Safe total intrafascial laparoscopic (TAIL™) hysterectomy: a prospective cohort study

This study directly compares total intrafascial laparoscopic (TAIL™) hysterectomy with vaginal (VH) and abdominal (AH) hysterectomy with regard to safety, operating time and time of convalescence. The study is a prospective cohort study (Canadian Task Force classification II-2), including data from patients of a single university-affiliated teaching institution, admitted between 1997 and 2008 for hysterectomy due to benign uterus pathology. Patient data were collected pre-, intra- and postoperatively and complications documented using a standardised data sheet of a Swiss obstetric and gynaecological study group (Arbeitsgemeinschaft Schweizerische Frauenkliniken, Amlikon/Switzerland). Classification of complications (major complications and minor complications) for all three operation techniques, evaluation of surgeons and comparison of operation times and days of hospitalisation were analysed. 3066 patients were included in this study. 993 patients underwent AH, 642 VH and 1,431 total intrafascial hysterectomy. No statistically significant difference for the operation times comparing the three groups can be demonstrated. The mean hospital stay in the TAIL™ hysterectomy, VH and AH groups is 5.8 ± 2.4, 8.8 ± 4.0 and 10.4 ± 3.9 days, respectively. The postoperative minor complications including infection rates are low in the TAIL™ hysterectomy group (3.8%) when compared with either the AH group (15.3%) or the VH group (11.2%), respectively. The total of minor complications is statistically significant lower for TAIL™ hysterectomy as for AH (O.R. 4.52, CI 3.25–6.31) or VH (O.R. 3.16, CI 2.16–4.62). Major haemorrhage with consecutive reoperation is observed statistically significantly more frequent in the AH group when compared to the TAIL™ hysterectomy group, with an O.R. of 6.13 (CI 3.05–12.62). Overall, major intra- and postoperative complications occur significant more frequently in the AH group (8.6%) when compared to the VH group (3%) and the TAIL™ hysterectomy group (1.8%). The incidence of major complications applying the standardised TAIL™ hysterectomy technique is not related to the experience of the surgeons. We conclude that a standardised intrafascial technique of total laparoscopic (TAIL™) hysterectomy using an anatomically developed special uterine device is associated with a very low incidence of minor and major intra- and postoperative complications. The direct comparison of complication rates with either vaginal or abdominal hysterectomy favours the total laparoscopic technique, and therefore, this technique can be recommended as a relatively atraumatic procedure. The operation times are comparable for all three techniques without any statistically significant differences. This technique for laparoscopic hysterectomy is shown to be equally safe when applied by experienced gynaecologic surgeons or by residents in training

Successful remission of extensive liver metastases in a breast cancer patient with acute liver failure using a combined chemotherapy regimen with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU)

Liver failure due to disseminated hepatic secondaries represents a therapeutic dilemma in patients with metastatic breast cancer (MBC). Reduced liver function and non-assessable toxicity are limiting factors in the selection of chemotherapeutic agents. Currently, there is no standard treatment after failure of anthracycline-and taxane-based first-line therapies, although there is a variety of well evaluated drugs such as capecitabine

Phase-contrast enhanced mammography: A new diagnostic tool for breast imaging

Phase contrast and scattering-based X-ray imaging can potentially revolutionize the radiological approach to breast imaging by providing additional and complementary information to conventional, absorption-based methods. We investigated native, non-fixed whole breast samples using a grating interferometer with an X-ray tube-based configuration. Our approach simultaneously recorded absorption, differential phase contrast and small-angle scattering signals. The results show that this novel technique - combined with a dedicated image fusion algorithm - has the potential to deliver enhanced breast imaging with complementary information for an improved diagnostic process

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Aim: Demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recom-mendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BRPeer reviewe

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Development and Clinical Evaluation of New Approaches in Breast Cancer Diagnosis: Differential Phase Contrast Mammography

Purpose, Objectives Differential phase contrast and scattering-based X-ray mammography is known to provide additional and complementary diagnostic information and may provide additional and complementary clinically relevant information compared with absorption-based mammography. This new diagnostic technology has the potential to play a crucial role in medical diagnostics. The preliminary results presented report on the first mammographic investigation of five native, i.e. - freshly dissected, breasts carried out with a grating interferometer and a conventional X-ray tube source. Four patients in this initial study had histopathologically-proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. Another investigation evaluated the method of differential phase contrast mammography to distinguish between benign and malignant microcalcifications with the benefit to increase accuracy of early breast cancer diagnosis. Two major types of microcalcifications may be distinguished within breast tissue. Type I microcalcifications consist of calcium oxalate dehydrate whereas type II microcalcifications are composed of calcium phosphates. Type I may most frequently be seen in benign lesions whereas type II may be indicative for proliferative lesions, including invasive carcinoma. The goal of this study is to distinguish the two types of microcalcifications by the use of a non-invasive approach. After these first evaluations of the mammographic investigation, in an additional step the new technology has been evaluated with regard to image quality and clinical relevance by the use of two blinded international multicenter reader studies. Patients and Methods We used a Talbot-Lau grating setup installed on a conventional, low-brilliance X-ray source: the interferometer operated at the 5th Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Pre-surgical images (conventional mammography, ultrasonography and magnetic resonance imaging (MRI)) supported the findings and clinical relevance was verified. Based on these results, indicating clinical relevance, we investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using the described grating-based differential phase contrast mammography (mammoDPC) device. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a two-part blinded reader study. The results were statistically analyzed in terms of image quality and clinical relevance. Results The first approach yielded complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the breast samples at the microscopic scale. This information can be transferred into imaging improvement and may be used to address clinically-relevant, yet unresolved questions such as: unequivocally discerning between malignant and pre-malignant changes and post-operative scars and distinguishing cancer-invaded regions within healthy tissue. First unpublished results presented here of phase contrast mammography indicate that this technique implies the potential to distinguish between different types of microcalcifications and therefore may serve as a crucial step forward to improve early breast cancer diagnosis. On the basis of the presented results, the comparison of mammoDPC with clinical digital mammography by the blinded reader studies revealed the general quality of the images to be significantly superior (p<0.001), sharpness and lesion delineation as well as general visibility of calcifications to be significantly more assessable (p<0.001) and delineation of surface structures to be significantly sharper (p<0.001). Spiculations were significantly better identified by the readers and the overall clinically relevant information provided by mammoDPC was judged to be superior (p<0.001). Conclusions With the approaches described to investigate native breast tissue samples by the use of the differential phase contrast mammography the first and unique ex-vivo images of fresh, native breast tissue could be obtained from mastectomy specimens using grating interferometry. By the use of fusion algorithms, we demonstrate that fused images of absorption, phase contrast and scattering signals acquired with mammoDPC have the potential to deliver enhanced digital mammography. This technique allows to distinguish between different types of microcalcifications within breast tissue and therefore may serve as a new non-invasive tool in early breast cancer diagnosis. The complementary information gained by this technique yielded clinical images of generally superior quality and has the potential to lead to improved radiological breast diagnostics. The promising presented results advanced us toward the ultimate goal: using grating interferometry in-vivo on humans in a clinical setting

Interaction of cartilage matrix protein with aggrecan. Increased covalent cross-linking with tissue maturation

Cartilage matrix protein (CMP) is a trimeric protein present in many types of cartilage extracellular matrix. It has recently been purified under native conditions that allowed the proposal of a structural model (Hauser, N., and Paulsson, M. (1994) J. Biol. Chem. 269, 25747-25753). To examine the functional properties of CMP we studied its interaction with aggrecan within cartilage extracellular matrix. Aggrecan-enriched fractions were purified from bovine tracheal cartilage of different ages under nondenaturing and denaturing conditions, respectively, and characterized by a combination of biochemical methods and electron microscopy. The fractions contained a pool of CMP noncovalently associated with aggrecan as well as a pool of CMP that appears covalently cross-linked to the aggrecan core protein. Only about two thirds of the CMP subunits could be released even upon reduction under denaturing conditions. It appears that CMP is attached by a nonreducible covalent interaction of one of its subunits with the protein core. The amount of CMP strongly bound to aggrecan increases with age. Electron microscopy revealed interaction sites for CMP in the extended chondroitin-sulfate attachment domain E2. In old tissue five distinct binding sites for CMP were found while in young cartilage only three of these were occupied. The extent of decoration of E2 with CMP increases with age