Maximizing Weight Loss After Roux-en-Y Gastric Bypass May Decrease Risk of Incident Organ Cancer

Background

Recent studies have suggested that metabolic surgery reduces cancer risk. This study aims to determine if incident cancer is associated with the extent of weight loss after Roux-en-Y gastric bypass (RYGB).

Methods

Patients at a large tertiary bariatric surgery center were retrospectively reviewed to identify patients with no history of cancer at the time of RYGB. Diagnoses in the electronic health record, a tumor registry, and chart review were used to identify postoperative incident solid organ cancer. The overall incidence of organ cancer was estimated using Kaplan-Meier analysis. The percent total body weight loss (%TWL) in the 48 months after surgery but prior to cancer was compared between those that developed organ cancer versus those that did not using repeated measures linear regression.

Results

The 2943 patients had a mean age of 45.6 years (SD?=?11.1), 81 % were female, and a mean baseline body mass index (BMI) of 47.2 kg/m² (SD?=?7.9). Median follow-up after surgery was 3.8 years (range?=?[<1, 12]). Incident organ cancer developed and was verified in 54 of the 2943 patients (1.8 %). Kaplan-Meier estimates for cancer at 3, 5, and 10 years postsurgery were 1.3, 2.5, and 4.2 %. After adjusting for age, BMI, sex, diabetes, hypertension, and dyslipidemia, patients that developed organ cancer achieved less weight loss (?1.5 % TWL, 95 % CI?=?[?2.9 %, ?0.1 %], p?=?0.034).

Conclusions

Greater weight loss after metabolic surgery may be associated with lower organ cancer risk.

     

Foreword: varicocele – unraveling the enigma

It was more than 40 years ago, as a first-year Urology resident, that I performed my first varicocele ligation (a Palomo procedure1) under the watchful eye and able hands of my staff physician. I dutifully read all I could the night before the procedure and became familiar with the names of Barfield, Macomber and Sanders, Tulloch, MacLeod, Ivanissevich, Palomo, Amelar and Dubin and others who had written about varicoceles being associated with abnormal semen parameters and a potentially surgically correctable cause of male infertility. During and after our uneventful surgical procedure, I was grilled as to the anatomy and known pathophysiology of a varicocele. I felt well-versed from my reading and proudly regurgitated all I had learned about the anatomy of the left testicular vein and pampiniform plexus, incompetent or absent valves in the vein, increased testicular temperature, sluggish flow of blood from the left testis and possible toxins from the opposing left adrenal gland vein entering the dilated, incompetent testicular vein – any or all of which could contribute to disturb spermatogenesis and cause infertility. It all seemed simple enough! I pretty much thought we knew all we needed to know about this so-called “bag of worms.”Fast-forward to the present and it becomes obvious how little we actually did know with respect to our understanding the concept of a varicocele and how it may or more commonly, may not affect spermatogenesis and fertility potential. This venous “enigma,”2 as it was so aptly termed by Dr. Turner,2 has fueled many hot debates at national and international scientific meetings among specialists in Urology, Gynecology, and Andrology. Most urologic surgeons appear to accept the fact that a varicocele is a commonly identified, potentially correctable cause for primary and secondary infertility. They also recognize that it is not a “fix” for everyone on whom they operate nor do most men with a varicocele need to have it corrected. Indeed, many men are found to have a varicocele on routine examination and may never have a fertility problem and are often unaware of the venous abnormality being present until this incidental finding is pointed out to them during the examination.If one queries the word “varicocele” in PubMed, almost 5000 scientific articles would appear, from the more recent month''s publications to an early paper dating back to 1846.3 A brief perusal of the more recent papers, particularly over the last couple of decades, leads one to appreciate how much our knowledge regarding varicoceles and their effect on the fertility and gonadal function has increased. Yet there still are many unknowns surrounding this anatomic venous anomaly.This special edition of the Asian Journal of Andrology takes us one step further in understanding the enigma of the varicocele and current controversies surrounding the indications or contraindications for ablative therapy. Drs. Agarwal and Esteves are to be heartedly congratulated on their ability to gather so many recognized, international authorities in male reproduction who share with us recent advances in understanding the pathophysiology of varicoceles and its variable affect on fertility and androgen function. In addition, world renowned surgeons and interventionalists discuss the indications, techniques and controversies regarding surgery for this venous anomaly for both adolescents and adult males.The availability and reported success of advanced assisted reproductive methods (In Vitro Fertilization with Intracytoplasmic Sperm Injection - IVF-ICSI), has dramatically altered the playing field for couples that find it difficult to conceive by natural means. Success in this area has led some reproductive endocrinologists to suggest that given a few live normal appearing sperm is all they need for intracytoplasmic sperm injection and, therefore, it does not matter if there is a varicocele or not in the male partner with suboptimal sperm quality. Disregarding the excessive costs, which are not inconsequential, and potential risks borne by the female partner undergoing ovarian stimulation and IVF, the need for repeated cycles and the inherent risks related to the greater incidence for multiple gestations, it would seem a grave disservice to a couple not to offer the option of a potentially curative solution to their infertility if the male partner has a varicocele and associated suboptimal semen quality.4,5It is obvious that since I performed my first varicocele ligation and tried to impress the staff surgeon with my thorough knowledge of varicocele anatomy and pathophysiology, there have been dramatic and meaningful advances in our understanding of the effects of varicoceles on the gonadal function of some men. We had, then, never heard the terms: reactive oxygen species and oxidative stress, DNA fragmentation, or heat-shock proteins. We never thought or had the means of looking for “subclinical varicoceles.” The conceptualization and realization of sophisticated assisted reproductive methods such as IFV/ICSI for impaired male factors were then pure speculation and fiction.The outstanding authors who have contributed to this special edition offer us a state-of-the-art view of the pathophysiology and treatment options for men with varicoceles. I would venture to predict that the next generation of researchers and surgeons will consider many of these current concepts as being as naοve and simplistic as those of the past. I do hope that the next generation of “experts” remembers the words of the 12^th century theologian, John of Salisbury:“We are like dwarfs sitting on the shoulders of giants. We see more, and things that are more distant, than they did, not because our sight is superior or because we are taller than they, but because they raise us up, and by their great stature add to ours”.     

Radial scar lesions of the breast diagnosed by needle core biopsy: analysis of cases containing occult malignancy

AIM: To identify and review cases of false negative needle core biopsy (NCB) in the preoperative investigation of radial scar/complex sclerosing lesion (RS/CSL) lesions - that is, benign NCB from RS/CSL which contained malignancy on excision. METHODS AND RESULTS: A total of 11 false negative NCB in RS/CSL lesions from 281 (3.9%) were identified (6 cases: B1, 2 cases: B2 and 3 cases: B3). In 6 of 11 cases a radial scar or stromal sclerosis was seen in NCB. Localisation biopsy showed duct carcinoma in situ in six cases, duct carcinoma in situ with invasive carcinoma in three and invasive carcinoma in two. In all 11 cases, needle tracks were identified as missing the malignant epithelium by a mean of 5 mm (median:4 mm; range:1-20 mm). In 9 of 11 cases, the malignancy was missed by <6 mm. CONCLUSIONS: Despite evidence of accurate targeting of lesions, the use of NCB instead of fine needle aspiration cytology has not eliminated the problem of false negative biopsy in RS/CSL, and excision is recommended.     

Environmental discontinuity hypothesis: Buffer dysfunctions as a source of human disease

Adaptive physiologic buffers enable organisms to respond to environmental variation with appropriate plasticity. Modern humans have substantially remodeled their environment such that many interactions with the environment have become relatively discontinuous functions compared to the past. Examples include sunlight, temperature, and altitude. We propose that environmental discontinuity represents a Darwinian maladaptation and may promote disease by inducing buffer dysfunctions. Skin pigmentation is an adaptive, dynamic buffer that normalizes sunlight exposure to balance the potential harm of damaging rays with the importance of sunlight in driving systemic biologic functions such as melatonin and vitamin D. Due to lifestyle characteristics such as indoor-outdoor living, well-intended sun-avoidance campaigns, and inhomogeneous use of apparel and sunblock techniques, modern humans increasingly experience sunlight variation as a discontinuous function. The resulting skin pigmentation buffer dysfunction may promote diseases associated with over- or under-exposure to sunlight, the most striking example being melanoma. In addition to promoting discontinuity of sunlight exposure, sun-avoidance campaigns may undermine sun-dependent biologic pathways such as melatonin and vitamin D that appear to protect against cancer. These issues may partly explain the rise in melanoma rates despite the implementation of sun-avoidance campaigns. Also discussed is the potential role that discontinuous temperature variation associated with modern lifestyles plays in diseases such as viral infection, heart failure, and acute coronary syndromes. Acute discontinuous changes in pressure and oxygen levels related to air travel may contribute to autonomic dysfunction, venous thromboembolism, and viral infections. Therapeutic implications are discussed.     

Unhappy meal: how our need to detect stress may have shaped our preferences for taste

Conventional wisdom says that our preferences for particular tastes evolved to ensure an adequate instinctual intake of metabolic resources. Yet we discern scant taste in many vital dietary components, such as vitamins, minerals, co-factors, essential fatty acids and amino acids. We propose that taste preferences evolved to serve a secondary function--that of xenohormesis. Stress causes organisms to convert complex sugars to simple sugars, as seen during fruit ripening, and to increase the proportion of high-energy saturated fats relative to unsaturated fats, as seen among farmed livestock. The presence of dietary simple sugars, saturated fats, and salt within an organism may echo its stress experience--an experience assimilated by others when consumed. As each successive consumer in the food chain incorporates the stress phenotypes of its dietary components, cues for stress may accumulate in a game of "you-are-what-you-eat". Detection of environmental stress embedded in diet may promote adaptive phenotype remodeling such as caloric hoarding to contend with potential ecologic challenges. The phenotype remodeling may be the result of direct stress signaling properties of fats, sugars, and salt. Since food ecosystems typically exhibit seasonality in composition, early detection of cues of ecologic stress during autumn, such as dehydration, lowered ambient temperatures, and impending resource scarcity, likely confers advantages in fitness. Taste preferences may represent a form of "Darwinian rubbernecking. Much like paying attention to vignettes of violence and trauma, recognizing proxies of ecologic stress and adapting accordingly may yield fitness advantages. Many aspects of agricultural modernization may increase the level of stress embedded in the food chain, catering to pre-existing taste preferences in a form of illegitimate signaling. Globalization and technology have transformed the dietary experience of autumn--when the food chain undergoes stress and therefore tastes the best--into a year-round bacchanal. Instead of experiencing ecologic stress through their diet in a seasonal pattern, modern humans have become creatures of chronic stress. Many human conditions related to stress dysfunctions may partly arise from maladaptive consumption of stressed foods. We anticipate that low-stress and stress-free food may have therapeutic potential in the treatment of diseases and the promotion of health.     

Identification of protein complexes in detergent-resistant membranes of Plasmodium falciparum schizonts

Merozoite surface proteins of the human malaria parasite Plasmodium falciparum are involved in initial contact with target erythrocytes, a process that begins a cascade of events required for successful invasion of these cells. In order to identify complexes that may play a role in invasion we purified detergent-resistant membranes (DRMs), known to be enriched in merozoite surface proteins, and used blue native-polyacrylamide gel electrophoresis (BN-PAGE) to isolate high molecular weight complexes for identification by mass spectrometry. Sixty-two proteins were detected and these mostly belonged to expected DRM proteins classes including GPI-anchored, multi-membrane spanning and rhoptry proteins. Proteins from seven known complexes were identified including MSP-1/7, the low (RAP1/2 and RAP1/3), and high (RhopH1/H2/H3) molecular weight rhoptry complexes, and the invasion motor complex (GAP45/GAP50/myosinA). Remarkably, a large proportion of identified spectra were derived from only 4 proteins: the GPI-anchored proteins MSP-1 and Pf92, the putative GPI-anchored protein Pf113 and RAP-1, the core component of the two RAP complexes. Each of these proteins predominated in high molecular weight species suggesting their aggregation in much larger complexes than anticipated. To demonstrate that the procedure had isolated novel complexes we focussed on MSP-1, which predominated as a distinct species at approximately 500 kDa by BN-PAGE, approximately twice its expected size. Chemical cross-linking supports the existence of a stable MSP-1 oligomer of approximately 500 kDa, probably comprising a highly stable homodimeric species. Our observations also suggests that oligomerization of MSP-1 is likely to occur outside the C-terminal epidermal growth factor (EGF)-like domains. Confirmation of MSP-1 oligomerization, together with the isolation of a number of known complexes by BN-PAGE, makes it highly likely that novel interactions occur amongst members of this proteome.