Fatty liver in the intensive care unit

PURPOSE OF REVIEW: Non-alcoholic steatohepatitis is a liver disease characterized by steatosis and steatohepatitis in subjects whose alcohol consumption is negligible. The primary form is associated with insulin resistance whereas secondary non-alcoholic steatohepatitis occurs notably during total parenteral nutrition or in patients in the intensive care unit. This review is mainly focused on recent developments in the understanding of the pathogenesis of this disease. RECENT FINDING: Pathogenesis involves the direct role of fatty acids in liver injury, oxidative stress, cytokines, genetic susceptibility or mitochondrial dysfunction. An increased delivery of free fatty acids to the liver contributes to the first hit, originating liver steatosis. The process may undergo a second hit, characterized by inflammation and hepatocellular degeneration. Mitochondrial dysfunction plays a key role by leading to abnormal generation of reactive oxygen species, which cause lipid peroxidation. The peroxidation products and cytokines favor progression from steatohepatitis to fibrosis. Fatty liver disease may also be encountered in the intensive care unit in patients receiving parenteral nutrition. However, an adapted glucose-lipid ratio as source of non-protein calories prevents the development of fatty liver. Moreover, recent evidence suggests the importance of the type of lipid infused (structured lipid emulsion or fish oils). The acute phase response associated with severe disease can also lead to the development of fatty liver in spite of adequate nutritional support. SUMMARY: The pathogenesis of non-alcoholic steatohepatitis is multifactorial, but there is growing evidence that mitochondrial dysfunction always plays a key role. Adapted nutrition may prevent in part fatty liver in the intensive care unit.     

Cytogenetic analysis of 52 Indian patients with de novo myelodysplastic syndromes—a comparative analysis of results with reports from Asia

Most published data on myelodysplastic syndromes (MDS) are derived from Western countries, which report MDS as a disease of the elderly. However, it was observed that Asian MDS patients were younger than subjects in Western reports. With this in mind, the study was conducted prospectively on 52 Indian patients to define chromosomal abnormalities and to understand ethno-geographical differences, if any, underlying the pathogenesis of MDS among this Asian population. Cytogenetic analysis was performed using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). The incidence of MDS was predominant in the age group of 41–60 years (44.23%), with a median age at diagnosis of 55 years. The disease was more frequent in males (33 patients, 63.46%) than females (19 patients, 36.53%). Of 48 patients successfully karyotyped, 17 had normal karyotype (35.4%) and 31 patients (64.5%) had a chromosomal abnormality. The most frequent chromosome abnormalities were del 5q/–5 in 13 patients (42%), –7/7q– in 10 patients (32.2%), +8 and del 20q– in 6 cases each (19.3%) and i(17)(q10) in 1 patient (3.2%). In addition to these non-random chromosomal abnormalities, some rare abnormalities were also encountered. A higher rate of transformation to acute myeloid leukaemia (AML) was observed in the Chinese population compared to other Asian countries. The incidence of chromosomal abnormalities varied considerably across the different Asian populations. The overall frequency of chromosomal abnormalities in our study was comparable to most Western reports. Further prospective studies are warranted to elucidate precisely the ethnic differences in the pathogenesis of MDS in the Indian population.     

Clinical practice guidelines: medical follow-up of patients with asthma--adults and adolescents

The follow-up of patients with asthma should focus on asthma control (disease course over a number of weeks).     

Retinol-binding protein, acute phase reactants and Helicobacter pylori infection in patients with gastric adenocarcinoma

AIM: To determine the serum levels of c-reactive protein (CRP), transferrin (TRF), a2-macroglobulin (A2M), ceruloplasmin (CER), a1-acid glycoprotein (AAG), pre-albumin (P-ALB) and retinol-binding protein (RBP) in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori (H pylori) infection. METHODS: We measured the serum levels of CRP, TRF, A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients (93 males; mean age: 63.1±11.3 years) with non-cardia gastric adenocarcinoma and 19 healthy subjects. RESULTS: The levels of CRP, CER, RBP, and AAG in cancer patients were significantly higher than those in healthy controls (P<0.0001), while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H pylori infection had significantly lower RBP values compared to non-infected ones (P<0.0001) and also higher values of CRP and AAG (P=0.09 and P=0.08, respectively). CONCLUSION: High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.     

Long-Term Outcome After Ampullectomy for Ampullary Lesions Associated With Familial Adenomatous Polyposis

PURPOSE Up to 90 percent of patients with familial adenomatous polyposis develop adenomas in the upper gastrointestinal tract. Besides pancreaticoduodenectomy, which remains indicated in duodenal and ampullary cancer, less aggressive surgical procedure (such as ampullectomy) must be evaluated in selected patients with familial adenomatous polyposis patients presenting low-risk benign duodenal adenomas. METHODS From 1995 to 2000, we performed a retrospective, observational study, which included eight patients (5 females) with familial adenomatous polyposis underwent ampullectomy (with frozen sections) for presumed benign polyposis lesions. Six patients had an ileal pouch-anal anastomosis performed 2 to 27 years before ampullectomy. The remaining two patients had ampullectomy during the same operation than ileal pouch-anal anastomosis. RESULTS No patient died postoperatively. Mean hospital stay was 15 ± 6.5 (range, 10–21) days. There was one major complication (pancreatic fistula), which was treated conservatively. Final pathologic examination of the specimens revealed that three patients had a severe dysplasia. Mean follow-up of the patients was 58 ± 37 (range, 24–119) months. During endoscopic follow-up, although all the patients underwent endoscopic resection of duodenal polyps, none presented recurrence at the ampullectomy site. CONCLUSIONS Ampullectomy could be safely proposed in selected familial adenomatous polyposis patients. Our low morbidity and the absence of recurrence after almost five years of follow-up suggests that such conservative treatment could be proposed before pancreaticoduodenectomy in patients with high-risk ampullary adenomas without invasive carcinoma.     

New adjuvants for parenteral and mucosal vaccines

Developing efficient adjuvants for human vaccines, in order to elicit broad and sustained immune responses at systemic or mucosal levels, remains a challenge for the vaccine industry. Conventional approaches in the past have been largely empirical and partially successful. Selection was based on the balance between toxicity and adjuvanticity, first in an animal model, and then in clinical trials. The advent of improved biochemical techniques has allowed for the purification or construction of new and well characterised adjuvants. In addition, recent advances in our understanding of the immune system, most particularly with respect to early proinflammatory signals, have led to the identification of new biological targets for vaccine adjuvants. In particular, one can now choose adjuvants able to selectively induce T helper (Th)-1 and/or Th2 responses, according to the vaccine target and the desired immune response. As our knowledge of the cell types and cytokines interacting in the immune responses increases, so does our understanding of the mode of action of adjuvants, as well as the way in which they produce adverse effects.     

Detection of the sentinal node in squamous-cell carcinoma of the oral cavity and oropharynx. Preliminary study

INTRODUCTION: The sentinel lymph node is defined as the first relay of the lymphatic drainage of the tumor. Isotopic detection of the sentinel lymph node and absence of its metastatic invasion should theoretically be predictive of total drainage of the tumor. The goal of this study was to evaluate sentinel lymph node detectability by lymphoscintigraphy in N0 and/or N1 squamous-cell carcinoma of oral cavity and oropharynx and to determine its negative predictive value. MATERIAL AND METHOD: Lymphoscintigraphy was used for sentinel lymph node detection. The procedure required peritumoral injection of technicium-labeled colloids to enable anatomical and cutaneous location of the sentinel lymph node. A one-way Tyco-Mallinckrodt probe was used for intraoperative detection of the sentinel lymph node. This prospective study included 21 patients with N0 or N1 squamous-cell carcinoma of the oral cavity and the oropharynx. The surgical attitude based on T and N was not modified in this prospective study without direct individual benefit for the patient. Neck dissection was achieved without difficulty. RESULTS: The sentinel lymph node was identified in 20 out of 21 subjects. The sentinel lymph node was not identified in one patient with recurrence T2N0M0 squamous-cell carcinoma of the oropharynx radiated 3 years earlier. The percentage of false-negatives was 12.5% (1 false-negative out of 8 positive patients), giving a sensibility of the detection method of 87.5% (IC (95%)=[47.35-99.68]). This false-negative patient had a T3N0M0 squamous-cell carcinoma of the oropharynx with a sentinel lymph node removed in territory III. Neck dissection revealed 1 N + R- in the sub-mandibular territory associated with 27 N-R-. The probability of not finding a metastatic node at neck dissection when the sentinel lymph node is not metastatic (negative predictive value) was 92.3% (12/13) (IC (95)=[63.97-99.81]). The specificity of the method was 100%, as was the positive predictive value, because no sentinel node was diagnosed positive wrongly on frozen sections among patients without true histological node metastasis. DISCUSSION: For routine care of patients with squamous-cell carcinoma of the oral cavity and the oropharynx detection of the sentinel lymph node is proposed primarily for patients with T1T2N0 staging. Larger tumors can modify the architecture and flow within the lymphatic ducts, and consequently even the concept of a sentinel lymph node. Systematic neck dissection is required or T3T4, even when N0. Our series of T1T2N0 tumors is too small to enable statistically significant conclusions. A low level of false-negative in a larger series would be necessary to propose this technique instead of convention neck dissection for T1T2 tumors of the oral cavity and oropharynx.     

Clinical aspects of dysosmia and presentation of European Olfactory Test of "sniffin sticks": a review

The medical community has neglected olfactory dysfunction for a long time. However, over the last two decades, remarkable progress has been made in terms of understanding the sense of smell and both the assessment and diagnosis of olfactory dysfunction. Currently, there are only a few validated olfactory tests. The most commonly used one is the University of Pennsylvania Smell Identification Test. Owing to its cultural biases, this test is mostly used in the United States. "Sniffin' Sticks" are one of the first European tests to be widely used. Since their development in 1996, they have been applied in numerous studies and have found increasing use in otolaryngology clinics. The goal of this article is to present Sniffin' Sticks and to provide a review of clinical olfactory research during recent years.