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Zhenquan Lu,1,* Jian Hou,1,* Xiao Li,2 Jun Zhou,2 Bingfeng Luo,1 Songwu Liang,1 Richard K Lo,1 Tak Man Wong,2 Guan-Ming Kuang2 1Department of Urology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guan-Ming Kuang, Email kuanggm@hku-szh.orgAbstract: Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis.Methods: Two datasets were collected. One dataset was from the authors’ institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied.Results: From the authors’ dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis.Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.Keywords: prostate cancer, bone metastasis, exosomes, bioinformatics analysis, miRNAs

Background: Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors., Methodology/principal Findings: We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge., Conclusions/significance: Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages., Competing Interests: The authors have declared that no competing interests exist.

Mantle cell lymphoma (MCL) is aggressive with poor prognosis. Due to t(11;14)(q13;q32), cyclin D1 is overexpressed. The in vitro activities of arsenic trioxide (As2O3) in MCL were investigated. In MCL lines Jeko-1 and Granta-519, As2O3 induced dose-dependent and time-dependent increases in apoptosis accompanied by cyclin D1 suppression. Downregulation of cyclin D1 resulted in decreased retinoblastoma protein phosphorylation, which led to repressed G1 progression to S/G2 phases. As2O3 did not affect cyclin D1 gene transcription. Instead, As2O3 activated glycogen synthase kinase-3beta (by tyrosine-216 phosphorylation) and IkappaB kinase alpha/beta (by serine-176/180 phosphorylation), both of which phosphorylated cyclin D1 at threonine-286, leading to its poly-ubiquitination and degradation in the proteasome. These observations were recapitulated partly in primary MCL samples obtained from patients refractory to conventional treatment. Our findings suggested that As2O3 might be clinically useful in MCL.

Many G protein-coupled receptors (GPCRs) are known to modulate cell growth and differentiation by stimulating the extracellular signal-regulated protein kinases (ERKs). In growth factor signaling, ERKs are typically stimulated through an elaborate network of modules consisting of adaptors, protein kinases, and the small GTPase Ras. The mechanism by which G protein signals tap into the ERK signaling pathway has thus far remain elusive. Members of the Gq family of G proteins, in particular Galpha16, have been shown to associate with tetratricopeptide repeat 1 (TPR1), an adaptor protein which preferentially binds to Ras. Here, we examined if TPR1 is indeed the missing link between Galpha16 signaling and Ras activation. Expression of Galpha16QL, a constitutively active mutant of Galpha16, in HEK 293 cells led to the formation of GTP-bound Ras and the subsequent phosphorylation of ERK. Likewise, stimulation of endogenou G16-coupled CCR1 chemokine receptors produced the same responses in human erythroleukemia cells. siRNA-mediated knockdown of TPR1 or expression of a dominant negative mutant of TPR1 effectively abolished the ability of Galpha16QL to induce Ras activation in HEK 293 cells. In contrast, these manipulations had no inhibitory effect on Galpha16QL induced activation of phospholipase Cbeta. Galpha16QL-induced phosphorylations of downstream targets including ERK, signal transducer and activator of transcription 3, and IkappaB kinase were significantly suppressed upon expression of the dominant negative mutant of TPR1. Furthermore, SOS2, a Ras guanine nucleotide exchange factor, was found to form a complex with TPR1 and Galpha16QL. Expression of SOS2 enhanced Galpha16QL-induced Ras activation and its subsequent signaling. Collectively, our results suggest that Galpha16 regulates multiple signaling pathways by activating Ras through its association with TPR1, but TPR1 is not required for Galpha16 to stimulate phospholipase Cbeta.

The hematopoietic-specific G(q) subfamily members, Galpha(16) and Galpha(14) proteins have recently been shown to be capable of stimulating the signal transducer and activator of transcription 3 (STAT3) as well as STAT1. In the present study we examined whether this activation was STAT-member specific as well as determining the possible involvement of Gbetagamma dimers. Despite clear stimulation of STAT3, the constitutively active mutants of Galpha(16) (Galpha(16)QL) and Galpha(14) (Galpha(14)QL) failed to induce the phosphorylation of several STAT family members, including STAT2, STAT4 and STAT5 in human embryonic kidney 293 cells. On the other hand, transient expression of specific combinations of Gbetagamma complexes induced STAT3 phosphorylation. Among the 48 combinations tested, 13 permutations of Gbetagamma stimulated STAT3 phosphorylation and all of them contain the neuronal-specific Ggamma(2), Ggamma(4), Ggamma(7) and Ggamma(9). These results suggested that the activation of STAT family members by Galpha(16) or Galpha(14) was selective and that distinct combinations of Gbetagamma complexes can also regulate the STAT signaling pathway., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Reporter gene assays are versatile and sensitive methods of assaying numerous targets in high-throughput drug-screening programs. A variety of reporter genes allow users a choice of signal that can be tailored to the required sensitivity, the available detection apparatus, the cellular system employed, and the required compatibility with multiplexed assays. Promoters used to drive reporter gene expression can be activated either by a broad range of biochemical pathways or by the selective activation of individual targets. In this chapter, we will introduce some of the considerations behind the choice of reporter gene assays and describe the methods that we have used to establish 96-well format luciferase and aequorin assays for the screening of ligands for G protein-coupled receptors.

Human prostacyclin receptor (hIP) stimulates STAT3 via pertussis toxin-insensitive G proteins in human erythroleukemia (HEL) cells. Since hIP can utilize G(s) and G(q) proteins for signal transduction and that both G proteins can induce STAT3 phosphorylation and activation via complex signaling networks, we sought to determine if one of them is predominant in mediating the hIP signal. Stimulation of STAT3 Tyr(705) and Ser(727) phosphorylations by the IP-specific agonist, cicaprost, was sensitive to inhibition of protein kinase A, phospholipase Cbeta, protein kinase C, calmodulin-dependent protein kinase II and Janus kinase 2/3. Unlike Galpha(16)-mediated regulation of STAT3 in the same cells, cicaprost-induced STAT3 Tyr(705) phosphorylation was resistant to inhibition of Src and MEK while STAT3 Ser(727) phosphorylation distinctly required phosphatidylinositol-3 kinase. This unique inhibitor-sensitivity pattern of STAT3 phosphorylation was reproduced in HEL cells by stimulating the G(16)-coupled C5a receptor in the presence of dibutyryl-cAMP, suggesting that the change in inhibitor-sensitivity was due to activation of the G(s) pathway. This postulation was confirmed by expressing constitutively active Galpha(16)QL and Galpha(s)QL in human embryonic kidney 293 cells and the inhibitor-sensitivity of Galpha(16)QL-induced STAT3 phosphorylations could be converted by the mere presence of Galpha(s)QL to resemble that obtained with cicaprost in HEL cells. In addition, the restoration of the Galpha(16)-mediated inhibitor-sensitivity upon cicaprost induction in Galpha(s)-knocked down HEL cells again verified the pivotal role of G(s) signal. Taken together, our observations illustrate that co-stimulation of G(s) and G(q) can result in the fine-tuning of STAT3 activation status, and this may provide the basis for cell type-specific responses following activation of hIP.

Hematopoietic restrictive Galpha(16) has long been known to stimulate phospholipase Cbeta (PLCbeta) and induce mitogen-activated protein kinase (MAPK) phosphorylation. Recently, we have demonstrated that Galpha(16) is capable of inducing the phosphorylation and transcriptional activation of transcription factors, such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB (NFkappaB). However, the downstream signaling regulation by Galpha(16) has not yet been documented. In the present study, we have determined the signaling mechanism by which constitutively active Galpha(16) mediates c-Fos transcriptional activation in human embryonic kidney (HEK) 293 cells. Overexpression of constitutively active Galpha(16), Galpha(16)QL, resulted in the stimulation of c-Fos transcriptional activation in HEK 293 cells. The participation of PLCbeta, c-Src/Janus kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signaling pathways in Galpha(16)QL-induced c-Fos transcriptional activation was demonstrated by the use of their specific inhibitors. However, c-Jun N terminal kinase (JNK), p38 MAPK and phosphatidylinositol-3 kinase (PI3K) were not required. Interestingly, the dominant negative mutant of STAT1, but not STAT3, suppressed c-Fos transcriptional activation induced by Galpha(16)QL, implying that STAT1 was involved in this signaling mechanism. To further examine the role of STAT1 in the signaling pathway of Galpha(16), we demonstrated that Galpha(16)QL was able to induce STAT1 activation. Also, stimulation of adenosine A1 receptor-coupled Galpha(16) was shown to induce ERK and STAT1 phosphorylations in a concentration-dependent manner. Using selective inhibitors, PLCbeta, c-Src/JAK and ERK, but not JNK, p38 MAPK and PI3K, were shown to be involved in Galpha(16)QL-induced STAT1 activation. Collectively, our results demonstrate for the first time that stimulation of Galpha(16) can lead to STAT1-dependent c-Fos transcriptional activation via PLCbeta, c-Src/JAK and ERK pathways.

Signal transducer and activator of transcription 3 (STAT3) can be stimulated by several G(s)-coupled receptors, but the precise mechanism of action has not yet been elucidated. We therefore examined the ability of Galpha(s)Q226L (Galpha(s)QL), a constitutively active mutant of Galpha(s), to stimulate STAT3 Tyr705 and Ser727 phosphorylations in human embryonic kidney 293 cells. Apart from Galpha(s)QL, the stimulation of Galpha(s) by cholera toxin or beta2-adrenergic receptor and the activation of adenylyl cyclase by forskolin, (Sp)-cAMP, or dibutyryl-cAMP all promoted both STAT3 Tyr705 and Ser727 phosphorylations. Moreover, the removal of Galpha(s) by RNA interference significantly reduced the beta2-adrenergic receptor-mediated STAT3 phosphorylations, denoting its capacity to regulate STAT3 activation by a G protein-coupled receptor. The possible downstream signaling molecules involved were assessed by using specific inhibitors and dominant negative mutants. Induction of STAT3 Tyr705 and Ser727 phosphorylations by Galpha(s)QL was suppressed by inhibition of protein kinase A, Janus kinase 2/3, Rac1, c-Jun N-terminal kinase (JNK), or phosphatidylinositol 3-kinase, and a similar profile was observed in response to beta2-adrenergic receptor stimulation. In contrast to the Galpha16-mediated regulation of STAT3 in HEK 293 cells (Lo, R. K., Cheung, H., and Wong, Y. H. (2003) J. Biol. Chem. 278, 52154-52165), the Galpha(s)-mediated responses, including STAT3-driven luciferase activation, were resistant to inhibition of phospholipase Cbeta. Surprisingly, Galpha(s)-mediated phosphorylation at Tyr705, but not at Ser727, was resistant to inhibition of c-Src, Raf-1, and MEK1/2 as well as to the expression of dominant negative Ras. Therefore, as with other Galpha-mediated activations of STAT3, the stimulatory signal arising from Galpha(s) is transduced via multiple signaling pathways. However, unlike the mechanisms employed by Galpha(i) and Galpha(14/16), Galpha(s) distinctively requires protein kinase A, JNK, and phosphatidylinositol 3-kinase for STAT3 activation.

The ability of the human prostacyclin receptor (hIP) to regulate the activities of signal transducers and activators of transcription (STATs) has not yet been documented. In the present study, we have delineated the mechanism by which hIP induces STAT3 phosphorylations in human erythroleukemia (HEL) cells. Stimulation of endogenous hIP by its specific agonist, cicaprost, resulted in STAT3 Tyr705 and Ser727 phosphorylations in a time- and concentration-dependent manner. Cicaprost-induced STAT3 Tyr705 and Ser727 phosphorylations were resistant to pertussis toxin (PTX) treatment, suggesting that these responses were mediated through PTX-insensitive G proteins. In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 MAPK, were shown to be phosphorylated by cicaprost in a time- and concentration-dependent manner via PTX-insensitive G proteins. The levels of the interaction between STAT3, ERK and JNK were enhanced by cicaprost treatment. The involvement of Raf-1, MEK1/2 and JNK in cicaprost-induced phosphorylations of STAT3 was illustrated by the use of their selective inhibitors. In contrast, p38 MAPK did not appear to be required. Similar observations were obtained with STAT1 upon stimulation by cicaprost. Taken together, these results demonstrate for the first time that hIP activation by cicaprost can lead to STAT1 and STAT3 phosphorylations via signaling pathways involving PTX-insensitive G proteins, ERK and JNK.

The hematopoietic-specific Galpha14 links a variety of G protein-coupled receptors to phospholipase Cbeta (PLCbeta) stimulation. Recent studies reveal that several Galpha subunits are capable of activating signal transducer and activator of transcription (STAT) proteins. In the present study, we investigated the mechanism by which Galpha14 mediates receptor-induced stimulation of STAT3. In human embryonic kidney 293 cells, coexpression of Galpha14 with delta-opioid receptor supported [D-Pen2, D-Pen5]enkephalin (DPDPE)-induced STAT3 phosphorylations at both Tyr705 and Ser727 in a pertussis toxin-insensitive manner. The constitutively active Galpha4QL mutant also induced STAT3 phosphorylations at these sites and promoted STAT3-dependent luciferase activity. Requirements for PLCbeta, protein kinase C (PKC), and calmodulin-dependent kinase II (CaMKII) in Galpha14QL-induced STAT3 activation were demonstrated by their respective inhibitors as well as by coexpression of their dominant-negative mutants. Inhibition of c-Src and Janus kinase 2 and 3 activities abolished STAT3 activation induced by Galpha14QL, but no physical association between Galpha14QL and c-Src could be detected by coimmunoprecipitation. Various intermediates along the extracellular signal-regulated kinase signaling cascade were apparently required for Galpha14QL-induced STAT3 activation; they included Ras/Rac1, Raf-1, and mitogen-activated protein kinase kinase-1/2. In contrast, functional blockade of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol-3 kinase had no effect on Galpha14QL-induced responses. PLCbeta, PKC, and CaMKII were shown to be involved in Galpha14QL-mediated c-Src phosphorylation. Similar results were obtained with human erythro-leukemia cells upon DPDPE treatment. These results demonstrate for the first time that Galpha14 activation can lead to STAT3 stimulation via a complex signaling network involving multiple intermediates.

The hematopoietic-specific Galpha16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Galpha16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Galpha16 mutant, Galpha16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Galpha16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cbeta, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Galpha16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Galpha16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Galpha16. Demonstration of the involvement of different kinases in Galpha16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins.

A number of G protein-coupled receptors (GPCRs) have been shown to stimulate signal transducers and activators of transcription (STAT) activities while STAT3 activation by G alpha(o) can lead to neoplastic transformation in fibroblasts. In the present study we examined the ability of GPCRs to activate STAT3 via G alpha(16), a G alpha subunit which is primarily expressed in hematopoietic cells. In HEK 293 cells expressing a STAT3-driven luciferase reporter, the G alpha(16)-coupled ORL(1) and fMLP receptors stimulated luciferase activity upon activation by their agonists. Agonist-induced STAT3 activity required coexpression of G alpha(16) and was resistant to PTX treatment. Upon activation of the ORL(1) and fMLP receptors, phosphorylation of STAT3 at Tyr(705) was detected by immunoblot analysis. Additional experiments indicated that GPCR-mediated STAT3 activation was dependent on JAK and Raf1 signaling, but did not require phosphatidylinositol 3-kinase. This is the first study that demonstrates the stimulatory effect of ORL(1) and fMLP receptors on STAT3 activity.

Melatonin is a pineal hormone involved in neuroendocrine processes in mammals. It has been shown that melatonin inhibits the enzymatic activities of adenylyl cyclases and the transcriptional activities of CREB. In this report, we demonstrate that 2-iodomelatonin (2IMT) treatment on COS-7 cells transfected with melatonin receptors (mt1 and MT2) induces c-Jun N-terminal kinase (JNK) activation, which is pertussis toxin (PTX)-sensitive, Ras/Rac-dependent and may involve Src-family protein tyrosine kinases. Moreover, PTX-insensitive Gs, Gz and G16 are capable of linking activated melatonin receptors to the stimulation of JNK. Agonist stimulation on PTX-pretreated COS-7 cells overexpressing mt1 receptor, Galpha(s) and adenylyl cyclase VI led to increased cAMP accumulation. Stimulation of endogenous mt1 receptors in MCF-7 cells was associated with the activation of both JNK and extracellular signal-regulated kinase (ERK). This report demonstrates the stimulatory effect of melatonin receptors on JNK, and provides experimental evidence for a functional coupling between the G(i)-coupled melatonin receptor and Gs, in terms of adenylyl cyclase activation.

We have used blood withdrawn electively and frozen for later use by the donor in 25 patients with bladder cancer who were treated by preoperative irradiation and radical cystectomy. Patients donated 1 to 5 units of blood (average 3.4 per patient). We transfused 10 patients with only autologous blood, whereas 15 required some homologous blood in addition to their own banked blood. The program was well tolerated and repeated blood donation did not compromise the effectiveness of preoperative irradiation. Our preliminary data show that this program reduces the dependence on volunteer donor homologous blood transfusions for cystectomy, thus, decreasing the potential risk of an adverse reaction and avoiding seasonal blood bank shortages.

A perinephric abscess in an adolescent, initially mistaken for a renal tumor, was managed conservatively with antibiotic therapy alone. Computed tomography revealed that resolution was complete, eliminating the need for surgical drainage. The case suggests the wisdom of altering traditional diagnostic and therapeutic approaches to lesions in the perinephric area.

The decay pattern and half-life estimation of serum tumor markers are useful parameters in the management of nonseminomatous germ cell tumors of the testis. We describe a graphical method of evaluating the temporal pattern of tumor marker clearance that can be used to identify patients with residual tumor after orchiectomy alone or retroperitoneal lymphadenectomy.

Twenty-two patients with squamous carcinoma of the penis underwent groin dissections for histologically proved inguinal lymph node metastases, either around the time that the primary tumor was treated (early therapeutic dissection, 14 patients) or later, after they had been clinically judged free of regional nodal metastases at diagnosis (late therapeutic dissections, 8 patients). Three- and five-year survival rates for the patients who underwent early therapeutic dissections were 71 per cent and 57 per cent, respectively, as opposed to 50 per cent and 13 per cent, respectively, for patients who underwent late therapeutic dissections. These findings suggest that a "wait and watch" policy in patients with clinically negative nodes at diagnosis is no longer justified.

A total of 31 men with clinical stage I nonseminomatous germ cell tumors of the testis was followed for 2 to 18 months (median 10 months) after inguinal orchiectomy. Of the patients 26 (84 per cent) have been continuously free of disease. Relapse occurred in 5 patients (16 per cent) at 2, 2, 4, 4 and 6 months, respectively, but they were rendered free of disease with combination chemotherapy. The results suggest that careful surveillance following orchiectomy is all that is required for patients who have nonseminomatous germ cell testicular tumors but no obvious regional or visceral metastases.

We reviewed 13 cases of verrucous carcinoma, accounting for 5 per cent of the penile cancers seen during a 25-year interval. Although the typical verrucous pattern predominated minute foci of invasive squamous carcinoma were identified in 3 patients. All patients were followed for at least 6 years and none has died of the malignancy. Wide surgical excision, usually requiring partial or total penectomy, is the treatment of choice.

A caput medusae developing around an ileal conduit stoma heralded the onset of portal hypertension and recurrent episodes of massive stomal bleeding in a patient with liver cirrhosis. A review of the literature suggests that conservative local measures remain the treatment of choice in the high risk cirrhotic patient.

To assess the operative morbidity, we reviewed retrospectively 101 groin dissections performed in 67 patients for management of squamous cell carcinoma of the penis. No patients died, but only 18 per cent experienced no postoperative complications. Early complications included flap necrosis in 50 per cent, seroma in 16 per cent, wound infection in 14 per cent, lymphocele in 9 per cent, and thrombophlebitis in 6 per cent. Leg edema developed in 50 per cent of those operated on and remained severe in about one third of these. The frequency of complications has changed little over the thirty-five-year time span of the study and is not related to the extent of the surgical procedure. In view of the high operative morbidity, caution should be exercised against using the surgical procedure injudiciously.

Magnetic resonance (MR) images of the scrotum were obtained at 1.5 T in 20 subjects, 13 patients with intrascrotal pathologic conditions and seven healthy subjects. Characteristic MR imaging signals obtained on T1- and T2-weighted images allowed differentiation of testis from epididymis and spermatic cord. Masses were differentiated from normal testicular parenchyma in all cases. Atrophic or ischemic testes had lower signal intensity than normal testes on T2-weighted images. Hematoma displayed a characteristic high intensity on both T1- and T2-weighted images. Intratesticular and extratesticular pathologic conditions were readily differentiated. These results suggest that MR imaging is useful in the diagnosis of scrotal and testicular abnormalities.