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Joe Rahamim

Bio: Joe Rahamim is an academic researcher from Derriford Hospital. The author has contributed to research in topics: Pleurodesis & Docetaxel. The author has an hindex of 5, co-authored 6 publications receiving 115 citations.

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Journal ArticleDOI
TL;DR: Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.
Abstract: Background: NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods: The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Results: There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion: Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

37 citations

Journal ArticleDOI
TL;DR: VATS data confirm the utility and safety of VATS in the right context but also suggest the potential diagnostic utility of VATs empyema fluid culture.
Abstract: INTRODUCTION Video-assiste dt horacoscopic surgery (VAT S) is the gold standard investigation for diagnosis of pleural exudates. It is invasive and it is important to ensure that it is performed to acceptable national standards. We assumed that VATS empyema fluid culture would not contribute further to microbiological diagnosis in referred culture-negative empyemas. PATIENTS AND METHODS Eighty-six consecutive external referrals for VATS for diagnosis of ac ytology-negative pleural exudate (or for further management of the exudate) were studied retrospectively .D iagnostic yield, pleurodesis efficacy and complications were compared to national standards and good practice recommendations. VATS empyema fluid microbiological culture results were compared to pre-VAT Se mpyema fluid culture results. RESULTS VATS was performed well within national standards with ad iagnostic yield of 82.3% for cytology-negative exudates, 100% pleurodesis efficacy ,5 .8% postoperative fever ,w ith only one significant complication (1.2% rate) and no deaths. Compliance with good practice pleural fluid documentation points was greater than 70%. VATS empyema fluid culture positivity (84.6%) was significantly higher than pre-VAT Sf luid culture (35%). CONCLUSIONS VATS was performed to acceptable standards. These data confirm the utility and safety of VATS in the right context but also suggest the potential diagnostic utility of VATS empyema fluid culture. Further studies are required to investigate this latter possibility further.

31 citations

Journal ArticleDOI
TL;DR: The use of ambulatory pleural catheters for managing malignant pleural effusion is a safe and effective strategy and should be considered the first choice option for patients with trapped lung or failed previous pleurodesis.
Abstract: Malignant pleural effusions are common and can be difficult to manage. We have reviewed our use of ambulatory drains (Pleurex drains) in this regard with particular reference to hospital stay, duration of drainage, and incidence of complications. Of 125 patients with malignant pleural effusion with trapped lung or failed previous pleurodesis who underwent insertion of ambulatory pleural drain, 41 patients were under local anesthesia and 84 patients were under general anesthesia. Mean age was 66.5 years with male:female = 80:45. Data were collected retrospectively from the clinical notes, and the family doctors’ clinics were contacted to enquire about the patients’ survival. When data collection concluded, 48 patients (38.4%) had died, giving mean survival following drain insertion of 84.1 days. There were no in-hospital deaths related to the procedure. One procedure was converted to a mini-thoracotomy to control bleeding from a lung tear. Mean duration of catheter placement was 87.01 days (5–434). Video-assisted thoracoscopic surgery was used in 77 patients (61.6%), and Seldinger’s technique was used in 48 patients (38.4%). Mesothelioma was the most common malignant cause. Minor complications were encountered in 15 patients (12%), and they were managed as outpatients. The use of ambulatory pleural catheters for managing malignant pleural effusion is a safe and effective strategy. It has only minor complications that are related to prolonged drainage. We feel that this strategy should be considered the first choice option for these patients.

26 citations

Journal ArticleDOI
PM Murphy, P Modi1, Joe Rahamim1, Tim Wheatley1, Stephen Lewis 
TL;DR: The nutritional management of patients following surgery for upper gastrointestinal carcinoma is not uniform with practice varying considerably between centres, and those centres with a dedicated dietitian are more likely to assess patients' nutritional status and provide nutritional support.
Abstract: INTRODUCTION Patients with oesophageal carcinoma are at high risk of malnutrition. The aim of this study was to assess current practice for the nutritional management of patients following surgery for oesophageal carcinoma. PATIENTS AND METHODS A postal questionnaire was sent to 82 dietetic departments of those hospitals in England identified as major centres for upper gastrointestinal surgery. RESULTS Of the 66 (80%) responses received, 22 (33%) centres routinely perform pre-operative nutritional screening/assessment on oesophageal carcinoma patients. Centres with dietetic support dedicated to these patients are more likely to perform a pre-operative nutritional assessment (n = 17; 55%) than those without (n = 5; 14%; P < 0.001; χ 2 = 12.17). Pre-operative nutritional support is routinely provided in only 11 (17%) centres with the majority of centres (n = 50; 75%), providing it if patients are considered malnourished only. A total of 47 (70%) centres routinely provide postoperative nutritional support with jejunal feeding being the most commonly chosen route. Dedicated dietetic support is provided at 31 (47%) centres. Those centres with a dedicated dietitian are more likely to provide early postoperative nutritional support (n = 27; 87%) than those without (n = 20; 57%; P = 0.007; χ 2 = 7.195) and more likely to review patients routinely following discharge from hospital (n = 25 [81%] with a dietitian versus n = 17 [49%] without; P = 0.007; χ 2 = 7.2). CONCLUSIONS The nutritional management of patients following surgery for upper gastrointestinal carcinoma is not uniform with practice varying considerably between centres. Those centres with a dedicated dietitian are more likely to assess patients’ nutritional status and provide nutritional support.

19 citations

Journal ArticleDOI
TL;DR: A 52-year-old woman large cell neuroendocrine carcinoma patient with progressive stage IV disease in the chest, liver, adrenal glands and, particularly, the brain, who achieved a marked response to a fourth-line combination of docetaxel, cisplatin and temozolomide is reported.
Abstract: At present, there is no clear consensus on the most appropriate treatment approach for large cell neuroendocrine carcinoma of the lung Large cell neuroendocrine carcinoma lesions differ from other nonsmall cell lung carcinomas in that they have a particularly aggressive clinical behaviour and extremely poor prognosis We report a 52-year-old woman large cell neuroendocrine carcinoma patient with progressive stage IV disease in the chest, liver, adrenal glands and, particularly, the brain, who achieved a marked response to a fourth-line combination of docetaxel, cisplatin and temozolomide This regimen significantly improved her quality of life and survival The good response obtained in this heavily pretreated patient adds to the evidence regarding the use of temozolomide in patients with lung cancer with brain metastases

6 citations


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Journal ArticleDOI
TL;DR: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.
Abstract: Background: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence-based recommendation...

258 citations

Journal ArticleDOI
TL;DR: Based on low-quality evidence in the form of case series, the TIPC may improve symptoms for patients with MPE and does not appear to be associated with major complications.
Abstract: Background Malignant pleural effusions (MPE) are a frequent cause of dyspnea and discomfort at the end of cancer patients' lives. The tunneled indwelling pleural catheter (TIPC) was approved by the FDA in 1997 and has been investigated as a treatment for MPE.

254 citations

Journal ArticleDOI
TL;DR: The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to ‘molecular chess’, and it is becoming clear that personalised strategies are required to obtain best results.
Abstract: The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients. The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to ‘molecular chess’. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

209 citations

Journal ArticleDOI
TL;DR: The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE and the LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication.
Abstract: Malignant pleural effusions (MPE) are a common pathology, treated by respiratory physicians and thoracic surgeons alike. In recent years, several well-designed randomised clinical trials have been published that have changed the landscape of MPE management. The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in the management of MPE with the aim of producing a comprehensive review of the scientific literature.Six areas of interest were identified, including the optimum management of symptomatic MPE, management of trapped lung in MPE, management of loculated MPE, prognostic factors in MPE, whether there is a role for oncological therapies prior to intervention for MPE and whether a histological diagnosis is always required in MPE.The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE. There was limited evidence regarding the management of trapped lung or loculated MPE. The LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication. There was no evidence to support the use of oncological therapies as an alternative to MPE drainage, and the literature supported the use of tissue biopsy as the gold standard for diagnosis and treatment planning.

188 citations

Journal ArticleDOI
TL;DR: Postoperative outcomes were studied in relation to adverse nutritional risk, advanced age and co‐morbidity in patients undergoing colorectal resection within an enhanced recovery after surgery programme.
Abstract: BACKGROUND: Postoperative outcomes were studied in relation to adverse nutritional risk (body mass index (BMI) below 20 kg/m(2)), advanced age (80 years or more) and co-morbidity (American Society of Anesthesiologists (ASA) grade III-IV) in patients undergoing colorectal resection within an enhanced recovery after surgery programme. METHODS: Outcomes were audited prospectively in 1035 patients. Morbidity and mortality were compared with those predicted using the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, and a multivariable model was used to determine independent predictors of outcome. RESULTS: Postoperative morbidity was lower than predicted (observed to expected 0.68; P < 0.001). Independent predictors of delayed mobilization were ASA III-IV (P < 0.001) and advanced age (P = 0.025). Prolonged hospital stay was related to advanced age (P = 0.002), ASA III-IV (P < 0.001), male sex (P = 0.037) and rectal surgery (P < 0.001). Morbidity was related to ASA III-IV (P = 0.004), male sex (P = 0.023) and rectal surgery (P = 0.002). None of the factors predicted 30-day mortality. CONCLUSION: Age and nutritional status were not independent determinants of morbidity or mortality. Pre-existing co-morbidity was an independent predictor of several outcomes.

168 citations