Obesity surgery and cancer. What are the unanswered questions?

Obesity has become a global epidemic with a soaring economic encumbrance due to its related morbidity and mortality. Amongst obesity-related conditions, cancer is indeed the most redoubtable. Bariatric surgery has been proven to be the most effective treatment for obesity and its associatedmetabolic and cardiovascular disorders. However, the understanding of whether and how bariatric surgery determines a reduction in cancer risk is limited. Obesity-related malignancies primarily include colorectal and hormone-sensitive (endometrium, breast, prostate) cancers. Additionally, esophago-gastric tumors are growing to be recognized as a new category mainly associated with post-bariatric surgery outcomes. In fact, certain types of surgical procedures have been described to induce the development and subsequent progression of pre-cancerous esophageal and gastric lesions. This emerging category is of great concern and further research is required to possibly prevent such risks. Published data has generated conflicting results. In fact, while overall cancer risk reduction was reported particularly in women, some authors showed no improvement or even increased cancer incidence. Although various studies have reported beneficial effects of surgery on risk of specific cancer development, fundamental insights into the pathogenesis of obesity-related cancer are indispensable to fully elucidate its mechanisms

Response to Sleeve gastrectomy may double the risk of esophageal adenocarcinoma in morbidly obese patients

We would like to thank Papadia et al. for their interest in our article, “Esophageal Adenocarcinoma After Sleeve Gastrectomy: Actual or Potential Threat? Italian Series and Literature Review” [1]. We also greatly appreciated their attempt at evaluating the relative risk (RR) of developing esophageal adenocarcinoma (EAC) in patients who undergo sleeve gastrectomy (SG). To do so, they extrapolated the reported number of SGs performed in Italy over the 3-year period (2012–2015) in which the EAC cases belonging to our series occurred. Papadia et al. [1] show how SG may raise the risk of developing EAC by an estimated 11-fold compared with the general population. Furthermore, they highlight how the RR of EAC in the SG subpopulation appears to be substantially greater compared with patients affected by morbid obesity (RR of 11.9 versus 4.8, respectively). The authors also share our concern regarding the young age (40.3 ± 16.7 yr) and early presentation (27.3 ± 7.6 mo) of EAC after surgery, pointing out how the progression from a normal esophageal mucosa to Barrett’s esophagus (BE) generally befalls over a considerably longer timeframe in patients with GERD that did not have SG. This observation is supported by several studies published by our group demonstrating how the incidence of BE, 58 months after SG, is as high as 17.2%—consistent with other reported rates (i.e., 15%–18.8%) [2,3]—and is correlated to the increased presence of a biliary-type refluxate [[4], [5], [6]], likely to be responsible for the accelerated mucosal injury of the distal esophagus [7]. Emblematic is the case reported in literature of the patient who had a preoperatively diagnosed short-segment BE and who inevitably developed an EAC 36 months later [8]. Although a sporadically reported case, this further emphasizes not only the importance of performing a preoperative esophagogastroduodenoscopy (EGD) to detect any mucosal lesion, but also how BE should constitute an absolute contraindication to SG due to its innate risk of malignant evolution. Finally, loss to follow-up still represents a major, long-standing issue after bariatric surgery, which contributes to precluding the chance of performing protocols of secondary prevention for the identification of any esophageal malignancy at its earliest stages. To this regard, close endoscopic surveillance is of paramount importance for a prompt detection. We also would like to reiterate the necessity of having international online registries, which could allow physicians to determine the actual incidence of EAC after SG and to comprehend its pathogenesis, management, and outcomes possibly better. Despite this potential downside, SG persists as a safe and effective procedure for the cure of obesity and its co-morbid conditions, concurrently carrying low rates of long-term complications and nutritional deficiencies. Additionally, due to its greater technical simplicity and shorter operative time compared with other common bariatric procedures, SG is also the treatment of choice in the super-obese group, easily granting the option for revisional surgery (i.e., RYGB, one anastomosis gastric bypass [OAGB], duodenal switch [DS], single anastomosis duodeno-ileal sleeve [SADI-S]) in case of weight regain or insufficient weight loss. Hence, SG should yet be regarded as a fundamental and valuable bariatric operation to be performed after a thorough preoperative workup and a close endoscopic follow up

The effect of sleeve gastrectomy on oxidative stress in obesity

High concentrations of free radicals are present in the blood of obese patients. Free radicals are associated with endothelial dysfunction, diabetes, and neoplastic transformation, all conditions that are closely related to obesity. The purpose of our study was to determine whether bariatric surgery modifies the production of free radicals in obese patients. In total, 20 patients with morbid obesity, who were candidates for laparoscopic sleeve gastrectomy (SG), and 18 controls were enrolled in the study. Oxidative stress was studied in obese subjects before and after sleeve gastrectomy. The evaluation of oxidative stress was carried out on blood samples using electron paramagnetic resonance, a refined spectroscopic technique used to identify and quantify the major free radicals, such as •OH, O2•, ONOO-, and NO. Oxidative stress was higher in subjects with morbid obesity prior to surgery, compared to the controls (CP• 9.9 ± 0.3 µM vs. 5.8 ± 0.2 µM). After SG, values decreased to levels comparable to those of controls (CP• 5.4 ± 0.2 µM). Further analysis identified O2• as the main free radical responsible for the oxidative stress. Obesity is associated with an increased blood concentration of free radicals. The normalization of free radicals after sleeve gastrectomy highlights another important benefit of this bariatric surgery technique

Comparison between circadian motor activity in pony and horse

In this study we investigated the influence of body mass on the daily rhythm of total motor activity in ponies and horses. Six clinically healthy Shetland pony breed with a body mass of 180 ± 30 kg and six healthy horses Sella Italiana breed with a body mass of 530 ± 20 kg were used. Animals were equipped with actigraphy-based data loggers, Actiwatch-Mini® to record total activity. The application of two-way ANOVA showed a highly significant effect of time of day and body mass on motor activity. Cosinor analysis identified the periodic parameters and their acrophases during the two days of monitoring. Mesor and amplitude were statistically higher in horses than in ponies and no statistically significant differences was found about acrophases and robustness. In conclusion we suppose that the difference in the amount of total motor activity, in animals that differ in breed, as pony and horse, may lie in physical differences. En este estudio hemos investigado la influencia de la masa corporal con respecto al ritmo circadiano de toda la actividad motora en los ponis y los caballos. Han sido utilizados seis sanos Shetland poni con una masa corporal de 180 ± 30 kg y seis sanos caballos biotipo Sella Italiana con una masa corporal de 530 ± 20 kg clínicamente sanos. Los animales han sido equipados con registrador de datos Actiwatch-Mini® para grabar toda la actividad motora. La aplicación de ANOVA dos vías mostró un efecto altamente significante de la hora del día y de la masa corporal sobre la actividad motora. El análisis del Cosinor ha identificado los parámetros periódicos y ellos acrofases en los dos días de seguimiento. Mesor y amplitud fueron estadísticamente más alto en los caballos que en los ponis y ninguna significativa diferencia estadística se encontró sobre las acrofases y robustez. En conclusión suponemos que las diferencias sobre la cantidad de toda la actividad motora en animales de diferente biotipo, como poni y caballo, podrían ser diferencias físicas

Spider surgical system versus multiport laparoscopic surgery. Performance comparison on a surgical simulator

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience

Two-stage laparoscopic biliopancreatic diversion with duodenal switch as treatment of high-risk super-obese patients: analysis of complications

The aim of this study is to retrospectively analyze the incidence of complications after two-stage laparoscopic biliopancreatic diversion with duodenal switch (Lap BPD-DS) in high-risk super-obese patients and explore the possible predictive factors of specific complications after laparoscopic sleeve gastrectomy (SG). High-risk patients-body mass index (BMI) > 50 kg/m(2) with at least two major comorbidities: type 2 diabetes, obstructive sleep apnea syndrome (OSAS), hypertension-undergoing two-stage laparoscopic BPD-DS were retrospectively analysed. The SG pouch volume was 100-150 ml; in the second stage, the common channel and the alimentary loop were 100 cm and 150 cm, respectively. Eighty-seven patients (50 female, 57.5%) underwent SG (two open). The mean age was 41.8 +/- A 10.22 years with BMI of 55.2 +/- A 6.69 kg/m(2). Four patients had Prader-Willy syndrome. Fourteen (16.46%) patients (6 female, 42.8%) had postoperative complications such as bleeding, fistula, pulmonary embolism, transitory acute renal failure, and abdominal abscess. One patient died at postoperative day 5 of pulmonary embolism. One patient was reoperated for hemoperitoneum by laparoscopy. The risk of complications after SG was lower in patients where reinforcement of the suture line was used (0.492), while it was higher in men (1.780). Neither difference was statistically significant [p = not significant (NS)]. After 9-24 months, 27 patients (BMI 43 +/- A 8 kg/m(2)) underwent a second stage of BPD-DS (two open). Major postoperative complications were registered in eight patients (29.6%): three bleeding, four duodeno-ileal stenosis and one rhabdomyolysis. Two cases of internal hernia required laparoscopic reoperation. The reoperation rate was 1/85 (1.2%) after SG and 2/27 (7.4%) after second stage. Complications after SG greatly decrease after the learning curve period and can be successfully managed without need of reoperation. Suture-line reinforcement, at least selectively in the middle-upper portion of the staple line and in super-super-obese patients, is recommended to decrease the incidence of specific complications

Neuropilin 1mediates keratinocyte growth factor signaling in adipose-derived stem cells: potential involvement in adipogenesis

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs

Novel Modality of Endoluminal Anastomotic Integrity Assessment with Fluoroangiography After Left-sided Colorectal Resections

Background Several methods have been described for the intraoperative evaluation of colorectal anastomotic integrity. Technological evolution has allowed to progress from basic mechanical methods to the use of more sophisticated techniques. This study describes a novel endoluminal modality of colorectal anastomotic assessment through the use of a Disposable Rigid Scope Introducer (DRSI) also allowing for intraoperative endoluminal perfusion evaluation by indocyanine green (ICG) fluoroangiography in patients undergoing left-sided colorectal resection. Methods The DRSI consists of an endoluminal introducer device made up of an insertion tube and port connected to an insufflation bulb to manually insufflate the sigmoid and rectum and is compatible with any laparoscopic camera, also allowing for ICG fluoroangiography for perfusion purposes. Results The DRSI was successfully used to assess anastomotic integrity after left-sided colorectal resections performed in 16 consecutive patients. The DRSI allowed to visualize by fluoroangiography the quality of tissue perfusion at the anastomotic site in all cases, contributing to the decision of avoiding loop ileostomies in low rectal resections. In 2 cases, the DRSI showed the presence of significant anastomotic bleeding which was successfully controlled by laparoscopic suture placement. No adverse event resulted from the use of this device. Conclusions The DRSI combines direct endoluminal visualization of the anastomosis together with real-time evaluation of its blood flow. This device holds great potential for prompt intraoperative detection of anastomotic alterations, possibly reducing the risk of postoperative anastomotic bleeding or leaks related to mechanical construction/perfusion issues. Potential advantages of this device warrant larger cohort studies and prospective randomized trials

Esophageal adenocarcinoma after sleeve gastrectomy. Actual or potential threat? Italian series and literature review

Background:Sleeve gastrectomy (SG) leads to esophageal mucosal damage in an elevated percent-age of cases, configuring a clinical condition of Barrett’s esophagus (BE) in a proportion as high as15–18.8%. BE may rarely evolve into esophageal adenocarcinoma (EAC).Objectives:To raise awareness of BE as a precancerous lesion which may progress toward malig-nancy after this popular bariatric procedure.Setting:Bariatric referral centers, Italy.Methods:All patients referred to our bariatric center who developed an EAC after SG between 2012and 2019 were reviewed and consecutively included in this study. The available scientific literatureregarding this complication is additionally reviewed.Results:The 3 male patients comprised in this case series underwent laparoscopic SG between 2012and 2015 in different bariatric referral centers. Age and body mass index at baseline ranged from 21–54 years and 43.1–75.6 kg/m2, respectively. All patients were lost to follow-up early after surgery (3.761.4 months), and were diagnosed with EAC at a mean of 27.367.6 months after SG. The 4 re-ported cases in the scientific literature developed an EAC at a mean of 32.5623 months fromSG. Overall, a diagnosis of EAC was made approximately 30.3617.1 months postoperatively, whichseems relatively and worryingly early after surgery. Conclusion:Although the rate and probability of progression from BE to EAC is still not well defined,assuming that the rising popularity and execution of SG leads to a growth in the BE incidence, then thepreoperative identification and stratification of cancer risk factors in this subset of patients is stronglyencouraged. Clinical and endoscopic follow-ups are essential to allow for prevention and early diag-nosis and for epidemiologic data collection purposes