Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study.

BACKGROUND: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. PATIENTS AND METHODS: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. RESULTS: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. CONCLUSIONS: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. GOV REGISTRATION: NCT03422601; EudraCT Number: 2009-010384-16.

[Review of the association between obesity and gastroesophageal reflux and its complications]. / Données actuelles concernant l'association de l'obésité au reflux gastro-oesophagien et à ses complications.

Esophageal adenocarcinoma and its precursor Barrett's esophagus are increasing in incidence in western populations. Gastroesophageal reflux and high body mass index (BMI) are known risk factors. Studies about Barrett's esophagus in obese patients have emphasised the role of central adiposity as a stronger risk factor than BMI in the development of specialized intestinal metaplasia and subsequently esophagus adenocarcinoma. The proinflammatory impact of adipocytokines of the abdominal fat associated with the metabolic syndrome is also relevant. Except cardiovascular diseases, type 2 diabetes and non alcoholic steatohepatitis, abdominal obesity and metabolic syndrome are responsible of an increase of prevalence of esophageal adenocarcinoma, but also other cancer sites. In this review, we study the up to date main epidemiologic and physiopathologic data concerning this association that could be important in future for a preventive action in obese patients, especially when metabolic syndrome is present.

[Microscopic colitis associated with celiac disease probably triggered by the administration of venlafaxine]. / Association d'une colite lymphocytaire à une maladie coeliaque probablement déclenchée par la prise de venlafaxine (Effexor).

The association of microscopic colitis with celiac disease is rare. A case of microscopic colitis associated with celiac disease and following administration of venlafaxine in a 67-year-old patient is described. The pathophysiologic hypotheses of such an association are discussed.

[Sporadic colonic juvenile polyps in adults]. / Polypes coliques juvéniles sporadiques de l'adulte.

Sporadic colonic juvenile polyps are uncommon in adults. We report three cases for which clinical manifestations were presence of occult blood in the stool, rectal bleeding or chronic diarrhea. Two of these polyps occurred in the caecum which is an uncommon localisation. Endoscopic characteristics of these polyps were indistinguishable from adenomas. Endoscopic resection was complicated in one case by bleeding.

Secretory diarrhoea with high faecal potassium concentrations: a new mechanism of diarrhoea associated with colonic pseudo-obstruction? Report of five patients.

OBJECTIVE: To report the mechanism of diarrhoea in patients with subacute colonic pseudo-obstruction, profuse secretory diarrhoea and hypokalemia. PATIENTS: Five consecutive patients who developed colonic pseudo-obstruction, profuse watery diarrhoea and severe hypokalemia. Investigations excluded mechanical intestinal obstruction. Usual cause of diarrhoea were ruled out. Abdominal distension and diarrhoea improved simultaneously in all cases after colonoscopic decompression or intravenous neostigmine. RESULTS: Faecal ionograms showed a low osmotic gap and high faecal potassium concentration explaining the hypokalemia: 100 to 180 mEq/kg (usually inferior than 50 mEq/l in case of secretory diarrhoea) and low faecal sodium concentrations. Potassium salts were the only factor identified as the driving osmotic force for the diarrhoea. CONCLUSION: Secretory diarrhoea is classically due to chloride active secretion with passive sodium secretion or to inhibition of sodium absorption. In five cases of Ogilvie's syndrome we evidenced an original mechanism of secretory diarrhoea due to active potassium secretion responsible of a profound hypokalemia. This novel type of diarrhoea may be a hallmark of colonic pseudo-obstruction due to colonic distension.

[Acute renal insufficiency after flurbiprofen treatment in a patient treated with angiotensin converting enzyme inhibitor]. / Insuffisance rénale aiguë après prise de flurbiprofène chez un patient sous inhibiteur de l'enzyme de conversion.

We report a case of acute renal insufficiency in a 77 year-old patient who took flurbiprofen as antiplatelet therapy. This is an important observation because it illustrates the potential risk of acute renal insufficiency, when using flurbiprofen before invasive medical examination or surgery in patients receiving long-term treatment with angiotensin converting enzyme inhibitors or angiotensin II inhibitors. This risk is probably underestimated in usual clinical practice.

[Humoral hypercalcemia revealing a malignant non hodgkin lymphoma]. / Hypercalcémie humorale révélant un lymphome malin non hodgkinien.

INTRODUCTION: Hypercalcemia is a rare complication of non-Hodgkin lymphoma. Usually, hypercalcemia occurs late in the disease course, except for high-grade lymphoma. Most often hypercalcemia is related to excessive level of circulating PTH-rP or sometimes, 1,25(OH)2D3. Concomitant high plasmatic concentration of PTH-rP and 1,25(OH)2D3 is uncommon. EXEGESIS: We report the case of a 82-year-old man who presented with abdominal pain and weight loss, leading to the diagnosis of diffuse large-B-cell lymphoma (high-grade lymphoma) associated with symptomatic hypercalcemia (3.21mmol/l). PTH-rP and 1,25(OH)2D3 plasmatic levels were high. Calcium concentration was normalized with glucocorticoids and sequential chemotherapy. CONCLUSION: This case report confirms that hypercalcemia, as consequence of excessive plasmatic level of PTH-rP secreted by tumoral cells, can occur early in the course of high-grade lymphoma. Glucocorticoids and chemotherapy are the best treatment options.

[Hyponatremia due to tramadol]. / Hyponatrémie due au tramadol.

We reported a 92-year-old woman with hyponatremia (117 mmol/l) occurring three days after the introduction of tramadol. Diagnosis of inappropriate antidiuretic hormone secretion was based on blood and urinary analysis and dosage of antidiuretic hormone. Natremia became normal after tramadol cessation and fluid restriction. Natremia must be measured when neurological abnormality occurs with tramadol treatment.

[Diagnosis of anemia in alcoholic cirrhosis]. / Diagnostic des anémies au cours des cirrhoses alcooliques.

PURPOSE: Anemia in patients with alcoholic liver cirrhosis is a common issue. The diagnosis could be difficult because of the multiplicity of causes, usually associated, and specificities in the diagnostic approach. This subject has not been reviewed for almost two decades. We propose a review based upon analysis of the literature and our clinical experience. CURRENT KNOWLEDGE AND KEY POINTS: Because of the alcoholism and the biological consequences of the liver disease, laboratory findings, especially the mean corpuscular volume, should be interpreted with caution in the diagnostic approach. Despite these drawbacks, the diagnosis of anemia is detailed according to the usual plan: normocytic, macrocytic and microcytic anemias. Finally, we propose practical guidelines. FUTURE PROSPECTS AND PROJECTS: Further prospective studies should assess the real burden of nutritional deficiencies, easily treatable. The prognostic significance of hemolytic anemias in patients with alcoholic liver cirrhosis should be studied.

[Etiologic spectrum of mesenteric panniculitis: report of 7 cases]. / Profil étiologique des panniculites mésentériques: à propos de sept cas.

OBJECTIVE: Mesenteric panniculitis is a rare disorder characterized by nonspecific inflammation and/or necrosis and/or fibrosis in the adipose tissue of the bowel mesentery. Its signification, primary or associated with other diseases, is a subject of controversy. METHODS: A descriptive and retrospective study of patients with an abdominal CT examination showing features of mesenteric panniculitis and for whom biopsy with immunohistochemical examination was obtained in all cases. RESULTS: Seven patients were enrolled (4 men and 3 women) with a median age of 62,1 years. None of the patients without an identified etiology had a history of abdominal surgery. An associated disease was identified in 4 cases: breast cancer (1), non-Hodgkin's lymphoma based on peripheric lymph nodes biopsy (2) and cryoglobulinemic vascularitis based on renal biopsy (1). In the 3 remaining cases, isolated mesenteric panniculitis was the only abnormality despite thorough imaging and pathologic investigations. CONCLUSION: Except an obvious malignancy context or a history of abdominal surgery, a pathologic examination of the mesenteric panniculitis lesions is necessary, especially to eliminate another mesenteric disorder. Mesenteric panniculitis is often associated with lymphoma.

FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study.

BACKGROUND: The purpose of the study was to prospectively evaluate the efficacy and tolerability of the FOLFIRI.3 regimen in patients with unresectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven advanced pancreatic adenocarcinoma were treated with the FOLFIRI.3 regimen, consisting of irinotecan 90 mg/m(2) as a 60-min infusion on day 1, leucovorin 400 mg/m(2) as a 2-h infusion on day 1, followed by 5-fluorouracil (5-FU) 2000 mg/m(2) as a 46-h infusion and irinotecan 90 mg/m(2), repeated on day 3, at the end of the 5-FU infusion, every 2 weeks. RESULTS: Forty patients were enrolled, of whom 29 (73%) had metastatic disease. A total of 441 cycles were delivered (1-53). Grade 3-4 neutropenia occurred in 35% of the patients, accompanied by fever in two cases. Other relevant grade 3-4 toxic effects were nausea-vomiting (27%) and diarrhea (25%). Grade 2 alopecia occurred in 48% of the patients. There were no treatment-related deaths. The confirmed response rate was 37.5%. Stable disease was observed in 27.5% of the patients. The median progression-free and overall survivals were 5.6 months and 12.1 months, respectively. The 1-year survival rate was 51%. CONCLUSION: The FOLFIRI.3 regimen seems to be active on advanced pancreatic cancer and to have a manageable toxicity profile. The lack of cross-resistance between FOLFIRI.3 and gemcitabine-based regimens allows efficient second-line therapies.

[Cerebral venous thrombosis and ulcerative colitis]. / Thrombose veineuse cérébrale et rectocolite hémorragique.

INTRODUCTION: Thromboembolic events are serious complications in patients with inflammatory bowel disease. EXEGESIS: An 18-year-old patient, with a one year history of ulcerative colitis, presented with cerebral venous thrombosis during the decreasing period of corticotherapy after an active phase of the disease. Under treatment, the neurological disorder rapidly improved. No inherited thrombophilia was found. CONCLUSION: The role of acquired and inherited risks factors is discussed.