Is imaging the future of axillary staging in breast cancer?

Axillary management in patients with breast cancer has become much less invasive with the introduction of sentinel lymph node biopsy (SLNB). However, over 70 % of SLNBs are negative, questioning the generic use of this invasive procedure. Emerging evidence indicates that breast cancer patients with a low axillary burden of disease do not benefit from axillary lymph node dissection (ALND). Non-invasive techniques such as paramagnetic iron oxide contrast-enhanced magnetic resonance imaging (MRI) may provide genuine alternatives to axillary staging and should be evaluated within clinical trials. Selective axillary surgery could then be offered based on imaging findings and for therapeutic intent. This non-operative approach would reduce morbidity further and facilitate interpretation of follow-up imaging. Key Points ? Modern imaging and biopsy greatly help the axillary staging of breast cancer. ? Superparamagnetic iron oxide (SPIO)-enhanced MRI offers a further advance. ? Sentinel lymph node biopsy may become redundant with SPIO-enhanced MRI. ? Selective therapeutic axillary surgery should be based upon preoperative imaging findings.     

Does the degree of background enhancement in breast MRI affect the detection and staging of breast cancer?

Objective  

The purpose of this study was to assess the influence of background enhancement on the detection and staging of breast cancer using MRI as an adjunct to mammography or ultrasound.     

What is the role of titin in active muscle?

Several properties of muscle defy explanation solely based on the sliding filament-swinging cross-bridge theory. Indeed, muscle behaves as though there is a dynamic "spring" within the sarcomeres. We propose a new "winding filament" mechanism for how titin acts, in conjunction with the cross-bridges, as a force-dependent spring. The addition of titin into active sarcomeres resolves many puzzling muscle characteristics.     

Is bone scintigraphy necessary in initial staging of prostate cancer patients?

Our aim was to determine whether serum prostate specific antigen (PSA) and total Gleason score (GS) on biopsy in newly diagnosed prostate cancer (PCa) can predict osseous metastases and eliminate the need for a bone scan as a routine procedure in initial staging. We studied retrospectively 155 patients with previously untreated PCa who underwent bone scintigraphy. Relationship between PSA, GS and bone metastases was examined. Sensitivity, specificity, likelihood ratio (LR) and odds ratio (OR) were calculated with corresponding 95% conidence interval. Results showed that thirty of all bone scans (19.35%) were positive for metastases. This proportion was significantly higher in patients with PSA>20ng/mL (31.66% , P=0.002) vs. PSA<10ng/mL (10.52%). For PSA<10ng/mL as well as 10ng/mL≤ PSA≤ 20ng/mL the test was not a predictor for bone metastases (OR=0.36; OR=0.55). For PSA>20 ng/mL (OR=3.53) the likelihood of bone metastases was increased by 13% . The proportion of positive scintigraphy findings was significantly lower in patients with GS≤ 7 (11.47% ) vs. GS≥ 8 (48.48% , P<0.0001). The GS≥ 8 was highly predictive for bone metastases (OR=7.260). The analysis showed that GS≥ 8 increases the risk of bone metastases by 29%. In conclusion, bone scintigraphy is not necessary in asymptomatic patients with localized disease, GS≤ 6 and PSA<10ng/mL, because of the negligible risk of bone metastases in that stage. Higher levels of GS and PSA may predict bone metastases.     

Carbon-11 choline or FDG-PET for staging of oesophageal cancer?

We investigated the feasibility of using carbon-11 choline (CHOL) positron emission tomography (PET) for the staging of oesophageal cancer, in comparison with fluorine-18 fluorodeoxyglucose (FDG) PET, using histopathological findings as the gold standard. Eighteen patients were studied: 16 patients with cancer of the oesophagus or gastro-oesophageal junction and two with in situ carcinoma/high-grade dysplasia. PET imaging was performed 5 min (CHOL) or 90 min (FDG) after injection of 370 MBq of the tracer. PET images were analysed by two independent and blinded physicians using visual and standardised uptake value (SUV) analysis. PET results were compared with surgical and histopathological findings. FDG-PET was able to detect all (100%) of the 16 malignant primary lesions, while CHOL-PET detected 73%. In situ carcinoma ( n=1) and high-grade dysplasia ( n=1) were not visualised with either tracer. Diffuse uptake of the tracers was noted in areas of Barrett's oesophagitis. Twelve patients had locoregional metastases (N1) that were not detected with either FDG or CHOL. Six patients had additional distant nodal (M1a) metastases; four of six (66%) were visualised by FDG, and three of five (60%) by CHOL-PET. On a lesion basis, FDG-PET detected 10/12 non-regional metastases (sensitivity 83%), while CHOL-PET detected 5/12 (sensitivity 42%). Haematogenous distant metastases (M1b) were positive on FDG-PET in three of four patients, and on CHOL-PET in two of four. SUV values were significantly higher for FDG (FDG 6.6+/-3.5, CHOL 5.5+/-2.5, P=0.04). CHOL-PET is able to visualise oesophageal carcinoma and its metastases, but appears to be inferior to FDG-PET. Presumably this is the result of lower tumoural uptake and considerable non-specific uptake of CHOL in liver, stomach wall, pancreas and small intestine. Further studies are needed to confirm these data.     

What is the role of bone scintigraphy in the diagnosis of infected joint prostheses?

AIM: To analyse the role played by bone scintigraphy in the diagnosis of infected joint prostheses. METHODS: The study included 77 patients, aged 32-77 years, in whom infection of a joint prosthesis (48 hip, 29 knee) was suspected. In all patients the following examinations were performed consecutively: a two-phase Tc methylene diphosphonate (Tc-MDP) bone scan, a Tc hexamethylproplyene amine oxime (Tc-HMPAO) labelled white blood cell (WBC) scan, and a Tc microcolloid bone marrow (BM) scan. The minimum interval between examinations was 48 h. The diagnoses were based on data obtained from bacteriological cultures. RESULTS: The bone scan was positive in all patients and 28 of them had an infection (sensitivity 100%, specificity 0%). The WBC scan was positive in 61 patients but only 27 had an infection. The WBC scan was negative in 16 patients, and the possibility of infection was discarded in 15 of these cases (sensitivity 96%, specificity 30%). The results of the bone marrow scan were not compatible with those of the WBC scan (suggestive of infection) in 27 patients: 26 of them had prosthesis infection. The results of both examinations were compatible in the other 34 patients and the possibility of infection was discarded in 33 of these patients (sensitivity 92.8%, specificity 98%). The addition of a BM scan to a WBC scan decreased the sensitivity from 96% to 92.8% but increased specificity from 30% to 98%. The addition of a bone scan to this dual combination did not alter the results. CONCLUSIONS: When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed, if positive, by a BM scan. This procedure reduces the cost, the time required for a diagnosis, and the dose of radiation received by the patient.     

What is the clinical role of non-invasive atherosclerosis imaging?

Non-invasive atherosclerosis findings have been demonstrated to provide incremental diagnostic and predictive values for ischemia, acute coronary syndrome, and cardiovascular outcomes. The challenge is to translate research findings to a clinical role. Here, we review the current utility of atherosclerotic imaging and the incremental value of plaque imaging. We also evaluate future clinical and research implications for three patient populations: asymptomatic prevention, stable chest pain, and acute chest pain.     

Is bone scintigraphy necessary in the initial surgical staging of chondrosarcoma of bone?

Objective  

To assess the value of whole-body bone scintigraphy in the initial surgical staging of chondrosarcoma of bone.     

Assessment of chest pain in the emergency room: What is the role of multidetector CT?

Chest pain is one of the most frequent complaints for patients seen in the emergency department. The current article describes the clinical stratification of patients who present to the emergency department with chest pain and discusses imaging options and analysis for these patients. It reviews conventional imaging approaches to assessing chest pain including chest radiography and stress testing. The main discussion focuses on the potential utility use of cross-sectional imaging, particularly multidetector CT, in the evaluation of chest pain in the emergency department.     

What is the complementary role of ultrasound evaluation in the diagnosis of acute appendicitis after CT?

The objective of our study was to estimate the complementary role of ultrasound evaluation in the diagnosis of acute appendicitis after abdominoplevic CT. A total of 104 patients initially underwent abdominopelvic CT before appendix US due to acute abdominal pain. All CT examinations were evaluated retrospectively for the presence of acute appendicitis. The findings of appendix on CT were classified into five categories (definite appendicitis, probably appendicitis, equivocal CT findings for diagnosis of appendicitis, probably not appendicitis, and normal looking appendix). Appendix US images and their radiologic reports were also evaluated retrospectively. Then, CT and US findings were correlated with clinical or pathologic diagnosis. Three all patients with definite appendicitis initially on CT again showed US findings of appendicitis. In the 32 patients of probably appendicitis on CT, US showed normal looking appendix in seven patients (21.8%, 7 of 32) who improved with medical treatment and discharged. In the 16 patients of equivocal CT findings for diagnosis of appendicitis, US showed appendicitis in seven patients (43.8%, 7 of 16) and normal looking appendix in nine patients. In the 12 patients of probably not appendicitis on CT, US showed acute appendicitis in two patients (16.7%, 2 of 12). In the 41 patients of normal looking appendix on CT, US showed acute appendicitis in five patients (12.2%, 5 of 41). US reevaluation enables us to avoid misdiagnosis of appendicitis on CT and improve diagnostic accuracy of acute appendicitis.     

Adult celiac disease: What is the role of MRI?

PURPOSE: To evaluate the ability of MRI to identify intra- and extraintestinal findings of celiac disease in an adult population. MATERIALS AND METHODS: Forty-one subjects (18 men and 23 women; mean age = 41.3 years; 31 with biopsy-proven celiac disease, and 10 healthy volunteers) underwent MRI of the small bowel. MR studies were performed on a 1.5-T magnet using T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) and true fast imaging in steady-state precession (True-FISP) sequences. The MR features and sensitivity, and the specificity and accuracy of some of these features are described. RESULTS: In the 31 celiac patients, MRI showed bowel dilatation in 61.3% (N = 19), increased number of ileal folds in 48.4% (N = 15), reversed fold pattern abnormality in 38.7% (N = 12), increased wall thickness in 16.1% (N = 5), duodenal stenosis in 6.5% (N = 2), intussusception in 12.9% (N = 4), mesenteric lymphadenopathy in 41.9% (N = 13), mesenteric vascular changes in 22.6% (N = 7), ascites in 6.5% (N = 2), and no abnormalities in 12.9% (N = 4). The volunteers had unremarkable exams. The overall specificity and accuracy were 100%, and sensitivity was 79% and 75% for increased number of ileal folders and reversed fold pattern abnormality, respectively. CONCLUSION: MRI is able to demonstrate intra- and extraintestinal features that may lead to the diagnosis of celiac disease in adults.     

What is the role of plain radiography in patients with foreign bodies in the gastrointestinal tract?

Foreign bodies (FBs) in the gastrointestinal (GI) tract can show a wide range of clinical manifestations ranging from spontaneous evacuation to severe complication. Plain radiography is a straightforward and important initial imaging modality in cases of FB ingestion or insertion and is also helpful for follow-up purposes. Careful evaluations of the plain radiographs can determine the presence and nature of FBs, and help predict their precise locations and facilitate risk assessment. In this review, a wide variety of FBs in the GI tract are illustrated, and the role of plain radiography in patient management is discussed.     

Does diabetes mellitus influence the efficacy of FDG-PET in the diagnosis of cervical cancer?

Purpose Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) may have additional value in the assessment of primary and recurrent cervical cancer. However, the degree of tumour uptake of ¹⁸F-2-fluoro-2-deoxy-d-glucose (FDG) uptake is sometimes influenced by diabetes mellitus (DM). Therefore, we conducted this prospective study to compare the diagnostic ability of FDG-PET in patients with cervical cancer complicated by DM and those without DM.Methods Patients with untreated locally advanced primary or clinically curable recurrent cervical carcinoma were enrolled. Both FDG-PET and MRI/CT scans were performed within 2 weeks. Patients were categorised into the following groups: hyperglycaemic DM (fasting blood sugar >126 mg/dl), euglycaemic DM and non-DM. The lesions were confirmed histologically or by clinical follow-up. The receiver operating characteristic curve method, with calculation of the area under the curve (AUC), was used to evaluate the discriminative power.Results From February 2001 to January 2003, 219 patients (75 with primary and 144 with recurrent cervical cancer) were eligible for analysis. Sixteen had hyperglycaemic DM, 12 had euglycaemic DM and 191 were in the non-DM group. The diagnostic power of PET in the hyperglycaemic DM, euglycaemic DM and non-DM groups did not differ significantly with regard to the identification of either metastatic lesions (AUC, 0.967/0.947/0.925, P>0.05) or primary tumours/local recurrence (AUC, 0.950/0.938/0.979, P>0.05). Considering all DM patients, PET showed a significantly higher detection power than MRI/CT scans in respect of metastatic lesions (AUC=0.956 vs 0.824, P=0.012).Conclusion In comparison with its accuracy in non-DM patients, the accuracy of PET in cervical cancer patients with mild to moderate DM was not significantly reduced.     

Regional radiotherapy in high-risk breast cancer: is the issue solved?

Adjuvant radiotherapy is the treatment standard for breast cancer with lymph node metastases after breast-conserving surgery or mastectomy. The inclusion of regional lymph nodes into the treatment volumes has been a question in recent clinical trials. Their impact on treatment standards and open questions is discussed.Radiotherapy plays an essential role in adjuvant treatment of breast cancer after breast-conserving surgery and in high-risk patients after mastectomy. However, the indications for inclusion of regional lymph nodes into radiotherapy treatment volumes have changed and are currently not homogeneously applied between countries and often not even between institutions in the same country. This commentary will focus on the indication for radiotherapy in patients with 1–3 lymph node metastases and on the use of regional radiotherapy, including parasternal irradiation in high-risk patients.Whereas the inclusion of the supra-/infraclavicular and upper axillary regions in high-risk patients with four or more involved lymph nodes is a treatment standard worldwide, the indications for local or locoregional radiotherapy in intermediate-risk patients with 1–3 lymph node metastases has long been a matter of discussion. In previous years, increasing evidence was provided support that post-mastectomy radiotherapy in this patient group is an advantage. In a subgroup analysis of randomized trials of the Danish Breast Cancer Group (DBCG82b/c) on 1152 node-positive patients with at least 8 lymph nodes removed by axillary dissection, radiotherapy to the chest wall, periclavicular, axillary and parasternal lymph nodes significantly reduced the rate of locoregional recurrences in both patients with 1–3 or with >3 involved lymph nodes compared with those with no radiotherapy. More important, the 15-year survival was also significantly improved in both patient groups.¹ This has been confirmed by a recent meta-analysis of the Early Breast Cancer Trialists'' Collaborative Group on the value of post-mastectomy radiotherapy of the chest wall, periclavicular, axillary and parasternal lymph nodes, which included 8135 females treated within 22 randomized trials. This analysis demonstrated that post-mastectomy radiotherapy leads to the same relative benefit in terms of locoregional tumour control as well as overall survival in the patient groups with 1–3 involved nodes as for patients with >3 lymph node metastases.² While these data provide a clear basis for the routine clinical use of post-mastectomy radiotherapy in the group of patients with 1–3 lymph node metastases, they did not answer the question whether local or locoregional radiotherapy should be applied.This latter question was addressed within the Canadian NCIC-CTG MA20 randomized trial, where 1832 patients with high-risk factors (of those 85% with lymph node metastases) after breast-conserving surgery received radiotherapy to the breast with or without additional regional radiotherapy to level III axillary, periclavicular and parasternal lymph nodes. Preliminary data showed a small but significant improvement of locoregional disease-free and overall survival by approximately 2% (from 94.5% to 96.8% and from 90.7% to 92.3%, respectively). Interestingly, metastases-free survival was significantly improved by the addition of regional radiotherapy from 87.0% to 92.4%.³ Similar results were obtained within the European Organisation for Research and Treatment of Cancer (EORTC) trial including 4004 patients randomized between inclusion or exclusion of the parasternal and medial supraclavicular nodes into locoregional radiotherapy.⁴The DBCG IMN study on 3072 patients applied locoregional radiotherapy, including parasternal lymph nodes only in right-sided and without parasternal lymph nodes in patients with left-sided breast cancer after mastectomy or breast-conserving radiotherapy.⁵ Inclusion of parasternal lymph nodes into the treatment volume again significantly improved the overall survival (75% vs 78%). For patients treated in the DBCG IMN study, it was estimated that the number needed to treat with IMN RT to avoid 1 death at 7 years was 33 patients, whilst in the “worst-case” scenario, the number of patients with no heart disease treated at an age of 50 years to cause 1 cardiac death at 10 years after parasternal radiotherapy was 3333.⁶ Only the smallest trial reported so far, the French multicentre randomized trial including 1334 patients failed to show a survival benefit after addition of parasternal radiotherapy to radiotherapy of the chest wall, axilla and supraclavicular nodes.⁷ In none of the trials was increased cardiac mortality reported after parasternal irradiation after average follow-up times of 10 years, however, final conclusions still need longer follow-up.In light of the overall conclusive results from the trials performed to date, the indication for adjuvant radiotherapy after mastectomy for patients with 1–3 involved lymph nodes should no longer be a matter of discussion. For the issue of inclusion of regional nodes, specifically parasternal nodes into the treatment volume, of patients with high-risk factors, it has to be concluded that this extension of the radiotherapy treatment volume leads to a small but significant improvement of survival for the average of the patient population, obviously by decreased distant metastases. Some countries (e.g. Denmark) considered this evidence by defining locoregional radiotherapy including parasternal radiotherapy as a treatment standard in all patients with lymph node metastases as well as in patients with pT3 tumours. Other countries (e.g. Germany) are still more ambiguous and recommend leaving the indication for the inclusion of parasternal lymph nodes to individual decision.⁸ Independent of such national differences in guidelines, the comparably small survival benefit after complete regional radiotherapy (including parasternal irradiation) can easily be outweighted in individual patients if, for example, cardiac sparing is not sufficiently considered. To take advantage of such small benefit, the use of radiotherapy techniques that optimize cardiac sparing is warranted and individual specific anatomical situations that hinder sufficient cardiac sparing should lead to a discussion of omission of parasternal radiotherapy in these patients. Whether longer follow-up or further subgroup analyses of the randomized trials will help to potentially define patients who benefit more from parasternal radiotherapy needs to be awaited.Another issue is the opposite treatment strategy, that is, treatment de-escalation, for patients with clinically negative but sentinel-node-positive axillary lymph nodes. These patients have been treated with similar success by axillary dissection or by locoregional radiotherapy of the remaining breast or thoracic wall and the axillary and parasternal lymphnodes⁹ or by local radiotherapy of the breast or thoracic wall alone.^10,11 Specifically, the patient cohorts of the Z0011 trial¹⁰ and the AMAROS trial⁹ show substantial overlap with those who received complete locoregional radiotherapy after surgical axillary treatment within the above-mentioned studies. As the results of these three trials do not contradict each other, it can currently only be concluded that axillary surgery may be omitted in specific groups of patients and that at least some of these patients likely benefit from regional radiotherapy.For future translational studies, the evaluation of molecular markers or genetic profiling of breast cancer to stratify patients for potential treatment decisions for or against regional radiotherapy will be of utmost importance. On a mid-term scale, such individualized strategies should not only include risk factors given by the tumour disease but also patient-related dose–volume-related risk factors for the development of toxicities.