Diagnosis and treatment of recurrent laryngeal cancer following initial nonsurgical therapy

Surgery is the preferred modality for curative treatment of recurrent laryngeal cancer after failure of nonsurgical treatments. Patients with initial early-stage cancer experiencing recurrence following radiotherapy often have more advanced-stage tumors by the time the recurrence is recognized. About one third of such recurrent cancers are suitable for conservation surgery. Endoscopic resection with the CO(2) laser or open partial laryngectomy (partial vertical, supracricoid, or supraglottic laryngectomies) have been used. The outcomes of conservation surgery appear better than those after total laryngectomy, because of selection bias. Transoral laser surgery is currently used more frequently than open partial laryngectomy for treatment of early-stage recurrence, with outcomes equivalent to open surgery but with less associated morbidity. Laser surgery has also been employed for selective cases of advanced recurrent disease, but patient selection and expertise are required for application of this modality to rT3 tumors. In general, conservation laryngeal surgery is a safe and effective treatment for localized recurrences after radiotherapy for early-stage glottic cancer. Recurrent advanced-stage cancers should generally be treated by total laryngectomy.

Consensus statement for inert gas washout measurement using multiple- and single- breath tests

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

A nurse is a nurse? A systematic review of the effectiveness of specialised nursing in breast cancer

The effectiveness of specialised nursing in breast cancer has received limited attention. This systematic literature review aims at (i) presenting and discussing role models of specialised nursing in the area of breast cancer and (ii) suggesting avenues for future research in this field. The ten studies included in the review differ with respect to the roles of specialised nurses as well as the measured outcome variables; thus, the comparability and generalisability of results are limited. Nevertheless, the review indicates that specialised nursing in breast cancer may contribute to improved physical and psycho-social well-being. In view of the limited comparability, the authors call for (i) a more uniform definition of models of specialised nursing in breast cancer care, as well as (ii) rigorous confirmatory studies to evaluate their effectiveness. These two aspects are pivotal in providing a reliable basis for future health care strategies.

Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93

Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS).

Controversies of adjuvant endocrine treatment for breast cancer and recommendations of the 2007 St Gallen conference

Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer.

The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer

PURPOSE: To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT). PATIENTS AND METHODS: Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT. RESULTS: No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LRF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P = .0010); among postmenopausal patients, LRF risk was decreased by 46% (P < .0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P < .0001). CONCLUSION: Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases.

Procalcitonin and brain natriuretic peptide as parameters in the postoperative course of patients with major pulmonary resection

Postoperative infections and cardiac events are the major morbidity factors after thoracic surgery and dominating causes of death. Therefore, a sensitive blood marker is needed for an early diagnosis of complications. Twenty-two patients admitted with lung cancer were enrolled in this study. Procalcitonin, brain natriuretic peptide, C-reactive peptide and interleukin-6 levels were recorded preoperatively and postoperatively on days 1-5. Laboratory values of patients with cardiac or infectious complications were compared to patients without complications. During postoperative course procalcitonin and brain natriuretic peptide levels elevated in all patients, but both had higher peak levels in patients with infectious or cardiac complication than without these complications. Interleukin-6 levels were increased on day one and showed a slower decrease in case of complications than without complications. In general, brain natriuretic peptide and procalcitonin levels are increased in the postoperative course after major pulmonary resection, but cardiac and infectious complications are associated with higher levels and a slower decrease than without complications. Interleukin-6 levels showed a slower decrease in patients with complications in the postoperative course than without complications. So the combination of procalcitonin, brain natriuretic peptide, and interleukin-6 seems to be useful for an optimized postoperative monitoring.

GPR87 is an overexpressed G-protein coupled receptor in squamous cell carcinoma of the lung

Lung cancer is the leading cause of cancer death worldwide. The overall 5-year survival after therapy is about 16% and there is a clear need for better treatment options, such as therapies targeting specific molecular structures. G-protein coupled receptors (GPCRs), as the largest family of cell surface receptors, represent an important group of potential targets for diagnostics and therapy. We therefore used laser capture microdissection and GPCR-focused Affymetrix microarrays to examine the expression of 929 GPCR transcripts in tissue samples of 10 patients with squamous cell carcinoma and 7 with adenocarcinoma in order to identify novel targets in non-small cell lung carcinoma (NSCLC). The relative gene expression levels were calculated in tumour samples compared to samples of the neighbouring alveolar tissue in every patient. Based on this unique study design, we identified 5 significantly overexpressed GPCRs in squamous cell carcinoma, in the following decreasing order of expression: GPR87 > CMKOR1 > FZD10 > LGR4 > P2RY11. All are non-olfactory and GRAFS (glutamate, rhodopsin, adhesion, frizzled/taste2, secretin family) classified. GPR87, LGR4 and CMKOR1 are orphan receptors. GPR87 stands out as a candidate for further target validation due to its marked overexpression and correlation on a mutation-based level to squamous cell carcinoma.

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.

Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences of breast cancer

BACKGROUND: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. METHODS: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. RESULTS: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. CONCLUSION: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

Narrow band imaging (NBI) during medical thoracoscopy: first impressions

Background This is the first ever evaluation of narrow band imaging (NBI), an innovative endoscopic imaging procedure, for the visualisation of pleural processes. Methods The pleural cavity was examined in 26 patients with pleural effusions using both white light and narrow band imaging during thoracoscopy under local anaesthesia. Results In the great majority of the patients narrow band imaging depicted the blood vessels more clearly than white light, but failed to reveal any differences in number, shape or size. Only in a single case with pleura thickened by chronic inflammation and metastatic spread of lung cancer did narrow band imaging show vessels that were not detectable under white light. Conclusion It is not yet possible to assess to what extent the evidence provided by NBI is superior to that achieved with white light. Further studies are required, particularly in the early stages of pleural processes.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

High life in the sky? Mortality by floor of residence in Switzerland

Living in high-rise buildings could influence the health of residents. Previous studies focused on structural features of high-rise buildings or characteristics of their neighbourhoods, ignoring differences within buildings in socio-economic position or health outcomes. We examined mortality by floor of residence in the Swiss National Cohort, a longitudinal study based on the linkage of December 2000 census with mortality and emigration records 2001-2008. Analyses were based on 1.5 million people living in buildings with four or more floors and 142,390 deaths recorded during 11.4 million person-years of follow-up. Cox models were adjusted for age, sex, civil status, nationality, language, religion, education, professional status, type of household and crowding. The rent per m² increased with higher floors and the number of persons per room decreased. Mortality rates decreased with increasing floors: hazard ratios comparing the ground floor with the eighth floor and above were 1.22 [95% confidence interval (CI) 1.15-1.28] for all causes, 1.40 (95% CI 1.11-1.77) for respiratory diseases, 1.35 (95% CI 1.22-1.49) for cardiovascular diseases and 1.22 (95% CI 0.99-1.50) for lung cancer, but 0.41 (95% CI 0.17-0.98) for suicide by jumping from a high place. There was no association with suicide by any means (hazard ratio 0.81; 95% CI 0.57-1.15). We conclude that in Switzerland all-cause and cause-specific mortality varies across floors of residence among people living in high-rise buildings. Gradients in mortality suggest that floor of residence captures residual socioeconomic stratification and is likely to be mediated by behavioural (e.g. physical activity), and environmental exposures, and access to a method of suicide.

Obesity and overweight associated with lower rates of colorectal cancer screening in Switzerland

Screening for colorectal cancer (CRC) is associated with reduced CRC mortality, but low screening rates have been reported in several settings. The aim of the study was to assess predictors of low CRC screening in Switzerland. A retrospective cohort of a random sample of 940 patients aged 50-80 years followed for 2 years from four Swiss University primary care settings was used. Patients with illegal residency status and a history of CRC or colorectal polyps were excluded. We abstracted sociodemographic data of patients and physicians, patient health status, and indicators derived from RAND's Quality Assessment Tools from medical charts. We defined CRC screening as colonoscopy in the last 10 years, flexible sigmoidoscopy in the last 5 years, or fecal occult blood testing in the last 2 years. We used bivariate and multivariate logistic regression analyses. Of 940 patients (mean age 63.9 years, 42.7% women), 316 (33.6%) had undergone CRC screening. In multivariate analysis, birthplace in a country outside of Western Europe and North America [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.45-0.97], male sex of the physician in charge (OR 0.67, 95% CI 0.50-0.91), BMI 25.0-29.9 kg/m2 (OR 0.66, CI 0.46-0.96) and at least 30.0 kg/m2 (OR 0.61, CI 0.40-0.90) were associated with lower CRC screening rates. Obesity, overweight, birthplace outside of Western Europe and North America, and male sex of the physician in charge were associated with lower CRC screening rates in Swiss University primary care settings. Physician perception of obesity and its impact on their recommendation for CRC screening might be a target for further research.