RESUMO
For all cancers there are four areas of importance: prevention, early diagnosis, optimising therapy and living with and beyond. For women diagnosed with gynaecological cancers, progress in these first three areas has been immense. However, living with and beyond has largely been ignored as a significant issue. As a group, patients treated for gynaecological cancer are more often young and more often suffer the most difficult long-term issues. Despite the growing number of long-term survivors, little has been done to ensure appropriate assessment and treatment of side-effects of cancer therapies, especially when radiotherapy has been used. For many affected patients their symptoms become part of everyday life, 'normality' is adjusted and these changes are tolerated even when severely limiting activities. Data show that even expert clinicians frequently do not appreciate the true impact of these problems and the focus of treatment and of follow-up remains fixed on 5-year survival and cancer recurrence, respectively. Many clinicians are unaware of what experts can do for toxicity and do not know where to refer their patients. However, rapid identification of patients with significant symptoms can lead to earlier diagnosis of treatable pathologies and improvement in patients' quality of life. In addition, the underlying pathophysiology of radiation-induced damage is potentially amenable to disease-modifying therapies. This review focuses on the factors that contribute to patients developing pelvic radiation disease, what can be done to mitigate the toxicity of treatment and highlights the challenges that must be addressed to reduce the gastrointestinal toxicity of pelvic radiotherapy.
Assuntos
Gastroenteropatias , Lesões por Radiação , Feminino , Humanos , Recidiva Local de Neoplasia , Pelve , Qualidade de Vida , Lesões por Radiação/etiologia , Radioterapia/efeitos adversosRESUMO
BACKGROUND: Patients with oesophago-gastric (OG) cancer may be at risk of malnutrition, troublesome gastrointestinal symptoms (GI) and reduced dietary intake in view of the tumour location and multimodality curative treatment approach. Longitudinal research is lacking. The present study aimed to assess (i) nutritional status and how it evolved over the first year; (ii) the association between nutritional status scores and GI symptom scores; and (iii) the nutrient and food group intake pattern. METHODS: This was a prospective, observational study of patients with an OG lesion planned for radical treatment, with assessment at diagnosis, 3 months and 12 months after the start of treatment. Nutritional assessment was performed using the Patient-Generated Subjective Global Assessment, GI symptoms measured using the modified Gastrointestinal Symptom Rating Scale and dietary intake assessed using a semi-quantitative food frequency approach. RESULTS: Eighty patients (61 males, 19 females; aged 46-89 years) were recruited. At baseline, 3 (n = 68) and 12 months (n = 57), 61%, 62% and 60%, respectively, were moderately/severely malnourished. Higher symptom burden was associated with poorer nutritional status at baseline (r = 0.55, P < 0.001), 3 months (r = 0.51, P < 0.001) and 12 months (r = 0.42, P = 0.001). At each respective time point, 37%, 38% and 42% were meeting their estimated average requirement for energy. No change in mean (SD) intake of energy, fibre, nutrient and food groups was observed over time. CONCLUSIONS: Patients with OG cancer have progressive weight loss, with malnutrition present over the majority of the 12-month study period. Optimising nutritional status and symptom management throughout the treatment pathway should be a clinical priority.
Assuntos
Dieta , Neoplasias Esofágicas/complicações , Comportamento Alimentar , Desnutrição/etiologia , Estado Nutricional , Neoplasias Gástricas/complicações , Redução de Peso , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Registros de Dieta , Ingestão de Energia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Terapia Nutricional , Necessidades Nutricionais , Estudos ProspectivosRESUMO
In patients with gastrointestinal (GI) disorders, identical symptoms may occur for many different reasons. This prospective study assessed whether experienced clinicians can predict accurately the underlying diagnosis or diagnoses contributing to specific symptoms based on the history and physical examination. Three clinicians assessed 47 patients referred for management of troublesome GI symptoms identified after treatment for cancer. Investigations were requested following our comprehensive, peer-reviewed algorithm. The clinicians then recorded their predictions as to the results of those investigations. After each patient had completed all their investigations, had received optimal management and had been discharged from the clinic, the predicted diagnoses were compared to those made. The clinicians predicted 92 diagnoses (1.9 per patient). After investigation, a total of 168 unique diagnoses were identified (3.5 per patient). Of the 92 predicted diagnoses, 41 (43%) matched the diagnosis. Of the 168 actual diagnoses identified, only 24% matched the prediction. None of the clinicians predicted the correct combination of diagnoses contributing to bowel symptoms. Clinical acumen alone is inadequate at determining cause for symptoms in patients with GI symptoms developing after cancer therapy.
Assuntos
Competência Clínica , Tomada de Decisão Clínica , Gastroenteropatias/diagnóstico , Neoplasias/terapia , Avaliação de Sintomas , Idoso , Algoritmos , Ácidos e Sais Biliares/metabolismo , Síndrome da Alça Cega/diagnóstico , Diarreia/diagnóstico , Feminino , Gastrite/diagnóstico , Gastroenterologistas , Humanos , Masculino , Estudos Prospectivos , Esteatorreia/diagnóstico , Deficiência de Vitamina D/diagnósticoRESUMO
AIM: Gastrointestinal (GI) symptoms during and after cancer therapy can significantly affect quality of life and interfere with treatment. This study assessed whether bile acid malabsorption (BAM) or bile acid diarrhoea (BAD) are important causes of diarrhoea associated with cancer treatment. METHOD: A retrospective analysis was carried out of consecutive patients assessed for BAM using ((75) Se) Selenium homocholic acid taurocholate (SeHCAT) scanning, after reporting any episodes of loose stool, attending a gastroenterology clinic in a cancer centre. RESULTS: Between 2009 and 2013, 506 consecutive patients (54.5% male; age range: 20-91 years), were scanned. BAM/BAD was diagnosed in 215 (42.5%). It was mild in 25.6%, moderate in 29.3% and severe in 45.1%. Pelvic chemoradiation had induced BAM in > 50% of patients. BAM was also frequent after treatment for conditions not previously associated with BAM, such as anal and colorectal cancer, and was present in > 75% of patients referred after pancreatic surgery. It was also unexpectedly frequent in patients who were treated for malignancy outside the GI tract, such as breast cancer and haematological malignancy. CONCLUSION: BAM/BAD are very common and under-appreciated causes of GI symptoms after cancer treatment. Health professionals should have a low threshold in suspecting this condition, as diagnosis and treatment can significantly improve quality of life.
Assuntos
Ácidos e Sais Biliares/metabolismo , Neoplasias da Mama/terapia , Quimiorradioterapia/efeitos adversos , Diarreia/etiologia , Neoplasias do Sistema Digestório/terapia , Neoplasias Hematológicas/terapia , Síndromes de Malabsorção/etiologia , Neoplasias Urogenitais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diarreia/diagnóstico por imagem , Diarreia/metabolismo , Fezes , Feminino , Humanos , Síndromes de Malabsorção/diagnóstico por imagem , Síndromes de Malabsorção/metabolismo , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Radioisótopos de Selênio , Índice de Gravidade de Doença , Ácido Taurocólico/análogos & derivados , Adulto JovemRESUMO
BACKGROUND: The symptoms and signs of small intestinal bacterial overgrowth (SIBO) are often identical to a variety of diseases and can lead to diagnostic confusion. AIMS: To review the diagnostic options for SIBO and present new investigative options for the condition. METHODS: A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts. Search terms included free text words and combinations of the following terms 'small intestinal bacterial overgrowth', 'small bowel bacterial overgrowth', 'diagnostic tests', 'treatment', 'antibiotics', 'probiotics', 'metabonomics', 'proton nuclear magnetic resonance spectroscopy', 'electronic nose' and 'field asymmetric ion mobility spectrometry'. RESULTS: All of the available methods to test for SIBO have inherent limitations and no 'gold-standard' diagnostic test for the condition exists. Accurate diagnosis of SIBO requires identification of bacterial species growing inappropriately within the small intestine and symptom response to antibiotics. Proton nuclear magnetic resonance spectroscopy, electronic nose technology and/or field asymmetric ion mobility spectrometry may represent better investigative options for the condition. CONCLUSIONS: Novel diagnostic options are needed to supplement or replace available tests.
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Intestino Delgado/microbiologia , Animais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/terapia , Testes Diagnósticos de Rotina/métodos , Humanos , PrevalênciaRESUMO
BACKGROUND: Radiotherapy-induced damage to noncancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option for the prevention and management of symptoms. AIM: To synthesise the evidence for the use of elemental formula low- or modified-fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the gastrointestinal tract during pelvic radiotherapy. METHODS: Four electronic databases were searched. Randomised controlled trials (RCT), controlled trials (CT) and case series in adult patients receiving radiotherapy for pelvic cancers employing nutritional interventions to reduce gastrointestinal toxicity were included. Methodological quality was assessed using a bespoke tool. RESULTS: Twenty-two original studies (2446 patients) were identified. Study quality was highly variable with only 37% scoring ≥10 points (maximum 17: bespoke scale). Few studies assessed compliance with the intervention. End-points varied and included symptom scales (IBDQ, CTC, Bristol Stool and RTOG). Evidence from RCTs was weak for elemental, low- or modified-fat, fibre and low-lactose interventions with 1/4, 3/4, 1/2, 0/1 trials respectively reporting favourable outcomes. Evidence for probiotics as prophylactic interventions was more promising (4/5 favourable), but dose, strains and methodologies varied. CONCLUSIONS: There is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula may be appropriate in severe toxicity. Probiotics offer promise, but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients. The methodological quality of nutritional intervention studies needs to be improved.
Assuntos
Dieta com Restrição de Gorduras , Gastroenteropatias/prevenção & controle , Trato Gastrointestinal/efeitos da radiação , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Suplementos Nutricionais , Comportamento Alimentar , Gastroenteropatias/etiologia , Humanos , Lesões por Radiação/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Repeated episodes of acute bowel obstruction is a potential complication following pelvic radiation therapy. It has been previously thought that hyperbaric oxygen therapy (HBOT) may not be useful for treatment of such obstructive episodes. We report our experience with the use of HBOT for recurrent radiation-induced acute bowel obstruction. METHODS: This is a retrospective case series. Radiological imaging had excluded the presence of recurrent or new cancer. Possible predisposing causes for acute obstruction had been treated and had not led to resolution of symptoms or had been excluded. RESULTS: During 2007-2010, five patients with recurrent episodes of acute obstructive bowel symptoms following previous therapeutic pelvic irradiation were referred for HBOT (four females and one male; median age 56; range 48-72). The primary tumours sites were the endometrium (n = 2), ovary, cervix and prostate (n = 1 each), and patients were treated 2-17 (median 9) years previously with radiotherapy. Before HBOT, patients were experiencing acute obstructive bowel symptoms at 1-6 weekly intervals. Four patients had progressive weight loss. Patients received 100 % oxygen in a multiplace hyperbaric chamber at a pressure of 2.4 atm absolute for up to 90 min once a day, 5 to 7 days weekly. All patients were initially referred for 40 sessions of HBOT. Three patients required a further extra 20 sessions for complete resolution of bowel symptoms. HBOT was well tolerated with no side effects. Patients have remained well after 6-24 months of follow-up. CONCLUSIONS: HBOT may be an effective treatment of radiation-induced bowel obstruction and deserves prospective evaluation.
Assuntos
Oxigenoterapia Hiperbárica/métodos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Adulto , Idoso , Feminino , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pelve/efeitos da radiação , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Inflammatory responses to pelvic radiotherapy can result in severe changes to normal gastrointestinal function with potentially severe long-term effects. Reduced or modified fat diets may confer benefit. METHODS: This randomised controlled trial recruited patients with gynaecological, urological or lower gastrointestinal malignancy due to receive radical radiotherapy. Patients were randomised to a low fat (20% total energy from long chain triglycerides), modified fat (20% from long chain triglycerides and 20% from medium chain triglycerides) or normal fat diet (40% total energy from long chain triglycerides). The primary outcome was a difference in change in Inflammatory Bowel Disease Questionnaire--Bowel (IBDQ-B) score, from the start to end of radiotherapy. RESULTS: A total of 117 patients with pelvic tumours (48% urological; 32% gastrointestinal; 20% gynaecological), with mean (SD) age: 65 (11.0) years, male:female ratio: 79:38, were randomised. The mean (SE) fall in paired IBDQ-B score was -7.3 (0.9) points, indicating a worsening toxicity. Differences between groups were not significant: P = 0.914 (low versus modified fat), P = 0.793 (low versus normal fat) and P = 0.890 (modified versus normal fat). The difference in fat intake between low and normal fat groups was 29.5 g [1109 kJ (265 kcal)] amounting to 11% (of total energy intake) compared to the planned 20% differential. Full compliance with fat prescription was only 9% in the normal fat group compared to 93% in the low fat group. CONCLUSIONS: A low or modified fat diet during pelvic radiotherapy did not improve gastrointestinal symptom scores compared to a normal fat intake. An inadequate differential in fat intake between the groups may have confounded the results.
Assuntos
Dieta com Restrição de Gorduras , Trato Gastrointestinal/efeitos da radiação , Inflamação/dietoterapia , Neoplasias Pélvicas/radioterapia , Radioterapia/efeitos adversos , Idoso , Feminino , Humanos , Inflamação/etiologia , Masculino , Cooperação do Paciente , Neoplasias Pélvicas/complicações , Resultado do TratamentoRESUMO
PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty-nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients.
Assuntos
Gastroenteropatias/etiologia , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/complicações , Gastroenterologia , Gastroenteropatias/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Inquéritos e Questionários , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Weight loss in patients with cancer is common and associated with a poorer survival and quality of life. Benefits from nutritional interventions are unclear. The present study assessed the effect of dietary advice and/or oral nutritional supplements on survival, nutritional endpoints and quality of life in patients with weight loss receiving palliative chemotherapy for gastrointestinal and non-small cell lung cancers or mesothelioma. METHODS: Participants were randomly assigned to receive no intervention, dietary advice, a nutritional supplement or dietary advice plus supplement before the start of chemotherapy. Patients were followed for 1 year. Survival, nutritional status and quality of life were assessed. RESULTS: In total, 256 men and 102 women (median age, 66 years; range 24-88 years) with gastrointestinal (n = 277) and lung (n = 81) cancers were recruited. Median (range) follow-up was 6 (0-49) months. One-year survival was 38.6% (95% confidence interval 33.3-43.9). No differences in survival, weight or quality of life between groups were seen. Patients surviving beyond 26 weeks experienced significant weight gain from baseline to 12 weeks, although this was independent of nutritional intervention. CONCLUSIONS: Simple nutritional interventions did not improve clinical or nutritional outcomes or quality of life. Weight gain predicted a longer survival but occurred independently of nutritional intervention.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Suplementos Nutricionais , Neoplasias Gastrointestinais/dietoterapia , Mesotelioma/dietoterapia , Estado Nutricional/efeitos dos fármacos , Cuidados Paliativos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Intervalos de Confiança , Dietética , Determinação de Ponto Final , Feminino , Seguimentos , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
AIMS: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. It is common for patients to develop gastrointestinal symptoms after treatment. The aim of this study was to determine the current practice of clinical oncologists in the UK with respect to late-onset bowel dysfunction after pelvic radiotherapy, and to discuss the wider issues surrounding current and future service provision for this patient group. MATERIALS AND METHODS: A questionnaire was developed to establish current practice. This was sent to the 314 clinical oncologists in the UK who treat pelvic malignancies up to a maximum of three times. RESULTS: One hundred and ninety (61%) responses were received. Most oncologists (76%) screen for gastrointestinal dysfunction after pelvic radiotherapy, usually through history taking rather than formal tools. Clinical oncologists view toxicity as a significant problem, with most estimating that up to 24% of patients at 1 year have bowel symptoms. Most oncologists refer less than 50% of their symptomatic patients, with most referring less than 10%. These referrals are 31% to a gastroenterologist, 23% to a gastrointestinal surgeon and 33% to both. Most (58%) do not have access to a gastroenterologist or a gastrointestinal surgeon with a specialist interest in their area. Sixty-five per cent of oncologists think a service is required specifically for patients with bowel dysfunction after pelvic radiotherapy, but half (52%) think that the current service in their area is inadequate. CONCLUSIONS: Clinical oncologists recognise late-onset bowel dysfunction after pelvic radiotherapy as a significant problem, but one that is linked to poor recognition of symptoms and an inadequate patchy service.
Assuntos
Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Neoplasias Pélvicas/radioterapia , Padrões de Prática Médica/estatística & dados numéricos , Lesões por Radiação/diagnóstico , Atitude do Pessoal de Saúde , Continuidade da Assistência ao Paciente/normas , Seguimentos , Gastroenteropatias/prevenção & controle , Inquéritos Epidemiológicos , Humanos , Neoplasias Pélvicas/complicações , Prognóstico , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Encaminhamento e ConsultaRESUMO
AIMS: About 17,000 patients receive radiotherapy for pelvic cancer in the UK annually. Up to 50% are left with altered bowel function affecting quality of life. The UK National Cancer Survivorship Initiative Vision acknowledges that the needs of cancer survivors are not being met and challenges professionals to develop new models of care. MATERIALS AND METHODS: A prospective, observational qualitative study was carried out to assess whether nurse-delivered care is feasible for patients with radiotherapy-induced bowel dysfunction. The experience of a senior nurse, directed by an algorithm of investigation with a comprehensive treatment pathway, is reported. RESULTS: Over 12 months, 59 new and 103 follow-up appointments were managed by the nurse. In total, 37 women and 73 men, with a median age of 69 years, were seen; 9 had been treated for gastrointestinal, 33 for gynaecological and 68 for urological cancers, 26 months (median) previously. Sixty minutes (new consultations) (median, range 35-80) and 40 minutes (follow-up consultations) (range 20-85) were required. Ordering investigations, treatment initiation, long-term care planning and discharge seemed to be manageable in 83% of patients. CONCLUSION: An experienced nurse, working within a defined scope of practice, with medical support can manage care in patients with mild or moderate symptoms arising after pelvic radiotherapy. An ongoing randomised controlled trial is assessing patient outcomes.
Assuntos
Gastroenteropatias/etiologia , Gastroenteropatias/enfermagem , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/enfermagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Continuidade da Assistência ao Paciente/normas , Feminino , Seguimentos , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Neoplasias Pélvicas/complicações , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Lesões por Radiação/etiologiaRESUMO
BACKGROUND: Recurrent, watery diarrhoea affects one-third of patients diagnosed with irritable bowel syndrome ('IBS-D'). Idiopathic bile acid malabsorption ('I-BAM') may be the cause. AIM: To determine the prevalence of I-BAM in patients suffering from IBS-D. METHODS: A systematic search was performed of publications reporting patients presenting with IBS-D type symptoms, who were subsequently confirmed as having I-BAM by SeHCAT scanning. RESULTS: Eighteen relevant studies, 15 prospective, comprising 1223 patients were identified. Five studies (429 patients) indicated that 10% (CI: 7-13) patients had severe bile acid malabsorption (SeHCAT 7 day retention <5% of baseline value). 17 studies (1073 patients) indicated that 32% (CI: 29-35) patients had moderate bile acid malabsorption (SeHCAT <10%). 7 studies (618 patients) indicated that 26% (CI: 23-30) patients had mild (SeHCAT <15%) bile acid malabsorption. Pooled data from 15 studies showed a dose-response relationship according to severity of malabsorption to treatment with a bile acid binder: response to colestyramine occurred in 96% of patients with <5% retention, 80% at <10% retention and 70% at <15% retention. CONCLUSIONS: Idiopathic adult-onset bile acid malabsorption is not rare. International guidelines for the management of irritable bowel syndrome need to be revised so that clinicians become more aware of this possibility.
Assuntos
Resinas de Troca Aniônica/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Resina de Colestiramina/uso terapêutico , Diarreia/etiologia , Síndrome do Intestino Irritável/fisiopatologia , Síndromes de Malabsorção/complicações , Adulto , Diarreia/epidemiologia , Relação Dose-Resposta a Droga , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Síndromes de Malabsorção/tratamento farmacológico , Síndromes de Malabsorção/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Loss of control of mucosal crypt cell proliferation resulting in a hyperproliferative field change occurs early in the adenoma-carcinoma sequence. Ki-67, the current gold-standard marker of cellular proliferation, is a cell cycle protein that may lack sensitivity in demonstrating altered mucosal crypt cell dynamics. Minichromosome maintenance protein 2 (MCM2) has a specific role in DNA replication and has been proposed as a new marker for screening for colorectal cancer. AIM: To compare the expression of Ki-67 with that of MCM2 in colorectal mucosa associated with colorectal cancer. METHODS: Ki-67 and MCM2 immunostaining was performed on serial sections taken from formalin-fixed, paraffin-embedded specimens. Labelling indices were calculated by counting the proportion of positively stained nuclei in representative areas of adenocarcinoma, and in equivalent superficial, middle and basal crypt compartments of mucosa sampled 1 cm from tumour (Ca1) and 10 cm from tumour (Ca10). RESULTS: Specimens were obtained from 43 patients (27 adenocarcinoma, 16 no-cancer controls). Most nuclei in specimens of adenocarcinoma stained positively for MCM2 and Ki-67. In Ca1 and Ca10 samples, significantly greater staining of MCM2 than Ki-67 was seen in all crypt compartments. Receiver operator characteristic curve analysis suggested that proliferation changes (assessed by either MCM2 or Ki-67 staining) in Ca10, but not in Ca1, mucosa significantly predicted origin from a carcinoma-associated colon. CONCLUSIONS: MCM2 was more sensitive than Ki-67 in identifying colorectal mucosal proliferation. Increased proliferation (assessed by either MCM2 or Ki-67 staining) in mucosa at 10 cm, but not at 1 cm, from carcinoma significantly predicted origin from a carcinoma-associated colon.
Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Mucosa Intestinal/metabolismo , Proteínas Nucleares/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Mucosa Intestinal/patologia , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Proteínas de Neoplasias/metabolismoRESUMO
INTRODUCTION: Loose stool affects up to 80% of all patients during pelvic radiotherapy and faecal incontinence may occur. Several causes for diarrhoea have been defined, though few oncologists target these causes in affected patients and most treat symptomatically only. It is not known whether small bowel bacterial overgrowth, a frequent cause of gastrointestinal symptoms in other contexts, occurs during radiotherapy. The frequency of new-onset lactose intolerance during pelvic radiotherapy is also not clear. AIMS AND METHODS: To perform an observational pilot study to estimate the incidence of small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy. Before treatment started and at weeks 4-5 of pelvic radiotherapy, a glucose hydrogen breath test and lactose tolerance test were performed. Gastrointestinal symptoms were assessed using the Vaizey incontinence questionnaire and the Radiation Therapy Oncology Group scoring system. RESULTS: Twenty two men and 17 women (median age 61, range 42-81) were recruited, four were treated for gastrointestinal, 17 were treated for gynaecological and 18 for urological cancers. Thirty-eight patients underwent glucose hydrogen breath tests and 26 patients underwent lactose breath tests at both time points. Ten patients (26%) were positive for the glucose hydrogen breath test: 60% of these developed new or worsening faecal incontinence during treatment and 60% had worsening bowel frequency. Four patients (15%) developed lactose intolerance. Of these 1 developed worsening faecal incontinence during treatment, 2 (50%) developed new-onset increase in bowel frequency or a change in the quality of bowel habit. CONCLUSION: Small bowel bacterial overgrowth and lactose intolerance may occur during radical pelvic radiotherapy and are likely to contribute to gastrointestinal symptoms in some patients.
Assuntos
Bactérias/crescimento & desenvolvimento , Intestino Delgado/microbiologia , Intolerância à Lactose/etiologia , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios/métodos , Diarreia/etiologia , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Radioterapia/efeitos adversosRESUMO
BACKGROUND: Reliable, non-invasive biological markers of the severity of radiotherapy-induced damage to the gastrointestinal tract are not available. Clinicians continue to use symptom scores as surrogate indicators of toxicity. AIM: To determine whether levels of potential biochemical markers of mucosal toxicity change during pelvic radiotherapy. METHODS: Fifty-nine patients (30:29 males:females) with mixed pelvic malignancies, receiving 45-70 Gy were recruited. At baseline and weeks 4 or 5 of radiotherapy, blood samples for citrulline, C-reactive protein, eosinophil cationic protein and stool samples for faecal calprotectin were obtained. Symptoms were measured using the Inflammatory Bowel Disease Questionnaire - Bowel Subset, Radiation Therapy Oncology Group and Vaizey Incontinence Questionnaires. Paired t-tests of change in marker values were calculated. RESULTS: Citrulline (P = 0.02) and faecal calprotectin (P = 0.01) values changed significantly between baseline and 4/5 weeks. Inflammatory Bowel Disease Questionnaire - Bowel Subset fell significantly (mean fall = 10 points, s.d.: 8.9). Changes in markers did not correlate with symptoms. CONCLUSIONS: Some biochemical markers of mucosal toxicity change significantly during treatment. Further studies must investigate the timing of changes of these biochemical markers, their relationship to gastrointestinal physiological change and the radiotherapy dose delivered to the gastrointestinal tract and whether changes in markers acutely can predict the degree of long-term gastrointestinal dysfunction.
Assuntos
Biomarcadores/metabolismo , Neoplasias Gastrointestinais/radioterapia , Mucosa Intestinal/efeitos da radiação , Lesões por Radiação/diagnóstico , Radioterapia/efeitos adversos , Neoplasias Urogenitais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Acute gastrointestinal symptoms affect 90% of patients during pelvic radiotherapy. Elemental diet is protective in animal models. A nonrandomized study suggested benefit from a partial elemental diet. A pilot study suggested that radiotherapy patients only tolerate oral elemental diet comprising one-third of total calories for 3 weeks. AIM: To assess the feasibility and efficacy of replacing one-third of normal diet with elemental diet during the first 3 weeks of pelvic radiotherapy in reducing acute gastrointestinal toxicity. METHODS: Patients were randomized to elemental diet or no intervention. Toxicity was assessed using the Inflammatory Bowel Disease Questionnaire, Vaizey Incontinence scale and Radiation Therapy Oncology Group tool. Faecal calprotectin measured intestinal mucosal inflammation. RESULTS: Twenty-nine women and 21 men, median age 61.5 years were randomized. Patients taking elemental diet did not have lower gastrointestinal toxicity ratings or inflammatory markers (P > 0.2). The mean dose taken was 21% (2-36%) of total caloric requirements. CONCLUSIONS: Patients cannot tolerate large volumes of oral elemental diet. The quantities consumed in this study produced no therapeutic benefit. Future studies should aim to replace a higher proportion of nutritional intake for a longer duration of radiotherapy treatment.
Assuntos
Diarreia/prevenção & controle , Nutrição Enteral/métodos , Alimentos Formulados , Trato Gastrointestinal/efeitos da radiação , Neoplasias Pélvicas/radioterapia , Adulto , Idoso , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necessidades NutricionaisRESUMO
Up to 300,000 patients per year undergo pelvic radiotherapy worldwide. Nine out of 10 will develop a permanent change in their bowel habit as a result. Five out of 10 of all patients will say that this change in their bowel habit affects quality of life and two to three out of 10 will say that this effect on quality of life is moderate or severe. Between one in 10 and one in 20 patients will develop very serious complications within the first 10 years after treatment. This number will increase to two out of 10 by 20 years from the end of treatment. Although research carried out into the basic molecular, cytokine and physiological changes underlying radiation-induced bowel symptoms and the optimal treatment that should be provided to symptomatic patients is scant, it does seem probable that a significant proportion of these patients can be cured or improved by specialist gastroenterological intervention. However, most patients never get referred to a specialist gastroenterologist and research into late radiation bowel damage has not been considered a priority. With the advent of more effective cancer therapies leading to greater numbers of affected long-term survivors, much more emphasis is urgently required to provide better information to patients at the start and after treatment, developing techniques that might reduce the frequency of significant bowel toxicity and researching better ways of measuring and treating late-onset side-effects.