Novel insights on testicular volume and testosterone replacement therapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study.

STUDY QUESTION: To investigate whether sperm recovery is related to clinical features, hormone parameters and testosterone replacement therapy (TRT) in patients with Klinefelter syndrome (KS). SUMMARY ANSWER: This study provides three interesting insights: (i) the probability to retrieve sperm is not related to testicular volume; (ii) TRT does not affect sperm retrieval rate (SRR); and (iii) reduced levels of LH and FSH represent a negative predictor of sperm retrieval in patients with TRT. WHAT IS KNOWN ALREADY: Classical KS shows a karyotype with one extra X chromosome in all of somatic cells and clinical manifestations characterized by hypergonadotropic hypogonadism and infertility. STUDY DESIGN, SIZE AND DURATION: We performed a retrospective cohort study. Data from 111 consecutive KS azoospermic patients undergoing testicular sperm extraction (TESE) were collected from 2005 to 2016. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data on anthropometric parameters, reproductive hormones and testicular volumes were collected. SRR was related to clinical characteristics and compared between TRT and untreated patients. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 38 patients (34.2%) had successful sperm recovery. The comparison of clinical characteristics did not differ between patients with and without sperm recovery. Sperm retrieval was successful also in subjects with smaller testes. The comparison of SRR in patients with or without TRT was not different (33.3% vs 34.6%). In TRT group, LH and FSH levels were significantly lower in subjects with no sperm retrieval (P values, respectively, <.05 and <.001). LIMITATIONS AND REASONS FOR CAUTION: Well-designed controlled studies are necessary to confirm these data aimed to set the best therapeutic approach for fertility management in hypogonadal patients with nonmosaic KS. WIDER IMPLICATIONS OF THE FINDINGS: Age at TESE, anthropometric measures, testis volume, sex hormones levels and semen parameters are not predictive parameters of SRR. Among TRT patients, reduced gonadotropin is related to failure in sperm retrieval.

A prospective policy development to increase split-liver transplantation for 2 adult recipients: results of a 12-year multicenter collaborative study.

OBJECTIVE: To analyze in a multicenter study the potential benefit of a new prospective policy development to increase split-liver procedures for 2 adult recipients. BACKGROUND: Split-liver transplantation is an important means of overcoming organ shortages. Division of the donor liver for 1 adult and 1 pediatric recipient has reduced the mortality of children waiting for liver transplantation but the benefits or disadvantages to survival when the liver is divided for 2 adults (adult-to-adult split-liver transplant, AASLT) compared with recipients of a whole graft have not been fully investigated. METHODS: We developed a computerized algorithm in selected donors for 2 adult recipients and applied it prospectively over a 12-year period among 7 collaborative centers. Patient and graft outcomes of this cohort receiving AASLT either as full right grafts or full left grafts were analyzed and retrospectively compared with a matched cohort of adults who received a conventional whole-liver transplant (WLT). Univariate and multivariate analysis was done for selected clinical variables in the AASLT group to assess the impact on the patient outcome. RESULTS: Sixty-four patients who received the AASLT had a high postoperative complication rate (64.1% grade III and IV) and a lower 5-year survival rate than recipients of a WLT (63.3% and 83.1%) CONCLUSIONS: AASLT should be considered a surgical option for selected smaller-sized adults only in experimental clinical studies in experienced centers.

Endovascular treatment with primary stenting of inferior cava vein torsion following orthotopic liver transplantation with modified piggyback technique.

PURPOSE: This study was undertaken to evaluate primary stenting in patients with inferior vena cava torsion after orthotopic liver transplantation performed with modified piggyback technique. MATERIALS AND METHODS: From November 2003 to October 2010, six patients developed clinical, laboratory and imaging findings suggestive of caval stenosis, after a mean period of 21 days from an orthotopic liver transplantation performed with modified piggyback technique. Vena cavography showed stenosis due to torsion of the inferior vena cava at the anastomoses and a significant caval venous pressure gradient. All patients were treated with primary stenting followed by in-stent angioplasty in three cases. RESULTS: In all patients, the stents were successfully positioned at the caval anastomosis and the venous gradient pressure fell from a mean value of 10 to 2 mmHg. Signs and symptoms resolved in all six patients. One patient died 3 months after stent placement due to biliary complications. No evidence of recurrence or complications was noted during the follow-up (mean 49 months). CONCLUSIONS: Primary stenting of inferior vena cava stenosis due to torsion of the anastomoses in patients receiving orthotopic liver transplantation with modified piggyback technique is a safe, effective and durable treatment.

Recurrent acute Budd-Chiari syndrome after right hepatectomy: US color-Doppler vascular pattern and left hepatic vein stenting for treatment.

After extended right hepatectomy remnant liver can be affected by outflow obstruction due to torsion of the inferior vena cava or kinking of the left hepatic vein. Remnant liver fixation is therefore suggested to avoid postoperative acute Budd-Chiari syndrome. Despite remnant liver reposition during surgery, a 76-years-old woman developed complete outflow obstruction. This clinical situation, due to left hepatic vein kinking, was suspected by US examination and confirmed by CT scan that showed a pathological intrahepatic vascular pattern. Patient required urgent relaparotomy and the liver was replaced in normal position. However, recurrence of outflow obstruction occurred and it was ultimately treated by inferior vena cava angiogram with left hepatic vein stenting.

Laparoscopic resection of hepatocellular carcinoma. Considerations on lesions in the posterosuperior segments of the liver.

AIM: The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR) of hepatocellular carcinoma (HCC) including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. MATERIAL OF STUDY: Between June 2005 and May 2009, we performed 22 LLR for HCC. The underlying cirrhosis was staged as Child A in 19 cases and Child B in 3. RESULTS: LLR included a non anatomic resection in 15 cases and an anatomic resection in 7. A conversion to laparotomy occurred in one (4.5%) patient for hemorrhage. Mortality and morbidity rates were 0% and 18.1% (4/20). Over a mean follow-up period of 29 months (range: 19-65 months), 11 (50%) patients presented recurrence, mainly at distance from the surgical site. DISCUSSION: A laparoscopic approach is more suitable when the lesion is located in the peripheral "laparoscopic" segments 2 to 6. Nevertheless, six resections were made in the posterosuperior segments. Although parenchymal-sparing resection is required by the presence of underlying liver disease, anatomic resection has always to be considered and pursued to reduce local recurrence. In our series the recurrence rate was similar to those reported for other laparoscopic studies and for open resection of HCC. CONCLUSIONS: LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncologic adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.

Para- and perirenal fat thickness is an independent predictor of chronic kidney disease, increased renal resistance index and hyperuricaemia in type-2 diabetic patients.

BACKGROUND: Many interfering factors may reduce the reliability of waist circumference (WC) measurement in estimating the risk for chronic kidney disease (CKD) associated with obesity. Therefore, we determined the independent associations of para- and perirenal ultrasonographic fat thickness with the main markers of kidney function. METHODS: A cross-sectional study was performed in 151 type-2 diabetic subjects. Para- and perirenal fat thickness was measured from the inner side of the abdominal musculature to the surface of the kidneys. CKD was defined as eGFR < 60 mL min(-1)1.73 m(-2). RESULTS: Using both univariate and multivariate regression analyses, eGFR, renal resistance index and uricaemia were best predicted by para- and perirenal fat thickness even when BMI and waist circumference were further added in the statistical model (r(2): 0.366, P = 0.001; r(2): 0.529, P = 0.005; r(2): 0.310, P = 0.026, respectively), whereas waist circumference and BMI did not contribute independently of para- and perirenal fat thickness. Albuminuria was predicted by waist circumference but not by para- and perirenal fat thickness. In subjects with waist circumference above the diagnostic values of metabolic syndrome (48M/59F), eGFR significantly and progressively declined across tertiles of para- and perirenal fat thickness (87.0 ± 27.9 vs 83.5 ± 26.0 vs 62.3 ± 30.6 mL min(-1) 1.73 m(-2), adjusted P < 0.0001) despite comparable waist circumference, and an increasing frequency of CKD was observed across tertiles of subjects with waist circumference both below and above the metabolic syndrome diagnostic values (P < 0.05). CONCLUSIONS: Para- and perirenal fat thickness is an independent predictor of kidney dysfunction in type-2 diabetes explaining an important proportion of the variance of eGFR, renal resistance index and uricaemia.

Reversed arterial flow in the paramedian segments of the liver after pancreaticoduodenectomy.

Variation of splanchnic arterial anatomy is frequent and may complicate pancreatic surgery, leading to life-threatening postoperative complications. We report a case of severe hepatic dysfunction after pancreaticoduodenectomy due to accidental section of the right hepatic artery. Bedside ultrasound examination showed a reversed arterial flow in the paramedian segments of the liver. Based on intraoperative and ultrasound findings, a retrograde arterial supply of the right liver from the left hepatic artery through spontaneous anastomosis between the arteries of segment 4 and the right paramedian segments was assumed and confirmed by postoperative CT examination.

Sperm Count and Hypogonadism as Markers of General Male Health.

BACKGROUND: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. OBJECTIVE: We tested whether semen quality and reproductive function could represent a marker of general male health. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. RESULTS AND LIMITATIONS: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. CONCLUSIONS: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. PATIENT SUMMARY: This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease.

BACKGROUND & AIMS: Patients with advanced liver disease often undergo invasive procedures, so the combination of thrombocytopenia, coagulopathy, and bleeding should be carefully assessed. We evaluated the prevalence of thrombocytopenia in a series of patients with liver cirrhosis who were being evaluated for orthotopic liver transplantation (OLT) and determined the number of invasive procedures and procedure-related incidences of bleeding in patients with thrombocytopenia. METHODS: We studied 121 consecutive patients who were being evaluated for OLT. Thrombocytopenia was defined as a platelet count <150,000/µL and severe thrombocytopenia as a platelet count <75,000/µL. The presence of significant coagulopathy was defined as an international normalized ratio >1.5. Invasive procedures and incidences of procedure-related bleeding were recorded for each patient. RESULTS: The prevalence of thrombocytopenia and severe thrombocytopenia were 84% and 51%, respectively. Among the 102 thrombocytopenic patients, 50 (49%) underwent an invasive procedure (32 with severe thrombocytopenia; 64%). Bleeding occurred in 10 of the patients who underwent an invasive procedure (20%). Among the 50 patients who underwent invasive procedure, 32 had severe thrombocytopenia and 18 had moderate thrombocytopenia. Bleeding occurred in 10 of the 32 patients (31%) with severe thrombocytopenia and in none of those with moderate thrombocytopenia. There was no difference in prevalence of significant coagulopathy between patients with severe thrombocytopenia who underwent invasive procedure and bled (3/10; 30%) and those who did not bleed (10/22; 45%). CONCLUSIONS: Thrombocytopenia has a high prevalence among patients with advanced liver disease. Bleeding related to invasive procedures occurs most frequently in patients with severe thrombocytopenia, whereas significant coagulopathy does not seem to be associated with bleeding.

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. METHODS/DESIGN: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. DISCUSSION: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. TRIAL REGISTER: Trial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36).

Simultaneous laparoscopic anterior resection and left hepatic lobectomy for stage IV rectal cancer.

We report the case of a 68-year-old female patient affected by rectal cancer and a synchronous metastatic lesion measuring 8 cm in diameter in the left hepatic lobe. After a laparoscopic ultrasonography exploration of the liver to detect possible occult metastases, a simultaneous colorectal resection and a left hepatic lobectomy including a partial resection of segment IV were performed. Five ports were used for the entire procedure. The resected specimens were extracted through a Pfannenstiel incision. The procedure was completed laparoscopically. Total operative time was 455 minutes with negligible intraoperative blood loss. The postoperative hospital stay was 12 days. At 4-month follow-up, the patient recovered completely. A computed tomography scan performed at this time showed no signs of recurrent disease. This report confirms the feasibility of the laparoscopic approach to simultaneous hepatic and colorectal resections in stage IV rectal cancer. The known advantages of the miniinvasive approach could make such complex procedures more endurable.

Long-term outcome of renal transplantation from older donors.

BACKGROUND: Long-term survival of kidney grafts from older donors is inferior to that of grafts from younger donors. We sought to determine whether selecting older kidneys according to their histologic characteristics before implantation would positively influence long-term outcome. METHODS: In a prospective cohort study, we assessed outcomes among 62 patients who received one or two histologically evaluated kidneys from donors older than 60 years of age. These outcomes were compared with outcomes among 248 matched recipients of single kidney grafts that had not been histologically evaluated and were either from donors 60 years of age or younger (124 positive-reference recipients who, according to available data, were expected to have an optimal outcome) or from those older than 60 years (124 negative-reference recipients, expected to have a worse outcome). The primary end point was graft survival. RESULTS: During a median period of 23 months, 4 recipients (6 percent) of histologically evaluated kidneys progressed to dialysis, as compared with 7 positive-reference recipients (6 percent) and 29 negative-reference recipients (23 percent). Graft survival in recipients of histologically evaluated kidneys did not differ significantly from that of grafts in positive-reference recipients but was superior to that of grafts in negative-reference recipients (hazard ratio for graft failure in the negative-reference recipients relative to the recipients of histologically evaluated kidneys, 3.68; 95 percent confidence interval, 1.29 to 10.52; P=0.02). The performance of preimplantation histologic evaluation predicted better survival both in the whole study group (P=0.02) and among recipients of kidneys from older donors (P=0.01). CONCLUSIONS: The long-term survival of single or dual kidney grafts from donors older than 60 years of age is excellent, provided that the grafts are evaluated histologically before implantation. This approach may help to expand the donor-organ pool for kidney transplantation.

Longitudinal evaluation of mycophenolic acid pharmacokinetics in pediatric kidney transplant recipients. The role of post-transplant clinical and therapeutic variables.

This longitudinal study assessed the influence of post-transplant clinical and therapeutic variables in 50 kidney transplant recipients aged 2-19 yr receiving a triple immunosuppressive regimen consisting of cyclosporine microemulsion (CsA), steroids and MMF (300-400 mg/m(2) body surface area twice daily), the full pharmacokinetic profile (10 points) of which was investigated on post-transplant days 6, 30, 180 and 360. Total plasma MPA was measured by Enzyme Multiplied Immunoassay Technique. CsA therapeutic drug monitoring (TDM) was performed via C2 blood monitoring, while MPA TDM via C0. MPA Cmax, tmax, AUC0-12 and AUC0-4 pharmacokinetic profile changed significantly during the first post-transplant year. C0 was a poor predictor of the total MPA exposure [as measured by the area under the concentration-time curve AUC)], while a truncated AUC was a good surrogate of the 12-h profile (r = 0.91; p < 0.001) Graft function and cyclosporine therapy influenced MPA pharmacokinetics, as shown by the univariate and multivariate analyses. We conclude that because after transplantation MPA exposure varied over time, a strict TDM is advisable in the pediatric population.

Laparoscopic staging and radiofrequency of hepatocellular carcinoma in liver ci rrhosis. A "bridge" treatment to liver transplantation.

BACKGROUND/AIMS: Surgical resection and liver transplantation are the only curative treatments for hepatocellular carcinoma, although limited to early stage disease. Our objective was to assess a novel operative combination of laparoscopic ultrasound with laparoscopic radiofrequency ablation of small hepatocellular carcinoma in potential candidates to liver transplantation when radiological evaluation is equivocal. We also evaluated the feasibility and efficacy of laparoscopic radiofrequency ablation. METHODOLOGY: Over a 2-year period, a laparoscopic ultrasound exploration and a laparoscopic radiofrequency ablation was performed in 15 patients (mean age 57+/-5.4 years; male/female 13/2) with hepatocellular carcinoma in liver cirrhosis. RESULTS: LRFA procedure was completed in all patients and a thermoablation of 36 hepatocellular carcinoma nodules was achieved. Laparoscopic ultrasound identified 12 new malignant lesions (46.1%) undetected by preoperative imaging. Six patients were up-staged as a result of the procedure and 3 were precluded from liver transplantation listing. A complete tumor necrosis was observed in 32 thermoablated nodules (88.8%) via spiral computed tomography 1 month after treatment. Seven patients underwent liver transplantation after a 5.8-month mean interval, and pathological staging of the explants agreed with laparoscopic staging for number/size of hepatocellular carcinoma nodules in all cases. Residual tumor was found in 2/12 (16.6%) thermoablated nodules, in two different liver specimens. CONCLUSIONS: Laparoscopic ultrasound accurately staged hepatocellular carcinoma in advanced cirrhosis with minimal morbidity and it can be used in potential candidates to liver transplantation. Laparoscopic radiofrequency ablation of hepatocellular carcinoma proved to be a safe and effective technique, representing a valid "bridge" treatment to liver transplantation or an effective palliative option.

Prognostic Value of Ultrasound Stratigraphy in Long-Term Weight Loss: Results from a Nutritional Counseling Program.

BACKGROUND: Weight control through lifestyle interventions represents a suitable strategy to avoid the metabolic, endocrine, and reproductive comorbidities associated with overweight and obesity. Reduced testosterone (T) levels are a worsening factor in overweight males. However, prognostic parameters of long-term weight loss are not readily available. Here, we tested the prognostic value of early variations of anthropometric and hormonal parameters, with a focus on ultrasound stratigraphy (US) and the reduction in body mass index (BMI) associated with nutritional counseling/lifestyle interventions at 6-month follow-up. METHODS: Ninety-five male subjects (BMI 25-34.9 kg/m2) who had undergone nutritional/lifestyle interventions, were retrospectively analyzed for: body weight and composition; US evaluation at the triceps (TRC), abdominal (ABD), and thigh (THI) areas; and circulating levels of T, luteinizing hormone, and follicle-stimulating hormone. Sixty patients (63.2%) completed the 6-month follow-up program. RESULTS: At 6 months, a significant reduction in BMI (26.38 ± 1.55 vs. 31.5 ± 5.0 basal, p < 0.001) and increase in T levels (18 ± 5.4 vs. 9.5 ± 2.3 nmol/L basal, p = 0.04) were observed. Subjects in the highest quartile of the BMI reduction at 6 months (ΔBMI 6 mo), compared to the lowest, showed a significant difference at the 2-month follow-up variation of BMI (p = 0.025), and fat and muscle thickness at the TRC (both p < 0.001) and ABD (p < 0.001 and p = 0.002, respectively) areas. Variation of TRC muscle thickness at 2 months was the only independent predictor of ΔBMI 6 mo in the multiple stepwise regression analysis. CONCLUSIONS: BMI evaluation and US represent useful monitoring tools in the follow-up of nutritional/lifestyle interventions for overweight-to-mildly obese patients. The important effects on motivation and adherence to the intervention program are to be considered.

Role of Viral Infections in Testicular Cancer Etiology: Evidence From a Systematic Review and Meta-Analysis.

The most represented histotype of testicular cancer is the testicular germ-cell tumor (TGCT), both seminoma and non-seminoma. The pathogenesis of this cancer is poorly known. A possible causal relationship between viral infections and TGCTs was firstly evoked almost 40 years ago and is still a subject of debate. In the recent past, different authors have argued about a possible role of specific viruses in the development of TGCTs including human papillomavirus (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Parvovirus B-19, and human immunodeficiency virus (HIV). The aim of this present review was to summarize, for each virus considered, the available evidence on the impact of viral infections on the risk of developing TGCTs. The review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all observational studies reported in English evaluating the correlations between viral infections (HPV, CMV, EBV, Parvovirus B19, and HIV) and TGCTs. The methodological quality of studies included in the meta-analysis was evaluated using a modified version of the "Newcastle-Ottawa Scale." Meta-analyses were conducted using the "Generic inverse variance" method, where a pooled odds ratio (OR) was determined from the natural logarithm (LN) of the studies' individual OR [LN (OR)] and the 95% CI. A total of 20 studies (on 265,057 patients) were included in the review. Meta-analysis showed an association with TGCTs only for some of the explored viruses. In particular, no association was found for HPV, CMV, and Parvovirus B-19 infection (p = ns). Conversely, EBV and HIV infections were significantly associated with higher risk of developing TGCTs (OR 7.38, 95% CI 1.89-28.75, p = 0.004; OR 1.71, 95% CI 1.51-1.93, p < 0.00001). In conclusion, we found adequate evidence supporting an oncogenic effect of HIV and EBV on the human testis. Conversely, available data on HPV and TGCTs risk are conflicting and further studies are needed to draw firm conclusions. Finally, current evidence does not support an effect of CMV and Parvovirus B-19 on testicular carcinogenesis.

Endocrine Disruption of Androgenic Activity by Perfluoroalkyl Substances: Clinical and Experimental Evidence.

BACKGROUND: Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety of toxicological effects is well supported in animals, including testicular toxicity and male infertility. For these reasons, the understanding of epidemiological associations and of the molecular mechanisms involved in the endocrine-disrupting properties of PFCs on human reproductive health is a major concern. OBJECTIVE: To investigate the relationship between PFC exposure and male reproductive health. DESIGN: This study was performed within a screening protocol to evaluate male reproductive health in high schools. PATIENTS: This is a cross-sectional study on 212 exposed males from the Veneto region, one of the four areas worldwide heavily polluted with PFCs, and 171 nonexposed controls. MAIN OUTCOME MEASURES: Anthropometrics, seminal parameters, and sex hormones were measured in young males from exposed areas compared with age-matched controls. We also performed biochemical studies in established experimental models. RESULTS: We found that increased levels of PFCs in plasma and seminal fluid positively correlate with circulating testosterone (T) and with a reduction of semen quality, testicular volume, penile length, and anogenital distance. Experimental evidence points toward an antagonistic action of perfluorooctanoic acid on the binding of T to androgen receptor (AR) in a gene reporter assay, a competition assay on an AR-coated surface plasmon resonance chip, and an AR nuclear translocation assay. DISCUSSION: This study documents that PFCs have a substantial impact on human health as they interfere with hormonal pathways, potentially leading to male infertility.

Laparoscopic US-guided radiofrequency ablation of unresectable hepatocellular carcinoma in liver cirrhosis: feasibility and clinical outcome.

BACKGROUND: Radiofrequency ablation (RFA) is a safe, effective treatment in patients with unresectable primary liver malignancies. The laparoscopic approach to RFA (LRFA) has proved to be superior to the percutaneous approach in lesions that are difficult or impossible to be treated in such a way or in severe liver disease. Recent advances in laparoscopic ultrasound (LUS) have greatly improved the accuracy in detecting intrahepatic hepatocellular carcinoma (HCC) nodules, many of which were missed by computed tomography (CT) or magnetic resonance imaging (MRI). Our aim was to assess the feasibility, clinical outcome, and efficacy of laparoscopic RFA under LUS guidance. METHODS: Between February 2006 and May 2007, 24 consecutive patients (male/female, 20/4) with unresectable HCC in liver cirrhosis were treated with LRFA under LUS guidance. Most patients were in Child-Pugh class A (54.1%). Mean age of the patients was 61.79 +/- 7.74 years (range, 45-76; median, 60). RESULTS: LRFA procedure was completed in all patients and a thermoablation of 62 HCC nodules was achieved. LUS identified 13 new malignant lesions (20%) undetected by preoperative imaging. Mean length of surgery was 148 minutes (range, 60-315). Six procedures were associated in 5 patients: adhesiolysis (3), liver resection (1), partial splenectomy (1), and cholecystectomy (1). A pneumothorax needing immediate drainage during the procedure occurred in 1 case. One patient died 4 weeks after surgery because of liver failure. Mean hospital stay was 6.9 days and postoperative morbidity rate was 4 of 24 (16.6%). A complete tumor necrosis was observed in 56 of the 62 thermoablated nodules (90.3%) through spiral CT 1 month after treatment. CONCLUSIONS: LRFA is a safe, feasible treatment modality to achieve tumor destruction in selected patients with unresectable HCC that are not treatable with the percutaneous approach. Further, LUS demonstrated great accuracy during the procedure permitting to detect new HCC nodules missed at preoperative imaging.

Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in infertile patients with HPV semen infection: a retrospective study.

In this study we aimed to evaluate the effect on reproductive outcome of HPV vaccination in male subjects of infertile couples with HPV semen infection. In this single-center study, we retrospectively enrolled 151 infertile couples with detection of HPV in semen, attending our Hospital Unit of Andrology between January 2013 and June 2015, counseled to receive adjuvant HPV vaccination. Seventy-nine accepted vaccination (vaccine group) whilst 72 did not (control group). Our protocol of follow-up, aimed to evaluate HPV viral clearance, consisted in semen analysis, INNO-LiPA and FISH for HPV in semen cells after 6 and 12 months from basal evaluation. Spontaneous pregnancies, miscarriages and live births were recorded. Progressive sperm motility and anti-sperm antibodies were improved in the vaccine group at both time points (p < 0,05 vs control arm). Forty-one pregnancies, 11 in the control group and 30 in the vaccine group, were recorded (respectively 15% and 38,9%, p < 0,05) and resulted into 4 deliveries and 7 miscarriages (control group) and 29 deliveries and one miscarriage (vaccine group, p < 0,05 vs control group). HPV detection on sperms was predictive of negative pregnancy outcome. Adjuvant vaccination associated with enhanced HPV healing in semen cells and increased rate of natural pregnancies and live births.

Cavo-portal transposition in rat: a new simple model.

BACKGROUND: Liver transplantation in presence of diffuse portal vein thrombosis is possible by using caval blood as portal inflow, through cavo-portal transposition. However, clinical results are heterogeneous and experimental studies are needed, but similar hemodynamic conditions are difficult to obtain, especially in small animals. Herein we describe a new simple model of cavo-portal transposition in rat. METHODS: Spontaneous porto-systemic shunts are induced by subcutaneous transposition of the spleen. The presence of porto-caval shunts through the spleen permits the interruption of the main portal vein without splanchnic hemodynamic consequences. Cavo-portal transposition is achieved by anastomosing the inferior vena cava and the main portal vein after division of the pancreatic-duodenal vein. RESULTS: Selective angiography revealed total splanchnic blood diversion to the systemic venous circulation through the neoformed collaterals; macroscopical examination showed the absence of any signs of acute portal hypertension with normal liver and gut appearance. CONCLUSION: This model of cavoportal transposition is simple, effective and it simulates the clinical hemodynamic condition since the porto-systemic shunts induced by splenic subcutaneous transposition correspond to the physiological inframesocolic collaterals during chronic portal thrombosis in man.