The Impact of Opioid Receptor Gene Polymorphism on Fentanyl and Alfentanil's Analgesic Effects in the Pediatric Perioperative Period.

Introduction: The polymorphism of the gene coding mu-opioid receptor (OPRM1) is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages. Methods: This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil. Postoperative pain was rated using Numerical Rating Scale (0-10). All the patients were genotyped forOPRM1 118A>G (rs1799971) gene polymorphism. Results: School children under the age of 11 with the OPRM1 AA genotype were shown to have a higher BMI (p<0.05). Children over the age of 12 carrying G allele OPRM1, had increased postoperative pain sensitivity and intensity (3.28±1.95 vs 4.91±2.17; p<0.05), as compared to AA allele carriers. Discussion: OPRM1 118A>G polymorphism may explain the variation in the perception of postoperative pain in children over the age of 12 and may be a useful predictor for adjusting the dose of analgesics, but the dose is relative to the patient's needs regardless of his genetic characteristics. In younger children, carriers of polymorphic OPRM1 118G allele may be protected from obesity, due to diminished MOP expression.

Banded Versus Non-banded Sleeve Gastrectomy: 5-Year Results of a 3-Year Randomized Controlled Trial.

PURPOSE: Banded sleeve gastrectomy (BSG) has been shown to enable better weight loss than non-banded sleeve gastrectomy (SG) in retrospective analyses. These findings were supported by two randomized controlled trials (RCT). However, to date, mid-term prospective data is not available. MATERIALS AND METHODS: We invited all 94 patients of an RCT comparing banded to non-banded sleeve gastrectomy at 3 years (DRKS00007729) for a 5-year follow-up visit. Eighty-two patients (BSG n = 42; SG n = 40) came for evaluation. Outcome measures were identical with the RCT to allow longitudinal comparison. Data analysis was descriptive and focused on biometric data, development of comorbidities, mid-term complications, quality of life, and type of body contouring surgery (BCS). RESULTS: The per-protocol analysis revealed a treatment difference of 9% (CI - 1.5 to 19.6) excess weight loss (EWL). Total weight loss (TWL) was 27.4% (CI 23.5-31.3) after SG and 31.6% (CI 27.3-35.5) after BSG. Twenty percent of patients after SG and 11.9% following BSG had been converted to a gastric bypass. Type 2 diabetes went into remission in most patients (SG 66.7% vs. BSG 63.6%). Antihypertensive medication was stopped or reduced in 81.3% after SG and 80% after BSG. Reflux symptoms were similar in both groups (symptoms [Formula: see text] 1/ week: SG 28.2% vs. BSG 26.8%). Frequency of postprandial regurgitation was higher after BSG (SG 23% vs. BSG 59%). Forty percent of patients had undergone BCS at time of follow-up. CONCLUSION: Five-year weight loss after BSG was 9% EWL and 4.2% TWL higher compared to SG. The main added morbidity following BSG was postprandial regurgitation.

The DECON pilot project investigates predictive markers for successful bariatric surgery.

Obesity is a chronic, multifactorial disease which is linked to a number of adverse endocrinological and metabolic conditions. Currently, bariatric surgery is one of the most effective treatments for individuals diagnosed with severe obesity. However, the current indications for bariatric surgery are based on inadequate metrics (i.e., BMI) which do not account for the complexity of the disease, nor the heterogeneity among the patient population. Moreover, there is a lack of understanding with respect to the biological underpinnings that influence successful and sustained weight loss post-bariatric surgery. Studies have implicated age and pre-surgery body weight as two factors that are associated with favorable patient outcomes. Still, there is an urgent medical need to identify other potential factors that could improve the specificity of candidate selection and better inform the treatment plan of patients with obesity. In this report, we present and describe the cohort of the DECON pilot project, a multicenter study which aims to identify predictive biomarkers of successful weight loss after bariatric surgery.

Parental Obesity Predisposition and Age of Onset Associate with Poor Response to Bariatric and Metabolic Surgery.

INTRODUCTION: Parental predisposition and age of onset may be independently associated with 1-year total weight loss (TWL) failure (< 20%) after metabolic-bariatric surgery (MBS). METHODS: This cohort study includes all cases of the German StuDoQ|MBE register (2015-2019) with data on parental predisposition, obesity onset, and at least 1-year follow up after primary MBS procedures (n = 14,404). We provide descriptive statistics of the cohort in terms of the main outcome and 1-year TWL failure, and provide characteristics of surgery type subgroups. Finally, we provide a multivariate logistic regression model of 1-year TWL failure. RESULTS: 58.8% and 45.7% of patients reported maternal and paternal predisposition for obesity, respectively. Average onset of obesity was 15.5 years and duration of disease 28.3 years prior to MBS. SG is the most frequently performed procedure (47.2%) followed by RYGB (39.7%) and OAGB (13.1%). Mean 1-year TWL is 32.7 ± 9.3%, and 7.8% (n = 1,119) of patients show TWL failure (< 20%). Multivariate analysis shows independent association of early onset of obesity (< 18 years), male sex, age at operation, pre-operative BMI, pre-operative weight loss, sleeve gastrectomy (SG), and type 2 diabetes (T2D) with 1-year TWL failure (p < 0.001). CONCLUSION: The proportions of MBS patients that report on paternal and maternal predisposition for obesity are 45.7% and 58.8% respectively, and average age at onset is 15.5 years. 7.8% of patients do not meet current target criteria of successful response to surgery at 1 year. Early onset, male sex, age at operation, pre-operative BMI, pre-operative weight loss, SG, and T2D are independently associated with weight loss failure.

Long-Term Diabetes Improvement After Duodenal Exclusion in Zucker Diabetic Fatty Rats Is Associated with Prevention of Strain-Specific Pancreatic Remodeling and Increased Beta Cell Proliferation.

BACKGROUND: Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas. MATERIALS AND METHODS: We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness. RESULTS: DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham. CONCLUSION: In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis.

Obesity Surgery.

BACKGROUND: In 2017, the prevalence of obesity (BMI ≥= 30 kg/m2) in Germany was approximately 16%. Obesity increases an individual's risk of developing type 2 diabetes (T2DM) and arterial hypertension; it also increases overall mortality. Consequently, effective treatment is a necessity. Approximately 20 000 bariatric operations are performed in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane databases and on current German clinical practice guidelines. RESULTS: The types of obesity surgery most commonly performed in Germany, Roux-en-Y gastric bypass and sleeve gastrectomy, lead to an excess weight loss of 27-69% ≥= 10 years after the procedure. In obese patients with T2DM, the diabetes remission rate ≥= 10 years after these procedures ranges from 25% to 62%. Adjusted regression analyses of data from large registries have shown that the incidence of malignancies is 33% lower in persons who have undergone obesity surgery compared to control subjects with obesity (unadjusted incidence 5.6 versus 9.0 cases per 1000 person-years). The operation can cause vitamin deficiency, surgical complications, gastroesophageal reflux, and dumping syndrome. Therefore, lifelong follow-up is necessary. CONCLUSION: In view of an increasing number of patients undergoing bariatric surgery, it will probably not be feasible in the future for lifelong follow-up to be provided exclusively in specialized centers.

Ligamentum teres augmentation (LTA) for hiatal hernia repair after minimally invasive esophageal resection: a new use for an old structure.

PURPOSE: Hiatal hernias with intrathoracic migration of the intestines are serious complications after minimally invasive esophageal resection with gastric sleeve conduit. High recurrence rates have been reported for standard suture hiatoplasties. Additional mesh reinforcement is not generally recommended due to the serious risk of endangering the gastric sleeve. We propose a safe, simple, and effective method to close the hiatal defect with the ligamentum teres. METHODS: After laparoscopic repositioning the migrated intestines, the ligamentum teres is dissected from the ligamentum falciforme and the anterior abdominal wall. It is then positioned behind the left lobe of the liver and swung toward the hiatal orifice. Across the anterior aspect of the hiatal defect it is semi-circularly fixated with non-absorbable sutures. Care should be taken not to endanger the blood supply of the gastric sleeve. RESULTS: We have used this technique for a total of 6 patients with hiatal hernias after hybrid minimally invasive esophageal resection in the elective (n = 4) and emergency setting (n = 2). No intraoperative or postoperative complications have been observed. No recurrence has been reported for 3 patients after 3 months. CONCLUSION: Primary suture hiatoplasties for hiatal hernias after minimally invasive esophageal resection can be technically challenging, and high postoperative recurrence rates are reported. An alternative, safe method is needed to close the hiatal defect. Our promising preliminary experience should stimulate further studies regarding the durability and efficacy of using the ligamentum teres hepatis to cover the hiatal defect.

Leg Volume in Patients with Lipoedema following Bariatric Surgery.

INTRODUCTION: Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. MATERIAL AND METHODS: In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10-18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. RESULTS: Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6-25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, p < 0.0001 and p = 0.0001; baseline vs. 2nd follow-up, p < 0.0001 and p = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control p > 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, p = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, p = 0.43). CONCLUSION: SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Immunomodulatory effects of galectin-1 in patients with chronic lymphocytic leukemia.

Galectin-1 (Gal-1) has been implicated in the progression of chronic lymphocytic leukemia (CLL) but also the development of immunodeficiency, which commonly accompany this malignancy. In this in vitro study, we investigated the effects of Gal-1 inhibition in the sera of immunocompromised CLL patients on immunomodulating properties of dendritic cells (DCs). DCs derived from peripheral blood mononuclear cells were treated with a healthy serum, CLL serum as well as the combination of CLL serum and Gal-1 inhibitor (OTX008). Following the treatment, the expression levels of DC maturation markers (CD80, CD83, CD86 and IDO-1) were determined as well as their cytokine profile and the ability to polarize the immune response in co-cultures with CD4+ T cells. After treatment with CLL serum, an increase in interleukin (IL)-10 production was observed in both DC cultures and co-cultures with CD4+ T cells. OTX008 caused a reduction in IL-10 production as well as IL-2, but no significant alteration in the expression of DC maturation markers or T regulatory cell (Treg) frequency was observed. The results of our study suggest that Gal-1 from CLL serum give rise to a specific IL-10+ CD4+ T cell phenotype, other than Treg, that could mediate immunodeficiency development in CLL patients.

Augmentation of Hiatal Repair with the Ligamentum Teres Hepatis for Intrathoracic Gastric Migration After Bariatric Surgery.

PURPOSE: The augmentation of hiatoplasty (HP) with the ligamentum teres hepatis (LTA) is a new concept for intrathoracic migration of a gastric sleeve or pouch (ITGM). We retrospectively analyzed all cases of hiatal hernia repair in a single center between 2015 and 2019. METHODS: A total of 171 patients underwent 307 hiatal hernia repairs after sleeve gastrectomy (SG) (n = 79), Roux-en-Y gastric bypass (RYGB) (n = 129), and one anastomosis gastric bypass (OAGB) (n = 99). Each hiatal hernia repair was defined as a "case" and assigned to the LTA group or the non-LTA group. The primary outcome was the recurrence of ITGM as detected by endoscopy or CT. RESULTS: The basic characteristics in the LTA group (78 cases) and the non-LTA group (229 cases) were comparable with the exception of the rate of revisional HP (72% vs. 21%), the rate of prior conversion to RYGB (33% vs. 17%), the initial BMI (45.9 ± 8.2 kg/m2 vs. 49.0 ± 8.8 kg/m2), and the follow-up (7 months (1-16) vs. 8 months (1-54)). The ITGM recurrence rate was 15% in the LTA group and 72% in non-LTA group (p < 0.001). Multivariate analysis showed that the length of ITGM and the type of surgical repair were independent risk factors. The addition of LTA to HP lowered the probability of ITGM recurrence by a factor of 0.35 (p = 0.015), but the conversion from SG or OAGB to RYGB did not reduce the risk. CONCLUSIONS: LTA reduces the risk of early ITGM recurrence. The long-term durability, however, needs to be further investigated.

The New Interest of Bariatric Surgeons in the Old Ligamentum Teres Hepatis.

The search for an operation that effectively prevents and treats intrathoracic gastric migration (ITGM) after bariatric surgery has revived a long-forgotten technique: ligamentum teres cardiopexy (LTC) by which a vascularized flap of the teres ligament is wrapped around the distal esophagus. The systematic search of publications in the English language revealed 4 studies (total number of patients 53) in the non-bariatric literature with an unsatisfactory resolution of GERD. There were 5 reports from the bariatric literature with small patient numbers (total 64) and a short follow-up (6-36 months). There were no objective signs of gastric remigration in 93% of investigated patients. Acknowledging the limitations of these preliminary reports, bariatric surgeons are encouraged to further investigate the potentials of LTC in their patients.

Banded Versus Nonbanded Sleeve Gastrectomy: A Randomized Controlled Trial With 3 Years of Follow-up.

OBJECTIVE: The aim of this study was to compare silicone-banded sleeve gastrectomy (BSG) to nonbanded sleeve gastrectomy (SG) regarding weight loss, obesity-related comorbidities, and complications. SUMMARY BACKGROUND DATA: As a primary bariatric procedure, SG leads to excellent weight loss, yet weight regain is a relevant issue in mid- to long-term follow-up. Retrospective analyses suggest that banding a sleeve using a silicone ring may decrease weight regain and improve weight loss. METHODS: The banded versus nonbanded sleeve gastrectomy single-center, randomized controlled trial was conducted from January 2015 to August 2019. The primary endpoint was defined as excess weight loss 3 years after surgery. Secondary endpoints included the surgery's impact on obesity-related comorbidities, quality of life, and complications. The study was registered under DRKS00007729. RESULTS: Among 94 patients randomized, 97% completed 3-year follow-up. Mean initial body mass index was 50.9 kg/m [95% confidence interval (CI), 49.6-52.2]. Mean adjusted excess weight loss 3 years after SG amounted to 62.3% (95% CI, 56.2-68.5) and 73.9% ( 95% CI, 67.8-80.0) after BSG (difference 11.6%, P = 0.0073). Remission of type 2 diabetes occurred in 66.7% (4/6) after SG and in 91.0% (10/11) following BSG (P = 0.21). Three years after surgery, ring implantation correlated with decreased frequency of symptomatic reflux episodes (P = 0.01) but increased frequency of regurgitation (P = 0.03). The rate of major complications was not different between the study groups (BSG, n = 3; SG, n = 2; P = 0.63). Quality of life was better following BSG (P = 0.001). CONCLUSIONS: BSG provided better weight loss than nonbanded SG 3 years after surgery. Regurgitation was the main clinically relevant negative effect after BSG.

CD4+ T cell phenotypes in the pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts due to enhanced platelet clearance and compromised production. Traditionally, ITP was regarded a B cell mediated disorder as anti-platelet antibodies are detected in most patients. The very nature of self-antigens, evident processes of isotype switching and the affinity maturation of anti-platelet antibodies indicate that B cells in order to mount anti-platelet immune response require assistance of auto-reactive CD4+ T cells. For a long time, ITP pathogenesis has been exclusively reviewed through the prism of the disturbed balance between Th1 and Th2 subsets of CD4+ T cells, however, more recently new subsets of these cells have been described including Th17, Th9, Th22, T follicular helper and regulatory T cells. In this paper, we review the current understanding of the role and immunological mechanisms by which CD4+ T cells contribute to the pathogenesis of ITP.

Effects of galectin-1 on immunomodulatory properties of human monocyte-derived dendritic cells.

Our study aimed to evaluate the effects of Gal-1 in dose depending manner on maturation and immunomodulatory properties of monocyte-derived (Mo) DCs in-vitro. The effects were analyzed by monitoring their phenotypic characteristics, cytokine profile, and the ability to direct the immune response in the co-culture with allogeneic CD4+T cells. Gal-1 reduced the expression of CD80 and CD86 molecules on MoDCs compared to untreated MoDCs. Gal-1 at concentrations of 1 and 6 µg/mL significantly reduced IL-12 production, while the concentration of 3 µg/mL led to its significant increase. Gal-1 in all concentrations induced a significant increase in the production of IL-10. Treatment of MoDCs with 3 and 6 µg/mL of Gal-1 stimulated the production of IL-2 and IFN-γ in the co-culture with CD4+T lymphocytes. This study demonstrated a dual immunomodulatory effect of Gal-1 on MoDCs in terms of immune stimulation and immune suppression, depending on the applied concentration.

Putting the Hindgut Hypothesis to the Test in a Diabetic Zucker Rat Model.

BACKGROUND: The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus. METHODS: Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly. RESULTS: In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups. CONCLUSION: This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.

Banded versus nonbanded sleeve gastrectomy: 5-year results of a matched-pair analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) achieves excellent weight loss, yet recent reports indicate weight regain in a substantial number of patients. OBJECTIVES: Inserting a nonadjustable gastric band may improve weight loss after SG. SETTING: University Hospital, Germany. METHODS: In a retrospective matched-pair analysis 51 patients who underwent banded SG (BSG) using a silicone ring between November 2010 and May 2017 were compared with patients who underwent conventional SG regarding weight loss, complications, and co-morbidity. Median follow-up was 5 years. RESULTS: Total weight loss was equal in the early follow-up (P = .118 and P = .111) but significantly better in BSG 3 and 5 years after surgery (BSG versus SG at 3 yr 38.7% ± 7.8, n = 33 versus 31.9 ± 10.7, n = 33, P = .002; BSG versus SG at 5 yr 37.6% ± 8.5, n = 27 versus 29.5 ± 12.9, n = 23, P = .008). Ring placement had no significant impact on clinical reflux signs (Fisher's exact test P > .999), yet 37 % of BSG patients reported ≥1 regurgitation per week (Fisher's exact test P = .013, odds ratio 12.4). CONCLUSION: BSG leads to better weight loss than nonbanded SG 5 years after surgery. This comes at the expense of a higher rate of regurgitation. At a time in which weight loss limitations of a stand-alone SG are becoming a clinical problem, banding the sleeve may be a strategy to improve weight loss with this procedure.

Hybrid Minimally Invasive Esophagectomy-Surgical Technique and Results.

BACKGROUND: Hybrid minimally invasive esophagectomy (HMIE) has been proven to be superior when compared with open esophagectomy, with a significant reduction of postoperative morbidity. In HMIE, the laparotomy is replaced by a minimally invasive laparoscopic approach. The radical mediastinal resection plus reconstruction is performed by a thoracic approach through a muscle-sparing thoracotomy. In this instructional article, we describe the surgical technique of HMIE in detail in order to facilitate possible adoption of the procedure by other surgeons. In addition, we give the monocentric results of our own practice. METHODS: Between 2013 and 2018, HMIE was performed in 157 patients. The morbidity and mortality data of the procedure is shown in a retrospective monocentric analysis. RESULTS: Overall, 54% of patients had at least one perioperative complication. Anastomotic leak was evident in 1.9%, and a single patient had focal conduit necrosis of the gastric pull-up. Postoperative pulmonary morbidity was 31%. Pneumonia was found in 17%. The 90 day mortality was 2.5%. Wound infection rate was 3%, and delayed gastric emptying occurred in 17% of patients. In follow up, 12.7% presented with diaphragmatic herniation of the bowel, requiring laparoscopic hernia reduction and hiatal reconstruction and colopexy several months after surgery. CONCLUSION: HMIE is a highly reliable technique, not only for the resection part but especially in terms of safety in reconstruction and anastomosis. For esophageal surgeons with experience in minimally invasive anti-reflux procedures and obesity surgery, HMIE is easy and fast to learn and adopt.

Recurring Anastomotic Leak-A Prospective Clinicopathological Investigation of a Distinct Disease Pattern.

BACKGROUND: Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. MATERIALS AND METHODS: Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. RESULTS: Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. CONCLUSIONS: RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.

The effect of pasireotide on intestinal anastomotic healing with and without whole-body irradiation in a rat model.

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.