Treg(s) in Cancer: Friends or Foe?

Immune escape is a hallmark of cancer. Regulatory T cells (Treg) have been described to maintain peripheral tolerance. The role of Treg in cancer is ambiguous, as they are central inhibitory regulators in solid tumors, whereas during inflammation-driven tumorigenesis they prevent cancer initiation by restraining inflammation. As a consequence, under conditions with chronic inflammation that may initiate malignant transformation, application rather than depletion of Treg may be helpful. In solid tumors, however, the success story of immune-activating antibodies targeting checkpoint molecules of T cell activation fuels the hope that Treg inactivation or depletion may additionally boost anti-tumor immune response. In this review we summarize important aspects on the dual role of Treg in cancer to provide a rationale for future Treg targeting attempts.

Novel treatment concepts for graft-versus-host disease.

Acute and chronic graft-versus-host disease (GVHD) are potentially lethal complications after stem cell transplantation (SCT). Steroids are the appropriate first-line treatment for both. However, if patients do not adequately benefit from steroid therapy, mortality is high and standardized treatment algorithms are lacking. This is mainly because of limited data from prospective, randomized clinical trials. In addition, most of the available treatment options only induce clinical benefits in a limited proportion of patients. Thus, there is an urgent clinical need to develop more potent immunosuppressive treatment strategies for patients suffering from acute or chronic steroid-refractory GVHD while maintaining the graft versus tumor effect to avoid a potential rise in relapse-related mortality. The increasing knowledge about host- as well as donor-derived variables favoring GVHD development and the increasing armamentarium of immune-modulatory agents entering preclinical and clinical research will probably allow more effective treatment of GVHD in the future. This review describes novel developments in the treatment of steroid-refractory GVHD, with a special focus on the rationale behind promising pharmacologic compounds or up-coming cellular therapies.

Reinforcement of cancer immunotherapy by adoptive transfer of cblb-deficient CD8+ T cells combined with a DC vaccine.

The success of cancer immunotherapy is limited by potent endogenous immune-evasion mechanisms, which are at least in part mediated by transforming growth factor-ß (TGF-ß). The E3 ubiquitin ligase Cbl-b is a key regulator of T cell activation and is established to regulate TGF-ß sensitivity. cblb-deficient animals reject tumors via CD8(+) T cells, which make Cbl-b an ideal target for improvement of adoptive T-cell transfer (ATC) therapy. In this study, we show that cblb-deficient CD8(+) T cells are hyper-responsive to T-cell receptor (TCR)/CD28-stimulation and are in part protected against the negative cues induced by TGF-ß in vitro. Notably, adoptive transfer of polyclonal, non-TCR transgenic cblb-deficient CD8(+) T cells is not sufficient to reject B16-ova or EG7 tumors in vivo. Thus, cblb-deficient ATC requires proper in vivo re-activation by a dendritic cell (DC) vaccine. In strict contrast to ATC monotherapy, this approach delayed tumor outgrowth and significantly increased survival rates, which is paralleled by increased CD8(+) T-cells infiltration to the tumor site and enrichment of ova-specific and interferon-γ (IFN-γ)-secreting CD8(+) T cell in the draining lymph node (LN). Moreover, CD8(+) T cells from cblb-deficient mice vaccinated with the DC vaccine show increased cytolytic activity in vivo. In summary, our data using cblb-deficient polyclonal, non-TCR-transgenic adoptively transferred CD8(+) T cells into immuno-competent non-lymphodepleted recipients suggest that targeting Cbl-b might serve as a novel 'adjuvant approach', suitable to augment the effectiveness of established anti-cancer immunotherapies.

Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls.

BACKGROUND: Obesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters. METHODS: Plasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD). RESULTS: Compared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients. CONCLUSIONS: The results suggest that both MO and CRC have low-grade inflammation as part of their etiology.

The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism.

RATIONALE: The neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. OBJECTIVE: Catestatin shares several functions with angiogenic factors. We therefore reasoned that catestatin induces growth of new blood vessels. METHODS AND RESULTS: Catestatin induced migration, proliferation, and antiapoptosis in endothelial cells and exerted capillary tube formation in vitro in a Matrigel assay, and such effects were mediated via G protein, mitogen-activated protein kinase, and Akt. Catestatin-induced endothelial cell functions are further mediated by basic fibroblast growth factor, as shown by blockade of effects by a neutralizing fibroblast growth factor antibody. Furthermore, catestatin released basic fibroblast growth factor from endothelial cells and stimulated fibroblast growth factor signaling. In addition to its function on endothelial cells, catestatin also exerted effects on endothelial progenitor cells and vascular smooth muscle cells. In vivo, catestatin induced angiogenesis in the mouse cornea neovascularization assay and increased blood perfusion and number of capillaries in the hindlimb ischemia model. In addition to angiogenesis, catestatin increased density of arterioles/arteries and incorporation of endothelial progenitor cells in the hindlimb ischemia model, indicating induction of arteriogenesis and postnatal vasculogenesis. CONCLUSION: We conclude that catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism.

Gene therapy with the angiogenic cytokine secretoneurin induces therapeutic angiogenesis by a nitric oxide-dependent mechanism.

RATIONALE: The neuropeptide secretoneurin induces angiogenesis and postnatal vasculogenesis and is upregulated by hypoxia in skeletal muscle cells. OBJECTIVE: We sought to investigate the effects of secretoneurin on therapeutic angiogenesis. METHODS AND RESULTS: We generated a secretoneurin gene therapy vector. In the mouse hindlimb ischemia model secretoneurin gene therapy by intramuscular plasmid injection significantly increased secretoneurin content of injected muscles, improved functional parameters, reduced tissue necrosis, and restored blood perfusion. Increased muscular density of capillaries and arterioles/arteries demonstrates the capability of secretoneurin gene therapy to induce therapeutic angiogenesis and arteriogenesis. Furthermore, recruitment of endothelial progenitor cells was enhanced by secretoneurin gene therapy consistent with induction of postnatal vasculogenesis. Additionally, secretoneurin was able to activate nitric oxide synthase in endothelial cells and inhibition of nitric oxide inhibited secretoneurin-induced effects on chemotaxis and capillary tube formation in vitro. In vivo, secretoneurin induced nitric oxide production and inhibition of nitric oxide attenuated secretoneurin-induced effects on blood perfusion, angiogenesis, arteriogenesis, and vasculogenesis. Secretoneurin also induced upregulation of basic fibroblast growth factor and platelet-derived growth factor-B in endothelial cells. CONCLUSIONS: In summary, our data indicate that gene therapy with secretoneurin induces therapeutic angiogenesis, arteriogenesis, and vasculogenesis in the hindlimb ischemia model by a nitric oxide-dependent mechanism.

The sphingosine 1-phosphate receptor agonist FTY720 potently inhibits regulatory T cell proliferation in vitro and in vivo.

CD4(+)CD25(+) regulatory T cell (Treg) entry into secondary lymphoid organs and local expansion is critical for their immunosuppressive function. Long-term application of the sphingosine-1 phosphate receptor agonist FTY720 exerts pleiotropic anti-inflammatory effects, whereas short-term FTY720 boosts antiviral immunity. In this study, we provide evidence that FTY720 potently inhibits Treg proliferation in vitro and in vivo without affecting their viability, phenotype, or in vitro immunosuppression. In contrast, adoptively transferred Treg exposed ex vivo to FTY720 lost their protective effects in murine models of acute glomerulonephritis and acute graft-vs-host disease. On a cellular level, FTY720 inhibits IL-2-induced STAT-5 phosphorylation, paralleled by a loss of FoxP3 expression during Treg expansion in vitro. Notably, loss of in vivo immunosuppression is not due to impaired migration to or localization within secondary lymphoid organs. We could even show a selective trapping of adoptively transferred Treg in inflammatory lymph nodes by FTY720. Finally, Treg isolated from animals systemically exposed to FTY720 also exhibit a significantly impaired proliferative response upon restimulation when compared with Treg isolated from solvent-treated animals. In summary, our data suggest that sphingosine-1 phosphate receptor-mediated signals induced by FTY720 abrogate their in vivo immunosuppressive potential by blocking IL-2 induced expansion, which is indispensable for their in vivo immunosuppressive activity.

Pacritinib protects dendritic cells more efficiently than ruxolitinib.

Targeting Janus kinase (JAK) has revolutionized the treatment of myeloproliferative neoplasms. The JAK inhibitor ruxolitinib has improved the outcome and quality of life of patients dramatically at the cost of increased risk of infections. As previously reported, ruxolitinib severely impairs the differentiation of peripheral blood mononuclear cells to monocyte-derived dendritic cells and inhibits the function of dendritic cells in vitro and in vivo, which expanded its use as an immunomodulatory compound. Pacritinib is a novel JAK inhibitor that will soon be approved for the treatment of myeloproliferative neoplasms, and early results are promising. We investigated the impact of the novel JAK inhibitor pacritinib on the function of monocyte-derived dendritic cells and compared it with that of ruxolitinib. In contrast to ruxolitinib, pacritinib exhibits only mild suppressive effects on dendritic cells. The upregulation of activation markers and CCR7 after TLR4 ligation is not or is only marginally affected by pacritinib. Pacritinib, at concentrations reflecting patients' plasma levels, reduces interleukin (IL)-12 secretion, whereas IL-6 and tumor necrosis factor α levels are unchanged at this concentration. In conclusion, the immunosuppressive effect of pacritinib on dendritic cells is significantly less pronounced than the effect of ruxolitinib. Therefore, our data may help to identify those patients with myelofibrosis who may benefit from pacritinib treatment.

Rheumatologic diseases impact the risk of progression of MGUS to overt multiple myeloma.

Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab-mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab-mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab-mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab-mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab-mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.

High IL-12 p35 and IL-23 p19 mRNA expression is associated with superior outcome in ovarian cancer.

OBJECTIVE: Interleukin-12 (IL-12) and IL-23 share a common p40 subunit that is either covalently linked to the p35 (IL-12) or to the p19 subunit (IL-23). Data from genetic animal models suggest that in contrast to the central role of IL-12 for tumor immune-surveillance, its close relative IL-23 rather promotes tumor growth. It was the aim of this project to evaluate the clinical significance of these findings. METHODS: Intra-tumoral mRNA expression levels of the IL-12 specific subunit p35 and the IL-23 specific subunit p19 were quantified in ovarian cancer specimens (n=112) and control samples from healthy ovary tissue specimens (n=20) and correlated with clinical outcome. RESULTS: Both cytokines were expressed at higher levels in ovarian cancer specimens as compared to healthy controls. p35 and p19 mRNA expression levels positively correlated in both malignant and healthy ovarian tissue. High p35 and p19 mRNA expression was associated with a significant better overall survival (OS) in the overall cohort. p35 mRNA correlated with superior outcome in advanced stage disease (FIGO III/IV), whereas the effect of high p19 mRNA expression was pre-dominant in early stage disease (FIGO I/II). Multivariate analysis revealed that p35 mRNA expression represents an independent predictor for OS but not for PFS in ovarian cancer. CONCLUSION: In contrast to the recently proposed opposing roles of IL-12 and IL-23 for cancer growth and progression in rodents, our data from a large patient cohort rather suggest that high intra-tumoral expression levels of p35 mRNA and p19 mRNA are associated with a superior clinical outcome.

"Overcoming the Fear That Haunts Your Success" - The Effectiveness of Interventions for Reducing the Impostor Phenomenon.

The impostor phenomenon (IP) refers to intense thoughts of fraudulence reported by high-achieving individuals. Since it has been shown to account for several personal and work-related complications, effective interventions are greatly needed. Against the background of mindset theory, we developed and tested two mindset interventions. We evaluated the impact of a coaching and a training intervention adopting a randomized controlled outcome design. One hundred and three young employees were randomly assigned to receive coaching (n = 36), training (n = 33), or no intervention (n = 34). Results reveal that coaching was an effective mindset intervention for sustainably reducing IP scores. Fear of negative evaluation emerged to mediate the relation between the coaching intervention and the reduced IP scores significantly. Moreover, coaching improved self-enhancing attributions and self-efficacy and reduced the tendency to cover up errors as well as the fear of negative evaluation. Training was superior in regard to knowledge acquisition. Specific implications are discussed.

Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression.

BACKGROUND/AIMS: Adipocytokines play a key role in the pathophysiology of non-alcoholic fatty liver diseases (NAFLD). Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic and immune processes. METHODS: We prospectively examined the effect of weight loss on systemic levels and/or hepatic expression of adiponectin/adiponectin receptors, leptin/leptin receptors, resistin and PBEF/Nampt/visfatin. Severely obese patients underwent laparoscopic adjustable gastric banding (LABG) and serum samples (n=30) were collected before, and after 6 and 12 months. Paired liver biopsies (before and 6 months after LABG) were obtained from 18 patients. RESULTS: Bariatric surgery improved insulin resistance, abnormal liver function tests and liver histology. Pronounced weight loss after 6 and 12 months was accompanied by a significant increase in serum adiponectin levels whereas both leptin and PBEF/Nampt/visfatin levels decreased. Resistin serum levels increased after 6 months but fell below baseline values after 12 months. Liver mRNA expression of adiponectin increased slightly after 6 months whereas leptin mRNA expression did not change. Interestingly, weight loss resulted in a significant decrease of hepatic mRNA expression of resistin, PBEF/Nampt/visfatin and both leptin receptor isoforms while expression of type 1 and 2 adiponectin receptor was not affected. Liver immunohistochemistry performed on index and follow-up liver biopsies revealed an increase in adiponectin staining, showed no effect on resistin/leptin positivity, and demonstrated a decrease in PBEF/Nampt/visfatin immunoreactivity. CONCLUSIONS: Weight loss after LABG surgery drives the adipocytokine milieu towards a more anti-inflammatory direction both systemically and in the liver.

Anti-leukemic activity of valproic acid and imatinib mesylate on human Ph+ ALL and CML cells in vitro.

The armamentarium of anti-leukemic drugs has increased substantially since anti-leukemic activities were recently found for a variety of non-classical cytostatic drugs, among them the histone deacetylase (HDAC) inhibitor valproic acid (VPA). This study investigated the effect of VPA on proliferation and apoptosis of human Philadelphia chromosome-positive (Ph+) acute lymphatic (ALL) and chronic myeloid leukemia (CML) cells and on colony formation of human chronic-phase CML progenitor cells. Strong anti-proliferative and pro-apoptotic effects of VPA were observed on human ALL and CML cell lines at concentrations achievable in vivo. These effects were most pronounced in ALL cell lines as well as in primary ALL cells. Notably, VPA revealed enhanced activity with imatinib mesylate, nilotinib, the farnesyl transferase inhibitor SCH66336, interferon-alpha and cytosine arabinoside. VPA inhibited the growth of colony-forming cells from 12 Ph+ chronic-phase CML patients but also of those from normal healthy controls in a dose-dependent fashion. HDAC-inhibiting activity of VPA was confirmed on ALL and CML cells. In conclusion, VPA, whether alone or in combination with other non-classical anti-leukemic compounds, exerts significant anti-leukemic effects on human ALL and CML cells.

T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance.

BACKGROUND: Adipose tissue inflammation may play a critical role in the pathogenesis of insulin resistance (IR). The present study examined the role of lymphocytes in adipose tissue inflammation and IR. METHODS AND RESULTS: In a mouse model of obesity-mediated IR, high-fat diet (HFD) induced IR already after 5 weeks, which was associated with a marked T-lymphocyte infiltration in visceral adipose tissue. In contrast, recruitment of macrophages was delayed with an increase of MAC3-positive staining and F4/80 mRNA expression after 10 weeks of HFD, suggesting a dissociation of macrophage invasion into adipose tissue and IR initiation. In patients with type 2 diabetes, lymphocyte content in adipose tissue biopsies significantly correlated with waist circumference, a marker of IR. Immunohistochemical staining of human adipose tissue revealed the presence of mainly CD4-positive lymphocytes as well as macrophage infiltration. Most macrophages were HLA-DR-positive, reflecting activation through IFNgamma, a cytokine released from CD4-positive lymphocytes. CONCLUSIONS: Proinflammatory T-lymphocytes are present in visceral adipose tissue and may contribute to local inflammatory cell activation before the appearance of macrophages, suggesting that these cells could play an important role in the initiation and perpetuation of adipose tissue inflammation as well as the development of IR.

Regulatory T-cells in the graft and the risk of acute graft-versus-host disease after allogeneic stem cell transplantation.

BACKGROUND: FOXP3+ regulatory T-cells (Treg) are important regulators of allo-reactivity and may therefore represent an important predictor for the risk of graft versus-host disease (GVHD) after allogeneic stem cell transplantation. METHODS: To determine the clinical significance of Treg-content in stem cell grafts, we analyzed 58 human leukocyte antigen (HLA)-identical sibling donors (34 patients received myeloablative and 24 patients reduced intense conditioning regimens) and correlated the Treg frequency with clinical outcome after stem cell transplantation (SCT). RESULTS: A mean value of 9.1 x 10(6) CD4+ FOXP3+ Treg per kg body weight (bw) of the recipient was transplanted (ranging from 0.7 to 33.7 x 10(6) Treg/kg bw). Graft content of Treg correlated with mononuclear cells and CD3+ T-cells. Patients receiving low numbers of Treg (Treg(low)) after myeloablative conditioning for SCT had a significantly increased cumulative incidence of 76% for acute GVHD when compared with 23% for individuals receiving high numbers of Treg (Treg(high)). This observation, however, was not made in patients after reduced intense conditioning-SCT. Notably, relapse rate was not significantly different between Treg(low) and Treg(high) patients in either patient group and overall survival was even increased in Treg(high) patients after myeloablative SCT. Finally, low Treg graft levels represent an independent prognostic factor in multivariate analysis for the appearance of acute GHVD. CONCLUSION: Donor-derived Treg might be of particular significance for the development of acute GVHD after myeloablative SCT using HLA-identical sibling donors.

Reconstructive procedures after massive weight loss.

BACKGROUND: Following excess weight loss in many patients, a dermolipectomy of the abdomen, arms and thighs becomes necessary. This kind of operation was offered to 88 former morbidly obese patients after having lost between 50% and 75% of their excess weight. METHODS AND RESULTS: Abdomen: Because of a distinct pannus, a dermolipectomy was performed in 66 females and 16 males. An average of 2800+/-1381 g of tissue was removed from the females and 3116+/-2195 g from the males. Operative time was 166+/-35 and 177+/-46 minutes for the female and male patients, respectively. Minor and major wound healing disorders occurred in 23% and 19% of the patients. In two females, a panniculectomy (12.4/13.5 kg) was performed after they had reached 150 kg of body weight. Thighs: A medial thigh lift was performed in 19 females (excision of varicose veins was included in 9 patients). In patients receiving a dermolipectomy only, 1212 g of tissue was removed in 172+/-81 minutes. Five patients had complications (wound infection, lymphatic fistula). With both dermolipectomy and varicectomy, 1358 g of tissue were removed in 294+/-80 minutes. Four patients developed a wound infection. Arms: 7 female patients had brachioplasty performed, with an average of 410 g of tissue removed from both arms over a period of 161+/-64 minutes. In one patient, a neurolysis of the ulnar nerve became necessary due to postoperative edema. CONCLUSIONS: Dermolipectomy and/or panniculectomy should be offered to bariatric patients who have lost massive amounts of weight.

The effect of loss of excess weight on the metabolic risk factors after bariatric surgery in morbidly and super-obese patients.

BACKGROUND: Changes in metabolic risk factors such as dyslipidemia and hyperinsulinemia as well as levels of sex hormones and leptin were studied in morbidly obese (MO) and super-obese (SO) patients during excess weight loss (EWL), separately in males and females. METHODS: In this prospective clinical intervention study, 431 patients were included (361 females and 70 males). There were 217 patients with MO (BMI 40-49.9 kg/m2) and 214 patients with SO (BMI > or =50 kg/m2). All patients underwent restrictive bariatric operations. Metabolic parameters (lipids, insulin, leptin, hepatic transaminases, uric acid, and sex hormones) were measured before obesity surgery and at defined postoperative points of EWL (25%, 50%, 75% and 100%). RESULTS: Successful weight reduction of 25% EWL was achieved by 94% of patients at 2 months. With this moderate EWL, most of the patients already improved their risk profile considerably, including normalization of insulin levels. Additional EWL led to a further amelioration of risk profile in all patients, including normalization of triglyceride levels. Male MO and SO patients had a worse metabolic situation preoperatively and a greater benefit after weight loss. Even though SO patients did not lose as much excess weight as MO patients, they did profit comparably. CONCLUSION: Bariatric surgery is a valuable tool not only to reduce excess weight in severely obese patients but also to improve the metabolic risk profile within a short time-frame. This benefit is most pronounced in high-risk males.

Gastro-gastric fistula between pouch and fundus following gastric banding and bypass.

A complication observed with revisional surgery involving a fistula between the former pouch after gastric banding and the fundus is described. A 59-year-old man with BMI 41 kg/m(2) presented for Roux-en-Y gastric bypass (RYGBP). He had previously undergone an open gastric banding operation, with the band removed for obstruction 1 year later. He presented to our hospital with a third incisional hernia which was so large that he suffered from abdominal angina following meals. A RYGBP and a hernia repair with mesh were performed. The postoperative contrast x-ray study disclosed a fistula between the pouch and fundus. A procedure to close the fistula became necessary. The reason for the fistula may have been an erosion at the former connection between the pouch and the fundus after gastric banding, although a preoperative gastroscopy had not revealed this fistula.

Psychological outcome two years after restrictive bariatric surgery.

BACKGROUND: An essential outcome criterion of obesity surgery besides weight loss is the improvement of medical and psychological health status. Both dimensions influence quality of life. This study evaluates depressive symptoms, self-esteem and health-related quality of life 2 years after bariatric surgery. METHODS: 149 patients (47 males (32%), 102 females (68%), mean age 38.8 +/- 10.3 years) were assessed by standardized questionnaires before and 1 and 2 years after gastric restrictive surgery. RESULTS: Mean BMI pre-surgery was 51.3 +/- 8.4 kg/m2. BMI decreased significantly to 38.6 +/- 6.8 kg/m2 at 1 year and to 37.9 +/- 7.4 kg/m2 at 2 years after surgery. Statistical analyses revealed a significant decrease in depressive symptoms and a significant improvement in self-esteem and the physical dimension of health-related quality of life. Pre-surgery, 40.5% (n=62) of the patients suffered from depressive symptoms of clinical relevance. These depressive symptoms persisted in 17.7% (n = 27) 1 year and in 16.4% (n = 25) 2 years after surgery. CONCLUSION: Parallel with a considerable weight loss after bariatric surgery, important aspects of mental health such as depressive symptoms and self-esteem improved significantly. These effects appear 1 year after surgery, but do not seem to change considerably afterwards.