Photodynamic therapy and cholangiocarcinoma: where are we now?

Le cholangiocarcinome non résécable reste grevé d’une mortalité très élevée avec une survie ne dépassant pas quelques mois. Cette mortalité est essentiellement due aux phénomènes septiques qui sont la conséquence de la cholestase chronique due à l’obstruction des voies biliaires. La priorité chez ces malades est donc de réaliser le meilleur drainage biliaire possible. Le traitement endoscopique ou radiologique palliatif par insertion de prothèse(s) biliaire(s) offre un bon drainage biliaire dont le bénéfice est souvent malheureusement transitoire, avec une récidive des symptômes au bout de quelques mois. La photothérapie dynamique (PDT) réalisée par voie endoscopique associée à l’insertion de prothèse(s) biliaire(s) représente une nouvelle alternative dont les résultats très encourageants méritent une attention toute particulière dans ce contexte où les résultats des traitements oncologiques classiques tels que la radiothérapie et la chimiothérapie restent décevants. Récemment, deux études randomisées et contrôlées ont montré un gain de survie significatif lorsque le drainage endoscopique par stent est associé à la PDT, passant de 3 à 7 mois à 16 à 21 mois de survie médiane. Ces bons résultats doivent maintenant être confirmés par de plus larges études randomisées, mais positionnent, d’ores et déjà, la PDT comme un « standard » à considérer dans le traitement palliatif du cholangiocarcinome non résécable.Unresectable cholangicarcinoma is associated with a very high mortality, with an overall survival of only few months. This mortality is mainly due to chronic angiocholitis which is the consequence of the biliary tract obstruction. In these patients, priority must be given to the best biliary drainage to avoid septic complications. Endoscopic or radiologic biliary drainage by plastic or metallic stent offers a good biliary drainage but is unfortunately associated with a recurrence of symptoms within a few months.Photodynamic therapy (PDT) performed by endoscopy associated with the insertion of biliary stents is a new treatment with very good results, which deserve a very special attention in unresetable cholangiocarcinoma, given the disappointing results of classical oncologic treatments such as radiotherapy or chemotherapy. Recently, two randomized and controlled studies showed a significant benefit on overall survival when biliary drainage by stenting is associated with PDT, with an overall survival evaluated to 3-7 months vs 16-21 months. These good results must be confirmed by larger studies, but they already position PDT as a “standard” to be considered in the palliative treatment of unresectable cholangiocarcinoma

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Low skeletal muscle mass in stented esophageal cancer predicts poor survival : A retrospective observational study

Background Methods In esophageal cancer, nutritional challenges are extremely common. Malignant obstruction resulting from esophageal cancer (EC) is often treated by the insertion of expandable stents, but little is known as to the role and evolution of sarcopenia in this patient population. The aim of this article was to determine the effects of body mass parameters on survival of advanced EC patients who received a stent for palliation of malignant obstruction. This was a retrospective observational study of 238 EC patients who had a stent inserted for palliation of malignant obstruction between 2005 and 2013. Skeletal muscle mass was calculated from abdominal computed tomography scans, and the patients were divided into sarcopenic and non-sarcopenic groups. A follow-up computed tomography scan was available in 118 patients. The primary outcome was survival, and complication rates and the need for an alternative enteral feeding route were secondary outcomes. Results Conclusions Sarcopenia occurred in 199 (85%) patients. Median survival was 146 (range: 76-226) days in the sarcopenia group and 152 (range: 71-249) days in the non-sarcopenic group (P = 0.61). Complication rates between the groups were not significantly different (P = 0.85). In Cox regression analysis, the skeletal muscle index was inversely correlated with overall survival (hazard ratio 0.98, 95% confidence interval 0.97-0.99; P = 0.033). Sarcopenia, defined by consensus thresholds, at the time of stent insertion cannot effectively predict poor survival in this patient cohort, but a lower skeletal muscle index correlates with poor prognosis as a continuous variable.Peer reviewe

Different outcome of six homozygotes for prothrombin A20210A gene variant

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk

Glutamine as an Immunonutrient

Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations

Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement

BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\-8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks) than in group 2 (28+/-11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience

Etude des facteurs prédictifs de pancréatite aiguë post-CPRE

Introduction. La CPRE est une technique endoscopique de référence dans le traitement des affections bilio-pancréatiques présentant une morbidité non négligeable, avec en particulier un taux de pancréatite aiguë post-CPRE évalué entre 1% et 40% selon les études. L'identification de facteurs prédictifs de cette complication est donc d'un intérêt majeur. But de l'étude. Identifier sur une série prospective de CPRE consécutives des facteurs permettant de prédire précocement la survenue d'une pancréatite aiguë post-CPRE. Patients et Méthodes. Cette étude prospective s'est déroulée de janvier 2008 à juillet 2009 au sein de l'unité d'endoscopie digestive du CHU de Rouen. Les patients inclus étaient ceux pour lesquels l'indication d'une CPRE à visée thérapeutique était posée. Le seul facteur d'exclusion était l'existence d'une pancréatite aiguë au moment de la CPRE. Les patients bénéficiaient d'un bilan biologique à H4 et J2 au décours de la CPRE. Résultats. Au total, 104 CPRE ont été réalisées au cours de l'étude. L'âge moyen des patients était de 73.5 ans. La pathologie lithiasique était l'indication principale avec 67% des examens contre 29% des examens qui étaient réalisés pour une suspicion d'obstruction tumorale de la voie biliaire. Ainsi, 11.5% des CPRE se sont compliquées d'une pancréatite aiguë et aucun décès lié à l'examen n'a été constaté. Les facteurs prédictifs de cette complication retrouvés en analyse univariée étaient un âge =15 minutes et des taux d'amylase et lipase à H4 > ION. En analyse multivariée, seuls l'âge = 15 minutes étaient associés significativement à la survenue d'une pancréatite aiguë (p=0.043 et p=0.015, respectivement). Conclusion. L'âge inférieur à 75 ans et un temps de cathétérisme de plus de 15 min étaient les deux facteurs indépendants permettant de prédire la survenue d'une pancréatite aiguë post CPRE. Les patients ainsi identifiés pourraient bénéficier d'une conduite à tenir diagnostique (bilan H4) et thérapeutique adaptée à ce risque.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF