• Perfusion Estimated with Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely with Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study.

      Donaldson, Stephanie B; Betts, Guy N J; Bonington, Suzanne C; Homer, Jarrod J; Slevin, Nicholas J; Kershaw, Lucy E; Valentine, Helen R; West, Catharine M L; Buckley, David L; School of Cancer and Enabling Sciences, University of Manchester, Manchester, United Kindom; North Western Medical Physics, The Christie, Manchester, United Kingdom. (2011-05-04)
      PURPOSE: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. RESULTS: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). CONCLUSIONS: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.
    • A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei.

      Farquharson, Adam L; Pranesh, Nagarajan; Witham, Gary; Swindell, Ric; Taylor, Malcolm B; Renehan, Andrew G; Rout, Shantanu; Wilson, Malcolm S; O'Dwyer, Sarah T; Saunders, Mark P; et al. (2008-08-19)
      Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m(-2) i.v. on day 1) and capecitabine (1250 mg m(-2) b.d. on days 1-14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.
    • Predictive factors for failure to identify sentinel nodes in head and neck squamous cell carcinoma.

      Hornstra, Marije T; Alkureishi, Lee W T; Ross, Gary L; Shoaib, Taimur; Soutar, David S; Plastic Surgery Unit, Canniesburn Hospital, Glasgow Royal Infirmary, Glasgow, United Kingdom. (2008-07)
      BACKGROUND: The aim of this study was to ascertain which factors determine success of sentinel node biopsy (SNB). METHODS: We conducted a retrospective review of 121 patients with head and neck squamous cell carcinoma undergoing SNB to stage the neck. All patients underwent the triple-diagnostic procedure of preoperative lymphoscintigraphy, intraoperative blue dye, and a gamma probe. Factors contributing to failure of SNB were identified. RESULTS: SNB was unsuccessful in 12 of 121 patients (10%). Seven of the 12 patients had cT1/cT2 tumors, and 6 of these were located in the floor of mouth. SN identification was more likely to be successful in patients with cN0 necks, but this did not reach statistical significance (92% vs 84%, p = .268). Factors associated with failure included T classification (p = .01), tumor site (p = .05), and negative preoperative lymphoscintigraphy (p = .0174). CONCLUSION: Successful sentinel lymph node harvest is related to primary tumor site, T classification, and the presence of nodes on preoperative lymphoscintigraphy.
    • Radiotherapy for the treatment of longstanding head and neck hemangioma.

      Douglas, Catriona Mairi; Ho, Kean F; Homer, Jarrod J; Slevin, Nicholas J; Department of Otolaryngology-Head and Neck Surgery, Christie Hospital, Manchester, UK. Catriona.douglas@christie.nhs.uk (2009-08)
    • Re: Squamous cell carcinoma of the oral tongue in patients younger than 30 years.

      Mani, Navin; Homer, Jarrod J; Department of Head and Neck Surgery, The Christie Hospital, Manchester, UK (2011-02)
    • Reciprocal relationship between expression of hypoxia inducible factor 1alpha (HIF-1alpha) and the pro-apoptotic protein bid in ex vivo colorectal cancer.

      Seenath, M M; Roberts, Darren L; Cawthorne, Christopher; Saunders, Mark P; Armstrong, G; O'Dwyer, Sarah T; Stratford, Ian J; Dive, Caroline; Renehan, Andrew G; Clinical and Experimental Pharmacology, Paterson Institute of Cancer Research, Manchester, UK. (2008-08-05)
      Hypoxia inducible factor 1 (HIF-1) represses the transcription of pro-apoptotic bid in colorectal cancer cells in vitro. To assess the clinical relevance of this observation, HIF-1alpha and Bid were assessed in serial sections of 39 human colorectal adenocarcinomas by immunohistochemistry. In high HIF-1alpha nuclear-positive cell subpopulations, there was a significant reduction in Bid expression (ANOVA, P=0.04). Given the role of Bid in drug-induced apoptosis, these data add impetus to strategies targeting HIF-1 for therapeutic gain.
    • Response and resistance to the endocrine prevention of breast cancer.

      Howell, Anthony; Bundred, Nigel J; Cuzick, Jack; Allred, D Craig; Clarke, Robert B; CRC Department Medical Oncology, University of Manchester Christie Hospital and Holt Radium Inst., Manchester, UK. (2008)
      The data from observational studies and clinical trials indicates that it is possible to prevent BC for prolonged periods using various endocrine manipulations. Ovarian suppression is thought to give lifelong protection and recent data indicate that the effectiveness of Tam continues after cessation of treatment at 5-8 years. It is clear from three randomised trials that SERMs prevent ERalpha+ tumors only in women at increased risk and at population risk of BC entered into these trials. The data from the Ral trials also suggests that this agent appears less effective than Tam in preventing DCIS. This is surprising since a large proportion of DCIS is ERalpha+. Equally surprising is the effectiveness of oophorectomy and Tam in mutation carriers, particularly BRCA1, which is associated with ERalpha+ tumors. The fact that ERT can be given without apparently abrogating the effect of oophorectomy and also to naturally postmenopausal women without increasing BC risk suggests that cyclical estrogen or estrogen + progestin are important for BC initiation and/or progression. The question arises whether the information we have concerning the responsiveness of ERalpha+ cells in TDLU, premalignant lesions, and invasive cancers give an indication of the targets for endocrine prevention. Data summarised in Table 1 indicate that TDLU are responsive to estrogen, ED, and SERMs/SERDs in premenopausal women and there may be the targets for the preventative effect of early oophorectomy particularly in BRCA1 carriers where we have demonstrated endocrine responsiveness of TDLU, which at this heterozygote stage are ERalpha+. The decline in numbers of atypical lobules in breasts without invasive cancer suggests that these are targets for the 'preventive' effect of the menopause, as suggested by Wellings. The data also suggest that ERalpha+ DCIS is responsive to estrogen and ED supporting premalignant lesions is a target as does the data from the NSABP P1 trial indicating a marked preventive effect of Tam in women previously diagnosed with atypical ductal hyperplasia and a preventative effect on CIS.
    • Scientific and clinical aspects of the use of cidofovir in recurrent respiratory papillomatosis.

      Donne, A J; Rothera, M P; Homer, Jarrod J; University Department of Otolaryngology and Head and Neck Surgery, Manchester Royal Infirmary, UK. ajdonne@doctors.org.uk (2008-07)
      OBJECTIVE: Cidofovir is the most contemporary adjuvant treatment for recurrent respiratory papillomatosis (RRP) and its use is increasing. Cidofovir is potentially harmful. Otolaryngologists should understand the science of cidofovir and review the current published data on the effects of this therapy. METHOD: Pubmed was searched using the terms cidofovir and papillomatosis. Comparisons were made between published articles. RESULTS: Thirteen articles were identified between 1998 and 2006, representing the treatment of 142 patients. Cidofovir did result in a significant improvement of papillomatous lesions in the majority (60%) of patients despite the use of different regimes of cidofovir administration. There was no unifying protocol in use. A partial response was demonstrated in 29% of patients. 7.5% had no response however, an additional 3.5% patients were lost to follow-up. No malignant change was reported. CONCLUSION: Cidofovir does appear to be effective in improving the outcome of patients with RRP. There are no reports of malignant transformation despite concerns raised by toxicology studies.
    • Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma.

      Stoeckli, Sandro J; Alkureishi, Lee W T; Ross, Gary L; Otorhinolaryngology, Head and Neck Surgery, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland. sandro.stoeckli@kssg.ch (2009-06)
      The appearance of lymph node metastases represents the most important adverse prognostic factor in head and neck squamous cell carcinoma. Therefore, accurate staging of the cervical nodes is crucial in these patients. The management of the clinically and radiologically negative neck in patients with early oral and oropharyngeal squamous cell carcinoma is still controversial, though most centers favor elective neck dissection for staging of the neck and removal of occult disease. As only approximately 30% of patients harbor occult disease in the neck, most of the patients have to undergo elective neck dissection with no benefit. The sentinel node biopsy concept has been adopted from the treatment of melanoma and breast cancer to early oral and oropharyngeal squamous cell carcinoma during the last decade with great success. Multiple validation studies in the context of elective neck dissections revealed sentinel node detection rates above 95% and negative predictive values for negative sentinel nodes of 95%. Sentinel node biopsy has proven its ability to select patients with occult lymphatic disease for elective neck dissection, and to spare the costs and morbidity to patients with negative necks. Many centers meanwhile have abandoned routine elective neck dissection and entered in observational trials. These trials so far were able to confirm the high accuracy of the validation trials with less than 5% of the patients with negative sentinel nodes developing lymph node metastases during observation. In conclusion, sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma can be considered as safe and accurate, with success rates in controlling the neck comparable to elective neck dissection. This concept has the potential to become the new standard of care in the near future.
    • Sequential treatment of giant basal cell carcinomas.

      Madan, Vishal; West, Chris A; Murphy, James V; Lear, John T; Central Manchester and Manchester Childrens' Hospital NHS Trust, Manchester, UK; The Dermatology Centre, Salford Royal NHS Foundation Trust, Salford, UK. (2008-06-19)
      Treatment of giant basal cell carcinomas (GBCC) can pose several challenges. In such instances, use of routine and recommended treatments for sporadic, average size basal cell carcinomas (BCC) is suboptimal, impractical and often leads to treatment failure. Surgical excision of such large lesions results in marked intra and postoperative morbidity. While individually, photodynamic therapy, topical imiquimod and surgical excision are all established treatments for BCC, their combined use in the treatment of GBCC has not been explored. Three patients with histologically proven GBCC were sequentially treated with three cycles of metvix photodynamic therapy followed by a 6-week course of topical imiquimod. This led to a reduction in the size of these lesions which were subsequently excised.
    • Shoulder morbidity after pectoralis major flap reconstruction for head and neck cancer.

      Merve, Ashriwad; Mitra, Indu; Swindell, Ric; Homer, Jarrod J; Department of Surgery, Christie Hospital, Manchester, United Kingdom. (2009-04-21)
      BACKGROUND.: The effect of pectoralis major flap (PMF) harvest on shoulder function, allowing for the effects of neck dissection, has not previously been objectively measured. METHODS.: Twenty-two patients who underwent PMF reconstruction were studied. The control group comprised 35 patients with neck dissection (without PMF). Neck dissections in both groups were classified into 3 grades; grade 1: no neck dissection/selective neck dissection; grade 2: modified radical neck dissection; grade 3: radical neck dissection/extended radical neck dissection. Objective shoulder assessments were carried out using Constant score. RESULTS.: Constant score deteriorated with grade of neck dissection (p < .005). The median Constant score for PMF group and neck dissection only group were 82 and 90, respectively (p = .40). Subgroup analysis within neck dissection grade did not show any significant difference, but the effect of PMF was noted to be greatest in grade 2 patients (p = .064). CONCLUSIONS.: There is minimal or low shoulder morbidity, additional to neck dissection, caused by PMF reconstruction in head and neck surgery. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.
    • Skin-sparing mastectomy.

      Baildam, Andrew D; The Christie Hospital Cancer Centre, Manchester, United Kingdom. (2011-09)
    • The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis.

      Gee, H E; Buffa, F M; Camps, C; Ramachandran, A; Leek, R; Taylor, M; Patil, M; Sheldon, H; Betts, Guy N J; Homer, J; et al. (2011-03-29)
      To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer.
    • A study to explore the patient's experience of peritoneal surface malignancies: pseudomyxoma peritonei.

      Witham, Gary; Willard, Carole; Ryan-Woolley, Bernadette; O'Dwyer, Sarah T; Peritoneal Tumour Service, Christie Hospital NHS Foundation Trust, Withington, Manchester M20 4BX, UK. G.Witham@mmu.ac.uk (2008-04)
      Pseudomyxoma peritonei (PMP) is a rare tumour originating from the appendix and producing extensive mucus accumulation within the abdomen and pelvis. Since UK government policy reinforces the importance of involving patients in the delivery of healthcare, it is essential to explore patients views so that service development can be fully responsive to the patients need. The primary objective of this study was to explore the impact of PMP on the lives of patients. The secondary objectives were to explore the sources of psychological support for patients, the symptoms experienced and their information concerns. In-depth interviews were conducted with a purposive sample of 13 patients. The interviews were tape recorded, with permission, transcribed in full and analysed for content and emerging themes. The emergent themes included significant uncertainty about the diagnosis and treatment of this rare condition. The difficulties associated with confirming an initial diagnosis and living with an uncertain prognosis were highlighted. Patients' choice and access to support by a specialist team were important themes. The data highlighted the particular needs of this under-researched patient group and provided evidence to further develop patient support, particularly using the Internet.
    • Supraorbital neuroma masquerading as local recurrence from a previously excised microcystic adnexal carcinoma.

      Seaward, J R; Kalipershad, Sujala N R; Ross, Gary L; Department of Plastic Surgery, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. jpras@jseaward.com (2010-03)
      We present a case of a 53 year old gentleman with a previous history of a microcystic adnexal carcinoma in the supraorbital region who represented with pain and tenderness 3 years postoperatively. Although this was thought to represent local recurrence, it proved to be a supraorbital neuroma.
    • Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

      Jegannathen, Apurna; Mais, Kathleen L; Sykes, Andrew J; Lee, Lip W; Yap, Beng K; Birzgalis, Andrew R; Homer, Jarrod J; Ryder, W David J; Slevin, Nicholas J; Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, UK. (2011-03)
      To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
    • Systematic reviews and meta-analyses in coloproctology: interpretation and potential pitfalls.

      Wille-Jørgensen, P; Renehan, Andrew G; Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. pwj01@bbh.regionh.dk (2008-01)
      A systematic review (SR) is the unbiased appraisal of systematically identified relevant studies. Implicit in its definition is a robust and scientifically valid process, and when performed as such, SR is an important clinical research tool and influence in health policy decision-making. This educational paper outlines that, from the original prototype based on randomized trials, there are now many other types of SRs including those based on: nonrandomized comparative studies, observational studies, prognostic studies, and studies of diagnostic and screening tools. While each of these has a similar 'anatomy' or format, at an individual class level, there are principles specific to each SR type. Several examples from the coloproctology literature are used as case-studies to illustrate potential pitfalls, and upon re-analysis, often reverse or attenuate the conclusions stated in the original publication. These examples serve to emphasize the need for health professionals to understand the process of SR and meta-analysis so that we all arrive at appropriate interpretations to the benefit of our patients.
    • Technical aspects of cytoreductive surgery.

      Kusamura, Shigeki; O'Dwyer, Sarah T; Baratti, Dario; Younan, Rami; Deraco, Marcello; Department of Surgery, National Cancer Institute of Milan, Milan, Italy. (2008-09-15)
      At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Five conflicting points were discussed: radicality of the peritonectomy procedure, cytoreduction of neoplastic nodules <2.5 mm, the timing of bowel anastomoses in relation to hyperthermic intraperitoneal chemotherapy (HIPEC) and indications of protective ostomies. According to the panel of experts a partial parietal peritonectomy restricted to the macroscopically involved regions could be indicated in all listed clinical conditions with the exception of peritoneal mesothelioma. No expert was of the opinion that a radical parietal peritonectomy is advisable irrespective of the disease being treated. All the experts agreed that electrovaporization of small (<2.5 mm) non-infiltrating metastatic nodules in the mesentery would be appropriate, even if theoretically the HIPEC affords microscopic cytoreduction. The panel also agreed that in the closed technique for HIPEC administration the intestinal anastomoses should be fashioned after completion of the perfusion. Finally when considering the place for protective ostomies the experts voted for a flexible approach allowing the surgeon to exercise discretion for individual patients.
    • A ten-year experience of multiple flaps in head and neck surgery: how successful are they?

      Ross, Gary L; Ang, Erik S W; Lannon, Declan; Addison, Patrick; Golger, Alex; Novak, Christine B; Lipa, Joan E; Gullane, Patrick J; Neligan, Peter C; Division of Plastic Surgery, Christie Hospital, Manchester, United Kingdom. (2008-04)
      Ablative surgery in the head and neck often results in defects that require free flap reconstruction. With improved ablation/reconstructive and adjuvant techniques, improved survival has led to an increase in the number of patients undergoing multiple free flap reconstruction. We retrospectively analyzed a single institution's 10-year experience (August 1993 to August 2003) in free flap reconstruction for malignant tumors of the head and neck. Five hundred eighty-two flaps in 534 patients were identified with full details regarding ablation and reconstruction with a minimum of 6-month follow-up. Of these 584 flaps, 506 were for primary reconstruction, 50 for secondary reconstruction, 12 for tertiary reconstruction, and 8 patients underwent two flaps simultaneously for extensive defects. Overall flap success was 550/584 (94%). For primary free flap surgery, success was 481/506 (95%), compared with 44/50 (88%) for a second free flap reconstruction and 9/12 (75%) for a third free flap reconstruction ( P < 0.05). Eight extensive defects were reconstructed with 16 flaps, all of which were successful. More than one free flap may be required for reconstruction of head and neck defects, although success decreases as the number of reconstructive procedures increases.
    • The use of a combined radial forearm flap and radial fascial flap for layered dural lining and an orbital defect reconstruction.

      Bondin, D; Ross, Gary L; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, UK. (2011-07)
      Variable reconstruction methods for craniofacial tumour resections have been devised with the primary purpose to improve quality of life and disease control. The reconstructive aims are to provide a watertight seal, cranial base support while allowing a cosmetically pleasing result. For defects involving the orbit, maintenance of the depth of the orbital socket remains important for prosthetic fitting and a bulky flap is not advisable for this purpose. This case demonstrates the use of a combination pericranial flap, radial forearm fascial flap and cutaneous radial forearm flap. We have been able to achieve a watertight seal of dura in multiple layers, provide adequate support to the cranial base while giving a non bulky reconstruction of the orbit.