RESUMEN
BACKGROUND: Mini-One Anastomosis Gastric Bypass is a new operation that provides comparable outcomes to the common bariatric procedures. Revisional surgery is still needed after a number of MGB-OAGB procedures. The aim of this study is to report the causes and management of these revisions. METHODS: From 2010 to 2018, 925 MGB-OAGB operations were performed at 7 bariatric units across the United Kingdom and included in this retrospective cohort study. The data was retrospectively collected and analysed. The primary end point was the identification of the causes and management of revisions. Follow up ranged from 6 months to 3 years. RESULTS: Twenty-two patients [2.3%] required revisional surgery after MGB-OAGB. Five patients [0.5%] developed severe diarrhoea managed by shortening the bilio-pancreatic limb to 150â¯cm. Four patients [0.4%] developed afferent loop syndrome and bile reflux was reported in another 3 [0.3%] cases; all were managed by either conversion to Roux en Y Gastric Bypass or a Braun anastomosis. Postoperative bleeding was controlled laparoscopically in 3 patients [0.3%]. Liver decompensation that was reported in 2 patients [0.2%] was treated by shortening the BPL in one patient and a reversal to normal anatomy in another. The liver failure resolved in both patients. Other indications for revision included two gastro-jejunal stenosis [0.2%], one perforated ulcer [0.1%], one patient [0.1%] with excessive weight loss and one case [0.1%] of protein malnutrition. None of the 22 patients undergoing revisional surgery after MGB-OAGB died. Lost to follow up rate was 0.2%. CONCLUSION: Complications requiring revisional surgery after MGB-OAGB are uncommon [2.3%] and the majority can be managed by bilio-pancreatic limb shortening, the addition of a Braun side-to-side anastomosis or conversion to RYGB. Bilio-pancreatic limb length of 200â¯cm or more resulted in serious complications of liver failure, protein malnutrition, excessive weight loss and diarrhoea.
Asunto(s)
Anastomosis Quirúrgica/métodos , Derivación Gástrica/métodos , Adulto , Anciano , Femenino , Derivación Gástrica/efectos adversos , Humanos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pérdida de PesoRESUMEN
INTRODUCTION: Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression. METHODS: We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin. RESULTS: In vitro, curcumin (50 µM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 µM) completely abolished the ability of DCA (300 µM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients. CONCLUSIONS: Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.
Asunto(s)
Adenocarcinoma/patología , Anticarcinógenos/farmacología , Antineoplásicos/farmacología , Apoptosis , Esófago de Barrett/patología , Curcumina/farmacología , Neoplasias Esofágicas/patología , FN-kappa B/metabolismo , Adenocarcinoma/tratamiento farmacológico , Anciano , Esófago de Barrett/tratamiento farmacológico , Bilis/química , Biopsia , Línea Celular Tumoral , Daño del ADN , Ensayo de Inmunoadsorción Enzimática/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is one of the commonest bariatric procedures in the UK. This study reports our experience with this procedure over the last 10 years. METHODS: A prospectively maintained database of all the patients undergoing LAGB at our centre between March 2000 and August 2010 was analysed. RESULTS: Five hundred seventy-five patients underwent LAGB at our centre. There was no mortality in this series. Early (30-day) morbidity rate was 2.2 %. Late complications (20 %) comprised: 78 repositioning of the inflation port in 65 patients, repositioning of band in 24 patients (4 %), removal of band in 20 patients (3.4 %), conversion to bypass in 41 patients (7 %), diagnostic laparoscopy in 1 patient and subtotal gastrectomy in 1 patient. Median follow-up was 29 months. The median of percentage of weight loss (%WL) and excess body weight loss (EBWL) was 18.3 and 40 %, respectively, at ≥ 5 years post-LAGB. Patients with body mass index (BMI) over 50 kg/m(2) were compared to those with BMI ≤ 50 kg/m(2). No significant difference was noted in the weight loss between both of these groups. No significant difference was noted with regards to weight loss between patients <60 and >60 years of age. CONCLUSIONS: In this cohort of patients, %WL and EBWL were 18.3 and 40 % ≥ 5 years after LAGB, respectively, and early and late complication rates were 2.2 and 20 %, respectively. Majority of late complications were in the first 100 patients. Multifactorial causes included the surgical learning curve and patient selection process.
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Gastroplastia , Laparoscopía , Obesidad Mórbida/cirugía , Pérdida de Peso , Adulto , Anciano , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Gastroplastia/efectos adversos , Gastroplastia/métodos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad Mórbida/sangre , Obesidad Mórbida/epidemiología , Calidad de Vida , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression. METHODS: We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin. RESULTS: In vitro, curcumin (50 μM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 μM) completely abolished the ability of DCA (300 μM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients. CONCLUSIONS: Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antineoplásicos/farmacología , Anticarcinógenos/farmacología , Apoptosis , Esófago de Barrett/patología , Curcumina/farmacología , Neoplasias Esofágicas/patología , FN-kappa B/metabolismo , Esófago de Barrett/tratamiento farmacológico , Bilis/química , Biopsia/métodos , Línea Celular Tumoral , Daño del ADN , Ensayo de Inmunoadsorción Enzimática/instrumentación , Ensayo de Inmunoadsorción Enzimática/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Proyectos Piloto , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
The development of Barrett's esophagus and its progression to adenocarcinoma are clearly linked to reflux of acid and bile. Our objective in this study was to develop an optimized ex vivo biopsy culture technique to study the molecular signaling events induced after insult with individual refluxate constituents. We illustrate the utility of this method by showing results for NF-kB centered cell signaling, and compare the results with those obtained from esophageal cell lines. We show that upregulation of the two NF-kB target genes show differences in pH preference, with IL-8 being preferentially upregulated by DCA at neutral pH, and IkB being upregulated by neutral DCA, acidic DCA, and acid alone. This was found to be true in both cell lines and biopsy cultures. The maximum responses were noted in both models when mixed reflux (DCA at pH 6) was utilized, perhaps reflecting the pH preference of DCA (pKa 6.2). Both the optimized ex vivo models, and the in vitro cell lines show that bile and acid are capable of inducing NF-kB dependent gene expression, with some interesting differences in preferred transcriptional target. In conclusion, in both cells and cultured biopsies, similar reflux driven gene expression changes were noted, with maximum effects noted with DCA exposures at pH 6.
Asunto(s)
Adenocarcinoma/genética , Esófago de Barrett/genética , Neoplasias Esofágicas/genética , Expresión Génica , Subunidad p50 de NF-kappa B/genética , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Colagogos y Coleréticos/farmacología , Ácido Desoxicólico/farmacología , Humanos , Concentración de Iones de Hidrógeno , Proteínas I-kappa B/efectos de los fármacos , Proteínas I-kappa B/genética , Técnicas In Vitro , Interleucina-8/efectos de los fármacos , Interleucina-8/genética , Interleucina-8/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Regulación hacia ArribaRESUMEN
Deoxycholic acid (DCA) is a secondary bile acid implicated in various cancers of the gastrointestinal (GI) tract. In oesophageal adenocarcinoma, DCA is believed to contribute to carcinogenesis during reflux where stomach contents enter the lower oesophagus. It is imperative that we understand the mechanisms whereby oesophageal carcinogens function in order that therapeutic options may be developed. We have previously shown that DCA can damage chromosomes and does so through its generation of reactive oxygen species (ROS). We show here, after detailed experiments, that DCA appears to have a non-linear dose response for DNA damage. DCA induces DNA damage (as measured by the micronucleus assay) at doses of 100 microM and higher in oesophageal OE33 cells, but fails to induce such DNA damage below this cut-off dose. We also show that in terms of NF-kappaB activation (as measured by up-regulation of two NF-kappaB target genes) by DCA, a similar dose response is observed. This dose-response data may be important clinically as DCA exposure to the oesophagus may be used as a way to identify the 10% of Barrett's oesophagus patients currently progressing to cancer from the 90% of patients who do not progress. Only quantitative studies measuring DCA concentrations in refluxates correlated with histological progression will answer this question. We further show here that ROS are behind DCAs ability to activate NF-kappaB as antioxidants (epigallocatechin gallate, resveratrol and vitamin C) abrogate DCAs ability to up-regulate NF-kappaB-controlled genes. In conclusion, low doses of DCA appear to be less biologically significant in vitro. If this were to be confirmed in vivo, it might suggest that reflux patients with low DCA concentrations may be at a lower risk of cancer progression compared to patients with high levels of DCA in their refluxate. Either way, antioxidant supplementation may possibly help prevent the deleterious effects of DCA in the whole GI tract.
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Daño del ADN , ADN/efectos de los fármacos , Ácido Desoxicólico/toxicidad , Esófago/efectos de los fármacos , Mutágenos/toxicidad , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Adenocarcinoma/inducido químicamente , Adenocarcinoma/etiología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Esófago de Barrett/complicaciones , Línea Celular Tumoral , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias Esofágicas/inducido químicamente , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Esófago/metabolismo , Esófago/patología , Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica , Humanos , Pruebas de MicronúcleosRESUMEN
OBJECTIVE: Nerve injury is one of the most common complications of varicose vein surgery and is a frequent cause for litigation but its incidence following lower limb arterial surgery has not been well documented. This study was undertaken to determine the incidence of nerve injury following lower limb arterial surgery. This was addressed in relation to long saphenous or femoral vein harvesting, or re-operative surgery. MATERIALS AND METHODS: A total of one hundred patients who had undergone lower limb arterial reconstruction in the previous five years were invited to participate in this study. Seventy-eight patients responded, of which 44 patients (66 operated legs) agreed to participate. They underwent neurological assessment of the lower limbs. RESULTS: 66.7% of limbs had objective evidence of sensory deficit following lower limb arterial surgery but none had motor deficit. Redo surgery or superficial femoral vein harvest had no influence on the incidence of nerve injury. Below knee incisions had a higher incidence of nerve injury than other approaches. Long saphenous vein harvest significantly increased the rate of nerve injury. CONCLUSIONS: There is a high incidence of sensory nerve damage following lower limb arterial surgery. In the present climate of increasing litigation it is important to know the likely incidence of post-operative nerve damage so that patients can be counselled appropriately during the process of obtaining informed consent.
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Arteria Femoral/cirugía , Vena Femoral/cirugía , Extremidad Inferior/inervación , Plexo Lumbosacro/lesiones , Complicaciones Posoperatorias , Vena Safena/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Nervio Femoral/lesiones , Humanos , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Masculino , Persona de Mediana Edad , Nervio Obturador/lesiones , Enfermedades Vasculares Periféricas/cirugía , Nervio Peroneo/lesiones , Procedimientos de Cirugía Plástica/métodos , Reoperación , Estudios Retrospectivos , Trastornos de la Sensación/etiología , Nervio Sural/lesiones , Recolección de Tejidos y ÓrganosRESUMEN
AIMS: To determine if immunohistochemistry (IHC) could be used to monitor nuclear factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre-malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa. The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA and protein levels were assessed in oesophageal tissues. METHODS: IHC was employed using an antibody against the nuclear localisation sequence (NLS) of the p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function, changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were also assessed in the histological sequence using real-time PCR. More global expression changes were also studied using membrane arrays. RESULTS: IHC was effective at monitoring overall NF-kappaB activity and IL-8 abundance. This method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in specific cell types. There were significant increases in nuclear NF-kappaB activity and IL-8 abundance across the histological series. Gene expression analysis also showed consistent up-regulation of IL-8, confirming the IHC data and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF-kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues. Down-regulation of I-kappaB gene expression may partly explain increased NF-kappaB activity. CONCLUSION: IHC, using antibodies against the NLS of p65, may be useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is amenable to high-throughput screening (whereas traditional electrophoretic mobility shift assay methods are not), this may lead to the development of a better screening tool for early cancer risk.