On the Acceptance of "Fake" Histopathology: A Study on Frozen Sections Optimized with Deep Learning.

BACKGROUND: The fast acquisition process of frozen sections allows surgeons to wait for histological findings during the interventions to base intrasurgical decisions on the outcome of the histology. Compared with paraffin sections, however, the quality of frozen sections is often strongly reduced, leading to a lower diagnostic accuracy. Deep neural networks are capable of modifying specific characteristics of digital histological images. Particularly, generative adversarial networks proved to be effective tools to learn about translation between two modalities, based on two unconnected data sets only. The positive effects of such deep learning-based image optimization on computer-aided diagnosis have already been shown. However, since fully automated diagnosis is controversial, the application of enhanced images for visual clinical assessment is currently probably of even higher relevance. METHODS: Three different deep learning-based generative adversarial networks were investigated. The methods were used to translate frozen sections into virtual paraffin sections. Overall, 40 frozen sections were processed. For training, 40 further paraffin sections were available. We investigated how pathologists assess the quality of the different image translation approaches and whether experts are able to distinguish between virtual and real digital pathology. RESULTS: Pathologists' detection accuracy of virtual paraffin sections (from pairs consisting of a frozen and a paraffin section) was between 0.62 and 0.97. Overall, in 59% of images, the virtual section was assessed as more appropriate for a diagnosis. In 53% of images, the deep learning approach was preferred to conventional stain normalization (SN). CONCLUSION: Overall, expert assessment indicated slightly improved visual properties of converted images and a high similarity to real paraffin sections. The observed high variability showed clear differences in personal preferences.

Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model.

The regulatory (neuro)peptide galanin and its three receptors (GAL1-3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL2R and GAL3R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn's disease and ulcerative colitis) expressed GAL2R and GAL3R but not GAL1R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL3R (GAL3R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL3R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL3R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL2R deletion did not influence the course of colitis. In conclusion, granulocyte GAL2R and GAL3R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL3R loss. Consequently, GAL3R poses a novel therapeutic target for IBD.

The clinical impact of DNA methylation frequencies of JAK2 negative regulators in patients with essential thrombocythemia.

Suppressors of cytokine signalling (SOCS) and protein tyrosine phosphatase (PTPN) proteins are negative regulators of Janus Kinase 2 (JAK2). They are thought to be involved in the molecular pathogenesis of essential thrombocythaemia (ET) particularly in patients with unmutated JAK2. In this study we compared DNA methylation of SOCS1, SOCS3 and PTPN6 in peripheral blood cells between 39 ET patients (24 JAK2 V617F mutated) and 22 healthy controls by methylation specific PCR (MSP) and analysed the clinical outcome of patients with respect to DNA methylation. In SOCS1, ET patients showed significantly less methylation (P<0.05) than healthy controls, and in SOCS3 and PTPN6 such a tendency was shown. However, there were no significant differences in the methylation frequencies between JAK2 wildtype and mutated ET patients. In addition, no correlation was detected between methylation of SOCS and PTPN and any clinical outcome parameters. Taken together, regarding the genomic regions investigated our data indicate a minor role of methylation of JAK2 negative regulators for the clinical course of ET.

Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes.

BACKGROUND: Sentinel node (SN) biopsy after preoperative chemotherapy (PC) in breast cancer patients is associated with a lower identification rate (IR) and an increased false-negative rate (FNR) compared with SN biopsy in untreated patients. Our aims were to examine the feasibility of SN mapping before PC and the possibility to assess the lymph node status after chemotherapy through a follow-up lymphatic mapping. METHODS: SN biopsy was performed in 45 clinically node-negative breast cancer patients before PC. A follow-up lymphatic mapping was done after completion of chemotherapy and irrespective of the lymph node status was followed by axillary lymph node dissection (ALND). RESULTS: SN mapping before chemotherapy identified a mean of 2.3 SNs in all patients (IR 100%). Nineteen patients revealed a negative SN; 26 patients had a positive SN (micrometastasis found in 6/26 patients). After PC follow-up lymphatic mapping was successful in 29 of 45 patients (IR 64%). IR for follow-up mapping was 80% for patients with a negative or micrometastatic SN before chemotherapy compared with 45% for patients with macrometastatic SNs (P = .027, Fisher exact test). None of the patients with a negative or micrometastatic SN before chemotherapy revealed positive lymph nodes after PC (P = .031, McNemar test) and the FNR for follow-up lymphatic mapping in these patients was 0%. Contrary to that, 15 of 20 patients with a macrometastasis before PC had positive nodes after chemotherapy, and the FNR of follow-up mapping in these patients was 50%. CONCLUSIONS: Patients with a negative SN before PC may forego complete ALND after PC, whereas this may not be valid for patients with macrometastatic SNs. Follow-up lymphatic mapping in patients with positive nodal status before chemotherapy is associated with a low IR and a high FNR.

Symmetrization reduction mammaplasty combined with sentinel node biopsy in patients operated for contralateral breast cancer.

BACKGROUND AND OBJECTIVES: Occult invasive cancer found in reduction mammaplasty specimen in the contralateral breast in breast cancer patients requires axillary lymph node dissection (ALND) to assess the lymph node status. Routine Sentinel node (SN) biopsy in these patients may avoid secondary ALND when an occult cancer is found and the SN is negative in the permanent histological examination. METHODS: One hundred sixty-nine breast cancer patients underwent contralateral reduction mammaplasty for symmetrization and with SN biopsy of the non-cancer breast. SN mapping was done using a vital blue dye alone (n = 136) or in combination with a radiocolloid (n = 33). RESULTS: A mean number of 1.4 SNs (range 1-3 SNs) was identified in 158 of 169 patients (identification rate 93.5%). One of 158 patients revealed a positive SN but no tumor was found in the reduction mammaplasty/mastectomy specimen, whereas the SN was negative in 157 patients. Histological examination of the 169 reduction mammaplasty specimen revealed 5 occult invasive cancers and 4 patients with high grade DCIS but due to a negative SN biopsy the patients were spared a secondary ALND. CONCLUSION: The small number of patients with occult contralateral cancers may not warrant routine SN mapping in patients scheduled for contralateral reduction mammaplasty.

[Subacute thyroiditis with cell destruction and temporary hyperthyroidism in Graves'disease--case report]. / Subakute Thyreoiditis mit Zellzerfall und passagerer Hyperthyreose in einer Basedow-Struma--Fallbericht.

We present the case of a 60-year old woman with painful swelling of the thyroid gland and temporary thyrotoxicosis. 30 years ago she had experienced a period of hyperthyroidism because of Graves' disease. This time thyrotropin-receptor-antibodies were negative, Tc-99 m scan revealed decreased uptake in both lobes (this pattern normalised later on) and fine needle aspiration presented leucocyte infiltration of the thyroid. Three months later hypothyroidism was observed requiring treatment with levothyroxine. The development of subacute thyroiditis and Graves' disease in the same person is rare, autoimmune factors and a possible relationship are discussed.