Aneurysmal subarachnoid hemorrhage during pregnancy: a comprehensive and systematic review of the literature

Neurosurgical Review - Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the...     

Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease in which fibroblasts accumulate in the alveolar wall within a type I collagen-rich matrix. Although lung fibroblasts derived from patients with IPF display durable pathological alterations in proliferative function, the molecular mechanisms differentiating IPF fibroblasts from their normal counterparts remain unknown. Polymerized type I collagen normally inhibits fibroblast proliferation, providing a physiological mechanism to limit fibroproliferation after tissue injury. We demonstrate that beta1 integrin interaction with polymerized collagen inhibits normal fibroblast proliferation by suppression of the phosphoinositide 3-kinase (PI3K)-Akt-S6K1 signal pathway due to maintenance of high phosphatase activity of the tumor suppressor phosphatase and tensin homologue (PTEN). In contrast, IPF fibroblasts eluded this restraint, displaying a pathological pattern of beta1 integrin signaling in response to polymerized collagen that leads to aberrant activation of the PI3K-Akt-S6K1 signal pathway caused by inappropriately low PTEN activity. Mice deficient in PTEN showed a prolonged fibroproliferative response after tissue injury, and immunohistochemical analysis of IPF lung tissue demonstrates activation of Akt in cells within fibrotic foci. These results provide direct evidence for defective negative regulation of the proliferative pathway in IPF fibroblasts and support the theory that the pathogenesis of IPF involves an intrinsic fibroblast defect.     

Testicular-sparing microsurgery for suspected testicular masses

OBJECTIVE: To describe a microsurgical technique for removing suspected testicular masses with sparing of the testicular parenchyma, and to describe case studies. PATIENTS AND METHODS: Six men were referred with testicular lesions (3-6 mm) detected on ultrasonography (US); in one, the lesion was palpable. US showed hypoechoic lesions and in two cases were mixed hypoechoic and anechoic. In these men, the testicular lesion was identified by US before surgery, giving three-dimensional coordinates to facilitate intraoperative recognition. A traditional inguinal incision was used and the funiculus clamped subinguinally without opening the canal. The testicle was isolated after sectioning the gubernaculum testis. In a separate operative field, an equatorial incision of the albuginea was made in a plane orthogonal to the major axis of the testicle, sparing the subtunical vasa. The parenchymal lobuli were dislodged and the seminiferous tubules dissociated, the nodule identified and completely removed, together with approximately 1 mm of surrounding healthy tissue. This technique can also be used for microsurgical testicular sperm extraction (MicroTESE), to retrieve sperm in infertile men. RESULTS: In two infertile men MicroTESE was also performed. Histology revealed one case each of seminoma, Leydig-cell tumour, Leydig cell hyperplasia, atrophy, normality in the incidental forms, and complicated cysts of the albuginea. In the follow-up for infertility reasons, no scarring was observable on the tunica albuginea in the men who had conservative therapy. One year later the patient with seminoma was free of disease. CONCLUSIONS: The increasingly frequent detection of benign testicular lesions, particularly in infertile men, calls for a surgical approach that must be as conservative as possible for the testicular parenchyma. We think that microsurgery should be the first-line technique in small suspected testicular lesions in infertile men.     

Testicular function following chemo-radiotherapy

Improvements in cancer survival raise infertility issues in young patients suffering from malignancies. The aim of the study is to review current knowledge on the effect of chemotherapy (CT) and radiotherapy (RT) for testis and hematological neoplasms on testicular function. Cisplatin-based regimens for testis neoplasm induce temporary azoospermia; permanent damage can occur with high doses (400-600 mg/m(2)). Alkylating agents are very effective for hematological neoplasm therapy but extremely dangerous to germinal epithelium. Damage can be irreversible. Spermatozoa cannot tolerate irradiation doses higher than 6 Gy. Leydig cells are damaged by doses higher than 15 Gy. A-Spermatogonia have been shown to survive after CT and RT and their recovery for post-treatment graft has been recently developed in animal models. Infertility counselling before treatment in young oncological patients is mandatory. Cryopreservation is the best option for fertility protection.     

Accuracy of Computational Cerebral Aneurysm Hemodynamics Using Patient-Specific Endovascular Measurements

Computational hemodynamic simulations of cerebral aneurysms have traditionally relied on stereotypical boundary conditions (such as blood flow velocity and blood pressure) derived from published values as patient-specific measurements are unavailable or difficult to collect. However, controversy persists over the necessity of incorporating such patient-specific conditions into computational analyses. We perform simulations using both endovascularly-derived patient-specific and typical literature-derived inflow and outflow boundary conditions. Detailed three-dimensional anatomical models of the cerebral vasculature are developed from rotational angiography data, and blood flow velocity and pressure are measured in situ by a dual-sensor pressure and velocity endovascular guidewire at multiple peri-aneurysmal locations in 10 unruptured cerebral aneurysms. These measurements are used to define inflow and outflow boundary conditions for computational hemodynamic models of the aneurysms. The additional in situ measurements which are not prescribed in the simulation are then used to assess the accuracy of the simulated flow velocity and pressure drop. Simulated velocities using patient-specific boundary conditions show good agreement with the guidewire measurements at measurement locations inside the domain, with no bias in the agreement and a random scatter of ≈25%. Simulated velocities using the simplified, literature-derived values show a systematic bias and over-predicted velocity by ≈30% with a random scatter of ≈40%. Computational hemodynamics using endovascularly measured patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics than those based on commonly accepted reference values for boundary conditions.     

Detection of testicular ultrasonographic lesions in severe male infertility

PURPOSE: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. MATERIALS AND METHODS: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. RESULTS: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. CONCLUSIONS: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.     

Surgical treatment of varicocele by a subinguinal approach combined with antegrade intraoperative sclerotherapy of venous vessels

OBJECTIVE: To evaluate the efficacy, in terms of recurrences, complications and operative duration, of a new technique for treating varicocele. PATIENTS AND METHODS: Between September 1999 and December 2002 we evaluated 307 men aged 17-51 years with varicocele. In all of the men the clinical diagnosis was confirmed by ultrasonography. The men were treated by a variant of the microsurgical technique described in 1994. A 2-3 cm distal subinguinal incision was made at the level of the superficial inguinal ring and the spermatic cord was exposed. The largest vein in the spermatic cord fat was cannulated. A 7-9 cm segment of the spermatic cord was clamped for 8-10 min; at the start of the ischaemia time, 1.5-3 mL of 3% atoxysclerol was injected into the cannulated vein. After sclerotherapy, the vein was ligated at the injection site, and the blood flow to the cord was restored. RESULTS: The mean operative duration was 25 min. Follow-up at 3 and 6 months after surgery, with objective examination and scrotal ultrasonography, revealed one case of clinical recurrence/persistence. The most common complication was penile lymphangitis (nine men) that regressed spontaneously; three men had temporary orchialgia. There were no cases of secondary hydrocele or testicular atrophy. CONCLUSIONS: The modified technique appears to be relatively easy and safe, and to of low cost. Given the promising results in terms of complications and persistence, the treatment appears to be a suitable first-line approach for the surgical treatment of varicocele.     

Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic erectile dysfunction: a randomised placebo controlled study

We compared the effectiveness of sildenafil citrate and alprostadil in improving arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55 patients with erectile dysfunction caused by atherosclerosis. A total of 35 patients with pure vasculogenic impotency were randomly assigned to alprostadil (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20 patients with nonvasculogenic impotency were randomly assigned to alprostadil (A group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection (capable of giving a full erection) once a week for 1 month, Sv and S took daily oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month. The PSV was measured with Duplex sonography and penile rigidity was assessed using the IIEF-15 questionnaire, both of which were administered before and after treatment. Although both treatments improved penile rigidity, they increased PSV only in the Av and Sv groups. Our results suggest that alprostadil and oral therapy should be the starting therapy in men with vasculogenic impotency, whereas alprostadil should be avoided as the first-line approach in men with nonvasculogenic impotency.     

High incidence of benign testicular neoplasms diagnosed by ultrasound

PURPOSE: We evaluated the clinical and histological significance of incidental ultrasonographic focal testicular lesions and assessed whether a conservative surgical approach may put the patient at higher oncological risk due to insufficient surgical eradication. MATERIALS AND METHODS: From October 2000 to May 2002 all patients with infertility, scrotal swelling, scrotal pain, varicocele, scrotal trauma or erectile dysfunction underwent scrotal ultrasonography. A total of 1,320 patients were investigated. Focal testicular lesions were found in 27 patients (2%), palpable nodules were present in 17 (63%) and nonpalpable incidental lesions were diagnosed in 10. Nodule diameter was 3 to 24 mm. All patients underwent explorative surgery via inguinotomy and preventive clamping of the spermatic cord. The nodules were completely removed with biopsy of the resection margins. Nonpalpable lesions were removed under ultrasonographic guidance. The testicle was only preserved when frozen section revealed a benign lesion and margins were negative. RESULTS: Of the 17 cases of palpable lesions (diameter 3 to 24 mm) conservative surgery was performed in 8 (47%). Definitive histological diagnosis showed Leydig cell tumor in 2 (25%), and large cell calcifying Sertoli's cell tumor, adenomatoid tumor, pseudofibrotic tumor of the tunica albuginea, epidermoid cyst, tubular fibrosis and non-Hodgkin's lymphoma in each 1 (12.5%). The remaining 9 patients (53%) underwent orchidectomy. Definitive histological examination revealed pure seminoma in 4 patients (44%), embryonal carcinoma in 4 (44%) and diffuse Leydig cell hyperplasia in 1 (12%). Seven of the 10 pts (70%) with nonpalpable nodules (diameter 4 to 16 mm) underwent conservative surgery. Histological study revealed focal Leydig cell hyperplasia in 1 case (10%), fibrosis in 3 (30%), infarction in 2 (20%) and mesothelial hyperplasia in 1 (10%). Orchiectomy was performed in the remaining 3 pts. Histology showed diffuse Leydig cell tumor in 2 pts (20%) and adenomatoid tumor with abscessed areas in 1 (10%). Neither atrophy nor local relapse was observed in pts who underwent conservative treatment during followup (mean: 1 month, range 19 to 9). CONCLUSIONS: The incidental diagnosis of testicular ultrasound alterations is increasing and 80% show a benign histology. In these cases a conservative surgical approach is the best option and it does not expose the patient to the risk of relapse.