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1.
Br J Surg ; 108(12): 1417-1425, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34694371

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the second most common solid organ cancer. Traditional treatment is with surgery and chemotherapy. Immunotherapy has recently emerged as a neoadjuvant therapy that could change treatment strategy in both primary resectable and metastatic CRC. METHODS: A literature review of PubMed with a focus on studies exploring upfront immunotherapy in operable CRC, either for primary resectable stage I-III cancers or for (potentially) operable liver metastasis. RESULTS: Immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has shown good results in both early-stage and advanced CRC. The effects of immune checkpoint inhibitors have so far been demonstrated in small phase I/II studies and predominantly in treatment-refractory stage IV disease with defect Mismatch repair (dMMR). However, recent data from phase I/II (NICHE-1) studies suggest an upfront role for immunotherapy in operable stage I-III disease. By blocking crucial immune checkpoints, cytotoxic T cells are activated and release cytotoxic signals that initiate cancer cell destruction. The very high complete response rate in dMMR operable CRC with neoadjuvant immunotherapy with nivolumab and ipilimumab, and even partial pathological response in some patients with proficient MMR (pMMR) CRC, calls for further attention to patient selection for neoadjuvant treatment, beyond MMR status alone. CONCLUSION: Early data on the effect of immunotherapy in CRC provide new strategic thinking of treatment options in CRC for both early-stage and advanced disease, with prospects for new trials.


Immunotherapy has proven to be highly effective as first-line treatment of metastatic colorectal cancer (CRC). Further, immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has provided very good results in both early-stage and advanced CRC. The high response rate in dMMR in operable colon cancers by preoperative use of double nivolumab and ipilimumab therapy warrants further investigation into its impact on long-term overall survival. Hence, immunotherapy has emerged as a neoadjuvant approach, possibly changing treatment strategy for both primary resectable and metastatic CRC. Larger phase III trials are needed to evaluate overall effects on survival.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Colon/patología , Humanos , Terapia Neoadyuvante , Neoplasias del Recto/patología
2.
Br J Surg ; 108(11): 1315-1322, 2021 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-34467970

RESUMEN

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.


Asunto(s)
Selección de Profesión , Internado y Residencia/estadística & datos numéricos , Permiso Parental/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Cirujanos/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto , Actitud del Personal de Salud , Femenino , Humanos , Masculino , Factores Sexuales , Adulto Joven
3.
Br J Surg ; 107(10): 1250-1261, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32350857

RESUMEN

BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.


ANTECEDENTES: La pandemia en curso tiene un efecto colateral sobre la salud en la prestación de atención quirúrgica a millones de pacientes. Se sabe muy poco sobre el manejo de la pandemia y sus efectos colaterales en otros servicios, incluida la prestación de servicios quirúrgicos. MÉTODOS: Se ha realizado una revisión de alcance de toda la literatura disponible relacionada con COVID-19 y cirugía utilizando bases de datos electrónicas, páginas web de sociedades, seminarios online y repositorios de pre-publicaciones. RESULTADOS: Se han publicado varias guías perioperatorias en un corto período de tiempo. Muchas recomendaciones son contradictorias y, en el mejor de los casos, se basan en datos anecdóticos. A medida que las regiones con el mayor volumen de operaciones per cápita se ven afectadas, se cancela o difiere un número sin precedentes de operaciones. Ninguna de las principales partes interesadas parece haber considerado cómo una pandemia priva de recursos a los pacientes que necesitan una intervención quirúrgica, con pacientes afectados de manera desproporcionada debido a la naturaleza del tratamiento (uso de anestesia, quirófanos, equipo de protección, contacto físico y necesidad de atención perioperatoria). No existen recomendaciones sobre cómo reanudar la actividad quirúrgica. La evaluación tras la pandemia y la planificación futura deben incluir a los servicios quirúrgicos como una parte esencial para mantener la atención quirúrgica adecuada para la población también durante un brote epidémico. La prestación de servicios quirúrgicos, debido a su naturaleza transversal y a sus efectos sinérgicos en los sistemas de salud en general, debe incorporarse a la agenda de la OMS para la planificación nacional de la salud. CONCLUSIÓN: Los pacientes se ven privados de acceso a la cirugía con una pérdida de función incierta y riesgo de un pronóstico adverso como efecto colateral de la pandemia. Los servicios quirúrgicos necesitan un plan de contingencia para mantener la atención quirúrgica durante la pandemia y en la fase post-pandemia.


Asunto(s)
COVID-19 , Atención a la Salud , Procedimientos Quirúrgicos Operativos , COVID-19/epidemiología , COVID-19/prevención & control , Salud Global , Humanos , Control de Infecciones/métodos , Control de Infecciones/normas , Pandemias , Atención Perioperativa/métodos , Atención Perioperativa/normas , Guías de Práctica Clínica como Asunto , Procedimientos Quirúrgicos Operativos/métodos , Procedimientos Quirúrgicos Operativos/normas
4.
Colorectal Dis ; 22(9): 1108-1118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32012414

RESUMEN

AIM: An anastomotic leak after surgery for colon cancer is a recognized complication but how it may adversely affect long-term survival is less clear because data are scarce. The aim of the study was to investigate the long-term impact of Grade C anastomotic leak in a large, population-based cohort. METHOD: Data on patients undergoing resection for Stage I-III colon cancer between 2008 and 2012 were collected from the Swedish, Norwegian and Danish Colorectal Cancer Registries. Overall relative survival and conditional 5-year relative survival, under the condition of surviving 1 year, were calculated for all patients and stratified by stage of disease. RESULTS: A total of 22 985 patients were analysed. Anastomotic leak occurred in 849 patients (3.7%). Five-year relative survival in patients with anastomotic leak was 64.7% compared with 87.0% for patients with no leak (P < 0.001). Five-year relative survival among the patients who survived the first year was 88.6% vs 81.3% (P = 0.003). Stratification by cancer stage showed that anastomotic leak was significantly associated with decreased relative survival in patients with Stage III disease (P = 0.001), but not in patients with Stage I or II (P = 0.950 and 0.247, respectively). CONCLUSION: Anastomotic leak after surgery for Stage III colon cancer was associated with significantly decreased long-term relative survival.


Asunto(s)
Fuga Anastomótica , Neoplasias del Colon , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Estudios de Cohortes , Neoplasias del Colon/cirugía , Humanos , Estadificación de Neoplasias , Sistema de Registros , Estudios Retrospectivos
5.
Br J Surg ; 106(1): 32-45, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30582640

RESUMEN

BACKGROUND: Gallbladder cancer is rare, but cancers detected incidentally after cholecystectomy are increasing. The aim of this study was to review the available data for current best practice for optimal management of incidental gallbladder cancer. METHODS: A systematic PubMed search of the English literature to May 2018 was conducted. RESULTS: The search identified 12 systematic reviews and meta-analyses, in addition to several consensus reports, multi-institutional series and national audits. Some 0·25-0·89 per cent of all cholecystectomy specimens had incidental gallbladder cancer on pathological examination. Most patients were staged with pT2 (about half) or pT1 (about one-third) cancers. Patients with cancers confined to the mucosa (T1a or less) had 5-year survival rates of up to 100 per cent after cholecystectomy alone. For cancers invading the muscle layer of the gallbladder wall (T1b or above), reresection is recommended. The type, extent and timing of reresection remain controversial. Observation time may be used for new cross-sectional imaging with CT and MRI. Perforation at initial surgery had a higher risk of disease dissemination. Gallbladder cancers are PET-avid, and PET may detect residual disease and thus prevent unnecessary surgery. Routine laparoscopic staging before reresection is not warranted for all stages. Risk of peritoneal carcinomatosis increases with each T category. The incidence of port-site metastases is about 10 per cent. Routine resection of port sites has no effect on survival. Adjuvant chemotherapy is poorly documented and probably underused. CONCLUSION: Management of incidental gallbladder cancer continues to evolve, with more refined suggestions for subgroups at risk and a selective approach to reresection.


Asunto(s)
Colecistectomía , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/terapia , Complicaciones Posoperatorias/terapia , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante/estadística & datos numéricos , Conversión a Cirugía Abierta/estadística & datos numéricos , Humanos , Hallazgos Incidentales , Laparoscopía/efectos adversos , Laparoscopía/estadística & datos numéricos , Metástasis de la Neoplasia , Siembra Neoplásica , Complicaciones Posoperatorias/patología , Pronóstico , Reoperación/estadística & datos numéricos , Medición de Riesgo
6.
Br J Surg ; 106(2): e138-e150, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30570764

RESUMEN

BACKGROUND: In 2015, six indicators were proposed to evaluate global progress towards access to safe, affordable and timely surgical and anaesthesia care. Although some have been adopted as core global health indicators, none has been evaluated systematically. The aims of this study were to assess the availability, comparability and utility of the indicators, and to present available data and updated estimates. METHODS: Nationally representative data were compiled for all World Health Organization (WHO) member states from 2010 to 2016 through contacts with official bodies and review of the published and grey literature, and available databases. Availability, comparability and utility were assessed for each indicator: access to timely essential surgery, specialist surgical workforce density, surgical volume, perioperative mortality, and protection against impoverishing and catastrophic expenditure. Where feasible, imputation models were developed to generate global estimates. RESULTS: Of all WHO member states, 19 had data on the proportion of the population within 2h of a surgical facility, 154 had data on workforce density, 72 reported number of procedures, and nine had perioperative mortality data, but none could report data on catastrophic or impoverishing expenditure. Comparability and utility were variable, and largely dependent on different definitions used. There were sufficient data to estimate that worldwide, in 2015, there were 2 038 947 (i.q.r. 1 884 916-2 281 776) surgeons, obstetricians and anaesthetists, and 266·1 (95 per cent c.i. 220·1 to 344·4) million operations performed. CONCLUSION: Surgical and anaesthesia indicators are increasingly being adopted by the global health community, but data availability remains low. Comparability and utility for all indicators require further resolution.


Asunto(s)
Cirugía General/estadística & datos numéricos , Salud Global/estadística & datos numéricos , Indicadores de Calidad de la Atención de Salud/estadística & datos numéricos , Humanos , Médicos/estadística & datos numéricos , Organización Mundial de la Salud
7.
Br J Surg ; 105(2): e110-e120, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29341153

RESUMEN

BACKGROUND: Blood is the most extensively studied body fluid and, because it contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment and detection of CTCs and ctDNA, their clinical applications and future opportunities in gastrointestinal cancers were the focus of this review. METHODS: The PubMed database was searched for literature up to 24 June 2017, with a focus on the past 10 years. Identified articles were further scrutinized for relevant references. Articles were those in English relating to colorectal, gastric and pancreatic cancer. RESULTS: Both CTCs and ctDNA are in low abundance compared with other cellular components of blood, but effective enrichment and highly sensitive techniques are available for their detection. Potential clinical applications of these liquid biopsies include screening, prognostic stratification, therapy administration, monitoring of treatment effect or resistance, and surveillance. Liquid biopsies provide opportunities to reduce the need for invasive tissue sampling, especially in the context of intratumoral heterogeneity and the need for tumour genotyping. CONCLUSION: Liquid biopsies have applications in gastrointestinal cancers to improve clinical decision-making.


Asunto(s)
Biomarcadores de Tumor/sangre , ADN Tumoral Circulante , Neoplasias Gastrointestinales/sangre , Células Neoplásicas Circulantes , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer/métodos , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Humanos , Biopsia Líquida/métodos , Pronóstico
8.
World J Surg ; 41(2): 410-418, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27734076

RESUMEN

BACKGROUND: Perforated peptic ulcer (PPU) is a surgical emergency associated with high short-term mortality. However, studies on long-term outcomes are scarce. Our aim was to investigate long-term survival after surgery for PPU. MATERIALS AND METHODS: A population-based, consecutive cohort of patients who underwent surgery for PPU between 2001 and 2014 was reviewed, and the long-term mortality was assessed. Survival was investigated by univariate analysis (log-rank test) and displayed using Kaplan-Meier survival curves. Multivariable analysis of risk factors for long-term mortality was assessed by Cox proportional hazards regression and reported as hazard ratio (HR) with 95 % confidence intervals (CI). RESULTS: A total of 234 patients were available for the calculation of ninety-day, one-year and two-year mortality, and the results showed rates of 19.2 % (45/234), 22.6 % (53/234) and 24.8 % (58/234), respectively. At the end of follow-up, a total of 109 of the 234 patients (46.6 %) had died. Excluding 37 (15.2 %) patients who died within 30 days of surgery, 197 patients had long-term follow-up (median 57 months, range 1-168) of which 36 % (71/197) died during the follow-up period. In multivariable analyses, age >60 years (HR 3.95, 95 % CI 1.81-8.65), active cancer (HR 3.49, 95 % CI 1.73-7.04), hypoalbuminemia (HR 1.65, 95 % CI 0.99-2.73), pulmonary disease (HR 2.06, 95 % CI 1.14-3.71), cardiovascular disease (HR 1.67, 95 % CI 1.01-2.79) and severe postoperative complications (HR 1.76, 95 % CI 1.07-2.89) during the initial stay for PPU were all independently associated with an increased risk of long-term mortality. Cause of long-term mortality was most frequently (18 of 71; 25 %) attributed to new onset sepsis and/or multiorgan failure. CONCLUSION: The long-term mortality after surgery for PPU is high. One in every three patients died during follow-up. Older age, comorbidity and severe postoperative complications were risk factors for long-term mortality.


Asunto(s)
Úlcera Péptica Perforada/mortalidad , Úlcera Péptica Perforada/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Hipoalbuminemia/mortalidad , Longevidad , Enfermedades Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/mortalidad , Análisis Multivariante , Neoplasias/mortalidad , Noruega/epidemiología , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Sepsis/mortalidad , Análisis de Supervivencia
9.
Br J Surg ; 103(2): e52-61, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26620724

RESUMEN

BACKGROUND: Emergency general surgery in the elderly is a particular challenge to the surgeon in charge of their care. The aim was to review contemporary aspects of managing elderly patients needing emergency general surgery and possible alterations to their pathways of care. METHODS: This was a narrative review based on a PubMed/MEDLINE literature search up until 15 September 2015 for publications relevant to emergency general surgery in the geriatric patient. RESULTS: The number of patients presenting as an emergency with a general surgical condition increases with age. Up to one-quarter of all emergency admissions to hospital may be for general surgical conditions. Elderly patients are a particular challenge owing to added co-morbidity, use of drugs and risk of poor outcome. Frailty is an important potential risk factor, but difficult to monitor or manage in the emergency setting. Risk scores are not available universally. Outcomes are usually severalfold worse than after elective surgery, in terms of both higher morbidity and increased mortality. A care bundle including early diagnosis, resuscitation and organ system monitoring may benefit the elderly in particular. Communication with the patient and relatives throughout the care pathway is essential, as indications for surgery, level of care and likely outcomes may evolve. Ethical issues should also be addressed at every step on the pathway of care. CONCLUSION: Emergency general surgery in the geriatric patient needs a tailored approach to improve outcomes and avoid futile care. Although some high-quality studies exist in related fields, the overall evidence base informing perioperative acute care for the elderly remains limited.


Asunto(s)
Tratamiento de Urgencia/métodos , Procedimientos Quirúrgicos Operativos/métodos , Directivas Anticipadas/ética , Anciano , Tratamiento de Urgencia/ética , Ética Médica , Predicción , Anciano Frágil , Evaluación Geriátrica/métodos , Accesibilidad a los Servicios de Salud , Hospitalización , Humanos , Cuidados a Largo Plazo/métodos , Inutilidad Médica , Cuidados Paliativos/ética , Cuidados Paliativos/métodos , Planificación de Atención al Paciente , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios/métodos , Factores de Riesgo , Procedimientos Quirúrgicos Operativos/ética
10.
Br J Surg ; 103(3): 226-32, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26511392

RESUMEN

BACKGROUND: The lack of uniform criteria for coding of gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) has hampered previous epidemiological studies. The epidemiology of GEP-NEN was investigated in this study using currently available criteria. METHODS: All patients diagnosed with GEP-NEN between January 2003 and December 2013 in a well defined Norwegian population of approximately 350 000 people were included. Age- and sex-adjusted incidence rates were calculated. The current 2010 World Health Organization criteria, European Neuroendocrine Tumour Society classification and International Union Against Cancer (UICC) classification were used. RESULTS: A total of 204 patients (114 male, 55.9 per cent) were identified. The median age at diagnosis was 61 (range 10-94) years. The annual overall crude incidence was 5.83 per 100,000 inhabitants, with an increasing trend (P = 0.033). The most frequent location was small intestine (60 patients, 29.4 per cent) followed by appendix (48 patients, 23.5 per cent) and pancreas (33 patients, 16.2 per cent). Grade 1 tumours were more common in gastrointestinal (100 patients, 58.5 per cent) than in pancreatic (9 patients, 27 per cent) NEN. According to the UICC classification, 77 patients (37.7 per cent) had stage I, 17 patients (8.3 per cent) stage II, 37 patients (18.1 per cent) stage III and 70 patients (34.3 per cent) had stage IV disease. No patient with stage I disease had grade 3 tumours; advanced tumour grade increased with stage. CONCLUSION: A high crude incidence of GEP-NEN, at 5.83 per 100,000 inhabitants, was noted together with a significant increasing trend over time.


Asunto(s)
Neoplasias Gastrointestinales/clasificación , Neoplasias Gastrointestinales/epidemiología , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Noruega/epidemiología , Prevalencia , Estudios Retrospectivos , Distribución por Sexo , Organización Mundial de la Salud , Adulto Joven
11.
Br J Surg ; 103(2): e29-46, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26771470

RESUMEN

BACKGROUND: Ageing is the inevitable time-dependent decline in physiological organ function that eventually leads to death. Age is a major risk factor for many of the most common medical conditions, such as cardiovascular disease, cancer, diabetes and Alzheimer's disease. This study reviews currently known hallmarks of ageing and their clinical implications. METHODS: A literature search of PubMed/MEDLINE was conducted covering the last decade. RESULTS: Average life expectancy has increased dramatically over the past century and is estimated to increase even further. Maximum longevity, however, appears unchanged, suggesting a universal limitation to the human organism. Understanding the underlying molecular processes of ageing and health decline may suggest interventions that, if used at an early age, can prevent, delay, alleviate or even reverse age-related diseases. Hallmarks of ageing can be grouped into three main categories. The primary hallmarks cause damage to cellular functions: genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis. These are followed by antagonistic responses to such damage: deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Finally, integrative hallmarks are possible culprits of the clinical phenotype (stem cell exhaustion and altered intercellular communication), which ultimately contribute to the clinical effects of ageing as seen in physiological loss of reserve, organ decline and reduced function. CONCLUSION: The sum of these molecular hallmarks produces the clinical picture of the elderly surgical patient: frailty, sarcopenia, anaemia, poor nutrition and a blunted immune response system. Improved understanding of the ageing processes may give rise to new biomarkers of risk or prognosis, novel treatment targets and translational approaches across disciplines that may improve outcomes.


Asunto(s)
Envejecimiento/fisiología , Células Madre Adultas/fisiología , Envejecimiento/genética , Comunicación Celular/fisiología , Senescencia Celular/fisiología , Epigénesis Genética/fisiología , Inestabilidad Genómica/fisiología , Humanos , Esperanza de Vida , Enfermedades Mitocondriales/etiología , Fenómenos Fisiológicos de la Nutrición/fisiología , Deficiencias en la Proteostasis/etiología , Telómero/fisiología
13.
Br J Cancer ; 111(5): 823-7, 2014 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-24691426

RESUMEN

Elevated microsatellite alterations at selected tetranucleotides (EMAST), a variation of microsatellite instability (MSI), has been reported in a variety of malignancies (e.g., neoplasias of the lung, head and neck, colorectal region, skin, urinary tract and reproductive organs). EMAST is more prominent at organ sites with potential external exposure to carcinogens (e.g., head, neck, lung, urinary bladder and colon), although the specific molecular mechanisms leading to EMAST remain elusive. Because it is often associated with advanced stages of malignancy, EMAST may be a consequence of rapid cell proliferation and increased mutagenesis. Moreover, defects in DNA mismatch repair enzyme complexes, TP53 mutation status and peritumoural inflammation involving T cells have been described in EMAST tumours. At various tumour sites, EMAST and high-frequency MSI share no clinicopathological features or molecular mechanisms, suggesting their existence as separate entities. Thus EMAST should be explored, because its presence in human cells may reflect both increased risk and the potential for early detection. In particular, the potential use of EMAST in prognosis and prediction may yield novel types of therapeutic intervention, particularly those involving the immune system. This review will summarise the current information concerning EMAST in cancer to highlight the knowledge gaps that require further research.


Asunto(s)
Repeticiones de Microsatélite/genética , Neoplasias/epidemiología , Neoplasias/genética , Detección Precoz del Cáncer/métodos , Humanos , Inestabilidad de Microsatélites , Neoplasias/diagnóstico , Prevalencia , Pronóstico
15.
Br J Surg ; 101(1): e51-64, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24338777

RESUMEN

BACKGROUND: Perforated peptic ulcer (PPU) is a common surgical emergency that carries high mortality and morbidity rates. Globally, one-quarter of a million people die from peptic ulcer disease each year. Strategies to improve outcomes are needed. METHODS: PubMed was searched for evidence related to the surgical treatment of patients with PPU. The clinical registries of trials were examined for other available or ongoing studies. Randomized clinical trials (RCTs), systematic reviews and meta-analyses were preferred. RESULTS: Deaths from peptic ulcer disease eclipse those of several other common emergencies. The reported incidence of PPU is 3.8-14 per 100,000 and the mortality rate is 10-25 per cent. The possibility of non-operative management has been assessed in one small RCT of 83 patients, with success in 29 (73 per cent) of 40, and only in patients aged less than 70 years. Adherence to a perioperative sepsis protocol decreased mortality in a cohort study, with a relative risk (RR) reduction of 0.63 (95 per cent confidence interval (c.i.) 0.41 to 0.97). Based on meta-analysis of three RCTs (315 patients), laparoscopic and open surgery for PPU are equivalent, but patient selection remains a challenge. Eradication of Helicobacter pylori after surgical repair of PPI reduces both the short-term (RR 2.97, 95 per cent c.i. 1.06 to 8.29) and 1-year (RR 1.49, 1.10 to 2.03) risk of ulcer recurrence. CONCLUSION: Mortality and morbidity from PPU can be reduced by adherence to perioperative strategies.


Asunto(s)
Úlcera Duodenal/cirugía , Laparoscopía/mortalidad , Úlcera Péptica Perforada/cirugía , Úlcera Gástrica/cirugía , Úlcera Duodenal/diagnóstico , Urgencias Médicas , Tratamiento de Urgencia/métodos , Humanos , Úlcera Péptica Perforada/diagnóstico , Úlcera Péptica Perforada/mortalidad , Medición de Riesgo , Factores de Riesgo , Úlcera Gástrica/diagnóstico , Resultado del Tratamiento
17.
Br J Surg ; 100(3): 373-80, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23225493

RESUMEN

BACKGROUND: With an increased use of magnetic resonance imaging, the indications for endoscopic retrograde cholangiopancreatography (ERCP) have changed. Consequently, the patterns and factors predictive of complications after ERCP performed during current routine clinical practice are not well known. METHODS: A prospective multicentre cohort study was undertaken in 11 Norwegian hospitals. Complications and mortality within 30 days after ERCP were analysed by univariable and multivariable regression analysis. RESULTS: There were 2808 ERCP procedures, of which 2573 (91·6 per cent) were therapeutic. More than half of the patients were aged 70 years or more. Common bile duct cannulation was achieved in 2557 procedures (91·1 per cent). Complications occurred in 327 (11·6 per cent) of the procedures, including cholangitis in 100 (3·6 per cent), pancreatitis in 88 (3·1 per cent), bleeding in 66 (2·4 per cent), perforation in 25 (0·9 per cent) and cardiovascular-respiratory events in 32 (1·1 per cent). In the multivariable regression analysis, older age, increasing American Society of Anesthesiologists fitness score, centre ERCP volumes of more than 150 procedures annually and precut sphincterotomy were predictive factors for severe complications. The overall 30-day mortality rate was 2·2 per cent (63 patients), with a procedure-related mortality rate of 1·4 per cent (39 patients). Malignancy was diagnosed in 46 (73 per cent) of the patients who died. CONCLUSION: ERCP is a procedure with considerable risk for complications. Morbidity and mortality are related to patient age and co-morbidity, as well as hospital volume of ERCP procedures and the type of intervention.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/diagnóstico , Enfermedades de los Conductos Biliares/mortalidad , Enfermedades Cardiovasculares/etiología , Colangiopancreatografia Retrógrada Endoscópica/mortalidad , Tamaño de las Instituciones de Salud , Humanos , Persona de Mediana Edad , Noruega/epidemiología , Pancreatitis/etiología , Hemorragia Posoperatoria/etiología , Estudios Prospectivos , Trastornos Respiratorios/etiología , Factores de Riesgo , Rotura/etiología , Adulto Joven
18.
Colorectal Dis ; 15(6): e301-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23582027

RESUMEN

AIM: Evaluation of ≥ 12 lymph nodes (LNs) is recommended after surgery for colon cancer. A harvest of ≤ 8 is considered poor, but few reports have evaluated risk factors associated with a poor harvest. This aims of this study were to analyse the clinical, surgical and pathological factors associated with poor LN harvest (LNH), the total number of examined nodes and the effect of LN number on stage. METHOD: All patients reported to the Norwegian Colorectal Cancer Registry during 2007 and 2008 who underwent curative resection for Stage I-III colon cancer were studied. Risk factors for poor LNH and the proportion of Stage III disease were analysed by univariate and multivariate analyses. RESULTS: A total of 2879 patients were included in the study. The median LNH was 14. Overall, 69.9% had ≥ 12 lymph nodes and 14.4% had ≤ 8 LN (poor harvest). Multivariate analysis showed that male sex, age > 75 years, sigmoid tumours, pT category 1-2, failure to use the pathology report template and distance of ≤ 5 cm from the bowel resection margin were all independent factors for poor LNH. Age < 65 years, pT category 3-4, and poor tumour differentiation were independent predictors of Stage III disease. An increased LNH did not increase the proportion of patients identified as being LN positive at the ≤ 8, 9-11 and ≥ 12 LN levels. CONCLUSION: Adequate LNH was achieved in the majority of curative colon cancer resections in this national cohort. Elderly, male patients with sigmoid cancers, and a short distal margin were at increased risk of a poor LNH.


Asunto(s)
Adenocarcinoma/patología , Neoplasias del Colon/patología , Escisión del Ganglio Linfático/estadística & datos numéricos , Ganglios Linfáticos/patología , Adenocarcinoma/cirugía , Factores de Edad , Anciano , Estudios de Cohortes , Neoplasias del Colon/cirugía , Femenino , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático/normas , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Noruega , Factores de Riesgo , Factores Sexuales , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/cirugía
20.
Colorectal Dis ; 14(3): 320-4, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21689321

RESUMEN

AIM: National guidelines recommend enrollment of patients in surveillance programmes following curative resection of colorectal carcinoma (CRC) in order to detect recurrence or distant metastasis at an asymptomatic/early stage when secondary curative treatment can be offered. Little is known about surgeons' adherence to such guidelines. In this national survey we analyse adherence and attitudes to postoperative follow up among Norwegian gastrointestinal surgeons involved in the care of patients with CRC. METHOD: We performed a nationwide survey of all hospitals performing surgery for colon and/or rectum cancer. The presence of a surveillance programme, the type of programme, adherence to national guidelines or report on any deviation thereof, location of follow up at the hospital or with a general practitioner (GPs) and the estimated annual volume of surgery were queried through mail and telephone. RESULTS: All hospitals (n=41) performing colorectal surgery responded, of which 25 (61%) conducted postoperative follow up by surgeons in the hospital outpatient clinics, four (10%) carried out follow up with a combination of hospital outpatient visits and visits to GPs, and 12 (29%) referred surveillance to the GP alone. For total reported patient numbers, almost two-thirds (60%) received surveillance according to national recommendations through outpatient visits with the surgeon or GP, while one-third (37%) were subject to other alternative routines. A small number (2%) received informal 'ad hoc' surveillance only. More liberal use of imaging outside guideline recommendations was reported for rectal cancer patients, while colon cancer patients treated in larger hospitals were more likely to be referred for GP surveillance. CONCLUSION: All hospitals reported having a strategy for surveillance after surgery for colon and rectal cancer, but there was considerable variance in strategy. A scientific audit of the true level of compliance, effectiveness and cost-benefit is warranted at a national level.


Asunto(s)
Neoplasias del Colon/cirugía , Adhesión a Directriz/estadística & datos numéricos , Vigilancia de la Población , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias del Recto/cirugía , Neoplasias del Colon/diagnóstico , Encuestas de Atención de la Salud , Hospitales/estadística & datos numéricos , Humanos , Metástasis de la Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Noruega , Guías de Práctica Clínica como Asunto , Neoplasias del Recto/diagnóstico
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