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Nonaka D.,Christie Hospital | Nonaka D.,University of Manchester | Rosai J.,Centro Diagnostico Italiano | Rosai J.,LabCorp
American Journal of Surgical Pathology | Year: 2012

Thirteen cases of type A thymoma are reported showing the characteristic architectural attributes of this tumor type (World Health Organization), such as lobulation, perivascular spaces, gland-like formations, and cystic changes, but also displaying atypical features, as defined by increased mitotic activity, mild to moderate nuclear atypia, and/or scattered small foci of necrosis. The tumors were similar to type B3 thymomas in many respects, except for the fact that the tumor cells were spindled instead of round/polygonal. The existence of these cases suggests the desirability of an expansion of the type A thymoma category, analogous to that currently used for type B tumors. The various nomenclature options that could be used to name these tumors have been discussed. © 2012 by Lippincott Williams & Wilkins.


Cunningham D.,Royal Marsden Hospital | Lang I.,National Institute of Oncology | Marcuello E.,Hospital de Sant Pau de Barcelona | Lorusso V.,Italian National Cancer Institute | And 7 more authors.
The Lancet Oncology | Year: 2013

Background: Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer. Methods: For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m2 orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939. Findings: From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]). Interpretation: The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. Funding: F Hoffmann-La Roche. © 2013 Elsevier Ltd.


Nonaka D.,Christie Hospital | Nonaka D.,University of Manchester | Bishop P.W.,Wythenshawe Hospital
American Journal of Surgical Pathology | Year: 2014

A group of tumors referred to as atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) predominantly occur in sun-damaged skin of the elderly, particularly in the head and neck region. Although this group of tumors is often regarded as of mesenchymal phenotype, the matter of histogenesis has not been entirely resolved. Evans H and Smith JL reported in 1980 that prognosis was not significantly different irrespective of whether there was a definite squamous cell carcinoma component or not, supporting a view that these are all carcinomata in nature (sarcomatoid carcinoma [SC]). There are a number of clinicopathologic studies of AFX in the literature but information on morphologically similar sarcoma-like tumors with immunohistochemical evidence of epithelial differentiation is sparse. One hundred sarcoma-like tumors (SLTs) of head and neck skin of the elderly, treated by surgical excision, were studied. Clinical information was obtained, and pathology reports and hematoxylin and eosin sections were reviewed to document size (maximum dimension), extent of invasion, mitotic count, vascular and perineural invasion, margin status, ulceration, necrosis, and the presence of actinic keratosis in adjacent/overlying skin. Immunostains examined included: pan-cytokeratins (CKs) (AE1/AE3, MNF116), high-molecular weight CKs (34βE12, CK5/6, CK14), p63, and melanocytic (S100, Melan A, HMB-45, MITF), vascular (CD31, CD34), and muscle markers (SMA, desmin, h-caldesmon) to exclude melanoma and definite sarcoma entities. The tumors were divided into AFX/PDS (G1), the SC group, which was subdivided into SLT with only p63 positivity (G2a) and SLT with CK positivity regardless of p63 status (G2b), and SLT with a minor morphologic squamous cell carcinoma component (G3). Clinicopathologic findings of each group were compared, in relation to outcomes. Age at diagnosis ranged from 51 to 96 years (median, 79 y), with M:F=11.5:1. There were 53 tumors in G1 (19AFX, 34PDS), 37 in G2 (25 in G2a, 12 in G2b), and 10 in G3. There was no statistically significant difference in clinical and pathologic parameters or survival among all 3 groups. CKs and p63 expression, size, extent of invasion, vascular invasion, perineural invasion, mitotic count, and ulcer did not affect outcome, whereas margin status and necrosis did by both univariate and multivariate analysis and by only univariate analysis, respectively. Sixty patients had multiple nonmelanomatous skin cancers. Actinic keratosis was observed in overlying/adjacent epidermis in 51 cases. Eight patients had prior radiotherapy to head skin cancers; 1 patient developed 2 separate tumors (G1 and G3) after radiotherapy. Four patients died of tumor (1 G1, 2 G2b, and 1 G3); of these, 3 cases had positive margin, and 1 had narrow margin. Our results have shown similarities of various clinicopathologic parameters between AFX/PDS and SC, raising the possibility that both entities are related, and some of the former entities may represent complete dedifferentiation (complete loss of epithelial phenotype) with a gain of mesenchymal phenotype. In addition, the difference between AFX and PDS appears to be the extent of invasiveness (stage) rather than a different histogenesis. Further investigations are needed. However, from a practical point of view, efforts should be made to excise this group of tumors with clear margins, as margin status appears to be the most important prognostic factor regardless of the presence or absence of epithelial differentiation. Copyright © 2014 by Lippincott Williams & Wilkins.


Iavazzo C.,Christie Hospital | Gkegkes I.D.,General Hospital of Attica KAT
Archives of Gynecology and Obstetrics | Year: 2016

Objective: Robotic hysterectomy is an alternative approach to the management of female genital tract pathology. Methods: A systematic literature review was performed to evaluate the till now available literature evidence on robotic assisted hysterectomy in obese and morbidly obese patients. Results: In total, robotic assisted hysterectomy was performed on 2769 patients. The most frequent indication for robotic hysterectomy was endometrial carcinoma (1832 out of 2769 patients, 66.2 %). Hypertension, diabetes mellitus, obstructive sleep apnea, chronic obstructive pulmonary disease and venous thromboembolism were the most common comorbidities reported. The conversion rate to laparotomy was 92 out of 2226 patients (4.1 %). The most frequent intraoperative complications for robotic hysterectomy were gastrointestinal injury (17 out of 2769 patients, 0.6 %), haemorrhage (five out of 2769 patients, 0.2 %) and bladder injury (five out of 2769 patients, 0.2 %). Wound infections/dehiscence (66 out of 2769 patients, 2.4 %), fever (56 out of 2769 patients, 2 %), pulmonary complications (55 out of 2769 patients, 1.9 %), urogenital complications (36 out of 2769 patients, 1.3 %) and postoperative ileus (28 out of 2769 patients, 1 %) were the most common postoperative complications. Death was reported in three out of 2769 patients (0.1 %). The ICU admitted patients were eight of 2226 patients (0.4 %). Conclusion: The robotic technique, especially in obese, can optimize the surgical approach and recovery of such patients with equally if not better outcomes compared to open and/or laparoscopic techniques. © 2016, Springer-Verlag Berlin Heidelberg.


O'Connor J.P.B.,University of Manchester | Jackson A.,University of Manchester | Parker G.J.M.,University of Manchester | Roberts C.,University of Manchester | Jayson G.C.,Christie Hospital
Nature Reviews Clinical Oncology | Year: 2012

About 100 early-phase clinical trials and investigator-led studies of targeted antivascular therapies-both anti-angiogenic and vascular-targeting agents-have reported data derived from T1-weighted dynamic contrast-enhanced (DCE)-MRI. However, the role of DCE-MRI for decision making during the drug-development process remains controversial. Despite well-documented guidelines on image acquisition and analysis, several key questions concerning the role of this technique in early-phase trial design remain unanswered. This Review describes studies of single-agent antivascular therapies, in which DCE-MRI parameters are incorporated as pharmacodynamic biomarkers. We discuss whether these parameters, such as volume transfer constant (K trans), are reproducible and reliable biomarkers of both drug efficacy and proof of concept, and whether they assist in dose selection and drug scheduling for subsequent phase II trials. Emerging evidence indicates that multiparametric analysis of DCE-MRI data offers greater insight into the mechanism of drug action than studies measuring a single parameter, such as K trans. We also provide an overview of current data and appraise the future directions of this technique in oncology trials. Finally, major hurdles in imaging biomarker development, validation and qualification that hinder a wide application of DCE-MRI techniques in clinical trials are addressed. © 2012 Macmillan Publishers Limited. All rights reserved.

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