Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.     

Die arthroskopische Entfernung des dorsalen Handgelenksganglions

Objective

Pain relief and improvement of hand function by ganglion cyst resection and/or creation of a dorsal capsular window with partial synovectomy. In the case of visible ganglion cysts consideration of aesthetic aspects.

Indications

Visible and occult persisting dorsal wrist ganglion cysts, recurrent ganglion cyst after open or arthroscopic resection and intraosseous ganglion cyst with an extraosseous portion.

Contraindications

Recent skin lesion of the wrist.

Surgical Technique

Standard setting for wrist arthroscopy. Portals: radiocarpal 3?4 and 6R, midcarpal radial (RMC) and midcarpal ulnar (UMC) portals. Start with arthroscopy in 3?4 portal. If there is insufficient visualization of the dorsal capsular fold, change the arthroscope to the 6R portal. From here a tangential view onto the dorsal capsule at the level of the scapholunate (SL) ligament can be obtained. If a large ganglion overlying the 3?4 portal or the RMC portal is present, UMC portals are primarily used. Intra-articular visualization of ganglion structures should always be attempted, especially for occult ganglion cysts. If the radiocarpal findings are inconspicuous, midcarpal arthroscopy from the UMC portal is performed to visualize the dorsal capsule at the SL ligament. Depending on the main localization of the visible alterations, ganglion or thickening of the capsule, a dorsal capsular window is created at the level of the SL ligament either radiocarpal or midcarpal or overlying both joints. Complete resection of the ganglion is controlled by palpation. Use of a 2.4 mm arthroscope with 30° angle of vision and 2.5 mm shaver (aggressive cutter). Low-suction drainage and soft padded dressing. An arthroscope with 70° angle of vision enables an even better view onto the dorsal capsule.

Postoperative management

Immediate wrist mobilization, avoidance of excessive loading for 3 weeks. Physiotherapy is necessary if wrist flexion is not regained 3  weeks postoperatively.

Results

From 2007 to 2010 a total of 92 wrists from 88 patients were treated by arthroscopic ganglion cyst resection, 44?% for occult and 17?% for recurrent ganglia. At a mean follow-up of 78?% after 29.5 months a high patient satisfaction of 90?% was achieved. The only complication was a complex regional pain syndrome (CRPS) in one patient. The recurrence rate was 12.5?%.

     

Max CAPR: High‐resolution 3D contrast‐enhanced MR angiography with acquisition times under 5 seconds

High temporal and spatial resolution is desired in imaging of vascular abnormalities having short arterial‐to‐venous transit times. Methods that exploit temporal correlation to reduce the observed frame time demonstrate temporal blurring, obfuscating bolus dynamics. Previously, a Cartesian acquisition with projection reconstruction‐like (CAPR) sampling method has been demonstrated for three‐dimensional contrast‐enhanced angiographic imaging of the lower legs using two‐dimensional sensitivity‐encoding acceleration and partial Fourier acceleration, providing 1mm isotropic resolution of the calves, with 4.9‐sec frame time and 17.6‐sec temporal footprint. In this work, the CAPR acquisition is further undersampled to provide a net acceleration approaching 40 by eliminating all view sharing. The tradeoff of frame time and temporal footprint in view sharing is presented and characterized in phantom experiments. It is shown that the resultant 4.9‐sec acquisition time, three‐dimensional images sets have sufficient spatial and temporal resolution to clearly portray arterial and venous phases of contrast passage. It is further hypothesized that these short temporal footprint sequences provide diagnostic quality images. This is tested and shown in a series of nine contrast‐enhanced MR angiography patient studies performed with the new method. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region. METHODS: We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration. RESULTS: Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis. CONCLUSIONS: We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.     

Mechanism of action of rituximab

Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). It has a unique mode of action and can induce killing of CD20+ cells via multiple mechanisms. The direct effects of rituximab include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and the indirect effects include structural changes, apoptosis, and sensitization of cancer cells to chemotherapy. In vitro studies have made a significant contribution to the understanding of these mechanisms of action and have led to the development of innovative and effective treatment strategies to optimize patient response. The most significant of these strategies is the combination of rituximab and CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), which is proving a highly effective combination in the treatment of NHL. However, all patients do not respond equally well to rituximab, and in vitro studies have identified a possible mechanism of resistance involving the anti-complement inhibitors CD55 and CD59. Neutralizing antibodies to CD55 and CD59 can overcome resistance to rituximab-mediated complement-mediated cytotoxicity in vitro. This paper overviews our understanding of the mechanisms of action of rituximab and identifies how this knowledge could be applied in a clinical setting to maximize response in both sensitive and resistant patients.     

A multicenter study of treatment of primary CNS lymphoma

OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.     

Karotisendarteriektomie und Karotisstenting Pilotstudie eines prospektiven, randomisierten und kontrollierten Vergleichs

INTRODUCTION: A prospective, randomized and controlled trial is conducted to compare carotid endarterectomy and carotid stenting in high grade symptomatic carotid artery stenoses. METHODS: According to the study design symptomatic patients with a angiographically high-grade (> or = 70%) internal carotid artery stenosis are included. Pre- and postinterventional diagnostics during the hospitalization period includes neurological assessment, duplex sonography of the cervical and cerebral arteries and magnetic resonance imaging of the brain. Follow-up examinations are scheduled after 1, 6 and 12 months and consist of a neurological assessment and duplex sonography. After 12 months selective angiography and magnetic resonance imaging of the brain will be performed additionally. During a period of 9 months up to now 23/137 patients treated for a carotid artery stenosis were included in the study, 11 patients underwent surgery and 12 patients carotid stenting. RESULTS: Carotid stenting and endarterectomy was primarily successful without residual stenosis > 30% in each patient without the occurrence of stroke or death. In 18 follow-up examinations (neurological assessment including duplex sonography) of 13 patients (13 follow-up examinations after 30 days, 5 after 6 months) no relevant restenosis and no stroke occurred. CONCLUSION: As of yet, carotid stenting was a safe procedure. Due to the small number of patients a definitive conclusion can not be drawn.     

Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience.

PURPOSE: To identify survival predictors and to design a prognostic score useful for distinguishing risk groups in immunocompetent patients with primary CNS lymphomas (PCNSL). PATIENTS AND METHODS: The prognostic role of patient-, lymphoma-, and treatment-related variables was analyzed in a multicenter series of 378 PCNSL patients treated at 23 cancer centers from five different countries. RESULTS: Age more than 60 years, performance status (PS) more than 1, elevated lactate dehydrogenase (LDH) serum level, high CSF protein concentration, and involvement of deep regions of the brain (periventricular regions, basal ganglia, brainstem, and/or cerebellum) were significantly and independently associated with a worse survival. These five variables were used to design a prognostic score. Each variable was assigned a value of either 0, if favorable, or 1, if unfavorable. The values were then added together to arrive at a final score, which was tested in 105 assessable patients for which complete data of all five variables were available. The 2-year overall survival (OS) +/- SD was 80% +/- 8%, 48% +/- 7%, and 15% +/- 7% (P =.00001) for patients with zero to one, two to three, and four to five unfavorable features, respectively. The prognostic role of this score was confirmed by limiting analysis to assessable patients treated with high-dose methotrexate-based chemotherapy (2-year OS +/- SD: 85% +/- 8%, 57% +/- 8%, and 24% +/- 11%; P =.0004). CONCLUSION: Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.