Palliative Portal Vein Stent Placement in Malignant and Symptomatic Extrinsic Portal Vein Stenosis or Occlusion

This article evaluates the results of portal vein (PV) stent placement in patients with malignant extrinsic lesions stenosing or obstructing the PV and causing symptomatic PV hypertension (PVHT). Fourteen patients with bile duct cancer (n=7), pancreatic adenocarcinoma (n=4), or another cancer (n=3) underwent percutaneous transhepatic portal venous stent placement because of gastroesophageal or jejunal varices (n=9), ascites (n=7), and/or thrombocytopenia (n=2). Concurrent tumoral obstruction of the main bile duct was treated via the transhepatic route in the same session in four patients. Changes in portal venous pressure, complications, stent patency, and survival were evaluated. Mean±standard deviation (SD) gradient of portal venous pressure decreased significantly immediately after stent placement from 11.2mmHg±4.6 to 1.1mmHg±1.0 (P<0.00001). Three patients had minor complications, and one developed a liver abscess. During a mean±SD follow-up of 134.4±123.3days, portal stents remained patent in 11 patients (78.6%); stent occlusion occurred in 3 patients, 2 of whom had undergone previous major hepatectomy. After stent placement, PVHT symptoms were relieved in four (57.1%) of seven patients who died (mean survival, 97±71.2days), and relieved in six (85.7%) of seven patients still alive at the end of follow-up (mean follow-up, 171.7±153.5days). Stent placement in the PV is feasible and relatively safe. It helped to relieve PVHT symptoms in a single sessio

Intérêt de l'imagerie à mi-parcours d'un traitement de chimiothérapie adjuvante chez les patients traités pour cancer colorectal

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Histoire naturelle des tumeurs endocrines digestives (étude rétrospective à propos de 25 patients)

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Intraoperative Contrast-Enhanced Ultrasound in Colorectal Liver Metastasis Surgery Improves the Identification and Characterization of Nodules

International audienceINTRODUCTION: The sensitivity of preoperative assessment of colorectal liver metastases (CRLM) ranges from 74 to 80%. Intraoperative ultrasound (IOUS) associated with contrast-enhanced intraoperative ultrasound (CE-IOUS) may be able to improve this. Thus, the aims of this study were to assess the value of IOUS and CE-IOUS for the surgical approach and to determine risk factors both for the detection of new nodules and for the modification of the surgical strategy.MATERIALS AND METHODS: Forty-three patients who underwent CRLM surgery were included. These patients had an MRI in the 8 weeks preceding surgery and benefited from intraoperative IOUS and CE-IOUS.RESULTS AND DISCUSSION: The use of IOUS/CE-IOUS permitted the identification of 43 additional lesions and an improved characterization of nodules in 23 patients with a resulting modification of surgical strategy. Lesions were down-staged in six patients and up-staged in six patients. Chemotherapy (p = 0.02) and the presence of nodules in the left lobe (p = 0.04) were predictive factors for finding new nodules at IOUS/CE-IOUS. The discovery of a new nodule systematically modified surgical management. IOUS/CE-IOUS improved intraoperative management of liver metastases. The techniques enable pertinent modification of surgical resections and a reduction of residual lesions.</p

Short article: Evaluation of O6-methylguanine-DNA methyltransferase as a predicting factor of response to temozolomide-based chemotherapy in well-differentiated metastatic pancreatic neuroendocrine tumors

International audienceOBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy.PATIENTS AND METHODS: All patients with metastatic PNETs treated with TMZ-based chemotherapy between 2010 and 2016 in two academic centers, for whom the tumor samples were available, were included. Clinical data were collected and the MGMT status of the tumors was analyzed using MS-PCR and IHC.RESULTS: Twenty-two patients (nine men, median age 61 years) were included. The loss of MGMT protein expression detected by IHC was observed in 13 (59%) patients and MGMT promoter hypermethylation was detected by MS-PCR in three (15%) out of 20 interpretable cases. MGMT status did not correlate significantly with the best radiological response according to the Response Evaluation Criteria In Solid Tumors criteria or with progression-free survival. There was no correlation between MGMT protein expression and MGMT gene promoter methylation.CONCLUSION: These results indicate that a deficient MGMT status in PNETs, determined by loss of protein expression in IHC or by the presence of MGMT gene promoter methylation measured by MS-PCR, is not associated with a better response to TMZ-based chemotherapy and cannot be used as a predictive marker to lead treatment decisions.</p

Radiation-induced cholangitis with hepatocellular carcinoma

International audienceSummaryThere are no reports of hepatocellular carcinoma complicating postradiotherapy cholangitis. We report the case of a 45-year-old patient who had undergone upper abdominal radiotherapy for Hodgkin's disease, 21&nbsp;years before, which was complicated years later by cholangitis with stricture of the common bile duct. Biliodigestive anastomosic surgery was scheduled due to recurrent angiocholitis, and hepatocellular carcinoma was discovered. The patient died from carcinoma some months later.</p

High-Density of FcγRIIIA+ (CD16+) Tumor-Associated Neutrophils in Metastases Improves the Therapeutic Response of Cetuximab in Metastatic Colorectal Cancer Patients, Independently of the HLA-E/CD94-NKG2A Axis

International audienceAntibody-dependent cellular cytotoxicity (ADCC) in the anti-tumor effect of cetuximab in metastatic colorectal cancer (mCRC) is only based on the impact of FcγRIIIA (CD16) polymorphisms as predictive of therapeutic response. However, nature, density and therapeutic impact of FcγRIIIA + (CD16) effector cells in tumor remain poorly documented. Moreover, the inhibition of cetuximab-mediated ADCC induced by NK cells by the engagement of the new inhibitory CD94-NKG2A immune checkpoint has only been demonstrated in vitro . This multicentric study aimed to determine, on paired primary and metastatic tissue samples from a cohort of mCRC patients treated with cetuximab: 1) the nature and density of FcγRIIIA + (CD16) immune cells, 2) the expression profile of HLA-E/β2m by tumor cells as well as the density of CD94 + immune cells and 3) their impact on both objective response to cetuximab and survival. We demonstrated that FcγRIIIA + (CD16) intraepithelial immune cells mainly correspond to tumor-associated neutrophils (TAN), and their high density in metastases was significantly associated with a better response to cetuximab, independently of the expression of the CD94/NKG2A inhibitory immune checkpoint. However, HLA-E/β2m, preferentially overexpressed in metastases compared with primary tumors and associated with CD94 + tumor infiltrating lymphocytes (TILs), was associated with a poor overall survival. Altogether, these results strongly support the use of bispecific antibodies directed against both EGFR and FcγRIIIA (CD16) in mCRC patients, to boost cetuximab-mediated ADCC in RAS wild-type mCRC patients. The preferential overexpression of HLA-E/β2m in metastases, associated with CD94 + TILs and responsible for a poor prognosis, provides convincing arguments to inhibit this new immune checkpoint with monalizumab, a humanized anti-NKG2A antibody, in combination with anti- FcγRIIIA/EGFR bispecific antibodies as a promising therapeutic perspective in RAS wild-type mCRC patients

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

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Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

International audienceBACKGROUND: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option.METHODS: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded.RESULTS: Twelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1-35+ months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia.CONCLUSION: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.</p

Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE)

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