Endoscopic biopsies from gastrointestinal carcinomas and their suitability for molecular analysis: a review of the literature and recommendations for clinical practice and research.

Endoscopic biopsies (EBs) are the gold standard for diagnosing gastrointestinal carcinoma yet no guidelines address EB use for prognostic and predictive molecular testing. This review summarizes the reported quantity and quality of EBs, their relationship with molecular test failure rates and the resultant concordance between EB and resection specimen. Studies reporting molecular testing on gastrointestinal carcinoma EBs published between 2002 and 2014 were identified. Details regarding EB quantity, quality, tumour content, molecular test failure rates as well as causes and concordance with resection specimens were reviewed. Seventy-five studies were identified. Eighteen (24%) reported the mean EB number per patient (median: 2.1, range: 1-6.6 EBs). Sixty-one (81%) reported the frequency of test failure (median: 0%, range: 0-100%). Twenty-two (29%) investigated EB and resection specimen concordance (range: 0-100%). EB quantity and quality affected neither concordance nor failure rate. In summary, few studies currently report EB quantity, EB quality or EB and resection specimen concordance. Reliable molecular testing in EBs appears achievable, and can be representative of resection specimens. Concordance depends upon the testing methodology and biomarker heterogeneity within the tumour. To improve patient care, EB sampling, processing and reporting requires standardization and needs optimization for each biomarker individually.

Xanthogranulomatous cholecystitis: a European and global perspective.

INTRODUCTION: Xanthogranulomatous cholecystitis (XGC) is often mistaken for, and may predispose to, gallbladder carcinoma (GB Ca). This study reviews the worldwide variation of the incidence, investigations, management and outcome of patients with XGC. METHODS: Data from 29 studies, cumulatively containing 1599 patients, were reviewed and results summarized by geographical region (Europe, India, Far East and Americas) with 95% confidence intervals (CIs) to present variability within regions. The main study outcomes were incidence, association with GB Ca and treatment of patients with XGC. RESULTS: Overall, the incidence of XGC was 1.3-1.9%, with the exception of India where it was 8.8%. The incidence of GB Ca associated with XGC was lowest in European studies (3.3%) varying from 5.1-5.9% in the remaining regions. Confusion with or undiagnosed GB Ca led to 10.2% of patients receiving over or under treatment. CONCLUSIONS: XGC is a global disease and is associated with GB Ca. Characteristic pathological, radiological and clinical features are shared with GB Ca and contribute to considerable treatment inaccuracy. Tissue sampling by pre-operative endoscopic ultrasound or intra-operative frozen section is required to accurately diagnose gallbladder pathology and should be performed before any extensive resection is performed.

Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response.

BACKGROUND: Cytotoxic chemotherapy improves survival for some, but not all, cancer patients. Non-responders may experience unnecessary toxicity and cancer progression, thus creating an urgent need for biomarkers that can predict the response to chemotherapy. So far, the search for such biomarkers has primarily been focused on the cancer cells and less on their surrounding stroma. This stroma is known to act as a key regulator of tumour progression and, in addition, has been associated with drug delivery and drug efficacy. Fibroblasts represent the major cell type in cancer-associated stroma and they secrete extracellular matrix proteins as well as growth factors. This Medline-based literature review summarises the results from studies on epithelial cancers and aimed at investigating relationships between the quantity and quality of the intra-tumoral stroma, the cancer-associated fibroblasts, the proteins they produce and the concomitant response to chemotherapy. Biomarkers were selected for review that are known to affect cancer-related characteristics and patient prognosis. RESULTS: The current literature supports the hypothesis that biomarkers derived from the tumour stroma may be useful to predict response to chemotherapy. This notion appears to be related to the overall quantity and cellularity of the intra-tumoural stroma and the predominant constituents of the extracellular matrix. CONCLUSION: Increasing evidence is emerging showing that tumour-stroma interactions may not only affect tumour progression and patient prognosis, but also the response to chemotherapy. The tumour stroma-derived biomarkers that appear to be most appropriate to determine the patient's response to chemotherapy vary by tumour origin and the availability of pre-treatment tissue. For patients scheduled for adjuvant chemotherapy, the most promising biomarker appears to be the PLAU: SERPINE complex, whereas for patients scheduled for neo-adjuvant chemotherapy the tumour stroma quantity appears to be most relevant.