Long-term Outcome and Late Side Effects in Endometrial Cancer Patients Treated with Surgery and Postoperative Radiation Therapy.

BACKGROUND: We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). METHODS: Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. RESULTS: After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT + VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT + VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT + VB (P = 0.002 and P = 0.01), respectively. CONCLUSIONS: Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.

Recurrent paroxysmal fever revealing ocular syphilis.

An increased prevalence of ocular syphilis has been reported in recent years reflecting a trend towards liberalisation of sexual practices in the era of Highly Active Anti-retroviral Treatment for HIV infection [1][2]. In view of the protean nature of the disease, pathognomonic features that could guide differential diagnosis of ocular inflammation towards syphilis are lacking. Ocular involvement can antedate or follow systemic manifestations of syphilitic infection, ranging widely and potentially involving all ocular tissue [3][4]. We report here an unusual case of chronic fever and fatigue the cause of which remained elusive for a period of three years, despite extensive investigations, until the development of bilateral panuveitis, raising the suspicion of syphilitc infection.

Postoperative Cognitive Dysfunction (POCD) and Inflammatory Markers in Elderly Patients

Introduction: Particularly in elderly patients, the brain responds to a systemic inflammatory response with an increased production of inflammatory mediators. This has hypothetically been linked to the development of postoperative cognitive dysfunction (POCD). Methods: We investigated 31 patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Cognitive function was measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB, validated German version) for which we developed a diagnostic cut-off in healthy elderly volunteers. Systemic C-reactive protein (CRP) and interleukin 6 (IL-6) were measured preoperatively, 2 days postoperatively, and 7 days postoperatively. Values for CRP, IL-6, operative characteristics and hospital length of stay in patients with POCD and without POCD were compared using the Mann- Whitney U test and are shown as median [range]. Results: Fourteen patients (45%) developed POCD. Values for CRP were not statistically different in patients with POCD and without POCD but tended to be higher in patients with POCD 2 days postoperatively. Patients with POCD had significantly higher IL-6 values on postoperative days 2 and 7 (table 1). These patients also had a significantly longer duration of anaesthesia (305 [195-620] vs.190 [150-560] min, p = 0.034), larger intraoperative blood loss (425 [0-1600] vs. 100 [0-1500] ml, p = 0.018) and longer hospital stays (15 [8-45] vs. 8 [4-40] days, p = 0.008). Table 1 POCD (n = 14) No POCD (n = 17) p value CRP (mg/dl) preop. 4.0 [1.0-245] 4.2 [0.3-36.2] 0.6 2 days postop. 223 [20-318] 98 [4.5-384] 0.07 7 days postop. 58 [15-147] 44 [11-148] 0.2 IL-6 (U/ml) preop. 2[2-28.1] 2 [2-7.3] 0.8 2 days postop. 56 [17-315] 20 [2-123] 0.009 7 days postop. 9[2-77] 4 [2-16] 0.03 Interpretation: In this small group of patients, high IL-6 values postoperatively were associated with POCD supporting a role for systemic inflammation in the development of POCD. In patients with POCD, duration of anaesthesia was significantly longer, and intraoperative blood losses were larger. These risk factors will need to be confirmed in a larger group of patients. The difference in length of stay may be indicative of postoperative complications, which have been linked to POCD earlier.

Cerebral vasculitis complicating postoperative meningitis: the role of steroids revisited.

Meningitis due to Streptococcus pneumoniae is a rare complication of trans-sphenoidal surgery. We present the case of a patient who developed pneumococcal meningitis with associated bacteraemia after elective endoscopic trans-sphenoidal resection of a pituitary macro-adenoma. After initial treatment with ceftriaxone and dexamethasone, the patient made a good recovery and dexamethasone was discontinued. Two days later the patient's condition deteriorated rapidly, presenting focal and diffuse neurological deficits. Cerebral MRI revealed widespread punctate ischaemic-type lesions affecting both anterior and posterior vascular territories bilaterally and involving features consistent with cerebral vasculitis. Antibiotic treatment was broadened to include meropenem and dexamethasone was restarted, but the patient remained in a comatose state and died 14 days later. Steroid treatment may play a dual role in this poorly characterised infectious complication of trans-sphenoidal pituitary surgery. This possibility is discussed and the options for prophylaxis are reviewed.

Pédiatrie 4. Comment traiter la fièvre de l'enfant en 2013 avec un peu d'évidence [How to treat pediatric fever in 2013 with little evidence-based?].

Treatment of pediatric fever is based on two main molecules, paracetamol and ibuprofen. Fever should be treated when associated with discomfort. The two molecules have almost similar efficacy and safety. Monotherapy should be preferred to a combined or alternating treatment. Antipyretics do not seem to prevent febrile seizures.

Decrease in hemoglobin levels following surgery influences the outcome in head and neck cancer patients treated with accelerated postoperative radiotherapy.

AIM: To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT). MATERIAL AND METHODS: Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52 months (range 12-95 months). RESULTS AND DISCUSSION: Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130 g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38 g/l (quartile value) compared with those with Hb decrease 38 g/l or more (61% versus 16%, P = 0.008). CONCLUSION: Decrease in Hb level by more than 38 g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicated.

Breast-conserving surgery for non-palpable breast cancer: relationship of lumpectomy resection margins measurements between remote perioperative ultrasound and postoperative histopathology

Purpose: Tumour-free resection margins (RMs) are mandatory in breast-conserving surgery. On-site intraoperative ultrasound (US)-guided tumour resection with extemporaneous histopathological assessment of RMs has been described. Remote intraoperative US assessment of RMs is an alternative. The purpose of this study was to evaluate the relationship of lumpectomy RMs measurements between remote intraoperative US and postoperative histopathology.Methods and Materials: In a retrospective IRB-approved review of 100 consecutive lumpectomies performed between October 2009 and April 2011 for presumed non-palpable breast cancer, 71 women (mean age 63.8years) were included. Twenty-nine patients were excluded because of absence of cancer at histopathology and/or incomplete data. Measurements of lumpectomy minimal RMs and tumour maximal diameter obtained on remote intraoperative US and postoperative histopathology were compared.Results: Minimal RMs were 0.35±0.32 (mean±SD) and 0.35±0.32cm on remote intraoperative US and postoperative histopathology, respectively. No significant difference was found between these measurements (p=0.37). Tumour maximal diameter was 1.02±0.51 (mean±SD) and 1.33±0.74cm on remote intraoperative US and postoperative histopathology, respectively. US measurements were significantly smaller (p<0.001). The 71 breast carcinoma (CA) consisted of: invasive canalar (n=49), invasive lobular (n=11), in situ (n=3) and other types of CA (n=8). Twenty-nine patients had intraoperative re-excision (24 without residual CA), while 16 patients were re-operated due to insufficient histopathological RMs (12 without residual CA).Conclusion: Good correlation of minimal RMs between remote intraoperative US and postoperative histopathology warrants use of both techniques in a complementary manner. Remote intraoperative US is helpful in taking rapid decision of re-excision and maintaining low re-operation rate after breast-conserving surgery for non-palpable cancer.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Einfluss von L-Carnitin-supplementierter total parenteraler Ernährung (TPE) auf die postoperative Fett- und Stickstoff-Utilisation [Effect of L-carnitine supplemented total parenteral nutrition on postoperative lipid and nitrogen utilization].

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were equally and randomly divided and received isonitrogenous (0.2 gN/kg.day) and isocaloric (35 kcal/kg.day TPN over 11 days without and with L-carnitine supplementation (12 mg/kg.day). Compared with healthy controls, the total body carnitine pool was significantly reduced in both groups prior to the operation. Without supplementation carnitine concentrations were maintained, while daily provision of carnitine resulted in an elevation of total carnitine mainly due to an increase of the free fraction. Without supplementation the cumulative urinary carnitine losses were 11.5 +/- 6.3 mmol corresponding to 15.5% +/- 8.5% of the estimated total body carnitine pool. Patients receiving carnitine revealed a positive carnitine balance in the immediate postoperative phase, 11.1% +/- 19.0% of the infused carnitine being retained. After 11 days of treatment comparable values for respiratory quotient, plasma triglycerides, free fatty acids, ketone bodies, and cumulative nitrogen balance were observed. It is concluded that in the patient population studied here carnitine supplementation during postoperative TPN did not improve fat oxidation or nitrogen balance.

Recovery of postoperative visual loss following treatment of severe anaemia.

A 29-year-old pregnant woman noted acute visual loss following emergent Caesarean section complicated by excessive uterine bleeding. Postoperative visual acuity was count fingers in both eyes. Funduscopic changes were consistent with a diagnosis of anaemia-associated ischaemic optic neuropathy and retinopathy. One month later, because of persistent anaemia and poor visual recovery, blood transfusion was given. Following transfusion, the patient's vision improved over the next 6 months. In an otherwise healthy patient, visual loss associated with postoperative blood loss may still be partially reversible with correction of the anaemia, even after a delayed period of time.

Beyond malaria--causes of fever in outpatient Tanzanian children.

BACKGROUND: As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children. METHODS: We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. CONCLUSIONS: These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.).