FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases: Results of the FFCD 1102 phase II trial.

AIM OF THE STUDY: The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. PATIENTS AND METHODS: Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. RESULTS: Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively. CONCLUSION: Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01674309.

Evolution of clinical and radiological features at diagnosis of achalasia during a 19-year period in central France.

OBJECTIVES: Symptoms of achalasia are often misinterpreted, resulting in delayed diagnosis. The aims of our study were (1) to estimate the evolution of clinical and radiological features of a large population of achalasic patients between two successive periods; and (2) to determine the influence of symptoms on diagnostic delay. METHODS: Between 1980 and 1998, all achalasia patients treated in our unit were assessed at the time of manometric diagnosis for clinical and radiological features. These data were compared between two successive periods (1980-1994 and 1994-1998). Then, a correlation between the diagnostic delay, clinical and radiological data and symptoms was investigated. RESULTS: Three hundred and forty-five consecutive achalasia patients were assessed (mean age at diagnosis, 56 years; mean diagnostic delay, 5.7 years). The duration of the disease was correlated with the oesophageal diameter (P = 0.0001). Dysphagia, chest pain and heartburn were more frequent in young patients (respectively, P = 0.003, 0.0001 and 0.001). Women had 1.7 times the risk of men for suffering of chest pain (95% CI, 1.1 -2.6) and 2.2 times the risk for heartburn (95% CI, 1.2-4.0). Pulmonary involvement was more frequent when the oesophagus was dilated (P = 0.0002), and 3.4 times more frequent when associated with regurgitations (95% CI, 1.3-8.9). The oesophageal diameter was significantly smaller (38 vs 48 mm) in the last period, but we have not observed any significant shortening of the diagnostic delay. No symptoms influenced the diagnostic delay. CONCLUSIONS: Despite a smaller oesophageal diameter at the time of diagnosis, during the period 1994-1998, diagnostic delay was not reduced. No clinical features associated with late diagnoses could be identified.

A novel high-throughput method for accurate, rapid, and economical measurement of multiple type 1 diabetes autoantibodies.

Prediction of Type 1 diabetes for study of preventive therapies requires screening the general population, where 85% of new cases occur. Even with HLA-based prescreening, nearly 20% of all children will need multiple serum autoantibody testings. High-throughput, economical, and accurate methods are therefore essential. We have developed such a radiobinding method, using 96-well microtiter plates and a novel immune complex capture method via membrane-bound Protein A. Each microtiter plate contained a standard negative control serum, and low-, medium-, and high-level positive control sera. All sera were evaluated in triplicate. This readily allowed quality control criteria both for triplicates of individual sera and for each 96-well plate. Inter-assay coefficients of variation (CVs) were all

[Severe mixed thrombopenia during interferon treatment for chronic viral hepatitis C]. / Thrombopénie mixte sévère au cours d'un traitement par interféron chez une femme atteinte d'une hépatite chronique virale C.

BACKGROUND: Thrombocytopenia occurred in a woman given alpha interferon for chronic hepatitis C without cirrhosis. Both central thrombocytopenia, clearly demonstrated, and peripheral thrombocytopenia, probably of autoimunne origin, were involved. CASE REPORT: A 55-year-old woman with active chronic hepatitis C (Metavir score A2, F2) was given alpha interferon. One month after treatment onset, she developed thrombocytopenia (32 G/L). A second bone marrow aspirate and osteomedullary biopsy evidenced megalokaryocytes and the platelet count responded to polyvalent immunoglobulins. Five months after discontinuing interferon, the platelet count progressively returned to normal. DISCUSSION: Central thrombocytopenia is classically described in patients given interferon and usually appears during the first weeks of treatment. In our case, the central mechanism was clearly demonstrated by the bone marrow aspirate and osteomedullary biopsy findings at a time when the platelet count was 32 G/L. A peripheral immunological participation was more difficult to prove but was strongly suggested by the persistence of thrombocytopenia despite the interruption of the interferon and the efficacy of immunoglobulins.

Risk factors for immediate complications after progressive pneumatic dilation for achalasia.

OBJECTIVE: The aim of this retrospective study was to determine the risk factors of early complications after progressive pneumatic dilation for achalasia. METHODS: Five hundred four dilations were performed in 237 consecutive achalasic patients between 1980 and 1994 with the same technique: low-pressure pneumatic dilation every other day with balloons of increasing diameter until success criteria were obtained (depending on manometric examination and esophageal x-ray transit performed 24 h after each dilation). Clinical, radiographical, endoscopical, and manometrical data as technical procedure characteristics for patients with perforations or other early complications were compared with those without complications. RESULTS: We observed 15 complications (6% of patients): 7 perforations (3%), 3 asymptomatic esophageal mucosal tears, 4 esophageal hematomas, and 1 fever. Perforations occurred in 6 of 7 patients during the first dilation. The mean age was 68.5 yr in the group with complications versus 56.4 yr for the remainder (p < 0.05). Two deaths occurred in patients older than 90 yr. Instability of the balloon during dilations was noted in 8 of 15 cases of complications versus 57 of 222 patients (p < 0.05). No other data differed significantly. CONCLUSIONS: This study showed a low prevalence of early complications using this progressive technique. Patients with hiatal hernia, esophageal diverticulum, or vigorous achalasia may safely undergo progressive pneumatic dilation. Only patients older than 90 yr should be referred for progressive pneumatic dilation with caution. Most of perforations arose during the first dilation, but there was no predictive pretherapeutic factor of perforation.

An islet-cell protein tyrosine phosphatase is a likely precursor to the 37-kDa autoantigen in type 1 diabetes: human and macaque sequences, tissue distribution, unique and shared epitopes, and predictive autoantibodies.

BACKGROUND: We sought to identify novel islet-cell autoantigens to better understand the pathogenesis, prediction, and immunotherapy of type 1 diabetes. MATERIALS AND METHODS: Macaque and human islet cDNA libraries expressed in mammalian cells were screened with human diabetes sera. A positive clone was sequenced directly and after 5' rapid amplification of cDNA ends (RACE). Northern blotting and in situ hybridization revealed the tissue distribution of the corresponding protein. Antigen, expressed by in vitro translation, and tryptic peptides were analyzed by SDS-PAGE. For the immunoprecipitations, 183 diabetic, 60 prediabetic, and 91 control sera were used. Truncated antigens were used in immunoprecipitations for epitope mapping. Recombinant antigen expressed in transfected fibroblasts was used in competition assays. RESULTS: Sequencing yielded an 111-kDa, 1,013 amino acid, transmembrane protein (M1851) containing consensus protein tyrosine phosphatase (PTPase) sequence. M1851 was 77% identical in the intracellular domain, but only 31% identical extracellularly, to the islet-cell autoantigen ICA512. mRNA localized to brain, prostate, pancreatic islets, and adrenal medulla. After limited trypsinization, the in vitro translated antigen was 37 kDa. M1851 was recognized by 47% of prediabetes sera, 31% of new diabetes sera, but only 1% of healthy controls. Only 1/73 sera binding M1851 failed to bind ICA512, whereas 42/114 binding ICA512 did not bind M1851. M1851 reactivity was not fully displaced by ICA512 in 24/49 sera. Removing the C-terminal 27, 80, or 160 amino acids of M1851 decreased reactivity by 70%, 90%, and 100%, respectively. CONCLUSIONS: This new islet-cell PTPase is likely to be the precursor to the 37-kDa tryptic fragment antigen. It is structurally related to ICA512 but has distinct diabetes autoantibody epitopes located at the C terminus.

[Acute reversible pan-dysautonomia: effect of erythromycin on gastrointestinal involvement]. / Pan-dysautonomie aiguë réversible: effet de l'érythromycine sur l'atteinte gastro-intestinale.

We describe a case of acute autonomic neuropathy in an 18-year-old woman. Gut dysfunction was sufficiently severe for the patient to undergo laparotomy for suspected mechanical-intestinal obstruction before the diagnosis was made. Apart from the gut, other organs affected included the pupils, sweat and lachrymal glands. Cardiovascular autonomic function tests showed the involvement of sympathetic adrenergic nerves. Small bowel barium X-ray showed resolution of gastric stasis and emergence of jejunum dilatation during intravenous administration of erythromycin but this treatment did not eliminate intestinal obstructive symptoms. The patient had an incomplete recovery in 3 months. Erythromycin might have therapeutic value in patients with intestinal motility dysfunction in acute dysautonomia.

[Acute thrombosis of the portal system. Treatment with alteplase and heparin or with heparin alone in 10 patients]. / Thrombose aiguë du système porte. Traitement par alteplase et héparine ou héparine seule chez 10 malades.

OBJECTIVES: We report the efficacy of alteplase (a recombinant tissue plasminogen activator) with heparin or heparin alone in the treatment of acute thrombosis of the portal venous system. METHODS: Ten consecutive patients with acute portal venous system thrombosis were studied. Five patients were treated with alteplase and heparin, and the remaining 5 patients, who were asymptomatic or had a contraindication to alteplase, were treated with heparin alone. RESULTS: In 3 of the 5 patients treated with alteplase, ultrasonography showed total resolution of the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the 5 patients treated with heparin alone, ultrasonography showed total resolution of the thrombus, and no change in one. No bleeding occurred. CONCLUSION: Treatment with heparin can result in complete recanalisation of acute portal venous system thrombosis. These data suggest that combined therapy with systemic alteplase does not increase the efficacy of heparin.

Computed tomographic findings after acute carbon monoxide poisoning.

Selective necrosis and degeneration of the globus pallidus are characteristic autopsy findings in patients with severe carbon monoxide (CO) poisoning. The objective of this study was to show that computed tomography (CT) may demonstrate these morphological changes in the brain during life, and provide a clue to prognosis. The authors reviewed the medical records of 19 consecutive patients with acute CO poisoning who underwent CT examination during hospitalization. Abnormal CT findings were found in 10 of the 19 patients (53%). The most common abnormal findings were low-density areas in the basal ganglia. These lesions were found in 7 of the 10 cases, and varied from small (limited to the globus pallidus) to large (extending to the internal capsule). Of the 10 patients with abnormal CT scans, 9 survived to hospital discharge but all had some degree of functional neurological impairment. Eighty-nine percent (8 of 9) of the patients with normal CT scans were discharged neurologically intact. Awareness of the potential for basal ganglia lesions in CO poisoning should lead to more accurate CT interpretation and may have significant prognostic implications.