Hypogonadism and liver fibrosis in HIV-infected patients.

PURPOSE: Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. METHODS: We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. RESULTS: Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. CONCLUSION: Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

Expanded Criteria Donor Kidney Transplantation: Comparative Outcome Evaluation Between Single Versus Double Kidney Transplantation at 8 Years: A Single Center Experience.

Transplantation of kidneys retrieved from expanded criteria donors is one of the options to expand the pool of available grafts, shorten the waiting time and increase the number of kidney transplant recipients. This study was a retrospective assessment of 99 patients who underwent renal transplantation during the period 2007-2015 with kidneys harvested from expanded criteria donors (ECD) as defined by the United Network for Organ Sharing (UNOS) following routine biopsy of all kidneys obtained by Karpinsky Score. They formed two groups: SKT (67 recipients that received a single kidney) and DKT (32 patients that received dual kidney transplant). An analysis of differences of two groups between graft and patient survival and graft function were performed after 8 years of observation. We observed between two groups the following statistical differences: Donor age (P < .001), basal high risk of recipients (P < .05), wait time before transplant (P < .05), recipient age (P < .001) delayed graft function (P < .005) while we observe similar values of donor renal function, outcome in graft and patient survival and graft function in recipients. The transplantation of kidneys obtained from expanded criteria donor, allows increase in the number of kidney transplants and in the respect of values of biopsy score and the donor renal function, showed in single or dual kidney transplantation with similar graft and patient survival.

"Intestinal-type" mucinous adenocarcinoma of the vulva: a report of two cases.

BACKGROUND: "Intestinal-type" mucinous carcinoma of the vulva is extremely rare with very few cases reported in the literature. CASE REPORT: The authors report two patients who had diagnosis of intestinal-type mucinous adenocarcinoma of the vulva after excisional biopsy. In both cases, restaging was perfomed with total body computed tomography (CT) scan, gastroscopy, and colonoscopy that showed no other site of disease. A radical vulvectomy with bilateral systematic inguinal lymphadenectomy was performed, and in both cases no residual disease was found. A patient developed metastatic (liver, bone marrow) colonic cancer 36 months after primary surgery, received multiple lines of chemotherapy, and died of disseminated disease 18 months after diagnosis. The other patient was found to have dysplastic polyp in the sigmoid colon, and is alive without disease at 39 months after primary diagnosis. CONCLUSION: Intestinal-type mucinous carcinoma of the vulva has a poor prognosis. Strict endoscopic follow-up of the colon is mandatory in such cases, considering the high propensity of associated gastrointestinal (GI) tumors.

Frequency of human papillomavirus infection and genotype distribution among women with known cytological diagnosis in a Southern Italian region.

INTRODUCTION: In the Puglia region (South Italy) about 200 new hospitalizations for cervical cancer are registered every year. The study investigated the frequency of Human Papillomavirus (HPV) infection and the genotype distribution of HPV in a sample of women with known cytology attending the outpatient clinics of four Gynecological Departments of the University of Bari over a four-year period (2005-2008). METHODS: Cervical samples from 1,168 women were analyzed for the presence of HPV-DNA through Polymerase Chain Reaction (PCR) in L1 region and reverse hybridization. The cytological results were associated with HPV positivity and type-specific prevalence. RESULTS: Overall, HPV infection was found in 355 (30.4%) women. HPV-DNA was found in 34.4% of women with a cytological diagnosis of ASCUS, in 46.8% of women with Low-grade Squamous Intraepithelial Lesion (LSIL) and in 87.0% of women with High-grade Squamous Intraepithelial Lesion (HSIL)/carcinoma. Also 16.0% of women with normal Pap smear were found to be HPV-DNA positive. The most common HPVgenotype was type 16 found in 27.3% of positives, followed by type 53 (11.5%), type 66 (9.2%) and type 31 (9.0%). HPV genotype 18 was found in 6.4% of positives. Types 16 or 18 were detected in about 34% (120/355) of all infected women, in about 33% of LSIL and in 60% of HSIL/ carcinoma HPV-positive women. Among low risk (LR) genotypes, type 61 was found in 10.7% of HPV positive women, type 62 in 8.4%, type 42 in 8.1% and type CP6108 in 7.8%. DISCUSSION AND CONCLUSIONS: The findings of the study give evidence that HPV infection is frequent in the studied cohort of women. The most widespread genotypes found were 16 and 53. These data may represent a benchmark for future evaluation after the recent introduction of vaccination against HPV in 12-year-old girls.

Groin recurrence in carcinoma of the vulva: management and outcome.

The aim of the study was to investigate the management and outcome of inguinal recurrence in vulvar carcinoma patients. A retrospective chart review was conducted on 140 patients with squamous cell carcinoma of the vulva treated between 1994 and 2006. Twenty-one patients were found to have groin recurrence. Median interval between primary treatment of vulvar cancer and groin recurrence was 7 months. Three patients refused any treatment, 3 received chemotherapy, 2 inguino-pelvic radiotherapy and 13 had resection of the groin recurrence. After surgery seven patients received irradiation of the groin and pelvis, and three patients received chemotherapy. One patient died following surgery; 19 patients died of disease with the median survival after diagnosis of inguinal recurrence of 9 months. Only one patient is alive without evidence of disease at 60 months following surgery. In univariate analysis, stage and grade at diagnosis, age and performance status at the recurrent disease, and the extent of residual tumour after resection of groin recurrence were predictors for survival. Groin recurrences from vulvar carcinoma carry a poor prognosis. Multi-modal treatment may result in a palliation of the disease, and a very limited number of patients have long-term survival.

Locally advanced cervical cancer associated with complete uterine prolapse.

Although uterine prolapse and carcinoma of the uterine cervix are not rare event, their association is very uncommon. An 86-year-old patient gravida 8, para 5 was admitted for vaginal bleeding from a uterine prolapse of 20 years of duration. On physical examination, a complete third-degree prolapsed uterus with an ulcerated lesion of 12 cm in maximum diameter involving both the anterior and posterior lips of the cervix was observed. Because of the poor performance status and high American Society of Anesthesiology scoring, the patient was admitted for a vaginal hysterectomy with upper vaginectomy in spinal anesthesia. However, she died of pulmonary embolism 20 days after surgery. A case of a cervical cancer with a complete uterine prolapse of 20 years of duration is reported. We believe that this case typically rare to see in a developed country might be a useful addition to the few published reports.

Spleen involvement in women with ovarian cancer.

The aim of this study was to determine the prognostic factors of spleen metastases in ovarian cancer. A retrospective chart review was conducted and ten patients with spleen metastases were evaluated. Eight were Stage III, one Stage I and one Stage IV. One patient had a spleen metastasis at the time of ovarian cancer diagnosis, whereas, the remaining patients 23.4+12 months after ovarian cancer diagnosis. Spleen involvement is a late complication that rarely occurs in ovarian cancer and confers a poor prognosis. The interval time between ovarian cancer diagnosis and appereance of spleen involvement is the most important prognostic factor.

Is there a role for neoadjuvant chemotherapy in early invasive cervical carcinoma?

OBJECTIVE: The purpose of this study was to determine if a survival advantage may exist from neoadjuvant chemotherapy (NACT) followed by radical surgery in early invasive (Stage IB1 and IIA) cervical carcinoma. METHODS: Using information from studies published on the topic of NACT in cervical carcinoma along with baseline control rates of standard treatment and patterns of failure, an estimate of how many patients with early invasive cervical cancer would benefit from this procedure was calculated. RESULTS: NACT followed by tailored radical surgery could result in a significant decrease (about 40%) in recurrence rate (13 vs 22%) and ultimately in survival compared to conventional treatment in early invasive cervical cancer. Moreover the introduction of NACT in all patients should result in a 75% decrease of adjuvant radiotherapy (10 vs 40%), and probably in a decrease in surgical and radiation related complications. CONCLUSION: A fraction of patients with early invasive cervical cancer (high-risk Stage IB-IIA cervical cancer) could benefit from NACT followed by tailored radical surgery. A randomized controlled trial to test this research question is very difficult due to the large population required. A subset population is identified which may benefit from NACT.

Conservative management of uterine leiomyosarcoma: report of a failure.

BACKGROUND: Conservative management of uterine leiomyosarcoma has rarely been reported in the literature. CASE REPORT: A 26-year-old woman was diagnosed with uterine leiomyosarcoma after resection of a 11 cm uterine mass. Conservative management was proposed, demolitive surgery was not performed and the patient received four courses of chemotherapy. Four months after completion of chemotherapy the patient developed a local recurrence and died of disease 48 months after the primary diagnosis. CONCLUSION: Reporting a failure after conservative management of uterine leiomyosarcoma is important in order to try to evaluate correct indications for fertility-sparing surgery.

Ovarian cancer in the elderly: feasibility of surgery and chemotherapy in 89 geriatric patients.

Gynecological oncologists are faced with an increasing proportion of geriatric ovarian cancer patients. Comorbidities are frequently a matter of concern in this age group, and what is adequate treatment for such patients is still debated. The aims of this study were to analyze the feasibility of standard surgery and chemotherapy in a series of elderly ovarian cancer patients (>/=70 years) and to investigate the influence of age (70-75 vs >75 years) on survival. We retrospectively evaluated 89 elderly patients treated at our department between 1985 and 2005. Comorbidities, type of surgical procedure, complications, drugs and schedules of chemotherapy, number of cycles, toxicity, and clinical outcome were registered. Comorbidities were present in 71.9%. Only six patients were inoperable. Among the 83 patients who underwent surgery, 76.4% received adequate surgical treatment. Severe postoperative complications occurred in 16.8%, operative mortality was zero. A total of 801 cycles of chemotherapy were administered to 77 patients (median 10; range 1-38). Overall, G3-G4 toxicity was documented in 61.0%. The rates of dose reduction, treatment delay, and discontinuation were 13.0%, 20.7%, and 3.9%, respectively. Patients who received adequate surgery and those with residual disease <1 cm did significantly better than their counterparts (P= 0.04 and P < 0.001, respectively). No difference in survival according to age (70-75 vs >75 years) was found. Standard surgery and chemotherapy were feasible in elderly ovarian cancer patients. The type of surgery and the amount of residual disease, but not the age of the patients, significantly influenced the clinical outcome.

Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a marker for potential molecularly targeted treatment?

Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better disease-free survival (P= 0.004) and actuarial survival (P= 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.

Cervical squamous intraepithelial lesions of low-grade in HIV-infected women: recurrence, persistence, and progression, in treated and untreated women.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are more predisposed than HIV-negative women to develop squamous intraepithelial lesions (SIL) of the uterine cervix, and cervical dysplasia may be of higher grade in HIV-positive women than in HIV-negative subjects, with more extensive and multi-centric involvement of the lower genital tract by human papillomavirus (HPV)-associated lesions. Moreover, recurrence and progression rate of cervical intraepithelial neoplasia (CIN) is particularly higher in immunocompromised women. DESIGN: Retrospective case-control study of HIV-positive women and HIV-negative controls, all affected by low-grade SIL of the uterine cervix, treated by loop excision or followed-up without treatment. Correlation of progression and recurrence of SIL with HIV status and CD4+ count. PATIENTS: From September 1990 to October 1997, 75 HIV-positive low-grade-SIL patients, 47 treated and 28 followed-up without treatment, and 75 HIV-negative low-grade-SIL controls, 45 treated and 30 followed-up. RESULTS: Among treated patients, 17/47 (36.2%) HIV-positive and 5/45 (11.1%) controls had recurrence (P < 0.0101, O.R. = 4.53, 95% CI = 1.5-13.7), progression of untreated lesion was seen in 15/28 (53.6%) HIV-positive and 7/30 (23%) controls (P < 0.05, O.R. = 3.79, 95% CI = 1.23-11.69). The risk of recurrence or progression of low-grade SIL linked to HIV seropositivity is about 4-5 times higher in comparison with seronegative counterpart, matched for age, risk factors and lesion size. More significantly, considering the cut-off of 200 CD4+/mm(3) in HIV-positive women, 13/17 cases of recurrence (P < 0.05, O.R. = 4.88, 95% CI = 1.28-18.58) and 10/15 cases with progression (P < 0.05, O.R. = 6.67, 95% CI = 1.24-35.73) were immunocompromised (<200 CD4+/mm3), with a significant higher risk of recurrence or progression linked to immunodeficiency status. Considering time of progression or recurrence, during follow-up, Kaplan-Meier curves shows that HIV-positive status and immunodeficiency are correlated with more rapid evolution of cervical dysplasia and HPV-related lesions: comparison of recurrence in treated patients report P < 0.005 and progression in untreated P<0.05 (Mantel-Haenszel log-rank test). CONCLUSIONS: Immunological status seems to be a determinant factor in prognosis of cervical SIL, HIV-positive women affected by this lesion, even if low-grade, need more aggressive management than the immunocompetent counterpart. Strict cytologic and colposcopic screening is recommended and CD4+ count and HPV-DNA testing may be useful risk indicators. Excisional procedures are preferred, while ablative treatments or wait and see policy may expose to some risk this type of population with poor compliance to follow-up.

Rapid growth of myxoid leiomyosarcoma of the vulva during pregnancy: a case report.

Smooth muscle tumors arising in the vulva are rare. Leiomyosarcoma is the most common variant of vulvar sarcoma, and very few cases have been reported during pregnancy. A 36-year-old woman presented with a progressively enlarging vulvar mass during pregnancy, diagnosed as a Bartholin's gland cyst. The lesion was resected at 38 weeks of gestation during cesarean section and diagnosis of myxoid leiomyosarcoma of the vulva was made. Six weeks later the patients were referred to our center and submitted to wide vulvar excision with groin lymph node dissection that revealed the presence of a small residual focus of leiomyosarcoma. At 30 months of follow-up the patient was well without any sign of recurrent disease. Leiomyosarcoma should be included in the differential diagnosis of vulvar masses; progressively enlarging vulvar lesion should be biopsied even during pregnancy. Leiomyosarcoma should be considered in the differential diagnosis of vulvar mass.

Evaluation of functional ovarian reserve in 60 patients.

Diminished ovarian reserve is a condition occurring in women at any adult age, although it is more frequent in women in their 30s and in couples with unexplained subfertility. Different tests are employed to diagnose the problem. The most common are basal tests for FSH, LH, oestradiol and inhibin B, or dynamic endocrine tests such as the clomiphene citrate challenge test and gonadotrophin analogue stimulating test. In recent years, great attention has been devoted to direct tests such as the antral follicle count and ovarian biopsy results. The basal FSH concentration is the most common test utilized for ovarian screening. An abnormal value is correlated with a decrease in pregnancy rate and an increase in cycle cancellation rate. Among other basal endocrine tests, inhibin concentrations appear promising, although more data are necessary before this can be included in clinical practice. The clomiphene citrate challenge test can unmask patients who might have not been detected by basal FSH screening alone, and appears to be more sensitive than day 3 FSH alone. A prospective study was performed on the simultaneous application of various markers of ovarian reserve (FSH, LH, oestradiol, inhibin B, antral follicle count) in the natural cycle preceding assisted reproductive therapy, in 60 women. The present study suggests that counting ovarian follicles by ultrasound appears, at the moment, the most reliable test of ovarian reserve, although it is influenced by subjective factors and more studies are needed in order to confirm its predictive value.

The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial.

BACKGROUND: A traditional asiatic phytoestrogen-rich diet is associated with a lower incidence of estrogen-dependent cancers and clinical consequences of postmenopausal estrogen deficiency. First Wilcox in 1990, showed an increase of the vaginal cell maturation with phytoestrogens on postmenopausal women, but this has not been confirmed in some subsequent studies. METHODS: In this study, we analyzed the effects of a 6-month soy-rich diet on the vaginal epithelium of asymptomatic postmenopausal women in a randomized clinical trial. 187 women were recruited for the study and divided into three groups: a phytoestrogen rich diet group; a hormonal replacement group, and a control group. A vaginal sample for hormonal cytology was taken before and at the end of the study, and sent unnamed to a cytologist. RESULTS: The karyopycnotic index (KI) increased significantly in the diet group and in the HRT group but not in the control group. The maturation value (MV) had an identical trend to the KI. CONCLUSION: We conclude that a soy rich diet is efficacious in increasing the maturation indices of vaginal cells. This effect could be a useful marker of the efficacy of a dietary intervention with phytoestrogen rich foods, and should be considered during preventive interventions against menopausal effects and vaginal atrophy.

Ultra short-term antimicrobial prophylaxis in patients undergoing surgery for gynecologic cancer.

OBJECTIVE: To evaluate the efficacy of ultra short-term antimicrobial prophylaxis with ceftazidime in patients undergoing radical gynecologic surgery. PATIENTS AND METHODS: Two hundred patients undergoing surgery for a malignant disease of the female genital tract were enrolled in a prospective trial to receive 2.0 g ceftazidime as a single dose, 30 minutes before induction of anaesthesia. After surgery, each patient was assessed to confirm febrile status and the presence of infections at the surgical site, urinary tract and respiratory tract. RESULTS: Postoperative morbidity occurred in 23 patients (11, 5%). Ten patients (5%) developed febrile morbidity, five (2, 5%) vaginal cuff infections, four asymptomatic bacteriuria and two each wound infiltration and urinary tract infection. Twelve patients had microbiological evidence of infection and Staphylococccus aureus was the most common pathogen isolated. Univariate analysis demonstrated that pre-existing systemic disease, extensive blood loss (more than 500 ml) and long duration of surgery (more than 150 minutes) were the only factors associated with a significant increase in postoperative febrile morbidity. CONCLUSIONS: Ultra short-term antimicrobial prophylaxis with ceftazidime is safe and effective in patients undergoing surgery for gynecologic cancer.

Uterine cavity assessment in infertile women: comparison of transvaginal sonography and hysteroscopy.

OBJECTIVES: To evaluate the diagnostic accuracy of transvaginal sonography (TVS) in detecting uterine cavity abnormalities in infertile patients, with reference to hysteroscopy as the gold standard method. STUDY DESIGN: At the Institute of Obstetrics and Gynaecology, University of Bari, 134 infertile women were investigated with both TVS and hysteroscopy. In all cases endometrial biopsy was performed. Sensitivity, specificity, and positive and negative predictive values were calculated for TVS, considering hysteroscopic diagnosis as the gold standard. Statistical analysis was performed by using McNemar test. RESULTS: There was one failed insertion of hysteroscope. Hysteroscopy diagnosed pathological findings in 58 out of 133 cases (44%). TVS was in agreement with 50 of the 58 (86%) of the pathological findings diagnosed at hysteroscopy. As a test for the detection of uterine cavity abnormalities, TVS in comparison with hysteroscopy had 84.5% sensitivity and 98.7% specificity, 98.0% positive predictive value and 89.2% negative predictive value. CONCLUSIONS: TVS is able to diagnose polyps, septum and submucous fibroids with quite significant accuracy, while hysteroscopy is indicated for their confirmation and removal. Thus, hysteroscopy provides both diagnostic and therapeutic capabilities, but TVS permits to proceed directly to operative hysteroscopy avoiding the need for a separate diagnostic procedure.

Avoiding early postoperative complications in liver surgery. A multivariate analysis of 254 patients consecutively observed.

BACKGROUND: The number of hepatic resections for benign and malignant lesions has constantly increased over the past 20 years, as a consequence, surgical experience acquired over the past few years has decreased post-operative morbidity and mortality rates. AIMS: Analysing the relation between potential preoperative risk factors and the occurrence of severe post-operative complications, an attempt is made to identify the variables determining surgical risk in elective hepatic surgery both in normal and cirrhotic liver. PATIENTS AND METHODS: The hospital records of 254 patients who underwent elective liver surgical procedures for hepatic lesions in our department, between 1984 and 1999, were reviewed. The following variables were entered into univariate and multivariate analysis: age, sex, nature of liver lesion (benign or malignant), presence of cirrhosis or cholestasis, synchronous resection of other organs, disorders of blood coagulation, intraoperative blood requirement, the extent of surgical procedures and Pringle's manoeuvre. RESULTS AND CONCLUSIONS: The multivariate analysis of the 254 surgical operations on the liver indicates that the most powerful independent predictors favouring a serious adverse effect includes intra-operative blood transfusions, advanced age and cirrhosis. Scrupulous preoperative clinical evaluation and expert surgical skills minimize intra-operative bleeding and proved to be the most significant factors influencing morbidity and mortality rates.

Malignant mixed mullerian tumor of the ovary: report of four cases.

INTRODUCTION: Malignant mixed mullerian tumor (MMMT) of the ovary is an extremely rare gynaecologic neoplasm that represents 1% of the malignances of this organ. Stage I disease is rare because it is asymptomatic in early stage. We describe four cases. CASE REPORTS: In the Department of Obstetrics and Gynecology of the University of Bari four cases of MMMT of the ovary were diagnosed. Three patients were in stage IIIC and one of them was a homologous MMMT; the fourth patient was affected by a heterologous stage IV MMMT. All women were treated with surgery and chemotherapy. Two patients are alive 14 and 12 months after diagnosis. The other two died after 37 months and one month, respectively. CONCLUSIONS: The malignant mixed mullerian tumor (MMMT) of the ovary is a particularly aggressive tumor, especially in advanced stages. The survival rate is very low in spite of surgery, chemotherapy and radiotherapy. The optimal treatment for this neoplasm is unknown because of its rarity. Our experience, when considering survival, seems to confirm the use of cisplatin and ifosfamide and to give new horizons to taxol.