Prognostic models in end stage liver disease.

Cirrhosis is a major cause of death worldwide, and is associated with significant health care costs. Even if milestones have been recently reached in understanding and managing end-stage liver disease (ESLD), the disease course remains somewhat difficult to prognosticate. These difficulties have already been acknowledged already in the past, when scores instead of single parameters have been proposed as valuable tools for short-term prognosis. These standard scores, like Child Turcotte Pugh (CTP) and model for end-stage liver disease (MELD) score, relying on biochemical and clinical parameters, are still widely used in clinical practice to predict short- and medium-term prognosis. The MELD score, which remains an accurate, easy-to-use, objective predictive score, has received significant modifications over time, in order to improve its performance especially in the liver transplant (LT) setting, where it is widely used as prioritization tool. Although many attempts to improve prognostic accuracy have failed because of lack of replicability or poor benefit with the comparator (often the MELD score or its variants), few scores have been recently proposed and validated especially for subgroups of patients with ESLD, as those with acute-on-chronic liver failure. Artificial intelligence will probably help hepatologists in the near future to fill the current gaps in predicting disease course and long-term prognosis of such patients.

Polyclonal and monoclonal B lymphocytes response in HCV-infected patients treated with direct-acting antiviral agents.

Hepatitis C virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinaemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study, we used flow cytometry to evaluate the effect of interferon-free antiviral treatment on peripheral blood lymphocytes in HCV-infected patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes was performed at baseline and at the end of treatment. In HCV-infected patients with lymphoproliferative disorders, we evaluated immunoglobulin (Ig) light chain κ/λ ratio variations as a measure of monoclonal B-cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, nine with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29 of 29 patients. We observed a significant reduction in the B-cell compartment (39% global reduction) in eight of nine HCV-infected patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV-infected patients without lymphoproliferative disorders (9% global reduction). Among HCV-infected patients with lymphoproliferative disorders, three showed an improvement/normalization of the immunoglobulin light chain ratio, whereas in the remaining six patients monoclonal B cells persisted to be clonally restricted even 1 year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B cells in the peripheral blood of HCV-infected patients affected by HCV-associated lymphoproliferative disorders; however, monoclonal populations can persist after viral eradication.

Early non-invasive selection of patients at high risk of severe hepatitis C recurrence after liver transplantation.

BACKGROUND: The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon (IFN)-free regimens. METHODS: In a retrospective study with prospectively collected data, we investigated whether the use of several non-invasive methods (fibrosis 4 index [FIB-4], AST-to-platelets ratio index [APRI], enhanced liver fibrosis test [ELF], IFN-γ-inducible protein 10 [IP-10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F ≥2) and/or portal hypertension (hepatic venous pressure gradient ≥6 mmHg) 12 months after transplant. Seventy-two hepatitis C virus (HCV)-infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study. RESULTS: The levels of all biomarkers were significantly higher in HCV-infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB-4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved. CONCLUSIONS: Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non-invasive methods.

Liver stiffness 1 year after transplantation predicts clinical outcomes in patients with recurrent hepatitis C.

The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p<0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM<8.7 kPa (p<0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p<0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.

Use of grafts from anti-HBc-positive donors in liver transplantation: a 5-year, single-center experience.

INTRODUCTION: Liver transplantation (OLT) is the treatment of choice for advanced hepatic disease. The growing gap between waiting list patients and the number of donations has led to acceptance of less than optimal donors. The aim of this study was to evaluate the 5-year experience with anti hepatitis B core antigen (HBc)-positive liver donors. PATIENTS AND METHODS: All recipients of anti-HBc-positive grafts from January 2005 to December 2010 were evaluated annually after OLT for liver disease etiology, Model for End-Stage Liver Disease (MELD) score, and the presence of hepatocellular carcinoma (HCC) liver biopsy histology and serology for hepatitis B virus (HBsAg, anti-HBs, HBV-DNA), hepatitis C virus, and hepatitis D virus as well as antiviral prophylaxis to prevent de novo HBV. RESULTS: Among the 249 OLT performed from January 2005 to December 2010, (9.3%) cases used grafts from anti-HBc-positive donors. Etiologics of liver disease among the recipients were HBV (n = 13; 32.5%), HCV (n = 13; 32.5%) or other causes (n = 14; 35%). In 20 of the 40 patients (50%), HCC was found in the explanted organ. Of 40 recipients of anti-HBc-positive grafts 11 died, and 7 (17.5%) required retransplantation. Various regimens were employed as post-transplantation antiviral prophylaxis: (l) Immune globulin (25.8%); (2) Oral antiviral drugs (9.7%); and (3) combined prophylaxis (51.6%) or no treatment (12.9%). No difference was observed in patient or graft survival in relation to the etiology of liver disease, the MELD score, or the presence of HCC at the time of OLT, except graft survival was significantly reduced among recipient who underwent transplantation for non-HBV or non-HCV liver diseases compared with those engrafted due to viral hepatitis (P = .0062). No difference was observed in histologic features (grading and staging) compared with the antiviral prophylactic therapy; the 2 patients (5%) who developed de novo HBV had not received prophylaxis after OLT. CONCLUSIONS: Matching anti-HBc-positive grafts to recipients without HBV infection before OLT, may be especially safe.

Risk factors in liver retransplantation: a single-center experience.

Liver retransplantation (Re-OLT) is one of the most debated issues in medicine over the past decade. Re-OLT, currently is accepted for patients with irreversible failure of a hepatic graft caused by primary nonfunction (PNF), hyperacute/chronic rejection, or hepatic artery thrombosis (HAT); whereas it is still controversial for patients with recurrent viral disease, in particular hepatitis C virus (HCV) cirrhosis. Patient and graft survival rates are lower than those observed after primary liver transplantation (OLT). The aim of the present study was to analyze the risk factors that adversely affect survival after Re-OLT in a single center. Medical data were collected for 23 patients who underwent Re-OLT from November 2002 to December 2008 including six men and seven women of mean age of 51.3 years. The most frequent indications for Re-OLT were: PNF (69.5%; 16/23), HCV recurrence (8.6%; 2/23), or HAT (8.6%; 2/23). Mean Model for End-Stage Liver Disease (MELD) at Re-OLT was 27.7 (range = 9-40). After a mean follow-up of 37.4 ± 30 (standard deviation) months, 43% (10/23) of patients had died, including 70% within the first 2 months after Re-OLT. Sepsis represented the commonest cause of death (40%). Re-OLT was performed for PNF among 90% of succumbing patients. As regards dead patients, 4/10 were HCV(+) whose causes of death were sepsis (n=2), alcoholic cirrhosis (n=2), and undetermined (n=1). Comparing patients who died after liver Re-OLT versus alive patients, we did not find any significant difference in terms of mean MELD (28.6 vs 27; P=NS), MELD > 25 (60% vs 61.5%, P=NS), donor age > 60 years (30% vs 15.3%, P=NS), HCV(+) (40% vs 62%, P = NS), or time interval from OLT to Re-OLT (12.2 vs 777.7 days, P=NS). Patient survivals after Re-OLT were 67% at 3 years and 50% at 5 years, which were lower than those of first transplantations, as reported by other European and International Centers. Forty percent of deaths after Re-OLT occurred among HCV(+) recipients, but for reasons unrelated to HCV infection.

Fibrosis progression and the pros and cons of antiviral therapy for hepatitis C virus recurrence after liver transplantation: a review.

The progression of fibrosis due to hepatitis C virus (HCV) recurrence after liver transplantation (OLT) is faster than in the pretransplant setting, leading to histologically documented cirrhosis within 5 years in 25% to 30% of cases. Whether it is associated with biliary complications or previous alcohol abuse, recurrent HCV is the main cause of graft failure and death after OLT. The most important donor risk factor for HCV recurrence is advanced donor age. The disease's course is even more aggressive if it is associated with anti-HCV positivity or graft steatosis. The type of calcineurin inhibitor does not seem to influence HCV recurrence. Avoiding or slowly tapering steroids has been associated with less disease recurrence, while steroid pulses to treat acute rejection episodes have been associated with a worse progression of fibrosis. Antiviral therapy (AT) is not always recommended in OLT patients, but is of some benefit. Fibrosis has been shown to ameliorate in sustained virological responders to AT and to progress significantly more in nonresponders. Using long-term maintenance, AT has recently been shown to increase the probability of biochemical and histological responses, regardless of the timing of the HCV recurrence. In conclusion, the donor- recipient match should be assessed to limit HCV recurrences and their severity; AT is recommended to reduce or reverse the progression of fibrosis.

Estimation of the harm to the waiting list as a crucial factor in the selection of patients with hepatocellular carcinoma for liver transplantation.

BACKGROUND: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT. METHODS: We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database. RESULTS: Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States. CONCLUSIONS: In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.

Comparison of de novo tumours after liver transplantation with incidence rates from Italian cancer registries.

AIM: The purpose of this study is to describe de novo post-liver transplant malignancies and compare their frequency with incidence rates from Italian cancer registries. PATIENTS AND METHODS: Four hundred and seventeen patients subjected to liver transplantation, from 1991 to 2005, surviving for at least 30 days and without a previous diagnosis of cancer (including hepatocellular carcinoma), were evaluated for the development of de novo malignancies excluding non-melanoma skin cancers. RESULTS: During a total follow-up time of 2856 person-years, 43 de novo malignancies were diagnosed in 43 liver transplantation recipients (10.3%). The most common cancers were non-Hodgkin lymphoma (9 cases), cancer of the head and neck (8 cases), Kaposi's sarcoma (6 cases) and esophageal carcinoma (5 cases). The 1, 3, 5 and 10 years estimated survival rates were 69%, 57%, 53% and 42%. Patients with de novo cancers had a lower 10-year survival rate than patients without cancers (58% versus 76%, p=0.005). The risk of cancer after liver transplantation was nearly 3-fold higher than that of the general population of the same age and sex (95% CI: 1.9-3.6). De novo tumour sites or types with significantly elevated SIR included Kaposi's sarcoma (SIR=144), non-Hodgkin lymphoma (SIR=13.8), esophagus (SIR=23.4), head and neck cancers (SIR=7) and cervix uteri (SIR=30.7). CONCLUSIONS: Tumours after liver transplantation are associated with lower long-term survival, confirming that cancer is a major cause of late mortality in liver transplantation.

Prospective validation of a new priority allocation model for liver transplant candidates: an interim analysis.

BACKGROUND: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results. METHODS: We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of >or=20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study. RESULTS: Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of >or=20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05). CONCLUSIONS: We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.

Risk of Kaposi sarcoma after solid-organ transplantation: multicenter study in 4,767 recipients in Italy, 1970-2006.

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.

Progression of hepatocellular carcinoma before liver transplantation: dropout or liver transplantation?

BACKGROUND: Tumor progression before liver transplantation (OLT) is the main cause of dropout from the waiting list (WL) of patients with hepatocellular carcinoma (HCC). The aim of this study was to show a correlation between adopted dropout criteria and dropout/intention-to-treat survival rates of WL HCC patients. METHODS: The study period was 2000 to 2007. The dropout criteria were macroscopic vascular invasion, metastases, or a poorly differentiated tumor. Adult patients with benign chronic liver disease enlisted for primary OLT in the same period represented the control group. RESULTS: Dropout probability of study (n = 128) versus control group (n = 377) subjects was similar: namely, 12% at 1 year in both groups (P = NS). Intention-to-treat survival curve of the HCC group overlapped that of the benign group (5-year survival rates were 73% and 71%, respectively; P = NS). At the time of listing, 103 study group patients were within the Milan criteria (MC): among these patients, 29 (28%) showed tumor progression beyond MC before OLT. Simulating the dropout of these 29 patients at the time of diagnosis of tumor progression, we compared the dropout probability of the 103 patients within MC with that of the control group. As a result, the 1- and 2-year dropout rates became 37% and 53%, respectively, in the study group, which were significantly higher than those in the controls (P < .01). CONCLUSION: HCC patients on the WL showed a significantly greater dropout rate than subjects with benign cirrhosis when too restrictive radiologic dropout criteria were used. The adoption of criteria more related to biological aggressiveness of a tumor decreased the dropout risk for HCC patients without impairing their intention-to-treat survival rates.

De novo tumors are a major cause of late mortality after orthotopic liver transplantation.

The purpose of this study was to describe de novo post-orthotopic liver transplantation (OLT) malignancies for comparison with incidence rates in Italian cancer registries. Three hundred thirteen OLT patients engrafted from 1991 to 2006 and surviving 12 months without a previous diagnosis of cancer were evaluated for the development of de novo malignancies excluding nonmelanoma skin cancers. During a total follow-up time of 1753 PYs, 40 (12.8%) de novo malignancies were diagnosed in 40 recipients. The most common cancers were non-Hodgkin lymphoma (NHL; 20%), cancer of the head and neck (17%), Kaposi sarcoma (KS; 17%), and esophageal tumors (12%). The 1-, 3-, 5-, and 10-year estimated survival rates were 70%, 56%, 48%, and 39%. Patients with de novo cancers showed a lower 10-years survival rate (P = .0047) than patients without (39% vs 75%). The risk of cancer after OLT was 3-fold higher than that of the general population of the same age and gender (95% confidence interval [CI], 2.0-4.3). De novo tumor sites or types with significantly elevated standardized incidence ratios (SIRs) included KS (SIRs = 212), NHL (SIRs = 13.7), oesophagus (SIRs = 18.7), melanoma (SIRs = 10.1), and head and neck cancers (SIRs = 4.6). Tumors after OLT were associated with lower long-term survival, confirming that cancer is a major cause of late mortality.

HCV histological recurrence and survival following liver transplantation in patients with and without hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatitis C virus (HCV)-related cirrhosis is one of the leading indication for liver transplantation (LT) and a major risk factor for the development of hepatocellular carcinoma (HCC). HCV recurrence after LT is universal. This study evaluated HCV recurrence and survival in patients transplanted for HCV and HCC. METHODS: We evaluated all adults transplanted for HCV cirrhosis between January 1999 and December 2006, HCC was diagnosed on the explant and HCV recurrence confirmed on protocol liver biopsies performed at 6 months and yearly after LT. The sustained viral response (SVR) was defined as HCV-RNA undetectable at 6 months after therapy discontinuation. The patient survival rates were assessed with Kaplan-Meier curves and the chi-square test was used when appropriate. RESULTS: Two hundred sixteen patients underwent LT for HCV including 153 men and 63 women of mean age 54 years with a mean follow-up of 35 months. There were 71 (33%) HCC(+) patients. At 1, 3, and 5 years from LT severe fibrosis (Scheuer 3-4) due to the HCV recurrence was reported in 18%, 14%, and 11% for HCC(+) and 14%, 16%, and 28% for HCC(-) patients respectively (P=NS). HCC recurred only in 3 (4%) patients at a mean follow-up of 3 years. Patients who received antiviral treatment after LT were 10% HCC(+) and 12% HCC(-) patients (P=NS). SVR was seen in 3/7 (43%) of HCC(+) and in 10/18 (55%) of HCC(-) patients (P=NS). At 1, 3, and 5 years the patient survivals was 91%, 86%, and 86% for HCC(+) and 94%, 86%, and 83% for HCC(-) patients, respectively (P=NS). CONCLUSIONS: Severe fibrosis due to HCV recurrence, which increases over time, involves one third of transplanted patients at 5 years after LT. The long-term survival was identical among HCC(+) compared to HCC(-) recipients. The recurrence of HCC was negligible and did not affect patient survival.

Algorithm for prioritization of patients on the waiting list for liver transplantation.

UNLABELLED: Prioritization of patients on the waiting list (WL) for OLT is still a critical issue. Numerous models have been developed to predict mortality before and after OLT. AIM: The aim of the study was to prospectively evaluate cirrhotics with and without hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) severity of liver disease on the WL and at transplant, mortality on the WL and after OLT, and their correlations. MATERIALS AND METHODS: An algorithm based on seven patient variables (MELD, CTP, UNOS, HCC, BMI, waiting time, age) was created by software dedicated to prioritize patients on the waiting list. RESULTS: We evaluated 118 patients including 75 men and 43 women of age range 19 to 66 years, who underwent OLT from July 2004 to June 2006. Mean CTP and MELD at listing were 8.44 (range 6-12) and 13 (range 2-24), respectively. Overall mortality on the WL at 24 months was 13%, which was significantly higher among patients with MELD > 25 compared to patients with MELD 0 to 15 (P < .0001) or MELD 16 to 25 (P = .0007) at listing. Mean MELD at OLT was 15 (range 7-36), which was significantly lower in patients with than without HCC (MELD 12 vs 16; P = .0003). Six hundred-day patient survival was significantly lower among patients with MELD > 25 compared to patients with MELD < 25 at OLT (P = .017), whereas no difference in survival was observed between patients with and without HCC. CONCLUSIONS: The sickest patients are characterized by high mortality both on the waiting list and after liver transplantation. Patients with HCC are transplanted in better condition compared to patients without HCC with the same survival.

The role of computerized axial tomography in the follow-up of patients with carcinoma of the ovary.

In order to assess the accuracy of CAT in the follow-up of the patients affected by ovarian carcinoma, we compared the results of this method to those of second-look laparotomy in 19 patients. In 16 out of 19 patients the CAT showed the presence or absence of disease correctly. There were 3 false negatives, caused by small diffuse peritoneal metastases, and no false positives. The results of this study show that CAT, though useful in studying the evolution of abdominal and pelvic carcinomas, cannot replace the surgical second-look in cases of ovarian cancers, due to the high incidence of false negatives.

Vulvar lesions at risk. Prevention, clinical methodology and therapy.

In confronting the problem of prevention and early diagnosis of vulvar lesions at risk, the diagnostic methodology for their recognition and the therapeutic measures best taken are discussed. Through the use of routine, ambulatory screening tests, it is possible to detect and recognize those pathological situations which may evolve towards neoplasia. Among these, the vulvar dystrophies, some viral infections and sexually-transmitted diseases are particularly at risk. Patients with oncologic precedents are also at risk as well as patients receiving immunosuppressive therapy.

Topical testosterone propionate in the therapy of vulvar dystrophies.

187 patients with atrophic, hypertrophic and mixed vulvar dystrophy were treated with 2% testosterone propionate ointment from 18 months to 7 years. Symptoms, macroscopic, and histologic picture were evaluated before and during treatment. About 75% of the patients achieved good and excellent symptom relief. Treatment efficacy differentiates according to the type of dystrophy, and in relation to the lesion's extension and the duration of symptoms, which consist mostly of pruritus. Side effects from therapy were negligible.

Hormone receptors in dystrophic and neoplastic vulvar disease. Preliminary considerations.

Hormone receptor assays for testosterone, estrogens and androgens were performed on 53 biopsy specimens of vulva from 40 patients, consisting of 6 with normal tissue, 14 with atrophic type dystrophy, 13 with hypertrophic type dystrophy, and 20 with malignancy. Atrophic and hypertrophic forms showed a different receptor pattern; hypertrophic forms were characterized by consistently higher levels of progesterone receptors not correlated with estrogen receptors. Neoplastic tissue showed no significant changes in values compared to normal or dystrophic forms, but range of variability was high. The bond between neoplastic forms and hormone activity seems without doubt less important than in the corresponding endometrial and mammary forms. The study of dystrophic forms, instead, should be further explored with a larger number of cases.

Vulvar neoplasias in patients with previous cancer history.

The presence of second neoplasia in association with vulvar neoplasia is significant. We confirm the usefulness of including a screening procedure for vulvar neoplasia in the follow-up of patients with gynecological cancer, especially those with carcinoma of the portio. Patients with a first gynecological neoplasia who present vulvar viral infection, or dystrophies, or who have undergone radiotherapy or immunosuppressive treatment are considered at high risk.