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.

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.

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.

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.

Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations?

Klinefelter Syndrome (KS) is the most common chromosomal disorder in men leading to non-obstructive azoospermia. Spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. We evaluated AR variations and polymorphism length in 135 non-mosaic KS patients, aimed to find possible correlation with clinical features, sex hormones and sperm retrieval. Among 135 KS patients we found AR variations in eight subjects (5.9%). All variations but one caused a single amino acid substitution. Four variations P392S, Q58L, L548F, A475V found in six patients had been previously described to be associated with different degrees of androgen insensitivity. Moreover we observed in two patients Y359F and D732D novel variations representing respectively a missense variation and a synonymous variation not leading to amino acid substitution. All the Klinefelter patients with AR gene variations were azoospermic. Spermatozoa were retrieved with TESE for two men (40%), sperm retrieval was unsuccessful in other 3 patients. This is the only study reporting AR variations in KS patients. Relevant clinical differences not emerged between AR mutated and not AR mutated KS patients, but does each variation play an important role in the trasmission to the offspring obtained by ART in this patients?

Hypovitaminosis D is associated with erectile dysfunction in type 2 diabetes.

Diabetes is an established risk factor for erectile dysfunction (ED). The pathophysiology of ED in diabetic men is multifactorial, but it mainly involves a vascular disorder related to a reduction of endothelial function. Recently, several studies have correlated ED risk factors with vitamin D deficiency. In this study, we evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] levels, erectile dysfunction, and vascular disease, in type 2 diabetes mellitus men (T2DM). In this observational study, 92 T2DM males (58.83 ± 9.73 years) underwent medical history collection, International Index of Erectile Function (IIEF-5) questionnaire, that allows the identification and grading of DE, physical examination, biochemical/hormonal blood tests, and penile echo-color Doppler ultrasonography. T2DM patients with lower 25(OH)D levels (<25 nmol/l) showed higher penile IMT (p < 0.05), waist circonference (p < 0.05), glucose concentrations (p < 0.05), and lower IIEF-5 score (p < 0.005), testosterone concentrations (p < 0.05), and cavernous peak systolic velocity (PSV) (p < 0.05), compared to patients with 25(OH)D >50 nmol/l. 25(OH)D levels were directly correlated with IIEF-5 (R = 0.39; p = 0.0001), testosterone (R = 0.24; p = 0.02), and PSV (R = 0.24; p = 0.04) and inversely with waist (R = -0.33; p = 0.002), HbA1c (R = -0.22; p = 0.03), triglyceride (R = -0.21; p = 0.06), and penile IMT (R = -0.30; p = 0.009). At multivariate analysis, 25(OH)D deficiency remained an independent predictor of DE. We demonstrate a significant association between 25(OH)D deficiency and erectile dysfunction in T2DM men. This association may be due to the influence of 25(OH)D deficiency on cardiovascular risk factor (glycaemia, HDL cholesterol, and triglycerides), testosterone plasma levels and endothelial dysfunction.

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

BACKGROUND: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). CONCLUSIONS: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

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.

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.

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.

CEUS Retrograde Cystography Is Helpful in Percutaneous Drainage of Complex Posttransplant Lymphocele.

After monolateral dual kidney transplantation, a 69 years old male patient developed symptomatic lymphocele with mild hydroureteronephrosis, impaired renal function, and right inferior limb oedema. A percutaneous ultrasound-guided drainage of the fluid collection was planned, but the complex mutual relations between the collection and the renal hilus did not allow to identify a suitable route for a safe drainage insertion during conventional ultrasound examination. A retrograde cystography using echographic contrast agent was, therefore, performed, and it clarified the position of both ureters and the renal vessels, permitting an harmless ultrasound-guided percutaneous lymphocele drainage. In conclusion contrast-enhanced ultrasound retrograde cystography may be helpful in percutaneous drainage of complex posttransplant lymphocele.

Laparoscopic right posterior sectionectomy for hepatocellular carcinoma using a modified liver-hanging maneuver.

BACKGROUND: Posterosuperior liver segments are the most difficult locations for laparoscopy to access. This location is considered by most surgeons to be a poor indication for a laparoscopic liver resection due to the limited visualization and the difficulty of controlling bleeding. The liver-hanging maneuver (LHM) is a technique taking aim at reducing intraoperative blood loss through an open approach. METHODS: We report our early experience on adopting a modified liver-hanging technique to perform a totally laparoscopic right posterior sectionectomy to remove a 5-cm hepatocellular carcinoma located in Couinaud's segments 6 and 7. RESULTS: The procedure was completed laparoscopically with acceptable time of surgery and blood loss. A 3.5-cm tumor-free resection margin was achieved. The patient was discharged on postoperative Day 10 without complications. No evidence of recurrence was seen at the 12-month follow-up. CONCLUSIONS: Total laparoscopic posterior sectionectomy using a modified LHM is a possible operative procedure greatly facilitating surgical manipulation. This maneuver was successfully used to mobilize the liver, to guide the hepatic transection, and to prevent bleeding. The potential advantages of this procedure should be evaluated in a comparative study on a large number of patients.

Laparoscopic liver resection for hepatocellular carcinoma in cirrhotic patients. Feasibility of nonanatomic resection in difficult tumor locations.

BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) in cirrhotic patients remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR) for HCC including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. MATERIALS AND METHODS: Between June 2005 and February 2009, we performed 20 LLR for HCC. Median age of the patients was 66 years. The underlying cirrhosis was staged as Child A in 17 cases and Child B in 3. RESULTS: LLR included anatomic resection in six cases and nonanatomic resection in 14. Eleven procedures were associated in nine (45%) patients. Median tumor size and surgical margins were 3.1 cm and 15 mm, respectively. A conversion to laparotomy occurred in one (5%) patient for hemorrhage. Mortality and morbidity rates were 0% and 15% (3/20). Median hospital stay was 8 days (range: 5-16 days). Over a mean follow-up period of 26 months (range: 19-62 months), 10 (50%) patients presented recurrence, mainly at distance from the surgical site. Treatment of recurrence was possible in all the patients, including orthotopic liver transplantation in three cases. 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 oncological 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.

Hepatic flow optimization in full right split liver transplantation.

Split liver transplantation for two adults offers a valuable opportunity to expand the donor pool for adult recipients. However, its application is mainly hampered by the physiological limits of these partial grafts. Small for size syndrome is a major concern during transplantation with partial graft and different techniques have been developed in living donor liver transplantation to prevent the graft dysfunction. Herein, we report the first application of synergic approaches to optimise the hepatic hemodynamic in a split liver graft for two adults. A Caucasian woman underwent liver transplantation for alcoholic cirrhosis (MELD 21) with a full right liver graft (S5-S8) without middle hepatic vein. Minor and accessory inferior hepatic veins were preserved by splitting the vena cava; V5 and V8 were anastomosed with a donor venous iliac patch. After implantation, a 16G catheter was advanced in the main portal trunk. Inflow modulation was achieved by splenic artery ligation. Intraportal infusion of PGE1 was started intraoperatively and discontinued after 5 d. Graft function was immediate with normalization of liver test after 7 d. Nineteen months after transplantation, liver function is normal and graft volume is 110% of the recipient standard liver volume. Optimisation of the venous outflow, inflow modulation and intraportal infusion of PGE1 may represent a valuable synergic strategy to prevent the graft dysfunction and it may increase the safety of split liver graft for two adults.

Early effects of portal flow modulation after extended liver resection in rat.

INTRODUCTION: The incidence of small-for-size-liver-syndrome after liver transplantation and extended liver resection may be reduced by portal flow modulation. However, many aspects of the small-for-size-liver-syndrome pathogenesis are still unclear. In this experimental study we evaluated the early effects of portal flow modulation after 80% hepatic resection in rats. MATERIALS AND METHODS: Rats were randomised in: sham operation (G1), conventional hepatic resection (G2), splenectomy and hepatic resection (G3), splenic transposition followed by hepatic resection after three weeks (G4). Six hours after operation, oxygen saturation of hepatic vein blood, glutathione, and standard liver markers were measured from hepatic venous blood. Glutathione measurement and histopatological examination were performed in the remnant liver. RESULTS: Total bilirubin and liver glutathione did not show differences between groups. Aspartate aminotransferase and alanine aminotransferase significantly increased in G2-G4 groups. Blood glutathione and oxygen saturation of hepatic vein blood were lower in G2 than in other groups. A gradient of micro-vesicular degeneration was more severe in G2 compared with G3 and G4. Apoptosis, hemorrhagic necrosis, mitochondrial damage and leucocyte adhesion were evident in G2. CONCLUSION: The portal flow modulation induced by splenectomy or splenic transposition was effective in limiting early damage after extended liver resection.

Liver Match, a prospective observational cohort study on liver transplantation in Italy: study design and current practice of donor-recipient matching.

BACKGROUND: The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. METHODS: Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. RESULTS: The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. CONCLUSIONS: The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.