Non-surgical treatment of hilar cholangiocarcinoma

Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60% of intrahepatic malignancies, and 2% of all cancers. The prognosis is extremely poor and the majority of Klatskin tumors are deemed unresectable upon diagnosis. Most patients with unresectable bile duct cancer die within the first year after diagnosis, due to hepatic failure, and/or infectious complications secondary to biliary obstruction. Curative treatments include surgical resection and liver transplantation in highly selected patients. Nevertheless, very few patients are eligible for surgery or transplant at the time of diagnosis. For patients with unresectable HC, radiotherapy, chemotherapy, photodynamic therapy, and liver-directed minimally invasive procedures such as percutaneous image-guided ablation and intra-arterial chemoembolization are recommended treatment options. This review focuses on currently available treatment options for unresectable HC and discusses future perspectives that could optimize outcomes.     

Do uterine fibroids affect IVF outcomes?

The effect of myomectomy on implantation and pregnancy rates prior to assisted reproduction treatments is controversial. This study was designed to assess clinical outcomes of IVF cycles in women with uterine fibroids. A retrospective single-centre assessment of clinical outcomes of IVF/intracytoplasmic sperm injection (ICSI) treatments in infertile women in a 4-year span was carried out. All patients underwent detailed transvaginal ultrasound and hysteroscopy to precisely identify presence, location and intracavitary growth of uterine fibroids. Cumulative pregnancy, ongoing pregnancy and live birth rates were considered primary outcome measurements. Fifty-one women with fibroids (97 treatment cycles), 63 patients with previous myomectomy (127 cycles), and 106 infertile women who did not demonstrate fibroids anywhere in the uterus (215 cycles) were considered for the analysis. No significant difference was found for pregnancy and live birth rates between groups. Women with fibroids>4 cm required an increased number of cycles to obtain an ongoing pregnancy, compared with the other groups. The data do not support pre-IVF myomectomy in women with small-to-moderate uterine fibroids, regardless of their location. This represents valuable information in the counselling of women with fibroids before reproductive assisted cycles.     

Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in children

This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 +/- 0.11 (n = 9) in healthy children and increased to 1.27 +/- 0.24 (n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 +/- 0.27 (n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1. 67 +/- 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.     

Symptom improvement as prognostic factor for survival in cancer patients undergoing palliative care: a pilot study

Background  

The Edmonton Symptom Assessment Scale (ESAS) is a validated tool for physical symptom assessment in palliative care practice which evaluates symptoms through a numeric scale from 0 to 10. The use of symptom improvement as a prognostic factor is controversial. To this purpose, a pilot study in advanced cancer patients now undergoing only palliative care was conducted.     

Cortical brain responses during passive nonpainful median nerve stimulation at low frequencies (0.5-4 Hz): an fMRI study

Previous findings have shown that the human somatosensory cortical systems that are activated by passive nonpainful electrical stimulation include the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), and bilateral insula. The present study tested the hypothesis that these areas have different sensitivities to stimulation frequency in the condition of passive stimulation. Functional MRI (fMRI) was recorded in 24 normal volunteers during nonpainful electrical median nerve stimulations at 0.5, 1, 2, and 4 Hz repetition rates in separate recording blocks in pseudorandom order. Results of the blood oxygen level-dependent (BOLD) effect showed that the contralateral SI, the bilateral SII, and the bilateral insula were active during these stimulations. As a major finding, only the contralateral SI increased its activation with the increase of the stimulus frequency at the mentioned range. The fact that nonpainful median-nerve electrical stimuli at 4 Hz induces a larger BOLD response is of interest both for basic research and clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.     

Four-Component Staphylococcus aureus Vaccine 4C-Staph Enhances Fcγ Receptor Expression in Neutrophils and Monocytes and Mitigates S. aureus Infection in Neutropenic Mice

Staphylococcus aureus is a human bacterial pathogen causing a variety of diseases. The occurrence of multidrug-resistant strains of Staphylococcus aureus underlines the need for a vaccine. Defining immune correlates of protection may support the design of an effective vaccine. We used a murine Staphylococcus aureus infection model, in which bacteria were inoculated in an air pouch generated on the back of the animal. Analysis of the air-pouch content in mice immunized or not with an adjuvanted multiantigen vaccine formulation, four-component S. aureus vaccine (4C-Staph), prior to infection allowed us to measure bacteria, cytokines, and 4C-Staph-specific antibodies and to analyze host immune cells recruited to the infection site. Immunization with 4C-Staph resulted in accumulation of antigen-specific antibodies in the pouch and mitigated the infection. Neutrophils were the most abundant cells in the pouch, and they showed the upregulation of Fcγ receptor (FcγR) following immunization with 4C-Staph. Reduction of the infection was also obtained in mice immunized with 4C-Staph and depleted of neutrophils; these mice showed an increase in monocytes and macrophages. Upregulation of the FcγR and the presence of antigen-specific antibodies induced by immunization with 4C-Staph may contribute to increase bacterial opsonophagocytosis. Protection in neutropenic mice indicated that an effective vaccine could activate alternative protection mechanisms compensating for neutropenia, a condition often occurring in S. aureus-infected patients.     

Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy

We identified a small family with autosomal recessive, infantile onset epilepsy and intellectual disability. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain‐expressed tyrosine kinase. Sequencing of the coding region of TNK2 in 110 patients with a similar phenotype failed to detect further homozygote or compound heterozygote mutations. Pathogenicity of the variant is supported by the results of our functional studies, which demonstrated that the variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Definitive proof of pathogenicity will require confirmation in unrelated patients. Ann Neurol 2013;74:496–501     

Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab

BACKGROUND: Under experimental chronic inflammation, tumor necrosis factor (TNF)-alpha plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-alpha is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. METHODS: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. RESULTS: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients. CONCLUSIONS: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation.     

Validation of a predictive survival model in Italian patients with cystic fibrosis

BackgroundIn 2001 Liou published a 5-year survival model using CFF Registry data.AimsTo evaluate its validity in predicting survival in Italian CF patients.MethodsIn a retrospective study on 945 patients, the 9 variables selected by Liou were analyzed, vital status on December 2008 recorded and observed and expected deaths compared. To develop a new model, patients were randomly divided into a derivation (n = 475) and a validation sample (n = 470).ResultsA significant difference was found between observed and expected deaths based on Liou's model (62 vs 94), with a 34% reduction in mortality (p < 0.05). A new model (based on FEV1, Staphylococcus aureus and Burkholderia cepacia complex infection, number of pulmonary exacerbations/year) was generated, that correctly predicted survival in the validation sample (31 observed vs 29 expected deaths, p = 0.660).ConclusionsThe Liou model did not adequately predict 5-year survival in our CF population that, compared to the one in which it was originally tested, could benefit from 10 years of improvement in treatments and practice patterns. A new generated model, based on only four variables, was more accurate in predicting 5-year survival in Italian CF patients.