Incidence, Risk Factors and a Novel Prevention Technique for Inguinal Hernia after Robot-Assisted Radical Prostatectomy.

INTRODUCTION: To evaluate the incidence and risk factors for postoperative inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) and to assess whether a newly developed prevention technique reduces the incidence of IH after RARP. METHODS: We included 161 consecutive patients (322 groins) who underwent RARP between September 2011 and October 2013. The prevention technique was as follows: (1) sufficient incision of peritoneum around the internal inguinal ring; (2) separation of spermatic vessels; (3) dissection of vas deferens. RESULTS: Postoperative IH occurred in 14 cases (19.4%) occurring in the observation group compared to 2 cases (2.2%) in the prevention group. Patent processus vaginalis (PPV) was the only risk factor. Time-to-event analysis demonstrated a significant decrease in IH incidence in the IH prevention group (p = 0.005). CONCLUSION: Our data reveal a higher incidence of IH after RARP, with the existence of PPV as the only identified risk factor. Our simple IH-prevention technique, which does not involve the use of artificial materials, appears safe and effective.

Practical Index of Urinary Incontinence Following Holmium Laser Enucleation of the Prostate: A Case-Series Study of the 24-Hour Pad Test Immediately after Catheter Removal.

INTRODUCTION: Epidemiological data regarding complications after holmium laser enucleation of the prostate (HoLEP) are scarce in Japan. We examined the associations of the 24-hour pad test results immediately after HoLEP with continence acquisition at 3 months postoperatively. MATERIALS AND METHODS: In this hospital-based case-series study, we reviewed medical charts of 341 patients without catheterization and 150 patients with catheterization at the time of surgery. The 24-hour pad test was conducted immediately after catheter removal to measure the leakage weight. Subjects were divided into 2 groups: leakage weight = 0 g (negative) and >0 g (positive). Urinary incontinence (UI) at 3 months postoperatively was self-reported by patients. RESULTS: Significant relationships were observed between pad test positivity and UI at 3 months postoperatively and between the pad test weight and the timing of continence acquisition in patients with and without catheterization. In multivariate analyses, the pad test positivity was associated significantly with the Overactive Bladder Symptom Score and enucleated tissue weight in patients without perioperative catheterization and with age in patients with catheterization. CONCLUSIONS: The 24-hour pad test immediately after catheter removal could indicate the need for early and active intervention to prevent continuous postoperative UI. Patients' symptoms and clinical items predictive of test positivity should be carefully assessed.

Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.

BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. METHODS: Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). RESULTS: Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.

Modified anterior approach to the bladder neck: simple and reproducible procedure for anterior bladder neck transection during robot-assisted radical prostatectomy.

To evaluate the feasibility and reproducibility of a simple technique for identifying the initial cutting point of the bladder neck during robot-assisted radical prostatectomy. To precisely identify the prostatovesical junction, we first pulled the anterior bladder wall in an upward direction with the second arm to identify the precise location of the prostatovesical junction where anterior bladder neck dissection is initiated. After one experienced surgeon had established this technique, three surgeons who were less experienced in robot-assisted radical prostatectomy utilized this method for 50 consecutive robot-assisted radical prostatectomy cases. The pathological results and the time required to transect the anterior bladder wall were evaluated. There were no cases of positive resection margin on the site of bladder neck. The mean resection time was not significantly different when comparing less experienced surgeons with the experienced surgeon (P = 0.29). In conclusion, this method is a simple and reproducible way to identify the bladder neck during robot-assisted radical prostatectomy. This technique is also useful (for laparoscopic or open radical prostatectomy) even in difficult scenarios, such as post-transurethral resection of prostate cases.

Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration-resistant prostate cancer: a prospective analysis of consecutive cases.

INTRODUCTION/BACKGROUND: Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes. PATIENTS AND METHODS: Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively. RESULTS: A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities. CONCLUSION: Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.

Relationship between prostate-specific antigen levels and ambient temperature.

We examined the association between prostate-specific antigen (PSA) and daily mean ambient temperature on the day of the test in healthy men who had three annual checkups. We investigated 9,694 men who visited a hospital for routine health checkups in 2007, 2008, and 2009. Although the means and medians of ambient temperature for the three years were similar, the mode in 2008 (15.8 °C) was very different from those in 2007 and 2009 (22.4 °C and 23.2 °C). After controlling for age, body mass index, and hematocrit, a multiple regression analysis revealed a U-shaped relationship between ambient temperature and PSA in 2007 and 2009 (P<0.001 and P=0.004, respectively), but not in 2008 (P=0.779). In 2007, PSA was 13.5% higher at 5 °C and 10.0% higher at 30 °C than that at 18.4 °C (nadir). In 2009, PSA was 7.3% higher at 5 °C and 6.8% at 30 °C compared with the level at 17.7 °C (nadir). In logistic regression analysis, a U-shaped relationship was found for the prevalence of a higher PSA (>2.5 ng/mL) by ambient temperature, with the lowest likelihood of having a high PSA at 17.8 °C in 2007 (P=0.038) and 15.5 °C in 2009 (P=0.033). When tested at 30 °C, there was a 57% excess risk of having a high PSA in 2007 and a 61% higher risk in 2009 compared with those at each nadir temperature. We found a U-shaped relationship between PSA and ambient temperature with the lowest level of PSA at 15-20 °C.

Relationship between dietary factors and prostate-specific antigen in healthy men.

INTRODUCTION: There is little evidence indicating whether dietary factors influence prostate-specific antigen (PSA) concentrations. We examined whether nutritional factors, including energy, protein, fat, and carbohydrate intake were associated with PSA in healthy men. SUBJECTS AND METHODS: We investigated 13,594 men aged 50 years and over who visited a hospital for a routine health checkup between 2003 and 2007. Dietary intake was assessed using a food frequency questionnaire. We performed a multiple linear regression to examine the association between PSA and dietary intake. RESULTS: After controlling for age, body mass index, and physical activity, PSA was significantly negatively associated with percent protein intake (p for trend < 0.001). Compared with the lowest quintile, PSA was 5.8% lower (95% CI: -8.9 to -2.5%) in the highest quintile. We also observed a significant positive association between percent fat intake and PSA concentration (p for trend 0.043). PSA was 3.4% greater (95% CI: 0-6.9%) among men in the highest quintile compared with those in the lowest quintile. CONCLUSIONS: Men who had a lower percent protein intake and higher percent fat intake had an elevated PSA level, although the magnitude of these associations was small.

[Organ-sparing surgery for contralateral testicular tumor following orchiectomy : a case report].

A 30-year-old man underwent a left high orchiectomy because of stage I testicular tumor in December, 2006. A palpable nodule was noticed in the contralateral testicle in March, 2008. No tumor marker was elevated. Imaging studies including ultrasonography and magnetic resonance imaging showed a 13 mm tumor consisting of both a solid portion and a hemorrhagic cyst. A malignant tumor could not be ruled out completely based on examinations and his medical history. Tumor resection with partial orchiectomy was planned after informed consent. Preoperative serum concentration of free testosterone was 8.4 pg/ml, and motile sperm were found in the semen analysis. The tumor was resected while the spermatic cord was clamped transiently. The pathological diagnosis of frozen sections confirmed no malignancy, and the final pathological result was mature teratoma, no evidence of malignancy. No androgen substitution has been required. Furthermore, a few normal motile sperm were detected in the ejaculated semen after the surgery. Organ-sparing surgery for the contralateral testicular tumor following orchiectomy, can be considered to avoid infertility and hormonal substitutions.

Relationship between changes in haemoglobin A1C and prostate-specific antigen in healthy men.

BACKGROUND: Although many studies have shown an inverse relationship between diabetes and prostate cancer, it still remains unclear why diabetes may reduce the risk of prostate cancer. An inverse association between haemoglobin A(1C) (HbA(1C)) and prostate-specific antigen (PSA) also has been reported in previous studies that assessed the association cross-sectionally. To fully understand the relationship between diabetes and prostate cancer, it is essential to examine the association in a longitudinal design. The effect of plasma volume should also be considered in examining the PSA level. The aim of this study was to determine whether changes in HbA(1C) were associated with PSA levels, independent of plasma volume changes, as indicated by haematocrit and weight. METHODS: We investigated 5917 Japanese men aged 50 and over who visited St. Luke's International Hospital, Tokyo for routine health check-ups in 2006 and 2007. We performed a multiple linear regression analysis to examine any association between changes in HbA(1C) and PSA over 1 year. RESULTS: Adjusting for age, body mass index at baseline and changes in weight and haematocrit, the increases in HbA(1C) and PSA were concordant (5.7% increase per 1-unit HbA(1C) change; 95% confidence interval, 2.8-8.5%; p<0.001). CONCLUSIONS: In contrast to previous cross-sectional observations showing an inverse association between HbA(1C) and PSA, longitudinal observations suggest a positive association between the two. Further studies are needed to investigate the association between diabetes and prostate cancer.

Anteroposterior dissection HoLEP: a modification to prevent transient stress urinary incontinence.

OBJECTIVES: The prevalence of transient stress urinary incontinence (SUI) after HoLEP has been reported to be as high as 44%. Anteroposterior dissection HoLEP was newly developed to protect the urethral sphincter and therefore lower the incidence rate of SUI. This study was conducted to determine the SUI incidence rate after anteroposterior dissection HoLEP. METHODS: Sixty-eight consecutive patients with benign prostatic hyperplasia underwent HoLEP from January to December 2008. The first 31 cases (Surgery 1) underwent HoLEP according to Gilling's method. The next 37 cases (Surgery 2) underwent anteroposterior dissection HoLEP, where adenoma was dissected antegradely. This antegrade movement of the cystoscope allows the apical gland to be removed from the sphincter without causing damage. Surgical quality indexes (hemoglobin change, operating time, resected prostate volume) between the 2 groups were compared. All patients were assessed at 2 weeks postoperatively for clinical SUI, international prostate symptom score (IPSS), quality of life (QoL), and peak flow rates (Q(max)). RESULTS: Patient characteristics and surgical quality indexes did not differ between the 2 groups. Clinical SUI was found in 25.2% of cases in the Surgery 1 group, but only 2.7% in the Surgery 2 group. IPSS, QoL and Q(max.) were significantly improved postoperatively in both groups. At 2 weeks, the QoL of the Surgery 2 group was significantly improved compared with that observed for Surgery 1 (1.5 ± 1.1 vs 2.4 ± 1.0, P = .02). The Q(max.) of Surgery 2 was significantly higher compared with Surgery 1 (19.8 ± 8.4 vs 13.0 ± 4.7 ml/s, P = .02). CONCLUSIONS: These results indicate that our anteroposterior dissection HoLEP is a promising procedure to avoid postoperative SUI and also to substantially improve QoL.

Plasma volume changes affect prostate specific antigen in healthy men.

PURPOSE: Several studies show that prostate specific antigen inversely correlates with body mass index. Hemodilution may be responsible for the lower prostate specific antigen in obese men. Hematocrit is the most popular indicator of plasma volume. We examined the effect of hematocrit changes on prostate specific antigen in healthy men during 2 years. We also investigated the association between prostate specific antigen and plasma volume changes based on combined changes in body weight and hematocrit. MATERIALS AND METHODS: We reviewed the records of 8,338 men who visited our institution for routine health assessments in 2005, 2006 and 2007. Using the combination of body weight and hematocrit changes in 1 year we defined hemodilution as weight gain with decreased hematocrit and hemoconcentration as weight loss with increased hematocrit. RESULTS: On multiple regression analysis controlling for patient age and weight change the hematocrit change was significantly associated positively with the prostate specific antigen change between 2005 and 2006 (1.2%/1 U), and between 2006 and 2007 (0.7%/1 U, each p <0.001). After controlling for age participants with hemoconcentration showed significantly greater prostate specific antigen changes than those with hemodilution, that is 6.1% between 2005 and 2006, and 4.8% between 2006 and 2007 (each p <0.001). CONCLUSIONS: Hematocrit change was positively associated with prostate specific antigen change. Compared to men with hemodilution significantly greater prostate specific antigen changes were observed in men with hemoconcentration. Thus, plasma volume may explain the inverse relationship between body mass index and prostate specific antigen.

Office-based transurethral resection of multiple bladder tumors using blue dye-mixed local anesthesia: a descriptive cohort study.

OBJECTIVE: Hospitalization and general anesthesia to perform transurethral resection of bladder tumors (BTs) may not be necessary for small recurrent BTs. We developed a new outpatient procedure. PATIENTS AND METHODS: Patients with recurrent small tumors who had previously undergone transurethral resection of BTs for low-grade, noninvasive BTs were eligible for this new procedure. Between July 2005 and 2007, 21 surgeries were performed on 11 patients. The patients' mean age was 65.6 years. The bladder was dilated with CO(2) using a 15.5F flexible cystoscope. Blue dye-mixed local anesthetic (2% xylocaine:indigo carmine 8:2) was injected into the tumor base. The tumor was resected using electric current via a hot cup. Patients went home without an indwelling catheter if there was no hematuria in the first urination after the procedure. RESULTS: Fifteen surgeries revealed one tumor, two had two tumors, two had three tumors, and two had six tumors. No complications requiring hospitalization occurred. Each resected specimen included a submucosal layer that allowed differentiation between pTa and pT1. No thermal degeneration was apparent in the resected stumps on pathological examination. Sixteen cases were urothelial carcinoma, and five cases were benign. Fifteen of the malignancies were noninvasive/low-grade tumors, but one case was microinvasive/high grade (G3pT1). During follow-up (mean, 8.8 months) recurrence in the bladder was found in 47%, but there was no orthotopic recurrence in the tumor-resected region. CONCLUSION: Our method allows safe resection of multiple recurrent BTs on an outpatient basis. This approach is a promising method for pathological diagnosis and favorable local control.

Relationship between prostate-specific antigen and hematocrit: does hemodilution lead to lower PSA concentrations in men with a higher body mass index?

OBJECTIVES: To examine whether a lower hematocrit was associated with a lower prostate-specific antigen (PSA), when stratifying by body mass index (BMI) in healthy men. PSA test is widely used in screening for prostate cancer. Many studies have found that PSA levels inversely correlate with BMI. It remains unclear whether hemodilution causes this inverse relationship. METHODS: We investigated 19,367 men who visited a hospital for a routine health checkup in 2007. We obtained information on age, BMI, PSA, hematocrit, and smoking status. BMI was categorized as < 18.5, 18.5-22.0, 22.0-25.0, 25.0-30.0, and > or = 30.0 kg/m(2). RESULTS: In all subjects, older age and lower BMI were weakly correlated with a higher PSA (r = 0.20, P <.001 and r = -0.05, P <.001, respectively). A multiple regression model for predicting PSA was constructed using age, current smoking status, and hematocrit for each BMI category. After controlling for age and smoking, PSA increased significantly with increasing hematocrit in participants with BMIs of 18.5-30 kg/m(2) (all P <.001). For example, in men with a BMI of 22-25 kg/m(2), slight increases (1.4% increase; 95% confidence interval, 1.0%-1.9%) were observed in PSA with a 1-unit increase in hematocrit. CONCLUSIONS: In healthy men with a BMI of 18.5-30 kg/m(2), a lower hematocrit was significantly associated with a lower PSA. Hemodilution may explain the lower PSA levels observed in men with a higher BMI, resulting in an inverse relationship between BMI and PSA.

[IgG4-related idiopathic retroperitoneal fibrosis: a case report].

A 75-year-old man visited our hospital with the complaint of lumbago due to bilateral hydronephrosis. Computed tomographic (CT) scan revealed a thick and homogeneous retroperitoneal soft-tissue mass with isodensity to the muscle, which extended from around the kidneys to the bladder. His serum IgG4 level was extremely high. He also had proptosis. He was diagnosed as having retroperitoneal fibrosis due to IgG4- related sclerosing disease, and treated with glucocorticoid and azathioprine. After 2 months, partial regression of the mass was observed.

[Cystoscopy-assisted partial cystectomy for paraganglioma of the urinary bladder].

A 39-year-old woman visited our hospital with a complaint of gross hematuria. Cystoscopy revealed a nodular tumor 3 cm in diameter in the posterior wall of the bladder. A transurethral resection was performed. This initial operation was complicated by unexpected intra-operative high blood pressure and visualization was obscured by bleeding. The histological diagnosis was paraganglioma. Therefore, a partial cystectomy was planned. Using cystoscopy, a 10 mm margin was identified and marked using electrocoagulation, followed by an open surgical procedure. After laparotomy, drainage veins were identified and ligated under the guidance of flexible cystoscopy lighting. Intra-operative blood pressure was stable during the operation, and the margin was negative for tumor.

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

BACKGROUND: The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. METHODS: Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. RESULTS: The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). CONCLUSIONS: The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.

A deserosalized muscle layer covering method for antireflux ureteroileostomy: a preliminary clinical trial.

PURPOSE: To achieve complete protection of the upper urinary tract in patients with a neobladder we designed and clinically applied the deserosalized muscle layer covering method, a new antireflux ureteroileal reimplantation technique in which the terminal ureter is implanted in the muscle layer of the ileum. We present the operative procedure and preliminary results. MATERIALS AND METHODS: We created an orthotopic ileal neobladder after radical cystectomy in 5 patients with invasive bladder cancer. The ureters were reimplanted into the reservoir using the deserosalized muscle layer covering method. The functional outcome of this procedure was evaluated by radiological studies. RESULTS: No patients died during the perioperative period and no reimplanted ureters showed ureteral reflux or ureteral stricture during the observation period. Video cystometrograms demonstrated the complete prevention of reflux during the voiding and storage phases. CONCLUSIONS: The deserosalized muscle layer covering method provided a nonobstructed unidirectional flow of urine in all renal units examined in this study. The efficacy of this method was proved during short-term followup.

De-serosalized muscle layer covering method for antireflux ureteroileostomy: a new operative technique and pressure study with ureterometry at the ureteroileal anastomotic site in dogs.

PURPOSE: In pursuit of a more effective antireflux ureteroileostomy with a lower postoperative complication rate we performed a new operative technique and evaluated intraureteral pressure with ureterometry to examine the mechanism of antireflux function. MATERIALS AND METHODS: A total of 11 beagle dogs were used in this study. A 3 x 2 cm. section of the ileal serosa was removed, the severed ureter was directly anastomosed to the de-serosalized area and 1 cm. of terminal ureter and the direct anastomotic site were covered with the de-serosalized ileal wall. The bladder was augmented with the ileum containing the ureter. Postoperative evaluations were performed monthly and ureterometry of the reimplanted ureter was done 6 months postoperatively. RESULTS: Complete reflux prevention and a low stricture rate were achieved with this procedure. Direct ureteroileal anastomosis caused stricture in 1 of the 11 ureters but the covering procedure to prevent ureteral reflux caused no ureteral strictures. When the bladder was empty, ureteral closure pressure at the intramural portion of the ureter was low. At the phase of high intravesical pressure ureteral closure pressure at the intramural ureter was as high as intravesical pressure. CONCLUSIONS: The de-serosalized muscle layer covering method prevented ureteral reflux completely with a low stricture rate. The antireflux function of this method seems to depend on the flexibility of the terminal ureter covered with the de-serosalized ileal wall. Reflux prevention in the low intravesical pressure phase seems to be due to extension of the ileal wall.

Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

BACKGROUND: Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. METHODS: In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. RESULTS: We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. CONCLUSIONS: The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone.

The correlation of serum carbohydrate antigen 19-9 with benign hydronephrosis.

PURPOSE: High serum carbohydrate antigen 19-9 in patients with hydronephrosis but without malignant disease is reportedly rare but to our knowledge the clinical features of hydronephrosis that affect this level have not yet been clarified. We examined the correlation of serum carbohydrate antigen 19-9 with hydronephrosis status in patients with benign hydronephrosis. MATERIALS AND METHODS: We used 123 serum samples from 68 patients with and 55 without hydronephrosis. All patients enrolled in this study had no malignant disease. Serum carbohydrate antigen 19-9 was measured by immunoradiometric assay and that level was correlated with clinical factors. RESULTS: Serum carbohydrate antigen 19-9 in patients with hydronephrosis was significantly higher than in those without hydronephrosis (p <0.0001). The serum level was elevated to greater than 37 units per ml. in 25% of the patients with but in only 1.8% of those without hydronephrosis. In the hydronephrosis group the clinical features that significantly correlated with the increased serum level were bilateral hydronephrosis, urinary tract infection, proteinuria, increased serum blood urea nitrogen, severe urinary tract occlusion and high grade hydronephrosis. CONCLUSIONS: Serum carbohydrate antigen 19-9 was significantly elevated in patients with benign hydronephrosis. Hydronephrosis causes false-positive results when screening for malignant disease by serum carbohydrate antigen 19-9 measurement.