Effectiveness and safety of dolutegravir two-drug regimens in virologically suppressed people living with HIV: a systematic literature review and meta-analysis of real-world evidence.

OBJECTIVES: Dolutegravir (DTG) is widely recommended within three-drug regimens. However, similar efficacy and tolerability have also been achieved with DTG within two-drug regimens in clinical trials. This study evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV). METHODS: This was a one-arm meta-analysis utilizing data from a systematic literature review. Data from real-world evidence studies of DTG + RPV and DTG + 3TC were extracted, pooled and analysed. The primary outcome was the proportion of patients with viral failure (VF; ≥ 50 copies/mL in two consecutive measurements and/or ≥ 1000 copies/mL in a single measurement) at week 48 (W48) and week 96 (W96). Other outcomes included virological suppression (VS; < 50 copies/mL) and discontinuations (W48 and W96). Estimates were calculated for VF, VS as per snapshot (VSS) and on treatment analysis (VSOT), and discontinuations. RESULTS: Pooled mean estimates of VF for DTG + 3TC and DTG + RPV were 0.8% [95% confidence interval (CI): 0.4-1.3] and 0.6% (95% CI: 0.0-1.6), respectively, at W48. VSS rate at W48 was 85.0% (95% CI: 82.3-87.5) for DTG + 3TC regimen and 92.4% (95% CI: 85.0-97.7) in the DTG + RPV regimen. The DTG + 3TC and DTG + RPV regimens led to discontinuations in 13.6% (95% CI: 11.1-16.2) and 7.2% (95% CI: 2.1-14.4) of patients, respectively, at W48. Similar results were observed at W96. CONCLUSIONS: Treatment with DTG + 3TC or DTG + RPV in clinical practice provides a low rate of VF and a high rate of VS when initiated in virologically suppressed PLHIV with diverse backgrounds.

Pregnancies in older women living with HIV in the UK and Ireland.

OBJECTIVES: The aim of the study was to compare maternal characteristics and pregnancy outcomes in women aged < 40 years and ≥ 40 years in a large unselected population of HIV-positive women delivering in the UK and Ireland between 2000 and 2014. METHODS: Comprehensive population-based surveillance data on all HIV-positive pregnant women and their children seen for care in the UK and Ireland are collected through the National Study of HIV in Pregnancy and Childhood. All singleton and multiple pregnancies reported by the end of June 2015 resulting in live birth or stillbirth to women diagnosed with HIV infection before delivery and delivering in 2000-2014 were included. Logistic regression models were fitted in analyses examining the association between older maternal age and specific outcomes (preterm delivery and stillbirth). RESULTS: Among 15 501 pregnancies in HIV-positive women, the proportion in older women (≥ 40 years) increased from 2.1% (73 of 3419) in 2000-2004 to 8.9% (510 of 5748) in 2010-2014 (P < 0.001). Compared with pregnancies in younger women, those in older women were more likely to result in multiple birth (3.0 vs. 1.9% in younger women; P = 0.03), stillbirth (adjusted odds ratio 2.39; P = 0.004) or an infant with a chromosomal abnormality (1.6 vs. 0.2%, respectively; P < 0.001). However, there was no increased risk of preterm delivery, low birth weight or mother-to-child HIV transmission among older mothers. CONCLUSIONS: There has been a significant increase over time in the proportion of deliveries to women living with HIV aged ≥ 40 years, which has implications for pregnancy management, given their increased risk of multiple births, stillbirth and chromosomal anomalies, as also apparent in the general population.

Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study.

OBJECTIVE: To investigate the association between duration of rupture of membranes (ROM) and mother-to-child HIV transmission (MTCT) rates in the era of combination antiretroviral therapy (cART). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) undertakes comprehensive population-based surveillance of HIV in pregnant women and children. SETTING: UK and Ireland. POPULATION: A cohort of 2398 singleton pregnancies delivered vaginally, or by emergency caesarean section, in women on cART in pregnancy during the period 2007-2012 with information on duration of ROM; HIV infection status was available for 1898 infants. METHODS: Descriptive analysis of NSHPC data. MAIN OUTCOME MEASURES: Rates of MTCT. RESULTS: In 2116 pregnancies delivered at term, the median duration of ROM was 3 hours 30 minutes (interquartile range, IQR 1-8 hours). The overall MTCT rate for women delivering at term with duration of ROM ≥4 hours was 0.64% compared with 0.34% for ROM <4 hours, with no significant difference between the groups (OR 1.90, 95% CI 0.45-7.97). In women delivering at term with a viral load of <50 copies/ml, there was no evidence of a difference in MTCT rates with duration of ROM ≥4 hours, compared with <4 hours (0.14% for ≥4 hours versus 0.12% for <4 hour; OR 1.14, 95% CI 0.07-18.27). Among infants born preterm with infection status available, there were no transmissions in 163 deliveries where the maternal viral load was <50 copies/ml. CONCLUSIONS: No association was found between duration of ROM and MTCT in women taking cART. TWEETABLE ABSTRACT: Rupture of membranes of more than 4 hours is not associated with MTCT of HIV in women on effective ART delivering at term.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

British HIV Association and Children's HIV Association position statement on infant feeding in the UK 2011.

To prevent the transmission of HIV infection during the postpartum period, the British HIV Association and Children's HIV Association (BHIVA/CHIVA) continue to recommend the complete avoidance of breast feeding for infants born to HIV-infected mothers, regardless of maternal disease status, viral load or treatment.

Pregnancy in HIV-infected teenagers in London.

OBJECTIVE: The aim of the study was to describe pregnancies in HIV-infected teenagers. METHODS: A review of the case notes of HIV-infected pregnant teenagers aged 13-19 years from 12 London hospitals was carried out for the period 2000-2007. RESULTS: There were 67 pregnancies in 58 young women, of whom one was known to have acquired HIV vertically. The overall mother-to-child transmission (MTCT) rate of HIV was 1.5% (one of 66). There were 66 live births. Median ages at HIV diagnosis and conception were 17 and 18 years, respectively. Sixty-three per cent of women were diagnosed with HIV infection through routine antenatal screening. Eighty-two per cent of pregnancies (41 of 50) were unplanned, with 65% of women (26 of 40) using no contraception. Forty-three per cent of the women (20 of 46) had a past history of a sexually transmitted infection (STI). In 63 pregnancies, antiretroviral therapy was started post-conception, with prevention of HIV MTCT the only indication in 81% of cases. Fifty-eight per cent of those on highly active antiretroviral therapy (HAART) had an undetectable HIV viral load by delivery. Eighty-seven per cent were uncomplicated pregnancies. Seventy-one per cent delivered by Caesarean section and 21% (14 of 64) had a preterm delivery (<37 weeks). In the 12 months after delivery, 45% of women received contraceptive advice and 25% of women became pregnant again. CONCLUSION: Obstetric and virological outcomes were favourable in this group of HIV-infected young women. However, the majority of pregnancies were unplanned with poor documentation of contraception use and advice and low rates of STI screening. A quarter of women conceived again within 12 months of delivery. Effective measures to reduce STIs, unplanned pregnancies and onward HIV transmission in HIV-infected teenagers are needed.

Immunosuppression among HIV-1-positive patients attending for care: experience from two large HIV centres in the United Kingdom.

OBJECTIVES: The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4 < 200 cells/microL) among HIV-infected patients attending two large inner London treatment centres. METHODS: Patients attending for care who had a CD4 count < 200 cells/microL during a 6-month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count > 200 cells/microL at any time under follow-up which had decreased (group A) or never had a CD4 count > 200 cells/microL (group B; late presenters). RESULTS: Of 4589 patients, 10.2% (467) had at least one CD4 count < 200 cells/microL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to < 200 cells/microL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS-defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B. CONCLUSION: The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.

Microstructured beta-tricalcium phosphate for alveolar cleft repair: a two-centre study.

The current standard of care in alveolar cleft repair is timing the procedure in the mixed dentition stage and making use of autologous bone to restore the maxillary defect. Using a synthetic bone substitute bypasses the risk of donor site morbidity and reduces the operation time. In this study, the outcome of alveolar cleft repair using microporous beta-tricalcium phosphate (ß-TCP) was investigated in patients with unilateral cleft lip and palate. Twenty patients were enrolled prospectively in this study, divided between two centres. Continuity of the alveolar process, recurrence of oronasal fistulas, and eruption of teeth into the repaired cleft were evaluated at 1year postoperative. Also, cone beam computed tomography scans were analyzed using a volume-based semi-automatic segmentation protocol. No adverse events were reported. The mean residual bone volume in the repaired cleft at 1year postoperative was 65%. There was no recurrence of oronasal fistula. Furthermore, 90% of the teeth adjacent to the cleft erupted spontaneously and all patients showed a continuous alveolar process. Secondary alveolar grafting using microporous ß-TCP can safely be used in the clinical situation. Residual calcified tissue, canine eruption, and complication rates at the recipient site are comparable to those with autologous grafts.

New mutations associated with resistance not detected following zidovudine monotherapy in pregnancy when used in accordance with British HIV Association guidelines.

OBJECTIVES: To determine whether mutations conferring drug resistance are detectable after zidovudine monotherapy (ZDVm) in pregnancy, using both standard genotyping and more sensitive cloning assays. METHODS: Post-delivery samples from women meeting the British HIV Association guidelines criteria for the use of ZDVm in the prevention of mother-to-child transmission (MTCT) and who received ZDVm were analysed using the Trugene HIV-1 genotyping assay. In order to detect drug-resistant minority species, samples from a sub-group of 14 women were evaluated for minority drug-resistant variants. Nested polymerase chain reaction (PCR) products from the reverse transcriptase (RT) gene (codons 1-258) were cloned into the pCR4 Blunt TOPO cloning vector. Sequences were submitted to the Stanford University HIV Drug Resistance Database for analysis. RESULTS: Eighty women met the inclusion criteria. Successful genotypes were obtained from 53. There were no new mutations conferring resistance to ZDV detected post-delivery using either standard genotyping or cloning for minority species. CONCLUSIONS: A short course of ZDVm in carefully selected women does not lead to the emergence of drug resistance based on either standard genotyping or cloning for the detection of minority species. Therefore, this strategy can still be considered in women wishing to prevent MTCT while minimizing antiretroviral exposure, without fear of compromising their future HIV care.

Multicentric Castleman's disease in HIV infection.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder. The precise incidence is unknown, although it is more common in HIV-positive than HIV-negative individuals. The pathological features of MCD strongly suggest a chronic antigen stimulation response, and human herpes virus 8 (HHV8) has been found to be universal in cases of HIV-related MCD. The presentation is non-specific with a wide differential diagnosis, which often results in a significant delay in its diagnosis. Diagnosis is made on the clinical presentation of a lymphoproliferative disorder, with evidence of multisystem involvement with classical histopathology on lymph node biopsy. Although no standard of care has been established for its treatment, symptomatic recurrences are often treated with corticosteroids and chemotherapy. The contribution of highly active antiretroviral treatment to the treatment of MCD remains debated. Novel treatments targeted at HHV8 show promising results, although evidence is currently limited to case reports. Randomized control trials assessing whether 'prophylactic' treatment with ganciclovir may prevent flares as currently used against cytomegalovirus disease in transplant patients are proposed. The prognosis of MCD in HIV-positive patients remains generally poor with a median survival of 48 months from diagnosis, and a 15-fold increased risk of non-Hodgkin's lymphoma.

Multicentric Castleman's disease in a patient with HIV.

Multicentric Castleman's disease (MCD) was originally described in non-HIV patients. It is a rare lymphoproliferative disorder, which is more commonly seen in HIV-positive patients and is associated with human herpes virus-8 (HHV-8). We describe a patient with advanced HIV who responded well to conventional highly active antiretroviral treatment. She was diagnosed with MCD soon after her diagnosis of HIV. She presented with multiple flares of her MCD. The case illustrates the difficulty of differentiating between episodes of septicaemia and a flare of MCD. The patient was treated with various chemotherapy regimens, which included several cycles of liposomal doxyrubicin and etoposide. There is currently no consensus on the treatment of MCD and various therapies are described in the literature, which include chemotherapy. Chemotherapy must be chosen with the immunosuppressive effects of the treatment being considered with caution. Both doxyrubicin and etoposide are well tolerated and successfully controlled the symptoms of MCD in our patient.

Multicenter study of human immunodeficiency virus-related germ cell tumors.

PURPOSE: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. PATIENTS AND METHODS: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. RESULTS: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. CONCLUSION: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.

Development and degeneration of retina in rds mutant mice: light microscopy.

Changes during the development and degeneration of the retina in 020/A mice, which are homozygous for the newly reported rds (retinal degeneration slow), gene were studied by histological and enzyme-histochemical methods with Balb/c mice carrying the normal allele as control. During normal development the total thickness of the retina grows from the time of birth till the age of 21 days and thereafter gradually diminishes, while the thicknesses of the component layers show a characteristic and differential change in course of their histogenesis. In the normal retina the perikarya of the cones are more frequent in the central than in the peripheral areas. The cone frequency in the central retina, but not in the periphery, increases with age and implies selective loss of rod cells in older animals. In the homozygous rds mice, the receptor layer remains rudimentary, but the other retinal layers show a normal trend of growth during the first 2 weeks after birth. Thereafter th morphological layers containing visual cell structures--the receptor, the outer nuclear, and the outer plexiform layers--begin to reduce. The loss of visual cells is readily marked by the reduction of the outer nuclear layer and is first evident at 2 weeks after birth. Degeneration is more rapid up to the age of 2-3 months, when the outer nuclear layer is reduced to half of its original thickness; thereafter degeneration progresses more slowly. The receptor and the outer plexiform layers are also simultaneously reduced. At 9 months, the peripheral parts of the retina, and at 12 months, the entire retina is completely lacking in visual cells. In the central retina of the mutant, rod and cone cell populations are equally affected up to the age of 6 months, as their relative frequency remains similar to the normal. In the peripheral retina, where cell loss is more pronounced, and in the central retina at 9 months an increase in relative frequency of cones is recorded and indicate increased susceptibility of the rods to later degenerative changes. The inner parts of the retina, including inner nuclear, inner plexiform, and ganglion cell layers, remain morphologically unaffected until irregular vascularization follows total loss of visual cells. The pigment epithelium is also affected at this late stage and appears depleted and patchy. In the normal retina, macrophages which are positively stained for the enzyme N-acetyl-beta-glucosaminidase appear in the inner layers with the growth of the retinal vasculature. In the mutant, increased frequency and stainability of the macrophages are discernible in the inner retina at 11 days. The macrophages migrate outwards and are observed in the outer nuclear layer and in the optic ventricle during the period of degeneration. These findings are compared with the observations in the other retinal degeneration mutants in rodents, and in retinitis pigmentosa in humans. The suitability of the rds mice as an animal model system for the human disease is emphasized.

Long-term increase in protein kinase C-gamma and muscarinic acetylcholine receptor expression in the cerebral cortex of amygdala-kindled rats--a quantitative immunocytochemical study.

Kindling is an animal model for epilepsy in which repeated application of an electrical stimulus to brain pathways results in an epileptic focus. The animal holds a permanent state of hyperexcitability to the stimulus for the rest of its life. Understanding the cellular and molecular processes underlying hyperexcitability could provide insight into epileptogenesis. Furthermore, it could elucidate cellular and molecular bases of synaptic plasticity in the central nervous system. In the present study the long-term effect of a kindled focus in the amygdala on the gamma-isoform of protein kinase C and the muscarinic cholinergic receptor as cellular messengers was evaluated in the cerebral cortex of rats. Following an average of 10 bilaterally generalized seizures kindling stimulation was terminated and rats were left undisturbed for approximately three months. Brains were processed by immunocytochemistry using monoclonal antibodies against protein kinase C-gamma and muscarinic cholinergic receptor protein. Digital image analysis of sections through the entire forebrain revealed an increase in optical density of both protein kinase C-gamma and the muscarinic cholinergic receptor in the piriform and entorhinal cortex of the hemisphere contralateral to the stimulation site in kindled rats. However, on the ipsilateral side no change was observed in comparison with electrode implanted nonkindled control rats. The observed increase in expression of muscarinic cholinergic receptor protein and a component of the phosphoinositide second messenger system (protein kinase C-gamma) located in specific areas of the cerebral cortex in kindled rats could serve as a basis for the permanent state of hyperexcitability in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Genital herpes. A guide to pharmacological therapy.

The pharmacological therapy for genital herpes simplex virus (HSV) infection remains dominated by aciclovir, although a number of related compounds are currently under investigation. Recommended treatment for initial genital HSV infection is oral aciclovir 200mg 5 times daily for 5 days, with intravenous therapy reserved for complicated episodes. Although topical aciclovir may be of benefit, no improvement in the systemic symptoms is provided by this formulation. No preparation prevents the onset of recurrent episodes. The management of recurrent episodes is more controversial, with studies of episodic treatment with both topical and oral aciclovir yielding mixed and at times conflicting results. Episodic treatment with oral aciclovir initiated early by the patient appears to have the most favourable results, and if initiated at the onset of prodromal symptoms may abort the episode in some patients. In patients with frequent recurrences, suppressive therapy with oral aciclovir should be considered. A starting dose of 200mg 4 times daily appears to be the most effective, although 400mg twice daily may suffice. The total daily dose should be reduced as far as possible, and treatment should be interrupted on a yearly basis to determine the need for continuing suppression. The management and pharmacological therapy of genital HSV in pregnancy remains controversial and studies of oral aciclovir in late pregnancy are currently under way. Genital HSV infection may be particularly severe in the immunocompromised host and suppressive oral aciclovir should be initiated promptly. HSV resistance to aciclovir is an increasing problem in such patients, in particular those infected with HIV, and may necessitate treatment with intravenous foscarnet.

Coping with stress in rats and mice: differential peptidergic modulation of the amygdala-lateral septum complex.

This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex. Interestingly, this VP system is sexually dimorphic and the VP synthesis in this system depends on circulating gonadal steroids. Studies in rats and mice show that the variation in the lateral septal VP network within the male gender is as large as the variation between the sexes as reported in the literature. Non-aggressive males are characterized by a far more extensive VP network and a higher VP content in the lateral septal area than aggressive males. A review of the literature on the function of lateral septal VP in the organization of behavior reveals not only a modulatory role of behavior in a social context, but also of fear- and anxiety-related behaviors. It is argued that these seemingly diverse functions might be explained by the concept of coping style. Extensive behavioral and physiological analyses in a variety of animal species show that males may be characterized by the way in which they cope with environmental challenges in general. Aggressive males tend to cope actively with their environment whereas non-aggressive males seem to accept the situation as it is more easily. In several tests, we determined the effects of chronic infusion of the V1 receptor antagonist locally into the lateral septal area in male rats. The main conclusion from these experiments is that LS VP does not modulate coping style in general. However, the experiments confirm the idea that LS VP has a certain degree of functional specificity in social behavior and social learning tasks. Together with the observation that the size and distribution of the vasopressinergic system may be highly variable between individual males in relation to their coping style, this suggests that the lateral septal vasopressinergic system is involved in the differential capacity of individuals to cope behaviorally with challenges of a social nature.

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.

Assisted conception in HIV discordant couples: evaluation of semen processing techniques in reducing HIV viral load.

Artificial insemination with motile spermatozoa prepared from HIV-infected men using standard procedures has been employed with many HIV-discordant couples. We have demonstrated that processing semen from HIV positive men can reduce HIV levels, measured as HIV1 RNA copies/ml using nucleic acid based sequence amplification (NASBA), to undetectable levels (less than 400 copies/ml) but not in all samples. We believe that all processed samples should be tested prior to insemination.

Cytogenetic support for primary prostatic cancer in a patient presenting with a soft tissue mass in the leg.

A 65-year old man presented with a soft tissue mass in the leg, clinically suspect of a sarcoma. Histologic examination suggested a metastatic adenocarcinoma of the prostate, which could not be confirmed by immunohistologic studies. However, cytogenetic analysis strongly supported this diagnosis. A primary prostatic carcinoma was indeed found and the patient died of widely disseminated disease. These findings illustrate the significance of chromosomal analysis in the search for a primary tumor in patients with an unknown primary.