RESUMO
PURPOSE: Radiotherapy is traditionally given in equally spaced weekday fractions. We hypothesize that heterogeneous interfraction intervals can increase radiosensitivity via reoxygenation. Through modeling, we investigate whether this minimizes local failures and toxicity for early-stage non-small cell lung cancer (NSCLC). METHODS: Previously, a tumor dose-response model based on resource competition and cell-cycle-dependent radiosensitivity accurately predicted local failure rates for early-stage NSCLC cohorts. Here, the model mathematically determined non-uniform inter-fraction intervals minimizing local failures at similar normal tissue toxicity risk, i.e., iso-BED3 (iso-NTCP) for fractionation schemes 18Gyx3, 12Gyx4, 10Gyx5, 7.5Gyx8, 5Gyx12, 4Gyx15. Next, we used these optimized schedules to reduce toxicity risk (BED3) while maintaining stable local failures (TCP). RESULTS: Optimal schedules consistently favored a "primer shot" fraction followed by a 2-week break, allowing tumor reoxygenation. Increasing or decreasing the assumed baseline hypoxia extended or shortened this optimal break by up to one week. Fraction sizes of 7.5 Gy and up required a single primer shot, while smaller fractions needed one or two extra fractions for full reoxygenation. The optimized schedules, versus consecutive weekday fractionation, predicted absolute LF reductions of 4.6%-7.4%, except for the already optimal LF rate seen for 18Gyx3. Primer shot schedules could also reduce BED3 at iso-TCP with the biggest improvements for the shortest schedules (94.6Gy reduction for 18Gyx3). CONCLUSION: A validated simulation model clearly supports non-standard "primer shot" fractionation, reducing the impact of hypoxia-induced radioresistance. A limitation of this study is that primer-shot fractionation is outside prior clinical experience and therefore will require clinical studies for definitive testing.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Fracionamento da Dose de Radiação , HipóxiaRESUMO
PURPOSE: Rectal prolapse is a common condition, with conflicting opinions on optimal surgical management. Existing literature is predominantly composed of case series, with a dearth of evidence demonstrating current, real-world practice. This study investigated recent national trends in management of rectal prolapse in the Republic of Ireland (ROI). METHODS: This population analysis used a national database to identify patients admitted in the ROI primarily for the management of rectal prolapse, as defined by the International Classification of Diseases, 10th Revision (ICD-10). Demographics, procedures, comorbidities, and outcomes were obtained for patients admitted from 2005 to 2015 inclusive. RESULTS: There were 2648 admissions with a primary diagnosis of rectal prolapse; 39.3% underwent surgical correction. The majority were treated with either a perineal resection (47.2%) or an abdominal rectopexy ± resection (45.1%). The population-adjusted rate of operative intervention increased over the study period, from 25 to 42 per million (p < 0.001), with no change in the mean age of patients over time (p = 0.229). The application of a laparoscopic approach increased over time (p = 0.001). Patients undergoing an abdominal rectopexy were younger than those undergoing a perineal procedure (64.1 ± 17.3 versus 75.2 ± 15.5 years, p < 0.001) despite having a similar Charlson Comorbidity Index (p = 0.097). The mortality rate for elective repair was 0.2%. CONCLUSIONS: Despite the popularization of ventral mesh rectopexy over the study period, perineal resection Delorme's procedure remains the most common procedure employed for the correction of rectal prolapse in the ROI, with specific approach determined by age.
Assuntos
Prolapso Retal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Demografia , Feminino , Humanos , Classificação Internacional de Doenças , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Fatores de TempoRESUMO
OBJECTIVES: To identify temporal patterns of patient-reported trismus during the first year post-radiotherapy, and to study their associations with maximal interincisal opening distances (MIOs). DESIGN: Single institution case series. SETTING: University hospital ENT clinic. PARTICIPANTS: One hundred and ninety-six subjects who received radiotherapy (RT) for head and neck cancer (HNC) with or without chemotherapy in 2007-2012 to a total dose of 64.6/68 Gy in 38/34 fractions, respectively. All subjects were prospectively assessed for mouth-opening ability (Gothenburg Trismus Questionnaire (GTQ), European Organization for Research and Treatment of Cancer quality of life Questionnaire (EORTC QLQ-H&N35), and MIO) pre-RT and at 3, 6 and 12 months after RT. MAIN OUTCOME MEASURES: Correlations between temporally robust GTQ symptoms and MIO as given by Pearson's correlation coefficients (Pr ); temporally robust GTQ-symptom domains as given by factor analysis; rates of trismus with respect to baseline by risk ratios (RRs). RESULTS: Four temporally robust domains were identified: Eating (3-7 symptoms), Jaw (3-7), Pain (2-5) and Quality of Life (QoL, 2-5), and included 2-3 persistent symptoms across all post-RT assessments. The median RR for a moderate/severe (>2/>3) cut-off was the highest for Jaw (3.7/3.6) and QoL (3.2/2.9). The median Pr between temporally robust symptoms and MIO post-radiotherapy was 0.25-0.35/0.34-0.43/0.24-0.31/0.34-0.50 for Eating/Jaw/Pain/QoL, respectively. CONCLUSIONS: Mouth-opening distances in patients with HNC post-RT can be understood in terms of associated patient-reported outcomes on trismus-related difficulties. Our data suggest that a reduction in MIO can be expected as patients communicate their mouth-opening status to interfere with private/social life, a clinical warning signal for emerging or worsening trismus as patients are being followed after RT.
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Neoplasias de Cabeça e Pescoço/radioterapia , Boca/anatomia & histologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Trismo/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Inquéritos e Questionários , Suécia/epidemiologia , Fatores de Tempo , Trismo/diagnóstico , Trismo/etiologiaRESUMO
AIM: Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C-reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer. METHOD: A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver-operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system. RESULTS: Two-hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936-33.238, P = 0.004). CONCLUSION: Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.
Assuntos
Fístula Anastomótica/etiologia , Proteína C-Reativa/análise , Colectomia/efeitos adversos , Neoplasias Retais/sangue , Idoso , Biomarcadores/sangue , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Curva ROC , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION Recent studies have advocated the use of perioperative fluid restriction in patients undergoing major abdominal surgery as part of an enhanced recovery protocol. Series reported to date include a heterogenous group of high- and low-risk procedures but few studies have focused on rectal cancer surgery alone. The aim of this study was to assess the effects of perioperative fluid volumes on outcomes in patients undergoing elective rectal cancer resection. METHODS A prospectively maintained database of patients with rectal cancer who underwent elective surgery over a 2-year period was reviewed. Total volume of fluid received intraoperatively was calculated, as well as blood products required in the perioperative period. The primary outcome was postoperative morbidity (Clavien-Dindo grade I-IV) and the secondary outcomes were length of stay and major morbidity (Clavien-Dindo grade III-IV). RESULTS Over a 2-year period (2012-2013), 120 patients underwent elective surgery with curative intent for rectal cancer. Median total intraoperative fluid volume received was 3680ml (range 1200-9670ml); 65/120 (54.1%) had any complications, with 20/120 (16.6%) classified as major (Clavien-Dindo grade III-IV). Intraoperative volume >3500ml was an independent risk factor for the development of postoperative all-cause morbidity (P=0.02) and was associated with major morbidity (P=0.09). Intraoperative fluid volumes also correlated with length of hospital stay (Pearson's correlation coefficient 0.33; P<0.01). CONCLUSIONS Intraoperative fluid infusion volumes in excess of 3500ml are associated with increased morbidity and length of stay in patients undergoing elective surgery for rectal cancer.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Hidratação/efeitos adversos , Hidratação/estatística & dados numéricos , Neoplasias Retais/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Prospectivos , Neoplasias Retais/epidemiologia , Reto/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND/AIMS: An increasing number of colon and rectal tumours are being resected using laparoscopic techniques. Identifying these tumours intraoperatively can be difficult. The use of tattooing can facilitate an easier resection; however, the lack of standardised guidelines can potentially lead to errors intraoperatively and potentially result in worse outcomes for patients. The aim of this study was to identify the most reliable method of preoperative tumour localisation from the available literature to date. METHODS: A literature review was undertaken to identify any articles related to endoscopic tattooing and tumour localisation during colorectal surgery. RESULTS: To date there is still mixed evidence regarding tattooing techniques and the choice of ink that should be used. There are numerous studies demonstrating safe tattooing techniques and highlighting the risks and benefits of different types of ink available. CONCLUSION: Based on the available studies we have recommended a standardised approach to endoscopic tattooing of colorectal tumours prior to laparoscopic resection.
Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Tatuagem/normas , Colonoscopia/métodos , Neoplasias Colorretais/patologia , HumanosRESUMO
BACKGROUND: There is a general lack of studies on staff retention and mental health status at the beginning of or prior to employment in call centres. AIMS: To evaluate the relationship between psychological status at the beginning of employment and staff retention after 6 months of employment. METHODS: The psychological well-being of new starters was evaluated using a questionnaire and Beck Depression Inventory (BDI). Early leavers were identified through a second survey performed 6 months later. RESULTS: Out of a cohort of 135 new starters, all of the 100 randomly selected employees returned their questionnaires. By the second round of the survey 6 months later, 30 employees had left. There was no significant difference between the BDI scores of leavers and those who remained in the company. Binary logistic regression showed no significant associations between leaving the company and gender, previous history of mental health diagnosis and history of mental health treatment. However, there was a significant association between age (25 or over) and leaving the company within the first 6 months of employment (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.04-6.01; P < 0.05). CONCLUSIONS: Previous mental health conditions or psychological status at the beginning of employment did not appear to contribute significantly to call centre employees leaving within 6 months. Further similar studies in other occupational sectors are recommended.
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Call Centers , Emprego/psicologia , Emprego/normas , Transtornos Mentais/complicações , Reorganização de Recursos Humanos/tendências , Adulto , Estudos de Coortes , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Recursos HumanosRESUMO
BACKGROUND: The mainstay of treatment in rectal cancer is neoadjuvant radio chemotherapy prior to surgery, in an attempt to downstage the tumour, allowing for more complete removal during surgery. In 40 % of cases however, this neoadjuvant radio chemotherapy fails to achieve tumour regression, partly due insufficient apoptosis signaling. X-linked Inhibitor of Apoptosis Protein (XIAP) is an anti-apoptotic protein that has been reported to contribute to disease progression and chemotherapy resistance. METHODS: We obtained rectal biopsy normal and matched tumour tissue from 29 rectal cancer patients with varying degrees of tumour regression, and using Western blot, examined anti-apoptotic XIAP and pro-apoptotic Smac protein levels in these tissues, with the aim to examine whether disturbed XIAP/Smac levels may be an indicator of neoadjuvant radio chemotherapy resistance. Expression of inhibitor of apoptosis proteins cIAP-1 and cIAP-2 was also examined. RESULTS: We found that levels of XIAP increased in accordance with the degree of radio chemotherapy resistance of the tissue. Levels of this protein were also significantly higher in tumour tissue, compared to matched normal tissue in highly resistant tissue. In contrast, Smac protein levels did not increase with radio chemotherapy resistance, and the protein was similarly expressed in normal and tumour tissue, indicating a shift in the balance of these proteins. Post treatment surgical resection tissue was available for 8 patients. When we compared matched tissue pre- and post- radio chemotherapy we found that XIAP levels increased significantly during treatment in both normal and tumour tissue, while Smac levels did not change. cIAP-1 and cIAP-2 levels were not differentially expressed in varying degrees of radio chemotherapy resistance, and neoadjuvant therapy did not alter expression of these proteins. CONCLUSION: These data indicate that disturbance of the XIAP/Smac balance may be a driver of radio chemotherapy resistance, and hence high levels of XIAP may be a useful indicator of neoadjuvant radio chemotherapy resistance in rectal cancer. Moreover, as XIAP levels increase with radio chemotherapy it is possible that a subset of more resistant tumour cells survive this treatment and may be resistant to further adjuvant treatment. Patients with resistant tumours highly expressing XIAP may benefit from alternative treatment strategies, such as Smac mimetics post neoadjuvant radio chemotherapy.
Assuntos
Biomarcadores Tumorais/análise , Quimiorradioterapia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Proteínas Mitocondriais/análise , Terapia Neoadjuvante , Proteínas de Neoplasias/análise , Tolerância a Radiação/fisiologia , Neoplasias Retais/química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/análise , Adulto , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose , Proteína 3 com Repetições IAP de Baculovírus , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Proteínas Inibidoras de Apoptose/análise , Proteínas Inibidoras de Apoptose/biossíntese , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Ubiquitina-Proteína Ligases/análise , Ubiquitina-Proteína Ligases/biossíntese , Ubiquitina-Proteína Ligases/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/biossíntese , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genéticaRESUMO
AIM: In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment. PATIENTS AND METHODS: Fifty-three (n = 53) patients with locally advanced rectal cancers treated with neoadjuvant CRT followed by surgery were identified from the pathology databases of 2 tertiary referral centres over a 4-year period. Immunohistochemical staining of treatment specimens was carried out using the 5-Methylcytidine (Eurogentec, Seraing, Belgium) antibody. Quantitative analysis of staining was performed using an automated image analysis platform. The modified tumour regression grading system was used to assess tumour response to neoadjuvant therapy. RESULTS: Seven (13%) patients showed complete pathological response while 46 (87%) patients were partial responders to neoadjuvant treatment. In 38 (72%) patients, significant reduction in methylation was observed in post-treatment resection specimens compared to pre-treatment specimens (171.5 vs 152.7, p = 0.01); in 15 (28%) patients, methylation was increased. Pre-treatment methylation correlated significantly with tumour regression (p < 0.001), T-stage (p = 0.005), and was able to predict complete and partial pathological responders (p = 0.01). CONCLUSION: Neoadjuvant CRT appears to alter the rectal cancer epigenome. The significant correlation between pre-treatment DNA methylation with tumour response suggests a potential role for methylation as a biomarker of response.
Assuntos
Adenocarcinoma/terapia , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Retais/terapia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Estudos de Coortes , Metilação de DNA/genética , Metilação de DNA/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Projetos Piloto , Prognóstico , Neoplasias Retais/genética , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.
Assuntos
Processamento de Imagem Assistida por Computador , Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Reto/efeitos da radiação , Tomografia Computadorizada por Raios X , Estudos de Coortes , Relação Dose-Resposta à Radiação , Humanos , Masculino , Órgãos em Risco/diagnóstico por imagem , Reto/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: To obtain a clear surgical margin, abdominoperineal excision (APE) for rectal cancer frequently leaves a large perineal defect surrounded by irradiated tissue. A vertical rectus abdominis myocutaneous (VRAM) flap may facilitate healing of this wound. The current study aims to determine the effect of VRAM flap perineal reconstruction following APE on patient quality of life (QOL). METHODS: This is a retrospective cohort study from a prospectively collected database. Data on QOL were assessed via telephone questionnaire using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30, EORTC QLQ-C29 and the Cleveland Clinic QOL questionnaires. RESULTS: Twenty-seven patients underwent primary perineal closure, and 12 patients underwent a VRAM flap perineal reconstruction. The mean duration of follow-up was 16.8 months. Overall, there was no significant difference in the Cleveland Clinic QOL score between groups (VRAM vs. no VRAM: 0.7 ± 0.2 vs. 0.7 ± 0.2, p 0.735). Patients in the VRAM group had lower levels of fatigue (5.5 ± 9.9 vs. 23.6 ± 19.2, p 0.004). Patients in the VRAM group had reduced sore skin scores around the stoma site (11.0 ± 16.2 vs. 31.8 ± 31.1, p 0.036). VRAM flap was associated with an increased incidence of abdominal wall hernia (VRAM vs. no VRAM: 25 % vs. 0 %, p 0.024). CONCLUSIONS: This study is limited by its non-randomized retrospective design and relatively small sample size. A significant difference in patient QOL was not demonstrated between VRAM flap and primary perineal closure after APE for rectal cancer. Further studies in this area are warranted.
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Retalho Miocutâneo , Qualidade de Vida , Neoplasias Retais/cirurgia , Reto do Abdome/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , CicatrizaçãoRESUMO
Colonic tumours are most frequently primary and lesions secondary to metastasis are uncommon. Malignant melanoma is an aggressive cancer, with a tendency to metastasize and recur. This report describes the case of a 66-year-old man who underwent wide local excision and adjuvant therapy for malignant melanoma three years prior to presentation with loose stools, abdominal cramps and iron deficiency anaemia. CT colonography showed a 6cm ileocaecal mass, and following a laparoscopic right hemicolectomy, histological examination revealed a metastatic melanoma to the ileocaecal valve. Subsequent positron emission tomography showed no residual metastatic disease. Malignant melanoma metastasis to the colon is a rare clinical entity. Metastectomy via laparoscopic right hemicolectomy is an appropriate and effective treatment.
Assuntos
Colectomia/métodos , Neoplasias do Íleo/cirurgia , Valva Ileocecal , Laparoscopia/métodos , Melanoma/secundário , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Íleo/secundário , Masculino , Melanoma/diagnóstico , Neoplasias Cutâneas , Tomografia Computadorizada por Raios X , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Radiation enteropathy is a recognized complication in patients who undergo neoadjuvant radiotherapy for locally advanced rectal cancer. Routine formation of defunctioning loop ileostomy in these patients may mask the development of stricturing, terminal ileal and radiation enteropathy which later may complicate the ileostomy closure. Our aim was to assess the preventive techniques and key warning signs. METHODS: We present two cases of ileostomy closure in patients with occult, radiation-induced, terminal ileal stricture and review the relevant literature. RESULTS: The first case was complicated by dehiscence of the ileal anastomosis due to undiagnosed, downstream stenosis of the irradiated terminal ileum. A similar terminal ileal stricture was diagnosed in the second case by contrast fluoroscopy enabling an elective ileocolic anastomosis. The literature indicates the importance of identifying such problems prior to loop ileostomy closure. CONCLUSIONS: Contrast studies before loop ileostomy closure are valuable in limiting the complications of radiation-induced distal ileal obstruction in selected patients.
Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante/efeitos adversos , Doenças do Íleo/etiologia , Íleo/efeitos da radiação , Obstrução Intestinal/etiologia , Lesões por Radiação/etiologia , Neoplasias Retais/terapia , Adulto , Anastomose Cirúrgica/efeitos adversos , Enterite/etiologia , Feminino , Humanos , Doenças do Íleo/cirurgia , Ileostomia , Íleo/cirurgia , Obstrução Intestinal/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversosRESUMO
AIM: A proportion of colonic polyps is not amenable to exclusively colonoscopic removal due to their location, size or tortuosity of the colon. A combined laparoscopic/colonoscopic polypectomy or endolaparoscopic polypectomy (ELP) is an alternative to formal segmental resection. We present our experience of ELP. METHOD: This is a retrospective review of a consecutive series of patients who underwent ELP for preoperatively diagnosed benign polyps between 2010 and 2013. Data are presented as median (interquartile range, IQR). RESULTS: Thirty patients commenced ELP. Eighteen were male and the median (IQR) age was 65.4 (61.6-73.5) years. Of 30 attempted cases, 22 (73%) underwent successful ELP surgery. Patients in whom combined ELP surgery was unsuccessful were converted to laparoscopic colectomy (one) or colonic mobilization and colotomy (seven). The median operation time for successful ELP was 105 (75-125) min. The complication rate was 13.3% and the median length of stay was 2.0 (1.0-3.0) days for successful ELP compared with 5.5 (3.5-6.8) days for converted patients (P = 0.014). The median polyp size was 14 (10-22) mm; eight (26.7%) had high-grade dysplasia with two cases of invasive cancer identified. CONCLUSION: A combined endoscopic-laparoscopic approach provides an alternative to segmental resection for treating challenging colonic polyps. This approach appears to be safe and effective and should be offered to selected patients with benign colonic polyps.
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Adenoma Viloso/cirurgia , Pólipos Adenomatosos/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Laparoscopia/métodos , Adenocarcinoma/cirurgia , Idoso , Estudos de Coortes , Neoplasias do Colo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative. METHOD: One-hundred and fifty-three patients with a T3/T4 and/or a node-positive rectal cancer underwent neoadjuvant 5-fluorouracil-based CRT followed by surgical resection. RESULTS: Thirty-six (23.5%) patients achieving complete pathological response (ypCR) had a 5-year disease-free survival (DFS) rate of 100% compared with a DFS rate of 74% for 117 (76.5%) patients without ypCR (P = 0.003). The Royal College of Pathologists (RCPath) TRG best condenses the Mandard five-point TRG by stratifying patients into three groups with distinct 5-year DFS rates of 100%, 86% and 67%, respectively (P = 0.001). In multivariate analysis, pathological nodal status and circumferential resection margin (CRM) status, but not TRG, remained significant predictors of DFS (P = 0.002, P = 0.035 and P = 0.310, respectively). CONCLUSION: Our findings support the notion that ypCR status, nodal status after neoadjuvant CRT and CRM status, but not TRG, are predictors of long-term survival in patients with locally advanced rectal cancer.
Assuntos
Adenocarcinoma/patologia , Quimiorradioterapia , Linfonodos/patologia , Terapia Neoadjuvante , Neoplasias Retais/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/terapia , Indução de Remissão , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
A tumour control probability computational model for fractionated radiotherapy was developed, with the goal of incorporating the fundamental interplay between hypoxia and proliferation, including reoxygenation over a course of radiotherapy. The fundamental idea is that the local delivery of oxygen and glucose limits the amount of proliferation and metabolically-supported cell survival a tumour sub-volume can support. The model has three compartments: a proliferating compartment of cells receiving oxygen and glucose; an intermediate, metabolically-active compartment receiving glucose; and a highly hypoxic compartment of starving cells. Following the post-mitotic cell death of proliferating cells, intermediate cells move into the proliferative compartment and hypoxic cells move into the intermediate compartment. A key advantage of the proposed model is that the initial compartmental cell distribution is uniquely determined from the assumed local growth fraction (GF) and volume doubling time (TD) values. Varying initial cell state distributions, based on the local (voxel) GF and TD, were simulated. Tumour response was simulated for head and neck squamous cell carcinoma using relevant parameter values based on published sources. The tumour dose required to achieve a 50% local control rate (TCD50) was found for various GFs and TD's, and the effect of fraction size on TCD50 was also evaluated. Due to the advantage of reoxygenation over a course of radiotherapy, conventional fraction sizes (2-2.4 Gy fx(-1)) were predicted to result in smaller TCD50's than larger fraction sizes (4-5 Gy fx(-1)) for a 10 cc tumour with GFs of around 0.15. The time to eliminate hypoxic cells (the reoxygenation time) was estimated for a given GF and decreased as GF increased. The extra dose required to overcome accelerated stem cell accumulation in longer treatment schedules was estimated to be 0.68 Gy/day (in EQD26.6), similar to published values derived from clinical data. The model predicts, for a 2 Gy/weekday fractionation, that increased initial proliferation (high GF) should, surprisingly, lead to moderately higher local control values. Tumour hypoxia is predicted to increase the required dose for local control by approximately 30%. Predicted tumour regression patterns are consistent with clinical observations. This simple yet flexible model shows how the local competition for chemical resources might impact local control rates under varying fractionation conditions.
Assuntos
Modelos Biológicos , Neoplasias/patologia , Neoplasias/radioterapia , Hipóxia Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Neoplasias/metabolismo , Oxigênio/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Single-access laparoscopic surgery is a recent vogue in the field of minimally invasive colorectal surgery. While selected series have indicated feasibility, we prospectively examined its usefulness for resectional surgery in routine practice. METHOD: All patients undergoing laparoscopic colorectal resection over a 12-month period were considered for a single-access approach by a single surgical team in a university hospital. This utilized a 'glove' port via a 3-5 cm periumbilical or stomal site incision, with standard rigid laparoscopic instruments then being used. RESULTS: Of 76 planned laparoscopic colorectal resections, 35 (47%) were performed by this single-incision laparoscopic modality without disruption of theatre list efficiency or surgical training obligations. The mean (range) age and body mass index of these 25 consecutive right-sided resections, eight total colectomies (seven urgent operations) and two anterior resections was 58 (22-82) years and 23.9 (18.6-36.2) kg/m(2) , respectively. The modal postoperative day of discharge was 4. For right-sided resections, the mean (range) postoperative stay in those undergoing surgery for benign disease was 4.0 days, while for those undergoing operation for neoplasia (n=18, mean age 71 years) it was 5.8 days and the average lymph node harvest was 13. Use of the glove port reduced trocar cost by 58% (60/£53) by allowing the use of trocar sleeves alone without obturators. CONCLUSION: Single-incision laparoscopic surgery is an effective option for abdominal surgery and seems especially suited for laparoscopic-assisted right-sided colonic resections. The glove port technique facilitates procedural frequency and familiarity and proves economically favourable.
Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Doenças Inflamatórias Intestinais/cirurgia , Laparoscopia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia/instrumentação , Luvas Cirúrgicas , Humanos , Laparoscopia/instrumentação , Pessoa de Meia-Idade , Assistência Perioperatória , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: Effective radiotherapy outcomes modeling could provide physicians with better understanding of the underlying disease mechanism, enabling to early predict outcomes and ultimately allowing for individualizing treatment for patients at high risk. This requires not only sophisticated statistical methods, but user-friendly visualization and data analysis tools. Unfortunately, few tools are available to support these requirements in radiotherapy community. METHODS: Our group has developed Matlab-based in-house software called DREES for statistical modeling of radiotherapy treatment outcomes. We have noticed that advanced machine learning techniques can be used as useful tools for analyzing and modeling the outcomes data. To this end, we have upgraded DREES such that it takes advantage of useful Statistics and Bioinformatics toolboxes in Matlab that provide robust statistical data modeling and analysis methods as well as user-friendly visualization and graphical interface. RESULTS: Newly added key features include variable selection, discriminant analysis and decision tree for classification, and k-means and hierarchical clustering functions. Also, existing graphical tools and statistical methods in DREES were replaced with a library of the Matlab toolboxes. We analyzed several radiotherapy outcomes datasets with our tools and showed that these can be effectively used for building normal tissue complication probability (NTCP) and tumor control probability (TCP) models. CONCLUSIONS: We have developed an integrated software tool for modeling and visualization of radiotherapy outcomes data within the Matlab programming environment. It is our expectation that this tool could help physicians and scientists better understand the complex mechanism of disease and identify clinical and biological factors related to outcomes.