Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy. Methods: This study is a confirmatory study of a blood-based RNA signature, called the GemciTest. This test measures the expression levels of nine genes using real-time polymerase chain reaction (PCR) processes. Clinical validation was carried out, through a discovery and a validation phases, on 336 patients (mean 68.7 years; range, 37-88 years) for whom blood was collected from two prospective cohorts and two tumor biobanks. These cohorts included previously untreated advanced PDAC patients who received either a gemcitabine- or fluoropyrimidine-based regimen. Results: Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) {5.3 vs. 2.8 months; hazard ratio (HR) =0.53 [95% confidence interval (CI): 0.31-0.92]; P=0.023} and overall survival (OS) [10.4 vs. 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, fluoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature. Conclusions: The GemciTest demonstrated that a blood-based RNA signature has the potential to aid in personalized therapy for PDAC, leading to better survival rates for patients receiving a gemcitabine-based first-line treatment.

FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer.

Immune checkpoint inhibitors (ICI) have high efficacy in metastatic colorectal cancer (mCRC) with microsatellite instability (MSI) but not in microsatellite stable (MSS) tumour due to the low tumour mutational burden. Selective internal radiation therapy (SIRT) could enhance neoantigen production thus triggering systemic anti-tumoral immune response (abscopal effect). In addition, Oxalipatin can induce immunogenic cell death and Bevacizumab can decrease the exhaustion of tumour infiltrating lymphocyte. In combination, these treatments could act synergistically to sensitize MSS mCRCs to ICI SIRTCI is a prospective, multicentre, open-label, phase II, non-comparative single-arm study evaluating the efficacy and safety of SIRT plus Xelox, Bevacizumab and Atezolizumab (anti-programmed death-ligand 1) in patients with liver-dominant MSS mCRC. The primary objective is progression-free survival at 9 months. The main inclusion criteria are patients with MSS mCRC with liver-dominant disease, initially unresectable disease and with no prior oncologic treatment for metastatic disease. The trial started in November 2020 and has included 10 out of the 52 planned patients.

Waldmann's disease: a rare cause of protein losing enteropathy in an adult patient

Primary intestinal lymphangiectasia or Waldmann’s disease is an uncommon cause of protein losing enteropathy with an unknown etiology and is usually diagnosed during childhood. It is characterized by dilation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia. Differential diagnosis should include erosive and nonerosive gastrointestinal disorders, conditions involving mesenteric lymphatic obstruction and cardiovascular disorders that increase central venous pressure. Since there are no accurate serological or radiological available tests, enteroscopy with histopathological examination based on intestinal biopsy specimens is currently the gold standard diagnostic modality of intestinal lymphangiectasia. We report a rare case of a primary intestinal lymphangiectasia in a 60-year-old Caucasian female who presented with asymptomatic hypoalbuminemia and hypogammaglobulinemia. After the diagnosis of a protein losing enteropathy, the patient underwent an enteroscopy and biopsies were taken, whose histological examination confirmed dilated intestinal lymphatics with broadened villi of the small bowel. Secondary causes of intestinal lymphangiectasia were excluded and the diagnosis of Waldmann’s disease was recorded. The patient was put on a high-protein and low-fat diet with medium-chain triglyceride supplementation with improvement (AU)

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Waldmann's disease: a rare cause of protein losing enteropathy in an adult patient.

Primary intestinal lymphangiectasia or Waldmann's disease is an uncommon cause of protein losing enteropathy with an unknown etiology and is usually diagnosed during childhood. It is characterized by dilation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia. Differential diagnosis should include erosive and non-erosive gastrointestinal disorders, conditions involving mesenteric lymphatic obstruction and cardiovascular disorders that increase central venous pressure. Since there are no accurate serological or radiological available tests, enteroscopy with histopathological examination based on intestinal biopsy specimens is currently the gold standard diagnostic modality of intestinal lymphangiectasia. We report a rare case of a primary intestinal lymphangiectasia in a 60-year-old Caucasian female who presented with asymptomatic hypoalbuminemia and hypogammaglobulinemia. After the diagnosis of a protein losing enteropathy, the patient underwent an enteroscopy and biopsies were taken, whose histological examination confirmed dilated intestinal lymphatics with broadened villi of the small bowel. Secondary causes of intestinal lymphangiectasia were excluded and the diagnosis of Waldmann's disease was recorded. The patient was put on a high-protein and low-fat diet with medium-chain triglyceride supplementation with improvement.

Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodarone for unresectable hepatocellular carcinoma.

BACKGROUND: There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma. AIM: The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group. METHODS: Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions. RESULTS: Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35-88) in the amiodarone group and 50% (95% CI 24-76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44-92) and 52% (95% CI 22-75) in the amiodarone group, and 57% (95% CI 28-78) and 40% (95% CI 15-65) in the control group, respectively. There was no difference between the two groups in terms of toxicity. CONCLUSIONS: The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma.

Role for endovascular therapy in chronic mesenteric ischemia.

Chronic mesenteric ischemia is a rare condition that is caused by stenosis or occlusion of the mesenteric arteries and usually manifests as abdominal pain. While surgical revascularization has been the standard treatment for symptomatic patients, recent advances in interventional devices and techniques have made endovascular treatment feasible and effective. Percutaneous transluminal angioplasty with stent placement is now recognized as a minimally invasive means of obtaining good long-term results with an acceptable recurrence rate; consequently, the technique is suggested for the primary treatment of chronic mesenteric ischemia. The present article discusses the indications and principles of endovascular treatment, and reviews the literature, with emphasis on short- and long-term outcomes, particularly morbidity and mortality rates.

Arterial embolotherapy for endoscopically unmanageable acute gastroduodenal hemorrhage: predictors of early rebleeding.

BACKGROUND & AIMS: Severe bleeding from gastrointestinal ulcers is a life-threatening event that is difficult to manage when endoscopic treatment fails. Transcatheter embolization has been proposed but factors that influence the angiographic outcome are not well documented. We aimed to identify predictors of recurrent bleeding within 30 days after transcatheter embolization for refractory hemorrhage from gastroduodenal ulcers. METHODS: This retrospective single-center study of 60 consecutive emergency embolization procedures included hemodynamically unstable patients (41 men, 19 women; mean age, 69.4 +/- 15 y), referred from 1999 to 2008 for selective angiography after failed endoscopic treatment. Predictors of early rebleeding were tested with univariate analysis and a multivariate logistic regression model. RESULTS: The procedural success rate was 95%, the primary clinical success rate was 71.9% (41 of 57), and secondary clinical success was achieved in 3 patients (77.2%) after repeat embolization. No major catheterization-related complications occurred. Periprocedural mortality was 26.7% (16 of 60). Early bleeding recurrence was associated with coagulation disorders (P = .007), longer time to angiography (P = .0005), greater preprocedural blood transfusion volume (P = .0009), 2 or more comorbidities (P = .005), and use of only coils (P = .003). Two factors were independent predictors of embolization failure: coagulation disorders (odds ratio, 6.18; P = .027) and the use of coils as the only embolic agent (odds ratio, 6.24; P = .022). The median follow-up time was 7 months (range, 1 day to 103 months). CONCLUSIONS: Angiographic embolization should be performed early in the course of bleeding, and not with coils alone, in critically ill patients. It is important to correct coagulation disorders throughout the embolization procedure.

Place of residence and distance to medical care influence the diagnosis of hepatitis C: a population-based study.

BACKGROUND/AIMS: In France, geographic access to medical care may affect the diagnosis of hepatitis C. The aims of this study were to compare the detection rates of hepatitis C in urban and rural areas after adjusting for distance to medical care, and evaluating the impact of the place of residence on patients' clinical characteristics. METHODS: Between 1994 and 2001, 1938 newly detected cases were recorded in a French population of 1,005,817 inhabitants. Age and sex-adjusted detection rates for 10(5) inhabitants were estimated for urban and rural areas and for classes of distance to the nearest practitioner. RESULTS: Detection rates were lower in rural than in urban areas [14.1, (95CI: 12.5-15.7) versus 24.7, (95CI: 23.5-26.0)] and decreased as the distance to the general practitioner increased [27.0, (95CI: 25.5-28.4) versus 13.7, (95CI: 12.1-15.3) for a cutoff value of 1.5 km]. In multivariate analyses, detection rates were only influenced by the distance to general practitioner. Hepatocellular carcinoma at diagnosis was more frequent among rural than among urban patients (adjusted OR = 2.28, 95CI: 0.97-5.39, P = 0.059). CONCLUSIONS: A poorer geographic access to care explained the lower detection of hepatitis C in rural areas. Hepatocellular carcinoma was more frequent in rural patients. It may result from later detection and/or involvement of environmental factors on hepatocarcinogenesis.