First-time versus recurrent penoscrotal extramammary Paget's disease: Clinicopathological characteristics and risk factors in 164 Chinese male patients.

BACKGROUND: Penoscrotal extramammary Paget's disease is a rare, slow-growing neoplasm with high frequency of local recurrence. AIMS: The aim of this study was to investigate the difference in clinicopathological characteristics between first-time and recurrent penoscrotal Paget's disease, and to discover the potential risk factors of recurrence. METHODS: Between January 2007 and February 2014, a total of 164 Chinese patients with biopsy-proven tramammary Paget's diseaseex in penis and scrotum underwent wide local resection in our institution. Among them, 142 patients with first-time disease and other 22 patients with recurrent disease were enrolled in this retrospective analysis. RESULTS: The median duration of symptoms was much shorter in recurrent disease than in first-timers (3 vs. 24 months, P < 0.001). Patients with recurrent disease tended to have lower lesion exudation rates (27.3% vs. 51.8%, P= 0.032). In addition, patients with distant stage were more likely to obtain recurrent disease compared with first-time disease (P = 0.005). Through immunohistochemical detection of extramammary Paget's specimen, we found that HER2/neu protein expression in the recurrent group was significantly higher than first-timers (P = 0.036). LIMITATIONS: In this study, the information on familial history of most patients was insufficient. Moreover, due to the lack of follow-up data of our included cases, we were unable to evaluate the prognosis after diagnosis of extramammary Paget's disease. CONCLUSION: Patients with penoscrotal Paget's disease, especially those with shorter duration of symptoms, exudation of lesions, distant-stage, Paget cells infiltrating into adnexa, and HER2/neu expression, should be followed up more carefully after surgery, as they were more likely to suffer recurrence.

Time-of-flight mass spectrometry in screening serum-specific protein in patients with scrotal Paget's disease.

The weak cationic chip (WCX2) and the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used to test the serum differential proteins in 20 healthy persons, 20 patients with chronic scrotal eczema, and 30 patients with scrotal Paget's disease and test the specificity and sensitivity of screening scrotal Paget's disease with differential proteins. We found that the differences between the 5 protein peaks of the normal group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da were statistically significant (P < .01) and the difference of 3 protein peaks between the scrotal eczema group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da was statistically significant (P < .05). SELDI-TOS-MS technique has certain application value in the early diagnosis of the scrotal Paget's disease and screening for the specific tumor markers.

Estrogen-receptor-alpha-positive extramammary Paget's disease treated with hormonal therapy.

The patient was an 80-year-old man with scrotal and penile extramammary Paget's disease and prostate cancer. Both diseases were in advanced stages. Tumor cells of extramammary Paget's disease strongly expressed estrogen receptor alpha. The patient was concurrently treated with two kinds of hormonal therapy: the anti-estrogen tamoxifen (20 mg/day orally) for extramammary Paget's disease and the anti-androgen bicalutamide (80 mg/day orally) for prostate cancer. The toxicity of the therapy was mild. All of the metastatic lesions remained stable for 2 months after initiation of dual hormonal therapy. During a follow-up period of 22 months, performance status was well maintained for 17 months. Hormonal therapy may be an alternative for selected cases of advanced extramammary Paget's disease.

Inhibins as biomarkers for reproductive cancers.

Inhibin is a dimeric (alpha and either betaA or betaB subunit) protein involved in the regulation of fertility. Inhibin A and B or its free alpha subunit monomer are elevated in various gonadal and prostate cancers and thus serve as useful diagnostic tools for certain ovarian tumors either as a serum marker or as an immunocytochemical marker for tissue sections. Serum inhibin levels are of value in the initial diagnosis and subsequent follow-up of sex cord stromal tumors, in particular granulosa cell tumors, and mucinous epithelial adenocarcinomas primarily after menopause. Immunocytochemistry using inhibin alpha subunit antisera can aid in the classification of sex cord stromal tumors and their differentiation from other cancers. Although serum inhibins are elevated in prostatic and testicular cancers, this is of little diagnostic value at the present time.

Darbepoetin alfa administered every 2 weeks alleviates anemia in cancer patients receiving chemotherapy.

The objectives of this study were to assess the safety and efficacy of darbepoetin alfa (Aranesp) administered every 2 weeks in anemic patients with solid tumors receiving chemotherapy. This was an open-label, randomized, active-controlled, multicenter dose-finding study evaluating a range of every-2-week darbepoetin alfa doses. The active control arm received epoetin alfa (Epogen, Procrit) at 40,000 U weekly with a dose increase to 60,000 U weekly for subjects with an inadequate response. The lowest clinically effective doses of darbepoetin alfa in this study were 3.0 and 5.0 microg/kg every 2 weeks, with no additional benefit observed at higher doses. The percentage of patients who achieved a hematopoietic response in the 3.0- and 5.0-microg/kg groups was 66% (95% confidence interval [CI] = 46%-86%) and 84% (95% CI = 67%-100%), respectively, compared with 63% (95% CI = 46%-81%) in the epoetin alfa group. Darbepoetin alfa administered at a dose of 3.0 microg/kg every 2 weeks is safe and effective for treating anemia in patients with solid tumors on chemotherapy, and is comparable to epoetin alfa. A dose increase to 5.0 microg/kg of darbepoetin alfa administered every 2 weeks may be appropriate in patients with an inadequate initial response.

Clinical trial simulation of a 200-microg fixed dose of darbepoetin alfa in chemotherapy-induced anemia.

Our objective was to assess, using clinical trial simulation, the feasibility of a fixed 200-microg dose of darbepoetin alfa (Aranesp) administered every 2 weeks in chemotherapy-induced anemia. A pharmacokinetic/pharmacodynamic model was developed using clinical data from 547 cancer patients who received darbepoetin alfa at various doses and schedules. Monte Carlo simulations were performed for weight-based (3 microg/kg every 2 weeks) and fixed-dose (200 microg every 2 weeks) regimens and were compared with observed clinical data. Mean hemoglobin changes from baseline to end of treatment were +1.61 g/dL, +1.83 g/dL, and +1.79 g/dL for observed data, the weight-based simulation, and the fixed-dose simulation, respectively. The rates of required transfusions (hemoglobin < or = 8 g/dL) were also similar between groups. For patients between 45 and 95 kg (over 90% of the population), the impact of a fixed dose on mean hemoglobin change was negligible. There was a slight weight effect at body weight extremes (< 45 kg and > 95 kg). Clinical outcomes from simulations of weight-based andfixed dosing of darbepoetin alfa were similar to those of observed weight-based data. Given the weight distribution of a typical cancer population, the majority would be expected to benefit equally from weight-based and fixed-dose darbepoetin alfa in the amelioration of chemotherapy-induced anemia.

Prostate cancer involving the bladder neck: recurrence-free survival and implications for AJCC staging modification. American Joint Committee on Cancer.

OBJECTIVES: In the American Joint Committee on Cancer (AJCC) TNM staging system, prostate cancer involving the bladder neck after radical prostatectomy is considered pT4 disease, suggesting a high risk of recurrence. The recurrence risk with pathologic invasion of the bladder neck, however, has not been definitively compared with that associated with extra-organ disease. We therefore compared the recurrence risk in cases with bladder neck involvement with that of cases with extraprostatic extension and/or seminal vesicle invasion. METHODS: The study cohort was composed of 1123 men with clinically localized prostate cancer treated with prostatectomy as monotherapy. The preoperative prostate-specific antigen (PSA) level, bladder neck involvement, margin positivity, Gleason score, and other pathologic categories were assessed as covariates contributing to the PSA-recurrence risk in univariate and multivariable models. RESULTS: Bladder neck involvement was found in 60 (5%) of 1123 cases. In univariate analysis, the bladder neck was the site-specific margin with the greatest PSA-recurrence risk of focal involvement (relative risk 1.52, 95% confidence interval [CI] 1.15 to 2.00, P = 0.0030). The PSA-recurrence relative risk with extraprostatic extension was 3.05 (95% CI 2.13 to 4.38, P <0.0001) and with seminal vesicle invasion was 8.59 (95% CI 5.76 to 12.82, P <0.0001). In the multivariable model, the PSA-recurrence risk with bladder neck involvement (relative risk 1.19, 95% CI 0.72 to 1.96, P = 0.5) was not a significant independent prognostic factor. Extraprostatic extension (relative risk 2.25, 95% CI 1.54 to 3.27, P <0.0001) and seminal vesicle invasion (relative risk 4.12, 95% CI 2.57 to 6.62, P <0.0001) were significant independent predictors of PSA recurrence. CONCLUSIONS: Any staging system should be evidence based. The current AJCC system for staging bladder neck involvement, however, is contrary to the available evidence. Reclassification of bladder neck involvement as part of the pT3 category should be considered.

Perineural invasion and seminal vesicle involvement predict pelvic lymph node metastasis in men with localized carcinoma of the prostate.

PURPOSE: We evaluate the contribution of perineural invasion and seminal vesicle biopsy results in predicting pelvic lymph node metastases in men with T1 or T2 adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 212 men with localized prostate cancer were evaluated for serum prostate specific antigen (PSA), clinical stage, Gleason score and the presence of perineural invasion. Each patient had undergone seminal vesicle biopsies and a laparoscopic pelvic lymph node dissection before definitive therapy. The pretreatment prognostic values, presence of perineural invasion and seminal vesicle involvement were compared to the results of the laparoscopic pelvic lymph node dissection. Differences in proportions were tested using the Pearson chi-square test. The effect of multiple variables was tested using a stepwise logistic regression analysis. RESULTS: PSA ranged from 1.6 to 190 ng./ml. (median 11), and 52% of patients had Gleason score 7 or greater and 67.5% had clinical stage T2b or greater disease. Of the 212 patients 37 (17.5%) had perineural invasion, 43 (20.3%) seminal vesicle involvement and 21 (10%) positive node dissections. A PSA greater than 20 ng./ml. (20 versus 6.8%, p = 0.006), Gleason score 7 or greater (15.5 versus 3.9%, p = 0.005), clinical stage T2b or greater (14 versus 0.6%, p = 0.004), presence of perineural invasion (27 versus 6%, p = 0.0001) and seminal vesicle involvement (32.6 versus 4.1%, p <0.0001) influenced nodal findings. However, in the logistic regression model only the positive seminal vesicle biopsy (p = 0.0006), presence of perineural invasion (p = 0.04) and PSA greater than 20 ng./ml. (p = 0.044) were significant variables. Of the 21 men with positive node dissections 18 (85.7%) had a positive seminal vesicle biopsy or perineural invasion. Separation of patients into a high risk group defined by a positive seminal vesicle biopsy or perineural invasion, or a low risk group defined as the absence of these features yielded a significant association with nodal involvement (28 versus 2%, p <0.0001). A separate analysis of the patients with a negative seminal vesicle biopsy demonstrated that only perineural invasion (19 versus 2%, p = 0.0002) and PSA greater than 20 ng./ml. (12 versus 2%, p = 0.01) conferred a greater risk of nodal metastases. A logistic regression analysis in the negative seminal vesicle biopsy group discarded all of the variables other than perineural invasion as significant. CONCLUSIONS: A positive seminal vesicle biopsy is the most significant predictor of pelvic lymph node metastases in men with T1 or T2 prostate cancer. Perineural invasion is also an independent predictor of nodal disease. Patients with either of these features should undergo pelvic lymph node dissection before receiving definitive therapy.

Serum copper and zinc concentrations in serum from patients with cancer and cardiovascular disease.

A single cross-sectional study for serum copper and zinc levels was evaluated in 20 patients with cancer (respiratory, digestive, haematological, gynaecological) and 21 patients with cardiopathy (acute myocardial infarction and ischemic cardiomyopathy). A control group of 84 healthy subjects was selected. The mean serum zinc levels in patients with gynaecological cancer and ischemic cardiomyopathy were significantly lower than the control group (P < 0.05). However, the mean serum copper level was not statistically different among patients with cancer (P < 0.05) and cardiomyopathy (P > 0.05) than the control group. Male patients did not have statistically different values for serum Cu (P > 0.05) and Zn (P < 0.05) than those found in female patients. Patients' age did not have any statistical influence (P > 0.05) on serum Cu and Zn levels.

Masculinizing and feminizing syndromes caused by functioning tumors.

Steroidogenic tumors are derived from cells of male and female reproductive tracts, adrenal glands, central nervous system, and, to a lesser degree, from the liver and pituitary gland. The symptoms caused by these tumors are related to their secretory products. Because enzymatic pathways are shared by both adrenal- and gonadal-derived tissues, and the conversion of some of these steroids occurs in the adipose tissue, positive identification of many lesions cannot be based on peripheral blood hormone levels alone, but require complex protocols to improve diagnostic accuracy. Furthermore, these tumors often are smaller than the size limit of conventional imaging modalities and thus demand more precise imaging techniques. Although diagnosis and localization may be challenging, the rewards of a positive prognosis, with complete reversal of symptoms, are more likely to occur with early detection and treatment. This article is a review of the clinical syndromes associated with pediatric steroidogenic tumors; suggested strategies to facilitate their diagnosis, localization, and treatment are provided.

[Clinical evaluation of serum basic fetoprotein in patients with urogenital malignancies and renal transplantation].

The serum basic fetoprotein (BFP) in patients with urogenital diseases was measured by enzyme immunoassay (EIA). The positive range of serum BFP was defined to be 75 ng/ml or more. In benign cases except for renal transplantation, the positive rate of serum BFP was 11.1% (5/45), and relatively high (21.4%, 3/14) in benign prostatic hypertrophy. In cases of urogenital cancers before treatment, the positive rate of serum BFP was 29.1% (16/55), and increased with the progression of clinical stage. Eleven of the patients with positive serum BFP before treatment were re-examined after treatment, and all of them exhibited a marked decrease of the titer of serum BFP. In seventeen renal transplant patients, the positive rate of serum BFP was 100% (8/8) in acute rejection, 66.7% (2/3) in chronic rejection and 0% (0/6) in rejection-free condition. We conclude that serum BFP is a clinically beneficial marker for renal transplant rejections and urogenital malignancies.

Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors.

The allocation of patients with advanced germ cell tumors (GCT) to different treatment programs based on clinical characteristics is standard in the design of clinical trials today. Studies have shown that substantial differences exist between entry criteria and that these differences could influence the outcome of clinical trials. The factors contributing to these differences are not clear due to patient selection biases. Two hundred five unselected and consecutive patients allocated to and treated in good-risk and poor-risk treatment programs at Memorial Sloan-Kettering Cancer Center (MSKCC) were reassigned risk status by the Indiana University (IU) Classification. The results were compared with those of the Southeastern Cancer Study Group (SECSG). The results using both criteria indicated substantial agreement in total end results and the identification of good-risk patients. The results in poor-risk patients differed substantially, with 39 patients (19%) classified as poor-risk by MSKCC criteria and 66 (32%) by Indiana criteria. The major discrepancy occurred in IU Stage 7, in which 26 of 32 patients (81%) achieved a complete response. The major factor contributing to this difference in risk assignment was the use of serum tumor markers. Serum tumor markers must be incorporated into risk assignment criteria for GCT clinical trials to minimize the number of good-risk GCT patients in poor-risk trials.

Proton nuclear magnetic resonance spectroscopy of plasma from healthy subjects and patients with cancer.

To evaluate the ability of proton nuclear magnetic resonance (NMR) spectroscopy to indicate the presence or absence of malignant disease, we analyzed plasma samples from 104 patients with untreated cancer of various types and from 164 healthy controls. All specimens were coded with random numbers, and the investigators were blind to patient category. A statistically significant difference (P less than 0.001) was found between the mean (+/- SD) line widths in the plasma samples from the controls (39.1 +/- 6.7 Hz) and the line widths in plasma from the patients with cancer (35.2 +/- 6.4 Hz). However, the values showed considerable overlap between the two groups. The average line widths in the 54 male (36.0 +/- 7.9 Hz) and the 110 female (40.5 +/- 5.6 Hz) controls were significantly different (P less than 0.001). Differences in the average line width were also found between 34 male controls 40 years old or older (33.9 +/- 6.5 Hz) and 20 younger men (39.6 +/- 8.8 Hz) (P = 0.008) and between 61 female controls 40 or older (38.8 +/- 5.7 Hz) and 49 younger women (42.5 +/- 4.7 Hz) (P less than 0.001). The average line widths in 36 women with cancer (35.5 +/- 6.8 Hz) and their controls matched for age and sex (39.0 +/- 6.3 Hz) were significantly different (P = 0.03) but again showed much overlap. In 29 men with cancer, the line widths were not different from those of controls matched for age and sex. We conclude that proton NMR spectroscopy is not generally reliable for the detection of cancer. Furthermore, our data demonstrate the importance of studying control groups matched for age and sex.

New cancer markers.

In recent years many new and improved cancer markers have become available. From a clinical point of view, the most useful of the new markers include CA 19-9 for pancreatic adenocarcinoma, CA 125 for epithelial ovarian cancer, CA 15-3 for breast cancer, prostate specific antigen for prostatic adenocarcinoma, placental alkaline phosphatase for testicular seminomas and neuron-specific enolase for small cell carcinoma of lung. None of these new markers are specific for cancer. Furthermore, none are organ specific, except prostate specific antigen for prostatic tissue. The main application of these markers is in monitoring patients with the specific malignancies indicated. Whether routine use of any of these new markers leads to higher quality of life or enhanced survival remains to be determined.

Neurofibromatosis, factor IX deficiency, and rhabdomyosarcoma.

A paratesticular rhabdomyosarcoma occurred in a child with factor IX deficiency and neurofibromatosis, illustrating the need to consider carefully the various etiologic possibilities of a soft-tissue mass in a child with neurofibromatosis and/or a bleeding disorder.

[Blood fibronectin changes in various neoplasms]. / Modifications sanguines de la fibronectine au cours de divers néoplasmes.

In 85 patients presenting with various cancers, changes in the frequencies of plasma fibronectin and of the carcino-embryonic antigen (CEA) were compared and the results were correlated with the degree of extension. Forty-six percent of patients with mammary adenocarcinoma had plasma fibronectin values higher than the age-related limit range, but only 18% had an increase in CEA. In patients with secondary metastases, the highest values were significantly different from those found in controls. In these cases, fibronectin was present in abnormal concentrations in more than 80% of the patients, and CEA in 50%. Positive fibronectin values were less frequent in other cancers, except those of the genital tract. Neither fibronectin nor CEA are organ-specific, yet these two tumoral markers differ in the frequency with which they appear, notably in patients with mammary carcinoma.

Human chorionic gonadotrophin and subunits--heterogeneity in serum of male patients with tumours of the genital tract.

The pattern of secretion of human chorionic gonadotrophin (hCG) and its subunits in male subjects with tumours of the genital tract was examined by gel filtration, radioimmunoassay, immunoradiometric assay, bioassay and binding to Concanavalin A. The predominant form of hCG was the intact molecule but all patients had increased levels of free beta subunit. The intact hCG was active in a mouse Leydig cell bioassay and was normally glycosylated. High concentrations of free alpha subunit were not found and the ratio of alpha subunit: beta subunit was less than that in normal pregnancy. It is concluded that hCG-secreting tumours of the male genital tract are similar to choriocarcinoma in the female in that large quantities of intact hormone are produced with a disproportionate increase in free beta sub-unit.

Hypercalcemia and elevated serum parathyroid hormone level in association with rhabdomyosarcoma.

Pseudohyperparathyroidism to sarcomas is very rare. A 16-year-old boy had a rhabdomyosarcoma and severe hypercalcemia associated with an elevated serum parathyroid hormone (PTH) level and osteolytic bone metastases. The four parathyroid glands were normal. Both the hypercalcemia and the serum PTH level responded to chemotherapy.