Marjut Leidenius

Motion restriction and axillary web syndrome after sentinel node biopsy and axillary clearance in breast cancer

BACKGROUND We evaluated the prevalence of motion restriction and axillary web syndrome (AWS) after sentinel node biopsy (SNB) and axillary clearance (AC) in a prospective study. AWS is a self-limiting cause of early postoperative morbidity after axillary surgery. Limited range of motion associated with palpable cords of tissue in the axilla are typical for AWS. METHODS Altogether 85 breast cancer patients who underwent SNB only (49 patients) or SNB and AC (36 patients) were examined before and after surgery. The range of shoulder flexion and abduction and the presence of AWS were registered. RESULTS The range of shoulder movements was restricted in 24 (45%) patients after SNB only and in 31 (86%) patients who also underwent AC (P = 0.002). AWS was encountered in 10 (20%) patients with SNB and in 26 (72%) with AC (P <0.00005). CONCLUSIONS In the SNB group, significantly less early postoperative morbidity was observed.

High-resolution CT by diffraction-enhanced x-ray imaging : mapping of breast tissue samples and comparison with their histo-pathology

The aim of this study was to introduce high-resolution computed tomography (CT) of breast tumours using the diffraction-enhanced x-ray imaging (DEI) technique and to compare results with radiological and histo-pathological examinations. X-ray CT images of tumour-bearing breast tissue samples were acquired by monochromatic synchrotron radiation (SR). Due to the narrow beam and a large sample-to-detector distance scattering is rejected in the absorption contrast images (SR-CT). Large contrast enhancement is achieved by the use of the DEI-CT method, where the effects of refraction and scatter rejection are analysed by crystal optics. Clinical mammograms and CT images were recorded as reference material for a radiological examination. Three malignant and benign samples were studied in detail. Their radiographs were compared with optical images of stained histological sections. The DEI-CT images map accurately the morphology of the samples, including collagen strands and micro-calcifications of dimensions less than 0.1 mm. Histo-pathological examination and reading of the radiographs were done independently, and the conclusions were in general agreement. High-resolution DEI-CT images show strong contrast and permit visualization of details invisible in clinical radiographs. The radiation dose may be reduced by an order of magnitude without compromising image quality, which would make possible clinical in vivo DEI-CT with future compact SR sources.

Human breast cancer in vitro: matching histo-pathology with small-angle x-ray scattering and diffraction enhanced x-ray imaging

Twenty-eight human breast tumour specimens were studied with small-angle x-ray scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm. Two examples of ductal carcinoma are illustrated by histology images, DEI, and maps of the collagen d-spacing and scattered intensity in the Porod regime, which characterize the SAXS patterns from collagen-rich regions of the samples. Histo-pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters show that in these regions the scattering signal differs significantly from scattering by the surrounding tissue, indicating a degradation of the collagen structure in the invaded regions. The DEI images show the borders between collagen and adipose tissue and provide a co-ordinate system for tissue mapping by SAXS. In addition, degradation of the collagen structure in an invaded region is revealed by fading contrast of the DEI refraction image. The 28 samples include fresh, defrosted tissue and formalin-fixed tissue. The d-values with their standard deviations are given. In the fresh samples there is a systematic 0.76% increase of the d-value in the invaded regions, averaged over 11 samples. Only intra-sample comparisons are made for the formalin-fixed samples, and with a long fixation time, the difference in the d-value stabilizes at about 0.7%. The correspondence between the DEI images, the SAXS maps and the histo-pathology suggests that definitive information on tumour growth and malignancy is obtained by combining these x-ray methods.

Toward High-Contrast Breast CT at Low Radiation Dose

This study was approved by the local research ethics committee, and patient informed consent was obtained. The purpose of this study was to demonstrate that high-spatial-resolution low-dose analyzer-based x-ray computed tomography (CT) can substantially improve the radiographic contrast of breast tissue in vitro when compared with that attained by using diagnostic mammography and CT. An excised human breast tumor was examined by using analyzer-based x-ray imaging with synchrotron radiation. The correspondence between analyzer-based x-ray images and diagnostic mammograms, CT images, and histopathologic findings was determined. Calcifications and fine details of soft tissue, which are at the contrast detection limit on diagnostic mammograms, are clearly visible on planar analyzer-based x-ray images. Analyzer-based x-ray CT yields high contrast from smoothly varying internal structures, such as tumorous mass lesions, corresponding to information on actual structures seen at histopathologic analysis. The mean glandular dose of 1.9 mGy in analyzer-based x-ray CT is approximately equivalent to the dose administered during single-view screening mammography. The improved visibility of mammographically indistinguishable lesions in vitro suggests that analyzer-based x-ray CT may be a valuable method in radiographic evaluation of the breast, thereby justifying further investigations.

Colorectal Dysplasia and Carcinoma in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

BACKGROUND The aim of this study was to evaluate the role of primary sclerosing cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative colitis (UC). METHODS Forty-five patients with UC and concomitant PSC and 45 pair-matched control patients with UC only were examined for colorectal dysplasia and carcinoma. RESULTS The median duration of UC was 11 years in the group with UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%) with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia; and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P < 0.05). CONCLUSION The results suggest that the risk of colorectal dysplasia and carcinoma in patients with UC is increased by concomitant PSC.

Predictive Factors for the Status of Non-sentinel Nodes in Breast Cancer Patients with Tumor Positive Sentinel Nodes

In patients with tumor positive sentinel nodes, axillary lymph node dissection is routinely performed while a majority of these patients have no tumor involvement in the non-sentinel nodes. The authors tried to identify a subgroup of patients with a tumor positive sentinel node without non-sentinel node tumor involvement. In 135 consecutive patients with tumor positive sentinel nodes and axillary lymph node dissection performed, the incidence of non-sentinel node involvement according to tumor and sentinel node related factors was examined. The size of the sentinel node metastasis, size of primary tumor and number of tumor positive sentinel nodes were the three factors significantly predicting the status of the non-sentinel nodes. The size of the sentinel node metastasis was the strongest predictive factor (P < 0.0001). In a subgroup of 41 patients with a stage T1 tumor and micrometastatic involvement in the sentinel node only 2 patients (5%) had non-sentinel node involvement. In patients with small primary tumors and micrometastatic involvement of the sentinel nodes, the chance of non-sentinel node involvement is small but cannot be discarded. Because the clinical relevance of micrometastases in lymph nodes is still unclear it is not advisable to omit axillary lymph node dissection even in these patients.

International Multicenter Tool to Predict the Risk of Nonsentinel Node Metastases in Breast Cancer

BACKGROUND Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.

Breast lymphedema after breast conserving treatment

The authors aimed to evaluate breast lymphedema after breast conserving therapy (BCT) and sentinel node biopsy (SNB) or axillary clearance (AC). Fifty-seven breast cancer patients with BCT underwent SNB only and 103 underwent AC (57 with tumor negative and 46 with positive axillary nodes). Clinical examination and breast ultrasonography (US) were performed one year after surgery. Clinical examination revealed breast edema in 48% of patients in the AC node positive group, in 35% in the AC node negative group, and in 23% in the SNB group (p<0.05 between SNB and AC node positive). US revealed subcutaneous edema in the operated breast in 69–70% of the patients in the AC groups and in 28% in the SNB group (p=0.001–0.0001 between the SNB and the AC groups). Breast lymphedema was less common one year after BCT in patients with SNB only than in those with more extensive axillary treatment.

The clinical value of parasternal sentinel node biopsy in breast cancer

BackgroundLymphoscintigraphy (LS) with sentinel node (SN) biopsy is proposed to provide a feasible method to complete lymphatic staging in breast cancer. The aim of this study was to evaluate the clinical value of parasternal SN biopsy.MethodsA total of 984 consecutive patients with clinical stage T1/2N0 invasive breast cancer who underwent LS and SN biopsy were included in the study. A prospectively collected database was used. An intratumoral injection of 50 to 145 MBq of 99mTc-labeled human albumin colloid (Nanocoll) was used for preoperative LS.ResultsLS showed the axillary SN in 844 (86%) cases and the parasternal SN in 138 (14%) cases. The median number of visualized parasternal SN was 2 (range, 1–6). Visualization of the parasternal SN was more common in patients with mediocentral tumors (81 of 399; 20%) and in patients with lateral tumors (56 of 585; 10%; P < .0001). Parasternal SNs were visualized more often, in 100 (17%) of 584 patients without axillary metastases compared with 38 (10%) of 400 patients with metastatic axillary nodes (P = .0006). Parasternal SNs were harvested successfully in 121 (88%) patients with visualization of those nodes. Parasternal SN metastases were detected in 18 patients, with a median of 1 metastasis (range, 1–4 metastases). Eight of these 18 patients were axillary node negative.ConclusionsParasternal SN biopsy results in upstaging in 2% of all breast cancer patients who undergo SN biopsy. The clinical value of the procedure seems insignificant, although it may influence the adjuvant treatment regimen in some patients.

Pain in 1,000 women treated for breast cancer: a prospective study of pain sensitivity and postoperative pain.

Background:This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women. Methods:One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone. Results:The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4–5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures. Conclusions:Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.In a study of 1,000 women undergoing breast surgery for cancer, a small portion of the variance in preoperative response to noxious heat and cold testing could be explained by anxiety, the presence of chronic pain, and the number of previous operations. There was a weak correlation between response to experimental pain testing and acute postoperative pain, with largely similar predictive factors across both.