Recurrence due to neoplastic seeding in head and neck cancer: report of two cases and review of the literature

AIMS AND BACKGROUND Tumor progression due to seeding of tumor cells after definitive treatment for squamous cell carcinomas of the head and neck is an uncommon condition that can considerably worsen the outcome of patients with head and neck cancer. METHODS AND STUDY DESIGN We report two cases of recurrence due to neoplastic seeding from oropharyngeal and oral cancer, respectively. We performed a literature review with MEDLINE as the main search engine. RESULTS Seeding was found to occur most often in tracheotomy scars and gastrostomy sites. The oral cavity, hypopharynx and oropharynx were the primary sites in most cases, and advanced tumor stage seemed to be a risk factor for seeding. Treatment options include salvage surgery, which requires thorough resections, radiotherapy when possible, and palliative management. The prognosis of such events is poor. CONCLUSION Although neoplastic seeding is a well-known phenomenon in cancer surgery, many questions remain unanswered, especially regarding preventive measures and management strategies.

Accelerated partial breast irradiation with interstitial brachytherapy as second conservative treatment for ipsilateral breast tumour recurrence: multicentric study of the GEC-ESTRO Breast Cancer Working Group

PURPOSE To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). MATERIAL AND METHODS Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. RESULTS Median follow-up after the IBTR was 3.9 years [range: 1.1-10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5-9.5] and 7.2% [range: 2.1-12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7-15.2] and 19.1% [range: 7.8-28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1-94.8] and 76.4% [range: 66.9-87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p=0.008) and OS (p=0.02); while tumour size was prognostic factor for DM (p=0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. CONCLUSION This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy.

Local recurrence after retropubic radical prostatectomy for prostate cancer does not exclusively occur at the anastomotic site

What's known on the subject? and What does the study add? Local recurrence after radical prostatectomy (RP) for clinically organ-confined prostate cancer is largely assumed to occur at the anastomotic site, as reflected in European and North American guidelines for adjuvant and salvage radiotherapy after RP. However, the exact site of local recurrence often remains undetermined. The present study shows that roughly one out of five patients with local recurrence after RP has histologically confirmed tumour deposits at the resection site of the vas deferens, clearly above the anastomotic site. This should be considered when offering ‘blind’ radiotherapy to the anastomotic site in patients with biochemical recurrence alone. Objective To determine the anatomical pattern of local recurrence and the corresponding clinical and pathological variables of patients treated with retropubic radical prostatectomy (RRP). Patients and Methods In all, 41 patients with biopsy confirmed local recurrence after extended pelvic lymph node dissection and RRP performed between January 1992 and December 2009 at a single tertiary referral academic centre were retrospectively studied. The site of local recurrence as assessed on computed tomography or magnetic resonance imaging was reviewed. Two sites were identified: the vesicourethral anastomotic site and the cranial resection margin of the surgical bed, where the vas deferens was transected and clipped. Age and serum prostate-specific antigen (PSA) level at RRP, pathological tumour and nodal stage, Gleason score, tumour location, surgical margin status, age and serum PSA level at the time of local recurrence, and time to diagnosis of local recurrence were assessed for the two sites and compared with the chi-square or Wilcoxon rank sum tests as appropriate. Results Local recurrence occurred at the anastomotic site in 31/41 (76%) patients and at the resection site of the vas deferens in nine of 41 (22%) patients. One patient had distinct lesions at both sites. There was no significant difference in any of the clinical and pathological variables between patients with local recurrence in the former and latter site. Conclusion Most local recurrences after RRP occur exclusively at the anastomotic site. However, 22% of locally recurrent cases had tumour at the resection site of the vas deferens. This should be taken into account when considering adjuvant or salvage radiation therapy.

Risk of very early recurrent cerebrovascular events in symptomatic carotid artery stenosis

OBJECT The risk of recurrence of cerebrovascular events within the first 72 hours of admission in patients hospitalized with symptomatic carotid artery (CA) stenoses and the risks and benefits of emergency CA intervention within the first hours after the onset of symptoms are not well known. Therefore, the authors aimed to assess (1) the ipsilateral recurrence rate within 72 hours of admission, in the period from 72 hours to 7 days, and after 7 days in patients presenting with nondisabling stroke, transient ischemic attack (TIA), or amaurosis fugax (AF), and with an ipsilateral symptomatic CA stenosis of 50% or more, and (2) the risk of stroke in CA interventions within 48 hours of admission versus the risk in interventions performed after 48 hours. METHODS Ninety-four patients were included in this study. These patients were admitted to hospital within 48 hours of a nondisabling stroke, TIA, or AF resulting from a symptomatic CA stenosis of 50% or more. The patients underwent carotid endarterectomy (85 patients) or CA stenting (9 patients). At baseline, the cardiovascular risk factors of the patients, the degree of symptomatic CA stenosis, and the type of secondary preventive treatment were assessed. The in-hospital recurrence rate of stroke, TIA, or AF ipsilateral to the symptomatic CA stenosis was determined for the first 72 hours after admission, from 72 hours to 7 days, and after 7 days. Procedure-related cerebrovascular events were also recorded. RESULTS The median time from symptom onset to CA intervention was 5 days (interquartile range 3.00-9.25 days). Twenty-one patients (22.3%) underwent CA intervention within 48 hours after being admitted. Overall, 15 recurrent cerebrovascular events were observed in 12 patients (12.8%) in the period between admission and CA intervention: 3 strokes (2 strokes in progress and 1 stroke) (3.2%), 5 TIAs (5.3%), and 1 AF (1.1%) occurred within the first 72 hours (total 9.6%) of admission; 1 TIA (1.1%) occurred between 72 hours and 7 days, and 5 TIAs (5.3%) occurred after more than 7 days. The corresponding actuarial cerebrovascular recurrence rates were 11.4% (within 72 hours of admission), 2.4% (between 72 hours and 7 days), and 7.9% (after 7 days). Among baseline characteristics, no predictive factors for cerebrovascular recurrence were identified. Procedure-related cerebrovascular events occurred at a rate of 4.3% (3 strokes and 1 TIA), and procedures performed within the first 48 hours and procedures performed after 48 hours had a similar frequency of these events (4.5% vs. 4.1%, respectively; p = 0.896). CONCLUSIONS The in-hospital recurrence of cerebrovascular events was quite low, but all recurrent strokes occurred within 72 hours. The risk of stroke associated with a CA intervention performed within the first 48 hours was not increased compared with that for later interventions. This raises the question of the optimal timing of CA intervention in symptomatic CA stenosis. To answer this question, more data are needed, preferably from large randomized trials.

Lake sediments as archives of recurrence rates and intensities of past flood events

Palaeoflood hydrology is an expanding field as the damage potential of flood and flood-related processes are increasing with the population density and the value of the infrastructure. Assessing the risk of these hazards in mountainous terrain requires knowledge about the frequency and severness of such events in the past. A wide range of methods is employed using diverse biologic, geomorphic or geologic evidences to track past flood events. Impact of floods are studied and dated on alluvial fans and cones using for example the growth disturbance of trees (Stoffel and Bollschweiler 2008; Schneuwly-Bollschweiler and Stoffel 2012: this volume) or stratigraphic layers deposited by debris flows, allowing to reconstruct past flood frequencies (Bardou et~al. 2003). Further downstream, the classical approach of palaeoflood hydrology (Kochel and Baker 1982) utilizes geomorphic indicators such as overbank sediments, silt lines and erosion features of floods along a river (e.g. Benito and Thorndycraft 2005). Fine-grained sediment settles out of the river suspension in eddies or backwater areas, where the flow velocity of the river is reduced. Records of these deposits at different elevations across a river’s profile can be used to assess the discharge of the past floods. This approach of palaeoflood hydrology studies was successfully applied in several river catchments (e.g. Ely et al. 1993; Macklin and Lewin 2003; O’Connor et al. 1994; Sheffer et al. 2003; Thorndycraft et al. 2005; Thorndycraft and Benito 2006). All these different reconstruction methods have their own advantages and disadvantages, but often these studies have a limited time coverage and the records are potentially incomplete due to lateral limits of depositional areas and due to the erosional power of fluvial processes that remove previously deposited flood witnesses. Here, we present a method that follows the sediment particle transported by a flood event to its final sink: the lacustrine basin.

Managing the risks of medical technology: Do hazard surveillance systems provide an early warning of medical device problems?

The Food and Drug Administration (FDA) is responsible for risk assessment and risk management in the post-market surveillance of the U.S. medical device industry. One of the FDA regulatory mechanisms, the Medical Device Reporting System (MDR) is an adverse event reporting system intended to provide the FDA with advance warning of device problems. It includes voluntary reporting for individuals, and mandatory reporting for device manufacturers. ^ In a study of alleged breast implant safety problems, this research examines the organizational processes by which the FDA gathers data on adverse events and uses adverse event reporting systems to assess and manage risk. The research reviews the literature on problem recognition, risk perception, and organizational learning to understand the influence highly publicized events may have on adverse event reporting. Understanding the influence of an environmental factor, such as publicity, on adverse event reporting can provide insight into the question of whether the FDA's adverse event reporting system operates as an early warning system for medical device problems. ^ The research focuses on two main questions. The first question addresses the relationship between publicity and the voluntary and mandatory reporting of adverse events. The second question examines whether government agencies make use of these adverse event reports. ^ Using quantitative and qualitative methods, a longitudinal study was conducted of the number and content of adverse event reports regarding breast implants filed with the FDA's medical device reporting system during 1985–1991. To assess variation in publicity over time, the print media were analyzed to identify articles related to breast implant failures. ^ The exploratory findings suggest that an increase in media activity is related to an increase in voluntary reporting, especially following periods of intense media coverage of the FDA. However, a similar relationship was not found between media activity and manufacturers' mandatory adverse event reporting. A review of government committee and agency reports on the FDA published during 1976–1996 produced little evidence to suggest that publicity or MDR information contributed to problem recognition, agenda setting, or the formulation of policy recommendations. ^ The research findings suggest that the reporting of breast implant problems to FDA may reflect the perceptions and concerns of the reporting groups, a barometer of the volume and content of media attention. ^

WHEN DOES THE TROUBLE START? OBESITY, DIABETES RISKS AND METABOLIC DISTURBANCES IN YOUNG PEOPLE WITH PSYCHOSIS

People with psychotic disorders have higher mortality rates compared to the general population. Most deaths are due to cardiovascular (CV) disease, reflecting high rates of CV risk factors such as obesity and diabetes. Treatment with antipsychotic drugs is associated with weight gain in clinical trials. However, there is little information about how these drugs affect children and young people, and how early in the course of treatment the elevation in CV risk factors begins. This information is essential in understanding the costs and benefits of these treatments in young people, and establishing preventive and early intervention services to address physical health comorbidities. This symposium reports both prospective and naturalistic data from children and adolescents treated with antipsychotic drugs. These studies demonstrate that adverse effects on cardiometabolic measures, notably BMI and insulin resistance, become apparent very soon after treatment is initiated. Further, children and adolescents appear to be even more sensitive to these effects than adults. Population-wide studies are also informative. Danish data showing that young people exposed to antipsychotics have a higher risk of diabetes, compared with young people who had a psychiatric diagnosis but were not exposed to antipsychotic drugs, will be presented. In addition, an Australian comparison between a large, nationally representative sample of people with psychosis and a general population sample shows that higher rates of obesity and other cardiometabolic abnormalities are already evident in people with psychosis by the age of 25 years. Young people living with psychosis are already disadvantaged by the demands of living with mental illness, stigma, and social factors such as unemployment and low income. The addition of obesity, diabetes and other comorbidities adds a further burden. The data presented highlights the need for careful selection of antipsychotic drugs, regular monitoring of physical health and early intervention when weight gain, glucose dysregulation, or other cardiometabolic abnormalities are detected.

Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Influence of intervertebral disc fenestration at the herniation site in association with hemilaminectomy on recurrence in chondrodystrophic dogs with thoracolumbar disc disease: a prospective MRI study

OBJECTIVE To describe the influence of fenestration at the disc herniation site on recurrence in thoracolumbar disc disease of chondrodystrophoid dogs. STUDY DESIGN Prospective clinical study. ANIMALS Chondrodystrophic dogs (n=19). METHODS Dogs were divided into 2 groups: group 1 (9 dogs) had thoracolumbar disc extrusion (Hansen type I) treated by hemilaminectomy and concomitant fenestration of the affected intervertebral disc and group 2 (10 dogs) had hemilaminectomy without fenestration. All dogs had 3 magnetic resonance imaging (MRI) examinations: preoperatively, immediately postoperatively to assess removal of herniated disc material, and again 6 weeks after surgery. RESULTS There were 13 male and 6 female dogs; mean age, 7.1 years. Thoracolumbar disc herniation was confirmed with MRI. Immediate post surgical MRI revealed that the herniated disc removal was complete in all but 1 dog and that fenestration did not lead to complete removal of nucleus pulposus within the intervertebral disc space. On the 3rd MRI examination, none of the group 1 dogs had further disc material herniation at the fenestrated site. Six of the 10 group 2 dogs had a recurrence of herniation leading to clinical signs in 3 dogs (pain in 2 dogs, paresis in 1 dog). CONCLUSION In thoracolumbar disc herniation, fenestration of the affected intervertebral disc space prevents further extrusion of disc material. CLINICAL RELEVANCE Fenestration reduces the risk of early recurrence of disc herniation and associated postoperative complications.

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.

BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

Cone beam computed tomography in implant dentistry: a systematic review focusing on guidelines, indications, and radiation dose risks.

PURPOSE The aim of the paper is to identify, review, analyze, and summarize available evidence in three areas on the use of cross-sectional imaging, specifically maxillofacial cone beam computed tomography (CBCT) in pre- and postoperative dental implant therapy: (1) Available clinical use guidelines, (2) indications and contraindications for use, and (3) assessment of associated radiation dose risk. MATERIALS AND METHODS Three focused questions were developed to address the aims. A systematic literature review was performed using a PICO-based search strategy based on MeSH key words specific to each focused question of English-language publications indexed in the MEDLINE database retrospectively from October 31, 2012. These results were supplemented by a hand search and gray literature search. RESULTS Twelve publications were identified providing guidelines for the use of cross-sectional radiography, particularly CBCT imaging, for the pre- and/or postoperative assessment of potential dental implant sites. The publications discovered by the PICO strategy (43 articles), hand (12), and gray literature searches (1) for the second focus question regarding indications and contraindications for CBCT use in implant dentistry were either cohort or case-controlled studies. For the third question on the assessment of associated radiation dose risk, a total of 22 articles were included. Publication characteristics and themes were summarized in tabular format. CONCLUSIONS The reported indications for CBCT use in implant dentistry vary from preoperative analysis regarding specific anatomic considerations, site development using grafts, and computer-assisted treatment planning to postoperative evaluation focusing on complications due to damage of neurovascular structures. Effective doses for different CBCT devices exhibit a wide range with the lowest dose being almost 100 times less than the highest dose. Significant dose reduction can be achieved by adjusting operating parameters, including exposure factors and reducing the field of view (FOV) to the actual region of interest.