Global mitochondrial protein import proteomics reveal distinct regulation by translation and translocation machinery.

Most mitochondrial proteins are translated in the cytosol and imported into mitochondria. Mutations in the mitochondrial protein import machinery cause human pathologies. However, a lack of suitable tools to measure protein uptake across the mitochondrial proteome has prevented the identification of specific proteins affected by import perturbation. Here, we introduce mePRODmt, a pulsed-SILAC based proteomics approach that includes a booster signal to increase the sensitivity for mitochondrial proteins selectively, enabling global dynamic analysis of endogenous mitochondrial protein uptake in cells. We applied mePRODmt to determine protein uptake kinetics and examined how inhibitors of mitochondrial import machineries affect protein uptake. Monitoring changes in translation and uptake upon mitochondrial membrane depolarization revealed that protein uptake was extensively modulated by the import and translation machineries via activation of the integrated stress response. Strikingly, uptake changes were not uniform, with subsets of proteins being unaffected or decreased due to changes in translation or import capacity.

Lipid and protein content profiling of isolated native autophagic vesicles.

Autophagy is responsible for clearance of an extensive portfolio of cargoes, which are sequestered into vesicles, called autophagosomes, and are delivered to lysosomes for degradation. The pathway is highly dynamic and responsive to several stress conditions. However, the phospholipid composition and protein contents of human autophagosomes under changing autophagy rates are elusive so far. Here, we introduce an antibody-based FACS-mediated approach for the isolation of native autophagic vesicles and ensured the quality of the preparations. Employing quantitative lipidomics, we analyze phospholipids present within human autophagic vesicles purified upon basal autophagy, starvation, and proteasome inhibition. Importantly, besides phosphoglycerides, we identify sphingomyelin within autophagic vesicles and show that the phospholipid composition is unaffected by the different conditions. Employing quantitative proteomics, we obtain cargo profiles of autophagic vesicles isolated upon the different treatment paradigms. Interestingly, starvation shows only subtle effects, while proteasome inhibition results in the enhanced presence of ubiquitin-proteasome pathway factors within autophagic vesicles. Thus, here we present a powerful method for the isolation of native autophagic vesicles, which enabled profound phospholipid and cargo analyses.

The iron chelator and OXPHOS inhibitor VLX600 induces mitophagy and an autophagy-dependent type of cell death in glioblastoma cells.

Induction of alternative, non-apoptotic cell death programs such as cell-lethal autophagy and mitophagy represent possible strategies to combat glioblastoma (GBM). Here we report that VLX600, a novel iron chelator and oxidative phosphorylation (OXPHOS) inhibitor, induces a caspase-independent type of cell death that is partially rescued in adherent U251 ATG5/7 (autophagy related 5/7) knockout (KO) GBM cells and NCH644 ATG5/7 knockdown (KD) glioma stem-like cells (GSCs), suggesting that VLX600 induces an autophagy-dependent cell death (ADCD) in GBM. This ADCD is accompanied by decreased oxygen consumption, increased expression/mitochondrial localization of BNIP3 (BCL2 interacting protein 3) and BNIP3L (BCL2 interacting protein 3 like), the induction of mitophagy as demonstrated by diminished levels of mitochondrial marker proteins [e.g., COX4I1 (cytochrome c oxidase subunit 4I1)] and the mitoKeima assay as well as increased histone H3 and H4 lysine tri-methylation. Furthermore, the extracellular addition of iron is able to significantly rescue VLX600-induced cell death and mitophagy, pointing out an important role of iron metabolism for GBM cell homeostasis. Interestingly, VLX600 is also able to completely eliminate NCH644 GSC tumors in an organotypic brain slice transplantation model. Our data support the therapeutic concept of ADCD induction in GBM and suggest that VLX600 may be an interesting novel drug candidate for the treatment of this tumor.NEW & NOTEWORTHY Induction of cell-lethal autophagy represents a possible strategy to combat glioblastoma (GBM). Here, we demonstrate that the novel iron chelator and OXPHOS inhibitor VLX600 exerts pronounced tumor cell-killing effects in adherently cultured GBM cells and glioblastoma stem-like cell (GSC) spheroid cultures that depend on the iron-chelating function of VLX600 and on autophagy activation, underscoring the context-dependent role of autophagy in therapy responses. VLX600 represents an interesting novel drug candidate for the treatment of this tumor.

The relationship between childhood maltreatment and problematic eating behaviors in bariatric surgery candidates.

PURPOSE: It is known that childhood maltreatment and problematic eating behaviors are higher in bariatric surgery patients compared to over- and normal-weight persons. The aim of the study is to investigate the relationship between childhood maltreatment and problematic eating behaviors such as restraint, eating concern, weight concern, shape concern, and emotional eating in bariatric surgery patients. MATERIALS AND METHODS: 112 consecutive obese individuals seeking bariatric surgery at a University Hospital were administered asset of scales, including Childhood Trauma Questionnaire (CTQ), Dutch Eating Behavior Questionnaire-Emotional Eating subscale (DEBQ-E), and Eating Disorder Examination-Questionnaire (EDE-Q) and sociodemographic form, cross-sectionally. After descriptive statistics, a regression analysis was conducted to understand the relationships of CTQ scores with EDE-Q total, and subscale scores and DEBQ-E. RESULTS: In the Pearson correlation analysis, a statistically significant positive correlation was found between CTQ total score with EDE-Q total score and all subscales scores. In linear regression analyses, it was found that emotional abuse (ß = 0.39, p = 0.02) and physical abuse (ß = 0.36, p = 0.01) predicted increased DEBQ-E scores. In addition, sexual abuse was found to significantly predict weight concern (ß = 0.26, p = 0.04) and shape concern (ß = 0.31, p = 0.01). CONCLUSION: Our findings showed that the dynamics of problematic eating behaviors may differ depending on the type of childhood trauma. Psychiatric evaluation of bariatric surgery patients is important in understanding the relationship between childhood maltreatment and problematic eating behaviors. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Comparison of Weight Loss, Ghrelin, and Leptin Hormones After Ligation of Left Gastric Artery and Sleeve Gastrectomy in a Rat Model.

BACKGROUND Ligation of the left gastric artery (LLGA), which supplies the fundus of the stomach, may reduce the appetite hormone ghrelin, resulting in weight control. The aim of this study was to compare LLGA and sleeve gastrectomy (SG) in terms of postoperative outcomes in a rat model. MATERIAL AND METHODS Fifteen male Wistar albino rats, weighing >350 grams (range 350-525 grams), were enrolled in LLGA (N=5), SG (N=5), and control (N=5) groups. Blood samples were drawn preoperatively and also during the first and fourth week postoperatively to assay ghrelin and leptin hormone levels. Body weight was measured in each group. RESULTS The maximum reduction in ghrelin level (41.5%) was found in the LLGA group. Considerable% total weight loss (TWL) (mean 24.1%) was observed in the SG group, and slight%TWL was noted in the control and LLGA groups (means of 0.1% and 2.1%, respectively). There was no significant difference in mean percent weight change between the LLGA and the SG groups (p=0.08). Blood sample analysis revealed no statistically significant changes in ghrelin or leptin levels between the groups (p=0.9 and p=0.3, respectively). CONCLUSIONS We present evidence that LLGA causes the same reduction in ghrelin hormone levels as SG at 4 weeks after surgery in a rat model. However, LLGA did not cause the same%TWL as SG. The mechanism of weight loss in SG is most likely due to restriction and to the effects of the procedure, rather than due to neurohormonal changes.

Diffusion tensor imaging findings in the hunger and satiety centers of the brain after bariatric surgery: a preliminary study.

PURPOSE: To investigate the alterations in the diffusion tensor imaging (DTI) parameters measured in the hunger and satiety centers of the brain before and after bariatric surgery (BS) in morbidly obese patients. METHODS: Fourty morbidly obese patients were evaluated before and after BS. Mean diffusivity (MD) and fractional anisotropy (FA) values were calculated from 14 related brain locations, and the DTI parameters were analyzed. RESULTS: After the BS, the mean BMI of the patients decreased from 47.53 ± 5.21 to 31.48 ± 4.21. The MD and FA values in the all of the hunger and satiety centers was found statistically significant different in the pre-surgery period compared to the post-surgery period (for each; p-value < 0.001). CONCLUSION: The FA and MD changes after BS may be attributed to reversible neuroinflammatory alterations in the hunger and satiety centers. Decreased MD and FA values after BS may be explained by the neuroplastic structural recovery in the related brain locations.

Routine use of positron-emission tomography/computed tomography for staging of primary colorectal cancer: does it affect clinical management?

BACKGROUND: The use of positron emission tomography-computed tomography (PET/CT) for the preoperative staging of patients with colon and rectal cancer has increased steadily over the last decade. The aim of this study was to evaluate the effect of PET/CT on the preoperative staging and clinical management of patients with colorectal cancer. METHODS: Between December 2010 and February 2012, 64 consecutive patients with colorectal cancer were evaluated with both PET/CT scans and conventional preoperative imaging studies. We prospectively recorded the medical reports of these patients. The PET/CT findings were compared with conventional imaging studies and the rate of over-staging or down-staging and changes in clinical management were evaluated. The correlation of the PET/CT with the conventional imaging was compared by a kappa agreement coefficient. Differences in the accuracy for N and T staging were assessed by χ2 and related-samples marginal homogeneity tests. RESULTS: Thirty-nine (60.9%) patients had rectal cancer and 25 (39.1%) had colon cancer. Based on PET/CT, additional lesions were found in 6 (9.4%) of the patients: hilar and paratracheal lesions in 4 patients, hepatic in 1 and supraclavicular in 1 patient. In four of six patients, detailed imaging studies or biopsies revealed chronic inflammatory changes. Hepatic and supraclavicular involvement was confirmed in two patients. Therefore, the false positivity rate of PET/CT was 6.25%. Based on the additional PET/CT, 2 (3.2%) patients had a change in surgical management. A chemotherapy regimen was administered to the patient with a 1.5 cm hepatic metastasis near the right hepatic vein; for another patient with an identified supraclavicular lymph node metastasis, a simultaneous excision was performed. CONCLUSIONS: Routine use of PET/CT for preoperative staging did not impact disease management for 96.8% of our patients. The results of our study conclude that PET/CT should not be routinely used for primary staging of colorectal cancer. More studies are required for identifying the subgroup of patients who might benefit from a PET/CT in their initial staging.

The E3 Ligase TRIM25 Impairs Apoptotic Cell Death in Colon Carcinoma Cells via Destabilization of Caspase-7 mRNA: A Possible Role of hnRNPH1.

Therapy resistance is still a major reason for treatment failure in colorectal cancer (CRC). Previously, we identified the E3 ubiquitin ligase TRIM25 as a novel suppressor of caspase-2 translation which contributes to the apoptosis resistance of CRC cells towards chemotherapeutic drugs. Here, we report the executioner caspase-7 as being a further target of TRIM25. The results from the gain- and loss-of-function approaches and the actinomycin D experiments indicate that TRIM25 attenuates caspase-7 expression mainly through a decrease in mRNA stability. The data from the RNA pulldown assays with immunoprecipitated TRIM25 truncations indicate a direct TRIM25 binding to caspase-7 mRNA, which is mediated by the PRY/SPRY domain, which is also known to be highly relevant for protein-protein interactions. By employing TRIM25 immunoprecipitation, we identified the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) as a novel TRIM25 binding protein with a functional impact on caspase-7 mRNA stability. Notably, the interaction of both proteins was highly sensitive to RNase A treatment and again depended on the PRY/SPRY domain, thus indicating an indirect interaction of both proteins which is achieved through a common RNA binding. Ubiquitin affinity chromatography showed that both proteins are targets of ubiquitin modification. Functionally, the ectopic expression of caspase-7 in CRC cells caused an increase in poly ADP-ribose polymerase (PARP) cleavage concomitant with a significant increase in apoptosis. Collectively, the negative regulation of caspase-7 by TRIM25, which is possibly executed by hnRNPH1, implies a novel survival mechanism underlying the chemotherapeutic drug resistance of CRC cells. The targeting of TRIM25 could therefore offer a promising strategy for the reduction in therapy resistance in CRC patients.

Fuzzy interactions between the auto-phosphorylated C-terminus and the kinase domain of CK1δ inhibits activation of TAp63α.

The p53 family member TAp63α plays an important role in maintaining the genetic integrity in oocytes. DNA damage, in particular DNA double strand breaks, lead to the transformation of the inhibited, only dimeric conformation into the active tetrameric one that results in the initiation of an apoptotic program. Activation requires phosphorylation by the kinase CK1 which phosphorylates TAp63α at four positions. The third phosphorylation event is the decisive step that transforms TAp63α into the active state. This third phosphorylation, however, is ~ 20 times slower than the first two phosphorylation events. This difference in the phosphorylation kinetics constitutes a safety mechanism that allows oocytes with a low degree of DNA damage to survive. So far these kinetic investigations of the phosphorylation steps have been performed with the isolated CK1 kinase domain. However, all CK1 enzymes contain C-terminal extensions that become auto-phosphorylated and inhibit the activity of the kinase. Here we have investigated the effect of auto-phosphorylation of the C-terminus in the kinase CK1δ and show that it slows down phosphorylation of the first two sites in TAp63α but basically inhibits the phosphorylation of the third site. We have identified up to ten auto-phosphorylation sites in the CK1δ C-terminal domain and show that all of them interact with the kinase domain in a "fuzzy" way in which not a single site is particularly important. Through mutation analysis we further show that hydrophobic amino acids following the phosphorylation site are important for a substrate to be able to successfully compete with the auto-inhibitory effect of the C-terminal domain. This auto-phosphorylation adds a new layer to the regulation of apoptosis in oocytes.

FACS-mediated isolation of native autophagic vesicles.

Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated method for isolation of native macroautophagic/autophagic vesicles and confirmed the quality of the preparations. We performed phospholipidomic and proteomic analyses to characterize autophagic vesicle-associated phospholipids and protein cargoes under different autophagy conditions. Lipidomic analyses identified phosphoglycerides and sphingomyelins within autophagic vesicles and revealed that the lipid composition was unaffected by different rates of autophagosome formation. Proteomic analyses identified more than 4500 potential autophagy substrates and showed that in comparison to autophagic vesicles isolated under basal autophagy conditions, starvation only marginally affected the cargo profile. Proteasome inhibition, however, resulted in the enhanced degradation of ubiquitin-proteasome system components. Taken together, the novel isolation method enriched large quantities of autophagic vesicles and enabled detailed analyses of their lipid and cargo composition.

Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells.

Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D3 receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential.

Curcumin protects against ischemia/reperfusion injury in rat skeletal muscle.

BACKGROUND: Curcumin has been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of curcumin were evaluated in skeletal muscle during I/R injury. MATERIALS AND METHODS: Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 2 h reperfusion. We measured plasma concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay (ELISA). The right gastrocnemius muscle was harvested and immediately stored at -30°C for the assessment of superoxide dismutase (SOD), catalase (CAT) activities, and measurement of glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. Curcumin (100 mg/kg), α-tocopherol, and normal saline (10 mL /kg1) were administered intraperitoneally 1 h prior reperfusion. RESULTS: Plasma TNF-α or IL-1ß levels increased significantly in I/R group. The plasma levels of these proinflammatory cytokines were reduced in curcumin group. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities, and increased levels of malondialdehyde, nitric oxide, and protein carbonyl content compared with the SHAM group. Levels of these parameters in muscle revealed significant reductions in the I/R + curcumin group compared witho the I/R group. Curcumin has more potent antioxidant activity than vitamin E in the skeletal muscle I/R. CONCLUSION: In this study, protective effects of curcumin against skeletal muscle ischemia-reperfusion injury have been revealed. We underscore the necessity of human studies with curcumin that would be hypothetically beneficial preventing skeletal muscle I/R injury.

Monitoring Mitochondrial Protein Import Using Mitochondrial Targeting Sequence (MTS)-eGFP.

Mitochondria are cellular organelles essential for the function and survival of eukaryotic cells. Nearly all mitochondrial proteins are nuclear-encoded and require mitochondrial import upon their synthesis in the cytosol. Various approaches have been described to study mitochondrial protein import, such as monitoring the entry of radiolabeled proteins into purified mitochondria or quantifying newly synthesized proteins within mitochondria by proteomics. Here, we provide a detailed protocol for a commonly used and straightforward assay that quantitatively examines mitochondrial protein import by monitoring the co-localization of mitochondrially targeted enhanced green fluorescent protein (eGFP) with the mitochondrial fluorescence dye MitoTracker TM Deep Red FM by live cell imaging. We describe the preparation and use of a stable mammalian cell line inducibly expressing a mitochondrial targeting sequence (MTS)-eGFP, followed by quantitative image analysis using an open-source ImageJ-based plugin. This inducible expression system avoids the need for transient transfection while enabling titration of MTS-eGFP expression and thereby avoiding protein folding stress. Overall, the assay provides a simple and robust approach to assess mitochondrial import capacity of cells in various disease-related settings. This protocol was validated in: Mol Cell (2021), DOI: 10.1016/j.molcel.2021.11.004 Graphical abstract.

Effects of Prolonged Intermittent Fasting Model on Energy Metabolism and Mitochondrial Functions in Neurons.

Background: Calorie restriction (CR) during daily nutrition has been shown to affect the prognosis of many chronic diseases such as metabolic syndrome, diabetes, and aging. As an alternative nutrition model, prolonged intermittent fasting (PF) in humans is defined by the absence of food for more than 12 h. In our previous human studies, CR and PF models were compared and it was concluded that the two models might have differences in signal transduction mechanisms. We have investigated the effects of these models on neurons at the molecular level in this study. Methods: Neurons (SH-SY5Y) were incubated with normal medium (N), calorie-restricted medium (CR), fasting medium (PF), and glucose-free medium (G0) for 16 h. Simultaneously, ketone (beta-hydroxybutyrate; bOHB) was added to other experiment flasks containing the same media. Concentrations of lactate, lactate dehydrogenase (LDH), bOHB, and glucose were measured to demonstrate the changes in the energy metabolism together with the mitochondrial functions of cells. Citrate synthase activity and flow cytometric mitochondrial functions were investigated. Results: At the end of incubations, lactate and LDH levels were decreased and mitochondrial activity was increased in all ketone-added groups (P < .01) regardless of the glucose concentration in the environment. In the fasting model, these differences were more prominent. Conclusion: Our results demonstrated that neurons use ketones regardless of the amount of glucose, and bOHB-treated cells had positive changes in mitochondrial function. We conclude that the presence of bOHB might reverse neuron damage and that exogenous ketone treatment may be beneficial in the treatment of neurological diseases in the future.

Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy.

Mitophagy is essential to maintain mitochondrial function and prevent diseases. It activates upon mitochondria depolarization, which causes PINK1 stabilization on the mitochondrial outer membrane. Strikingly, a number of conditions, including mitochondrial protein misfolding, can induce mitophagy without a loss in membrane potential. The underlying molecular details remain unclear. Here, we report that a loss of mitochondrial protein import, mediated by the pre-sequence translocase-associated motor complex PAM, is sufficient to induce mitophagy in polarized mitochondria. A genome-wide CRISPR/Cas9 screen for mitophagy inducers identifies components of the PAM complex. Protein import defects are able to induce mitophagy without a need for depolarization. Upon mitochondrial protein misfolding, PAM dissociates from the import machinery resulting in decreased protein import and mitophagy induction. Our findings extend the current mitophagy model to explain mitophagy induction upon conditions that do not affect membrane polarization, such as mitochondrial protein misfolding.

USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K.

Oncogenic transformation of lung epithelial cells is a multistep process, frequently starting with the inactivation of tumour suppressors and subsequent development of activating mutations in proto-oncogenes, such as members of the PI3K or MAPK families. Cells undergoing transformation have to adjust to changes, including altered metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors. Here, we report that the ubiquitin carboxyl-terminal hydrolase 28 (USP28) enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes such as c-JUN, c-MYC, NOTCH and ∆NP63 at early stages of malignant transformation. USP28 levels are increased in cancer compared with in normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small-molecule inhibitor resets the proteome of transformed cells towards a 'premalignant' state, and its inhibition synergizes with clinically established compounds used to target EGFRL858R -, BRAFV600E - or PI3KH1047R -driven tumour cells. Targeting USP28 protein abundance at an early stage via inhibition of its activity is therefore a feasible strategy for the treatment of early-stage lung tumours, and the observed synergism with current standard-of-care inhibitors holds the potential for improved targeting of established tumours.

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide.

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.

[Scar endometriosis in the rectus abdominis muscle]. / Rektus abdominis kasi yerlesimli skar endometriyozisi.

Endometriosis is defined as the presence of ectopic functional endometrial tissue outside the uterine cavity. The most common locations are within the pelvis. Unusual sites ofendometriosis outside the pelvis have been reported, including the bladder, intestine, appendix, surgical scars, hernia sac, lung, kidney, and extremities. The diagnosis of scar endometriosis is usually not difficult and is based on history and physical examination. We report here two cases who developed endometriosis on the abdominal wall in the rectus abdominis muscle and were treated with local excisions.

Rare Entities of Histopathological Findings in 755 Sleeve Gastrectomy Cases: a Synopsis of Preoperative Endoscopy Findings and Histological Evaluation of the Specimen.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most preferred technique in morbidly obese patients for weight loss. There is a controversy about the routine preoperative evaluation of the stomach and the routine microscopic examination of all LSG specimens. Our aim is to analyze the results of both preoperative upper gastrointestinal endoscopy and endoscopic biopsies and also the results of histopathological examination of LSG specimens. MATERIALS AND METHODS: The data of patients who underwent LSG from January 2011 to November 2016 were analyzed retrospectively from a prospectively collected database. Seven hundred fifty five of 819 patients who met the inclusion criteria were included in this study. Data on patients' demographic variables [age, gender, BMI (kg/m2)], preoperative upper GI endoscopy and biopsy results, postoperative histopathological results of the specimens, and the process of the patients with malignant histopathological investigation in the follow-up period were collected. RESULTS: This study involves 755 patients with a mean age of 39.6 ± 11.7 years and has 496 (65.6%) to 259 (34.4%) female to male ratio. None of the patients harbored macroscopic or microscopic malignant pathological finding in the preoperative assessment. Hiatal hernia was detected in 78 (10.2%) patients and gastric/duodenal ulcers were detected in 52 (6.8%) patients in endoscopy. Incidental malignant and/or premalignant histopathological findings-intestinal metaplasia (1.4%) and malignant lesions (0.5%)-were rarely found in the evaluation of the surgical specimens. CONCLUSIONS: Both preoperative endoscopic assessment and postoperative histopathological examination of the specimen are mandatory in LSG patients.

Food addiction and the outcome of bariatric surgery at 1-year: Prospective observational study.

PURPOSES: The objectives of the current study were to determine the prevalence of food addiction in bariatric surgery candidates and whether food addiction is associated with weight loss after bariatric surgery. METHODS: This prospective observational study was performed on morbidly obese patients who had been found suitable for bariatric surgery. Follow-up was conducted at the 6 and 12 month post-surgery. The Yale Food Addiction Scale (YFAS) was used to determine food addiction. RESULTS: One hundred seventy-eight patients were included. Pre-operative food addiction was found in 57.8% of patients. Food addiction prevalence decreased at the 6 and 12 month follow ups, to 7.2% and 13.7% respectively. There were no statistically differences between those with food addiction and those without addiction with regard to weight loss measured as percent of excess BMI at the 12 month follow-up. CONCLUSION: Food addiction as measured by the YFAS decreases significantly after bariatric surgery. The presence of food addiction before surgery was not associated with weight loss as measured EBL%. However, in view of the increase in BMI, 2 years after surgery longer follow up studies are warranted.