The "Immunoscore" in rectal cancer: could we search quality beyond quantity of life?

Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit.

Therapeutic Implications of the Immunoscore in Patients with Colorectal Cancer.

Four decades were needed to progress from the first demonstration of the independent prognostic value of lymphocytes infiltration in rectal cancers to the first recommendation from the international guidelines for the use of a standardized immune assay, namely the "Immunoscore" (IS), to accurately prognosticate colon cancers beyond the TNM-system. The standardization process included not only the IS conceptualization, development, fine-tuning, and validation by a large international consortium, but also a demonstration of the robustness and reproducibility across the world and testing of international norms and their effects on the IS. This is the first step of a major change of paradigm that now perceives cancer as the result of contradicting driving forces, i.

A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy.

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (IS) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait").

Experimental Design: Biopsies from two independent cohorts ( = 131, = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3 and CD8 T cells and quantified by digital pathology to determine IS.

Children and adolescents with epilepsy in rehabilitation centers: A French prospective transversal study.

Introduction: The reason why some children and adolescent with epilepsy (CAWE) still challenge the "inclusive" educative policy needs to be explored.

Methods/patients: We conducted a transversal study in French medical, social, and educative rehab centers (MSERCs) dedicated to CAWE to describe the profile of 263 centers-involved (CI)-CAWE. Centers-involved CAWE were prospectively followed from September 2012 to August 2013.

The Immunoscore in the Clinical Practice of Patients with Colon and Rectal Cancers.

In the fine balance between tumor invasion and our defensive systems, the role played by the adaptive immune response at the tumor site is critical. Beyond the fact that all the immune components of the innate and adaptive response can be observed to varying degrees in the tumor microenvironment, it appears that a high density of T cytotoxic and memory lymphocytes, in a context of Th1 immune orientation in the tumor and its invasion front, provides a prognostic marker of paramount importance for colorectal cancer and more generally all solid tumors. The understanding of the role of immunity in cancer, tailored during one century of intensive research, has led to a complete paradigm shift.

[Immunology and personalized medicine in oncology].

The comprehension of "what cancer is" was bespoke these two last decades, switching from the traditional centro-cellular vision of cancer to a new holistic vision which integrates the tumor microenvironment and its immune component. Although in both visions, the result is, in fine, the emergence of a clone of cancer cells whose genome is modified, the genesis of the emergence of this clone and of its expansion is quite different offering a new explanatory framework and allowing the design of new predictive bio-markers as well as the development of innovative therapies. Recent data demonstrate that the immune infiltrate of the tumor is determinant for the outcome of patients bearing a solid cancer.

Prognostic and predictive values of the immunoscore in patients with rectal cancer.

Purpose: To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.

Experimental Design: The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients.

[Cellular and molecular deregulations driving the metastatic phenotype].

Cancerogenesis is initiated by DNA instability that induces modifications in stem cells. Regulation is organ specific and depends on morphogenetic factors. DNA instability is alternatively related to chromosomal aberrations or DNA replication errors.

Genomic profile of colon cancer metastases.

Background: In colon cancer, the occurrence of metastases is associated with microsatellite stability. As metastatic cells derive from a clonal expansion of primary tumor cells, specific genomic alterations are expected in addition to the common genomic profile.

Patients And Methods: Genome-wide allelotyping was performed on 75 liver metastases samples from sporadic colon cancer.

High-resolution genotyping of chromosome 8 in colon adenocarcinomas reveals recurrent break point but no gene mutation in the 8p21 region.

The prognosis of patients with colorectal cancer is largely determined by the tumor stage. In this respect, colorectal cancer with lymph node metastases has the worst prognosis. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation.

High frequency of chromosome 14 deletion in early-onset colon cancer.

Purpose: Several genes have been recognized, when mutated in the germline, to highly predispose to colorectal cancer, impairing the DNA mismatch repair system in hereditary nonpolyposis colon cancer syndrome, or APC/MYH in adenomatous polyposis. However, 10 percent of microsatellite stable colorectal cancer is reported to develop in an unexplained context of genetic predisposition. This study was designed to depict the genetic mechanisms underlying early-onset microsatellite stable colon cancers.

Pathogenesis and treatment of Budd-Chiari syndrome combined with portal vein thrombosis.

Objectives: Combined Budd-Chiari syndrome and Portal Vein Thrombosis (BCS-PVT) is a challenging clinical condition with as yet unknown outcome. The aim of the present study was to investigate etiology, treatment options, and prognosis of patients with BCS-PVT.

Methods: Patients diagnosed with nonmalignant BCS between 1984 and 2001 were identified in a large international study and classified into isolated BCS (n = 204), BCS-PVT without spleno-mesenteric vein thrombosis (SMVT; n = 15), and BCS-PVT with SMVT (n = 18).

Retention of chromosome arm 5q in stage II colon cancers identifies 83% of liver metastasis occurrences.

The decision to use chemotherapy in the treatment of colon cancer patients depends on the risk of developing metastases, as estimated by clinicopathological staging combining body imaging and pathological findings. The aim of this study was to identify all chromosome arms that, when allelotyped, correlate with the metastatic process, add prognostic information to pathology, and are of relevance for predicting metachronous metastases. A 5-year follow-up survey enrolled 401 MSS (microsatellite stable) colon cancer patients who were divided into three groups.

Determinants of survival and the effect of portosystemic shunting in patients with Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) is a rare disorder that is characterized by hepatic venous outflow obstruction. The aim of this study was to assess determinants of survival and to evaluate the effect of portosystemic shunting. In this international multicenter study, 237 patients with BCS, diagnosed between 1984 and 2001, were investigated.

Clinicopathological forms and prognostic index in Budd-Chiari syndrome.

Background: A recent study in patients with Budd-Chiari syndrome showed the value of a prognostic index including age, Pugh score, ascites and serum creatinine. Surgical portosystemic shunt did not appear to improve survival.

Aims: To validate these findings in an independent sample; to evaluate a classification into three forms according to the presence of features of acute injury, chronic lesions, or both of them (types I, II or III, respectively); and to assess whether taking into account this classification would alter our previous conclusions.