Pitfalls in post-mortem CT-angiography – intravascular contrast induces post-mortem pericardial effusion

We present a case where multi-phase post-mortem computed tomography angiography (PMCTA) induced a hemorrhagic pericardial effusion during the venous phase of angiography. Post-mortem non-contrast CT (PMCT) suggested the presence of a ruptured aortic dissection. This diagnosis was confirmed by PMCTA after pressure controlled arterial injection of contrast. During the second phase of multi-phase PMCTA the presence of contrast leakage from the inferior cava vein into the pericardial sac was noted. Autopsy confirmed the post-mortem nature of this vascular tear. This case teaches us an important lesson: it underlines the necessity to critically analyze PMCT and PMCTA images in order to distinguish between artifacts, true pathologies and iatrogenic findings. In cases with ambiguous findings such as the case reported here, correlation of imaging findings with autopsy is elementary.     

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis

Purpose

Oral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model.

Methods

Irradiation was either applied alone or in combination with daily DS treatment (4?mg/kg, subcutaneously) over varying time intervals. Irradiation comprised single dose irradiation with graded doses to the lower tongue surface or daily fractionated irradiation of the whole tongue. Fractionation protocols (5?×?3?Gy/week) over one (days 0–4) or two weeks (days 0–4, 7–11) were terminated by an additional local single dose irradiation to a defined treatment field on the lower tongue surface to induce the mucosal radiation response. The additional single dose irradiation (top-up) on day 7 (after one week of fractionation) or day 14 (after 2 weeks of fractionation) comprised graded doses in order to generate full dose–effect curves. Ulceration of the epithelium of the lower tongue, corresponding to confluent mucositis, was analysed as clinically relevant endpoint. Additionally, the time course parameters, latent time and ulcer duration were analysed.

Results

DS treatment significantly reduced the incidence of ulcerations. DS application over longer time intervals resulted in a more pronounced reduction of ulcer frequency, increased latent times and reduced ulcer duration.

Conclusion

DS has a significant mucositis-ameliorating activity with pronounced effects on mucositis frequency as well as on time course parameters.

     

Cost analysis of a wait-and-see strategy after radiochemotherapy in distal rectal cancer

Background

Nonoperative management (NOM) of rectal cancer after radiochemotherapy (RtChx) in patients with a clinical complete response is an emerging strategy with the goal to improve quality of life without compromising cure rates. However close monitoring with both magnetic resonance imaging (MRI) and rectoscopy is required for the early detection of possible local regrowths. We therefore performed a cost analysis comparing the costs of immediate surgery with the costs for MRI and rectoscopy during surveillance as in the upcoming CAO/ARO/AIO-16 trial.

Methods

MRIs and rectoscopies of patients with a clinical complete response after RtChx over the course of 5 years were simulated and compared with immediate surgery after RtChx. Transition probabilities between health stages (no evidence of disease, local regrowth and salvage surgery, distant failure) were derived from the literature. Costs for ambulatory imaging and endoscopic studies were calculated according to the “Gebührenordnung für Ärzte” (GOÄ), costs for surgery based on the diagnosis-related groups system. Three different scenarios with higher costs for salvage surgery or higher regrowth rates were simulated.

Results

A patient without disease recurrence will generate costs for MRI and rectoscopy of 6344?€ over 5 years compared with costs of 14,511 € for immediate radical surgery. When 25% local regrowths with subsequent salvage surgery were included in the model, the average costs per patient are 8299?€. In our simulations a NOM strategy was cost-saving compared with immediate surgery in all three scenarios.

Conclusion

A NOM strategy with an intensive surveillance using MRI and rectoscopy will produce costs that are expected to remain below those of immediate surgery.

     

Significance of runaway calcium homeostasis in type Ⅱ pneumocytes in development of radiation-induced lung injury

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Evaluation of response to induction chemotherapy in esophageal cancer: is barium esophagography or PET-CT useful?

ObjectiveTo determine whether sequential barium esophagograms can predict histopathological response to treatment in esophageal cancer.Materials and methodsTwo radiologists retrospectively reviewed esophagograms pre- and post- chemotherapy in 32 patients for tumor length decrease of at least 15% and luminal width increase of at least 15%. Positron emission tomography–computed tomography (PET-CT) was reviewed for tumor maximum standardized uptake value (SUV_max) decrease of at least 35%. The reference standard was 90% or more tumor necrosis at histopathologic examination of the excised specimen.ResultsPathologic response ranged from 10% to 100% necrosis. For prediction of tumor response, the sensitivity, specificity, positive and negative predictive values for length ranged from 43.8 to 56.3% and for width from 41.2% to 66.7% and for SUV_max from 47.1% to 53.3%.ConclusionPerformance characteristics for barium esophagograms in our group of patients were similar to PET-CT in predicting tumor response. Both tests were inadequate in predicting tumor response.     

Non-motor predictors of freezing of gait in Parkinson’s disease

BackgroundThe etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.Research questionWe aimed to determine the predictive value of non-motor features in freezing of gait development.MethodsData were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.ResultsPatients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SignificanceOur findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.     

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

Objective

We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan).

Methods

The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle³® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V_{20 Gy} and V_{30 Gy} of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability.

Results

Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V_{20 Gy}, and heart V_{30 Gy} in the DV-gEUD plan were lower than those in the DV plan (p<0.05).

Conclusions

A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution.

Advances to knowledge

The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV.Breast cancer is the most common cancer and the leading cause of cancer deaths in females worldwide, with about 500 000 fatalities each year. In the USA and Europe, breast cancer constitutes, on average, one in four cancer cases among females [1,2]. Breast cancer among females in Asian countries mostly occurs between the ages of 40 and 50 years; however, in females in Western countries, it mostly occurs between the ages of 50 and 60 years [2,3].Bilateral breast cancer (BBC) is very rare, accounting for only 1–3% of all breast cancer cases [4-6]. Generally, no treatment guidelines exist for BBC. The treatment of BBC relies on surgery, chemotherapy and radiation therapy; additionally, BBC has previously demonstrated a poor prognosis. Current evidence indicates that the survival rate of patients with BBC is similar to that of patients with unilateral breast cancer [7,8]. The difficulty in treatment planning for BBC varies greatly, case by case, and is thus a great challenge for radiotherapy. Important issues have been raised concerning how to reduce the dose of radiation to normal tissues, how to maintain a certain tumour control probability (TCP) and how to improve the quality of life for patients with BBC.Most intensity-modulated radiotherapy (IMRT) planning systems apply dose–volume (DV)-based objective functions for dose optimisation, and an acceptable plan can be generated in most cases. For more complex plans, more iterations are required because many parameters need to be finely tuned. A successful improvement tool—the generalised equivalent uniform dose (gEUD)—was developed with fewer parameter settings [9-13] to improve the quality of plans. However, gEUD-based optimisation cannot demonstrate such advantages on the first run; more iterations are required to sculpt the dose distribution [14].To overcome the disadvantages mentioned above, we started with a DV-generated plan, and then improved it by adding gEUD-based improvements. The goal was to reduce the number of iterations and to improve the optimum dose distribution. This method first determined the approximate solutions for most of the treatment targets by DV-based optimisation, and then adjusted the DV histogram (DVH) by gEUD-based optimisation to obtain a superior solution. This study also compared and evaluated the differences between two different methods for the treatment of BBC—(i) a DV plan with DV-based optimisation (DV plan), and (ii) a DV-gEUD plan with mainly DV-based optimisation assisted by gEUD-based optimisation (DV-gEUD plan)—thus providing a quantitative indicator model for reference.     

DEGRO practical guidelines: radiotherapy of breast cancer I

Background and purpose

The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012.

Methods

A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms “breast cancer”, “radiotherapy”, and “breast conserving therapy”. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer.

Results

Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48–0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75–0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified.

Conclusion

After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.     

DEGRO practical guidelines: radiotherapy of breast cancer II

Purpose

To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery.

Methods

The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were “non invasive breast cancer”, “ductal carcinoma in situ, “dcis”, “borderline breast lesions”, “lobular neoplasia”, “radiotherapy” and “radiation therapy”. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ.

Results

Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose–volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing.

Conclusion

Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets—even in low risk subgroups (LoE 1a).     

Imaging features of sporadic breast cancer in women under 40 years old: 97 cases

Objectives

To evaluate characteristic features of mammography, ultrasound and magnetic resonance imaging (MRI) of sporadic breast cancer in women <40 years and to determine correlations with pathological and biological factors.

Methods

A retrospective review of radiological, clinicopathological and biological features of sporadic breast cancers for women under 40 years at our institution between 2007-2012 covering 91 patients. Mammography was available for 97 lesions, ultrasound for 94 and MRI for 38.

Results

The most common imaging features were masses, nearly all classified BI-RADS 4 or 5. On mammography microcalcifications alone accounted for 31 %, all suspicious. There were 42.6 % luminal B, 24.5 % luminal A, 19.1 % HER2-enriched and 10.6 % triple-negative (TN) tumours by immunohistochemistry. HER2 overexpression was correlated with the presence of calcifications at mammography (P?=?0.03). TN cancers more often had an oval shape and abrupt interface at ultrasound and rim enhancement on MRI. MRI features were suspicious for all cancers and rim enhancement of a mass was a significant predictor of triple-negative tumours (P?=?0.01).

Conclusions

The imaging characteristics of cancers in patients under 40 years without proven gene mutations do not differ from their older counterparts, but appear correlated to phenotypic profiles, which have a different distribution in young women compared to the general population.

Key Points

? Young women have more luminal B/HER2+ phenotypes than older women. ? The appearance of cancers is correlated with their biological profiles. ? Sporadic breast cancer imaging in young women is generally classified BI-RADS 4/5. ? Triple-negative cancers can be misinterpreted as benign, requiring thorough imaging analysis.     

Systemic administration of heparin ameliorates radiation-induced oral mucositis—preclinical studies in mice

Purpose

The present study investigates the impact of systemic application of heparins on the manifestation of radiation-induced oral mucositis in a well-established mouse model.

Materials and methods

Male C3H/Neu mice were irradiated with either single-dose or fractionated irradiation protocols with 5?×?3 Gy/week, given over one (days 0–4) or two (days 0–4, 7–11) weeks. All fractionation protocols were concluded by a local test irradiation (day 7/14) using graded doses to generate complete dose–effect curves. Daily doses of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively) were applied subcutaneously over varying time intervals. The incidence and the time course of mucosal ulceration, corresponding to confluent mucositis in patients (RTOG/EORTC grade 3), were analysed as clinically relevant endpoints.

Results

Systemic application of heparins significantly increased the iso-effective doses for the induction of mucosal ulceration, particularly in combination with fractionated irradiation protocols. Moreover, a tentative prolongation of the latent time and a pronounced reduction of the ulcer duration were observed.

Conclusion

These data provide the first evidence for a protective and/or mitigative effect of heparins for radiation-induced oral mucositis. Further studies are ongoing investigating the underlying mechanism.

     

Specificity of choline metabolites for in vivo diagnosis of breast cancer using 1H MRS at 1.5 T

The purpose was to determine if in vivo proton magnetic resonance spectroscopy (¹H MRS) at 1.5 T can accurately provide the correct pathology of breast disease. Forty-three asymptomatic volunteers including three lactating mothers were examined and compared with 21 breast cancer patients. Examinations were undertaken at 1.5 T using a purpose-built transmit-receive single breast coil. Single voxel spectroscopy was undertaken using echo times of 135 and 350 ms. The broad composite resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), myo-inositol and taurine, was found not to be a unique marker for malignancy providing a diagnostic sensitivity and specificity of 80.0 and 86.0%, respectively. This was due to three of the asymptomatic volunteers and all of the lactating mothers also generating the broad composite resonance at 3.2 ppm. Optimised post-acquisitional processing of the spectra resolved a resonance at 3.22 ppm, consistent with PC, in patients with cancer. In contrast the spectra recorded for three false-positive volunteers, and the three lactating mothers had a resonance centred at 3.28 ppm (possibly taurine, myo-inositol or GPC). This improved the specificity of the test to 100%. Careful referencing of the spectra and post-acquisitional processing intended to optimise spectral resolution of in vivo MR proton spectra from human breast tissue resolves the composite choline resonance. This allows the distinction of patients with malignant disease from volunteers with a sensitivity of 80% and specificity of 100%. Therefore, resolution of the composite choline resonance into its constituent components improves the specificity of the in vivo ¹H MRS method, but does not overcome the problem of 20% false-negatives.     

Long-term outcomes in patients younger than 60 years of age treated with brachytherapy for prostate cancer

Purpose

The purpose of the study was to report the outcomes and late toxicities in patients younger than 60 years of age with long-term follow-up treated with low dose rate (LDR) brachytherapy for localized prostate cancer.

Methods

Between January 2000 and December 2009, 270 consecutive patients were treated with favourable localized prostate cancer; the median follow-up was 111 months (range 21–206). All patients received one implant of LDR brachytherapy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Events, Version 4.0 (CTAE v4.02) by the National Cancer Institute.

Results

The overall survival according to Kaplan–Meier estimates was 99 (±1%) at 17 years. The 17-year rate for failure in tumour-free survival (TFS) was 97% (±1%), whereas for biochemical control it was 95% (±1%) at 17 years, 97% (±1%) of patients being free of local recurrence. No intraoperative or perioperative complications occurred. Acute genitourinary (GU) grade II toxicity was 4% at 12 months. No other chronic toxicity was observed after treatment. At 6 months, 94% of patients reported no change in bowel function.

Conclusions

LDR brachytherapy provides patients younger than 60 years of age with low and intermediate-risk prostate cancer excellent outcomes and has a low risk of significant long-term GU or gastrointestinal morbidity.

     

Does the association of 18F-FDG uptake intensity and lesion topography reveal histological phenotype and tumor differentiation in esophageal cancer?

In daily clinical practice, the esophageal squamous cell cancer (ESCC) is considered to be more (18)F-FDG avid than adenocarcinoma (EAD). To date, the few studies concerning the existence of a real metabolic difference based on esophageal cancer (EC) histology, show divergent and not definitive results. A retrospective analysis of (18)F-FDG PET/CT of 87 patients with ESCC and EAD was performed to investigate the role played by both histopathological subtype and tumor differentiation in the characterization of glucose metabolic profile of EC. Esophageal squamous cell cancer was well differentiated (WD) in 42 cases and poorly differentiated (PD) in 12 patients. Twenty-one of the 33 patients had WD EAD, while 12 had a PD EAD. The (18)F-FDG maximal standardized uptake value (SUV(max)) was determined for all lesions and used for inter and intra-group comparison. In ESCC, the SUV(max) ranged from 4 to 31 with a mean value of 16±6. In EAD, the SUV(max) ranged from 2 to 25 with a mean value of 10±6. A statistically significant difference (P<0.0001) was found between ESCC and EAD. According to histological classification and tumor differentiation, we obtained the following results: a) the SUV(max) values of WD ESCC and WD EAD were 17±5 (range: 7-31) and 7±3 (range: 2-12) respectively (P<0.00001), b) the SUV(max) values of PD ESCC and PD EAD were 11±4 (range: 4-19) and 17±6 (range: 7-25) respectively (P<0.05). Moreover, a statistically significant difference of SUV(max) values was found between WD and PD ESCC (P<0.005) as well as between WD and PD differentiated EAD (P<0.0001). In order to predict tumor histology (ESCC, EAD) from both SUV(max) and lesion location, a multivariate discriminant analysis was performed on the whole population with a resulting diagnostic accuracy equal to 82% (P<0.00001). In conclusion, we provide additional arguments about (18)F-FDG uptake difference between ESCC and EAD as well as between poorly and well-differentiated forms of both EC histological subtypes.