[Prioritising breast cancer care during the corona crisis]. / Prioritering van borstkankerzorg tijdens coronacrisis.

Over the past few months, regular care has been postponed where possible in order to increase the healthcare capacity for COVID-19 patients. The pressure imposed on the healthcare system by the new coronavirus has led to the need for the prioritising of breast cancer care. Several professional scientific and medical organisations have published proposals to prioritise oncological care. Due to the poor prognosis, care for patients with progressive disease during neoadjuvant systemic therapy and a triple negative, may not be postponed. In certain groups of patients, including those with ductal carcinoma in situ or an endocrine sensitive tumour, treatment may be postponed or modified, although with certain reservations.At the initiative of the NationaalBorstkankerOverleg Nederland, prospective data are currently being collected in order to gain more insight into the impact of COVID-19 on breast cancer care.

Structure of sticky-hard-sphere random aggregates: The viewpoint of contact coordination and tetrahedra.

We study more than 10^{4} random aggregates of 10^{6} monodisperse sticky hard spheres each, generated by various static algorithms. Their packing fraction varies from 0.370 up to 0.593. These aggregates are shown to be based on two types of disordered structures: random regular polytetrahedra and random aggregates, the former giving rise to δ peaks on pair distribution functions. Distortion of structural (Delaunay) tetrahedra is studied by two parameters, which show some similarities and some differences in terms of overall tendencies. Isotropy of aggregates is characterized by the nematic order parameter. The overall structure is then studied by distinguishing spheres in function of their contact coordination number (CCN). Distributions of average CCN around spheres of a given CCN value show trends that depend on packing fraction and building algorithms. The radial dependence of the average CCN turns out to be dependent upon the CCN of the central sphere and shows discontinuities that resemble those of the pair distribution function. Moreover, it is shown that structural details appear when the CCN is used as pseudochemical parameter, such as various angular distribution of bond angles, partial pair distribution functions, Ashcroft-Langreth and Bhatia-Thornton partial structure factors. These allow distinguishing aggregates with the same values of packing fraction or average tetrahedral distortion or even similar global pair distribution function, indicative of the great interest of paying attention to contact coordination numbers to study more precisely the structure of random aggregates.

Neoadjuvant chemotherapy in breast-conserving surgery - Consequences on margin status and excision volumes: A nationwide pathology study.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is increasingly used in patients with operable disease due to the potential of converting patients requiring mastectomy to breast conserving surgery (BCS) or lowering resection volumes to improve cosmetic outcome. This nationwide retrospective study aims to determine margin status and specimen volume in patients with invasive breast cancer who underwent BCS after NACT. METHODS: All patients who underwent BCS in 2012-2013 for invasive breast cancer were selected from a nationwide network and registry of histology and cytopathology in the Netherlands (PALGA). RESULTS: Of the 9901 patients, 626 (6.3%) received NACT. After primary surgery 949 (10.2%) patients had tumour-involved margins compared to 152 (24.3%) after NACT. Close margins (≤1 mm) were seen in another 111 (17.7%) patients after NACT. The adjusted odds ratio for involved margins after NACT was 2.94, meaning a three times higher risk of involved margins compared with primary surgery. In patients with lobular carcinoma (54.9%) and no response to NACT (42.1%) higher tumour-involved margins were seen. High resection volumes >60 cc were observed in 224 (36%) patients after NACT of which 37 (16.5%) had tumour involved margins and 32 (14.3%) close margins ≤1 mm. CONCLUSION: The primary goal of the surgeon performing BCS after NACT, to reach tumour-free margins, is not accomplished in one out of four patients. Patients especially at risk are patients with ILC and no pathological tumour response. Excessive resection volumes after NACT do not guarantee tumour-free margins. Further research is necessary to analyze whether we are counterproductive when NACT is given in order to lower resection volumes.

A nationwide pathology study on surgical margins and excision volumes after breast-conserving surgery: There is still much to be gained.

AIM OF THE STUDY: The current study aims to assess margin status in relation to amount of healthy breast tissue resected in breast-conserving surgery (BCS) on a nationwide scale. METHODS: Using PALGA (a nationwide network and registry of histology and cytopathology in the Netherlands), all patients who underwent BCS for primary invasive carcinoma in 2012-13 were selected (10,058 excerpts). 9276 pathology excerpts were analyzed for a range of criteria including oncological margin status and distance to closest margin, specimen weight/volume, greatest tumor diameter, and with or without localization method. Calculated resection ratios (CRR) were assessed to determine excess healthy breast tissue resection. RESULTS: Margins for invasive carcinoma and in situ carcinoma combined were tumor-involved in 498 (5.4%) and focally involved in 1021 cases (11.0%) of cases. Unsatisfactory resections including (focally) involved margins and margins ≤ 1 mm were reported in 33.8% of patients. The median lumpectomy volume was 46 cc (range 1-807 cc; SD 49.18) and median CRR 2.32 (range 0.10-104.17; SD 3.23), indicating the excision of 2.3 the optimal resection volume. CONCLUSION: The unacceptable rate of tumor-involved margins as well as margins ≤ 1 mm in one third of all patients is also achieved at the expense of healthy breast tissue resection, which may carry the drawback of high rates of cosmetic failure. These data clearly suggest the need for improvement in current breast conserving surgical procedures to decrease tumor-involved margin rates while reducing the amount of healthy breast tissue resected.

Intestinal ischaemia caused by mesenteric inflammatory veno-occlusive disease.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischaemia. Previously described cases of MIVOD demonstrate vasculitis in mesenteric veins with thrombotic occlusion. It is important to distinguish MIVOD from other diseases, such as mesenteric venous thrombosis and systemic diseases. We present a case of a 39-year-old Turkish male in whom MIVOD was diagnosed after exclusion of other causes of ischaemic enteritis.

[Granulomatous mastitis: a rare cause of breast swelling]. / Een zeldzame oorzaak van een mammagezwel: granulomateuze mastitis.

Three women, aged 37, 39 and 29 years, presented with unilateral painful swelling of the breast. Ultrasound revealed inflammation with abscess formation. Histological biopsies contained granulomatous tissue without necrosis. Corynebacterium species were cultured in the first two patients. All 3 patients were diagnosed with granulomatous mastitis and were successfully treated with doxycycline. Granulomatous mastitis is a rare disorder that may mimic breast carcinoma. It occurs most frequently in fertile women. Diagnosis is based on histological biopsy which shows granulomas without necrosis, while other causes of granulomatous inflammation, especially tuberculosis, have been excluded. The aetiology is not fully understood. It is hypothesised that the granulomatous mastitis is caused by a type IV allergic reaction. Recently an association with Corynebacterium species was suggested. Best practice treatment methods are unclear. Most patients are treated with surgical intervention and steroids, but the rate of recurrence is high (50%). Treatment with doxycycline must be considered in patients with cultured Corynebacterium species.

Monoclonal antibodies against the human mannose receptor as a specific marker in flow cytometry and immunohistochemistry for macrophages.

Recently we developed mouse monoclonal antibodies (mAb) against the isolated human 175-kDa mannose receptor. In the present study we tested whether these mAb are suitable for the detection of the mannose receptor on cultured macrophages using flow cytometry and on cells in human tissues using immunohistochemistry. Human monocytes did not react with the mAb in flow cytometry. Mannose receptor expression became detectable on monocytes cultured for 3 days (macrophages), and was maximal from 4 days onward. The mannose receptor was up-regulated on dexamethasone-treated (immunosuppressed) macrophages, and down-regulated on lipopolysaccharide-treated (activated) macrophages. Immunohistochemically the staining pattern of our mAb was compared with the marker of monocytes/macrophages KP1. In a bone marrow smear, only macrophages were stained with our mAb, whereas all myeloid cells were stained with KP1. In the thymus and lymph node, mannose receptor-positive branched cells (macrophages and dendritic cells) were detected in connective tissue, thymus cortex (not medulla), and in the T cell area (not the B cell area) of lymph nodes, whereas KP1 stained branched cells in all areas. It was concluded that the mAb are useful tools in flow cytometry and immunohistochemistry for the specific detection of cells expressing mannose receptor.

A novel bone marrow frozen section assay for studying hematopoietic interactions in situ: the role of stromal bone marrow macrophages in erythroblast binding.

Bone marrow macrophages are found in intimate contact with erythroblasts. Exact mechanisms and functions of this interaction are unclear. New insights into erythroblast binding were obtained using a newly developed bone marrow frozen section assay. This modified Woodruff and Stamper assay has some important advantages compared to other adhesion assays. Erythroblasts specifically adhered to bone marrow macrophages forming clusters, as appear in vivo. Selective depletion of bone marrow macrophages by intravenous injection of dichloromethyl-enediphosphonate resulted in a release of immature erythroid cells to the peripheral blood. Furthermore no erythroblasts adhered to bone marrow sections without macrophages. Evaluating the binding of erythroblasts to bone marrow macrophages we found that this binding is temperature and cation dependent. The receptor for erythroblasts present on macrophages recognizes a sialyated protein as ligand on erythroblasts, since neuraminidase treatment of erythroblasts resulted in a decrease in binding. A possible candidate for the erythroblast receptor on macrophages is the ED2 antigen. ED2 is a differentiation antigen present on resident macrophages that has some biochemical features characteristic of an adhesion molecule. Erythroblast binding to bone marrow was inhibited using a monoclonal antibody directed against ED2.

Characterization and expression of the antigen present on resident rat macrophages recognized by monoclonal antibody ED2.

Because of the absence of a specific marker for labeling resident macrophages in the rat, there is almost no information available regarding the properties of individual resident macrophages in different organs. The recently described and in our laboratory developed mAb ED2, has been shown to exclusively recognize resident macrophages. The present study examines expression, function and structure of the ED2 antigen to obtain more information about the marker and therefore, more information about resident macrophages. In earlier studies, the expression of ED2 could not be induced by a range of macrophage stimulating factors under non-adherent culture conditions. We show a highly inducible expression of the ED2 antigen under adhering, non proliferating conditions as well as in long-term bone marrow cultures. ED2 appears to recognize a surface protein on resident macrophages consisting of three protein chains of 175, 160, and 95 kDa.