Artificial milk preference of newborn lambs is prenatally influenced by transfer of the flavor from the maternal diet to the amniotic fluid.

The present study examined in lambs whether exposure to flavors derived from pregnant mother's diet and transferred to amniotic fluid (AF) could induce a preference for artificial milk containing one of these flavors. To test this hypothesis, cumin was added to the maternal diet in the last month of gestation. Preference for artificial milk containing p-cymene, one of the chemosensory compounds of cumin, was tested within the first two days after birth in maternally deprived lambs born from mothers fed a cumin-flavored diet (Cumin group), or an unflavored diet (Control group). Aromatic profile of AF from cumin-fed mothers was analyzed by GC-MS/MS to determine whether p-cymene could be detected. While the control group avoided the flavored artificial milk on day 1, the Cumin group did not and showed a preference for the cumin-scented formula on day 2. GC-MS/MS profile of AF revealed that four of the main volatile cumin compounds, p-cymene, p-cymenene, ß-pinene and γ-terpinene were present in variable amounts in all samples, p-cymene being the most frequently detected. These findings indicate that newborn lambs can memorize flavors from the mother's diet present in AF and that prenatal experience influences their preference for an artificial milk containing one specific flavor.

Differential effects of oxytocin on olfactory, hippocampal and hypothalamic neurogenesis in adult sheep.

New neurons are continuously added in the dentate gyrus of the hippocampus, the olfactory bulb and the hypothalamus of mammalian brain. In sheep, while the control of adult neurogenesis by the social environment or the photoperiod has been the subject of several studies, its regulation by intrinsic factors, like hormones or neurotransmitters is less documented. We addressed this question by investigating the effects of central oxytocin administration on hippocampal, olfactory and hypothalamic neurogenesis. Endogenous markers, Ki67, Sox2 and DCX were used to assess cell proliferation, progenitor cells density and cell survival respectively in non-gestant ewes receiving a steroid treatment followed by intracerebroventricular injections of either oxytocin or saline. The results showed that oxytocin treatment significantly decreases the density of neuroblasts in the olfactory bulb, increases the density of neuroblasts in the ventromedian nucleus of the hypothalamus while no change is observed in both ventral and dorsal dentate gyrus. In addition, no change in the density of progenitor cells is found in the three neurogenic niches. These findings show for the first time that in females, oxytocin can regulate adult neurogenesis by acting on neuroblasts but not on progenitor cells and that this regulation is region specific.

[Alcool and pancreatic complications]. / Alcool et complications pancréatiques.

Alcohol consumption is the main cause of development of chronic pancreatitis and the second etiology of acute pancreatitis. The mortality of acute pancreatitis depends on its necrotic haemorrhagic character and the initial inflammatory response, while pain, malnutrition and diabetes are the main issues in the management of chronic pancreatitis. As medical and endoscopic techniques progress, surgical indications have become increasingly rare but remain indispensable for some patients. The multidisciplinary approach of these patients is the key to the success of care.

La consommation d'alcool est la cause principale de développement d'une pancréatite chronique et la seconde étiologie de la pancréatite aiguë. La mortalité de la pancréatite aiguë dépend de son caractère nécrotico-hémorragique et de la réponse inflammatoire initiale tandis que les complications de type douleur, dénutrition et diabète sont les principaux enjeux de la prise en charge de la pancréatite chronique. Au fur et à mesure de l'avancée des techniques médicales et endoscopiques, les indications chirurgicales sont devenues de plus en plus rares, mais restent indispensables pour certains patients. L'approche pluridisciplinaire de ces patients est la clé du succès de la prise en charge.

Disruption of adult olfactory neurogenesis induces deficits in maternal behavior in sheep.

Profound behavioral changes occur in the mother at parturition, a time when the maternal brain undergoes extensive remodeling of neural circuits, especially in olfactory structures. Adult neurogenesis, a form of brain plasticity, could constitute an adaptive response to motherhood. The present study hypothesized that chemical disruption of olfactory neurogenesis would impair the establishment of maternal behavior in sheep. In addition, because ewes are able to learn the olfactory signature of their offspring, we also examined whether disruption of olfactory neurogenesis altered recognition of the familiar lamb. At one month of gestation, ewes received either infusion of the antimitotic drug Ara-C or saline into the lateral ventricles via one-month-long osmotic minipumps. Ara-C infusion dramatically decreased olfactory neurogenesis but spared hippocampal neurogenesis. Mothers exhibiting more than a 70% reduction in olfactory neurogenesis emitted fewer maternal bleats during the first hours after parturition. Reduction of olfactory neurogenesis also negatively affected discrimination of the familiar lamb. Differences in ewes' aggressive behavior toward familiar and alien lambs were observed in sham mothers, but not in mothers with reduced olfactory neurogenesis. In addition, when ewes were given the choice between familiar and unfamiliar anesthetized lambs, so that only olfactory cues were available, mothers with a reduction in neurogenesis greater than 70% were not able to discriminate their own lamb from an alien lamb. These results indicate that adult-born olfactory neurons are to some extent involved in the establishment of maternal behavior in sheep by contributing to the processing of offspring odors.

Exposure to young preferentially activates adult-born neurons in the main olfactory bulb of sheep mothers.

New neurons are continuously added to the main olfactory bulb (MOB) of the mammalian brain. While their function has been demonstrated in olfactory learning, it is less known in an ethological context such as mothering. We addressed this question by investigating whether in sheep mothers the adult-generated olfactory neurons contribute to the processing of odors involved in attraction to lambs and in memorization of its individual signature. Parturient ewes, after having 2 days of contact with their lamb and being separated from them for 3 h, were exposed for 2 h either to their own lamb, an unfamiliar lamb or a familiar adult sheep and then sacrificed. A control group was composed of mothers not exposed to any lambs for 5 h before sacrifice. Bromodeoxyuridine, a marker of cell division, was injected 3 months before parturition and revealed through immunocytochemistry in combination with markers of activation or neuronal maturation. The percentage of adult-born cells activated in the granular layer of the MOB was compared between the four groups. Results show that the whole population of olfactory neuroblasts and in particular the 3-month-old neuroblasts, are preferentially activated by lamb exposure and that the preferential activation is specific to olfactory neurogenesis since no activation was observed in newborn neurons of the dentate gyrus. However, neither neuroblasts nor mature neurons of the MOB differentiate between familiar and unfamiliar lamb exposure. Therefore, our data shows that adult-born neurons contribute to the processing of infantile odors which are determinant for maternal behavior.

[CONTROVERSIES REGARDING THE ACCURACY AND LIMITATIONS OF FROZEN SECTION IN THYROID PATHOLOGY: AN EVIDENCE-BASED ASSESSMENT]. / INTÉRÊTS ET LIMITES DE L'EXAMEN EXTEMPORANÉ EN PATHOLOGIE THYROÏDIENNE. Revue systématique de la littérature et évaluation fondée sur les preuves.

Palpable thyroid nodules are present clinically in 4-7% of the population and their prevalence increases to 50%-67% when using high-resolution neck ultrasonography. By contrast, thyroid carcinoma (TC) represents only 5-20% of these nodules, which underlines the need for an appropriate approach to avoid unnecessary surgery. Frozen section (PS) has been used for more than 40 years in thyroid surgery to establish the diagnosis of malignancy. However, a controversy persists regarding the accuracy of FS and its place in thyroid pathology has changed with the emergence of fine-needle aspiration (FNA). A PubMed Medline and SpringerLink search was made covering the period from January 2000 to June 2012 to assess the accuracy of ES, its limitations and indications for the diagnosis of thyroid nodules. Twenty publications encompassing 8.567 subjects were included in our study. The average value of TC among thyroid nodules in analyzed studies was 15.5 %. ES ability to detect cancer expressed by its sensitivity (Ss) was 67.5 %. More than two thirds of the authors considered PS useful exclusively in the presence of doubtful ENA and for guiding the surgical extension in cases confirmed as malignant by FNA; however, only 33% accepted FS as a routine examination for the management of thyroid nodules. The influence of FS on surgical reintervention rate in nodular thyroid pathology was considered to be negligible by most studies, whereas 31 % of the authors thought that FS has a favorable benefit by decreasing the number of surgical re-interventions. In conclusion, the role of FS in thyroid pathology evolved from a mandatory component for thyroid surgery to an optional examination after a pre-operative FNA cytology. The accuracy of FS seems to provide no sufficient additional benefit and most experts support its use only in the presence of equivocal or suspicious cytological features, for guiding the surgical extension in cases confirmed as malignant by FNA and for the identification of other potentially confusing intraoperative findings.

Solid pseudopapillary tumor of the pancreas: a report of six cases.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare pancreatic neoplasm. The aim of this study was to discuss the clinical presentation, management, and outcome of patients with this kind of tumor. MATERIALS AND METHODS: A retrospective review was performed in 6 patients with SPTP surgically treated between January 2004 and September 2011 in our hospital. RESULTS: All the 6 patients were female. The mean age of the patients was 39 years (range, 18 to 67 years). The main clinical presentation was abdominal pain or discomfort, however a third of the patients were asymptomatic. The mean size of the tumor was 9.7 cm (range, 2.5 to 18 cm). Three tumors had a well defined capsule, 3 tumors extended in the pancreas. Four of the 6 tumors had a cystic component, and calcifications were observed in one tumor. No lymph node involvement, no lymphatic invasion and no nerve invasion were observed. One tumor showed an infiltration of the splenic vein, and another patient had a liver metastasis with complete resection. Distal pancreatectomy (n = 3), local resection (n = 1), cephalic duodenopancreatectomy (n = 1), and distal pancreatectomy associated with a right hepatectomy (n = 1) were performed. The main postoperative complication in the short-term was bleeding (n = 1), and long-term the development of an insulin-requiring diabetes (n = 2). No patient received adjuvant therapy. Overall mortality rate was 0%. All patients were still alive without recurrent disease with a median follow up of 36.2 months. CONCLUSION: Patients with SPTP have an excellent prognosis after its complete removal, even if it is a minimized resection.

Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme.

BACKGROUND: Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. METHODS: All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. RESULTS: A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). CONCLUSION: Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized.

A more than 20% increase in deceased-donor organ procurement and transplantation activity after the use of donation after circulatory death.

BACKGROUND: Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS: Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS: There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors ≥60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS: This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source.

Dynamics of olfactory and hippocampal neurogenesis in adult sheep.

Although adult neurogenesis has been conserved in higher vertebrates such as primates and humans, timing of generation, migration, and differentiation of new neurons appears to differ from that in rodents. Sheep could represent an alternative model to studying neurogenesis in primates because they possess a brain as large as a macaque monkey and have a similar life span. By using a marker of cell division, bromodeoxyuridine (BrdU), in combination with several markers, the maturation time of newborn cells in the dentate gyrus (DG) and the main olfactory bulb (MOB) was determined in sheep. In addition, to establish the origin of adult-born neurons in the MOB, an adeno-associated virus that infects neural cells in the ovine brain was injected into the subventricular zone (SVZ). A migratory stream was indicated from the SVZ up to the MOB, consisting of neuroblasts that formed chain-like structures. Results also showed a long neuronal maturation time in both the DG and the MOB, similar to that in primates. The first new neurons were observed at 1 month in the DG and at 3 months in the MOB after BrdU injections. Thus, maturation of adult-born cells in both the DG and the MOB is much longer than that in rodents and resembles that in nonhuman primates. This study points out the importance of studying the features of adult neurogenesis in models other than rodents, especially for translational research for human cellular therapy.

Delayed graft function does not harm the future of donation-after-cardiac death in kidney transplantation.

INTRODUCTION: Delayed graft function (DGF) occurs more frequently in kidney transplants from donation after cardiac death (DCD) than from donation after brain death (DBD). We investigated the effect of DGF on posttransplantation outcomes among grafts from controlled DCD kidneys. PATIENTS AND METHODS: This single-center retrospective study recruited 80 controlled DCD kidneys transplanted from January 2005 to December 2011. Mean patient follow-up was 28.5 months. RESULTS: There were no primary nonfunction grafts; the DGF rate was 35.5%. Overall graft survival rates between groups with versus without DGF were 92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5 years, respectively (P = not significant (NS)). Patients with versus without DGF showed the same survival rates at the corresponding time 92.4% vs 97.2%, 92.4% vs 93.9%, and 84.7% vs 93.9% (P = NS). Estimated glomerular filtration rate was significantly lower in the DGF compared with the non-DGF group at hospital discharge (29 vs 42 mL/min; P = .00) and at 6 months posttransplantation (46 vs 52 mL/min; P = .04), but the difference disappeared thereafter: 47 vs 52 mL/min at 1 year, 50 vs 48 mL/min at 3 years, and 54 vs 53 mL/min at 5 years (P = NS). DGF did not increase the risk of an acute rejection episode (29.6% vs 30.6%; P = NS) or rate of surgical complications (33.3% vs 26.5%; P = NS). However, DGF prolonged significantly the length of hospitalization in the DGF versus the non- DGF group (18.9 vs 13 days; P = .00). Donor body mass index (BMI) ≥ 30 kg/m(2), recipient BMI ≥30 kg/m(2), and pretransplantation dialysis duration increased the risk of DGF upon multivariate logistic regression analysis. CONCLUSIONS: Apart from the longer hospital stay, DGF had no deleterious impact on the future of kidney allografts from controlled DCD, which showed comparable graft and patient survivals, renal function, rejection rates, and surgical complications as a group without DGF. Therefore, DGF should no longer be considered to be a medical barrier to the use of kidney grafts from controlled DCD.

Evolution of native kidney function after pancreas transplantation alone.

INTRODUCTION: This study investigated changes in kidney function over time among a cohort of patients undergoing pancreas transplantation alone (PTA) from January 2002 to December 2011. PATIENTS AND METHODS: Ten of eighteen PTA patients bearing functioning grafts for at least 1 year were recruited for the analysis. Primary endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation (mL/min/1.73 m(2)) comparing baseline (pretransplantation) to 6-month, 1-year, 3-year, and 5-year posttransplantation values. Mean follow-up time was 75.7 ± 20.5 months (range, 46-106.5). RESULTS: Baseline eGFR was 89.3 ± 27.9 (range, 58-145). eGFR decreased to 75.7 ± 26.2, 71 ± 20.6, 66.5 ± 14.8, and 62.1 ± 11.2 at 6 months, 1, 3, and 5 years representing -15.2%, -20.5%, -15.8%, and -22.6% percentage decreases respectively (P < .05 for all pairwise comparisons). The Baseline SCr was 8.6 ± 2.3 mg/L (range, 5-13). SCr progressively increased to 10.1 ± 3, 10.5 ± 3.1, 10.9 ± 3.1, and 11.3 ± 1.7 at 6 months, 1, 3, and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P < .05 for all pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR <60 at transplantation versus 3 and 5 years thereafter, respectively. No patient developed a SCr > 25 mg/L or eGFR <30 or needed dialysis or kidney transplantation. Five of ten patients had micro-albuminuria or proteinuria before transplantation. Tacrolimus levels were within recommended therapeutic ranges over time. CONCLUSION: Kidney function deteriorated significantly after PTA. Understanding of risk factors for the development of renal impairment is important to preserve kidney function and to select appropriate candidates for PTA.

Cardiac paraganglioma: diagnostic work up and review of the literature.

Paraganglioma of the heart are potentially invasive, highly vascularized tumors for which complete resection may be curative. Derived from the cardiac wall in most instances, resectability can be assessed after integration of the data provided by MRI in T2 sequence, and coronarography. A fully documented case of a large cardiac pheochromocytoma of the left atrium and AV groove is reported and the pertinent literature on the subject is here presented.

Categories of donation after cardiocirculatory death.

The interest in donation after cardiocirculatory death (DCD) was renewed in the early 1990s, as a means to partially overcome the shortage of donations after brain death. In some European countries and in the United States, DCD has become an increasingly frequent procedure over the last decade. To improve the results of DCD transplantation, it is important to compare practices, experiences, and results of various teams involved in this field. It is therefore crucial to accurately define the different types of DCD. However, in the literature, various DCD terminologies and classifications have been used, rendering it difficult to compare reported experiences. The authors have presented herein an overview of the various DCD descriptions in the literature, and have proposed an adapted DCD classification to better define the DCD processes, seeking to provide a better tool to compare the results of published reports and to improve current practices. This modified classification may be modified in the future according to ongoing experiences in this field.

Pancreas preservation for pancreas and islet transplantation: a minireview.

Pancreas preservation by cold storage using University of Wisconsin solution was the mainstay method used for pancreas transplantation during the past 2 decades. Other solutions, such as HTK, Celsior, and SCOT 15, could not demonstrate any advantage for short preservation periods. But the advent of clinical islet transplantation and the larger use of controlled non-heart-beating donors have prompted the transplantation community to develop methods for increasing pancreas graft quality while preventing ischemic reperfusion damages. Oxygenation by 1- or 2-layer methods during pancreas preservation, as well as the use of perfluorocarbons, might increase the islet yield. Based on the former methods, there is a renewed interest in machine perfusion and oxygenation in pancreas preservation for pancreas transplantation and islet preparation.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

Esophageal cancer surgery in patients older than 75: long term results.

PURPOSE: The purpose of this study was to evaluate short and long term results after esophageal cancer resection in patients older than 75. METHODS: We retrospectively analyzed the database of esophageal cancer surgically treated in our department between January 2003 and December 2009 to identify patients older than 75. The preoperative, operative, postoperative and long term characteristics were analyzed. RESULTS: Among 137 patient, 23 were older than 75. The histological subtype was adenocarcinoma in 100%. The surgical techniques were a "Lewis-Santy" procedure in 43%, a trans-hiatal resection in 22%, a "Sweet" procedure in 13%, a stripping in 13% and a McKeown procedure in 9%. The in-hospital postoperative mortality was 13%. The in-hospital postoperative morbidity (Dindo-Clavien Grade >2, deceased patients included) was 26%. In univariate analysis, no statistically significant risk factor of morbidity was found. A Charlson Comorbidity Index >2 was, in univariate analysis, the sole risk factor of postoperative mortality (p = 0.0362). The mean hospital stay was 22 +/- 12 days. The median survival was 24.2 months. The 5-year overall survival was 39% and the 5-year disease free survival was 26%.57% of long-term deaths were not cancer related. CONCLUSION: Esophageal surgery performed in selected patients older than 75 has an acceptable morbidity and mortality but when a severe complication occurs, it leads to death in half of the cases. Surgery enables a long term survival benefit. This study confirmed our attitude of not considering age as a contra-indication for esophageal surgery but rather considering general status, self-reliance and associated comorbidities for patients' selection.

[Clinical case of the month. Cystic lymphangioma of the mesentery]. / Le cas clinique du mois. Le lymphangiome kystique du mésentère.

Cystic lymphangioma of the mesentery is a benign condition, probably of malformative origin, and frequently appearing in infancy. Its symptomatology can be very polymorphic. Its diagnosis is suspected by ultrasonography and computed tomography, and definitely confirmed by pathology. About a recent case of cystic lymphangioma of the mesentery diagnosed and operated on at the university hospital of Liège in an adult patient, the authors review its classification and its therapeutic strategy. Surgical resection is indicated in symptomatic cystic lymphangioma.

Contribution of donors after cardiac death to the deceased donor pool: 2002 to 2009 University of Liege experience.

OBJECTIVE: In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS: We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS: We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION: The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.