Well-Differentiated Papillary Mesothelioma with Omental Calcifications: A Case Report and Review of the Literature.

BACKGROUND Omental calcifications of the peritoneum are typically small and asymptomatic. However, larger psammomatous bodies that cause symptoms such as abdominal pain and bloating are often associated with tumors such as primary serous papillary carcinoma, mesothelioma, or metastatic ovarian cancer. CASE REPORT We describe omental calcifications in a 68-year-old woman who had been asymptomatic for the last 10 years. The case details the histomorphologic features and immunohistochemical signature of a 4.0×3.5×1.0 cm mass consisting of mature adipose tissue that was surgically removed together with an 8.5×6.5×1.8 cm irregular intra-abdominal/mesenteric mass composed of yellow-red fatty tissue. Microscopic sections contained fat with variable clustered classic/psammomatous calcifications, some with a thin epithelioid periphery, in association with a very focal and subtle papillary surface epithelial/mesothelial proliferation. Tumor cell invasion was not observed during examination. Immunohistochemical staining showed that mesothelial cells in the mass were strongly positive for calretinin and focally positive for EMA, CK903, and vimentin. Strong nuclear positivity for PAX8 was also reported. Additional stains were added in response to this pattern, showing strong positivity for CK8, moderate positivity for BAP1, focal positivity for ER, minimal positivity for CD56, and negativity for CK5/6 and D2-40. Three possible explanations are suggested for the phenomenon observed in the pathology slides: reactive mesothelial hyperplasia, well-differentiated papillary mesothelioma, or serous papillary carcinoma of the peritoneum. CONCLUSIONS Findings suggest that these calcifications are a benign, reactive phenomenon, and that the abundance of psammoma bodies may be related to ongoing crops of papillary mesothelial hyperplasia or benign well-differentiated papillary mesothelioma.

Staging Melanoma: What's Old and New.

The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.

Serratia Liver Abscess Infection and Cardiomyopathy in a Patient with Diabetes Mellitus: A Case Report and Review of the Literature.

BACKGROUND Liver abscesses remain difficult to diagnose and treat. Risk factors include diabetes mellitus, liver cirrhosis, and immunodeficiency. The majority are pyogenic, resulting from bacterial infection. Research identifies species in the Serratia genus as the cause of pyogenic liver abscesses in only 0.25% of cases and only 1 Serratia species in each case appears to have been identified. To the best of our knowledge, the present case report is the first to involve overlapping Serratia species in a single liver abscess infection that induced cardiomyopathy. CASE REPORT A 45-year-old woman presented to our Emergency Department (ED) for severe generalized weakness. Initial test results indicated a diagnosis of microcytic anemia, hypomagnesemia, hypokalemia, hypocalcemia, hyperglycemia, type 2 diabetes mellitus, and severe heart failure. A computed tomography scan showed a 10-cm rim-enhancing fluid collection in the right hepatic lobe. Fluid drained from the suspected abscess tested positive for Serratia marcescens and Streptococcus viridans. The patient was treated with ceftriaxone and metronidazole, which she tolerated well. The abscess decreased to less than 9.8 mm. Twenty-one weeks after discharge, the patient received a cholecystectomy. Fluid drained from the residual abscess cultured positive for a different Serratia species, S. odorifera. CONCLUSIONS Diabetes mellitus and acute cholecystitis were key factors in the initial infections and abscess. We also suspect this is a rare case of cardiomyopathy induced by a Serratia infection. The source of the Serratia odorifera is less certain, as it postdates placement of a percutaneous drain, raising the potential for a nosocomial infection but not precluding the possibility that both Serratia species were previously present.

Photodynamic therapy (PDT) using HPPH for the treatment of precancerous lesions associated with Barrett's esophagus.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett's esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT. STUDY DESIGN/MATERIALS AND METHODS: Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2 . At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175, or 200 J/cm of 665 nm light. RESULTS: Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced grade 3 and 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 hours), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 hours), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year. CONCLUSIONS: HPPH-PDT for precancerous lesions in Barrett's esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT.

Free radicals and male reproduction.

Male factor accounts for almost 50% cases of infertility. The exact mechanism of sperm dysfunction is not known in many cases. Extensive research in the last decade has led to the identification of free radicals (reactive oxygen species) as mediators of sperm dysfunction in both specific diagnoses and idiopathic cases of male infertility. Elevated levels of reactive oxygen species are seen in up to 30-80% of men with male infertility. The role of free radicals has been studied extensively in the process of human reproduction. We know now that a certain level of free radicals is necessary for normal sperm function, whereas an excessive level of free radicals can cause detrimental effect on sperm function and subsequent fertilisation and offspring health. Oxidative stress develops when there is an imbalance between generation of free radicals and scavenging capacity of anti-oxidants in reproductive tract. Oxidative stress has been shown to affect both standard semen parameters and fertilising capacity. In addition, high levels of free radicals have been associated with lack of or poor fertility outcome after natural conception or assisted reproduction. Diagnostic techniques to quantify free radicals in infertile patients can assist physicians treating patients with infertility to plan for proper treatment strategies. In vivo anti-oxidants can be used against oxidative stress in male reproductive tract. Supplementation of in vitro anti-oxidants can help prevent the oxidative stress during sperm preparation techniques in assisted reproduction.

Relationship between oxidative stress, varicocele and infertility: a meta-analysis.

Varicocele is one of the leading causes of male infertility, and is present in almost 40% of infertile males. Recent understanding of the role of oxidative stress in male reproduction has led some researchers to postulate oxidative stress as the possible cause of sperm dysfunction in varicocele patients. The objective of the present study was to examine the published literature on the role of oxidative stress in patients with varicocele as the aetiology of their infertility. Twenty-three human studies were identified after an extensive search dealing with the role of oxidative stress in varicocele-associated infertility. Out of these studies, four were selected that measured similar types of reactive oxygen species (ROS) by a similar method of measurement. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients have significantly higher concentrations of ROS than controls, with the mean difference being 0.73 (95% CI 0.40, 1.06, P < 0.0001). This translated to an ROS concentration of 4.37 x 10(4) cpm/20 x 10(6) spermatozoa/ml on the linear scale. Total antioxidant capacity levels were found to be significantly lower in the infertile varicocele patients, with 386 fewer trolox equivalents than the controls (95% CI -556.56-216.96, P < 0.00001). From the results, it can be concluded that there is increased oxidative stress in varicocele patients; however, more studies are needed to confirm this finding.

Sperm DNA damage assessment: a test whose time has come.

Multiple techniques have been developed to measure the amount of sperm DNA damage in an effort to identify more objective parameters for evaluation of infertile men. We now have evidence to support that integrity of sperm DNA influences a couple's fertility and helps predict the chances of pregnancy and its successful outcome. The available tests of sperm DNA damage require additional large-scale clinical trials before their integration into routine clinical practice.

Identification of male factor infertility using a novel semen quality score and reactive oxygen species levels.

PURPOSE: To determine whether patients with male factor infertility can be accurately identified by calculating a novel semen quality score and measuring levels of reactive oxygen species during routine infertility screening. METHODS: Semen samples from 133 patients and 91 healthy donors were evaluated with manual and computer-assisted semen analysis. A principal component analysis model was employed to calculate a semen quality score. In brief, this score was calculated by base 10 logarithms multiplied by varying weights given to 9 sperm parameters. Reactive oxygen species levels were measured using chemiluminescence assay. RESULTS: The semen quality score had a sensitivity of 80.45% and accuracy of 77% at a cutoff of 93.1 in identifying patients with male factor infertility. The area under the receiver operating characteristic curves for the semen quality score was 84.28% (95% CI: 65.22%-100%). Reactive oxygen species levels [log10 (reactive oxygen species +1)] were significantly higher in male factor infertility patients. Reactive oxygen species had a sensitivity of 83.47% and specificity of 60.52% with an accuracy of 75% at a cutoff of 1.25 in identifying male factor infertility patients. The area under the receiver operating characteristic curve for reactive oxygen species levels was 78.92% (95% CI: 72.60%-85.23%). Semen quality scores were significantly and negatively correlated with reactive oxygen species levels in the donors and the male factor infertility patients. CONCLUSIONS: The semen quality score and reactive oxygen species levels in semen samples appear to be strongly associated with male factor infertility. Because both of these parameters are more sensitive than individual sperm parameters in identifying male factor infertility, they should be included in routine infertility screening.

Identification of male factor infertility using a novel semen quality score and reactive oxygen species levels

OBJETIVO: Determinar se pacientes portadores do fator de infertilidade masculina podem ser precisamente identificados através do cálculo de um novo escore de qualidade de sêmen e pela medida de espécies reativas de oxigênio durante uma avaliação rotineira de infertilidade. MÉTODOS: Amostras de sêmen de 133 pacientes e de 91 doadores saudáveis foram avaliadas através de análise manual e computadorizada de sêmen. Um modelo de análise do componente principal foi empregado para calcular o escore de qualidade de sêmen, utilizando logaritmos base 10, multiplicados por ponderações variáveis de 9 parâmetros espermáticos. Os níveis de espécies reativas de oxigênio foram medidos através de testes de quimiluminescência. RESULTADOS: O escore de qualidade de sêmen apresentou sensibilidade de 80.45% e precisão de 77% para um "cutoff" de 93.1 na identificação do fator de infertilidade masculina. A área sob a curva "receiver operating characteristic" para o escore de qualidade de sêmen foi de 84.28% (95% intervalo de confiança: 65.22%-100%). Os níveis de espécies reativas de oxigênio [log10 (espécies reativas de oxigênio +1)] foram siginificativamente mais elevados nos pacientes portadores de fator de infertilidade masculina. A medica de espécies reativas de oxigênio apresentou sensibilidade de 83.47% e especificidade de 60.52% com uma precisão (definida como pacientes portadores do fator de infertilidade masculina com diagnóstico positivo e doadores corretamente excluídos) de 75% para um "cutoff" de 1.25 na identificação de pacientes portadores do fator de infertilidade masculina. A área sob a curva "receiver operating characteristic" para níveis de espécies reativas de oxigênio foi de 78.92% (95% intervalo de confiança: 72.60%-85.23%). Os escores de qualidade de sêmen correlacionaram negativamente com os níveis de espécies reativas de oxigênio tanto nos doadores e nos pacientes portadores do fator de infertilidade masculina. CONCLUSÕES: O escore de qualidade de sêmen e os níveis espécies reativas de oxigênio nas amostras de sêmen parecem associar-se fortemente com o fator de infertilidade masculina. Na medida em que os dois parâmetros mostraram-se mais sensíveis que parâmetros espermáticos individuais na identificação do fator de infertilidade masculina, deveriam ser incluídos na avaliação rotineira de infertilidade.

Correlation of reactive oxygen species levels with the fertilization rate after in vitro fertilization: a qualified meta-analysis.

Our meta-analysis analyzed the relationship between levels of reactive oxygen species (ROS) and fertilization rate after in vitro fertilization (IVF), and showed a statistically significant correlation between the ROS levels and the IVF fertilization rate (estimated overall correlation -0.374 [95% CI, -0.520, -0.205]). We conclude that ROS has a statistically significant effect on the fertilization rate after IVF, and that the measurement of ROS levels in semen specimens before IVF may be useful in predicting the IVF outcome and in counseling patients.

Characterization of oxidative stress status by evaluation of reactive oxygen species levels in whole semen and isolated spermatozoa.

We defined the basal levels of reactive oxygen species (ROS) in normal donors in neat (whole unprocessed) semen specimens, and in mature and immature spermatozoa isolated by a double-density gradient technique. In addition, we demonstrated that the ROS levels were significantly lower in neat semen compared with washed spermatozoa. The reference values of ROS in neat semen and mature spermatozoa can be used to define the pathologic levels of ROS in infertile men and may guide in therapeutic interventions.

Disruption of spermatogenesis by the cancer disease process.

In the past, cancer survivors tended to be most concerned about disease recurrence and treatment side effects. As survival rates have increased, however, patients are now also concerned about quality-of-life issues such as preserving fertility potential. It is well known that cancer treatment adversely affects male fertility via direct effects on the testis and/or through the endocrine glands. Evidence also suggests that the disease process itself may affect a man's fertility by influencing spermatogenesis. However, the causes of poor semen quality in cancer patients are not well understood. Multiple factors are likely involved, including preexisting defects in germ cells, systemic effects of cancer, and endocrine and immunological disturbances. This paper will summarize available evidence on different factors involved in impaired spermatogenesis in patients with various cancers with emphasis on testicular cancer and Hodgkin lymphoma. Cryopreservation of spermatozoa is a simple and practical approach available to all patients with cancer who wish to preserve their fertilizing potential before cancer therapy.

Comparative study on density gradients and swim-up preparation techniques utilizing neat and cryopreserved spermatozoa.

AIM: To 1) compare post-wash and post-thaw parameters of sperm processed with PureSperm density gradient technique and swim-up method; and 2) test the efficacy of two commonly available density gradient media PureSperm and ISolate. METHODS: This prospective study used semen specimens from 22 patients. Specimens from nine patients were processed by both PureSperm density gradient and swim-up method. These specimens were then cryopreserved. Thirteen specimens were processed by both PureSperm (40 % and 80 %) and Isolate (50 % and 90 %) double density gradient techniques. The two fractions processed by both PureSperm and swim-up were analyzed for post-wash sperm characteristics. Post-thaw analysis was done after 24 hours. Sperm fractions obtained after processing with PureSperm and ISolate were compared for post-wash sperm characteristics and ROS levels. RESULTS: Specimens prepared with PureSperm had significantly higher median total motile sperm counts (TMSC) (32.2 x 10(6) vs. 17.6 x 10(6)), recovery rates (69.2 % vs. 50.0 %), and longevity at 4 hours (83.0 % vs. 55.0 %) compared to specimen prepared by swim-up. Post-thaw specimens also had a higher recovery and longevity at 4 hours with PureSperm as compared to the swim-up. Semen specimens processed by PureSperm had significantly higher total sperm count, TMSC, and percentage recovery rates (30.0 % vs. 19.7 %) than ISolate. CONCLUSION: Semen quality is better preserved in fresh and cryopreserved semen prepared with PureSperm density gradient compared to swim-up. A significant enrichment of sperm is observed with PureSperm compared to ISolate. Higher recovery rates of mature motile sperm obtained after PureSperm sperm preparation may be beneficial for successful ART.

Sildenafil citrate and vacuum constriction device combination enhances sexual satisfaction in erectile dysfunction after radical prostatectomy.

OBJECTIVES: To assess the effectiveness of combining sildenafil citrate with a vacuum constriction device (VCD) in men (after radical prostatectomy) unsatisfied with the results of the VCD alone. METHODS: A total of 31 patients unsatisfied with the early use of VCD alone after radical prostatectomy (mean follow-up of 4.5 months) were instructed to take 100 mg of sildenafil 1 to 2 hours before VCD use for sexual intercourse. Patients used combination therapy for a minimum of five attempts before assessment with the abridged International Index of Erectile Function (IIEF) questionnaire and a visual analogue scale to gauge rigidity. The effect of combination therapy on the total IIEF-5 score and penile rigidity score were assessed. RESULTS: Of the 31 patients, 7 (22%) had no improvement with the addition of sildenafil with VCD and discontinued the drug, and 24 (77%) reported improved penile rigidity and sexual satisfaction. The IIEF-5 score revealed statistically significant improvement in each domain, and patients reported that sildenafil enhanced their erections 100% of the time. The penile rigidity scores on a scale of 0 to 100 with the VCD alone averaged 55% (range 23% to 85%) for the men and 59% (range 26% to 90%) for their partners. With the addition of sildenafil, it increased to 76% for the men and 82% for their partners. Of the 24 men, 7 (30%) reported a return of natural erections at 18 months using combination therapy, with 5 of 7 reporting erections sufficient for vaginal penetration. CONCLUSIONS: In this study, the addition of sildenafil with VCD improved sexual satisfaction and penile rigidity in patients unsatisfied with VCD alone after radical prostatectomy.

Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size.

Increased levels of reactive oxygen species (ROS) are associated with clinical varicoceles; however, its correlation with varicocele grade and testis size is unknown. In our study, seminal ROS levels showed significant correlation with left varicocele grade and significantly elevated seminal ROS levels were seen in men with left varicocele grade 2 and 3 compared to grade 1.

Relationship between acrosin activity of human spermatozoa and oxidative stress.

AIM: To study the association between seminal oxidative stress and human sperm acrosin activity. METHODS: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. RESULTS: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (1 multiply 10(6)/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P 0.001). CONCLUSION: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

Relationship of interleukin-6 with semen characteristics and oxidative stress in patients with varicocele.

OBJECTIVES: To examine levels of interleukin-6 (IL-6) in fertile semen donors and patients with varicocele and examine its association with semen characteristics and levels of reactive oxygen species (ROS). METHODS: We conducted a prospective study consisting of 15 fertile donors (controls) and 35 infertile patients with varicocele. Semen analysis was performed according to the World Health Organization guidelines. IL-6 levels were measured using the enzyme-linked immunosorbent assay. ROS (x10(4) counted photons per minute per 20 x 10(6) sperm) and total antioxidant capacity (molar trolox equivalents) were measured using a chemiluminescence assay. RESULTS: The sperm concentration and motility were significantly greater in the donors compared with the infertile patients with varicocele (P <0.0001 and P = 0.01, respectively). The IL-6 (log10 [IL-6 +1]) and ROS (log10 [ROS +1]) levels were significantly greater in infertile patients with varicocele than in the donors (IL-6: 2.1 [1.7, 2.4] versus 0.7 [0, 1.9], P = 0.003; ROS: 1.8 [1.2, 2.6] versus 1.0 [0.7, 1.6], P = 0.04). The total antioxidant capacity levels were significantly lower in the varicocele patients (1166.7 +/- 366.2) than in the donors (1556.4 +/- 468.1; P = 0.003). The IL-6 levels correlated significantly with the ROS levels in the infertile patients with varicocele (r = -0.39; P = 0.01). CONCLUSIONS: Infertile patients with varicocele exhibited elevated levels of IL-6 and ROS and decreased levels of total antioxidant capacity. Pro-inflammatory cytokine IL-6 and oxidative stress may play a role in the pathophysiology of infertility in these patients.

Chemiluminescence technique for measuring reactive oxygen species.

Accurate assessment of reactive oxygen species (ROS) concentrations may help in the diagnosis of infertility. The chemiluminescence technique, which uses a luminometer to measure ROS, is a common method of assessment. A better understanding of the chemiluminescence technique will allow its proper application in reproductive medicine. A wide range of luminometers are available in the market, and laboratories should select the instruments that suit their individual needs.

Cryopreservation of human spermatozoa: comparison of two cryopreservation methods and three cryoprotectants.

OBJECTIVE: To evaluate the ability of two cryopreservation methods and three cryoprotectants to preserve sperm quality. DESIGN: A prospective clinical study. SETTING: Male infertility clinic at a tertiary healthcare center. PATIENT(S): Twenty infertile men and 10 healthy donors. INTERVENTION(S): In the first experiment, semen was cryopreserved by either the Irvine Scientific method (IS) or the Cleveland Clinic Foundation (CCF) method. In the second experiment, semen was cryopreserved by the IS method and one of three cryoprotectants: TES and Tris yolk buffer, Sperm Freezing Medium, or Enhance Sperm Freeze. MAIN OUTCOME MEASURE(S): Postthaw sperm motility, cryosurvival, and kinematics. RESULT(S): Percentages of postthaw sperm motility and cryosurvival were higher in the IS cryopreservation method compared with in the CCF method (15.94 +/- 9.19 vs. 12.07 +/- 7.31 and 47.42 +/- 17.44 vs. 35.76 +/- 17.56). However, the CCF method resulted in significantly better sperm kinematics. Postthaw motility in the donors and patients was highest in the samples frozen in TES and Tris yolk buffer medium. CONCLUSION(S): The IS method was associated with more flash freezing compared with the CCF method and resulted in better preservation of sperm motility and a higher cryosurvival rate. TES and Tris yolk buffer was most effective at protecting sperm from the negative effects of the cryopreservation process. This may be due to the presence of egg yolk along with glycerol.

Role of free radicals in female reproductive diseases and assisted reproduction.

Infertility is a common problem experienced by many couples. Numerous treatments are available for female infertility. However, in some cases, the treatment is empirical in nature because the aetiology of infertility is not fully understood. Recently, reactive oxygen species (ROS) have been shown to have an important role in the normal functioning of reproductive system and in the pathogenesis of infertility in females. Reactive oxygen species may also play a role in other reproductive organ diseases of women such as endometriosis. Oxidative stress develops when there is an imbalance between the generation of ROS and the scavenging capacity of antioxidants in the reproductive tract. It affects both natural and assisted fertility. Because assisted reproductive techniques are used extensively in the treatment of infertility, it is critical to understand the in-vitro conditions that affect fertilization and embryo development. Treatments that reduce oxidative stress may help infertile women with diseases that are caused by this imbalance. Such strategies include identifying the source of excessive generation of ROS, treating the primary cause, and in-vitro and in-vivo supplementation of antioxidants. Research is in progress to identify the mechanisms that are involved in the aetiology of female reproductive diseases caused by ROS, and to create effective strategies that can counteract oxidative stress.