range 68–98%) 80.6 ⫾ 13.5 [%] (range 57–106%) 76.7% ⫾ 18.4 [%] (range 53–98%) 0
%EBMIL ¼ percent of excess body mass index loss; %EWL ¼ percent of excess weight loss; n ¼ number of patients
experienced severe vomiting and reflux, in whom obstruction at the distal part of LGP was confirmed with a gastrografin upper gastrointestinal radiography. At the 4th postoperative day, all sutures were undone and replication was performed using guide bougie no. 32 at the same session, to prevent future obstruction, and vomiting and reflux were relieved immediately afterwards. Temporary vomiting was observed in 1 patient, and epigastric pain was manifested in 1 individual. However, both conditions resolved spontaneously after few days. One patient experienced gastroesophageal reflux disease 1 month postoperatively, which resolved spontaneously 3 months after surgery; all patients experienced %EWL Z 50% after 6 months. Values for %EWL and %EBMIL at 6 months and 1, 2, 3, and 4 years postoperatively are summarized in Table 1. No patient was lost to follow-up. Some adolescents had recently undergone LGP with o2 years of follow-up visits available. Nine patients (out of the 12) had 2 years of follow up visits. Mean (SD) %EWL and %EBMIL at 2 years postoperatively were 68.2 ⫾ 9.9% and 79.0 ⫾ 9.0, respectively. Remission of all medical co-morbidities was observed during the follow-up period. Discussion Obesity has increased considerably in children and adolescents. Conservative management usually does not provide sustainable sufficient weight loss and is associated with high rate of drop out [8,9]. Bariatric surgery, which is associated with considerable weight loss, is gaining popularity for the treatment of morbid obesity in adolescents.
237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 T1 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291
4
292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346
A. Zeinoddini et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
The application of bariatric surgery in adolescents has tripled between 2000 and 2003 [15]. This is the first report of LGP in adolescents. Although bariatric procedures usually provide considerable and sustainable weight loss in adolescents, concern regarding their potential serious complications remains. RYGB and LAGB are the 2 most commonly weight loss procedures that have been performed in adolescents. However, according to a systematic review and meta-analysis of bariatric surgery in pediatric patients, 8% (28/352) of patients who underwent LAGB needed reoperation to correct complications, including band slippage, intragastric band migration, gastric dilation, psychological intolerance of the band, tubing crack, and hiatal hernia. In their review of 140 patients who underwent RYGB, there was 1 death and 8 life-threatening complications, including shock, pulmonary embolism, severe malnutrition, immediate postoperative bleeding, and gastrointestinal obstruction. Three additional patients died, which were not directly related to RYGB. Finally, they concluded that bariatric surgeries are associated with sustained and clinically significant weight loss in pediatrics. However, they may lead to severe complications [10]. Therefore, attempts on finding a bariatric procedure, which provides significant weight loss with a minimal risk of complications, is ongoing. LGP is a recently developed restrictive bariatric operation, which limits the gastric volume by invaginating the greater curvature of the stomach rather than gastric resection. The present study found LGB to be safe and effective in the medium term treatment of morbid obesity and obesity related co-morbidities in adolescents. We reported % EBMIL for weight loss, as adolescent height increased % EWL is believed not be to be an ideal predictor of weight loss in adolescents [16]. To provide an easier comparison between our findings with other reports, % EWL is also reported here. %EBMIL at 2 and 4 years postoperatively were 79.0% and 76.7%, respectively, and mean %EWL were 63%, 68%, 68%, and 62% at 1, 2, 3, and 4 years follow-up visit, respectively. No failure (%EWL o 50%) occurred during the follow-up period, and all cases experienced %EWL 450%. LGP provided weight loss comparable to other bariatric procedures in adolescents [17–19]. Furthermore, in the present study, there were no deaths or the need for rehospitalization. Considering the less-invasive nature of LGP compared to other bariatric procedures, postoperative complications in this study were minimal. In a systematic review of 307 adults who underwent LGP, no deaths were reported and with complications occurring in 8% of patients [20]. Herein, all obesity related comorbidities improved after LGP, and did not reappear during the follow-up period. The authors believe that LGP might be an ideal weight loss procedure for adolescents. Despite its safety and efficacy, some other concerns should be considered while choosing an appropriate bariatric procedure for adolescents. Informed consent taken from
an adolescent remains a challenging issue; even with good decision making capacity confirmed by a psychologist, some patients who undergo bariatric surgery may later come to regret it [10]. Therefore, an ideal bariatric procedure for adolescents should be reversible [10]. Although LAGB could be easily removed, it is associated with some drawbacks. Possible foreign device-related complications include device-related infection and band slippage. Furthermore, considering the limited lifetime of mechanical devices, adolescents may need to undergo device replacement several times during their lifetime. Some studies reported high reoperation rates after LAGB. O’Brien et al. [21] in a randomized controlled trial comparing LAGB with a supervised lifestyle intervention in 50 adolescents, reported that revisional procedures were needed in 8 (33%) during a 2-year follow-up period, which were mostly due to proximal pouch dilation and tubing injury [21]. Furthermore, it should be mentioned that all patients undergoing LAGB remain at risk for eventual failure. LGP is a potentially reversible procedure; however, it does not need foreign body placement nor adjustment. One of the important characteristics of an optimal weight loss surgery includes minimal risk of nutritional deficiency, especially in children and adolescents, and not interfere with physical growth [10]. Children and adolescents may have lower compliance to postoperative regimes compared to adults. In 1 study, only 13% of pediatric patients continued using nutritional supplements as instructed [22]. According to a systematic review on weight loss operations in adolescents, protein-calorie malnutrition and micronutrient deficiency were the most frequent complications after RYGB [10]. Remarkably, there were no nutritional deficiencies seen in this small group of adolescents after LGP, since no section of the gastrointestinal system was bypassed or resected. LSG, a restrictive bariatric procedure, has shown promising shortterm results in adolescents. However, a portion of the stomach is permanently removed during LSG; it is accompanied with the risk of leakage or bleeding along the stomach stapling edges. Furthermore, as a portion of stomach is removed, it is irreversible. The advantages of the present study include its prospective nature, as well as the consecutive inclusion of all eligible patients and no loss to follow-up. Contrariwise, some limitations are encountered in this study including its small sample size and uncertain reproducibility. Finally, due to the small sample size, we remained within the limits of drawing a more comprehensive conclusion. Conclusion The present study provided evidence that LGP could be an ideal conservative weight loss surgical procedure for adolescents, providing optimal weight loss. Nonetheless,
347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401
Laparoscopic Gastric Plication in Adolescents / Surgery for Obesity and Related Diseases ] (2014) 00–00
Q3
402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 Q5 431 432 433
larger well-designed studies with long follow-up periods are warranted to draw a comprehensive conclusion. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. References [1] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA 2012;307:483–90. [2] Choudhary AK, Donnelly LF, Racadio JM, Strife JL. Diseases associated with childhood obesity. Am J Roentgenol 2007;188: 1118–30. [3] Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350: 2362–74. [4] Strauss RS, Pollack HA. Social marginalization of overweight children. Arch Pediatr Adolesc Med 2003;157:746–52. [5] Schwimmer JB, Burwinkle TM, Varni JW. Health-related quality of life of severely obese children and adolescents. JAMA 2003;289: 1813–9. [6] Goldfield GS, Moore C, Henderson K, Buchholz A, Obeid N, Flament MF. Body dissatisfaction, dietary restraint, depression, and weight status in adolescents. J Sch Health 2010;80:186–92. [7] The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P. Association of adolescent obesity with risk of severe obesity in adulthood. JAMA 2010;304:2042–7. [8] Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005;293:2873–83. [9] Whitlock EP, O’Conner EA, Williams SB, Beil TL, Lutz KW. 2010. [10] Treadwell JR, Sun F, Schoelles K. Systematic review and metaanalysis of bariatric surgery for pediatric obesity. Ann Surg 2008;248: 763–76.
5
[11] Alqahtani AR, Antonisamy B, Alamri H, Elahmedi M, Zimmerman VA. Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years. Ann Surg 2012;256:266–73. [12] Talebpour M, Amoli BS. Laparoscopic total gastric vertical plication in morbid obesity. J Laparoendosc Adv Surg Tech A 2007;17:793–8. [13] Darabi S, Talebpour M, Zeinoddini A, Heydari R. Laparoscopic gastric plication versus mini-gastric bypass surgery in the treatment of morbid obesity: a randomized clinical trial. Surg Obes Relat Dis 2013;9:914–9. [14] Talebpour M, Motamedi SM, Talebpour A, Vahidi H. Twelve year experience of laparoscopic gastric plication in morbid obesity: development of the technique and patient outcomes. Ann Surg Innov Res 2012;6:7. [15] Tsai WS, Inge TH, Burd RS. Bariatric surgery in adolescents: recent national trends in use and in-hospital outcome. Arch Pediatr Adolesc Med 2007;161:217–21. [16] Cole TJ, Faith MS, Pietrobelli A, Heo M. What is the best measure of adiposity change in growing children: BMI, BMI %, BMI z-score or BMI centile? Eur J Clin Nutr 2005;59:419–25. [17] Inge TH, Miyano G, Bean J, et al. Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk factors after surgical weight loss in adolescents. Pediatrics 2009;123:214–22. [18] Scheimann AO, Nadler EE, Driscoll DJ, et al. Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years by Alqahtani AR, Antonisamy B, Alamri H, Elahmedi M, Zimmerman VA. Ann Surg. Epub 2013 Sep 16. [19] Al-Qahtani AR. Laparoscopic adjustable gastric banding in adolescent: safety and efficacy. J Pediatr Surg 2007;42:894–7. [20] Abdelbaki TN, Huang CK, Ramos A, Neto MG, Talebpour M, Saber AA. Gastric plication for morbid obesity: a systematic review. Obes Surg 2012;22:1633–9. [21] O'Brien PE, Sawyer SM, Laurie C, et al. Laparoscopic adjustable gastric banding in severely obese adolescents: a randomized trial. JAMA 2010;303:519–26. [22] Rand CS, Macgregor AM. Adolescents having obesity surgery: a 6-year follow-up. South Med J 1994;87:1208–13.
434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465
