A rare case of retroperitoneal teratoma with evidence of papillary thyroid carcinoma: a case report.

BACKGROUND: Teratomas are germ cell tumors composed of somatic tissues from up to three germ layers. Primary retroperitoneal teratomas usually develop during childhood and are uncommon in adults and in the retroperitoneal space. While there are only a few cases of retroperitoneal thyroid tissue, we report a unique case of a retroperitoneal papillary thyroid carcinoma. CASE PRESENTATION: A 41-year-old woman presented in our institution due to intermitted unspecific abdominal pain. Magnetic resonance imaging detected a multi-cystic solid retroperitoneal mass ventral to the psoas muscle and the left iliac artery. After surgical removal of the retroperitoneal mass, histology sections of the specimen indicated evidence of papillary thyroid carcinoma cells. A staging computed tomography scan of the body showed no further manifestations. To reduce the risk of recurrence, total thyroidectomy was performed followed by radioiodine therapy with lifelong hormone substitution. CONCLUSIONS: Primary retroperitoneal teratoma with evidence of papillary thyroid carcinoma is a rare condition. Preoperative diagnosis is difficult due to its non-specific clinical manifestation and lack of specific radiologic findings. Histopathology analysis is necessary for diagnosis. Although surgery is considered the first line treatment, there is still discussion about the extent of resection and the need for total thyroidectomy with adjuvant radioiodine therapy.

Low serum iPTH at the end of surgery is the earliest predictor of postoperative hypocalcemia after total thyroidectomy.

BACKGROUND: The most frequent complication of total thyroidectomy remains hypocalcemia due to low postoperative levels of serum intact parathyroid hormone (iPTH). The purpose of this study was to investigate the role of decreased iPTH at the end of surgery in predicting hypocalcemia. In addition, we examined the percentage decrease of iPTH as potential indicator of hypocalcemia. METHODS: We retrospectively collected the data of patients who underwent total thyroidectomy for benign and malignant diseases at our institution between 2010 and 2022. The iPTH level was measured before and at the end of surgery, and serum calcium levels on the first postoperative day. Demographic, clinical, and biochemical characteristics of patients with low iPTH were compared with patients with normal iPTH levels using ANOVA for continuous variables and χ2-tests for categorical variables. Multivariable logistic regression analysis evaluated the association of iPTH at the end of surgery and the relative reduction of iPTH with postoperative hypocalcemia. RESULTS: The mean age of the 607 patients in this study was 55.6 years, and the female-to-male ratio was 5:1. Goiter was the most common indication for surgery (N = 382, 62.9%), followed by Graves' disease (N = 135, 22.2%). The mean preoperative iPTH was 49.0 pg/ml, while the mean postoperative iPTH was 29.3 pg/ml. A total of 197 patients (32.5%) had an iPTH level below normal, 77 patients (39%), had iPTH levels of 10-15.0 pg/ml and 120 patients (61%) of < 10.0 pg/ml at the end of surgery. Among all patients, 124 (20.4%) developed hypocalcemia on the first postoperative day. The mean percentage of decrease of iPTH was highest among patients with iPTH < 10 pg/ml (76.9%, p < 0.01); this group of patients had also the highest rate of postoperative hypocalcemia on day one (45.0% vs. 26.0% vs 12.2%, p < 0.01). CONCLUSIONS: Measurement of iPTH at the end of total thyroidectomy predicts patients who are at risk for postoperative hypocalcemia. The combination of low serum iPTH with a decrease in iPTH level of ≥ 50% may improve prediction of hypocalcemia compared to iPTH levels alone allowing for early calcium substitution in these patients at high risk of developing postoperative hypocalcemia.

Laparoscopic versus robotic-assisted, left-sided colectomies: intra- and postoperative outcomes of 683 patients.

BACKGROUND: Robotic-assisted colorectal surgery has gained more and more popularity over the last years. It seems to be advantageous to laparoscopic surgery in selected situations, especially in confined regions like a narrow male pelvis in rectal surgery. Whether robotic-assisted, left-sided colectomies can serve as safe training operations for less frequent, low anterior resections for rectal cancer is still under debate. Therefore, the aim of this study was to evaluate intra- and postoperative results of robotic-assisted laparoscopy (RAL) compared to laparoscopic (LSC) surgery in left-sided colectomies. METHODS: Between June 2015 and December 2019, 683 patients undergoing minimally invasive left-sided colectomies in two Swiss, high-volume colorectal centers were included. Intra- and postoperative outcome parameters were collected and analyzed. RESULTS: A total of 179 patients undergoing RAL and 504 patients undergoing LSC were analyzed. Baseline characteristics showed similar results. Intraoperative complications occurred in 0.6% of RAL and 2.0% of LSC patients (p = 0.193). Differences in postoperative complications graded Dindo ≥ 3 were not statistically significant (RAL 3.9% vs. LSC 6.3%, p = 0.227). Occurrence of anastomotic leakages showed no statistically significant difference [RAL n = 2 (1.1%), LSC n = 8 (1.6%), p = 0.653]. Length of hospital stay was similar in both groups. Conversions to open surgery were significantly higher in the LSC group (6.2% vs.1.7%, p = 0.018), while stoma formation was similar in both groups [RAL n = 1 (0.6%), LSC n = 5 (1.0%), p = 0.594]. Operative time was longer in the RAL group (300 vs. 210.0 min, p < 0.001). CONCLUSION: Robotic-assisted, left-sided colectomies are safe and feasible compared to laparoscopic resections. Intra- and postoperative complications are similar in both groups. Most notably, the rate of anastomotic leakages is similar. Compared to laparoscopic resections, the analyzed robotic-assisted resections have longer operative times but less conversion rates. Further prospective studies are needed to confirm the safety of robotic-assisted, left-sided colectomies as training procedures for low anterior resections.

Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression.

The common age-related neurodegeneration of Parkinson's disease can result from dominant causes like increased dosage of vesicle-associated alpha-synuclein (SNCA) or recessive causes like deficiency of mitophagy factor PINK1. Interactions between these triggers and their convergence onto shared pathways are crucial, but currently conflicting evidence exists. Here, we crossed previously characterized mice with A53T-SNCA overexpression and with Pink1 deletion to generate double mutants (DMs). We studied their lifespan and behavior, histological and molecular anomalies at late and early ages. DM animals showed potentiated phenotypes in comparison with both single mutants (SMs), with reduced survival and strongly reduced spontaneous movements from the age of 3 months onwards. In contrast to SMs, a quarter of DM animals manifested progressive paralysis at ages >1 year and exhibited protein aggregates immunopositive for pSer129-SNCA, p62 and ubiquitin in spinal cord and basal brain. Brain proteome quantifications of ubiquitination sites documented altered degradation of SNCA and the DNA-damage marker H2AX at the age of 18 months. Global brain transcriptome profiles and qPCR validation experiments identified many consistent transcriptional dysregulations already at the age of 6 weeks, which were absent from SMs. The observed downregulations for Dapk1, Dcaf17, Rab42 and the novel SNCA-marker Lect1 as well as the upregulations for Dctn5, Mrpl9, Tmem181a, Xaf1 and H2afx reflect changes in ubiquitination, mitochondrial/synaptic/microtubular/cell adhesion dynamics and DNA damage. Thus, our study confirmed that SNCA-triggered neurotoxicity is exacerbated by the absence of PINK1 and identified a novel molecular signature that is detectable early in the course of this double pathology.

Linear compared to circular stapler anastomosis in laparoscopic Roux-en-Y gastric bypass leads to comparable weight loss with fewer complications: a matched pair study.

OBJECTIVE: In the course of laparoscopic Roux-en-Y gastric bypass (LRYGB), a tight gastroenterostomy (GE) may lead to higher weight loss but possibly to an increase of local complications such as strictures and ulcers. Different operative techniques for Roux-en-Y reconstruction may also influence the rate of internal hernias, a typical late complication of LRYGB. The objective of this study was to compare weight loss, rates of strictures, internal hernias, and ulcerations of linear versus circular stapler anastomosis. METHODS: Retrospective analysis of prospectively collected data in a 3:1-matched pair study. A total of 228 patients with a minimal follow-up of 2 years were matched according to BMI at baseline, age, and gender. The follow-up rate was 100 % at 1 and 2 years postoperatively; the mean follow-up time was 3.8 ± 1.63 years. In group C (circular), 57 patients were operated with a 25-mm circular stapler technique (average BMI 44.7 ± 5.18 kg/m(2), age 44.1 ± 10.8 years, 80.7 % female). In group L (linear), 171 patients were operated using a linear stapler (approximately 30 mm, average BMI 43.8 ± 5.24 kg/m(2), age 43.7 ± 12.5 years, 70.8 % female). A propensity score matching and a logrank test were used for statistical analysis. RESULTS: The average excessive BMI loss (EBMIL) after 1 year was not statistically different (70.6 ± 20.2 % in group C vs 72.5 ± 20.4 % in group L) as well as after 2 years (71.6 ± 22.5 % in group C vs 74.6 ± 19.6 % in group L). The average operation time was 155 ± 53 min in group C and 109 ± 57 min in group L (p = 0.0001). In group L, patients had significantly lower overall stricture rates at the GE compared to group C (0 [0 %] vs. 4 [7 %], p = 0.0004), a lower rate and severity of internal hernias (10 [5.8 %] vs. 7 [12.3 %] p = 0.466), and equal local ulcerations rates (3 [1.8 %] vs. 1 [1.8 %] p = 0.912). CONCLUSION: Linear stapler anastomosis in LRYGB compared to circular anastomosis leads to equal weight loss and less strictures. The lower rate of internal hernias in linear stapler anastomosis was not significantly different.

Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation--impact of Ras-/Rho-prenylation.

Alterations in small GTPase mediated signal transduction pathways have emerged as a central step in the molecular pathogenesis of glioblastoma (GBM), the most common malignant brain tumor in adults. Farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) are derived from mevalonate, whose production is catalyzed by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Prenylation by FPP and GGPP is required for membrane insertion and oncogenic function of Ras- and Rho-proteins, within the stimulation of the Ras-Raf-MEK-ERK pathway. A straightforward prediction from HMG-CoA reductase inhibitor studies is that statins decrease FPP and GGPP levels and diminish ERK signaling ensuring less proliferation and migration of cancer cells. Perillyl alcohol (POH), a naturally occurring monoterpene inhibits prenyltransferases and is able to inhibit cancer cell growth, but the underlying mechanism is still unclear. We here report that lovastatin (LOV) and POH impair the regulation of the mevalonate- and the Ras-Raf-MEK-ERK pathway in U87 and U343 glioblastoma cells. Both compounds affected the post-translational modification of H-Ras and Rac1. While LOV diminished the substrates of the transferase reaction that catalyze prenylation, POH inhibited the enzymes itself. Our data highlight the impact of isoprenoids for post-translational modification of small GTPases promoting proliferation, migration and invasion capabilities in glioma cells.

Selective increase of in vivo firing frequencies in DA SN neurons after proteasome inhibition in the ventral midbrain.

The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'.

Early results of the Swiss Multicentre Bypass or Sleeve Study (SM-BOSS): a prospective randomized trial comparing laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective alternative to the current standard procedure, laparoscopic Roux-en-Y gastric bypass (LRYGB). Prospective data comparing both procedures are rare. Therefore, we performed a randomized clinical trial assessing the effectiveness and safety of these 2 operative techniques. METHODS: Two hundred seventeen patients were randomized at 4 bariatric centers in Switzerland. One hundred seven patients underwent LSG using a 35-F bougie with suturing of the stapler line, and 110 patients underwent LRYGB with a 150-cm antecolic alimentary and a 50-cm biliopancreatic limb. The mean body mass index of all patients was 44 ± 11.1 kg/m, the mean age was 43 ± 5.3 years, and 72% were female. RESULTS: The 2 groups were similar in terms of body mass index, age, sex, comorbidities, and eating behavior. The mean operative time was less for LSG than for LRYGB (87 ± 52.3 minutes vs 108 ± 42.3 minutes; P = 0.003). The conversion rate was 0.9% in both groups. Complications (<30 days) occurred more often in LRYGB than in LSG (17.2% vs 8.4%; P = 0.067). However, the difference in severe complications did not reach statistical significance (4.5% for LRYGB vs 1% for LSG; P = 0.21). Excessive body mass index loss 1 year after the operation was similar between the 2 groups (72.3% ± 22% for LSG and 76.6% ± 21% for LRYGB; P = 0.2). Except for gastroesophageal reflux disease, which showed a higher resolution rate after LRYGB, the comorbidities and quality of life were significantly improved after both procedures. CONCLUSIONS: LSG was associated with shorter operation time and a trend toward fewer complications than with LRYGB. Both procedures were almost equally efficient regarding weight loss, improvement of comorbidities, and quality of life 1 year after surgery. Long-term follow-up data are needed to confirm these facts.

Robotic versus laparoscopic low anterior resection following neoadjuvant chemoradiation therapy for stage II-III locally advanced rectal cancer: a single-centre cohort study.

Neoadjuvant chemo-radiotherapy (nCRT) of locally advanced rectal cancer is associated with challenging surgical treatment and increased postoperative morbidity. Robotic technology overcomes laparoscopy limitations by enlarged 3D view, improved anatomical transection accuracy, and physiologic tremor reduction. Patients with UICC stage II-III rectal cancer, consecutively referred to our institution between March 2015 and June 2020 (n = 102) were treated with robotic (Rob-G, n = 38) or laparoscopic (Lap-G, n = 64) low anterior resection (LAR) for total meso-rectal excision (TME) following highly standardized and successful nCRT treatment. Feasibility, conversion rates, stoma creation, morbidity and clinical/pathological outcome were comparatively analysed. Sex, age, BMI, ASA scores, cTN stages and tumour distance from dentate line were comparable in the two groups. Robotic resection was always feasible without conversion to open surgery, which was necessary in 11/64 (17%) Lap-G operations (p = 0.006). Primary or secondary stomata were created in 17/38 (45%) Rob-G and 52/64 (81%) Lap-G patients (p < 0.001). Major morbidity occurred in 7/38 (18.4%) Rob-G and 6/64 (9.3%) Lap-G patients (p = 0.225). Although median operation time was longer in Rob-G compared with Lap-G (376; IQR: 330-417 min vs. 300; IQR: 270-358 min; p < 0.001), the difference was not significant in patients (Rob-G, n = 6; Lap-G, n = 10) with ≥30 BMI (p = 0.106). Number of resected lymph nodes, ypTN staging and circumferential resection margins (CRM) were comparable. Resection was complete in 87% of Rob-G and 89% of Lap-G patients (p = 0.750). Robotic LAR is not inferior to laparoscopic LAR following nCRT. Larger, randomized studies are needed to confirm lower conversion in robotic, compared to laparoscopic resection.

[Rectal erosion caused by a prosthesis for treatment of vaginal prolapse (Prolift)]. / Érosion rectale d'une prothèse pour cure de prolapsus vaginal (Prolift).

Contexte : La place des prothèses non résorbables dans la chirurgie du prolapsus vaginal a pris beaucoup d'ampleur ces dernières années. Les complications tardives commencent à apparaître. Cas : Nous vous présentons le cas d'une érosion tardive dans le bas rectum. Pour autant que nous sachions, il s'agit de la première mention de cette complication tardive de la prothèse Prolift. Dans ce cas, il s'agit probablement d'une nécrose de décubitus attribuable à une prothèse trop longue. Conclusion : Les prothèses non résorbables sont certainement une option dans le traitement des prolapsus vaginaux; toutefois, les complications de ces implants devraient être connues et les patientes devraient être avisées des risques.

Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial.

BACKGROUND: The exclusion of the proximal small intestine is thought to play a major role in the rapid improvement in the metabolic control of diabetes after gastric bypass. OBJECTIVE: In this randomized, prospective, parallel group study, we sought to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) with those of laparoscopic sleeve gastrectomy (LSG) on fasting, and meal-stimulated insulin, glucose, and glucagon-like peptide-1 (GLP-1) levels. METHODS: Thirteen patients were randomized to LRYGB and 14 patients to LSG. The mostly nondiabetic patients were evaluated before, and 1 week and 3 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before and after food intake in both groups for insulin, GLP-1, glucose, PYY, and ghrelin concentrations. This trial was registered in www.clinicaltrials.gov (NCT00356213) before the first patient was randomized. RESULTS: Body weight and body mass index decreased markedly (P < 0.002) and comparably after either procedure. Excess BMI loss was similar at 3 months (43.3 +/- 12.1% vs. 39.4 +/- 9.4%, P > 0.36). After surgery, patients had markedly increased postprandial plasma insulin and GLP-1 levels, respectively (P < 0.01) after both of these surgical procedures, which favor improved glucose homeostasis. Compared with LSG, LRYGB patients had early and augmented insulin responses as early as 1-week postoperative; potentially mediating improved early glycemic control. After 3 months, no significant difference was observed with respect to insulin and GLP-1 secretion between the 2 procedures. CONCLUSION: Both procedures markedly improved glucose homeostasis: insulin, GLP-1, and PYY levels increased similarly after either procedure. Our results do not support the idea that the proximal small intestine mediates the improvement in glucose homeostasis.

Midterm results of primary vs. secondary laparoscopic sleeve gastrectomy (LSG) as an isolated operation.

BACKGROUND: We investigated early and midterm results of laparoscopic sleeve gastrectomy (LSG) as an isolated primary and secondary operation after failed gastric banding. METHODS: Between May 2004 and October 2007, a total of 70 patients (female 77%, mean age 43 (21-65) years, mean initial body mass index (BMI) 46 (35-61) kg/m(2)) were prospectively evaluated and operated by LSG. In 41 patients, LSG was performed as a primary operation (group 1) and in 29 patients as a secondary procedure after failed gastric banding (group 2). The overall average follow-up time after LSG was 24 (12-53) months; follow-up rate 1 year after operation was 100%, after 2 years 98%, and after 3 years 95%. RESULTS: There were no intraoperative complications, no conversion with shorter operation time in group 1 (91 vs. 132 min, p = 0.001). Early morbidity of LSG was 5% (major) and 7% (minor); mortality was zero. Average excessive BMI loss after 1 year was 65% (9-127%), after 2 years 63% (13-123%), and after 3 years 60% (9-111%). Midterm morbidity was 13%. There was no significant difference between the two groups regarding early and midterm morbidity, reoperation rate for complications (11.4%), or insufficient weight loss (7%). CONCLUSIONS: LSG is a safe bariatric procedure with good weight loss in the first 3 years postop. It can be used as an isolated initial treatment and as a secondary treatment after failed gastric banding. However, in the absence of long-term results, we suggest LSG to be performed only in controlled trials.

Predictors of outcome in treatment of morbid obesity by laparoscopic adjustable gastric banding: results of a prospective study of 380 patients.

BACKGROUND: We investigated the outcome predictors of laparoscopic gastric banding (LAGB) for morbidly obese patients. METHODS: From December 1996 to November 2004, a total of 380 consecutive unselected patients (78% female; median age 40 yr, range 17-66; body mass index 44.3 kg/m(2), range 35-75) were prospectively evaluated and underwent LAGB. The follow-up rate after a median of 5 years (range 1.5-9.4) was 98%. A survival model was applied, and a multivariate Cox proportional hazard model was used to calculate the hazard ratios for the influential factors. RESULTS: Of the 380 patients, 128 (33.7%) had their bands removed. Of these 128 patients, 2.4% declined another operation, 18.2% underwent biliopancreatic diversion with duodenal switch, 7.1% underwent laparoscopic Roux-en-Y gastric bypass, and 6% underwent laparoscopic sleeve gastrectomy. The excess weight loss of the remaining 252 patients (66.3%) with a band in situ (including 21 patients after rebanding) was 40%, and only 25% reached an excess weight loss >50%. Older age, binge eating disorder, and sweet-eating behavior were predictors of a poor outcome after LAGB. In contrast, sex, primary body mass index, and co-morbidities had no influence on outcome. CONCLUSION: LAGB was less successful in older patients and in patients with binge eating disorder or sweet-eating behavior. These patients might be candidates for a different bariatric procedure.

Prospective study of a two-stage operative concept in the treatment of morbid obesity: primary lap-band followed if needed by sleeve gastrectomy with duodenal switch.

BACKGROUND: We investigated the success rate of a two-stage operative concept for treatment of morbid obesity: primary laparoscopic adjustable gastric banding (LAGB, Lap-Band) for all morbidly obese patients, followed by sleeve gastrectomy with biliopancreatic diversion (duodenal switch or DS) in case of failure. METHODS: From Dec 1996 to May 2004, 366 consecutive patients (female 78%, mean age 41 (17-66) years, BMI 44.3 (35-75) kg/m2 were prospectively evaluated, using the two-stage operative concept. The follow-up rate after a mean of 4.1 (1-8.4) years was 98%. Primary outcome measure was BAROS score, defined according to weight loss, quality of life, reduction in co-morbidities, complications and re-operations. RESULTS: A very good-to-excellent result was found in 118 patients (32%), 141 (39%) had a good results, 76 (21%) a fair result, and 31 (8%) were failures. 39 patients needed re-banding due to slippage, 68 a DS, and 11 patients had band removal. Early morbidity of the Lap-Band was 3.8%, that of DS 13%, and mortality was zero. The excess weight loss at last follow-up of all the patients was 44% (40% after Lap-Band/rebanding, and 82% 2 years after DS). CONCLUSION: The two-stage concept with primary LAGB, followed by DS in case of failure, leads to a good result in 71% of morbidly obese patients. LAGB alone does not appear to be an adequate procedure for every morbidly obese patient.

Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

Impaired mitochondrial function is important in obesity and the development of insulin resistance and diabetes. The aim of this study was to identify human adipocyte-derived mitochondrial proteins associated with obesity. Mitochondrial proteins from 20 abdominal omental adipose tissue biopsies (13 obese and 7 control subjects) were separated by anion-exchange chromatography coupled to SDS-PAGE. Protein contents were compared and identified by MALDI-TOF-TOF mass spectrometry. Proteins of interest were validated, verified and quantified using immuno dot blot assays in a total of 76 mitochondrial preparations from both obese and non-obese patients. Mass spectrometric comparison of 20 mitochondrial proteomes yielded 62 proteins that were differentially expressed in adipose tissue of obese subjects. The immunological quantification of 12 mitochondrial proteins from 76 omental adipose tissue biopsies revealed four proteins, citrate synthase, HADHA, LETM1 and mitofilin inversely being associated with BMI, and mitofilin being inversely correlated with gender. BIOLOGICAL SIGNIFICANCE: The finding that obese human subjects have reduced levels of important mitochondrial proteins in adipocytes of omental adipose tissue as compared to non-obese controls gives new insights in the impairment of mitochondrial function in this specialized compartment of human adipose tissue in obesity and may eventually lead to the definition of valuable obesity markers.

Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular vulnerability against proteasomal inhibition.

The family of lysosome-associated membrane proteins (LAMP) includes the ubiquitously expressed LAMP1 and LAMP2, which account for half of the proteins in the lysosomal membrane. Another member of the LAMP family is LAMP3, which is expressed only in certain cell types and differentiation stages. LAMP3 expression is linked with poor prognosis of certain cancers, and the locus where it is encoded was identified as a risk factor for Parkinson's disease (PD). Here, we investigated the role of LAMP3 in the two main cellular degradation pathways, the proteasome and autophagy. LAMP3 mRNA was not detected in mouse models of PD or in the brain of human patients. However, it was strongly induced upon proteasomal inhibition in the neuroblastoma cell line SH-SY5Y. Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux. Prevention of LAMP3 induction enhanced apoptotic cell death. In summary, these data demonstrate that LAMP3 regulation as part of the UPR contributes to protein degradation and cell survival during proteasomal dysfunction. This link between autophagy and the proteasome may be of special importance for the treatment of tumor cells with proteasomal inhibitors.

Bolus obstruction of pouch outlet by a granular bulk laxative after gastric banding.

BACKGROUND: Constipation is an occasional problem after gastric banding and is often caused by insufficient liquid intake. As a result, the use of laxatives is widespread in such patients. Depending on the laxative, improper use can lead to bolus obstruction above the band, as occurred in this case. CASE REPORT: A 59-year-old female with uncomplicated laparoscopic adjustable gastric banding presented 2 months after surgery with food and liquid intolerance and dysphagia after ingestion of a granular bulking laxative. Despite deflating the band, the bolus could not be washed out. Endoscopic extraction was required, revealing a 4x2 cm bolus of the laxative and a small compression ulcer. DISCUSSION: Patients not complying with nutritional recommendations after gastric banding may have insufficient liquid intake and, consequently, constipation. Under these conditions, the use of a granular bulking laxative entails the risk of esophageal obstruction above the band. CONCLUSION: Nutritional counseling after gastric banding should include the recommendation of liquid intake of at least 1.5 l/day. If constipation occurs, osmotic or paraffin oil laxatives should be used instead of bulking laxatives.

Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in vitro and in vivo effects on human endothelial cells and on pancreatic cancer.

Several inhibitors of angiogenesis have been identified in bovine and shark cartilage. One of them is troponin I, which is the molecule responsible for the inhibition of the actomyosin ATPase during muscle contraction. In this study we sought to investigate if the active site of troponin I (peptide Glu94-Leu123; pTnI) is also the one responsible for the antiangiogenic properties of this protein. The effects of pTnI on endothelial cell tube formation and endothelial cell division were investigated using human umbilical vein endothelial cells, Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and production of vascular endothelial growth factor by pancreatic cancer cells (CAPAN-1) were also investigated, as was its efficacy in a mouse model of pancreatic cancer metastases. Our results show that concentrations as low as 1 pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that endothelial cell division was inhibited at 96 hours by 3 microg/ml pTnI (P=0.0001). No effects were seen using troponin peptide 124-181 as a control. pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1 downregulated ICAM-1 expression on human umbilical vein endothelial cells up to 10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor production was seen by treating CAPAN-1 cells with up to 1 microg/ml pTnI. After intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P=0.03). The active region of troponin I is the one responsible for its antiangiogenic effect. The mechanism of action of this peptide is probably multifactorial.

Five-year results of laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity, but studies reporting long-term results are still rare. The objective of this study was to present the 5-year outcome concerning weight loss, modification of co-morbidities, and late complications. METHODS: This is a retrospective analysis of a prospective cohort with a minimal follow-up of 5 years. A total of 68 patients underwent LSG either as primary bariatric procedure (n = 41) or as redo operation after failed laparoscopic gastric banding (n = 27) between August 2004 and December 2007. At the time of LSG, the mean body mass index (BMI) was 43.0 ± 8.0 kg/m(2), the mean age 43.1 ± 10.1 years, and 78% were female. The follow-up rate was 100% at 1 year postoperatively, 97% after 2 years, and 91% after 5 years; the mean follow-up time was 5.9 ± 0.8 years. RESULTS: The average excessive BMI loss was 61.5% ± 23.4% after 1 year, 61.1% ± 23.4% after 2 years, and 57.4% ± 24.7% after 5 years. Co-morbidities improved considerably; a remission of type 2 diabetes could be reached at 85%. The following complications were observed: 1 leak (1.5%), 2 incisional hernias (2.9%), and new-onset gastroesophageal reflux in 11 patients (16.2%). Reoperation due to insufficient weight loss was necessary in 8 patients (11.8%). CONCLUSIONS: LSG was effective 5.9 years postoperatively with an excessive BMI loss of almost 60% and a considerable improvement or even remission of co-morbidities.