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1.
Surgeon ; 20(3): e7-e12, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33962892

RESUMEN

BACKGROUND: Surgery is a major component of health-care provision. Operative intervention often employs minimally invasive approaches incorporating digital cameras creating a 'digital twin' of both intracorporeal appearances and operative performance. Video recordings provide richer detail than the traditional operative note and can couple with advanced computer technology to unlock new analytic capabilities capable of driving surgical advancement via quality improvement initiatives and new technology design. Surgical video is however an under-utilized technology resource, in part, because ownership along with broader issues including purpose, privacy, confidentiality, copyright and inclusion in outputs have been poorly considered using outdated categorisation. METHOD: A first principles perspective on operative video classification as a useful public interest resource enshrining fundamental stakeholder (patients, physicians, institutions, industry and society) rights, roles and responsibilities. RESULT: A facility of noble purpose, understandable to all, for fair, accountable, safe and transparent access to large volumes of anonymised surgical videos of intracorporeal operations that enables advances through cross-disciplinary research is proposed. Technology can be exploited to protect all relevant parties respecting both citizen data-rights and the special status doctor-patient relationship. Through general consensus, the capability can be understood, established and iterated to perfection. CONCLUSION: Overall we argue that new and specific classification of surgical video enables responsible curation and serves the public good better than the current model. Rather than being thought of as a bicycle where discrete ownership is ascribed, such data are better viewed as being more like a park, a regulated amenity we should preserve for better human life.


Asunto(s)
Macrodatos , Relaciones Médico-Paciente , Ciclismo , Humanos , Mejoramiento de la Calidad , Grabación en Video
2.
Ann Surg ; 269(4): 700-711, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-29315090

RESUMEN

OBJECTIVE: To determine the incidence of anastomotic-related morbidity following Transanal Total Mesorectal Excision (TaTME) and identify independent risk factors for failure. BACKGROUND: Anastomotic leak and its sequelae are dreaded complications following gastrointestinal surgery. TaTME is a recent technique for rectal resection, which includes novel anastomotic techniques. METHODS: Prospective study of consecutive reconstructed TaTME cases recorded over 30 months in 107 surgical centers across 29 countries. Primary endpoint was "anastomotic failure," defined as a composite endpoint of early or delayed leak, pelvic abscess, anastomotic fistula, chronic sinus, or anastomotic stricture. Multivariate regression analysis performed identifying independent risk factors of anastomotic failure and an observed risk score developed. RESULTS: One thousand five hundred ninety-four cases with anastomotic reconstruction were analyzed; 96.6% performed for cancer. Median anastomotic height from anal verge was 3.0 ±â€Š2.0 cm with stapled techniques accounting for 66.0%. The overall anastomotic failure rate was 15.7%. This included early (7.8%) and delayed leak (2.0%), pelvic abscess (4.7%), anastomotic fistula (0.8%), chronic sinus (0.9%), and anastomotic stricture in 3.6% of cases. Independent risk factors of anastomotic failure were: male sex, obesity, smoking, diabetes mellitus, tumors >25 mm, excessive intraoperative blood loss, manual anastomosis, and prolonged perineal operative time. A scoring system for preoperative risk factors was associated with observed rates of anastomotic failure between 6.3% to 50% based on the cumulative score. CONCLUSIONS: Large tumors in obese, diabetic male patients who smoke have the highest risk of anastomotic failure. Acknowledging such risk factors can guide appropriate consent and clinical decision-making that may reduce anastomotic-related morbidity.


Asunto(s)
Fuga Anastomótica/epidemiología , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal , Anastomosis Quirúrgica/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Humanos , Incidencia , Internacionalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Adulto Joven
3.
Gut ; 67(4): 654-662, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28148540

RESUMEN

OBJECTIVE: Lower GI bleeding (LGIB) is a common reason for emergency hospital admission, although there is paucity of data on presentations, interventions and outcomes. In this nationwide UK audit, we describe patient characteristics, interventions including endoscopy, radiology and surgery as well as clinical outcomes. DESIGN: Multicentre audit of adults presenting with LGIB to UK hospitals over 2 months in 2015. Consecutive cases were prospectively enrolled by clinical teams and followed for 28 days. RESULTS: Data on 2528 cases of LGIB were provided by 143 hospitals. Most were elderly (median age 74 years) with major comorbidities, 29.4% taking antiplatelets and 15.9% anticoagulants. Shock was uncommon (58/2528, 2.3%), but 666 (26.3%) received a red cell transfusion. Flexible sigmoidoscopy was the most common investigation (21.5%) but only 2.1% received endoscopic haemostasis. Use of embolisation or surgery was rare, used in 19 (0.8%) and 6 (0.2%) cases, respectively. 48% patients underwent no inpatient investigations. The most common diagnoses were diverticular bleeding (26.4%) and benign anorectal conditions (16.7%). Median length of stay was 3 days, 13.6% patients rebled during admission and 4.4% were readmitted with bleeding within 28 days. In-hospital mortality was 85/2528 (3.4%) and was highest in established inpatients (17.8%, p<0.0001) and in patients experiencing rebleeding (7.1%, p<0.0001). CONCLUSIONS: Patients with LGIB have a high burden of comorbidity and frequent antiplatelet or anticoagulant use. Red cell transfusion was common but most patients were not shocked and required no endoscopic, radiological or surgical treatment. Nearly half were not investigated. In-hospital mortality was related to comorbidity, not severe haemorrhage.


Asunto(s)
Transfusión Sanguínea , Colonoscopía , Embolización Terapéutica , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica , Pacientes Internos , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Colonoscopía/métodos , Embolización Terapéutica/métodos , Urgencias Médicas , Femenino , Hemorragia Gastrointestinal/mortalidad , Hemostasis Endoscópica/métodos , Humanos , Tiempo de Internación , Masculino , Auditoría Médica , Persona de Mediana Edad , Readmisión del Paciente , Estudios Prospectivos , Factores de Riesgo , Sigmoidoscopía/métodos , Resultado del Tratamiento , Reino Unido
5.
Surg Endosc ; 32(2): 1073-1076, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28643063

RESUMEN

BACKGROUND: Standard surgical practice for colorectal cancer involves resection of the primary lesion and all draining lymph nodes. Accurate intraoperative assessment of nodal status could allow stratified resectional extent. One-step nucleic acid (OSNA) can provide a rapid method of interrogating nodal tissue, whilst near-infrared (NIR) laparoscopy together with indocyanine green (ICG) can identify relevant nodal tissue intraoperatively. METHODS: ICG was administered around the tumour endoscopically prior to the operation. Fluorescent nodes identified by NIR were marked and submitted for whole-node OSNA analysis. Further fresh lymph nodes dissected from the standard resection specimen were examined and analysed by both conventional histology and OSNA. In addition, the status of the fluorescent nodes was compared to that of non-ICG nodes to assess their predictive value. RESULTS: Sixteen patients were recruited with a total final lymph node count of 287. 78 fresh lymph nodes were identified on fresh dissection for both histological and OSNA assessment with an analytical concordance rate of 98.7% (77/78). OSNA sensitivity was 1 (0.81-1, 95% CI) and specificity 0.98 (0.91-1, 95% CI). Six patients had a total of nine nodes identified intraoperatively by ICG fluorescence. Of these nine nodes, one was positive for metastasis on OSNA. OSNA analysis of the ICG-labelled node matched the final histological nodal stage in 3/6 patients (two being N0 and one N1). The final pathological nodal stage of the other three was N1 or N2, while the ICG nodes were negative. CONCLUSION: OSNA is highly concordant with standard histology, although only a minority of nodes identifiable by full pathological analysis were found for OSNA on fresh dissection. OSNA can be combined with NIR and ICG lymphatic mapping to provide intraoperative assessment of nodal tissue in patients with colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/cirugía , Verde de Indocianina/farmacología , Laparoscopía/métodos , Ganglios Linfáticos/patología , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Neoplásico/análisis , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/secundario , Colorantes/farmacología , Estudios de Factibilidad , Femenino , Fluorescencia , Humanos , Periodo Intraoperatorio , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos
6.
Surg Endosc ; 32(9): 4036-4043, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29785456

RESUMEN

BACKGROUND: Iatrogenic ureteric injury is a serious complication of colorectal surgery. Incidence is estimated to be between 0.3 and 1.5%. Of all ureteric injuries, 9% occur during colorectal procedures. Ureteric stents are utilised as a method to reduce the risk of injury; however, these are not without risk and do not guarantee prevention of injury. Fluorescence is a safe and effective alternative for intraoperative ureteric localisation. This proof of principle study aims to assess the use of methylene blue to fluoresce the ureter during colorectal surgery. METHOD: Patients undergoing elective colorectal surgery were included in this open label, non-randomised study. Methylene blue was administered intravenously at varying doses (0.25-1 mg/kg) over 5 min, 10-15 min prior to entering 'ureteric territory.' Fluorescence was assessed using the PINPOINT Deep Red laparoscopic system at fixed time points by the surgeon and an independent observer. RESULTS: 42 patients received methylene blue; 2 patients were excluded from analysis. Of the 69 ureters assessed, 64 were seen under fluorescence. Of these, 14 were not visible under white light. 50 ureters were observed with both fluorescence and white light with 14 of these being seen earlier with fluorescence. In ten cases, fluorescence revealed the ureter to be in a different location than suspected. CONCLUSION: Fluorescence is a promising method to allow visualisation of the ureter, where it is not identified easily under standard operative conditions, thereby improving safety and reducing operative time and difficulty.


Asunto(s)
Fluorescencia , Enfermedad Iatrogénica/prevención & control , Complicaciones Intraoperatorias/prevención & control , Azul de Metileno , Uréter/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Colon/cirugía , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Recto/cirugía
7.
Surg Innov ; 25(5): 525-535, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29902950

RESUMEN

Surgery remains the mainstay of curative treatment for primary rectal cancer. For mid and low rectal tumors, optimal oncologic surgery requires total mesorectal excision (TME) to ensure the tumor and locoregional lymph nodes are removed. Adequacy of surgery is directly linked to survival outcomes and, in particular, local recurrence. From a technical perspective, the more distal the tumor, the more challenging the surgery and consequently, the risk for oncologically incomplete surgery is higher. TME can be performed by an open, laparoscopic, robotic or transanal approach. There is a lack of consensus on the "gold standard" approach with each of these options offering specific advantages. The International Symposium on the Future of Rectal Cancer Surgery was convened to discuss the current challenges and future pathways of the 4 approaches for TME. This article reviews the findings and discussion from an expert, international panel.


Asunto(s)
Cirugía Colorrectal/organización & administración , Cirugía Colorrectal/tendencias , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Cirugía Endoscópica por Orificios Naturales
8.
Ann Surg ; 266(1): 111-117, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-27735827

RESUMEN

OBJECTIVE: This study aims to report short-term clinical and oncological outcomes from the international transanal Total Mesorectal Excision (taTME) registry for benign and malignant rectal pathology. BACKGROUND: TaTME is the latest minimally invasive transanal technique pioneered to facilitate difficult pelvic dissections. Outcomes have been published from small cohorts, but larger series can further assess the safety and efficacy of taTME in the wider surgical population. METHODS: Data were analyzed from 66 registered units in 23 countries. The primary endpoint was "good-quality TME surgery." Secondary endpoints were short-term adverse events. Univariate and multivariate regression analyses were used to identify independent predictors of poor specimen outcome. RESULTS: A total of 720 consecutively registered cases were analyzed comprising 634 patients with rectal cancer and 86 with benign pathology. Approximately, 67% were males with mean BMI 26.5 kg/m. Abdominal or perineal conversion was 6.3% and 2.8%, respectively. Intact TME specimens were achieved in 85%, with minor defects in 11% and major defects in 4%. R1 resection rate was 2.7%. Postoperative mortality and morbidity were 0.5% and 32.6% respectively. Risk factors for poor specimen outcome (suboptimal TME specimen, perforation, and/or R1 resection) on multivariate analysis were positive CRM on staging MRI, low rectal tumor <2 cm from anorectal junction, and laparoscopic transabdominal posterior dissection to <4 cm from anal verge. CONCLUSIONS: TaTME appears to be an oncologically safe and effective technique for distal mesorectal dissection with acceptable short-term patient outcomes and good specimen quality. Ongoing structured training and the upcoming randomized controlled trials are needed to assess the technique further.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Neoplasias del Recto/cirugía , Recto/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/cirugía , Índice de Masa Corporal , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Humanos , Complicaciones Intraoperatorias , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Terapia Neoadyuvante , Estadificación de Neoplasias , Complicaciones Posoperatorias , Neoplasias del Recto/patología , Sistema de Registros , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
9.
Dis Colon Rectum ; 60(6): 577-585, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28481851

RESUMEN

BACKGROUND: There remains a lack of international consensus on the appropriate management of lateral nodal disease. Although the East manages this more aggressively with lateral lymph node dissections, the West aims to eradicate small-volume disease with neoadjuvant chemoradiotherapy and lateral nodal disease is not considered for routine surgical treatment. However, recent studies have shown that, despite neoadjuvant treatment, a significant number of patients with lateral nodal disease develop local recurrence in the lateral compartment after total mesorectal excision. OBJECTIVE: The aim of this study is to assess the role of the pretreatment features of lateral nodes on MRI in regard to local recurrence. DESIGN: All patients operated on for low locally advanced rectal cancer over a 5-year period were evaluated retrospectively. SETTINGS: This study was conducted at a single expert center. PATIENTS: The MRIs of a total of 313 patients were reviewed, and only those with rectal cancers up to 8 cm from the anorectal junction, measured on MRI, were selected. This left 185 patients; of these, 58 patients had clinical T1 or T2 tumors as assessed on MRI, identifying 127 patients who had cT3/T4 tumors that were included in this study. MAIN OUTCOME MEASURES: The primary outcomes measured were lateral local recurrence and multivariate analyses. RESULTS: The lateral local recurrence rate was significantly higher (33.3% 4-year rate) in patients with nodes larger than 10 mm than in patients with smaller nodes (10.1%, p = 0.03), despite patients being irradiated in the lateral compartment. LIMITATIONS: Because this is a relatively uncommon disease, patient numbers are low, and a multicenter study is needed to further address lateral nodal disease in low rectal cancer. CONCLUSIONS: Chemoradiotherapy with total mesorectal excision might not be sufficient in a selected group of patients. Further research is needed about which pretreatment features of the lateral nodes predict local recurrence and what is needed to prevent these from developing. See Video Abstract at http://links.lww.com/DCR/A338.


Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias del Recto/mortalidad , Estudios Retrospectivos
10.
Int J Colorectal Dis ; 32(6): 777-787, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28032183

RESUMEN

AIM: Our aim was to assess bowel function and its effect on overall quality of life (QOL) when compared to healthy controls after colectomy. METHODS: Patients undergoing resection of colorectal neoplasia were recruited pre-operatively and followed up at 6 and 12 months, to assess 'early' bowel function. Patients who underwent surgery 2 to 4 years previously were recruited for assessment of 'intermediate' bowel function. Healthy relatives were recruited as controls. The Memorial Sloan-Kettering Cancer Centre and EQ-5D questionnaires were used to assess bowel function and QOL, respectively. Statistical assessment included regression analyses, parametric and non-parametric tests. The association between QOL and Memorial Sloan-Kettering Cancer Centre (MSKCC) scores was evaluated using Spearman's rank correlation. RESULTS: Ninety-one patients were recruited for assessment of 'early' and 85 for 'intermediate' bowel function. There were 85 controls. Patients had a significantly higher number of bowel movements at each follow-up (p < 0.001). At 12 months after surgery, patients reported difficulty with gas-stool discrimination. The 'intermediate' group were found to have lower scores for flatus control (<0.001) and total frequency score (p 0.03), indicating worse function. Patients with higher total MSKCC scores, no symptoms of urgency and those able to control flatus reported better QOL (p 0.006, 0.007 and 0.005, respectively) at 6 and 12 months. Gas-stool differentiation and complete evacuation correlated with better QOL in the 'intermediate' bowel function group (p 0.02 and 0.02, respectively). CONCLUSION: Colonic resection adversely affects elements of bowel function up to 4 years after surgery. Good colonic function, represented by higher MSKCC scores, correlates with better QOL.


Asunto(s)
Colectomía , Neoplasias Colorrectales/cirugía , Calidad de Vida , Anciano , Estudios de Casos y Controles , Defecación , Demografía , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
11.
Dis Colon Rectum ; 58(9): 857-61, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26252847

RESUMEN

BACKGROUND: The Internet is a vast resource for patients to search for health information on the treatment of Crohn's disease. OBJECTIVE: This study examines the quality of Web sites that provide information to adults regarding Crohn's disease, including treatment options and surgery. DESIGN: Two search engines (Google and Yahoo) and the search terms "surgery for Crohn's disease" were used. The first 50 sites of each search were assessed. Sites that fulfilled the inclusion criteria were evaluated for content and scored by using the DISCERN instrument, which evaluates the quality of health information on treatment choices. RESULTS: One hundred sites were examined, of which 13 were duplicates. Sixty-two sites provided patient-orientated information. The other sites included 7 scientific articles, 3 blogs, 2 links, 6 forums, 3 video links, and 4 dead links. Of the 62 Web sites that provided patient information for adults, only 15 (24.2%) had been updated within the past 2 years. Only 9 (14.5%) were affiliated with hospitals and clinics. The majority of sites (33, 53.2%) were associated with private companies with commercial interests. Only half of the Web sites provided details on treatment options, and most Web sites did not provide any information on symptoms and procedure details. Just 5 Web sites (8.1%) described the risks of surgery, and only 7 (11.3%) provided any information on the timescale for recovery. Overall, only 1 Web site (1.6%) was identified as being "good" or "excellent" with the use of the DISCERN criteria. LIMITATIONS: Although the internet is constantly evolving, this study captures data at a specific time point. Search results may vary depending on geographical location. This study only assessed English language websites. CONCLUSIONS: The quality of patient information on surgery for Crohn's disease is highly variable and generally poor. There is potential for the Internet to provide valuable information, and clinicians should identify high-quality Web sites to guide their patients.


Asunto(s)
Información de Salud al Consumidor/normas , Enfermedad de Crohn/terapia , Internet , Calidad de la Atención de Salud/estadística & datos numéricos , Adulto , Información de Salud al Consumidor/estadística & datos numéricos , Humanos , Motor de Búsqueda
12.
Dis Colon Rectum ; 58(10): 938-42, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26347965

RESUMEN

BACKGROUND: Noninflammatory masses in the ischiorectal fossa are rare. OBJECTIVE: This study aimed to review our experience with ischiorectal fossa tumors and to address the question of whether percutaneous biopsy should be undertaken. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a tertiary institution. PATIENTS: From April 2007 to November 2014, all consecutive ischiorectal fossa masses treated in a referral center were retrospectively reviewed. They were all presented and discussed in a multidisciplinary team meeting. Magnetic resonance imaging was performed in all the patients. Inflammatory pathologies, such as abscess, were excluded from the analysis. INTERVENTIONS: Percutaneous biopsy and surgical excision of ischiorectal fossa tumors were reviewed. MAIN OUTCOME MEASURES: Perioperative, pathological, and oncological outcomes were measured. RESULTS: Eleven patients were identified (8 female; median age, 50 years; range, 25-90). Percutaneous biopsy was undertaken in 8 patients. All biopsies were diagnostic and altered preoperative management in 3 cases (aggressive angiomyxoma (n = 2), desmoid fibromatosis (n = 1)). Overall final diagnosis was benign in 3 patients, locally aggressive neoplasm in 3, and malignant in 5 cases (leiomyosarcomas (n = 2), liposarcomas (n = 2), and angiomyosarcoma (n = 1)). Surgical approaches were perineal in 8 patients, abdominoperineal in 1 patient, and totally abdominal in 1 patient. One patient (age 90 years) was managed nonsurgically. After resection, 2 positive margins were observed (R1 rate, 20%). After a mean follow-up of 24.3 months, 3 patients have experienced local recurrence, which required further surgery in 2 cases. LIMITATIONS: This study is limited by the small number of patients. CONCLUSIONS: Noninflammatory masses in the ischiorectal fossa are rare, but they are commonly malignant and should be imaged by MRI. Unless the radiological appearances are diagnostic, percutaneous biopsy is recommended and alters management in about one-third of cases.


Asunto(s)
Biopsia/métodos , Fibromatosis Agresiva , Mixoma , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Pélvicas , Diagnóstico Diferencial , Disección/efectos adversos , Disección/métodos , Femenino , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Mixoma/patología , Mixoma/cirugía , Evaluación de Resultado en la Atención de Salud , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/patología , Neoplasias Pélvicas/cirugía , Reoperación , Reproducibilidad de los Resultados , Estudios Retrospectivos , Reino Unido
13.
Proc Natl Acad Sci U S A ; 109(51): 21046-51, 2012 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-23213241

RESUMEN

A significant proportion of colorectal cancer (CRC) patients are resistant to anti-ERBB1 [avian erythroblastic leukemia viral (v-erb-b) oncogene homolog, receptor for EGF] monoclonal antibodies (Mabs). We evaluated both immune and nonimmune effects of cetuximab (anti-ERBB1 Mab), trastuzumab (anti-ERBB2 Mab), pertuzumab (anti-ERBB2 Mab), and lapatinib (dual ERBB1 and ERBB2 tyrosine kinase inhibitor) in a large well-characterized panel of 64 CRC cell lines to find response predictive tumor characteristics. There was a significant correlation between the direct effects of cetuximab and lapatinib. Both agents were associated (P = 0.0004) with "triple' wild-type status in KRAS, BRAF, and PIK3CA exon 20. Most cell lines were resistant to the direct effects of anti-ERBB2 Mabs, suggesting that the effects of lapatinib might mainly be through ERBB1. Microarray mRNA expression profiles of sensitive and resistant cell lines showed that although ERBB1 receptor or ligand levels did not associate with cetuximab sensitivity, high levels of ERBB2 (P = 0.036) and amphiregulin (P = 0.026) predicted sensitivity to lapatinib. However, higher ERBB1 expression predicted susceptibility to cetuximab-induced antibody-dependent cellular cytotoxicity and occurred independently of KRAS/BRAF/PIK3CA mutations (P = 0.69). Lapatinib may be an effective alternative therapy to cetuximab in triple wild-type tumors. Microarray analysis provides suggestive biomarkers for resistance. ERBB1 levels, independent of mutation status, predict immune killing. Therefore, anti-ERBB1 antibodies may be considered in CRC tumors with higher ERBB1 expression and favorable FcγR polymorphisms.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Cetuximab , Genes ras , Humanos , Sistema Inmunológico , Lapatinib , Modelos Genéticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo Genético , Quinazolinas/farmacología , Trastuzumab
14.
Clin Colon Rectal Surg ; 28(3): 158-64, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26491408

RESUMEN

Colorectal surgery is one of the most common procedures performed around the world with more than 600,000 operations each year in the United States, and more than a million worldwide. In the past two decades, there has been a clear trend toward minimal access and surgeons have embraced this evolution. Widespread adoption of advanced minimally invasive procedures is often limited by procedural complexity and the need for specific technical skills. Furthermore, the loss of 3D vision, limited overview of the surgical field, and diminished tactile sensation make major colorectal procedures more challenging and have an impact on the surgeons' learning curves. New technologies are emerging that can compensate for some of the sensory losses associated with laparoscopy. High-definition picture acquisition, 3D camera systems, and the use of biomarkers will allow improved identification of the target structures and help differentiate them from surrounding tissues. In this article, we describe some of the new technologies available and, in particular, focus on the possible implications of biomarkers and fluorescent laparoscopic imaging.

15.
Dis Colon Rectum ; 57(3): 370-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24509462

RESUMEN

BACKGROUND: Interstitial cells of Cajal, expressing the proto-oncogene c-kit, have been shown to regulate the spontaneous activity of the gastrointestinal tract. They have been described in the human internal anal sphincter; however, their function is still unclear. OBJECTIVE: We examined the effects of the c-kit tyrosine kinase inhibitor imatinib mesylate on sphincter strips to investigate the function of the interstitial cells. DESIGN: This was a case series study. SETTIGS: This was a single-center study conducted at the University of Oxford. PATIENTS: Internal anal sphincter strips were collected from 10 patients undergoing abdominoperineal resection or proctectomy and mounted in organ bath. Responses to electrical field stimulation and chemical agents were monitored in the absence of drugs and after the administration of increasing doses of imatinib mesylate. Immunohistochemistry was performed to identify interstitial cells. MAIN OUTCOME MEASURES: The role of the interstitial cells in the internal anal sphincter was assessed. RESULTS: Imatinib mesylate significantly reduced the tone and the spontaneous activity of the strips. In the absence of drugs, the tone generated was 147.7 ± 33.0 mg/mg of tissue. Administration of ≥5 µM of imatinib mesylate caused a dose-dependent reduction in the tone. Strips exhibited spontaneous activity characterized by intermittent low-amplitude contractions superimposed on basal tone (135.6 ± 4.6 contractions in 10 minutes). Imatinib mesylate significantly reduced the number of contractions at concentration >5 µM. No differences were observed in the responses to electrical field stimulation, carbachol, or phenylephrine. Immunohistochemistry showed c-kit-positive cells. LIMITATIONS: This study was limited by the relatively small number of patients enrolled and thus the difficulty of finding human tissue for laboratory studies. CONCLUSIONS: Our results suggest that the interstitial cells modulate the tone and the spontaneous activity of the internal anal sphincter. This provides a foundation for new approaches to preclinical and clinical research. Moreover, these cells may represent a target for drugs inhibiting the c-kit receptor and provide a new approach for treating anorectal diseases.


Asunto(s)
Canal Anal/citología , Canal Anal/efectos de los fármacos , Benzamidas/farmacología , Células Intersticiales de Cajal/fisiología , Piperazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Estimulación Eléctrica , Femenino , Humanos , Mesilato de Imatinib , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-kit/fisiología
16.
Colorectal Dis ; 16(8): O297-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24506165

RESUMEN

AIM: Minimally invasive approaches for stoma closure offer considerable benefits for patients. Single port access via an end ileostomy site after stoma take-down in patients with prior total colectomy and a rectal stump remnant could allow restoration of ileorectal continuity by anastomosis but has not been detailed previously. METHODS: After mobilisation of the end ileostomy, the anvil of a circular stapler is secured into the open end of the distal ileum and the intestine returned into the abdominal cavity. A single port access device (in this description, a 'surgical glove port') is placed then into the stoma site and full laparoscopy performed. Once the rectal stump is identified and prepared, an intracorporeal anastomosis can be constructed in a tension-free manner using a Knight-Griffin technique. Leak-testing can also be performed and the operation concluded with closure of the solitary incision. RESULTS: In selected cases, adhesiolysis and anastomosis can be safely performed in toto. If the peritoneal environment is challenging, access can be escalated to multiport laparoscopy or even laparotomy. CONCLUSION: Initiation of ileorectal anastomosis construction by single port laparoscopy at least allows peritoneal assessment but can provide for the operation's completion. This can confer maximum patient benefit for the most minimally invasive option.


Asunto(s)
Anastomosis Quirúrgica/métodos , Íleon/cirugía , Laparoscopía/métodos , Recto/cirugía , Colectomía/métodos , Humanos , Ileostomía/métodos , Grapado Quirúrgico/métodos , Adherencias Tisulares/cirugía
17.
Surg Endosc ; 28(7): 2221-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24566744

RESUMEN

BACKGROUND: Anastomotic leakage is a devastating complication of colorectal surgery. However, there is no technology indicative of in situ perfusion of a laparoscopic colorectal anastomosis. METHODS: We detail the use of near-infrared (NIR) laparoscopy (PinPoint System, NOVADAQ, Canada) in association with fluorophore [indocyanine green (ICG), 2.5 mg/ml] injection in 30 consecutive patients who underwent elective minimally invasive colorectal resection using the simultaneous appearance of the cecum or distal ileum as positive control. RESULTS: The median (range) age of the patients was 64 (40-81) years with a median (range) BMI of 26.7 (20-35.5) kg/m(2). Twenty-four patients had left-sided resections (including six low anterior resections) and six had right-sided resections. Of the total, 25 operations were cancer resections and five were for benign disease [either diverticular strictures (n = 3) or Crohn's disease (n = 2)]. A high-quality intraoperative ICG angiogram was achieved in 29/30 patients. After ICG injection, median (range) time to perfusion fluorescence was 35 (15-45) s. Median (range) added time for the technique was 5 (3-9) min. Anastomotic perfusion was documented as satisfactory in every successful case and encouraged avoidance of defunctioning stomas in three patients with low anastomoses. There were no postoperative anastomotic leaks. CONCLUSION: Perfusion angiography of colorectal anastomosis at the time of their laparoscopic construction is feasible and readily achievable with minimal added intraoperative time. Further work is required to determine optimum sensitivity and threshold levels for assessment of perfusion sufficiency, in particular with regard to anastomotic viability.


Asunto(s)
Colon/irrigación sanguínea , Colon/cirugía , Angiografía con Fluoresceína/métodos , Laparoscopía , Recto/irrigación sanguínea , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Enfermedades del Colon/cirugía , Colorantes , Femenino , Humanos , Verde de Indocianina , Masculino , Persona de Mediana Edad , Enfermedades del Recto/cirugía , Flujo Sanguíneo Regional
18.
Ann Surg ; 258(5): 722-30, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24096768

RESUMEN

OBJECTIVES: To determine whether body fat distribution, measured by waist circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality and morbidity after colorectal surgery than body mass index (BMI) or body surface area (BSA). BACKGROUND: Obesity measured by BMI is not a consistent risk factor for postoperative mortality and morbidity after abdominal surgery. Studies in metabolic and cardiovascular diseases have shown WC and WHR to be better outcome predictors than BMI. METHODS: A prospective multicenter international study was conducted among patients undergoing elective colorectal surgery. The WHR, BMI, and BSA were derived from body weight, height, and waist and hip circumferences measured preoperatively. Uni- and multivariate analyses were performed to identify risk factors for postoperative outcomes. RESULTS: A total of 1349 patients (754 men) from 38 centers in 11 countries were included. Increasing WHR significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2), postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR = 13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR = 1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of abdominal wound complication. In multivariate analysis, the WHR predicted intraoperative complications, conversion, medical complications, and reinterventions, whereas BMI was a risk factor only for abdominal wall complications; BSA did not reach significance for any outcome. CONCLUSIONS: The WHR is predictive of adverse events after elective colorectal surgery. It should be used in routine clinical practice and in future risk-estimating systems.


Asunto(s)
Cirugía Colorrectal/mortalidad , Circunferencia de la Cintura , Relación Cintura-Cadera , Anciano , Índice de Masa Corporal , Superficie Corporal , Femenino , Mortalidad Hospitalaria , Humanos , Complicaciones Intraoperatorias/mortalidad , Masculino , Persona de Mediana Edad , Morbilidad , Complicaciones Posoperatorias/mortalidad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo
20.
Lancet Oncol ; 13(12): e525-36, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23182193

RESUMEN

Elderly people represent almost all patients diagnosed with and treated for rectal cancer, and this trend is likely to become more apparent in the future. Surgical management and treatment decisions for this disease are becoming increasingly complex, but only a few reports deal specifically with older patients. In this systematic review, we provide an overview of published studies of outcomes after curative surgery for rectal cancer in elderly people (>70 years). We identified 48 studies providing information about postoperative results, survival, surgical approach, stoma formation, functional results, and quality of life after rectal resection for cancer. We found that advanced chronological age should not, by itself, exclude patients from curative rectal surgery or from other surgical options that are available for younger patients. Although overall survival is lower in elderly patients than in younger patients, cancer-specific survival does not decrease with age. However, the level of evidence for most studies was weak, emphasising the need for high-quality clinical trials for this population.


Asunto(s)
Neoplasias del Recto/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Fuga Anastomótica , Humanos , Laparoscopía , Complicaciones Posoperatorias , Calidad de Vida , Neoplasias del Recto/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento
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