Assessment of algorithms for mitosis detection in breast cancer histopathology images

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low inter-observer agreement. With the wider acceptance of whole slide images in pathology labs, automatic image analysis has been proposed as a potential solution for these issues. In this paper, the results from the Assessment of Mitosis Detection Algorithms 2013 (AMIDA13) challenge are described. The challenge was based on a data set consisting of 12 training and 11 testing subjects, with more than one thousand annotated mitotic figures by multiple observers. Short descriptions and results from the evaluation of eleven methods are presented. The top performing method has an error rate that is comparable to the inter-observer agreement among pathologists

Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial)

Background: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. Methods: The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. Discussion: In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient

Efficacy of dose-escalated chemoradiation on complete tumour response in patients with locally advanced rectal cancer (RECTAL-BOOST); a phase 2 randomised controlled trial

Purpose Pathological complete tumour response following chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with favourable prognosis and allows organ-sparing treatment strategies. We aimed to investigate the effect of an external radiation boost to the tumour prior to chemoradiation on pathological or sustained clinical complete tumour response in LARC. Methods and materials This multicentre, non-blinded, phase 2, randomised controlled trial followed the trials within cohorts-design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can accept or refuse this), whereas patients in the control group are not notified about the randomisation. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of two radiotherapy centres were eligible. Patients were randomised to no boost or an external radiation boost (5 x 3 Gy) without concurrent chemotherapy directly followed by standard pelvic chemoradiation (25 x 2 Gy with concurrent capecitabine). The primary outcome was pathological complete response (pCR, i.e. ypT0N0) in patients with planned surgery at 12 weeks or, as surrogate for pCR, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCTXXXXXX. Results Between Sept 2014 and July 2018, 128 patients were randomised. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4-stage and a low rectal tumour (31.3% versus 17.2% and 56.3% versus 45.3% respectively), and more patients had a cN2-stage (59.4% versus 70.3% respectively). Rate of pathological or sustained clinical complete tumour response was similar between the groups: 23 of 64 (35.9%, 95%CI 24.3-48.9) in the intervention group versus 24 of 64 (37.5%, 95%CI 25.7-50.5) in the control group (OR=0.94 95%CI 0.46-1.92). Near-complete or complete tumour regression was more common in the intervention group: 34 of 49 (69.4%) versus 24 of 53 (45.3%) in the control group (OR=2.74, 95%CI 1.21-6.18). Grade >3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR=1.22 95%CI 0.35-4.22). Conclusion Dose escalation with an external radiotherapy boost to the tumour prior to neoadjuvant chemoradiation did not increase the pathological or sustained clinical complete tumour response rate in LARC

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections

Expression of Connective Tissue Growth Factor in Male Breast Cancer : Clinicopathologic Correlations and Prognostic Value

Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC). The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC) and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109) with high expression in 31/109 cases (28.4%), but expression in tumor cells was only seen in 9.2% (10/109) of cases. High stromal CTGF expression correlated with high grade and high proliferation index (> 15%) assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002). Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied

Baseline clinicopathologic features of 109 male breast cancers (MBC) and 75 female breast cancers (FBC).

<p>Baseline clinicopathologic features of 109 male breast cancers (MBC) and 75 female breast cancers (FBC).</p

5 year survival curves for low and high stromal CTGF expression in male breast cancer.

<p>5 year survival curves for low and high stromal CTGF expression in male breast cancer.</p

Associations between stromal CTGF expression and clinicopathologic features in male breast cancer.

<p>Associations between stromal CTGF expression and clinicopathologic features in male breast cancer.</p