| 1. |
- Abrahamsson, Niclas, 1976-
(författare)
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On the Impact of Bariatric Surgery on Glucose Homeostasis
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.
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| 2. |
- Edholm, David
(författare)
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Gastric Bypass : Facilitating the Procedure and Long-term Results
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastric bypass achieves weight loss in the morbidly obese. Preoperative weight loss is used to reduce the enlarged fatty liver that otherwise reduces visibility during surgery. The purpose of gastric bypass is to provide patients with long-term weight loss. The aim of this thesis was to investigate the result of preoperative low calorie diet on liver volume and to evaluate the long-term result of gastric bypass.Paper I showed that four weeks of low calorie diet reduces intrahepatic fat by 40% and facilitates surgery mainly through improved visualisation. Paper II demonstrated that all of the reduction of liver volume occurs during the first two weeks of treatment with low calorie diet. In paper I liver volume was reduced by 12% and in paper II by 18%. Paper III focused on long-term results and showed that gastric bypass achieves a mean 63% excess body mass index loss in obese patients after 11 years. However, of these 40% undergo abdominoplasty and 2% require additional bariatric surgery. Only 24% adhere to the lifelong recommendation on multivitamins and 72% to Vitamin B12 recommendations. Paper IV evaluated gastric bypass as a revisional procedure after earlier restrictive surgery had failed. Similar weight results as after primary gastric bypass are attained. No patient taking vitamin B12 supplementation was deficient at follow-up, regardless of whether the vitamin was taken as a pill or as intramuscular injections.
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| 3. |
- Elias, Khalid, 1975-
(författare)
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Changes in Gastrointestinal Function and Patient-scored Symptoms after Bariatric Surgery
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The obesity pandemic is rapidly increasing. Individuals with obesity are affected by obesity-related comorbidities, reduced life expectancy, and reduced quality of life. The most effective treatment for obesity and its comorbidities is bariatric surgery, restoring the physical component of quality of life. These procedures change bowel anatomy and physiology, giving rise to different gastrointestinal symptoms.In the first paper, we used data on quality of life from the Scandinavian Obesity Surgery Registry (SOReg) together with two validated disease-specific questionnaires to study bowel function and fecal incontinence after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS). In the second paper, we collected SOReg data on acid-related symptoms and diarrhea before and up to 5 years after RYGB, sleeve gastrectomy (SG) and BPD/DS. The association between the two symptoms and postoperative complications was studied. In the third paper, we studied bowel transit times and intraluminal pressure with a wireless motility capsule (WMC) before and after BPD/DS, comparing the result to lean controls. In the fourth paper, we analyzed gut peptide profiles before and after BPD/DS.In Paper I, RYGB resulted in reduced bowel motions but increased problems with abdominal pain, whereas BPD/DS resulted in increased number of bowel motions and more problems with flatus. General quality of life was improved after both operations. Paper II showed that the presence of acid-related symptoms and diarrhea was associated with increased risk for postoperative complications. RYGB relieved acid-related symptoms, but SG worsened them. Diarrhea increased 6-fold after BPD/DS. In Paper III, small bowel transit time was shortened, and motility was decreased in the distal small bowel after BPD/DS. Paper IV showed a clear reduction in postprandial levels of glucose and insulin and described in detail gut peptide profiles.In conclusion, general quality of life was improved after bariatric procedures although BPD/DS negatively affected bowel habits. The presence of acid-related symptoms and diarrhea increased the risk of postoperative complications. The novel use of WMC was safe, allowing future use for evaluation of bowel motility, both pre- and postoperatively. Glucose homeostasis was improved after BPD/DS with resolved insulin resistance. Postoperative hormone profiles will aid in maintaining weight loss.
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| 4. |
- Hedberg, Jakob, 1972-
(författare)
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Gastrointestinal Physiology and Results following Bariatric Surgery
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The number of operations for morbid obesity is rising fast. We have examined aspects of postoperative physiology and results after bariatric surgery. The pH in the proximal pouch after Roux-en-Y gastric bypass (RYGBP) was investigated with catheter-based and wire-less technique. Gastric emptying, PYY-levels in the fasting state and after a standardized meal was evaluated after biliopancreatic diversion with duodenal switch (DS). A clinical trial was undertaken, comparing DS to RYGBP in patients with BMI>48. Main outcome variables were safety and long-term weight results as well as abdominal symptoms and laboratory results. Patients with stomal ulcer had significantly lower pH in their proximal gastric pouch as compared to asymptomatic control subjects. Long-time pH measurements with the wire-less BRAVO-system were feasible and demonstrated pH<4 in median 10.5% of the time in asymptomatic post-RYGBP patients. After DS, the T50 of gastric emptying was 28±16 minutes. PYY-levels were higher after DS than in age-matched control subjects. BMI-reduction was greater after DS (24 BMI-units) than after RYGBP (17 BMI-units) in median 3.5 (2.0-5.3) years after surgery (p<0.001). Fasting glucose and HbA1c levels were lower one and three years after DS as compared to RYGBP. On the other hand, DS-patients reported having more diarrhea and malodorous flatus. This thesis has resulted in deepened knowledge. Acid produced in the proximal pouch is an important pathogenetic factor in the development of stomal ulcer after RYGBP. However, symptom-free patients have an acidic environment in the proximal Roux-limb as well. After DS, gastric emptying is fast, but not instantaneous, and PYY-levels are high. DS results in superior weight reduction and better glucose control as compared to RYGBP in patients with BMI>48. We believe that DS has a place in surgical treatment of the super-obese, even though symptoms of diarrhea and malodorous flatus are more common after DS.
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| 5. |
- Jestin Hannan, Christine
(författare)
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Esophageal and Gastroesophageal Junctional Cancer : Improving Patient selection, Treatment and Care
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Esophageal cancer is the sixth most common cause of cancer-related death. Choice of surgical approach and individualized treatment is crucial. The aims of this thesis were to evaluate the introduction of minimally invasive esophagectomy (MIE) regarding oncological results and postoperative complications. To investigate radiological differences in pulmonary complications between MIE and open technique by studying computed tomography (CT). To evaluate geographical differences in intention for curative treatment and their association to survival. As well as to further explore these differences by comparing assessments of tumor stage (TNM) and treatment recommendations in anonymized cases at regional multidisciplinary cancer conferences (MCC).A comparison of 51 MIE (21 hybrid and 30 totally minimally invasive) and 65 open resections in 2007-2016, showed an increased lymph node yield in the MIE group, 18 (13–23) vs. 12 (8–16) median (IQR), p<0.001. The result was confirmed in a multivariate regression model (adjusted odds ratio 3.15 [1.11–8.98], p=0.03). Postoperative complications did not differ between the groups.When comparing CT after open esophagectomy (n=20) and MIE (n=20), no ipsilateral differences in the areas of atelectasis or pleural effusion were seen. Nor did the groups differ in the proportion of patients with clinically important atelectasis (dx: 30% vs. 25%, sin: 65% vs. 65%) or pleural effusion (dx: 15% vs. 15%, sin: 65% vs. 45%).A total of 5959 esophageal cancer patients, diagnosed 2006-2015 in Sweden, were identified from the National Register for Esophageal and Gastric Cancer (NREV). In a multivariable analysis, a higher rate of treatment with curative intent (time ratio 1.17 [1.05-1.30], p<0.001) and a higher resection rate (time ratio 1.24 [1.12-1.37], p<0.001) were associated with improved survival.Fifty anonymized esophageal cancer cases were distributed to five expert MCCs. In estimations of T-stage, the MCCs were in total agreement in eight of 50 cases (16%). For N-stage, total agreement was seen in 17 cases (34%) and for clinical M-stage in 34 cases (68%). The MCCs agreed on recommended treatment in 26/50 cases (52%). In conclusion, the introduction of MIE resulted in a larger lymph node yield, without increased risk for complications. No difference in postoperative pleural effusion and atelectasis was seen on computed tomography five days after open esophagectomy compared with MIE. Patients diagnosed in a county with a higher curative intention rate and a higher rate of surgery had better five-year survival and there are differences in assessment of esophageal cancer patients at different MCCs.
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| 6. |
- Katsogiannos, Petros, 1979-
(författare)
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Bariatric surgery as treatment of type 2 diabetes – clinical and mechanistic aspects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bariatric surgery can rapidly improve glycemic control and cardiovascular risk factors in patients with T2D and obesity. These improvements appear to be partly independent of weight loss, however, the underlying mechanisms remain incompletely understood. A randomized controlled trial was designed where 19 patients with obesity and T2D were either operated with a Roux-en-Y gastric bypass (RYGB) operation or continued with standard-of-care treatment and followed up for 2 years, providing the data for Paper I-III.In paper I, we focused on changes in whole-body glucose metabolism in relation to changes in adipose tissue metabolism and morphology. We observed an early adipose tissue remodeling and a reduction in adipocyte size that however, did not correlate to the early improvements in metabolic control.In paper II, we analyzed the neuroendocrine changes after RYGB. We observed changes within 4 weeks with signs of enhanced parasympathetic outlow, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose, suggesting that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in T2D.In paper III the patients from the RYGB group were interviewed 2 years after surgery to examine the effects of surgery on health-related quality of life (HRQoL). We found that the improved HRQoL after RYGB was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness.In paper IV, we compared changes in circulating cytokine and adipokine levels in obese patients with- and without T2D. We observed that the cytokine profile of these patients is altered when compared to lean healthy control subjects and persist to a large extent after RYGB despite the weight loss and improved metabolic status.In conclusion, we observed that in the early post-operative period, neurohormonal changes appear to be more important than adipose tissue changes in improving insulin sensitivity and leading to diabetes remission.In the qualitative part of our study, we observed that the improved HRQoL was not solely explained by weight loss
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| 7. |
- Linder, Gustav, 1981-
(författare)
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Esophageal- and Gastroesophageal Junctional Cancer : Aspects on Staging, Treatment and Results
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Esophageal- and gastroesophageal junctional (GEJ) cancer is the sixth cause of cancer-related death worldwide. Some improvements in care are attributed to nationwide disease-specific registries, preoperative staging and increased understanding of mechanisms affecting patient selection. Surgery, however, is a cornerstone for treatment where minimally invasive surgery and increased understanding of perioperative physiology may be beneficial. The aims of this thesis were to validate the Swedish national registry for esophageal and gastric cancer (NREV) and to explore mechanisms in patient selection, perioperative physiology, treatment-related outcomes and staging.A validation study with re-abstracted data on 400 patients determined NREV comparable to other similar registries and to have a completeness of 95.5 %. Overall accuracy was 91.1 % throughout the registry and timeliness to reporting was adequate.In a cohort of 4112 patients from NREV, high education level was associated with an increased probability of being allocated to curative treatment, as was the presence of a multidisciplinary treatment conference. High education level was associated with improved survival.By measuring intramucosal pH (pHi) in 32 patients, to describe perfusion in the gastric conduit during esophagectomy, a reduction in perfusion was seen at all surgical steps altering vascular supply to the conduit but foremost after gastric tube construction by linear stapling. Patients with low pHi on the first postoperative day were more prone to anastomotic insufficiency.In 116 patients undergoing esophagectomy (65 open and 51 minimally invasive), a retrospective cohort study regarding surgical oncological results and postoperative complications was conducted. Lymph node yield was increased, peroperative blood loss and in-hospital stay were reduced with minimally invasive esophagectomy. Postoperative complications were unaffected by surgical approach. In a prospective study of nineteen patients, whole-body integrated PET/MRI was compared to PET/CT in preoperative staging. PET/MRI was safe and feasible. Accuracy and correlations between modalities were good regarding tumor characteristics and N- and M-staging. In T-staging there were discrepancies indicating differences between modalities.The thesis presents data on the quality of NREV for future research and elaborates on patient selection, staging, perioperative physiology and treatment-related outcomes for patients with esophageal- and GEJ cancer.
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| 8. |
- Löfling Skogar, Martin, 1983-
(författare)
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Bariatric Surgery : Outcomes after Gastric Bypass and Duodenal Switch
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is associated with increased morbidity and mortality. A BMI >40 kg/m2 shortens life expectancy by about 10 years. The obesity related comorbidities diabetes, hypertension, dyslipidemia and sleep apnea contributes to the increased risk of cardiovascular events. There is also an increased risk of some forms of cancer (e.g. colon, breast, and prostate cancer) as well as mental illness (depression and low self-esteem). Bariatric surgery is indicated for those with a BMI >35 kg/m2. Unfortunately, there are an increasing number of patients seeking bariatric surgery who are super obese (BMI >50 kg/m2), a condition more difficult to treat because of insufficient weight loss with standard operations, like the Roux-en-Y Gastric Bypass (RYGB). Therefore some surgeons advocate the Duodenal Switch (DS) in super obese patients, because DS results in greater and more sustained weight loss. However, DS is a technically more challenging operation and is associated with an increased risk of malnutrition and surgical complications. There are also concerns about an excessive loss of fat-free mass during weight loss after RYGB and especially after DS.This thesis focuses on weight-loss, effect on comorbidities, quality of life and complications after DS and RYGB, respectively, with comparisons between the two procedures in patients with super obesity. DS resulted in a superior weight loss compared to RYGB (paper I, II and III) and body composition after weight loss did not differ compared with non-operated controls with the same BMI after surgery, for neither DS nor RYGB (paper I). Both DS and RYGB resulted in an improved metabolic control (paper II and III), but the effect on diabetes and hypertension was greater and maintained in the long-term after DS (paper III). Both DS and RYGB resulted in an improved physical quality of life, with greater improvements after DS (paper III). However, complications and long-term adverse effects were more common after DS (paper II and IV).In conclusion, the superior weight loss and greater improvements in several obesity-related comorbidities after DS must be weighed against the increased risk of complications and long-term adverse effects compared to RYGB.
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| 9. |
- Sima, Eduardo, 1975-
(författare)
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Gastric bypass : Technical aspects and long-term results
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Roux-en-Y gastric bypass (RYGBP) achieves superior short- and long-term weight loss compared to other weight loss modalities. Different operative techniques have been developed to technically facilitate the surgical procedure, with consequences in the form of an array of postoperative complications and gastrointestinal symptoms. Furthermore, as our follow-up on operated patients extends beyond the first postoperative years, it becomes apparent that a significant number of patients experience unsatisfactory weight result. Current research is just starting to chart factors associated with postoperative long-term weight regain with the ultimate goal of preventing it.In Paper I it is found that the linear stapled technique for the gastrojejunostomy in laparoscopic RYGBP is associated with shorter operative time, in-hospital stay and a lower incidence of surgical site infections and anastomotic strictures compared to the circular stapled technique. Paper II demonstrates that, despite no differences in weight result, the 21-mm circular stapled technique for the gastrojejunostomy is associated with a higher incidence of vomiting and endoscopic anastomotic dilatations compared to the 25-mm circular stapled technique and the linear stapled technique in the long-term after RYGBP. Paper III shows that despite differences in body composition, long-term weight responders and non-responders after RYGBP did not differ in resting, glucose-induced or activity-related energy expenditure. Lastly Paper IV shows long-term weight result is associated with fasting levels of leptin and ghrelin, and that the response of these hormones to a glucose load might contribute to perpetuate obesity.
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| 10. |
- Stevens, Katharina, 1988-
(författare)
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The Effects of Bariatric Surgery upon the Maintenance of Calcium and Vitamin D Levels
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is a growing pandemic, and consequently the population that has undergone a bariatric procedure is steadily rising. Through various mechanisms, bariatric surgery alters the gastrointestinal anatomy, thereby obtaining weight loss while being associated with various nutrient deficiencies including vitamin D. Over time, vitamin D deficiency may lead to elevated levels of parathyroid hormone (PTH) and the depletion of bone, in order to maintain circulating calcium levels. The aim of this thesis was to study the effects of bariatric surgery upon calcium homeostasis. In paper I we sought to investigate whether lifestyle factors could explain the difference in bone mineral density (BMD) seen among Roux-en-Y gastric bypass (RYGBP) patients. The second paper is a population-based study that examines the postoperative trends of vitamin D and PTH among patients that have undergone either a RYGBP or a sleeve gastrectomy (SG) (the two currently most popular bariatric procedures worldwide). In paper III the purpose was to explore whether medications to treat dyspepsia had an impact upon calcium homeostasis postoperatively among RYGBP patients. And finally, the purpose of the fourth paper was to study an intramuscular injection as an alternative method for the treatment of vitamin D deficiency among patients who had undergone a biliopancreatic diversion/duodenal switch (BPD/DS) procedure. The results from paper I do not indicate that lifestyle factors are a cause of the reduced BMD observed after a RYGBP, therefore the procedure itself is a likely cause of reduced BMD. The analysis conducted in paper II points to the impact that bariatric procedures (specifically RYGBP and SG) have over time regarding vitamin D deficiency. The results showed both differences between procedures as well as a successive decline in vitamin D parallelled by a rise in PTH with time after surgery. In paper III our results indicate that regular PPI therapy is strongly associated with a much higher incidence of pathological PTH levels, suggesting that the combination of the procedure and the medication may have deleterious effects upon calcium homeostasis. Finally, when managing vitamin D deficiency after a BPD/DS procedure, we showed that intramuscular injections had a substantial effect upon both vitamin D levels and PTH levels.
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