The peptidyl-prolyl isomerase PIN1 relieves cyclin-dependent kinase 2 (CDK2) inhibition by the CDK inhibitor p27.

PIN1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans isomerization of peptide bonds between proline and phosphorylated serine/threonine residues. By changing the conformation of its protein substrates, PIN1 increases the activities of key proteins that promote cell cycle progression and oncogenesis. Moreover, it has been shown that PIN1 stabilizes and increases the level of the cyclin-dependent kinase (CDK) inhibitor p27, which inhibits cell cycle progression by binding cyclin A- and cyclin E-CDK2. Notwithstanding the associated increase in the p27 level, PIN1 expression promotes rather than retards cell proliferation. To explain the paradoxical effects of PIN1 on p27 levels and cell cycle progression, we hypothesized that PIN1 relieves CDK2 inhibition by suppressing the CDK inhibitory activity of p27. Here, we confirmed that PIN1-expressing cells exhibit higher p27 levels but have increased CDK2 activities and higher proliferation rates in the S-phase compared with Pin1-null fibroblasts or PIN1-depleted hepatoma cells. Using co-immunoprecipitation and CDK kinase activity assays, we found that PIN1 binds the phosphorylated Thr187-Pro motif in p27 and reduces p27's interaction with cyclin A- or cyclin E-CDK2, leading to increased CDK2 kinase activity. In conclusion, our results indicate that although PIN1 increases p27 levels, it also attenuates p27's inhibitory activity on CDK2 and thereby contributes to increased G1-S phase transitions and cell proliferation.

PIN1 inhibits apoptosis in hepatocellular carcinoma through modulation of the antiapoptotic function of survivin.

PIN1, a peptidyl-prolyl-isomerase, binds a specific motif comprising a phosphorylated serine or threonine preceding a proline (p-Ser/Thr-Pro) residue in proteins. Through cis-trans isomerization, it induces conformational changes and modulates functions of many proteins that are involved in cell cycle progression, cell proliferation, and oncogenesis. PIN1 is overexpressed in hepatocellular carcinomas (HCC) and contributes to hepatocarcinogenesis. We investigated the role of PIN1 and the significance of its interaction with the inhibitor of apoptosis protein survivin in evading apoptosis in HCC cells. Using cell line and xenograft models, we determined that PIN1 overexpression inhibits apoptosis through suppression of caspase-3 and caspase-9 activity. In addition, down-regulation of survivin in PIN1-overexpressing cells attenuated the antiapoptotic effect induced by PIN1, suggesting that the inhibition of apoptosis is mediated through PIN1-survivin interaction. Coimmunoprecipitation assays showed that PIN1 interacted with survivin via the phosphorylated Thr34-Pro35 motif and enhanced binding among survivin phosphorylated at Thr34, hepatitis B X-interacting protein (HBXIP), and pro-caspase-9. Taken together, these results suggest that the inhibition of apoptosis by PIN1 in HCC cells is mediated through modulation of the antiapoptotic function of survivin by increasing its binding to pro-caspase-9 via HBXIP. Such functional interaction between PIN1 and survivin may therefore play an important role in hepatocarcinogenesis and chemoresistance.

Prospection deficits in patients with first-episode schizophrenia: a cross-sectional comparative study.

Prospection refers to the ability to simulate and pre-experience future events. Schizophrenia patients have difficulty in anticipating pleasure in future events, but previous studies examined prospection deficits in chronic schizophrenia patients. This study aimed to investigate prospection deficits in first-episode schizophrenia patients. Thirty first-episode schizophrenia patients and 31 healthy controls completed the Affective Prospection Task, which utilized pictorial cues to involve positive, neutral and negative prospection. Participants' ratings regarding the phenomenal characteristics of their prospected events were collected, and their prospected narratives were coded using a valid scoring manual. We also assessed intelligence, working memory and logical memory. The results showed, in all participants, valence of the cues significantly influenced participants' sense of pre-experience, temporal distance, emotion experience, vividness and participation of the prospected events, as well as the richness of sensory details. The two groups did not differ in self-report phenomenal characteristics of their prospected events. For coded characteristics, schizophrenia patients' prospected narratives were less rich in thought/emotion than controls, even after controlling for intelligence and memory deficits. We extended empirical evidence for prospection deficits from chronic schizophrenia samples to first-episode schizophrenia patients.

Prevalence and determinants of psychiatric disorders in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic rheumatological disorder among southern Chinese patients in Hong Kong, with an estimated prevalence of 0.33%-0.35%. The resulting chronic pain, disability, social stress, and isolation contribute to the development of psychiatric symptoms. OBJECTIVE: The authors identify the prevalence and determining factors of psychiatric disorders in patients with RA. METHOD: Consecutive RA patients (N=200) were recruited from a rheumatology outpatient clinic. Psychiatric disorders were diagnosed by a psychiatrist using the Chinese-bilingual Structured Clinical Interview for DSM-IV Axis I disorders, Patient Research Version. Sociodemographic and clinical data and subjective health status and perceived social support data were also collected. Factors associated with the occurrence of psychiatric disorders were studied by multivariate analysis. RESULTS: A total of 47 patients were diagnosed with a current psychiatric disorder (depressive disorders, 14.5%; anxiety disorders, 13.0%; schizophrenia, 0.5%). Major depressive disorder and generalized anxiety disorder were the commonest current mood and anxiety disorders, respectively. Independent predictors for a current psychiatric disorder were poverty and perceived poor social support. Limited social interaction, perceived poor social support, high pain intensity, and a family history of psychiatric disorders were independently associated with a current depressive disorder, whereas poverty and perceived poor social support were associated with a current anxiety disorder. CONCLUSION: Depression and anxiety are common in Chinese patients with RA. Patients who lack social support or rely on economic assistance are more prone to the development of psychiatric disorders.

Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma.

PIN1 is a peptidyl-prolyl cis/trans isomerase that specifically binds and catalyzes the cis/trans isomerization of the phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif of its interacting proteins. Through this phosphorylation-dependent prolyl isomerization, PIN1 is involved in the regulation of various important cellular processes including cell cycle progression, cell proliferation, apoptosis and microRNAs biogenesis; hence its dysregulation contributes to malignant transformation. PIN1 is highly expressed in hepatocellular carcinoma (HCC). By fine-tuning the functions of its interacting proteins such as cyclin D1, x-protein of hepatitis B virus and exportin 5, PIN1 plays an important role in hepatocarcinogenesis. Growing evidence supports that targeting PIN1 is a potential therapeutic approach for HCC by inhibiting cell proliferation, inducing cellular apoptosis, and restoring microRNAs biogenesis. Novel formulation of PIN1 inhibitors that increases in vivo bioavailability of PIN1 inhibitors represents a promising future direction for the therapeutic strategy of HCC treatment. In this review, the mechanisms underlying PIN1 over-expression in HCC are explored. Furthermore, we also discuss the roles of PIN1 in HCC tumorigenesis and metastasis through its interaction with various phosphoproteins. Finally, recent progress in the therapeutic options targeting PIN1 for HCC treatment is examined and summarized.

Effect of vardenafil on blood pressure profile of patients with erectile dysfunction concomitantly treated with doxazosin gastrointestinal therapeutic system for benign prostatic hyperplasia.

PURPOSE: We investigated the effect of the combination of the doxazosin gastrointestinal therapeutic system and 10 mg vardenafil on the hemodynamic status of patients with benign prostatic hyperplasia and erectile dysfunction. MATERIALS AND METHODS: This was a double-blinded, randomized, placebo controlled crossover trial. Patients with benign prostatic hyperplasia and erectile dysfunction treated with the doxazosin gastrointestinal therapeutic system on a regular basis, with no other antihypertensive events, were recruited. Subjects took 10 mg vardenafil or placebo in a randomized crossover fashion with a washout period of at least 7 days between each treatment. The supine and standing blood pressure of the subjects was recorded from 1 hour before to 6 hours after the administration of vardenafil or placebo. The primary outcome of the study was the maximal change in standing systolic blood pressure of the subjects from 1 half hour before to 6 hours after the administration of drugs. RESULTS: A total of 37 patients, 25 (67.6%) and 12 (32.4%) on the doxazosin gastrointestinal therapeutic system at 4 mg and 8 mg, respectively, completed the trial. The combination drug therapy resulted in a maximal decrease in standing systolic blood pressure of 6.18 mm Hg (95% CI -12.02, -0.33; p = 0.039). Only 1 patient had an asymptomatic standing systolic blood pressure of less than 85 mm Hg. Otherwise no symptomatic hypotension or clinically significant adverse cardiovascular event was observed during the study. CONCLUSIONS: In patients on the doxazosin gastrointestinal therapeutic system for benign prostatic hyperplasia a single 10 mg dose of vardenafil had no symptomatic hemodynamic effects.

PIN1 in Cell Cycle Control and Cancer.

Cell cycle progression is tightly controlled by many cell cycle-regulatory proteins that are in turn regulated by a family of cyclin-dependent kinases (CDKs) through protein phosphorylation. The peptidyl-prolyl cis/trans isomerase PIN1 provides a further post-phosphorylation modification and functional regulation of these CDK-phosphorylated proteins. PIN1 specifically binds the phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif of its target proteins and catalyzes the cis/trans isomerization on the pSer/Thr-Pro peptide bonds. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of various cell cycle-regulatory proteins including retinoblastoma protein (Rb), cyclin D1, cyclin E, p27, Cdc25C, and Wee1. In this review, we discussed the essential roles of PIN1 in regulating cell cycle progression through modulating the functions of these cell cycle-regulatory proteins. Furthermore, the mechanisms underlying PIN1 overexpression in cancers were also explored. Finally, we examined and summarized the therapeutic potential of PIN1 inhibitors in cancer therapy.

Pneumovesicum method in en-Bloc laparoscopic nephroureterectomy with bladder cuff resection for upper-tract urothelial cancer.

BACKGROUND AND PURPOSE: A novel technique for managing the distal ureter and bladder cuff during laparoscopic nephroureterectomy is introduced. TECHNIQUE: The procedure consists of three steps: (1) cystoscopy and PediPort (Tyco) insertion; (2) establishment of pneumovesicum and intramural ureter mobilization; and (3) laparoscopic nephroureterectomy. The use of PediPorts, a 5-mm lens, and Ski needles greatly facilitates the pneumovesicum. The ureteral orifice is closed, and the intramural ureter is dissected out with the patient in the lithotomy position. Laparoscopic nephroureterectomy is then accomplished with the patient in the lateral position. RESULTS: The postoperative course was uneventful, and the pathology examination showed clear margins. CONCLUSION: Pneumovesicum is a minimally invasive approach that provides an excellent endoscopic view. It is an oncologically sound method, as the ureteral orifice is closed early, and the chance of cancer-cell spillage is minimized by the use of gas instead of liquid in the bladder. Moreover, the procedure is not technically demanding.

Undifferentiated sex cord-stromal tumor in a young adult.

Undifferentiated sex cord-stromal tumor in post-puberty male is extremely rare. There were only three reported cases in the literature. We reported a 19-year-old patient presented with an asymptomatic right testicular nodule with normal level of serum marker for germ cell tumor. Excisional biopsy and subsequent orchidectomy was preformed and the final pathology supported the diagnosis of undifferentiated sex cord-stromal tumor. He was then put on regular surveillance with no adjuvant therapy given. He remained disease free 18 months after the operation. A summary of the literatures and discussion on the management of this rare tumor was provided.

Use of the University of California Los Angeles Integrated Staging System (UISS) to predict survival in localized renal cell carcinoma in an Asian population.

OBJECTIVES: To evaluate the applicability of the University of California Los Angeles Integrated Staging System (UISS) in predicting the prognosis of Chinese patients with localized renal cell carcinoma after radical nephrectomy, with reference to that reported by Patard et al in an international multicenter study (J Clin Oncol 2004, 22:3316-3322). METHODOLOGY: One hundred and twenty-eight Chinese patients with localized renal cell carcinoma were stratified into low risk (LR), intermediate risk (IR) and high risk (HR) groups according to the UISS, based on the TMN staging and Fuhrman grading of the tumor and the Eastern Cooperative Oncology Group performance status of the patients. The survival curves of each risk group were then calculated. RESULTS: The number of patients in the LR, IR and HR was 24 (18.8%), 94 (73.4%) and 10 (7.8%) respectively. The estimated 2-year survival rates were 100%, 89.9% and 100% for the LR, IR and HR groups respectively. Whereas the estimated 5-year survival rates were 93.3%, 72.4% and 80% for the LR, IR and HR groups respectively. The LR and IR patients had comparable 2-year and 5-year estimated survival rates with those reported by Patard et al. However, the estimated survival rate for HR patients was better than that reported. CONCLUSIONS: UISS provided a valuable tool in predicting the survival of Chinese patients with localized renal cell carcinoma of LR and IR groups, as reported in other international centers. Further large scale study may be needed to confirm the applicability in HR population.

miR-874-3p is down-regulated in hepatocellular carcinoma and negatively regulates PIN1 expression.

PIN1 is a peptidyl-prolyl cis/trans isomerase (PPIase) that regulates multiple signaling pathways to control cell fate and is found to be over-expressed in cancers, including hepatocellular carcinoma (HCC). However, the regulation of PIN1 in HCC remains poorly defined. Micro-RNAs (miRNAs) have been reported to play a pivotal role in oncogenesis by targeting the 3'-untranslated region (UTR) of mRNAs encoded by oncogenes and tumour suppressor genes, thereby suppressing the levels of both oncoproteins and tumour suppressors. In this report, we aimed to identify miRNAs that suppress PIN1 expression and to determine their role in HCC. By searching the TargetScan database, miR-874-3p was identified as a potential negative regulator of PIN1. miR-874-3p was demonstrated to bind the 3'UTR of PIN1 mRNA directly to suppress expression of PIN1. Functionally, over-expression of miR-874-3p in HCC cell line PLC/PRF/5 inhibited cell growth and colony formation in-vitro, and promoted cellular apoptosis. Furthermore, these tumour suppressive functions conferred by miR-874-3p were abrogated by over-expression of PIN1. Similarly, expression of miR-874-3p in PLC/PRF/5 with PIN1 knocked-down did not further suppress cellular proliferation, suggesting that PIN1 was a major target of miR-874-3p. More importantly, miR-874-3p was found to be down-regulated in HCC tissues and its expression was negatively correlated with that of PIN1. Down-regulation of miR-874-3p was also associated with poorly differentiated tumour cells, more advanced staging, and inferior patient outcomes. In addition, over-expression of miR-874-3p suppressed tumour growth in vivo. Taken together, our data suggested that miR-874-3p plays a tumour suppressive role in HCC through down-regulation of PIN1.

Understanding the role of PIN1 in hepatocellular carcinoma.

PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, ß-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation. PIN1 has been found to be over-expressed in many cancers, including human hepatocellular carcinoma (HCC). It has been shown previously that overexpression of PIN1 contributes to the development of HCC in-vitro and in xenograft mouse model. In this review, we first discussed the aberrant transcription factor expression, miRNAs dysregulation, PIN1 gene promoter polymorphisms and phosphorylation of PIN1 as potential mechanisms underlying PIN1 overexpression in cancers. Furthermore, we also examined the role of PIN1 in HCC tumourigenesis by reviewing the interactions between PIN1 and various cellular and viral proteins that are involved in ß-catenin, NOTCH, and PI3K/Akt/mTOR pathways, apoptosis, angiogenesis and epithelial-mesenchymal transition. Finally, the potential of PIN1 inhibitors as an anti-cancer therapy was explored and discussed.

Patients with bipolar disorder show differential executive dysfunctions: A case-control study.

Executive deficits in euthymic bipolar I disorder were examined in a fractionated manner based on the "Supervisory Attentional System" (SAS) model, and the relationship between the degree of executive impairment and the demographic and clinical characteristics of bipolar I participants was explored. A battery of neurocognitive tests capturing specific components of executive function was administered on 30 patients with bipolar I disorder in euthymic state, and compared with 30 healthy controls who were matched by age, gender and IQ. A differential impairment in executive function was demonstrated in euthymic bipolar I participants by using a fractionated approach of the SAS. Euthymic bipolar I patients were found to have significantly poorer performance in immediate and delayed visual memory; and in the executive domains of "initiation", "sustained attention", and "attention allocation and planning". Those with a greater number of executive impairments had lower IQ and higher negative sub-scores on PANSS. These findings might provide a the basis for further studies on identifying the executive components that are associated with particular disease characteristics of bipolar disorder, and those with poorer functional outcome, so that rehabilitation can be focused on the selective domains concerned.

Is surveillance necessary for inverted papilloma in the urinary bladder and urethra?

BACKGROUND: A case series of inverted papilloma of the urinary bladder and urethra is presented, together with a review of the literature with respect to multiplicity, recurrence rate and association with transitional cell carcinoma, and a discussion on surveillance of the lesion. METHODS: Cases of inverted papilloma of the lower urinary tract in a single centre were reviewed. Patient and tumour characteristics, recurrence and associated transitional cell carcinoma are reported. RESULTS: Twenty patients were included (18 male, two female). The mean age was 60.8 years (range 35-78 years). All had solitary tumours ranging from 3 mm to 30 mm in size. Median cystoscopic follow up was 30 months (range 2-140 months). There was no recurrence. One patient was associated with subsequent transitional cell carcinoma 44 and 76 months later. Together with the present 20 cases, review of the English literature with respect to inverted papilloma of the lower urinary tract identified a total of 322 cases reported, with a recurrence rate of 3.85%. Moreover, 1.55%, 5.90% and 1.54% were associated with previous, simultaneous and subsequent transitional cell carcinoma, respectively. CONCLUSIONS: Recurrence is not uncommon and risk of subsequent transitional cell carcinoma is not rare, such that non-invasive surveillance with flexible cystoscopy is recommended for inverted papilloma of the lower urinary tract.

Supine position is safe and effective for percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: The prone position has been widely adopted in conventional percutaneous nephrolithotomy (PCNL). Following its introduction in 1998, we changed our routine practice of PCNL from the prone to the supine position, which had numerous benefits and was safe and effective. Tract formation and stone fragmentation and retrieval were accomplished with the patient supine. PATIENTS AND METHODS: We report our experience with 62 patients (67 renoureteral units) treated in the supine position and describe the technique in detail. RESULTS: The primary stone clearance rate was 76%, and the mean number of sessions of PCNL was 1.3. There was no procedure-related major complication. There were also no splanchnic injuries. One kidney loss (emergency nephrectomy for control of hemorrhage) was noted but was not directly related to the procedure (profuse bleeding after accidental traction on the balloon nephrostomy tube by the patient 1 week after PCNL). Modification of positioning was made to suit the body build of Chinese patients. CONCLUSION: There are several advantages to the supine position for the patient and the urologist, with greater versatility of stone manipulation along the whole upper urinary tract. There are a few limitations of the supine position, but they can be overcome. Performing PCNL with the patient in the supine position is a sound alternative to the conventional prone position.

A rare cause of acute urinary retention: urethral metastasis from renal cell carcinoma.

Metastatic renal cell carcinoma in the urethra is exceedingly rare, with only three cases of metachronous metastases previously reported. We report a 78-year-old man with acute urinary retention secondary to urethral metastasis presented as the first clinical manifestation. Subsequent investigation confirmed a primary in the right kidney. Radical nephrectomy and total penectomy were performed aiming for cure, though the patient died with brain metastases 22 months after the surgery. The incidence and route of spread of the disease are discussed. The presentation, treatment and outcome of the reported cases are reviewed.

The CDK subunit CKS2 counteracts CKS1 to control cyclin A/CDK2 activity in maintaining replicative fidelity and neurodevelopment.

CKS proteins are evolutionarily conserved cyclin-dependent kinase (CDK) subunits whose functions are incompletely understood. Mammals have two CKS proteins. CKS1 acts as a cofactor to the ubiquitin ligase complex SCF(SKP2) to promote degradation of CDK inhibitors, such as p27. Little is known about the role of the closely related CKS2. Using a Cks2(-/-) knockout mouse model, we show that CKS2 counteracts CKS1 and stabilizes p27. Unopposed CKS1 activity in Cks2(-/-) cells leads to loss of p27. The resulting unrestricted cyclin A/CDK2 activity is accompanied by shortening of the cell cycle, increased replication fork velocity, and DNA damage. In vivo, Cks2(-/-) cortical progenitor cells are limited in their capacity to differentiate into mature neurons, a phenotype akin to animals lacking p27. We propose that the balance between CKS2 and CKS1 modulates p27 degradation, and with it cyclin A/CDK2 activity, to safeguard replicative fidelity and control neuronal differentiation.

Anti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered as auxotrophic for arginine and BCT-100, a new recombinant human arginase, has been synthesized for arginine deprivation to inhibit arginine-dependent tumor growth. The aim of the present study was to evaluate the effects of BCT-100 on the inhibition of in vitro cell proliferation of HCC cell lines and in vivo tumor growth. The molecular mechanism involved was also studied. The anti-tumor efficacy of BCT-100 on cell proliferation, cell cycle distribution and cellular apoptosis were determined in human hepatoma HepG2 and PLC/PRF/5 cells. Protein expression in the Wnt/ß-catenin and Akt signaling pathways were analyzed by western blotting. Tumors were also established subcutaneously and BCT-100, in combination with oxaliplatin, was administrated i.p. to study the anti-tumor growth of the drugs. Treatment with BCT-100 was found to inhibit cell proliferation and enhance caspasedependent cellular apoptosis. Cell cycle arrest at S phase was observed. Inhibition of Wnt/ß-catenin and Akt signaling pathways, with a reduction in survivin and XIAP protein expressions, were also observed. Furthermore, combined treatment of BCT-100 and chemotherapy with oxaliplatin demonstrated synergistic inhibiting effect on tumor growth and the overall survival probability was enhanced as compared with BCT-100 or oxaliplatin treatment alone. These preclinical data demonstrate robust anti-tumor activity of BCT100 in HCC, thus providing the basis for its exploitation as a potential therapeutic agent in arginine-driven tumors. The positive effect of testing BCT100 with oxaliplatin in PLC/PRF/5 tumours also supports the rationale of combining BCT-100 and oxaliplatin in the clinical treatment of HCC.

Pneumovesicum approach to en-bloc laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial cancer: midterm oncological results.

INTRODUCTION: We reported the pneumovesicum (PV) approach to lower ureter and bladder cuff excision and closure. We believe that this approach bears the closest resemblance to the laparoscopic skill set of intravesical dissection and suturing. Herein, we report the midterm oncological results of the approach's use in a series of patients with upper tract urothelial cancer. MATERIALS AND METHODS: From July 2004 to May 2010, 10 patients with upper tract urothelial cancer who underwent PV-assisted laparoscopic nephroureterectomy (LNU) were reviewed. Laparoscopic ports were inserted into the bladder via a suprapubic route, and carbon dioxide PV was induced. Laparoscopic dissection of the lower ureter and excision of the bladder cuff were then performed. The bladder defect was securely closed using laparoscopic suturing, and standard LNU followed. RESULTS: Nine men and one woman with a mean age of 71.6 years (47-82) underwent the procedure. Six of the patients had renal pelvic tumor, two had upper ureter tumor, one had midureter tumor, and one had synchronous renal pelvis and upper ureter tumor. In terms of final pathology, there were three, two, and five patients with T1, T2, and T3 diseases, respectively. All of the patients had grade 2 (G2) disease, except for two with grade 3 (G3) disease. Over a median follow-up of 46 months (22-67 months), four patients developed superficial bladder tumor recurrence. The bladder and systemic recurrence rates were 40% and 10%, respectively. There was no port site recurrence. CONCLUSION: Based on our midterm follow-up information, it can be concluded that the PV approach to en-bloc bladder cuff excision and LNU for upper tract urothelial cancer provides intermediate oncological results comparable to those of other approaches to en-bloc excision of the bladder cuff.

Breast metastasis from prostate cancer and interpretation of immunoreactivity to prostate-specific antigen.

A case of prostate cancer metastasized to the breast is presented, the latter being prostate-specific antigen (PSA) positive. This is the first of such cases reported in Hong Kong and China in the English literature. As PSA expression also can be found in primary breast cancer, prostatic acid phosphatase staining was employed to confirm the diagnosis. The relationship of PSA and non-prostatic tissues is reviewed. The differential diagnosis of breast enlargement in patients known to have prostate malignancy also is discussed.