• 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.
    • The management of vulval cancer.

      Crosbie, Emma J; Slade, Richard J; Ahmed, Ahmed S; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, United Kingdom. Emma.Crosbie@Manchester.ac.uk (2009-11)
      Referral of women with vulval carcinoma to tertiary centres is now established practise in the UK. The centralisation of care for these women promotes the development of specialist teams of gynaecological oncologists, clinical oncologists, pathologists and clinical nurse specialists with expertise in the management of this relatively rare tumour. The primary care physician plays an essential role in the early detection and subsequent urgent referral of women with suspicious vulval lesions. Improved education and awareness campaigns may encourage women to report vulval symptoms early. Where vulval carcinoma is diagnosed at an early stage, surgical excision is likely to be curative. There is, however, a move away from radical surgery for all patients irrespective of stage of disease towards an individualised approach, which takes into account the size and position of the tumour. The challenge is to reduce morbidity associated with treatment without compromising on cure rates. Restricting groin lymphadenectomy to women with lymph node metastases may be possible with the advent of sentinel node technology and it is anticipated that expertise in this area will show significant advances over the coming years. There is still a place for radical surgery, often in combination with other treatment modalities, in the management of advanced or recurrent disease. This article will review the evidence for the current management of vulval carcinoma.
    • Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity.

      Harriss, D J; Atkinson, G; Batterham, A; George, K; Cable, N Tim; Reilly, Thomas; Haboubi, Najib; Renehan, Andrew G; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK. (2009-09)
      OBJECTIVE: Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta-analysis of prospective observational studies to quantify gender-specific risk associated with increased leisure-time physical activity (LT-PA). METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. We used random-effects meta-analyses to estimate summary risk ratios (RR) and 95% confidence intervals (95% CI) for uppermost vs lowermost categories of physical activity. To investigate dose-response, we explored risks ratios as a function of cumulative percentiles of physical activity distribution. RESULTS: Fifteen datasets from 14 articles, including 7873 incident cases, were identified. For colon cancer, there were inverse associations with LT-PA for men (RR: 0.80; 95% CI: 0.67-0.96) and women (0.86; 0.76-0.98). LT-PA did not influence risk of rectal cancer. The dose-response analysis was consistent with linear pattern reductions in risk of colon cancer in both genders. There was evidence of moderate between-study heterogeneity but summary estimates were broadly consistent across potential confounding factors. CONCLUSION: Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.
    • Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index.

      Harriss, D J; Atkinson, G; George, K; Cable, N Tim; Reilly, Thomas; Haboubi, Najib; Zwahlen, Marcel; Egger, Matthias; Renehan, Andrew G; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Henry Cotton Campus, Liverpool, UK. (2009-07)
      OBJECTIVE: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics. METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI. RESULTS: We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations. CONCLUSION: Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.
    • Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

      Atula, T; Hunter, K D; Cooper, L A; Shoaib, T; Ross, Gary L; Soutar, D S; Canniesburn Plastic Surgery Unit, Jubilee Building, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, United Kingdom. timo.atula@hus.fi (2009-05)
      BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.
    • 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.
    • 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)
    • 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.
    • What does failure after surgery or radiation mean?

      Clarke, Noel W; Christie and Salford Royal Hospitals, Manchester, UK (2008)
    • 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.
    • 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.
    • 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.
    • Aggressive angiomyxoma of the vulva and perineum: a case report.

      Umeadi, Uchenna P; Ahmed, Ahmed S; Winter-Roach, Brett; Murphy, James V; Shenjere, Patrick; Slade, Richard J; Christie Hospital NHS Foundation Trust, Manchester, UK. ucheup@hotmail.com (2008-10)
    • Acromegaly, growth hormone and cancer risk.

      Renehan, Andrew G; Brennan, Bernadette M; School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. arenehan@picr.man.ac.uk (2008-08)
      Acromegaly is an endocrine disorder characterized by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor I (IGF-I) associated with premature mortality from cardiopulmonary diseases and certain malignancies. In particular, there is a two-fold increased risk of developing colorectal cancer. Possible mechanisms underlying this association include elevated levels of circulating GH and IGF-I, but several other plausible processes may be relevant. In a parallel literature, there has been debate whether GH replacement therapy is associated with increased cancer risk in three scenarios: (1) tumour recurrence in children with previously treated cancer; (2) second neoplasms (SNs) in survivors of childhood cancer treated with GH; and (3) de-novo cancer in non-cancer patients treated with GH. The general evidence suggests no increased risk in scenario 1. Through a maze of complex study designs, there is inconclusive evidence of a very modest increase in cancer risk in treated GH-deficiency patients in scenarios 2 and 3, but it is likely that the cumulative risk equates to that of the general population. This emphasizes the need for patient selection balanced against the known morbidity of untreated GH deficiency.
    • Meta-analysis in medical research: potentials and limitations.

      Zwahlen, Marcel; Renehan, Andrew G; Egger, Matthias; Department of Social and Preventive Medicine, University of Berne, Berne, Switzerland. zwahlen@ispm.unibe.ch (2009-05-12)
      Meta-analysis, the statistical combination of results from several studies to produce a single estimate of a treatment effect or size of an association, continues to attract controversy. We illustrate and discuss the promises and limitations of meta-analysis. Meta-analysis of clinical trials can prevent delays in the introduction of effective treatments or lead to the timely identification of adverse effects. However, meta-analyses are liable to numerous biases, both at the level of the individual study and the selection of studies for inclusion in meta-analysis. The biases and confounding factors that threaten the validity of individual studies will also affect meta-analyses of observational studies. We argue that meta-analyses should only be performed within the framework of systematic reviews that have been prepared using methods that minimize bias and address the combinability of studies.
    • 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.
    • Oncoplastic surgery for breast cancer.

      Baildam, Andrew D; University Hospital of South Manchester Foundation Trust and the Christie Hospital, Manchester M20 4BX, UK. aetab2@btinternet.com (2008-01)
    • 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.
    • The impact of radiotherapy on swallowing and speech in patients who undergo total laryngectomy.

      De Casso, Carmen; Slevin, Nicholas J; Homer, Jarrod J; University Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary, Manchester, UK. cdecasso@doctors.org.uk (2008-12)
      OBJECTIVES: Quality of life studies have shown no detrimental effect with radiotherapy (RT) in patients who have a total laryngectomy. We wished to determine the effect of RT (initial or postoperative) specifically on the swallowing and voice function in patients treated by total laryngectomy (TL) for carcinoma of the larynx. DESIGN: Multicenter chart review. SETTING: Multicenter study in the Greater Manchester and Lancashire area. PARTICIPANTS: A total of 121 postlaryngectomy patients all of whom had completed definitive treatment at least 6 months before this study. Twenty-six patients had total laryngectomy as a single modality treatment and 95 had total laryngectomy and radiotherapy. MAIN OUTCOME MEASURES: Swallowing (solid food, soft diet or fluid/PEG) and voice development. RESULTS: Swallowing was better in the group who had no radiotherapy (P = 0.0037). There was no difference in voice function between the two groups. We also demonstrated that females had a worse swallowing outcome (P = 0.0101), as did advanced nodal stage (P = 0.001). CONCLUSIONS: RT adversely affects the swallowing results but not the speech results after TL when given either as initial treatment or postoperatively. This should be kept in mind in the decision-making process in the treatment of patients with carcinoma of the larynx.
    • 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.