Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis.

BACKGROUND: Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ. OBJECTIVE: The main objective was to evaluate the accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis in patients with a clinical suspicion of mastocytosis. METHODS: We included all adult patients evaluated in our centre between December 2009 and 2013 for suspected mastocytosis as part of a standardized procedure and who had a bone marrow and serum tryptase assay on the same day. The diagnosis of systemic mastocytosis was established on the basis of the World Health Organization criteria as the gold standard. The accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis was assessed by a receiver operating characteristics curve analysis. The different sensitivity and specificity values, corresponding to the set of possible bone marrow tryptase level cut-off values, were estimated with 95% confidence intervals. RESULTS: Seventy-three patients were included. The diagnosis of systemic mastocytosis was established in 43 patients (58.9%). The median bone marrow tryptase level was 423 µg/L [95% CI: 217-868] in the systemic mastocytosis group and 7.5 µg/L [95% CI: 4.6-17.1] in the non-systemic mastocytosis group (P < 0.001). A cut-off value of 50 µg/L for bone marrow tryptase identified systemic mastocytosis with a sensitivity of 93.0% [95% CI: 80.9-98.5%] and a specificity of 90.0% [95% CI: 73.5-97.9%]. CONCLUSION AND CLINICAL RELEVANCE: The bone marrow tryptase level appears to be a valuable diagnostic criterion for confirming systemic mastocytosis. If this diagnosis can reliably be excluded by evaluation of the bone marrow tryptase level, there would be no need to perform a bone marrow biopsy.

The early life nutritional environment and early life stress as potential pathways towards the metabolic syndrome in mid-life? A lifecourse analysis using the 1958 British Birth cohort.

BACKGROUND: Lifecourse studies suggest that the metabolic syndrome (MetS) may be rooted in the early life environment. This study aims to examine the pathways linking early nutritional and psychosocial exposures and the presence of MetS in midlife. METHODS: Data are from the National Child Development Study including individuals born during 1 week in 1958 in Great Britain and followed-up until now. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III classification. Mother's pre-pregnancy body mass index (BMI) was used as a proxy of the early nutritional environment and Adverse Childhood Experiences (ACE) as a proxy for early psychosocial stress. Socioeconomic characteristics, pregnancy and birth conditions were extracted as potential confounders. Adult health behaviors, BMI, socioeconomic environment and psychological state were considered as mediating variables. Multivariate models were performed by including variables sequentially taking a lifecourse approach. RESULTS: 37.5 % of men and 19.8 % of women had MetS. Participants with an obese/overweight mother presented a higher risk of MetS than those whose mother had a normal pre-pregnancy BMI. Men exposed to two ACE or more, and women exposed to one ACE, were more at risk of MetS compared to unexposed individuals. After including confounders and mediators, mother's pre-pregnancy BMI was still associated with MetS in midlife but the association was weakened after including participant's adult BMI. ACE was no longer associated with MetS after including confounders in models. CONCLUSIONS: The early nutritional environment, represented by mother's pre-pregnancy BMI, was associated with the risk of MetS in midlife. An important mechanism involves a mother-to-child BMI transmission, independent of birth or perinatal conditions, socioeconomic characteristics and health behaviors over the lifecourse. However this mechanism is not sufficient for explaining the influence of mother's pre-pregnancy BMI which implies the need to further explore other mechanisms in particular the role of genetics and early nutritional environment. ACE is not independently associated with MetS. However, other early life stressful events such as emergency caesarean deliveries and poor socioeconomic status during childhood may contribute as determinants of MetS.

Long-term carcinologic results of advanced esthesioneuroblastoma: a systematic review.

Surgical resection followed by radiotherapy can be considered like the optimal treatment modality for limited esthesioneuroblastoma. However, therapeutic management of locally advanced tumors remains a challenge. The aim of our study was to access and compare the oncologic results of the different treatment modalities in advanced esthesioneuroblastoma. We performed a systematic review using the Medline, and Cochrane database in accordance with PRISMA criteria and included all the cases of advanced esthesioneuroblastoma published between 2000 and 2013. We also retrospectively included 15 patients with an advanced esthesioneuroblastoma managed at our tertiary care medical center. Long-term survival rates defined as the time from diagnosis or randomization to the date of death or last follow-up were evaluated for each treatment with Kaplan-Meier survival curve analyses. 283 patients have been included. The mean follow-up was 78 months. Five-year highest survival rates were obtained in patients treated by surgery associated with radiotherapy. Ten-year highest survival rates were obtained in patients treated by the association of surgery, radiotherapy and chemotherapy (p = 0.0008). Within the surgical group, 5-year highest survival rates were obtained in patients treated by endoscopic resection (p = 0.003). Surgical resection combined with radiotherapy offers the gold standard of care. Adjuvant chemotherapy seems to improve the long-term survival in patients with locally advanced esthesioneuroblastoma. Endoscopic resection in advanced tumors should be discussed on a case-by-case basis.

[The evaluation of pharmacological drugs, medical devices, and non-pharmacological or public health interventions: Experimental design limitations. Moving towards new methods?] / Évaluer les effets d'un médicament, de dispositifs médicaux et d'interventions non médicamenteuses ou de santé publique : limites de l'essai expérimental. Vers de nouvelles méthodes ?

In the field of health, evidence-based medicine and associated methods like randomised controlled trials (RCTs) have become widely used. RCT has become the gold standard for evaluating causal links between interventions and health results. Originating in pharmacology, this method has been progressively expanded to medical devices, non-pharmacological individual interventions, as well as collective public health interventions. Its use in these domains has led to the formulation of several limits, and it has been called into question as an undisputed gold standard. Some of those limits (e.g. confounding biases and external validity) are common to these four different domains, while others are more specific. This paper describes the different limits, as well as several research avenues. Some are methodological reflections aiming at adapting RCT to the complexity of the tested interventions, and at overcoming some of its limits. Others are alternative methods. The objective is not to remove RCT from the range of evaluation methodologies, but to resituate it within this range. The aim is to encourage choosing between different methods according to the features and the level of the intervention to evaluate, thereby calling for methodological pluralism.

The results of seton drainage combined with anti-TNFα therapy for anal fistula in Crohn's disease.

AIM: Combined infliximab and sphincter-sparing surgery can be effective in perianal fistula associated with Crohn's disease (CD). This study aimed to assess the efficacy of local surgery combined with infliximab on sustained fistula closure and to identify predictive factors for response after this combined treatment. METHOD: Between 2000 and 2010, 81 patients with fistulising perianal CD were included in this observational study. Drainage with a loose seton was followed by infliximab therapy. The primary end-points were the rate of complete fistula closure and time required for this to occur. RESULTS: The fistula was complex in 71 (88%) of the 81 patients. Local proctological surgery was carried out in 77 (95%), including seton drainage in 62 (80.5%) of these. This was continued for a median duration of 3.8 months and the patient then received infliximab therapy. The median follow-up after treatment was 64 months (2-263). Initial complete closure of the fistula occurred in 71 (88%) cases at a median interval of 12.4 months (1-147) from the start of treatment. Recurrence was observed in 29 (41%) patients at a median interval of 38.5 months (2-48) from the start of treatment. They were treated again with combined treatment with successful closure in 19 (65.5%) patients. The total rate of closure of the fistula was 75.3%. Female gender, anal stenosis, rectovaginal and complex fistula formation were factors independently associated with failure of combined treatment. CONCLUSION: Seton drainage for several months combined with infliximab therapy is effective in closing the fistula in 75% of patients with complex perianal fistula formation associated with CD.

Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples.

AIMS: The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis. PATIENTS AND METHODS: In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates. RESULTS: We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KRT7 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%). CONCLUSION: We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses.

[Cochlear implants in elderly: performance outcomes in the long term]. / L'implant cochléaire chez le sujet âgé: évolution des performances à long terme.

OBJECTIVES: To study and compare the evolving capacities of speech discrimination with cochlear implants in older patients compared to patients implanted at a younger age. METHODOLOGY: A retrospective study comparing a group of 52 patients aged over 65 with a control group of 58 patients aged between 30 and 50 years, followed for 5 years after implantation. We analyzed and compared the evolution of speech discrimination in silence (disyllabic words, sentences) and noise (sentences, S/N ratio: +10 dB) after implantation. RESULTS: In the group of elderly patients, the speech discrimination in silence remains stable over time (for disyllabic words, score at 6 months: 72.8 +/- 20.2%; score at 5 years: 73.7% +/- 19.7). Discrimination in noise tends to improve (mean score at 6 months: 70.5% +/- 21.5; score at 5 years: 76.9% +/- 16.9). The results obtained are in silence are comparable to the results of the group of patients aged between 30 and 50. In noise, their performance remains lower than the control group (mean differences between scores: -10.8; confidence interval at 95%: -17.9, -5.3). CONCLUSION: The cochlear implant is effective over the long term in elderly patients, for speech discrimination in quiet and in noise. In silence, their performance is comparable to younger patients with implants.

Severe SARS-CoV-2 pneumonia: Clinical, functional and imaging outcomes at 4 months.

INTRODUCTION: Given the pathophysiology of coronavirus disease 19 (COVID-19), persistent pulmonary abnormalities are likely. METHODS: We conducted a prospective cohort study in severe COVID-19 patients who had oxygen saturation<94% and were primarily admitted to hospital. We aimed to describe persistent gas exchange abnormalities at 4 months, defined as decreased diffusing capacity of the lungs for carbon monoxide (DLco) and/or desaturation on the 6-minute walk test (6MWT), along with associated mechanisms and risk factors. RESULTS: Of the 72 patients included, 76.1% required admission to an intensive care unit (ICU), while 68.5% required invasive mechanical ventilation (MV). A total of 39.1% developed venous thromboembolism (VTE). After 4 months, 61.4% were still symptomatic. Functionally, 39.1% had abnormal carbon monoxide test results and/or desaturation on 6MWT; high-flow oxygen, MV, and VTE during the acute phase were significantly associated. Restrictive lung disease was observed in 23.6% of cases, obstructive lung disease in 16.7%, and respiratory muscle dysfunction in 18.1%. A severe initial presentation with admission to ICU (P=0.0181), and VTE occurrence during the acute phase (P=0.0089) were associated with these abnormalities. 41% had interstitial lung disease in computed tomography (CT) of the chest. Four patients (5.5%) displayed residual defects on lung scintigraphy, only one of whom had developed VTE during the acute phase (5.5%). The main functional respiratory abnormality (31.9%) was reduced capillary volume (Vc<70%). CONCLUSION: Among patients with severe COVID-19 pneumonia who were admitted to hospital, 61% were still symptomatic, 39% of patients had persistent functional abnormalities and 41% radiological abnormalities after 4 months. Embolic sequelae were rare but the main functional respiratory abnormality was reduced capillary volume. A respiratory check-up after severe COVID-19 pneumonia may be relevant to improve future management of these patients.

The "Deglutition Handicap Index" a self-administrated dysphagia-specific quality of life questionnaire: temporal reliability.

OBJECTIVE: The aim of this study is to contribute to the psychometric validation of the self-administrated dysphagia-specific quality of life questionnaire, the Deglutition Handicap Index. Created on the model of the "Voice Handicap Index". this questionnaire consists of 30 statements on deglutition related aspects in daily life (5 point-rating scale). It is subdivided in three domains of 10 items: physical (symptoms), functional (nutritional and respiratory consequences) and emotional (psychosocial consequences). MATERIAL AND METHOD: 57 patients were included suffering of any kind of swallowing disorders. 17 questionnaires were eliminated because 1 to 3 items were not anchored. A test retest performed in an interval of 2 weeks, allowed the measure of the intraclasse correlation coefficient and the limits of agreement with Bland and Altman graphics. RESULTS: The intraclasse correlation coefficient was respectively 0.77 (0.64-0.90), 0.87 (0.79-0.94), 0.90 (0.84-0.96), 0.91 (0.85-0.96) for the Physical, Functional, Emotional and Total Scores. The limits of agreement are 9 points for the subscales and 20 points for the total score. CONCLUSION: The DHI has been validated in term of content, concurrent and construct validity. The reliability was satisfied in term of internal consistency. It is now validated for the temporal reliability. The DHI is the solely specific quality of life questionnaire related to deglutition available for all kind of oropharyngeal swallowing disorders in adults available in clinical practice.

[Construction and validation of a quantitative assessment of speech intelligibility for speech disorders]. / Elaboration et validation d'un test quantitatif d'intelligibilité pour les troubles pathologiques de la production de la parole.

UNLABELLED: Intelligibility of speech measure is based on the perception of the listeners. OBJECTIVE: The aim of this study was the construction and the validation of a quantitative test of speech disorders severity allowing the the follow up and the measure of management impact. MATERIAL AND METHOD: After a first step of construction and feasibility, the psychometric validation was performed. 37 patients with a speech disorder and 13 normal subjects were recorded. The reference was the global score obtained by reading a text. The whole recordings were scored by a panel of 5 judges. The test was composed by a automatic series of words (the months of the year) with a phono-orthographic score, the semantic transcription of a list of words and sentences, a qualitative score of spontaneous speech obtained by the description of a photography. RESULTS: The intra and inter judges reliability are correct (intraclasse coefficient of 0.97 and 0.98). The different parts of the test are well correlated to the reference proof (r = 0.75 to 0.82). Chronbach alpha is 0.98, the limits of agreement are 14.88 +/- 3 on a maximum score of 88. The dispersion is enough for a good differentiation of the patients. (11 to 88, avec mean 62.93, SD 22.45) with a significant difference p < 0.002 between the control group and the population with speech disorders. CONCLUSION: This test constructed on the concept of a composite assessment is validated.

[Application of detecting and taking overdispersion into account in Poisson regression model]. / Intérêt de la détection et de la prise en compte d'une surdispersion dans un modèle de Poisson: illustration à partir d'un exemple.

BACKGROUND: Researchers often use the Poisson regression model to analyze count data. Overdispersion can occur when a Poisson regression model is used, resulting in an underestimation of variance of the regression model parameters. Our objective was to take overdispersion into account and assess its impact with an illustration based on the data of a study investigating the relationship between use of the Internet to seek health information and number of primary care consultations. METHODS: Three methods, overdispersed Poisson, a robust estimator, and negative binomial regression, were performed to take overdispersion into account in explaining variation in the number (Y) of primary care consultations. We tested overdispersion in the Poisson regression model using the ratio of the sum of Pearson residuals over the number of degrees of freedom (chi(2)/df). We then fitted the three models and compared parameter estimation to the estimations given by Poisson regression model. RESULTS: Variance of the number of primary care consultations (Var[Y]=21.03) was greater than the mean (E[Y]=5.93) and the chi(2)/df ratio was 3.26, which confirmed overdispersion. Standard errors of the parameters varied greatly between the Poisson regression model and the three other regression models. Interpretation of estimates from two variables (using the Internet to seek health information and single parent family) would have changed according to the model retained, with significant levels of 0.06 and 0.002 (Poisson), 0.29 and 0.09 (overdispersed Poisson), 0.29 and 0.13 (use of a robust estimator) and 0.45 and 0.13 (negative binomial) respectively. CONCLUSION: Different methods exist to solve the problem of underestimating variance in the Poisson regression model when overdispersion is present. The negative binomial regression model seems to be particularly accurate because of its theorical distribution ; in addition this regression is easy to perform with ordinary statistical software packages.

Variation in pickleweed root-associated microbial communities at different locations of a saline solid waste management unit contaminated with petroleum hydrocarbons.

The main purpose of this study was to explore the potential influences of pickleweed vegetation on the abundance, diversity and metabolic activities of microbial communities in four distinct areas of a petroleum-contaminated solid waste management unit (SWMU) located in Contra Costa County, northern California. The four areas sampled include two central areas, one of which is central vegetated (CV) and one unvegetated (UV), and two peripheral vegetated areas, one of which is located to the west side of the SWMU (V-West) and one located to the east side (V-East). Measurements were made of total petroleum hydrocarbons (TPH), polyaromatic hydrocarbons (PAH), soil physicochemical properties, and various aspects of microbial communities including metabolic activities, microbial abundances (PLFAs), diversity and composition based on amplicon sequencing. The peripheral V-East and V-West sites had 10-times lower electrical conductivity (EC) than that of the CV and UV sites. The high salinity levels of the CV and UV sites were associated with significant reductions in bacterial and fungal abundances (PLFA) when compared to V-East but not when compared to V-West. TPH levels of CV and UV were not significantly different from those of V-West but were substantially lower than V-East TPH (19,311 mg/kg of dry soil), the high value of which may have been associated with a pipeline that ran through the area. Microbial activities (in terms of soil respiration and the activities of three soil enzymes, i.e., urease, lipase, and phosphatase) were greatest in the vegetated sites compared to the UV site. The prokaryotic community was not diverse as revealed by the Shannon index with no significant variation among the four groups of samples. However, the fungal community of the peripheral sites, V-East and V-West had significantly higher OTU richness and Shannon index. Structure of prokaryotic communities inhabiting the rhizosphere of pickleweed plants at the three sites differed significantly and were also different from those found in the UV region of the central site according to pairwise, global PERMANOVA and ANOSIM analyses. The differences in OTU-based rhizosphere-associated bacterial and fungal communities' composition were explained mainly by the changes in soil EC and pH. The results suggest that saline TPH-contaminated areas that are vegetated with pickleweed are likely to have increased abundances, diversity and metabolic activities in the rhizosphere compared to unvegetated areas, even in the presence of high salinity.

Estimating controlled direct effects in the presence of intermediate confounding of the mediator-outcome relationship: Comparison of five different methods.

In mediation analysis between an exposure X and an outcome Y, estimation of the direct effect of X on Y by usual regression after adjustment for the mediator M may be biased if Z is a confounder between M and Y, and is also affected by X Alternative methods have been described to avoid such a bias: inverse probability of treatment weighting with and without weight truncation, the sequential g-estimator and g-computation. Our aim was to compare the usual linear regression adjusted for M to these methods when estimating the controlled direct effect between X and Y in the causal structure and to explore the size of the potential bias. Estimations were computed in several simulated data sets as well as real data. We observed an increased bias of the controlled direct effect estimation using linear regression adjusted for M for larger effects of X on M and larger effects of Z on M The sequential g-estimator and g-computation gave unbiased estimations with adequate coverage values in every situation studied. With continuous exposure X and mediator M, inverse probability of treatment weighting resulted in some bias and less satisfactory coverage for large effects of X on M and Z on M.

MRI of acute osteomyelitis in long bones of children: Pathophysiology study.

INTRODUCTION: The classic pathophysiology of acute osteomyelitis in children described by Trueta has a metaphyseal infection as the starting point. This hypothesis was recently brought into question by Labbé's study, which suggested a periosteal origin. Thus, we wanted to study this disease's pathophysiology through early MRI examinations and to look for prognostic factors based on abnormal findings. MATERIAL AND METHODS: This was a prospective, multicentre study that included cases of long bone osteomyelitis in children who underwent an MRI examination within 7days of the start of symptoms and within 24hours of the initiation of antibiotic therapy. We also collected clinical, laboratory and treatment-related data. RESULTS: Twenty patients were included, including one with a bifocal condition. The lower limb was involved in most cases (19/21). Staphylococcus aureus was found most frequently. Metaphyseal involvement was present in all cases. No isolated periosteal involvement was found in any of the cases. No prognostic factors were identified based on the various abnormal findings on MRI. CONCLUSION: Our study supports the metaphyseal origin of acute osteomyelitis in children. LEVEL OF EVIDENCE: II.

Effects of long-term bilateral and unilateral fitting of different hearing aid types on the ability to locate sounds.

Aided localization ability of 87 hearing-impaired listeners was tested for horizontal and vertical sound sources, at two signal levels, and for two orientations to the loudspeaker array (facing, sideways). Some listeners wore behind-the-ear (BTE) aids, others in-the-ear (ITE) aids. Some were bilaterally fitted, others unilaterally fitted. Listeners were tested only with types of aids and fittings that they were accustomed to wearing. The results strongly supported bilateral fitting for moderately and severely hearing-impaired listeners. However, for mildly impaired listeners, those fitted unilaterally performed as well, on average, as those fitted bilaterally. This suggests a need to consider individual listening requirements and also to provide such listeners with experience in unilaterally-aided listening before assessing the possible advantages of bilateral fitting. When hearing level was controlled, there was no overall difference in the performance of ITE and BTE aid wearers. This discrepancy with other research may be explained by measures (removal of intensity cues, permitting of head movement) designed to make the test situation more representative of real-life listening.

[A prospective and comparative study of 262 laparoscopic cholecystectomies]. / Estudio prospectivo y comparativo de 262 colecistectomías laparoscópicas.

A prospective, comparative study is made of 262 patients (195 males, 67 females) subjected to laparoscopic cholecystectomy. Two groups were considered: simple cholelithiasis (SC) (187 cases), and complicated cholelithiasis (CC) (75 cases: 63 acute cholecystitis, 8 hydrocholecystitis, 4 pancreatitis). Mean age was 51 among the SC cases, and 57 in the CC patients. Mean operating time was 67 and 96 minutes for the SC and groups, respectively. Preoperative complications were more frequent in the CC group (51.4%) than in the SC patients (24%)--immediate laparotomies being performed in 2 and 25% of the SC and CC patients, respectively. Mortality was zero, with similar morbidity in both groups. Mean hospitalization time was 4.9 and 3.4 days for the CC and SC groups, respectively.

[Celioscopic cholecystectomy in simple and complicated cholelithiasis. Apropos of 392 cases]. / Cholécystectomie coelioscopique dans la lithiase vésiculaire simple et compliquée.

In a study including 392 patients we compared two groups of patients according to the indication for laparoscopic cholecystectomy: group I: 293 patients treated for simple cholelithiasis (n = 291) or gallbladder polyps (n = 2). Group II: 99 patients operated for complicated cholelithiasis. For each patient, 14 pre, intra and postoperative parameters were analysed and compared. Mean operative time was 80 minutes. Primary and secondary laparotomies were necessary in 5.8% and 1.3% of cases respectively. Biliary injury was the most frequent complication (1.3%). Mean hospital stay was 4.5 days. In terms of mean age, operative time, intraoperative incidents and complications, and primary laparotomy. There was a significant difference between the two groups (p less than 0.001). There were 4 secondary laparotomies in group II and one in group I. These results suggests that laparoscopic cholecystectomy is a safe technique with a low mortality rate (0.25%). The comparative study proves that this technique, first indicated for simple cholelithiasis, is also applicable to the majority of complicated cholelithiasis.

[Diagnostic traps and procedure to follow in radio-invisible biliary calculi]. / Pièges diagnostiques et conduite à tenir dans la lithiase biliaire radio-invisible

Instead of the term biliary microlithiasis, the authors prefer the general concept of radio-invisible biliary lithiasis. The size, the homogeneity, the site and chemical composition of the gall stones, which are the usual criteria of biliary microlithiasis, also are valid for radio-invisibility; thus the diagnostic traps are the only original characteristics of a pathology with hazy outlines, defined as one which escapes well conducted a radiological exploration. Biliary micro-lithiasis therefore raises a triple problem. The indications for biliary surgical exploration, in spite of normal cholangiography, seem to us undoubted in acute relapsing pancreatitis, once the usual medical causes have been eliminated. It should be more relative in pure biliary pain which first requires, not only repeated cholangiography, but also constant clinical and laboratory signs which suggest that the symptoms are organic and that gall stones are in formation. After laparotomy, cholecystectomy is required, not only in perceptible lithiasis, but also when the gall bladder bile contains mud, débris, sand or cholesterol spheroids. In the other cases, the choice between abstention or cholecystectomy depends on the clinical and laboratory context. The surgical attitude with regard to the common bile duct is discussed in three possibilities depending on the case, e.g. routine exploration, abstention or exploration in certain cases.