Histological growth pattern as a biomarker in patients undergoing surgery for liver metastases

La chirurgie reste le seul traitement potentiellement curatif chez les patients porteurs de métastases hépatiques (MH) d’origine colorectale (MHCCR) ou non-colorectale (MHNCR). Cependant, il n’existe actuellement pas de critères permettant de distinguer les patients qui vont bénéficier de la chirurgie de ceux chez qui des MH isolées sont la première manifestation d’une maladie disséminée. En conséquence, la majorité des patients récidive après la chirurgie. La recherche de nouveaux marqueurs permettant de caractériser individuellement le comportement métastatique chez ces patients représente donc un objectif majeur. Pour aborder cette question, nous nous sommes intéressés à des paramètres pouvant refléter le microenvironnement tumoral des MH, comme la captation de glucose (évaluée par FDG/PET scan) et le profil histologique de croissance (PHC).Chez les patients opérés pour MHCCR, nous avons observé des survies globales à 5 et 10 ans de 44.5 et 26%. Dans ces cas, aucun des facteurs de risque traditionnels ne permettait de distinguer les patients ayant bénéficié de la chirurgie (survie sans récidive ≥5 ans ou patients LTS) de ceux chez qui elle avait été inefficace (récidive non résécable <1 an ou patients ER). Dans cette population, nous avons montré que la captation de glucose des MH était plus élevée chez les patients ER, permettant d’établir un nouveau modèle de risque, défini comme le metabolic Clinical Risk Score (mCRS). L’étude du PHC des MHCCR a confirmé l’existence de 2 présentations principales: un profil desmoplastique (PHC-D), dans lequel les MH sont entourées par une réaction fibroblastique et un infiltrat immunitaire, et un profil infiltratif ou de remplacement (PHC-R) dans lequel les cellules cancéreuses infiltrent directement le foie, en l’absence d’infiltrat immunitaire. Chez les patients opérés pour MHCCR, nous avons montré le PHC-D représentait un facteur indépendant de bon pronostic et que la combinaison du mCRS avec le PHC permettait d’améliorer très significativement la prédiction des résultats de la chirurgie. Nous avons également montré que le PHC des MHCCR pouvait dépendre des caractéristiques des tumeurs primitives et qu’il existait une association entre la faible différenciation et la présence de cellules en migration dans les tumeurs colorectales et le développement de MHCCR avec un PHC non desmoplastique. Ces résultats ont été globalement confirmés chez les patients opérés pour MHNCR. Dans ce groupe, les survies globales à 5 et 10 ans étaient de 56 et 27% et aucun des facteurs de risque habituellement considérés ne permettait de distinguer les groupes LTS et ER. Comme dans les MHCCR, nous avons observé la présence de PHC distincts, de type PHD-D ou PHC-R, associé à une valeur pronostique indépendante supérieure à celle de tous les autres facteurs de risques. Enfin, dans une étude regroupant les patients opérés pour MHCCR et MHNCR, nous avons confirmé la valeur pronostique indépendante du PHC, indépendamment de l’origine des tumeurs primitives, suggérant, qu’individuellement, la biologie tumorale et les interactions hôte-cancer jouaient un rôle prédominant.Dans leur ensemble, nos résultats indiquent que la caractérisation du microenvironnement tumoral des MH permet de distinguer des modes de progression métastatique différents. La prédiction de ces paramètres et la compréhension des mécanismes associés à leur développement pourraient permettre d’améliorer l’individualisation du traitement chez les patients porteurs de MH.Doctorat en Sciences médicales (Médecine)info:eu-repo/semantics/nonPublishe

The concept of oligometastases in colorectal cancer: From the clinical evidences to new therapeutic strategies

Purpose of review The concept of oligometastases, defining cancers with limited metastatic capacity and attaining a limited number of secondary sites, is now widely accepted, particularly in colorectal cancer. Currently, however, accurate predictive markers for oligometastatic tumors are still lacking. For this reason, it remains challenging to translate this concept into clinical recommendations. In the present work, we review recent publications on oligometastases in colorectal cancer, showing the evidences for such presentation and underlying the need for the identification of biomarkers, necessary to further develop new therapeutic strategies. Recent findings This review of recently published series confirms that long-term survival and cure could be obtained in patients undergoing surgical resection for colorectal metastases, particularly in the cases of liver metastases. Similar results are observed in other secondary sites such as in pulmonary metastases. Furthermore, in patients with unresectable metastases, significant survival benefit could be still obtained using nonresectional targeted approaches, as thermal ablation or stereotactic radiotherapy. Although these clinical evidences could now serve as proof-of-concept for the existence of an oligometastatic phenotype in colorectal cancer, neither clinical characteristics nor biological biomarkers have been established to be able to prospectively define the patients that will benefit from such therapeutic approaches targeting the metastatic sites. This emphasizes the need for further studies aiming at better defining early clinical and biological characteristics of these patients. As, currently, the reliable identification of the oligometastatic patients could only rely on the demonstration of favorable long-term outcomes after metastases-directed therapies, we propose that retrospective studies will be pivotal to analyze this question. Summary Extensive research is undergoing to define biologically the oligometastatic phenotype in colorectal cancer. Currently, the selection of the patients for potentially curative metastasectomy remains mostly empirical.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Retained capsule endoscopy in Crohn's disease patient, diagnosed on upright abdominal film

SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

The lack of selection criteria for surgery in patients with non-colorectal non-neuroendocrine liver metastases

Background: The benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM. Methods: Data for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence 50 mm and delay between primary and NCRNNELM <24 months for OS and DFS, respectively. AFC score was not prognostic while high-risk mCRS (scores 3-4) was predictive for the poorer OS. The clinicopathologic parameters were similar in the ER and LTS groups, except the presence of N+ primary tumor, and the size of liver metastases was significantly higher in the ER group. Conclusion: In patients with resectable NCRNNELM, no predictive factors or scores were found to accurately preoperatively differentiate individual cases in whom surgery would be futile from those in whom surgery could be associated with a significant oncological benefit.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A rare presentation of small diaphragmatic epidermoid cyst with extremely elevated serum CA19-9 level

Epidermoid cysts are rare lesions that can occur anywhere in the body. They are associated with elevated serum levels of CA 19-9. The spleen represents the most common site of intra-abdominal localisation. Only two cases of diaphragmatic epidermoid cyst are reported in the literature. We present the case of a 61-year-old woman with a small suprasplenic subdiaphragmatic cyst discovered during the investigation of left flank pain. The establishment of an adequate diagnosis was challenging due to the difficulty in specifying the exact localisation of the cyst, the extremely elevated CA 19-9 level of 19,000 and the high uptake on 18-fluoro-2-deoxy-D-glucose positron emission tomography. The definitive diagnosis followed complete surgical excision. Intra-abdominal epidermoid cysts are usually discovered incidentally on imaging for another reason. The cyst is lined by squamous epithelium responsible for the secretion of CA 19-9. The elevation of serum CA 19-9 is due to small rupture or increased intraluminal pressure followed by diffusion to the bloodstream. Surgery with en-bloc resection represents the optimal treatment to avoid any risk of recurrence. The definitive diagnosis is established by demonstrating positive immunohistopathological staining of epithelial cell to CA 19.9.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A rare presentation of IgG4 related disease as a gastric antral lesion: Case report and review of the literature

Introduction: Immunoglobulin G4 related disease is a recently recognized systemic fibro-inflammatory disorder affecting virtually every organ in the body, characterized by lympho-plasmacytic dense infiltrates rich in IgG4 positive plasmacytes along with storiform fibrosis, inconstantly associated with elevated serum IgG4 levels. Few cases of Immunoglobulin G4 related disease occurring solely in the stomach have been published. Presentation of case: We herein present a rare case of a 57 year old male patient presenting with an incidentally discovered asymptomatic pre-pyloric submucosal gastric lesion confused with a gastro-intestinal stromal tumor with failed endoscopic biopsy attempts due to tumor mobility. The patient underwent wedge resection of the lesion which was diagnosed postoperatively as Immunoglobulin G4 related disease. Discussion: Immunoglobulin G4 related disease presenting as a solitary lesion in the stomach is a very rare condition. It should be kept in the differential diagnosis of a submucosal mass or polyp. The treatment is medical with systemic steroid therapy. Conclusion: Obtaining a tissue biopsy is of extreme importance to avoid unnecessary surgery.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Unusual presentation of a hepatocellular carcinoma as a potential late side effect of radiotherapy in a patient treated for Wilms tumor in childhood

Abstract Background The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT. Case presentation A 49-year old man, treated at the age of 6 weeks for a right WT by a right nephrectomy and adjuvant radiotherapy, presented with a right abdominal mass. Imaging demonstrated a 100-mm tumor invading the inferior segment of the right liver, the right colon and the right psoas muscle. The patient had no previous history of liver disease, nor of alcohol consumption, and hepatitis serologies were negatives. Biopsy demonstrated a poorly differentiated tumor of unknown origin. A panel of tumor markers was negative. Explorative surgery has been performed allowing en bloc R0 tumor resection, including resection of segments VI and VII of the liver, right hemicolectomy and resection of the anterior sheet of the right psoas muscle. Pathological examination revealed a poorly differentiated HCC. No signs of cirrhosis or chronic liver disease were observed in the non-tumor liver. Twenty weeks after surgery, the patient developed a multifocal tumor recurrence that was treated with intra-arterial 90Yttrium radioembolization. Conclusion In this case, the absence of risk factors for HCC, such as cirrhosis, viral hepatitis and chronic liver disease, highly suggests the development of HCC to be related to previous high-dose radiation therapy given for a right WT to a field involving the inferior part of the liver. This observation shows radiotherapy to/near the liver, particularly in childhood, to be a potential risk factor for HCC, stressing the need for a long-term specific follow-up in patients irradiated in childhood

Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery.

Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC.info:eu-repo/semantics/publishe