Correlation of tumor-associated antigens MAGE, NY-ESO-1 and P53 expression with clinical and pathological relationships of patients with oral squamous cell carcinoma

Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.

Female asylum seekers with musculoskeletal pain: the importance of diagnosis and treatment of hypovitaminosis D.

BACKGROUND: Hypovitaminosis D is well known in different populations, but may be under diagnosed in certain populations. We aim to determine the first diagnosis considered, the duration and resolution of symptoms, and the predictors of response to treatment in female asylum seekers suffering from hypovitaminosis D. METHODS: Design: A pre- and post-intervention observational study. Setting: A network comprising an academic primary care centre and nurse practitioners. Participants: Consecutive records of 33 female asylum seekers with complaints compatible with osteomalacia and with hypovitaminosis D (serum 25-(OH) vitamin D < 21 nmol/l). Treatment intervention: The patients received either two doses of 300,000 IU intramuscular cholecalciferol as well as 800 IU of cholecalciferol with 1000 mg of calcium orally, or the oral treatment only. Main outcome measures: We recorded the first diagnosis made by the physicians before the correct diagnosis of hypovitaminosis D, the duration of symptoms before diagnosis, the responders and non-responders to treatment, the duration of symptoms after treatment, and the number of medical visits and analgesic drugs prescribed 6 months before and 6 months after diagnosis. Tests: Two-sample t-tests, chi-squared tests, and logistic regression analyses were performed. Analyses were performed using SPSS 10.0. RESULTS: Prior to the discovery of hypovitaminosis D, diagnoses related to somatisation were evoked in 30 patients (90.9%). The mean duration of symptoms before diagnosis was 2.53 years (SD 3.20). Twenty-two patients (66.7%) responded completely to treatment; the remaining patients were considered to be non-responders. After treatment was initiated, the responders' symptoms disappeared completely after 2.84 months. The mean number of emergency medical visits fell from 0.88 (SD 1.08) six months before diagnosis to 0.39 (SD 0.83) after (P = 0.027). The mean number of analgesic drugs that were prescribed also decreased from 1.67 (SD 1.5) to 0.85 (SD 1) (P = 0.001). CONCLUSION: Hypovitaminosis D in female asylum seekers may remain undiagnosed, with a prolonged duration of chronic symptoms. The potential pitfall is a diagnosis of somatisation. Treatment leads to a rapid resolution of symptoms, a reduction in the use of medical services, and the prescription of analgesic drugs in this vulnerable population.

Chronology of extraintestinal manifestations relative to IBD diagnosis in the Swiss IBD Cohort

Background and Aims: Due to a p aucity of s uch data we aimed to a ssess the type and f requency o f extraintestinal manifestations ( EIM) in I BD p atients and to e valuate their chronologic behavior. Methods: A nalysis of d ata from t he Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which c ollects data since 2 005 on a large sample o f IBD patients f rom hospitals and private practices across Switzerland. Results: A t total o f 1,143 patients were a nalyzed ( 572 (50%) female, mean age 42.1 ± 14.4 years), 629 with Crohn's disease (CD), 501 with ulcerative colitis (UC), and 13 with indeterminate colitis ( IC). Of t hese, 3 74 (32.7%) presented o ne to five E IM (65% w ith CD, 3 3% w ith UC, 2% w ith IC). O f those patients suffering from EIM, 4 1.7% p resented two, 1 2.4% t hree, 5 .3% four, and 3.2% f ive E IM d uring lifetime. T he initial EIM presented with the following frequencies: p eripheral a rthritis (PA) 6 3.4%, ankylosing spondylitis (AS) 8 .1%, primary sclerosing cholangitis (PSC) 6%, uveitis 5.7%, oral a phthosis 5.7%, erythema nodosum (EN) 5 %, other 3 .6%, pyoderma gangrenosum 1.8%, psoriasis 0.7%. In only 7.1% of cases, the EIM m anifested before IBD diagnosis was made (median time 28 months b efore IBD diagnosis, I QR 7 -60 months), in 9 2.9% EIM m anifested a fter e stablished IBD d iagnosis (median 72 months, IQR 9-147 months). Conclusions: EIM are a frequent problem in IBD patients. The vast m ajority of E IM m anifest a fter I BD d iagnosis has b een established. P eripheral a rthritis, a nkylosing spondylitis, a nd PSC represent the most frequent first manifestations of an EIM.

Photodynamic Diagnosis in Non-Muscle-Invasive Bladder Cancer

Objective This paper reviews the development and clinical validation of photodynamic diagnosis (PDD) of bladder cancer. Methods The authors reviewed the literature on the development of PDD, in particular the evidence for the clinical efficacy of hexaminolevulinate PDD in the diagnosis of bladder cancer. Results After initial work on ultraviolet cystoscopy following oral tetracycline, the focus of PDD research shifted to the use of synthetic porphyrins. First, the prodrug delta-aminolevulinic acid (ALA) was shown to cause a transient but significant accumulation of protoporphyrin IX (PpIX) in malignant or premalignant bladder tissue. Excitation by blue light leads to PpIX fluorescence (red), which distinguishes tumour from normal tissue (blue). Hexaminolevulinate (HAL, Hexvix), an ester of ALA, was then developed and has greater bioavailability and stability than the parent compound. It has been approved for clinical use in the diagnosis of bladder cancer. Clinical studies have shown that HAL PDD detects tumours, including carcinoma in situ (CIS), that are missed by conventional white-light cystoscopy. Conclusions HAL PDD is a valuable aid to the detection of bladder tumours, including CIS.

Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe.

OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination. METHODS: Data from 20 registries of congenital malformations in 12 European countries were included in the study. RESULTS: There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening.

Les sinusites d'origine dentaire: diagnostic et prise en charge [Diagnosis and management of sinusitis of odontogenic origin]

Les sinusites maxillaires sont des infections fréquentes de la sphère ORL. On retrouve une étiologie dentaire dans environ 10% des cas. L'extension des infections dentaires dans le sinus maxillaire est possible en raison de la proximité des racines des dents postérieures avec le bas fond sinusien. Une source odontogène doit être suspectée chez les patients ayant une anamnèse de douleur ou d'infection dentaires, de soins dentaires récents et qui présentent une sinusite unilatérale prolongée ou résistant à un traitement conservateur habituel. Les infections d'origine dentaire possèdent une flore bactérienne mixte. Le diagnostic et la prise en charge nécessitent un bilan radiologique précis. Le traitement doit prendre en charge conjointement la cause dentaire et la sinusite. Un geste chirurgical peut être indiqué dans un deuxième temps afin de restaurer la fonction sinusienne. Maxillary sinusitis are common infections. A dental origin is found in about 10% of the cases. The roots of the posterior maxillary teeth are adjacent to the sinus floor. Extensions of dental infections are therefore possible to the sinus. An odontogenic source should be considered in patients with a history of dental pain or recent oral surgery and those with extended unilateral sinusitis or unilateral sinusitis resistant to conventional treatment. Maxillary sinusitis of dental origin are polymicrobial infections. Conventional radiographs and CT-scans are required for the diagnosis and proper management. Dental treatments to remove the underlying cause combined with oral antibiotics to treat the infection are required. Endoscopic or open surgery may be necessary to complete the treatment and restore adequate sinusal function.

Chylothorax in children: guidelines for diagnosis and management.

STUDY OBJECTIVE: To establish guidelines for the diagnosis and management of chylothorax in children. DESIGN: Retrospective study. PATIENTS: Fifty-one patients with a diagnosis of chylothorax. Twelve patients were excluded because of incomplete data or incorrect diagnosis. The following parameters were analyzed: triglyceride level, total cell number, and lymphocyte percentage; amount of pleural effusion on day of diagnosis, day 5, and day 14; and total time of pleural effusion. Prospectively, the same parameters were analyzed in a control group of 10 patients with pleural drainage. INTERVENTION: Patients with chylothorax were treated primarily with fat-free oral nutrition; if chyle did not stop, total parenteral nutrition with total enteric rest was started. If conservative therapy was not successful, pleurodesis was performed. RESULTS: In children with chylothorax triglyceride, triglyceride content ranged from 0.56 to 26.6 mmol/L; all values except one were > 1.1 mmol/L. In 36 of 39 patients (92%), the cell count was > 1,000 cells/microL. In 33 of 39 patients (85%), lymphocytes were > 90%. In patients without chylothorax triglyceride, triglyceride levels ranged from 0.1 to 0.71 mmol/L (median, 0.38 mmol/L) and cell count was from 20 to 1400 cells/microL (median, 322 cells/microL), with a maximum of 60% lymphocytes. With fat-free nutrition, chyle disappeared in 29 of 39 patients. Five patients died, and five required pleurodesis. CONCLUSIONS: Pleural effusion in children is chyle when it contains > 1.1 mmol/L triglycerides (with oral fat intake) and has a total cell count > or 1,000 cells/microL, with a lymphocyte fraction > 80%. Chylous effusions usually last long; however, after 6 weeks, the majority of the effusions (29 of 39 patients) had ceased. Late surgical interventions reduce the number of thoracotomies substantially, but can lead to very long hospitalization times. Early surgical interventions (after < 3 weeks) lead to a high number of thoracotomies, but certainly reduce hospitalization time.

Different PTH response to oral peptone load and oral calcium load in patients with normocalcemic primary hyperparathyroidism, primary hyperparathyroidism, and healthy subjects.

BACKGROUND: Normocalcemic primary hyperparathyroidism (PHPT-N) is a condition that may have similar long-term implications to primary hyperparathyroidism (PHPT); however, differential diagnosis and treatment for parathyroid disorders are not clearly defined. We investigated the effect of an oral peptone and an oral calcium load on calcium-regulating hormones in PHPT-N compared with PHPT and healthy controls to provide a new potential diagnostic tool. DESIGN: Case-control study. METHODS: We evaluated serum gastrin, PTH, ionized calcium, and phosphate responses to oral calcium (1 g) and peptone (10 g) load in 22 PHPT and 20 PHPT-N patients matched for PTH serum values. Moreover, 30 healthy subjects were enrolled as controls. In 12 patients for each group, we also performed the oral peptone test adding aluminum hydroxide (AH) to suppress phosphate absorption. RESULTS: In PHPT patients, PTH increased significantly 30 min after the oral peptone load, while no significant increase was found in PHPT-N and controls. After oral calcium load, PTH remained stable in PHPT while it decreased dramatically in PHPT-N patients, and ionized calcium increased significantly in each of the three groups. Peptones plus AH induced a blunted PTH increase in the three groups. CONCLUSIONS: Considering the marked difference in PTH response elicited by peptones in PHPT compared with PHPT-N, we suggest that the oral peptone test could be added to the diagnostic evaluation of PHPT patients. In case of absent response to peptones, patients should have their serum calcium levels assessed twice a year in accordance with recent guidelines.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients.

This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be summarized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of 14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treatment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifungal regimen of choice is liposomal amphotericin B +/- flucytosine. In ocular candidiasis, liposomal amphotericin B +/- flucytosine is recommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.

Oral and intravenous methadone use: some clinical and pharmacokinetic aspects.

A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. As expected, due to the shunt of metabolism in the gut wall and of the liver first-pass effect, higher concentration to dose ratios of (R)-methadone, which is the active enantiomer, were measured in the intravenous group (23% increase). This difference reached an almost statistically significant value (P = 0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.

Oral chloramphenicol therapy for multiple liver abscesses in hyperimmunoglobulinemia E syndrome.

In a patient with Hyper-IgE-syndrome multiple liver abscesses developed in spite of prophylactic treatment with trimethoprim and sulfamethoxazol. Ultrasound confirmed the clinical diagnosis and percutaneous needle aspiration under ultrasonographic guidance and culture of the aspirated pus allowed specific antibiotic treatment by oral chloramphenicol alone without surgical drainage. The isolated Staph.aureus strain was resistant to trimethoprim and sulfamethoxazol.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS.

Mucosal candidiasis is frequent in immunocompromised HIV-infected highly active antiretroviral (HAART) naive patients or those who have failed therapy. Mucosal candidiasis is a marker of progressive immune deficiency. Because of the frequently marked and prompt immune reconstitution induced by HAART, there is no recommendation for primary antifungal prophylaxis of mucosal candidiasis in the HIV setting in Europe, although it has been evidenced as effective in the pre-HAART era. Fluconazole remains the first line of therapy for both oropharyngeal candidiasis and oesophageal candidiasis and should be preferred to itraconazole oral solution (or capsules when not available) due to fewer side effects. For patients who still present with fluconazole-refractory mucosal candidiasis, oral treatment with any other azole should be preferred based on precise Candida species identification and susceptibility testing results in addition to the optimization of HAART when feasible. For vaginal candidiasis, topical therapy is preferred.

Chirurgie thoracique majeure et dénutrition préopératoire: rationnel, diagnostic et prise en charge [Thoracic surgery and underfeeding scientific evidences, diagnosis and treatment]

Underfeeding causes a significant increase of postoperative complications, particularly respiratory and infectious complications. Thoracic surgery is frequently required in patients suffering wasting diseases (cancer, COPD, cystic fibrosis), which increase the risk of malnutrition. The most important risk factors are preoperative hypoalbuminemia and BMI < 20. The deleterious effects of underfeeding may be corrected by a preoperative nutritional support for 7 to 15 days using oral supplements or enteral feeding: respiratory muscle strength is improved, immunity is restored, and overall complications are reduced. Therefore preoperative diagnosis of underfeeding is of utmost importance. In case of emergency surgery, the nutritional assessment on admission enables the introduction of early postoperative artificial feeding.

Diagnostic des onychomycose a moisissures et importance pour le traitement [Diagnosis of non dermatophyte onychomycosis ant its relevance for treatment].

PCR methods are reliable and suitable to in situ identify dermatophytes, yeasts and non dermatophyte moulds (NDM) in onychomycosis. Onychomycosis insensitive to standard treatment with topical agents as well as with oral terbinafine or itraconazole revealed Fusarium spp., Acremonium spp. and Aspergillus spp. as infectious agents. However, NDM onychomycosis could be efficiently cured using topical amphotericin B. In conclusion, correct fungal species identification is important in onychomycoses in order to prescribe adequate treatments since dermatophytes and moulds have different sensitivities to antifungal drugs.