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Metabolic and bariatric surgery offers benefits to women beyond weight loss
Gynecologic Oncology 138 (2015) 221–222
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Editorial
Metabolic and bariatric surgery offers benefits to women beyond weight loss
There is no denying the impact of obesity on healthcare, the effects of which are seen in every medical specialty. Obese patients present a special challenge to clinicians, especially those in surgical specialties, related to body habitus, alterations in normal physiology, and the multiple medical co-morbidities that may alter or limit conventional treatment options, placing patients at increased risk for complications. Morbid obesity, defined as a body mass index (BMI) N 40 kg/m2, is known to be an independent risk factor for several co-morbid conditions including type 2 diabetes and cardiovascular disease. However, it also significantly increases the risks of cancer, especially in post-menopausal women [1]. The prevalence and severity of obesity have since led the American Medical Association to classify obesity as a disease in 2013 [2]. The cause of this epidemic is not well understood due to its multifaceted etiology involving a complex interplay of factors related to genetics, environment and behavior. Even more convoluted are devising treatment strategies to prevent and treat this disease. Conventional attempts to alter energy balance, through diet and/or exercise, have not been met with any meaningful success, despite the multibillion dollar weight loss industry that continues to offer the public meal replacements, supplements, medications, “detoxification” products, metabolism enhancers and latest fad in exercise. In 1991, the failure of these non-surgical strategies to produce significant and sustainable weight loss led the National Institute of Health to recommend only two treatment options, both of which were surgical, for the durable control of weight; the Roux-en-Y gastric bypass and the vertical banded gastroplasty [3]. Since that time, the number of bariatric operations being performed has increased exponentially, and while the types of operations have evolved, the Roux-en-Y gastric bypass continues to be the gold standard, with the sleeve gastrectomy increasing in popularity. Large national databases, developed for centers with bariatric certification by the ASMBS and ACS, have shown bariatric surgery to be safe, effective and, in prospective, randomized trials, significantly superior to intensive medical management with respect to weight loss and resolution of comorbidities, especially diabetes [4,5]. It has become clear that the surgery-specific alterations in gastrointestinal anatomy do more than simply restrict intake, they alter gut physiology, providing benefits beyond simply weight loss. Additionally, it has become evident that visceral adipose tissue is more than a simple storage mechanism for excess energy, but is metabolically active tissue that may hold the clues to obesity-associated increases in cancer risk as it relates to estrogen levels, insulin, insulin-like growth factor-1, adipokines, regulators of tumor growth and alterations in immune responses. Several studies have shown that the increased association of obesity and cancer is greatly reduced by the effects of bariatric surgery.
http://dx.doi.org/10.1016/j.ygyno.2015.07.099 0090-8258/© 2015 Published by Elsevier Inc.
Christou, et.al [6], retrospectively compared 6781 obese patients, matched for age and sex, and demonstrated a 76% reduction in the incidence of cancer. The Swedish Obesity Study (SOS) [7], one of the largest prospective trials looking at the effects of metabolic surgery, determined, in 4000 patients divided into 2 arms, that surgery was able to reduce cancer mortality by 42.5%. Interestingly, some studies suggest that metabolic surgery-associated decreases in cancer incidence and mortality benefit women more than men [8]. While a majority of the bariatric surgery literature, addressing its effects on cancer, focuses on decreased incidences in a general manner, there is less information on the effects of surgery on specific types of cancer. In an attempt to understand the effect of bariatric surgery on endometrial cancer, Modesitt et.al., in this issue of Gynecologic Oncology, prospectively examined morbidly obese patients undergoing weight loss surgery, focusing on endometrial pathology, changes in metabolic profiles, change in weight, and quality of life (QOL) both before and after surgery. Patients in this study underwent 1 of the 3 most commonly performed operations in the United States; the Roux-en-Y gastric bypass (n = 41), vertical sleeve gastrectomy (n = 17) and adjustable gastric banding (n = 8). Of the 66 patients who had surgery, 30 underwent endometrial biopsy with the most common finding being proliferative (n = 13, 43%), followed by insufficient (n = 8, 27%), secretory (n = 6, 20%), simple hyperplasia (n = 2, 6.7%) and complex atypical hyperplasia (n = 1, 3.3%). After surgery, with a weight loss of 33 kg, re-biopsy of the patient with complex hyperplasia demonstrated normal atrophic endometrium, although it is unclear as to the type of bariatric surgery performed. Regarding QOL, approximately 70% (n = 47) of the women completed the QOL survey both before and after surgery and results demonstrated a significant improvement for the physical component score, but not the mental component score. Finally, in terms of changes to metabolic profiles, results in the 20 women who underwent pre- and post-operative serum sampling showed significant differences between the samples with regard to glucose metabolism and homeostasis (i.e. reduced glucose, pyruvate and lactate, elevated chiro-inositol, and decreased branched chain amino acids), inflammatory mediators (i.e. decreased kynurenine, kynurenate, 3-indoxyl sulfate, and long-chained amino acids), nucleotide metabolism (i.e. elevated adenosine and inosine, reduced hypoxanthine, xanthine, urate and allantoin) and steroid hormones (i.e. decrease in DHEAS and 4androsten metabolites). These are all factors implicated in the increased risks of endometrial cancer in obesity and show beneficial change after bariatric surgery. The study by Modesitt et al. suggests that surgery-induced weight loss may be protective against endometrial carcinogenesis, and points
222
Editorial
to mechanisms other than changes in hormone levels. However, as outlined by the authors themselves, there were several limitations, including sample size, compliance with follow up, and patient demographics that prevent any conclusions from being drawn. It is no surprise to bariatric surgeons that these operations offer significant, durable weight loss, improve quality of life and reverse the toxic physiologic environment caused by obesity. More studies like these are needed to better understand the role of obesity in carcinogenesis, particularly in those patients that carry the highest risk such as post-menopausal women and endometrial cancer. Further, it will be important not only to look at the effects of weight loss, but also the effects of specific operations (e.g. Roux-en-Y gastric bypass versus sleeve gastrectomy) to determine if benefits are related to weight loss and/or changes associated with alterations in gastrointestinal anatomy. While it is clear that weight loss, and therefore, bariatric surgery, is an important adjunct to treatment and prevention, more information will allow us to choose the best bariatric operation for each disease and perhaps help design new operations tailored towards a desired effect. Current medical standards demand a multidisciplinary approach to disease specific states, evidence-based practices, and treating the patient as a whole. However, for many patients obesity is their underlying disease and yet we continue to treat their symptoms in isolation, i.e. — diabetes, hypertension, non-alcoholic steatohepatitis, or endometrial cancer. Ideally, when evaluating an obese patient it is not only essential to understand, evaluate, diagnose and manage the myriad of medical and surgical risks inherent to this disease, but it is also imperative that we educate our patients to help them understand the health consequences of being obese and offer them treatments that include meaningful weight loss. Telling a patient, particularly one who is morbidly obese, to simply eat less and exercise will undoubtedly fail. While bariatric surgery is not for everyone, studies such as this suggest that surgery-induced weight loss is something every gynecologist should be willing to discuss with their obese patients who are at risk for cancer, infertility, and/or obstetric complications. Educating our patients is a first step towards treating them as a whole, and collaboration between
medical and surgical specialties will ensure obese patients receive optimal care. Conflict of interest None to declare.
References [1] G.K. Reeves, K. Pirie, V. Beral, J. Green, E. Spencer, D. Bull, Cancer incidence and mortality in relation to body mass index in the Million Women study: cohort study, BMJ 335 (2007) 1134. [2] M. Frellick, AMA declares obesity a disease, Medscape Medical NewsJune 19 2013. (http://www.medscape.com/viewarticle/806566 Accessed July 3, 2013). [3] Gastrointestinal Surgery for Severe Obesity (reprinted from NIH Consens Dev Conf Consens Statement, 9(1)Mar 25-27 1991. [4] P.R. Schauer, S.R. Kashyap, K. Wolski, S.A. Brethauer, J.P. Kirwan, C.E. Pothier, S. Thomas, B. Abood, S. Nissen, D. Bhatt, Bariatric surgery versus intensive medical therapy in obese patients with diabetes, N. Engl. J. Med. 366 (17) (2012 Apr 26) 1567–1576. [5] J.B. Dixon, P.E. O'Brien, J. Playfair, L. Chapman, L.M. Schachter, S. Skinner, J. Proietto, M. Bailey, M. Anderson, Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial, JAMA 299 (3) (2008) 316–323. [6] N.V. Christou, M. Lieberman, F. Sampalis, J.S. Sampalis, Bariatric surgery reduces cancer risk in morbidly obese patients, Surg. Obes. Relat. Dis. 4 (2008) 691–695. [7] L. Sjostrom, K. Narbro, C.D. Sjostrom, et al., Effects of bariatric surgery on mortality in Swedish obese subjects, N. Engl. J. Med. 357 (2007) 741–752. [8] T.D. Adams, A.M. Stroup, R.E. Gress, et al., Cancer incidence and mortality after gastric bypass surgery, Obesity (Silver Spring) 17 (2009) 796–802.
Bradley J. Needleman⁎ Sabrena F. Noria Ohio State University, Wexner Medical Center, The Division of Gastrointestinal and General Surgery, N723 Doan Hall, 410 W 10th Ave., Columbus, OH 43210-1228, USA ⁎Corresponding author. E-mail address: [email protected] (B.J. Needleman).
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Editorial
Metabolic and bariatric surgery offers benefits to women beyond weight loss
There is no denying the impact of obesity on healthcare, the effects of which are seen in every medical specialty. Obese patients present a special challenge to clinicians, especially those in surgical specialties, related to body habitus, alterations in normal physiology, and the multiple medical co-morbidities that may alter or limit conventional treatment options, placing patients at increased risk for complications. Morbid obesity, defined as a body mass index (BMI) N 40 kg/m2, is known to be an independent risk factor for several co-morbid conditions including type 2 diabetes and cardiovascular disease. However, it also significantly increases the risks of cancer, especially in post-menopausal women [1]. The prevalence and severity of obesity have since led the American Medical Association to classify obesity as a disease in 2013 [2]. The cause of this epidemic is not well understood due to its multifaceted etiology involving a complex interplay of factors related to genetics, environment and behavior. Even more convoluted are devising treatment strategies to prevent and treat this disease. Conventional attempts to alter energy balance, through diet and/or exercise, have not been met with any meaningful success, despite the multibillion dollar weight loss industry that continues to offer the public meal replacements, supplements, medications, “detoxification” products, metabolism enhancers and latest fad in exercise. In 1991, the failure of these non-surgical strategies to produce significant and sustainable weight loss led the National Institute of Health to recommend only two treatment options, both of which were surgical, for the durable control of weight; the Roux-en-Y gastric bypass and the vertical banded gastroplasty [3]. Since that time, the number of bariatric operations being performed has increased exponentially, and while the types of operations have evolved, the Roux-en-Y gastric bypass continues to be the gold standard, with the sleeve gastrectomy increasing in popularity. Large national databases, developed for centers with bariatric certification by the ASMBS and ACS, have shown bariatric surgery to be safe, effective and, in prospective, randomized trials, significantly superior to intensive medical management with respect to weight loss and resolution of comorbidities, especially diabetes [4,5]. It has become clear that the surgery-specific alterations in gastrointestinal anatomy do more than simply restrict intake, they alter gut physiology, providing benefits beyond simply weight loss. Additionally, it has become evident that visceral adipose tissue is more than a simple storage mechanism for excess energy, but is metabolically active tissue that may hold the clues to obesity-associated increases in cancer risk as it relates to estrogen levels, insulin, insulin-like growth factor-1, adipokines, regulators of tumor growth and alterations in immune responses. Several studies have shown that the increased association of obesity and cancer is greatly reduced by the effects of bariatric surgery.
http://dx.doi.org/10.1016/j.ygyno.2015.07.099 0090-8258/© 2015 Published by Elsevier Inc.
Christou, et.al [6], retrospectively compared 6781 obese patients, matched for age and sex, and demonstrated a 76% reduction in the incidence of cancer. The Swedish Obesity Study (SOS) [7], one of the largest prospective trials looking at the effects of metabolic surgery, determined, in 4000 patients divided into 2 arms, that surgery was able to reduce cancer mortality by 42.5%. Interestingly, some studies suggest that metabolic surgery-associated decreases in cancer incidence and mortality benefit women more than men [8]. While a majority of the bariatric surgery literature, addressing its effects on cancer, focuses on decreased incidences in a general manner, there is less information on the effects of surgery on specific types of cancer. In an attempt to understand the effect of bariatric surgery on endometrial cancer, Modesitt et.al., in this issue of Gynecologic Oncology, prospectively examined morbidly obese patients undergoing weight loss surgery, focusing on endometrial pathology, changes in metabolic profiles, change in weight, and quality of life (QOL) both before and after surgery. Patients in this study underwent 1 of the 3 most commonly performed operations in the United States; the Roux-en-Y gastric bypass (n = 41), vertical sleeve gastrectomy (n = 17) and adjustable gastric banding (n = 8). Of the 66 patients who had surgery, 30 underwent endometrial biopsy with the most common finding being proliferative (n = 13, 43%), followed by insufficient (n = 8, 27%), secretory (n = 6, 20%), simple hyperplasia (n = 2, 6.7%) and complex atypical hyperplasia (n = 1, 3.3%). After surgery, with a weight loss of 33 kg, re-biopsy of the patient with complex hyperplasia demonstrated normal atrophic endometrium, although it is unclear as to the type of bariatric surgery performed. Regarding QOL, approximately 70% (n = 47) of the women completed the QOL survey both before and after surgery and results demonstrated a significant improvement for the physical component score, but not the mental component score. Finally, in terms of changes to metabolic profiles, results in the 20 women who underwent pre- and post-operative serum sampling showed significant differences between the samples with regard to glucose metabolism and homeostasis (i.e. reduced glucose, pyruvate and lactate, elevated chiro-inositol, and decreased branched chain amino acids), inflammatory mediators (i.e. decreased kynurenine, kynurenate, 3-indoxyl sulfate, and long-chained amino acids), nucleotide metabolism (i.e. elevated adenosine and inosine, reduced hypoxanthine, xanthine, urate and allantoin) and steroid hormones (i.e. decrease in DHEAS and 4androsten metabolites). These are all factors implicated in the increased risks of endometrial cancer in obesity and show beneficial change after bariatric surgery. The study by Modesitt et al. suggests that surgery-induced weight loss may be protective against endometrial carcinogenesis, and points
222
Editorial
to mechanisms other than changes in hormone levels. However, as outlined by the authors themselves, there were several limitations, including sample size, compliance with follow up, and patient demographics that prevent any conclusions from being drawn. It is no surprise to bariatric surgeons that these operations offer significant, durable weight loss, improve quality of life and reverse the toxic physiologic environment caused by obesity. More studies like these are needed to better understand the role of obesity in carcinogenesis, particularly in those patients that carry the highest risk such as post-menopausal women and endometrial cancer. Further, it will be important not only to look at the effects of weight loss, but also the effects of specific operations (e.g. Roux-en-Y gastric bypass versus sleeve gastrectomy) to determine if benefits are related to weight loss and/or changes associated with alterations in gastrointestinal anatomy. While it is clear that weight loss, and therefore, bariatric surgery, is an important adjunct to treatment and prevention, more information will allow us to choose the best bariatric operation for each disease and perhaps help design new operations tailored towards a desired effect. Current medical standards demand a multidisciplinary approach to disease specific states, evidence-based practices, and treating the patient as a whole. However, for many patients obesity is their underlying disease and yet we continue to treat their symptoms in isolation, i.e. — diabetes, hypertension, non-alcoholic steatohepatitis, or endometrial cancer. Ideally, when evaluating an obese patient it is not only essential to understand, evaluate, diagnose and manage the myriad of medical and surgical risks inherent to this disease, but it is also imperative that we educate our patients to help them understand the health consequences of being obese and offer them treatments that include meaningful weight loss. Telling a patient, particularly one who is morbidly obese, to simply eat less and exercise will undoubtedly fail. While bariatric surgery is not for everyone, studies such as this suggest that surgery-induced weight loss is something every gynecologist should be willing to discuss with their obese patients who are at risk for cancer, infertility, and/or obstetric complications. Educating our patients is a first step towards treating them as a whole, and collaboration between
medical and surgical specialties will ensure obese patients receive optimal care. Conflict of interest None to declare.
References [1] G.K. Reeves, K. Pirie, V. Beral, J. Green, E. Spencer, D. Bull, Cancer incidence and mortality in relation to body mass index in the Million Women study: cohort study, BMJ 335 (2007) 1134. [2] M. Frellick, AMA declares obesity a disease, Medscape Medical NewsJune 19 2013. (http://www.medscape.com/viewarticle/806566 Accessed July 3, 2013). [3] Gastrointestinal Surgery for Severe Obesity (reprinted from NIH Consens Dev Conf Consens Statement, 9(1)Mar 25-27 1991. [4] P.R. Schauer, S.R. Kashyap, K. Wolski, S.A. Brethauer, J.P. Kirwan, C.E. Pothier, S. Thomas, B. Abood, S. Nissen, D. Bhatt, Bariatric surgery versus intensive medical therapy in obese patients with diabetes, N. Engl. J. Med. 366 (17) (2012 Apr 26) 1567–1576. [5] J.B. Dixon, P.E. O'Brien, J. Playfair, L. Chapman, L.M. Schachter, S. Skinner, J. Proietto, M. Bailey, M. Anderson, Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial, JAMA 299 (3) (2008) 316–323. [6] N.V. Christou, M. Lieberman, F. Sampalis, J.S. Sampalis, Bariatric surgery reduces cancer risk in morbidly obese patients, Surg. Obes. Relat. Dis. 4 (2008) 691–695. [7] L. Sjostrom, K. Narbro, C.D. Sjostrom, et al., Effects of bariatric surgery on mortality in Swedish obese subjects, N. Engl. J. Med. 357 (2007) 741–752. [8] T.D. Adams, A.M. Stroup, R.E. Gress, et al., Cancer incidence and mortality after gastric bypass surgery, Obesity (Silver Spring) 17 (2009) 796–802.
Bradley J. Needleman⁎ Sabrena F. Noria Ohio State University, Wexner Medical Center, The Division of Gastrointestinal and General Surgery, N723 Doan Hall, 410 W 10th Ave., Columbus, OH 43210-1228, USA ⁎Corresponding author. E-mail address: [email protected] (B.J. Needleman).