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.

[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.

[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.

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.

[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.

[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.

[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.

[Inflammatory pseudotumor of lymph node]. / Pseudotumeur inflammatoire ganglionnaire.

INTRODUCTION: Inflammatory pseudotumor of lymph node is a rare case in the etiology of fever of unknown origin. OBSERVATION: We report the observation of a woman, aged 40, hospitalized with intermittent fever revealing under-diaphragm adenopathy related to inflammatory pseudotumor of lymph node. CONCLUSION: Inflammatory pseudotumor of lymph node is a rare pathology whose nosological definition is unclear. It should probably be considered as belonging to a category different from the inflammatory pseudotumor of other organs. The diagnosis presents itself in case of isolated adenopathy or prolonged fever and is based on an anatomopathology that essentially calls to mind a lymphoma. The evolution of the condition is shown to be favorable : it can lead to a spontaneous remission, or call for a non-steroid anti-inflammatory treatment, or a steroid therapy.

[Hemolytic uremic syndrome as a complication of gemcitabine treatment: report of six cases and review of the literature]. / Syndrome hémolytique et urémique secondaire à la gemcitabine: à propos de six observations et revue de la littérature.

UNLABELLED: Hemolytic uremic syndrome is a rare condition during gemcitabine therapy. METHODS: We report six new cases of hemolytic uremic syndrome related to gemcitabine, three issued from a retrospective study of 136 consecutive patients treated with gemcitabine for which a systematic screening of this side effect has been performed and 29 cases with clinical data available identified in the literature in order to better characterised frequency and clinical presentation of this side effect. RESULTS: In our series, frequency of HUS is 2.2% and is higher than this previously reported (0.015%) or estimated with the data of clinical trials analysed (0.072 %). For 35 cases with clinical data available, the patients were always treated for a local advanced and/or metastatic disease. For our cases and for literature cases, at the time of diagnosis of hemolytic uremic syndrome, mean number of doses received (mean+/-standard deviation. Minimum/maximum)) (personal cases: 26.5+/-6.6. 16/36, literature cases: 21+/-11. 8/54), cumulative dose received (g/m2) (personal cases : 24.5+/-6.3. 16/31.6, literature cases: 21.7+/-12.4. 2.4/54) and duration of treatment (months) (personal cases: 8.2+/-1.9. 5.6/11, literature cases: 8.5+/-4.0. 3/18) are very closed and high individual variations observed for these factors are not consistent with a time and/or dose dependant toxicity. New-onset hypertension or exacerbation of underlying hypertension is the most common clinical manifestation, with mild anemia; thrombocytopenia is inconstant. The degree of severity of renal failure is highly variable. The existence of subacute clinical form with progressive worsening of the symptoms and biological form at the time of diagnosis suggest the interest of a systematic clinical and biological screening of this side effect, before each injection of gemcitabine. Early prognosis is linked to the evolution of hemolytic uremic syndrome and after hemolytic uremic syndrome healing, cancer progression. Treatment include gemcitabine discontinuation, antihypertensive drugs and if necessary fresh frozen plasma. CONCLUSIONS: Systematic clinical and biological screening of hemolytic uremic syndrome during gemcitabine therapy should allow to better know this complication, to recognize and treat it earlier with a potential positive impact for patients.

[Pancreatic peritoneal fistula with bisalbuminemia]. / Fistule pancréatico-péritonéale avec bisalbuminémie.

INTRODUCTION: Pancreatic fistulas are a complication that occur in 3 to 15% of cases during the progression of chronic or acute pancreatitis, usually alcohol-induced. Bisalbuminemia is characterised by two albumin fractions on serum protein electrophoresis. The presence of Bisalbuminemia is inconsistent and has only rarely been reported. OBSERVATION: A 42 year-old man, excessive drinker, developed pancreatic ascites related to a pancreatic-peritoneal fistula and associated with transitory bisalbuminemia. Treatment was medical with good short term results. DISCUSSION: Ascites was secondary to a pancreatic-peritoneal fistula. It can be constitutional or acquired and transitory, and secondary to prolonged treatment with b-lactamines in a patient with kidney failure or a pancreatic fistula.

Acute poststreptococcal glomerulonephritis associated with thrombotic microangiopathy in an adult.

The simultaneous occurrence of acute poststreptococcal glomerulonephritis and thrombotic microangiopathy is rare. A 47-year-old woman was admitted with acute renal failure, hematuria, edematous nephrotic syndrome and severe hypertension. This acute nephritic syndrome occurred two weeks after left leg erysipelas. The patient also had signs of intravascular hemolysis, low serum levels of C3 and C4 and elevated antistreptolysin-O titer. Kidney biopsy confirmed postinfectious glomerulonephritis with diffuse hypercellularity and humps, and simultaneous subendothelial hyalin deposits and fibrinoid arteriolar thrombi. The patient received four antihypertensive drugs, acetylsalicyclic acid and plasma infusions. Renal function improved, hypertension was controlled and serum levels of C3 and C4 complement components returned to normal within three months. This case illustrates the occurrence of thrombotic microangiopathy in association with acute poststreptococcal glomerulonephritis. This simultaneous appearance supports a role of neuraminidase in this disease.

Acute laryngeal paralysis induced by the migration of a totally implantable venous access device's catheter tip.

The authors report a case of acute vagus nerve paralysis that appeared during a course of chemotherapy. The drugs had been administered through a totally implantable venous access device (TIVAD), whose catheter tip had migrated into the right internal jugular vein (IJV) and was surrounded by a complete venous thrombosis. The supposed aetiology of this paralysis was a leakage of the cytotoxic drug (5-fluorouracil) from the vessel wall into the surrounding carotid space, because of the stagnation of the chemotherapeutic agent above the thrombosis. Four months after cessation of chemotherapy, the laryngeal paralysis was still evident.

[Isolated ascites revealing a hypothyroidism. Study of 2 cases]. / Ascite isolée et révélatrice d'une hypothyroïdie. Etude de deux cas.

Ascites is an uncommon feature of hypothyroidism. We report two patients with hypothyroidism revealed by ascites. Among the 44 myxedema ascites cases found in the literature, there were observed 17 cases of ascites as the first manifestation of hypothyroidism. In this rare presentation of hypothyroidism, diagnosis is often delayed. Biological analysis of ascites usually shows high protein and cholesterol concentrations and a low or high cell count with a high proportion of lymphocytes. An increase in capillary permeability may play a role in the pathogenesis of ascites.

[Yellow nail syndrome associated with intestinal lymphangiectasia]. / Syndrome des ongles jaunes associé à des lymphangiectasies intestinales.

The yellow nail syndrome, a combination of yellow discoloured nails, lymphedema and pleural effusions, is a rare clinical condition. We report a case of the yellow nail syndrome associated with intestinal lymphangiectasia revealed by chylous ascites and protein-losing gastroenteropathy. This association reported in only three cases in the literature leads us to discuss the relations between yellow nail syndrome, primitive intestinal lymphangiectasia and primary lymphatic disorders.