Incontinentia Pigmenti. / Incontinencia pigmenti.

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare neuroectodermal dysplasia. It is an X-linked dominant disorder caused by mutations in the IKBKG/NEMO gene on Xq28. Approximately 80% of patients have a deletion of exons 4 to 10. Incontinentia pigmenti has an estimated incidence of 0.7 cases per 100,000 births. In hemizygous males, it is usually lethal, while in females, it has a wide spectrum of clinical manifestations. Incontinentia pigmenti is a multisystemic disease that invariably features skin changes. These changes are the main diagnostic criteria and they evolve in 4 stages, in association with other abnormalities affecting the central nervous system, eyes, teeth, mammary glands, hair, nails, skin, and other parts of the body. The aim of this brief review is to highlight the clinical features of this genodermatosis and underline the importance of case-by-case interdisciplinary management, including genetic counseling.

Long-term results after stapled hemorrhoidopexy: a survey study with mean follow-up of 12 years.

BACKGROUND: Hemorrhoidal prolapse is a common benign disease. The introduction of circular-stapled hemorrhoidopexy as an alternative to the conventional hemorrhoidectomy led to a new spectrum of postoperative outcomes and complications. The aim of the present study was to evaluate long-term results after stapled hemorrhoidopexy. METHODS: All the patients who had stapled hemorrhoidopexy using a PPH03 stapler, from January 2003 to December 2005, were retrospectively collected in a dedicated database. Between March and May 2016, all the patients were asked by phone to complete a questionnaire. The study evaluated anatomical recurrence, symptom recurrence and frequency, and satisfaction after surgery. The postoperative complications recorded were hemorrhage, hematoma, urinary retention, anastomotic stenosis, persistent anal pain, tenesmus, and impaired anal continence evaluated also with the Faecal Incontinence Severity Index score. RESULTS: One hundred and ninety four patients were identified and 171 completed the questionnaire. The mean follow-up was 12 ± 0.8 years (range 11-13 years). Anatomical self-reported prolapse recurrence was 40.9% (n = 70). In 75.6% (n = 129) of patients, the severity and frequency of symptoms improved. The overall complication rate was 56.7% (n = 40) with a serious adverse event rate of 8.7% (n = 15). The overall tenesmus rate was 38.2% (n = 65) and the overall impaired continence rate was 39.1% (n = 67). Medical therapy was still required occasionally by 40.3% (n = 69) of the patients and 9.3% (n = 16) of the patients underwent surgery for recurrence. Patient satisfaction rate was good (≥ 3 on a scale of 1 to 5) in 81.2% (n = 139) of cases. CONCLUSIONS: The study showed that stapled hemorrhoidopexy using the first-generation devices is safe and feasible but associated with a high recurrence and incontinence rate. More stringent selection criteria in association with the use of large volume devices can lead to better results in the future.

Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.

Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

Giant endometrial cyst of the liver: a case report and review of the literature.

Endometriosis is a benign condition described as the presence of endometrial- like tissue found outside the uterine cavity. Hepatic endometriosis is one of the rarest localization of extrapelvic endometriosis, only 22 cases have been reported in the literature. The preoperative diagnosis of hepatic endometriosis is rather difficult because in about the half of the patient affected they had no history of endometriosis. Moreover radiological images reveal no characteristic findings for hepatic endometriosis. It is often described as cystic mass with or without solid component, difficult to distinguish from hepatic abscess, hematoma, cystoadenoma or malignant neoplasia. We report a case of a 27-year-old female with a large cystic mass involving the left lobe of the liver. The patient underwent laparoscopic exploration and converted to laparotomy for resection of giant hepatic endometriosis.

Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.

Mendelian primary immunodeficiency diseases (MPIDs) are rare disorders affecting distinct constituents of the innate and adaptive immune system. Although they are genetically heterogeneous, a substantial group of MPIDs is due to mutations in genes affecting the nuclear factor-κB (NF-κB) transcription pathway, essential for cell proliferation and cell survival and involved in innate immunity and inflammation. Many of these genes encode for crucial regulatory components of the NF-κB pathway and their mutations are associated with immunological and developmental signs somehow overlapping in patients with MPIDs. At present, nine different MPIDs listed in the online mendelian inheritance in man (OMIM) are caused by mutations in at least nine different genes strictly involved in the NF-κB pathway that result in defects in immune responses. Here we report on the distinct function of each causative gene, on the impaired NF-κB step and more in general on the molecular mechanisms underlining the pathogenesis of the disease. Overall, the MPIDs affecting the NF-κB signalosome require a careful integrated diagnosis and appropriate genetic tests to be molecularly identified. Their discovery at an ever-increasing rate will help establish a common therapeutic strategy for a subclass of immunodeficient patients.

Simple enucleation versus standard partial nephrectomy for clinical T1 renal masses: perioperative outcomes based on a matched-pair comparison of 396 patients (RECORd project).

OBJECTIVES: To compare simple enucleation (SE) and standard partial nephrectomy (SPN) in terms of surgical results in a multicenter dataset (RECORd Project). MATERIALS AND METHODS: patients treated with nephron sparing surgery (NSS) for clinical T1 renal tumors between January 2009 and January 2011 were evaluated. Overall, 198 patients who underwent SE were retrospectively matched to 198 patients who underwent SPN. The SPN and SE groups were compared regarding intraoperative, early post-operative and pathologic outcome variables. Multivariable analysis was applied to analyze predictors of positive surgical margin (PSM) status. RESULTS: SE was associated with similar WIT (18 vs 17.8 min), lower intraoperative blood loss (177 vs 221 cc, p = 0.02) and shorter operative time (121 vs 147 min; p < 0.0001). Surgical approach (laparoscopic vs. open), tumor size and type of indication (elective/relative vs absolute) were associated with WIT >20 min. The incidence of PSM was significantly lower in patients treated with SE (1.4% vs 6.9%; p = 0.02). At multivariable analysis, PSM was related to the surgical technique, with a 4.7-fold increased risk of PSM for SPN compared to SE. The incidence of overall, medical and surgical complications was similar between SE and SPN. CONCLUSIONS: Type of NSS technique (SE vs SPN) adopted has a negligible impact on WIT and postoperative morbidity but SE seems protective against PSM occurrence.

Comparison between tungsten and steel polypectomy snares: evaluation of depth of colonic thermal wall injury in a pig model.

BACKGROUND AND STUDY AIMS: Thermal injury of the colonic wall during polypectomy may induce complications such as bleeding and perforation. To date, the role of the snare material in these injuries has not been examined. The aim of this study was to evaluate the depth of colonic post-polypectomy thermal wall injury induced by tungsten and steel endoscopic snares, in an effort to reduce electrosurgery-related complications. MATERIALS AND METHODS: This was a single tertiary center experimental study in a porcine model. A total of 90 polypectomies where performed in three live pigs under general anesthesia, using both steel and tungsten snares by cut, coagulation, and blend current modes. The pigs were then euthanized and their colons examined histologically. RESULTS: Steel snares induced significantly deeper tissue injury than tungsten snares in the pure cut mode (Pearson χ2 = 6.136, P = 0.013). The ordinal logistic regression analysis showed that the current mode and snare material were significantly associated with the ordinal score for the depth of injury. Thus, cut mode was positively associated with a lower score and coagulation mode with a higher score. In addition, tungsten was significantly associated with a lower depth of tissue injury. CONCLUSIONS: Due to its inherent electrical properties, tungsten is very well suited for manufacture into electrosurgical endoscopic devices. Thus, tungsten snares may be advantageous for routine use in endoscopic polypectomy, although further studies are needed to confirm these promising findings in human patients.

Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial.

Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction.

Nuclear factor-kappa-B-inhibitor alpha (NFKBIA) is a developmental marker of NF-κB/p65 activation during in vitro oocyte maturation and early embryogenesis.

BACKGROUND: The oocyte-to-embryo transition (OET) requires a co-ordinated transcriptional programme acting through evolutionarily conserved events, and transcription factors (TFs) are known to control these processes. Here, we focus on nuclear factor (NF)-κB, a TF involved in several cellular processes, studying NFκB-inhibitor (NFKBIA) mRNA and its protein product, IκBα, during OET. NFKBIA and IκBα are part of a regulatory loop, as IκBα is the major down-regulator of NF-κB activation while NFKBIA transcription is activated by NF-κB. METHODS AND RESULTS: We found a dynamic correlation between NFKBIA transcript, expression of IκBα-protein and activation of NF-κB/p65 in bovine oocyte and embryo. During the transition from immature to in vitro matured bovine oocyte, we observed a decrease in maternal NFKBIA mRNA and a parallel increase of the IκBα-protein (both P < 0.05). In the embryo, NFKBIA neo-synthesis is activated as a consequence of embryo genome activation (EGA), and IκBα decreases. NF-κB/p65-binding activity was detectable at low levels in immature oocyte, disappeared in dormant metaphase II oocyte and was strong in the embryo, during embryonic NFKBIA synthesis. The level of NF-κB/p65 DNA binding correlates with the timing of meiotic silencing during bovine oocyte maturation and embryonic transcription reprogramming. CONCLUSIONS: The IκBα/NF-κB circuit appears to be a tightly stage-controlled mechanism that could govern OET, being activated at EGA. Our findings represent the first characterization of NFKBIA and IκBα as maternal effectors in both the bovine oocyte and embryo. We suggest a role for NFKBIA as a marker of NF-κB/p65 activation in the human oocyte and early embryo.

Anterior urethroplasty and effects on sexual life: which is the best technique?

Established beliefs concerning outcomes following anterior urethral reconstruction are changing, both with regards to the genital cosmetics and to the impact on sexual activity. Today, the aim of stricture repair is not only to reinstate urinary function but also to safeguard sexual activity and guarantee genital cosmesis. A thorough evaluation of anterior urethroplasty results should include the sexual viewpoint which appears to play an important role in overall post-operative patient satisfaction. The most commonly reported sexual problems following anterior urethroplasty include: erectile and ejaculatory dysfunction, penile curvature or shortening, dissatisfaction with genital cosmetic appearance, sensorial impairment of glans. The prevalence of specific post-operative sexual problems may be related to the site of reconstruction (penile or bulbar) and to the technique of urethroplasty employed. In penile urethral reconstruction, the wide use of buccal mucosa grafts seems to excel the use of skin flaps which easily distort the cosmesis and elasticity of the penis. In bulbar reconstructions, graft augmentation techniques seem to impact less on sexual outcome than excision anastomotic techniques. Therefore, the policy of primarily indicating an excision anastomotic procedure, whenever possible, should come under scrutiny. Eventual sexual outcomes should be incorporated in the choice of the optimal anterior urethral reconstruction and in pre-operative patient counselling.

Small (

PURPOSE: We prospectively compared gadoliniumenhanced magnetic resonance imaging (dynamic MRI), superparamagnetic iron oxide (SPIO) (ferucarbotran) MRI and multidetector-row computed tomography (MDCT) and the combination of dynamic MRI plus MDCT vs. dynamic MRI plus SPIO-MRI (double-contrast MRI: DC-MRI) for the detection of small (1 cm and the highest specificity (83.3%) superior to dynamic MRI (p<0.0001). In the per-lesion analysis, SPIO-MRI demonstrated a positive predictive value higher than dynamic MRI (p=0.0059) and than both the combinations dynamic MRI/MDCT and DC-MRI (p=0.0021 and p=0.0087, respectively). DC-MRI showed the highest sensitivity (97.7%) and accuracy (78.9%), detecting hypovascular and atypical HCCs >1 cm. Furthermore its per-patient negative predictive value was the highest (100%), and significantly higher than all the other methods. CONCLUSIONS: DC-MRI is the most sensitive and accurate method and can be confidently used as a single-step procedure for the detection of small HCCs, with the exception of lesions <1 cm.

Malignant progression of a small HCC nodule: hypovascular 'early HCC' converted to hypervascular 'small HCC' within six months.

We report a case of hepatocellular carcinoma superimposed on chronic hepatitis C virus (HCV) hepatitis in which final diagnosis of hepatocellular carcinoma was delayed because there was no consensus on hypervascularity with two diagnostic methods at the time of presentation. A 3 cm lesion was initially observed as hypovascular at multidetector-row computed tomography. Conversely, two months later the lesion appeared hypervascular at contrast-ultrasonography and gadolinium-enhanced dynamic magnetic resonance, and hyperintense after superparamagnetic iron oxide-enhanced T2W studies. Only in the late follow-up it was definitively confirmed as hypervascular in the arterial phase of multidetector-row computed tomography. This case clearly highlights some pitfalls in the European Association for the study of the liver guidelines for hepatocellular carcinoma management, which were readdressed in the last American Association for the Study of Liver Diseases (AASLD) and in the forthcoming international proposals, leading to more pragmatic suggestions for clinical practice.

Unresectable hilar cholangiocarcinoma: multimodality treatment with percutaneous and intraluminal plus external radiotherapy.

The efficacy of multimodality treatment for unresectable hilar cholangiocarcinoma was evaluated in terms of outcome, survival and quality of life. Eleven patients were enrolled in the following protocol: percutaneous drainage of both right and left biliary systems; Iridium-192 intraluminal brachytherapy; replacement of the drainages with endoprotheses; external radiotherapy. Six patients completed the protocol and 5 were treated with brachytherapy alone. Mean survival was 10.5 months, similar to surgical results and higher than the control group treated with percutaneous stenting (2.75 months) or biliary drainage alone (1.75 months), with an average hospital stay of 10-15 days and no procedure-related mortality.

Activation of beta1-adrenoceptors excites striatal cholinergic interneurons through a cAMP-dependent, protein kinase-independent pathway.

The role of noradrenergic neurotransmission was analyzed in striatal cholinergic interneurons. Conventional intracellular and whole-cell patch-clamp recordings were made of cholinergic interneurons in rat brain slice preparations. Bath-applied noradrenaline (NA) (1-300 microm) dose-dependently induced both an increase in the spontaneous firing activity and a membrane depolarization of the recorded cells. In voltage-clamped neurons, an inward current was induced by NA. This effect was not prevented by alpha-adrenoceptor antagonists, whereas it was mimicked by the beta-adrenoceptor agonist isoproterenol and blocked by the beta1 antagonists propranolol and betaxolol. Interestingly, forskolin, activator of adenylate cyclase, mimicked and occluded the membrane depolarization obtained at saturating doses of both dopamine and NA. Accordingly, SQ22,536, a selective adenylate cyclase inhibitor, reduced the response to NA. Analysis of the reversal potential of the NA-induced current did not provide homogeneous results, indicating the involvement of multiple membrane conductances. Because cAMP is known to modulate Ih, the effects of ZD7288, a selective inhibitor of Ih current, were examined on the NA-induced membrane depolarization/inward current. ZD7288 mostly reduced the response to NA. However, both KT-5720 and H-89, selective protein kinase A (PKA) blockers, failed to prevent the excitatory action of NA. Likewise, calphostin C, antagonist of PKC, genistein, inhibitor of tyrosine kinase, and 8-Bromo-cGMP, blocker of PKG, did not affect the response to NA. Finally, double-labeling experiments combining beta1-adrenoceptor and choline acetyltransferase immunocytochemistry by means of confocal microscopy revealed a strong beta1-adrenoceptor labeling on cholinergic interneurons. We conclude that NA depolarizes striatal cholinergic interneurons via beta1-adrenoceptor activation, through a cAMP-dependent but PKA-independent mechanism.

Localization of ataxin-2 within the cerebellar cortex of the rat.

Spinocerebellar ataxia type 2 is caused by a polyglutamine stretch in the protein ataxin-2 that is due to an expansion of a CAG repeat in the spinocerebellar ataxia-2 gene. The function of wild-type ataxin-2 has not been clarified. A widespread distribution of this protein throughout the brain has been reported. We examined the expression of ataxin-2 in cortical cerebellar cells of the adult rat. We performed a single label immunohistochemical study of ataxin-2 and a single label immunofluorescence study of ataxin-2 and zebrin on adjacent sections, to compare the distribution of the observed parasagittal band pattern. We also performed a double label immunofluorescence study of ataxin-2 and one of each parvalbumin, calbindin, and calretinin. Single label studies revealed that between 50% and 70% of the Purkinje cells express ataxin-2. The abundance of ataxin-2 was different between hemisphere and vermis, with a clear prevalence for the former. Furthermore, the distribution of ataxin-2-positive Purkinje cells showed a peculiar alternating parasagittal band pattern. Among the other cortical cerebellar cells only basket and granule cells showed ataxin-2 staining. Our dual label studies showed that about 50% of calbindin and more than 70% of parvalbumin-immunoreactive Purkinje cells were also labeled for ataxin-2. The uneven distribution of ataxin-2 expression in the Purkinje cell layer does not support the hypothesized link between ataxin-2 content and cell vulnerability. The differences in ataxin-2 expression among the cell types of cerebellar cortex, on the other hand, suggest a possible correlation between ataxin-2 content and cell function.

Videourodynamic studies in men with lower urinary tract symptoms: a comparison of community based versus referral urological practices.

PURPOSE: We compared the clinical and urodynamic characteristics of men referred for evaluation of lower urinary tract symptoms in community based versus referral urological practices and examined the various pathophysiological mechanisms of these symptoms. MATERIALS AND METHODS: We reviewed a multicenter urodynamics database of 963 consecutive men referred for the evaluation of persistent lower urinary tract symptoms at 2 community based and 1 urological referral center. Of the 963 patients in the database 422 (44%) were excluded from study due to neurological disorder in 41%, previous urinary or pelvic surgery in 27% and the use of medications known to affect voiding in 24%. A total of 541 patients with a mean age plus or minus standard deviation of 64.4 +/- 13.8 years met study inclusion criteria and were analyzed further. We compared the clinical and urodynamic characteristics of patients at the community and referral centers. RESULTS: Lower urinary tract symptoms were equally common in men presenting to community and referral centers. The most common symptom was difficult voiding, followed by frequency, urgency and nocturia in 58%, 54%, 43% and 40% of the study population, respectively. Urodynamic diagnoses were also similar in the 2 groups. Although bladder outlet obstruction was diagnosed in 69% of patients, it was the only urodynamic finding in a third of the patients with obstruction. The main concomitant urodynamic diagnoses were detrusor overactivity, bladder hyposensitivity, impaired detrusor contractility, low bladder compliance and bladder hypersensitivity in 47%, 10%, 10%, 9% and 3% of obstructed cases, respectively. CONCLUSIONS: The pathophysiology of lower urinary tract symptoms in men is multifactorial, and similar at community practice and tertiary referral centers. The disparity in urodynamic findings and subjective symptoms emphasizes the need for a thorough and early clinical and urodynamic evaluation.

[Non-surgical treatment of aortic aneurysms and dissections: indications, strategies and outcome]. / Trattamento non chirurgico degli aneurismi e delle dissezioni aortiche: indicazioni, strategie, risultati.

PURPOSE: The endovascular treatment of the thoracic aorta is an effective alternative to open surgical repair and offers a therapeutic option even to patients at high risk for surgery. Our experience in the treatment of different diseases of descending thoracic aorta is reported. MATERIAL AND METHODS: Between July 1997 and January 2001, 50 patients were selected for endovascular treatment: 36/50 patients presented high risk for conventional surgery. Six patients presented clinical and imaging features suggesting impending rupture and were treated on emergency basis. The stent-graft prosthesis was individually manufactured or selected on the basis of spiral CT or MRI measurements. RESULTS: Endovascular stent positioning and deployment was technically successful in 49 cases. In one patient the tortuosity of the aortic arch prevented graft deployment. Complete aneurysm exclusion was achieved in 48 cases as assessed by post-procedure angiography and TEE. One proximal endoleak was noted and surgical conversion was performed 40 days later. There were no intraoperative mortality or complications. One patient presented extension of dissection at the 8th postoperative day and required of surgical repair. CT scan showed an endoleak in 4 cases that sealed spontaneously in three cases while the fourth case was treated by graft extension. In the long term two secondary endoleak were observed (12 and 24 months after the procedure). CONCLUSIONS: Endovascular stent-graft repair provides a less invasive opportunity to patients affected by thoracic aortic disease. Careful cases selection is the first postulate for the efficacy and safety of the procedure.