Reproducibility in the diagnosis of needle core biopsies of non-palpable breast lesions: an international study using virtual slides published on the world-wide web.

AIMS: To conduct an internet-based study using virtual slides (VS) of sterotactic core biopsy specimens of non-palpable breast lesions in order to evaluate interobserver reproducibility between pathologists. METHODS AND RESULTS: A total of 18 breast lesions, determined to be histologically complex by two pathologists, were selected. Digitized VSs were then created using QuickTime Virtual Reality technology (Apple, Cupertino, CA, USA) and posted on the world-wide web. In all, 10 pathologists completed the evaluations of 18 VSs using the five diagnostic categories (B1-B5) from the European guidelines for quality assurance in breast cancer screening and diagnosis. Their results were compared with those of every other participating pathologist, and were then individually compared with the results of a highly experienced breast pathologist (referee). Of the 18 cases, 10 (56%) were classified by the referee as borderline (B3 and B4). Comparisons with reference values showed a less than satisfactory level of reproducibility (median kappa(w) = 0.60). As regards interobserver reproducibility, results showed that, in general, the level of agreement was not satisfactory (median kappa(w) = 0.53). CONCLUSIONS: Overall, the findings are comparable to those quality control studies using circulating slides when analysis is done on borderline cases.

Microsatellite Instability and Survival in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: About 15-20% of colorectal cancers (CRCs) have deficiency in a mismatch repair (MMR) protein. MMR has a high level of microsatellite instability (MSI-H). We have conducted this review and meta-analysis to determine the prognostic role of MSI-H status in stage II CRC. MATERIALS AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, and SCOPUS for studies reporting data on overall survival (OS) and disease-free or relapse-free survival (DFS or RFS) for MSI-H compared to microsatellite stable (MSS) CRC. RESULTS: A total of 39 studies were analysed, including 12,110 patients. MSI-H status was associated with a significantly reduced risk of death (HR=0.64, 95%CI=0.52-0.8, p<0.01) and relapse (HR=0.59, 95%CI=0.45-0.77, p<0.01) in stage II CRC. CONCLUSION: MSI-H represents an important prognostic determinant in stage II CRC and may be considered when estimating the risk of recurrence in stage II CRC.

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy.

Neoadjuvant imatinib in a locally advanced gastrointestinal stromal tumour (GIST) of the rectum: a rare case of two GISTs within a family without a familial GIST syndrome.

Gastrointestinal stromal tumours are rare tumours of the gastrointestinal tract. We describe the case of a 57-year-old man with a locally advanced gastrointestinal stromal tumour of the rectum. We started Gleevec. The pathological examination documented a complete pathological response. An already described mutation in KIT exon 11 was observed in the gastrointestinal stromal tumour of the rectum. At the same time as the treatment of our patient, his brother received a neoadjuvant therapy for a locally advanced rectal adenocarcinoma. During the surgical procedure, a gastric lesion was excised and the pathological examination showed a low-grade gastrointestinal stromal tumour. We analysed DNA extracted from the tumoral mass and normal tissue of both patients. No mutations, either in KIT or in PDGFRA, were detected in the subserosal stomach gastrointestinal stromal tumour. After 18 months, both patients are free from recurrence. Our clinical case suggests that preoperative imatinib therapy may enable radical surgery in patients with an inoperable disease.

Prognostic value of diffuse versus intestinal histotype in patients with gastric cancer: a systematic review and meta-analysis.

BACKGROUND: There are two distinct types of gastric carcinoma (GC), intestinal, more frequently sporadic and linked to environmental factors, and diffuse (undifferentiated) that is highly metastatic and characterized by rapid disease progression and a poor prognosis. However, there are many conflicting data in the literature concerning the association between histology and prognosis in GC. This meta-analysis was performed to provide demonstration if histology according to Lauren classification is associated with different prognosis in patients with GC. METHODS: We searched PubMed, the Cochrane Library, SCOPUS, Web of Science, CINAHL, and EMBASE for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival (OS) were evaluated. RESULTS: A total of 73 published studies including 61,468 patients with GC were included in this meta-analysis. Our analysis indicates that GC patients with diffuse-type histology have a worst prognosis than those with intestinal subgroup in all studies (HR 1.23; 95% CI, 1.17-1.29; P<0.0001), in both loco-regional confined (HR 1.21; 95% CI, 1.12-1.30; P<0.0001) and advanced disease (HR 1.25; 95% CI, 1.046-1.50; P=0.014), in Asiatic (HR 1.2; 95% CI, 1.14-1.27; P<0.0001) and Western patients (HR 1.3; 95% CI, 1.19-1.41; P<0.0001), and in those not exposed (HR 1.15; 95% CI, 1.07-1.24; P<0.0001) or exposed (HR 1.27; 95% CI, 1.17-1.37; P<0.0001) to (neo)adjuvant therapy. CONCLUSIONS: Our results indicated that histology might be a useful prognostic marker for both early and advanced GC patients, with intestinal-type associated with a better outcome. This information could be used for stratification purpose in future clinical trials.