ABSTRACT
BACKGROUND: The prognostic value of tumor multinodularity in intrahepatic cholangiocarcinoma (ICC) remains debated. We aimed to evaluate the impact of tumor multinodularity according to the presence and distribution of multiples ICC's nodules. METHODS: A retrospective review of a prospectively maintained database of patients undergoing resection for ICC from January 1995 to September 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. Tumoral nodules were defined according to their number (single and multiple) and localization (satellites and contralateral). RESULTS: Out of 120 selected patients, 64 (53%) had single and 56 (47%) had multiple lesions. Multiple lesions included tumors with satellites (n = 40; 71.5%) and tumors with contralateral lesions (n = 16; 28.5%). Patients with multiple tumors had significantly larger mean main lesion size (p = 0.02), required a higher rate of perioperative transfusion (p = 0.04), had a greater rate of lymph node involvement (p < 0.0001), vascular invasion (p = 0.04), and poor differentiation (p = 0.04) than single tumors. Patients with single tumors experienced a 5-year survival significantly longer (40%) than patients with multiple tumors (14%; p = 0.004). Patients having tumors with satellites had inferior median overall survival and 5-year survival rates (20 months, 7%) compared with patients with contralateral tumors (33.6 months, 29%) (p = 0.09). Multivariable analysis identified tumor multinodularity, morbidity, tumor size < 5 cm, poor differentiation, and lymph node involvement as independent prognostic factors for overall survival. CONCLUSIONS: Tumor multinodularity represents an independent risk factor for survival in ICCs and identifies a category of patients in need of more effective perioperative treatment.
Subject(s)
Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/diagnosis , Hepatectomy/methods , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cell Differentiation , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/surgery , Diffusion Magnetic Resonance Imaging/methods , Female , Follow-Up Studies , France/epidemiology , Humans , Incidence , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trendsABSTRACT
Developmental genes contribute to cancer, as reported for the homeobox gene Cdx2 playing a tumor suppressor role in the gut. In this study, we show that human colon cancers exhibiting the highest reduction in CDX2 expression belong to the serrated subtype with the worst evolution. In mice, mosaic knockout of Cdx2 in the adult intestinal epithelium induces the formation of imperfect gastric-type metaplastic lesions. The metaplastic knockout cells do not spontaneously become tumorigenic. However, they induce profound modifications of the microenvironment that facilitate the tumorigenic evolution of adjacent Cdx2-intact tumor-prone cells at the surface of the lesions through NF-κB activation, induction of inducible nitric oxide synthase, and stochastic loss of function of Apc This study presents a novel paradigm in that metaplastic cells, generally considered as precancerous, can induce tumorigenesis from neighboring nonmetaplastic cells without themselves becoming cancerous. It unveils the novel property of non-cell-autonomous tumor suppressor gene for the Cdx2 gene in the gut.
Subject(s)
CDX2 Transcription Factor/genetics , Carcinogenesis/genetics , Carcinogenesis/pathology , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Animals , Cecum/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Heterozygote , Humans , Intestines/pathology , Metaplasia , Mice , NF-kappa B/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Nitric Oxide Synthase Type II/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Tumor MicroenvironmentABSTRACT
Most patients with testicular seminoma have been treated with a curative intent for decades. Second cancers after radiotherapy for testicular seminoma before 1990 are a growing issue, and are related to previous generation of dose planning and delineating strategies. Among those cancers, hepatocellular carcinoma is an extremely rare occurrence, especially when affecting patients with healthy, noncirrhotic liver. Here, we describe such a case in a patient of our institution, and subsequently review the relevant literature and large epidemiologic studies. Understanding those late and serious toxicity features may help cancer care teams to screen and treat those patients appropriately.
ABSTRACT
Internal quality control (IQC) is a necessary component of total quality management. We report our experience with an internal audit scheme focusing on the histological diagnosis. We outline other strategies of IQC and analyze the causes of errors and ways to prevent them. Some practical guidelines to initiate this type of procedure are presented. Our audit was designed to check the accuracy of diagnosis, the clarity and completeness of the report, the quality of the documents leading to the diagnosis, and the turn-around time. It consisted of a retrospective analysis of 4185 randomly selected cases (representing 2% of all cases), over nine years. The control took place once a week and was done by two pathologists working as a team. The mean time spent by each pathologist was 45 minutes per week. Errors were scored using a 3-level grading scheme depending on their potential harm or impact on patient care. The overall rate of errors was 1.1%, and 0.1% of errors were potentially harmful to the patients. A single case (0.02%), in which a cancer was missed, had a real impact on patient care. Retrospective analysis of randomly selected cases mirrors the overall activity of a surgical pathology department. Nevertheless, each lab has to develop its own strategy of IQC, based on its size, its functioning, and its objectives. Although it may be difficult to initiate quality assurance when medical time is already limited, it is a helpful procedure in a more and more demanding medical and societal context and a pragmatic step towards "culture of quality".