Outcomes of the One Anastomosis Gastric Bypass with Various Biliopancreatic Limb Lengths:a Retrospective Single-Center Cohort Study

Introduction: One anastomosis gastric bypass (OAGB) is an effective and safe treatment for morbidly obese patients. Longer biliopancreatic (BP) limb length is suggested to result in better weight loss outcomes, but to date, no data are available for the OAGB to substantiate this. We hypothesized that applying a longer BP-limb length in the higher BMI classes would result in more weight reduction so that the attained BMI would be comparable to patients with a lower BMI, thereby compensating for differences in baseline BMI. Method: A retrospective cohort study in patients who underwent a primary OAGB at a teaching hospital in the Netherlands between January 2015 and December 2016. BP-limb length was tailored based on preoperative BMI. Patients were divided into three different groups depending on the length of the BP-limb: 150, 180, and 200 cm. Weight loss outcomes after 1 and 3 years and resolution of comorbidities were compared between these groups. Results: Of the 632 included patients, a BP-limb length of 150 cm was used in 172 (27.2%), 180 cm in 388 (61.4%), and 200 cm in 72 (11.4%) patients. Despite more BMI loss, %EWL was lower and attained BMI remained higher in the groups with longer BP-limb lengths. After adjustment for the confounder preoperative BMI, longer BP-limb lengths were not associated with higher BMI loss. There was no difference in remission rates of comorbidities. Conclusion: Attained BMI remained higher in spite of tailoring BP-limb length according to baseline BMI with no differences in remission rates of comorbidities

Tailoring limb length based on total small bowel length in one anastomosis gastric bypass surgery (TAILOR study):study protocol for a randomized controlled trial

Background: The one anastomosis gastric bypass (OAGB) is being performed by an increasing number of bariatric centers over the world. However, the optimal length of the biliopancreatic (BP) limb remains a topic of discussion. Retrospective studies suggest the benefit of tailoring BP-limb length; however, randomized trials are lacking. The aim of this study is to investigate whether tailoring the length of the BP-limb based on total small bowel length (TSBL) leads to better results in terms of weight loss, vitamin deficiencies, and bowel movements compared to a fixed BP-limb length. Methods: The TAILOR study is a double-blind single-center randomized controlled trial. Patients scheduled for primary OAGB surgery will be randomly allocated either to a standard BP-limb of 150 cm or to a BP-limb length based on their TSBL: TSBL 700 cm, BP-limb 210 cm. The primary outcome is to compare the percent total weight loss (%TWL) at 5 years between the two groups. Secondary outcomes include nutritional deficiencies, remission of comorbidities, symptoms of dumping, quality of life, and daily bowel movements. The study includes a total of 212 patients and is designed to detect a 5% difference in the primary endpoint. Discussion: The TAILOR study will provide new insights into the effect of different BP-limb lengths and the role of the TSBL in the OAGB. The study is designed to provide guidance for bariatric surgeons to determine the optimal BP-limb length in the OAGB

Evaluating AI-generated CBCT-based synthetic CT images for target delineation in palliative treatments of pelvic bone metastasis at conventional C-arm linacs

Purpose: One-table treatments with treatment imaging, preparation and delivery occurring at one treatment couch, could increase patients’ comfort and throughput for palliative treatments. On regular C-arm linacs, however, cone-beam CT (CBCT) imaging quality is currently insufficient. Therefore, our goal was to assess the suitability of AI-generated CBCT based synthetic CT (sCT) images for target delineation and treatment planning for palliative radiotherapy. Materials and methods: CBCTs and planning CT-scans of 22 female patients with pelvic bone metastasis were included. For each CBCT, a corresponding sCT image was generated by a deep learning model in ADMIRE 3.38.0. Radiation oncologists delineated 23 target volumes (TV) on the sCTs (TVsCT) and scored their delineation confidence. The delineations were transferred to planning CTs and manually adjusted if needed to yield gold standard target volumes (TVclin). TVsCT were geometrically compared to TVclin using Dice coefficient (DC) and Hausdorff Distance (HD). The dosimetric impact of TVsCT inaccuracies was evaluated for VMAT plans with different PTV margins. Results: Radiation oncologists scored the sCT quality as sufficient for 13/23 TVsCT (median: DC = 0.9, HD = 11 mm) and insufficient for 10/23 TVsCT (median: DC = 0.7, HD = 34 mm). For the sufficient category, remaining inaccuracies could be compensated by +1 to +4 mm additional margin to achieve coverage of V95% &gt; 95% and V95% &gt; 98%, respectively in 12/13 TVsCT. Conclusion: The evaluated sCT quality allowed for accurate delineation for most targets. sCTs with insufficient quality could be identified accurately upfront. A moderate PTV margin expansion could address remaining delineation inaccuracies. Therefore, these findings support further exploration of CBCT based one-table treatments on C-arm linacs.</p

Laparoscopic Small Bowel Length Measurement in Bariatric Surgery Using a Hand-Over-Hand Technique with Marked Graspers:an Ex Vivo Experiment

Introduction Tailoring limb length in bariatric surgery is a subject of many studies. To acquire the optimal limb length, accurate measurement of the small bowel length is essential. Objective To assess the intra- and inter-individual variability of laparoscopic bowel length measurement using a hand-over-hand technique with marked graspers. Method Four bariatric surgeons and four surgical residents performed measurements on cadaver porcine intestine in a laparoscopic box using marked graspers. Each participant performed 10 times a measurement of three different lengths: 150, 180, and 210 cm. Acceptable percentage deviation from the goal lengths was defined as less than 10%, while unacceptable deviations were defined as more than 15%. Results The bariatric surgeons measured the 150-, 180-, and 210-cm tasks with 4% (CI 0.4, 9), - 6% (CI - 11, - 0.8), and 1% (CI - 4, 6) deviation, respectively. In total, the bariatric surgeons estimated 58 out of 119 times (49%) between the margins of 10% deviation and 36 times (30%) outside the 15% margin. Considerable inter-individual differences were found between the surgeons. The surgical residents underestimated the tasks with 12% (CI - 18, - 6), 16% (CI - 19, - 13), and 18% (CI - 22, - 13), respectively. Conclusion Bariatric surgeons estimated bowel length with on average less than 10% deviation. However, this still resulted in 30% of the measurements with more than 15% deviation. There were considerable inter-individual differences between the surgeons and residents structurally underestimated the bowel length. Ascertainment of measurement accuracy and adequate training is essential for bariatric procedures in which limb length is of importance

Applying an Anti-reflux Suture in the One Anastomosis Gastric Bypass to Prevent Biliary Reflux:a Long-Term Observational Study

INTRODUCTION: The one anastomosis gastric bypass (OAGB) is an effective treatment to induce sustained weight loss in morbidly obese patients. Concerns remain regarding the development of reflux. The aim of this study was to investigate the effect of an "anti-reflux suture" as anti-reflux modification to prevent reflux. METHOD: This is a single-center retrospective cohort study of patients who underwent a primary OAGB at the Center Obesity North-Netherlands (CON) between January 2015 and December 2016. Reflux was defined as symptoms of acid/bilious regurgitation or pyrosis. This was consequently asked and reported at each follow-up visit. Outcomes of patients with an anti-reflux suture were compared to those without. RESULTS: In 414 (59%) of the 703 included patients, an anti-reflux suture was applied. Follow-up at 3 years was 74%. The incidence of reflux did not differ between patients with or without an anti-reflux suture (57 versus 56%, respectively; P = 0.9). The presence of an anti-reflux suture was significantly associated with a lower incidence of conversion to Roux-en-Y gastric bypass (RYGB) for reflux (OR 0.56, 95%CI 0.34-0.91). Patients preoperatively diagnosed with gastroesophageal reflux disease (GERD) were 5.2 times more likely to need a conversion to RYGB for reflux (95%CI 2.7-10.1). CONCLUSION: The presence of preoperative GERD should be weighted heavily in the decision to perform an OAGB as this is a major risk factor for conversion surgery due to reflux. The anti-reflux suture might be a valuable addition to the procedure of the OAGB because it results in fewer conversion surgeries for reflux

The one anastomosis gastric bypass: insight and improvement of the surgical aspects

The thesis focused on the one anastomosis gastric bypass (OAGB) procedure, a widely used surgical procedure for the treatment of obesity. Its objective was to offer valuable insights and refine various surgical aspects of OAGB, aiming to optimize techniques and improve postoperative outcomes. Investigation into a late complication of OAGB, biliary reflux, revealed a beneficial effect of an anti-reflux suture. Furthermore, the optimal length of the biliopancreatic (BP) limb in OAGB surgery was investigated to achieve optimal postoperative outcomes by maximizing weight loss while minimizing adverse effects. Initially, the accuracy of laparoscopic measurement techniques for bowel length determination was assessed. Following investigations examined the technique of adjusting the length of the biliopancreatic (BP) limb based on preoperative BMI. However, this method did not produce the intended postoperative results. The thesis introduced the TAILOR study, a randomized clinical trial investigating if tailoring the BP-limb length according to total small bowel length (TSBL) offers advantages over a fixed BP-limb length in terms of weight loss, nutritional deficiencies, and resolution of comorbidities. Preliminary findings show the feasibility and safety of this approach, although one year after surgery, an adjusted BP-limb length based on TSBL did not result in superior postoperative outcomes compared to a fixed BP-limb length. However, the five-year results of the TAILOR study will be essential for drawing definitive conclusions

Evaluating AI-generated CBCT-based synthetic CT images for target delineation in palliative treatments of pelvic bone metastasis at conventional C-arm linacs

Purpose: One-table treatments with treatment imaging, preparation and delivery occurring at one treatment couch, could increase patients’ comfort and throughput for palliative treatments. On regular C-arm linacs, however, cone-beam CT (CBCT) imaging quality is currently insufficient. Therefore, our goal was to assess the suitability of AI-generated CBCT based synthetic CT (sCT) images for target delineation and treatment planning for palliative radiotherapy. Materials and methods: CBCTs and planning CT-scans of 22 female patients with pelvic bone metastasis were included. For each CBCT, a corresponding sCT image was generated by a deep learning model in ADMIRE 3.38.0. Radiation oncologists delineated 23 target volumes (TV) on the sCTs (TVsCT) and scored their delineation confidence. The delineations were transferred to planning CTs and manually adjusted if needed to yield gold standard target volumes (TVclin). TVsCT were geometrically compared to TVclin using Dice coefficient (DC) and Hausdorff Distance (HD). The dosimetric impact of TVsCT inaccuracies was evaluated for VMAT plans with different PTV margins. Results: Radiation oncologists scored the sCT quality as sufficient for 13/23 TVsCT (median: DC = 0.9, HD = 11 mm) and insufficient for 10/23 TVsCT (median: DC = 0.7, HD = 34 mm). For the sufficient category, remaining inaccuracies could be compensated by +1 to +4 mm additional margin to achieve coverage of V95% &gt; 95% and V95% &gt; 98%, respectively in 12/13 TVsCT. Conclusion: The evaluated sCT quality allowed for accurate delineation for most targets. sCTs with insufficient quality could be identified accurately upfront. A moderate PTV margin expansion could address remaining delineation inaccuracies. Therefore, these findings support further exploration of CBCT based one-table treatments on C-arm linacs.</p

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient. A modified patient-derived tumor organoids system allows the expansion of tumor-specific T cells from blood for personalized analysis of their anti-cancer properties

IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction.

CONTEXT: The X-linked immunoglobulin superfamily, member 1 (IGSF1), gene is highly expressed in the hypothalamus and in pituitary cells of the POU1F1 lineage. Human loss-of-function mutations in IGSF1 cause central hypothyroidism, hypoprolactinemia, and macroorchidism. Additionally, most affected adults exhibit higher than average IGF-1 levels and anecdotal reports describe acromegaloid features in older subjects. However, somatotrope function has not yet been formally evaluated in this condition. OBJECTIVE: We aimed to evaluate the role of IGSF1 in human and murine somatotrope function. PATIENTS, DESIGN, AND SETTING: We evaluated 21 adult males harboring hemizygous IGSF1 loss-of-function mutations for features of GH excess, in an academic clinical setting. MAIN OUTCOME MEASURES: We compared biochemical and tissue markers of GH excess in patients and controls, including 24-hour GH profile studies in 7 patients. Parallel studies were undertaken in male Igsf1-deficient mice and wild-type littermates. RESULTS: IGSF1-deficient adult male patients demonstrated acromegaloid facial features with increased head circumference as well as increased finger soft-tissue thickness. Median serum IGF-1 concentrations were elevated, and 24-hour GH profile studies confirmed 2- to 3-fold increased median basal, pulsatile, and total GH secretion. Male Igsf1-deficient mice also demonstrated features of GH excess with increased lean mass, organ size, and skeletal dimensions and elevated mean circulating IGF-1 and pituitary GH levels. CONCLUSIONS: We demonstrate somatotrope neurosecretory hyperfunction in IGSF1-deficient humans and mice. These observations define a hitherto uncharacterized role for IGSF1 in somatotropes and indicate that patients with IGSF1 mutations should be evaluated for long-term consequences of increased GH exposure.: We acknowledge support from the Wellcome Trust to NS (100585/Z/12/A), GRW and JHDB (Strategic Award 101123/Z/13/A; Joint Investigator Awards 110140/Z/15/Z and 110141/Z/15/Z) and The National Institute for Health Research Biomedical Research Centre Cambridge (MG, NS). The Disease Model Core is supported by the UK MRC Metabolic Diseases Unit [MC_UU_00014/5] and the Wellcome Trust Major Award [208363/Z/17/Z]). PLT was funded by the UK MRC (U117562207). The Core biochemical Assay Laboratory is supported by MRC Metabolic Diseases Unit [MC_UU_00014/5]. DJB was supported by grants from the Canadian Institutes of Health Research (MOP-133557) and the Natural Sciences and Engineering Research Council of Canada (2015-05178)