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1.
Cancers (Basel) ; 14(20)2022 Oct 18.
Article in English | MEDLINE | ID: mdl-36291872

ABSTRACT

New techniques are being developed to improve the results of laparoscopic surgery for rectal cancer. This paper analyzes the learning curves for transanal total mesorectal excision (taTME) and robot-assisted surgery in our colorectal surgery department. We analyzed retrospectively data from patients undergoing curative and elective surgery for rectal cancer ≤12 cm from the anal verge. We excluded extended surgeries. We used cumulative sum (CUSUM) curve analysis to identify inflection points. Between 2015 and 2021, 588 patients underwent surgery for rectal cancer at our center: 67 taTME and 79 robot-assisted surgeries. To overcome the operative time learning curve, 14 cases were needed for taTME and 53 for robot-assisted surgery. The morbidity rate started to decrease after the 17th case in taTME and after the 49th case in robot-assisted surgery, but it is much less abrupt in robot-assisted group. During the initial learning phase, the rate of anastomotic leakage was higher in taTME (35.7% vs. 5.7%). Two Urological lesions occurred in taTME but not in robot-assisted surgery. The conversion rate was higher in robot-assisted surgery (1.5% vs. 10.1%). Incorporating new techniques is complex and entails a transition period. In our experience, taTME involved a higher rate of serious complications than robot-assisted surgery during initial learning period but required a shorter learning curve.

3.
J Surg Res ; 268: 465-473, 2021 12.
Article in English | MEDLINE | ID: mdl-34418650

ABSTRACT

BACKGROUND: Efforts to determine whether metformin can increase the effectiveness of neoadjuvant chemoradiotherapy in rectal cancer have increased in recent years. However, retrospective studies have yielded inconclusive results. OBJECTIVES: The aim of this study was to compare oncological outcomes and survival after neoadjuvant chemoradiotherapy in patients with rectal cancer taking metformin versus in those not taking metformin. METHODS: This study analyzed 423 consecutive patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy and curative surgery between January 2010 and May 2020; of these, 59 were taking metformin and 364 were not taking metformin. RESULTS: Patients taking metformin had a lower proportion of tumor regression (6.8% versus 22.0%, P = 0.012) as well as a lower proportion of patients achieving a pathological complete response (6.8% versus 20.6%, P = 0.011). In the multivariate analysis, independent predictors of pathologic complete response were not taking metformin (OR: 5.26, 95% CI: 1.12-24.85, P= 0.035) and cT2 stage (OR: 3.49, 95% CI: 1.10-11.07, P= 0.034); the interval was also an independent predictor of tumor regression (OR: 1.78, 95% CI: 1.06-2.96, P= 0.028). No differences were observed in survival between groups. CONCLUSION: Metformin was not associated with better tumor responses or survival after neoadjuvant treatment.


Subject(s)
Metformin , Rectal Neoplasms , Chemoradiotherapy , Humans , Metformin/therapeutic use , Neoadjuvant Therapy/methods , Neoplasm Staging , Retrospective Studies , Treatment Outcome
4.
Cir. Esp. (Ed. impr.) ; 99(5): 368-373, mayo 2021. tab, graf
Article in Spanish | IBECS | ID: ibc-192543

ABSTRACT

INTRODUCCIÓN: La pandemia por SARS-CoV-2 ha causado un importante impacto en nuestro medio, con la necesidad de demorar la cirugía programada y urgente. Las cifras referentes a la disminución de la actividad quirúrgica y el impacto del periodo aún no se conocen con exactitud. Se estima una mortalidad de hasta un 20% en los pacientes operados con infección peroperatoria por SARS-CoV-2 MÉTODOS: Del 14/03 al 11/05 del 2020 se han recogido los datos de los pacientes ingresados en el servicio de Cirugía General y Digestiva del Hospital Universitari Dr. Josep Trueta de Girona, para analizar el impacto de la pandemia sobre la cirugía electiva y urgente. RESULTADOS: Durante el periodo de ocupación pico de la Unidad de Medicina Intensiva de nuestro centro (con un máximo de 303,8%), la cirugía electiva y la urgente se redujeron un 93,8% y un 72,7%, respectivamente. La mortalidad de los pacientes operados con infección por SARS-CoV-2 en nuestro estudio (n = 10) fue del 10%; las complicaciones fueron del 80% (siendo graves un 30%). CONCLUSIONES: El presente estudio muestra una reducción global de la actividad quirúrgica tanto electiva como urgente durante la pandemia. La mortalidad global de los pacientes operados con infección por SARS-CoV-2 ha sido baja, pero la tasa de complicaciones graves ha sido superior a la global


INTRODUCTION: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. METHODS: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. RESULTS: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). CONCLUSIONS: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual


Subject(s)
Humans , Male , Female , Middle Aged , Coronaviridae Infections/epidemiology , Pneumonia, Viral/epidemiology , Pandemics , Surgical Procedures, Operative/statistics & numerical data , Emergencies , Elective Surgical Procedures/statistics & numerical data , Coronaviridae Infections/mortality , Pneumonia, Viral/mortality , Tertiary Healthcare , Prospective Studies
5.
Dig Surg ; 38(3): 237-246, 2021.
Article in English | MEDLINE | ID: mdl-33906192

ABSTRACT

INTRODUCTION: Obesity is usually considered a risk factor for surgical complications. Laparoscopic adrenalectomy has replaced open adrenalectomy as the standard operation for adrenal tumors. OBJECTIVE: To compare the safety of laparoscopic adrenalectomy to treat adrenal tumors in obese versus nonobese patients. METHODS: This observational cohort study analyzed consecutive patients who underwent laparoscopic adrenalectomy with a lateral transperitoneal approach at a single center (2003-2020). Data and outcomes of obese (body mass index ≥30 kg/m2) and nonobese patients were compared. To analyze the association between operative time and other variables, we used simple and multivariate linear regression. RESULTS: N = 160 (90 obese/70 nonobese) patients underwent laparoscopic adrenalectomy. Cushing syndrome and pheochromocytoma were the most frequent indications. Obese patients were older (58 vs. 52 years, p < 0.001). A greater proportion of obese patients were ASA grade III + IV (71.1 vs. 48.6%, p = 0.004). Obesity was associated with a longer operative time (72.5 vs. 60 min, p < 0.001) and greater blood loss (40 vs. 20 mL, p = 0.022). There were no differences in conversion, morbidity, or hospital stay. After adjustment for confounding factors, operative time was positively correlated with BMI ≥30 kg/m2, learning curve, estimated blood loss, 2D laparoscopy, and specimen size. CONCLUSION: Lateral transperitoneal laparoscopic adrenalectomy is safe in patients with a BMI 30-35 kg/m2, so these patients also benefit from this minimally invasive surgery.


Subject(s)
Adenoma/surgery , Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Laparoscopy , Obesity/complications , Pheochromocytoma/surgery , Adenoma/complications , Adolescent , Adrenal Gland Neoplasms/complications , Adult , Aged , Blood Loss, Surgical/statistics & numerical data , Case-Control Studies , Female , Humans , Length of Stay/statistics & numerical data , Linear Models , Male , Middle Aged , Operative Time , Pheochromocytoma/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Risk Factors , Treatment Outcome , Young Adult
7.
Updates Surg ; 73(2): 693-702, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32940830

ABSTRACT

Laparoscopy is the standard technique for resecting adrenal tumors, but short-term outcomes such as length of stay (LOS) vary widely between centers. We aimed to identify factors associated with LOS after lateral transperitoneal laparoscopic adrenalectomy (LTLA). We analyzed consecutive patients undergoing unilateral LTLA between April 2003 and April 2020. Prolonged LOS was defined as a stay longer than the 75th percentile of the overall cohort. To identify potential factors associated with prolonged LOS, we compared collected data from patients with LOS ≤ 2 days versus LOS > 2 days and elaborated multivariate logistic regression models. We included 150 patients (73 men and 77 women, median age 54 years), with benign (n = 128) and malignant tumors (n = 22). The median LOS after LTLA was 2 days; 64 (42.7%) patients had prolonged hospitalization. Variables significantly associated with prolonged LOS in the univariate analysis included ASA III + IV (p = 0.016), pheochromocytoma (p < 0.001), learning curve (p = 0.032), surgery on Thursday or Friday (p < 0.001), 2D laparoscopy (p = 0.003), operative time (p < 0.001), estimated blood loss (p < 0.001), drainage (p < 0.001), specimen size (p = 0.011), conversions (p = 0.002), complications (p = 0.019), and hospital stay (p < 0.001). After adjustment for patient, surgical, and tumor characteristics, risk factors associated with prolonged LOS in the multivariate analysis were specimen size > 9 cm (OR:13.03, p = 0.005), surgery on Thursday or Friday (OR:6.92, p = 0.001), estimated blood loss ≥ 60 ml (OR:6.22, p = 0.021), and drainage (OR:5.29, p = 0.005). Prolonged length of stay after LTLA was associated with specimen size > 9 cm, operating on Thursday or Friday, estimated blood loss ≥ 60 mL, and drainage.


Subject(s)
Adrenal Gland Neoplasms , Laparoscopy , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Female , Humans , Infant, Newborn , Length of Stay , Male , Operative Time , Retrospective Studies
8.
Langenbecks Arch Surg ; 406(2): 309-318, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33244719

ABSTRACT

PURPOSE: Laparoscopic surgery for rectal cancer is technically complex. This study aimed to identify risk factors for suboptimal laparoscopic surgery (involved margins, incomplete mesorectal excision, and/or conversion to open surgery) in patients with rectal cancer. METHODS: We included patients undergoing laparoscopic anterior resection for rectal cancer between June 2009 and June 2018. We defined the outcome variable suboptimal laparoscopic surgery as conversion to open surgery or inadequate histopathological specimens (margins < 1 mm or involved and/or poor-quality mesorectal excision). To identify independent predictors of suboptimal laparoscopic surgery, we analyzed 15 prospectively recorded demographic, clinical, and anthropometric variables obtained from our rectal cancer unit's database. Subanalyses examined the same variables with respect to conversion and to inadequate histopathological specimens. RESULTS: Of the 323 patients included, 91 (28.2%) had suboptimal laparoscopic surgery. In the multivariate analysis, the independent factors associated with all suboptimal laparoscopic surgery were tumor location ≤ 5 cm from the anal verge (OR = 2.95, 0.95% CI 1.32-6.60; p = 0.008) and the intertuberous distance (OR = 0.79, 0.95% CI 0.65-0.96; p = 0.019). In the subanalyses, the promontorium-retropubic axis was an independent predictor of conversion (OR 0.70, 0.95% CI 0.51-0.96; p = 0.026), and tumor location ≤ 5 cm from the anal verge (OR 3.71, 0.95% 1.51-9.15; p = 0.004) was an independent predictor of inadequate histopathological specimens. CONCLUSIONS: Predictive factors for suboptimal laparoscopic anterior resection for rectal cancer were tumor location and the intertuberous distance. These results could help surgeons decide whether to use other surgical approaches in complex cases. TRIAL REGISTRATION: The study was registered at Clinicaltrials.org (No. NCT03107650).


Subject(s)
Laparoscopy , Rectal Neoplasms , Conversion to Open Surgery , Humans , Rectal Neoplasms/surgery , Risk Factors , Treatment Outcome
9.
Cir Esp (Engl Ed) ; 99(5): 368-373, 2021 May.
Article in English, Spanish | MEDLINE | ID: mdl-32819710

ABSTRACT

INTRODUCTION: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. METHODS: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. RESULTS: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). CONCLUSIONS: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.


Subject(s)
COVID-19 , Surgical Procedures, Operative/statistics & numerical data , COVID-19/epidemiology , Elective Surgical Procedures/statistics & numerical data , Emergency Treatment/statistics & numerical data , Female , Hospitals, University , Humans , Male , Middle Aged , Prospective Studies , Spain/epidemiology
10.
Cir Esp ; 99(5): 368-373, 2021 May.
Article in Spanish | MEDLINE | ID: mdl-38620504

ABSTRACT

Introduction: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. Methods: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. Results: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n = 10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). Conclusions: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.

11.
Int J Surg ; 83: 220-229, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33038521

ABSTRACT

BACKGROUND: Low anterior resection syndrome affects 60%-90% of patients with anastomoses after colorectal resection. Consensus regarding the best anastomosis is lacking. OBJECTIVE: To compare outcomes after end-to-end versus side-to-end anastomoses. DESIGN: Randomized clinical trial. SETTINGS: University hospital (April 2016-October 2017). PATIENTS: Patients aged ≥18 years with rectal or sigmoid adenocarcinoma. INTERVENTIONS: Patients were randomized to undergo mechanical end-to-end or side-to-end (n = 33) anastomosis after laparoscopic resection. MAIN OUTCOME MEASURES: Primary outcome was to assess intestinal function (COREFO and LARS questionnaires) 12 months after surgery or ileostomy closure. Secondary outcomes were postoperative complications and intestinal function and quality of life (SF-36® questionnaire) at different time points after surgery or ileostomy closure. RESULTS: No significant differences in intestinal function were observed between the two groups 12 months after surgery. Subanalysis of low-mid rectum tumors with end-to-end anastomosis yielded better function at 12 months. Postoperative complications did not differ between the two groups (p = 0.070), but reinterventions were more common in the side-to-end group (p = 0.040). Multivariate analysis found neoadjuvant treatment was independently associated with intestinal dysfunction at 12 months (ß = 0.41, p = 0.033, COREFO; ß = 0.41, p = 0.024, LARS). CONCLUSIONS: End-to-end anastomosis yielded low rates of severe complications and reintervention, as well as better intestinal function at 12 months in the subgroup with tumors in the low-mid rectum. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02746224.


Subject(s)
Adenocarcinoma/surgery , Anastomosis, Surgical/methods , Rectal Neoplasms/surgery , Rectum/surgery , Sigmoid Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Single-Blind Method
12.
Langenbecks Arch Surg ; 405(8): 1163-1173, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32909079

ABSTRACT

PURPOSE: Laparoscopy is the standard technique for resecting adrenal tumors worldwide. The main drawbacks of conventional 2D laparoscopy are limited depth perception and tactile feedback. Currently available high-quality 3D laparoscopy systems might improve surgical outcomes for adrenalectomy. We compare the safety and efficacy of 3D versus 2D laparoscopy in the treatment of adrenal tumors. METHODS: This case-control study analyzed prospectively collected data from patients with benign or malignant adrenal tumors treated laparoscopically at a single academic medical center between April 2003 and March 2020. We collected demographic, diagnostic, preoperative, and operative variables, and used multiple linear and logistic regression to analyze differences in various short-term outcomes between the two approaches while adjusting for potential confounders. RESULTS: We included 150 patients: 128 with benign tumors and 22 with malignant tumors; 95 treated with 3D laparoscopy (case group); and 55 with 2D laparoscopy (control group). After adjustment for patient, surgical, and tumor characteristics, a 2D vision was associated with a longer operative time (ß = 0.26, p = 0.002) and greater blood loss (ß = 0.20, p = 0.047). There was no significant difference in rates of conversion to open surgery (odds ratio [OR] = 1.47 (95% CI 0.90-22.31); p = 0.549) or complications (3.6% vs. 2.1%; p = 0.624). CONCLUSIONS: With experienced surgeons, laparoscopic adrenalectomy was safer and more feasible with the 3D system than with the 2D system, resulting in less operative blood loss and shorter operative time with no differences in rates of conversion to open surgery or postoperative complications. For adrenal tumors, 3D laparoscopy offers advantages over 2D laparoscopy.


Subject(s)
Adrenal Gland Neoplasms , Laparoscopy , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Case-Control Studies , Humans , Retrospective Studies
13.
Updates Surg ; 72(2): 453-461, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32232742

ABSTRACT

BACKGROUND: We currently do not know the optimal time interval between the end of chemoradiotherapy and surgery. Longer intervals have been associated with a higher pathological response rate, worse pathological outcomes and more morbidity. The aim of this study was to evaluate the effect and safety of the current trend of increasing time interval between the end of chemoradiotherapy and surgery (< 10 weeks vs. ≥ 10 weeks) on postoperative morbidity and pathological outcomes. This study analyzed 232 consecutive patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy from January 2012 to August 2018. 125 patients underwent surgery before 10 weeks from the end of chemoradiotherapy (Group 1) and 107 patients underwent surgery after 10 or more weeks after the end of chemoradiotherapy (Group 2). Results have shown that wait for ≥ 10 weeks did not compromise surgical safety. Pathological complete response and tumor stage was statistically significant among groups. The effect of wait for ≥ 10 weeks before surgery shown higher tumor regression than the first group (Group 1, 12.8% vs Group 2, 31.8%; p < 0.001). On multivariate analysis, wait for ≥ 10 weeks was associated with pathological compete response. Patients from the second group were four time more likely to achieve pathologic complete response than patients from the first group (OR, 4.27 95%CI 1.60-11.40; p = 0.004). Patients who undergo surgery after ≥ 10 weeks of the end of chemoradiotherapy are four time more likely to achieve complete tumor remission without compromise surgical safety or postoperative morbidity.


Subject(s)
Chemoradiotherapy, Adjuvant , Neoadjuvant Therapy , Rectal Neoplasms/surgery , Rectal Neoplasms/therapy , Time-to-Treatment , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Multivariate Analysis , Rectal Neoplasms/pathology , Remission Induction , Safety , Time Factors , Treatment Outcome
14.
J Mol Med (Berl) ; 93(1): 83-92, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25249007

ABSTRACT

UNLABELLED: Transgenic overexpression of adipose tissue (AT) transducin-like enhancer of split 3 (TLE3) mimicked peroxisome proliferator-activated receptor gamma (PPARγ) agonists, improving insulin resistance in mice. This study aimed to investigate TLE3 gene expression (qRT-PCR) and protein (Western blot) in subjects with a wide spectrum of obesity and insulin sensitivity and in an independent cohort of obese subjects following surgery-induced weight loss. TLE3 was analyzed in human adipocytes and after treatment with rosiglitazone. Given the findings in humans, TLE3 was also investigated in mice after a high-fat diet (HFD) and in PPARγ knockout mice. Subcutaneous (SC) AT TLE3 was increased in subjects with type 2 diabetes (T2D). In fact, SC TLE3 was associated with increased fasting glucose (r = 0.25, p = 0.015) and S6K1 activity (r = 0.671, p = 0.003), and with decreased Glut4 (r = -0.426, p = 0.006) and IRS-1 expression (-31 %, p = 0.007) and activation (P-IRS-1/IRS-1, -17 %, p = 0.024). TLE3 was preferentially expressed in mature adipocytes and increased during in vitro differentiation in parallel to PPARγ. Weight loss led to improved insulin sensitivity, increased AT PPARγ and decreased TLE3 (-24 %, p = 0.0002), while rosiglitazone administration downregulated TLE3 gene expression in fully differentiated adipocytes (-45 %, p < 0.0001). The concept that TLE3 may act as a homeostatic linchpin in AT was also supported by its increased expression in HFD-fed mice (39 %, p = 0.013) and PPARγ knockout (74 %, p = 0.001). In summary, increased AT TLE3 in subjects with T2D and in AT from HFD-fed and PPARγ knockout mice suggest that TLE3 may play an adaptive regulatory role that improves AT function under decreased PPARγ expression. KEY MESSAGE: TLE3 is expressed in mature adipocytes concomitantly with PPARγ. Subcutaneous adipose TLE3 is increased in T2D patients. Adipose TLE3 is upregulated in genetically ablated PPARγ and HFD-fed mice. TLE3 may be a homeostatic linchpin in insulin resistance and defective PPARγ.


Subject(s)
Adipose Tissue/metabolism , Co-Repressor Proteins/genetics , Diabetes Mellitus, Type 2/genetics , Obesity, Morbid/genetics , PPAR gamma/genetics , Adipocytes/metabolism , Adult , Animals , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Female , Gene Expression , Humans , Insulin Resistance , Male , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Obesity, Morbid/metabolism , RNA, Messenger/metabolism
15.
J Nutr Biochem ; 24(7): 1266-75, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23333090

ABSTRACT

Lactoferrin is considered an epithelial protein present in different gland secretions. Administration of exogenous lactoferrin is also known to modulate adipogenesis and insulin action in human adipocytes. Here, we aimed to investigate lactoferrin gene expression (real-time polymerase chain reaction) and protein (enzyme-linked immunosorbent assay) levels in human (n=143) and mice adipose tissue samples, in adipose tissue fractions and during human preadipocyte and 3T3-L1 cell line differentiation, evaluating the effects of inducers (rosiglitazone) and disruptors (inflammatory factors) of adipocyte differentiation. Lactoferrin (LTF) gene and protein were detectable at relatively high levels in whole adipose tissue and isolated adipocytes in direct association with low-density lipoprotein-related protein 1 (LRP1, its putative receptor). Obese subjects with type 2 diabetes and increased triglycerides had the lowest levels of LTF gene expression in subcutaneous adipose tissue. Specifically, LTF gene expression was significantly increased in adipocytes, mainly from lean subjects, increasing during differentiation in parallel to adipogenic genes and gene markers of lipid droplets. The induction or disruption of adipogenesis led to concomitant changes (increase and decrease, respectively) of lactoferrin levels during adipocyte differentiation also in parallel to gene markers of adipogenesis and lipid droplet development. The administration of lactoferrin led to autopotentiated increased expression of the LTF gene. The decreased lactoferrin mRNA levels in association with obesity and diabetes were replicated in mice adipose tissue. In conclusion, this is the first observation, to our knowledge, of lactoferrin gene expression in whole adipose tissue and isolated adipocytes, increasing during adipogenesis and suggesting a possible contribution in adipose tissue physiology through LRP1.


Subject(s)
Adipocytes/metabolism , Adipose Tissue/metabolism , Biomarkers/metabolism , Inflammation/metabolism , Lactoferrin/genetics , 3T3-L1 Cells , Adult , Animals , Female , Fibroblasts/metabolism , Humans , Male , Mice , Middle Aged
16.
Article in English | MEDLINE | ID: mdl-24683474

ABSTRACT

BACKGROUND: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy. PATIENT FINDINGS: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-ß (TR ß (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 µg/kg per day of l-T4. CONCLUSION: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH. LEARNING POINTS: High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy.The exact role of TR ß mutants in thyroid carcinogenesis is still undefined.We report the first case of multiple Hürthle cell adenomas associated with RTH.

19.
Diabetes ; 60(1): 168-76, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20956498

ABSTRACT

OBJECTIVE: Metformin has been well characterized in vitro as a substrate of liver-expressed organic cation transporters (OCTs). We investigated the gene expression and protein levels of OCT-1 and OCT-2 in adipose tissue and during adipogenesis and evaluated their possible role in metformin action on adipocytes. RESEARCH DESIGN AND METHODS: OCT1 and OCT2 gene expressions were analyzed in 118 adipose tissue samples (57 visceral and 61 subcutaneous depots) and during human preadipocyte differentiation. To test the possible role of OCT1 mediating the response of adipocytes to metformin, cotreatments with cimetidine (OCT blocker, 0.5 and 5 mmol/l) and metformin were made on human preadipocytes and subcutaneous adipose tissue (SAT). RESULTS: OCT1 gene was expressed in both subcutaneous and visceral adipose tissue. In both fat depots, OCT1 gene expression and protein levels were significantly increased in obese subjects. OCT1 gene expression in isolated preadipocytes significantly increased during differentiation in parallel to adipogenic genes. Metformin (5 mmol/l) decreased the expression of lipogenic genes and lipid droplets accumulation while increasing AMP-activated protein kinase (AMPK) activation, preventing differentiation of human preadipocytes. Cotreatment with cimetidine restored adipogenesis. Furthermore, metformin decreased IL-6 and MCP-1 gene expression in comparison with differentiated adipocytes. Metformin (0.1 and 1 mmol/l) decreased adipogenic and inflammatory genes in SAT. OCT2 gene expression was not detected in adipose tissue and was very small in isolated preadipocytes, disappearing during adipogenesis. CONCLUSIONS: OCT1 gene expression and protein levels are detectable in adipose tissue. Increased OCT1 gene expression in adipose tissue of obese subjects might contribute to increased metformin action in these subjects.


Subject(s)
Adipocytes/physiology , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Obesity/genetics , Organic Cation Transporter 1/genetics , Acetyl-CoA Carboxylase/metabolism , Acetyltransferases/genetics , Adenylate Kinase/metabolism , Adipocytes/pathology , Azo Compounds , Cell Differentiation , Coloring Agents , Fatty Acid Synthase, Type I/genetics , Gastric Bypass , Gene Expression , Gene Expression Regulation/drug effects , Humans , Obesity/drug therapy , Obesity/pathology , Obesity/surgery , Organic Cation Transport Proteins/genetics , Organic Cation Transporter 2 , PPAR gamma/genetics , RNA/genetics
20.
Obes Surg ; 20(9): 1319-22, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19255813

ABSTRACT

Obesity, the most significant metabolic problem in the world today, is associated with a wide range of diseases, including endocrine disorders. Paraganglioma is a rare chromaffin cell tumor that develops from the neural crest cells of the neuroendocrine system. Retroperitoneal paragangliomas can represent a surgical challenge due to their close relation to large vessels. We report two cases of functioning retroperitoneal paraganglioma in type-I obese patients (case 1: female; weight, 77 kg; body mass index, 30.1 kg/m(2); case 2: male; weight, 92 kg; body mass index, 31.1 kg/m(2)) who underwent elective endocrine surgery. The tumors (one interaortocaval and the other above the iliac artery) were completely excised by laparotomy without postoperative complications.


Subject(s)
Obesity/complications , Paraganglioma, Extra-Adrenal/complications , Retroperitoneal Neoplasms/complications , Adult , Female , Humans , Male , Paraganglioma, Extra-Adrenal/diagnosis , Paraganglioma, Extra-Adrenal/surgery , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/surgery
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