Correction to: Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

Following publication of the original article [1], the authors reported an added data on Table 1 in their paper. The original article [1] has been updated.

Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

BACKGROUND: Evaluation of core needle biopsies (CNB) is a standard procedure for the diagnosis of breast cancer. However, tissue processing and image preparation is a time- consuming procedure and instant on-site availability of high-quality images could substantially improve the efficacy of the diagnostic procedure. Conventional microscopic methods, such as frozen section analysis (FSA) for detection of malignant cells still have clear disadvantages. In the present study, we tested a confocal microscopy scanner on fresh tissue from CNB with intention to develop an alternative device to FSA in clinical practice. PATIENTS AND METHODS: In 24 patients with suspicious breast lesions standard of care image-guided biopsies were performed. Confocal images have been obtained using the Histolog™ Scanner and evaluated by two independent pathologists. Hematoxylin-Eosin (H&E) histological sections of the biopsies were routinely processed in a blinded fashion with respect to the confocal images. RESULTS: In total 42 confocal images were generated from 24 biopsy specimens, and available for analysis within a few minutes of taking the biopsy. This resulted in 2 × 42 = 84 pathologic evaluations. In four cases, a pathologic diagnosis was not possible with confocal microscopy. An exact correlation based on the B-classification was reached in 41 out of 80 examinations and in another 35 cases in a broader sense of correspondence definition (i.e. malignant vs. benign). CONCLUSIONS: As a reliable on-site method, the Histolog™ Scanner provides a visualization of cellular details equivalent to the H&E standards, permitting rapid and accurate diagnosis of malignant and benign breast lesions. Furthermore, this device offers great potential for immediate margin analysis of specimen in breast conserving therapy.

Can axillary reverse mapping avoid lymphedema in node positive breast cancer patients?

BACKGROUND: Tracing lymphatic drainage of the ipsilateral arm of node positive breast cancer patients, termed "axillary reverse mapping" (ARM), has recently been described in several reports. We analyzed our experience with this new technique in patients scheduled for axillary lymph node dissection (ALND) and evaluated its usefulness for reducing the incidence of lymphedema. METHODS: Blue dye was injected subcutaneously along the intermuscular groove of the upper inner arm; radioisotope was injected subcutaneously in the interdigital webspace of the hand. All blue and radioactive lymph vessels and lymph nodes were recorded. Only unsuspicious "ARM lymph nodes" located in the lateral part of the axillary basin were preserved. All other level I and II axillary lymph nodes were removed. Resected ARM nodes were immediately separated from all other lymph nodes. RESULTS: ARM was performed in 143 patients subsequently undergoing ALND. ARM lymph nodes were successfully identified in 112 cases (78%). In 55 patients at least one ARM lymph node had to be removed. In 14 of these, tumor involvement was confirmed. In 71 patients one or more ARM nodes were preserved. During a median follow-up time of 19 months no axillary recurrence was noted. 35 of 114 evaluated patients developed lymphedema. Preservation of ARM lymph nodes did not significantly decrease the incidence of lymphedema. CONCLUSION: ARM is feasible for patients with node positive breast cancer. However, we found no evidence that it reduces the incidence of lymphedema.

Frequency and risk factors of lower limb lymphedema following lymphadenectomy in patients with gynecological malignancies.

OBJECTIVE: Lower limb lymphedema (LLL) is a major cause of morbidity in patients with gynecological malignancies after surgical treatment involving lymph node (LN) dissection. The aim of this study was to estimate the prevalence of LLL in such patients and detect risk factors for its occurrence. MATERIALS AND METHODS: A retrospective analysis of all patients undergoing lymphadenectomy in newly-diagnosed gynecological malignancies at the University Hospital of Zurich between 2000 and 2007 was performed. Data from 313 patients were collected. Twenty patients with pre-existing edema or missing information were excluded before analysis. Time-to-LLL was estimated using the Kaplan-Meier estimate and potential risk factors were evaluated by a Cox regression model. RESULTS: Estimated prevalence of LLL one year after surgery was 32%, increasing to 58% eight years after surgery. Median time to diagnosis of LLL was 5.2 years. The number of removed lymph nodes was significantly associated with time-to-LLL. Diagnosis of postoperative lymphocysts and local infections were accompanied by a significantly elevated risk for the development of LLL. Furthermore, time-to-LLL decreased with a higher body mass index (BMI) of the patient. In contrast, chemo- and radiotherapy, age, positive LNs, site of lymphadenectomy, and type of cancer were not observed to be associated with the occurrence of LLL. CONCLUSIONS: LLL is a frequent postoperative complication in patients undergoing lymphadenectomy for gynecological malignancies. It is thus imperative to sufficiently educate patients about the risk and symptoms of LLL prior to surgery. The data clearly show an association between time-to-LLL and number of dissected LNs, stressing the need to prospectively analyze the prevalence of LLL and carefully plan LN sampling as increasing knowledge is gained regarding the therapeutic benefit of sentinel and systemic lymphadenectomy in patients with different stages of gynecological malignancies.

E5 oncoprotein mutants activate phosphoinositide 3-kinase independently of platelet-derived growth factor receptor activation.

The E5 oncoprotein of bovine papillomavirus type 1 is a Golgi-resident, 44-amino acid polypeptide that can transform fibroblast cell lines by activating endogenous platelet-derived growth factor receptor beta (PDGF-R). However, the recent discovery of E5 mutants that exhibit strong transforming activity but minimal PDGF-R tyrosine phosphorylation indicates that E5 can potentially use additional signal transduction pathway(s) to transform cells. We now show that two classes of E5 mutants, despite poorly activating the PDGF-R, induce tyrosine phosphorylation and activation of phosphoinositide 3-kinase (PI 3-K) and that this activation is resistant to a selective inhibitor of PDGF-R kinase activity, tyrphostin AG1296. Consistent with this independence from PDGF-R signaling, the E5 mutants fail to induce significant cell proliferation in the absence of PDGF, unlike wild-type E5 or the sis oncoprotein. Despite differences in growth factor requirements, however, both wild-type E5 and mutant E5 cell lines form colonies in agarose. Interestingly, activation of PI 3-K occurs without concomitant activation of the ras-dependent mitogen-activated protein kinase pathway. The known ability of constitutively activated PI 3-K to induce anchorage-independent cell proliferation suggests a mechanism by which the mutant E5 proteins transform cells.