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We report our clinical experience with the external oblique intercostal block in three consecutive adult patients who underwent liver surgery for resection of metastases. Enhanced recovery guidelines for liver surgery recommend intrathecal opioids and peripheral regional anaesthetic techniques in the context of multimodal analgesia to achieve adequate postoperative analgesia and early functional recovery. However, both laparoscopic and open approaches to liver surgery involve incisions in the upper abdomen, an anatomical area not well covered by previously described peripheral regional anaesthetic techniques. The external oblique intercostal block is a novel motor- and opioid-sparing technique which blocks both the anterior and lateral cutaneous branches of the thoracoabdominal nerves which innervate the upper abdominal quadrant. In all cases in this series, we performed the blocks in a short period of time and without complications. All patients remained pain- and opioid-free in the postoperative period and achieved enhanced recovery outcomes early. We found the external oblique intercostal block to be a simple, convenient, effective and opioid-sparing regional anaesthetic technique for postoperative analgesia after liver surgery. By minimising opioid use and by obviating the need for central neuraxial anaesthesia techniques in the postoperative period, this block could be incorporated into enhanced recovery protocols for hepatobiliary surgery.
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We aim to review the available literature on patients with morbid obesity treated with banded (BRYGB) or non-banded Roux-en-Y gastric bypass (NBRYGB), in order to compare the clinical outcomes and intraoperative parameters of the two methods. A systematic literature search was performed in PubMed, Cochrane library and Scopus databases, in accordance with the PRISMA guidelines. Eight studies met the inclusion criteria incorporating 3899 patients. This study reveals similar rates of complications, mortality, remission of type 2 diabetes, hypertension, dyslipidaemia, gastroesophageal reflux and obstructive sleep apnoea, along with similar % excess weight loss (%EWL) at 1 and 2 years postoperatively. In contrast, according to an analysis of two eligible studies the BRYGB procedure was associated with increased %EWL at 5 years postoperatively. These results should be interpreted with caution due to the small number of statistical arms and randomized controlled studies. However, the present article represents the best available evidence in the field. Well-designed, randomized controlled studies, comparing BRYGB to NBRYGB, are necessary to further assess their clinical outcomes.
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Derivación Gástrica/métodos , Obesidad Mórbida/cirugía , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/terapia , Dislipidemias/etiología , Dislipidemias/terapia , Derivación Gástrica/efectos adversos , Derivación Gástrica/mortalidad , Reflujo Gastroesofágico/etiología , Reflujo Gastroesofágico/terapia , Humanos , Hipertensión/etiología , Hipertensión/terapia , Obesidad Mórbida/complicaciones , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/terapia , Resultado del Tratamiento , Pérdida de PesoRESUMEN
GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.
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Adenocarcinoma/genética , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Moléculas de Adhesión Celular/genética , Neoplasias Colorrectales/genética , Adenocarcinoma/patología , Anciano , Antígenos de Neoplasias/biosíntesis , Biomarcadores de Tumor/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/patología , Molécula de Adhesión Celular Epitelial , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Laparoscopic transabdominal preperitoneal (TAPP) repair is indicated for recurrent and bilateral inguinal hernias and traditionally is performed under general anesthesia. However, the feasibility of performing TAPP under spinal anesthesia has been recently reported by our team. AIM: To assess the long-term results of TAPP repair under spinal anesthesia for primary inguinal hernia. MATERIALS AND METHODS: Between January 2006 and October 2009, 94 consecutive patients with primary unilateral inguinal hernia were submitted to laparoscopic transabdominal preperitoneal repair under spinal anesthesia. We looked at the immediate postoperative outcome as well as the long-term outcome, mainly recurrences and incidence of chronic pain. RESULTS: One patient experienced a scrotal hematoma, one patient a trocar site infection, two patients were diagnosed with an operation-related orchitis, while 31 patients (33 %) developed symptoms of urinary retention. At a median follow-up of 35 months (range 14-59), four patients (4.3 %) were diagnosed with a recurrence, while 89 % of patients reported satisfied from the procedure in the long-term. Chronic pain was not encountered in any of the patients studied. Four patients (4.3 %) reported an intermitted foreign body sensation and/or rigidity and two patients (2.1 %) numbness in the operated inguinal area. CONCLUSION: Laparoscopic TAPP hernia repair under spinal anesthesia is associated with satisfactory short- and long-term results. Use of regional anesthesia instead of the traditional general anesthesia does not seem to adversely affect the quality of repair, and moreover, it offers the patient an attractive anesthetic alternative.
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Anestesia Raquidea , Hernia Inguinal/cirugía , Herniorrafia/métodos , Dolor Postoperatorio/etiología , Adulto , Anciano , Anciano de 80 o más Años , Dolor Crónico/etiología , Femenino , Estudios de Seguimiento , Herniorrafia/efectos adversos , Humanos , Hipoestesia/etiología , Laparoscopía , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Recurrencia , Sensación , Mallas Quirúrgicas/efectos adversos , Factores de TiempoRESUMEN
PURPOSE: Tension-free repair with mesh placement has become the gold standard for open inguinal hernia surgery. Traditionally, non absorbable materials have been used for mesh manufacture. The purpose of this pilot study was to evaluate the efficacy of using a totally absorbable prosthetic mesh for open inguinal hernia repair. METHODS: Ten patients with elective inguinal hernias were set to undergo open tension-free inguinal hernia repair with the use of polyglycolic acid-trimethylene carbonate absorbable mesh. In this pilot study, we looked primarily at recurrence and chronic pain assessed 1 year after the operation, while immediate postoperative complications were also recorded. RESULTS: All patients were discharged from the hospital the day after surgery. In three patients (30%), a Foley catheter was inserted to relieve symptoms of urinary retention. None of the patients had any immediate postoperative complication. At the 1st year follow up, none of the patients had clinical signs of recurrence. However, one patient experienced intermittent pain in the operated inguinal area. CONCLUSIONS: Open inguinal hernia repair with the use of polyglycolic acid-trimethylene absorbable mesh proved efficient in the given patient sample. Further studies with a larger number of patients and longer follow up are needed in order to confirm the possible favourable effects of this mesh type.
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Implantes Absorbibles , Hernia Inguinal/cirugía , Mallas Quirúrgicas , Implantes Absorbibles/efectos adversos , Anciano , Enfermedad Crónica , Dioxanos , Estudios de Seguimiento , Humanos , Dolor/etiología , Proyectos Piloto , Ácido Poliglicólico , Recurrencia , Mallas Quirúrgicas/efectos adversos , Resultado del TratamientoRESUMEN
This paper highlights our experience of the transfer of hydrodynamic gene therapy (HGT) from the large animal, the pig, into clinical practice. The modification of balloon catheters and the development of a minimally invasive technique to allow selective isolation of liver segments for HGT in the large animal and human are described. Finally, our preliminary results from a phase I clinical study of HGT for thrombopoietin (TPO) in cirrhotic patients with thrombocytopenia are discussed. Based on these provisional data, minimally invasive selective HGT of liver segments appears to be technically safe, but further work is required to optimize the efficiency of gene transfer in order to achieve clinical benefit.
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Terapia Genética , Cirrosis Hepática/terapia , Trombocitopenia/terapia , Adulto , Animales , Femenino , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Plásmidos , Porcinos , Trombocitopenia/complicaciones , Trombopoyetina/genéticaRESUMEN
We determined, for the first time, the human telomerase reverse transcriptase (hTERT) mRNA expression, using real-time quantitative PCR, in liver tissues from patients with hepatocellular cancer (HCC; n = 13), chronic hepatitis B (n = 19) and C (n = 13). Liver tissues from the 45 patients and 17 patients without liver disease in whom liver biopsy was performed during cholecystectomy (control group), were investigated for telomerase activity (TA) and hTERT mRNA expression using the LightCycler technology. TA was detected in all HCC tissues compared with 15.6% of chronic hepatitis (P < 0.001) and none of controls (P < 0.001). TA levels and hTERT mRNA were higher in HCC compared with chronic hepatitis (P < 0.001) and normal livers (P < 0.001). hTERT mRNA expression was correlated with TA (P < 0.05). Chronic hepatitis patients who tested negative for TA and hTERT mRNA had significantly lower disease duration (58 +/- 85 months) compared with those tested positive (144 +/- 50 months; P < 0.05). Detection of TA and quantification of hTERT mRNA expression in liver tissues could be useful and additional markers for HCC diagnosis and may serve as prognostic markers for HCC development in chronic viral hepatitis patients. However, we were not able to draw general conclusions at this moment, as the number of chronic hepatitis patients positive for hTERT mRNA was relatively small. Real-time quantification of hTERT mRNA expression as a diagnostic/prognostic marker in patients with chronic hepatitis B and C and its relationship with hepatocarcinogenesis needs further evaluation.
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Carcinoma Hepatocelular/enzimología , Hepatitis B Crónica/enzimología , Hepatitis C Crónica/enzimología , Neoplasias Hepáticas/enzimología , Telomerasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Femenino , Hepacivirus , Virus de la Hepatitis B , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Hepatitis C Crónica/genética , Hepatitis C Crónica/patología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Telomerasa/biosíntesisRESUMEN
BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has become the most common surgical treatment for gastroesophageal reflux disease (GERD). Controversies still exist regarding the operative technique and the durability of the procedure. METHODS: A retrospective study of 808 patients undergoing 838 LNF for GERD at a tertiary referral center was undertaken. Demographic, perioperative, and follow-up data had been entered onto the unit database. RESULTS: During a median follow-up period of 60 months (range, 2-120 months), heartburn decreased to 3% of the patients (19/645) and regurgitation to 2% (11/582) (p < 0.01). Respiratory symptoms improved in 69 (85%) of 81 patients (p < 0.01). The incidence of postoperative dysphagia was unaffected by the use of an intraesophageal bougie (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.82-1.64; p = 0.41) or division of the short gastric vessels (OR, 0.84; 95% CI, 0.42-1.07; p = 0.72). In the immediate postoperative period, the incidence of abdominal symptoms increased by 10% (p < 0.01) and dysphagia by 16% (p < 0.01). After 10 postoperative years, only 3% (30/484) were found to have abdominal symptoms, whereas the incidence of dysphagia declined to zero. CONCLUSION: The findings show that LNF is a safe and effective procedure with long-term durability. Abdominal symptoms and dysphagia are the principal postoperative complaints, which improve with time. Personal preference should dictate the use of a bougie, division of the short gastric vessels, or both.
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Fundoplicación/métodos , Reflujo Gastroesofágico/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Four cases of perianal abscesses due to foreign bodies (FBs) impacted in the anal canal are reported. The clinical presentation mimics common causes of acute anal pain. Digital rectal examination under local or general anaesthesia and/or proctoscopy can establish the diagnosis, but may miss the presence of an FB. Incision and drainage of the abscess along with removal of the FB results in immediate pain relief and long-term cure. Impacted FBs must not be overlooked as an unusual cause of perianal abscess.
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Absceso/etiología , Canal Anal , Cuerpos Extraños/complicaciones , Absceso/cirugía , Anciano , Drenaje/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Morbid obesity is a significant clinical problem in the western world. Various surgical restrictive procedures have been described as an aid to weight reduction when conservative treatments fail. Adjustable laparoscopic gastric banding (LAPBAND) has been popularized as an effective, safe, minimally invasive, yet reversible technique for the treatment of morbid obesity. Radiological input is necessary in the follow-up of these patients and the diagnosis of complications peculiar to this type of surgery. In this review we will highlight the technical aspects of radiological follow-up and the lessons learnt over the last 5 years.
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Gastroplastia/efectos adversos , Gastroplastia/métodos , Laparoscopía/métodos , Obesidad Mórbida/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Dilatación Patológica/etiología , Diseño de Equipo , Falla de Equipo , Estudios de Seguimiento , Gastroplastia/instrumentación , Humanos , Laparoscopía/efectos adversos , Obesidad Mórbida/cirugía , Radiografía , Infección de la Herida Quirúrgica/etiología , Pérdida de PesoRESUMEN
BACKGROUND: We present our experience with palliative transanal electrocoagulation therapy (TEC) for rectal cancer. METHODS: Eight patients with biopsy-proven localised low rectal adenocarcinoma were treated with palliative TEC. Inclusion criteria were: high risk patients with anal adenocarcinoma less than 3 cm in diameter, localised less than 7 cm from the anal verge, limited to the rectal wall. Under local anaesthesia all patients underwent TEC using the traditional cautery. RESULTS: No mortality and morbidity was found. Four patients required a second procedure and one patient had a third session . Two patients died within 2 years from distal metastasis. The remaining six patients are alive and free of local recurrence (follow-up 9 months to 4 years). CONCLUSIONS: In poor surgical candidates, palliative TEC of rectal adenocarcinoma may have a role as an alternative to radical surgical treatment.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Electrocoagulación/métodos , Cuidados Paliativos/métodos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Selección de Paciente , Proctoscopía , Estudios Prospectivos , Neoplasias del Recto/mortalidad , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Metastasis to the pancreas from renal cell carcinoma (RCC) is distinctly uncommon. Most cases are detected at an advanced stage of the disease and are thus unsuitable for resection. A solitary RCC metastasis to the head of pancreas is rarely encountered and, although it is potentially amenable to surgical resection, surgeons may be hesitant to perform pancreatoduodenectomy. CASES OUTLINES: Two patients with a solitary RCC metastasis to the head of pancreas were treated by pancreatoduodenectomy, while a third with multiple RCC metastases declined any treatment. Two of the patients were asymptomatic, and one presented with anaemia and mild abdominal pain. Computed tomography (CT) and angiography were used to exclude other metastases and to assess resectability of the pancreatic tumour. All three patients are still alive, those with resectable disease at 2 years and 9 years and the one with irresectable disease at 4 years. DISCUSSION: Isolated RCC metastasis to the pancreas is a rare event. Patients present either on follow-up imaging or with symptoms such as mild abdominal pain, weight loss, jaundice, anaemia or gastrointestinal bleeding (whether occult or overt). Dynamic spiral CT can visualise the tumour and exclude distant metastasis. Angiography often reveals a highly vascularised tumour and will help to assess resectability. In the absence of widespread disease, pancreatic resection can provide long-term survival in metastatic RCC, although few cases have been reported with lengthy follow-up. The prognosis is better than for pancreatic adenocarcinoma.
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BACKGROUND: The laparoscopically-placed adjustable gastric band (LAGB) is a minimally invasive, adjustable and completely reversible operation. We report 3 years experience. METHODS: Between May 1998 and January 2001, we operated on a consecutive series of 50 patients (8 male/42 female). Mean age of patients was 37 years (30-48). Mean preoperative BMI was 43 kg/m2 (range 38-55). RESULTS: Mean operative time was 130 minutes (range 75-150), and the conversion rate was 6%. Mean hospital stay was 2.8 days (range 2-10). Postoperatively 7/50 (14%) of patients had dysphagia and subsequently 2 (4%) developed gastric pouch dilatation. 2/50 (4%) had non-fatal pulmonary embolism and 2/50 (4%) developed gastroesophageal reflux. Overall morbidity was 32%. There has been no mortality. 6 weeks postoperatively, patients had adjustment of the band by the radiologists. Follow-up has been up to 30 months. Mean excess weight loss at 6 months was 30% (range 26-35%, N = 50), at 12 months 52% (range 44-55%, N = 42), at 24 months 60% (range 55-65%, N = 14) and at 30 months 62% (range 58-64%, N = 8). 5 patients have reached their ideal body weight. CONCLUSIONS: LAGB is safe and effective, even early in the learning curve. The radiologist plays a distinct role. A multi-disciplinary team approach is essential for optimal results. Long-term results are pending.
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Vendajes/efectos adversos , Laparoscopía/efectos adversos , Obesidad Mórbida/diagnóstico por imagen , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias , Radiología , Estómago/diagnóstico por imagen , Estómago/cirugía , Adulto , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Radiografía , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: We measured the serum levels of four trace elements (Cu, Zn, Mn, Pb) and Mg in surgical patients receiving total parenteral nutrition (TPN). The clinical implications and the results are discussed. METHODS: Two groups of patients were studied: the first group (n = 40) was our study group and the second (n = 40) was the control group. Four measurements of each trace element (TE) in blood serum were carried out: one before initiating TPN, one 24 h after, one 3 d later, and the last one immediately after discontinuing TPN. Each measurement was repeated twice. The Perkin-Elmer atomic absorption spectrophotometer (model 2380) with furnace graphite HGA-300 was used to measure the TE levels and an acetylene flame was used to measure the Mg levels. RESULTS: Levels of all the TEs, except Pb, were lower before the administration of TPN compared with the control group (P < 0.05). The levels of TEs during and immediately after TPN were generally lower in comparison with the initial measurement before the administration of TPN. CONCLUSION: The results of this study suggest that it may be necessary to 1) add Cu, Zn, Mn, and Mg to the parenteral nutritional solution and 2) follow the fluctuations in serum levels during the administration of TPN.
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Magnesio/análisis , Nutrición Parenteral Total/normas , Oligoelementos/análisis , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Cobre/administración & dosificación , Cobre/sangre , Femenino , Humanos , Plomo/sangre , Magnesio/administración & dosificación , Masculino , Manganeso/administración & dosificación , Manganeso/sangre , Persona de Mediana Edad , Necesidades Nutricionales , Estado Nutricional , Espectrofotometría Atómica/métodos , Oligoelementos/administración & dosificación , Zinc/administración & dosificación , Zinc/sangreRESUMEN
BACKGROUND: Surgical resection remains the gold standard in dealing with liver tumours. Blood loss, biliary leak and postoperative liver function are still the main concerns of surgeons operating on the liver, even though different techniques have been developed to allow safer liver resection. A novel concept for liver resection is described using a radiofrequency energy (RF) assisted technique. METHOD: A patient with a large colorectal liver metastasis located in segments VI, VII, VIII underwent a right hepatectomy using this technique. At laparotomy the tumour was staged with intraoperative ultrasonography, and a 'cooled tipped' radiofrequency probe was used to achieve a 'zone of desiccation' in the liver parenchyma 2 cm away from the edge of the tumour. Liver parenchyma was subsequently divided with a surgical scalpel. RESULTS: The resection time was 80 min with a blood loss of 30 ml. The patient was discharged on the ninth postoperative day without complications. DISCUSSION: Liver resection assisted by RF energy is feasible and safe. This technique could offer a new method for 'transfusion-free' resection without the need for sutures, ties, staples, tissue glue or admission to the intensive care unit.
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BACKGROUND: The introduction of an endoscopically-placed Bariatric Intragastric Balloon (BIB) provided the opportunity to reexamine weight reduction methods and also study potential weight loss without resorting to surgical intervention. METHODS: 10 severely obese patients with mean age 33 years and mean body mass index 39, underwent BIB placement, 7 as a sole weight reduction procedure and 3 requiring weight reduction before repair of large incisional hernias. All patients were followed at 2-week intervals by a nurse practitioner and dietitian for 6 months. RESULTS: Mean weight loss was 18.6 kg (range 6.6-40.0), equivalent to 40% excess weight loss (EWL), range 10-81%. EWL was 54% (29-81%) in those patients who had two balloons placed, who lost an average of 30.3 kg (24.0-40.0 kg). In the patients who had only one balloon placed, mean weight loss was 10.4 kg (8.8-12.5), equal to an EWL of 19% (10-37%). CONCLUSION: These results lead us to consider BIB placement as a successful short-term measure for weight loss or for patients requiring at least weight loss before other surgery.
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Obesidad Mórbida/cirugía , Prótesis e Implantes , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We studied endothelial-mediated microvascular blood flow in neuropathic diabetic patients to determine the association between endothelial regulation of the microcirculation and the expression of endothelial constitutive nitric oxide synthetase (ecNOS) in the skin. Vasodilation on the dorsal foot in response to heating and iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were measured using single-point laser Doppler and laser Doppler imaging in diabetic patients with neuropathy (DN), with neuropathy and vascular disease (DI), with Charcot arthropathy (DA), and without complications (D), and in healthy control subjects (C). The response to heat was reduced in the DN (321 [21-629] percentage of increase over the baseline, median [interquartile range]) and DI (225 [122-470]) groups but was preserved in the DA (895 [359-1,229]), D (699 [466-1,029]), and C (810 [440-1,064], P < 0.0001) groups. The endothelial-mediated response to acetylcholine was reduced in the DN (17 [11-25]), DA (22 [2-34]), and DI (13 [2-30]) groups compared with the D (47 [24-58]) and C (44 [31-70], P < 0.001) groups. The non-endothelial-mediated response to sodium nitroprusside was also reduced in the DI (4 [0-18]), DN (17 [9-26]), and DA (21 [11-31]) groups compared with the D (37 [19-41]) and C (44 [26-67], P < 0.0001) groups. There was a significant reduction in vasodilation in the DI group compared with all other groups (P < 0.0001). Full thickness skin biopsies from the dorsum of the foot of 15 DN, 10 DI, and 11 C study subjects were immunostained with antiserum to human ecNOS, the functional endothelial marker GLUT1, and the anatomical endothelial marker von Willebrand factor. The staining intensity of ecNOS was reduced in both diabetic groups. No differences were found among the three groups in the staining intensity of von Willebrand factor and GLUT1. We conclude that the endothelium-dependent and endothelium-independent vasodilations are impaired in diabetic patients predisposed to foot ulceration and that neuropathy is the main factor associated with this abnormality. Reduced expression of ecNOS may be a major contributing factor for endothelial dysfunction. These data provide support for a close association of neuropathy and microcirculation in the pathogenesis of foot ulceration.