Isolated bilateral macrostomia: literature review and case report.

AIM: Macrostomia, or lateral cleft lip, which is known as Tessier cleft type 7, is one of the rarest facial anomalies. The purpose of this review is to describe the main characteristics, epidemiology, aetiology and treatment of this anomaly. METHODS: We present an overview of surgical techniques as well as a review of all 36 cases of bilateral asyndromic macrostomia reported to this da in the literature. Furthermore, we report the case of a 4-month male infant with bilateral transverse cleft lip and analyse the treatment decision and the procedure itself. CONCLUSION: Early diagnosis and surgical intervention are crucial in treating children with these malformations. Adequate timely reconstruction plays a main role in both physical and psychological rehabilitation.

Epidemiology of maxillofacial trauma in the elderly: A European multicenter study.

INTRODUCTION: The progressive aging of European population seems to determine a change in the epidemiology, incidence and etiology of maxillofacial fractures with an increase in the frequency of old patients sustaining craniofacial trauma. The objective of the present study was to assess the demographic variables, causes, and patterns of facial fractures in elderly population (with 70 years or more). MATERIALS AND METHODS: The data from all geriatric patients (70 years or more) with facial fractures between January 1, 2013, and December 31, 2017, were collected. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, etiology, site of facial fractures, synchronous body injuries, Facial Injury Severity Score (FISS). RESULTS: A total of 1334 patients (599 male and 735 female patients) were included in the study. Mean age was 79.3 years, and 66% of patients reported one or more comorbidities. The most frequent cause of injury was fall and zygomatic fractures were the most frequently observed injuries. Falls were associated with a low FISS value (P<.005). Concomitant injuries were observed in 27.3% of patients. Falls were associated with the absence of concomitant injuries. The ninth decade (P<.05) and a high FISS score (P<.005) were associated with concomitant body injuries too. CONCLUSIONS: This study confirms the role of falls in the epidemiology of facial trauma in the elderly, but also highlights the frequency of involvement of females, and the high frequency of zygomatic fractures.

Management of mandibular condylar fractures in patients with atrophic edentulous mandibles.

INTRODUCTION: Treatment of condylar fractures in patients with atrophic edentulous mandibles is a peculiar field that has been little considered in the literature. The aim of the study was to assess the demographic and clinical variables as well as management and outcome of mandibular condylar fractures in edentulous patients with atrophic mandibles that were treated at several European departments of oral and maxillofacial surgery. METHODS: The data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between January 1, 2008, and December 31, 2017. Only patients that were diagnosed with condylar fractures of the edentulous atrophic mandible were included. RESULTS: A total of 52 patients met the inclusion criteria and were included in the study: 79% of patients reported one or more comorbidities. Thirty-four unilateral neck or subcondylar fractures, 9 bilateral neck or subcondylar condylar fractures, 7 unilateral head condylar fractures, and 2 bilateral head condylar fractures were diagnosed. No treatment was performed in 37 cases, whereas in 4 patients a closed treatment was decided, and 11 patients underwent open reduction and internal fixation. Outcome was considered to be satisfying in 48 patients, with no complications. CONCLUSIONS: The golden rule still remains that the diagnosis of a subcondylar or neck fracture in an edentulous patient should constitute an indication for open reduction and internal fixation. However, an appropriate choice of management options has to be individualized on a case by case basis, also depending on the patient consent.

Cross-correlation of serum chromogranin A, %-F-PSA and bone scans in prostate cancer diagnosis.

Circulating Chromogranin A (CgA), total PSA (TPSA) and F-PSA concentrations were measured in 211 patients (pt) with newly diagnosed prostate cancer (PC) and in 25 controls with benign prostatic hypertrophy (BPH). TPSA values ranging 3.5-5.5 ng/ml were found in 14 PC pt (6.6%), 5.5-9.9 ng/ml in 29 pt (13.7%), 10-19.9 ng/ml in 75 pt (35.6%), 20-50 ng/ml in 64 pt (30.3%) and > 50 ng/ml in 29 pt (13.7%). In those groups of PC pt false negative % F-PSA level > 18 was respectively measured in 0 out of 14, 2 out of 29 (6.9%) 6 out of 75 (8.0%), 61 out of 4 (9.4%) and 6 out of 29 (20.7%) pt, or totally in 20 out of 211 (9.5%) pt. Among 20 PC pt with false negative %F-PSA data elevated CgA level (> 80 ng/ml) was found in 18 subjects (18 out of 20 90%) or respectively in 0, 1/2 (50%), 516 (83%), 6 out of 6 (100%) and 6 out of 6 (100%) patients. Bone scintigraphy was performed in all pt with TPSA concentration > 10 ng/ml at the time of diagnosis. Bone lesions were respectively found in 4 out of 75 (5.3%) pt with TPSA 10-20 ng/ml, 12 out of 64 (14%) pt with TPSA level from 20-50 mg/ml and in 25k9 (75.9%) pt with. TPSA above 50 ng/ml. Overall osseous metastases were recorded in 41 out of 211 pt (19.4%) with newly diagnosed PC and in 18 of these Stage D2 pt (43.9%) elevated CgA concentration were measured Among them elevated CgA level and tumor dissemination matched with false negative %F-PSA parameter (> 18%) in 4 out of 18 (22.2%) pt as well as in 37 out of 191 (19.4%) pt with %F-PSA < 18% (p > > 0.05). In parallel, a positive CgA level in newly presented PC pt was closely associated with %F-PSA false negativity (18 out of 20, 90%). A negative correlation between TPSA elevation and the magnitude of CgA serotest level indicate differences in their biological origin and activities. According to the data reported herein we advocate the assessment of serum Chromogranin A concentration in first presented patients with clinically proven PC, elevated T-PSA level and %F-PSA parameter > 18%. Neuroendocrine structures are resistant toward hormonal treatment and hence CgA measurement is strongly suggested in all candidates for a systemic hormone therapy.

Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients.

Neuroendocrine (NE) differentiation in prostate cancer (PC) has attracted much attention since it has been shown to be associated with androgen independence and bad prognoses. In this study 34 patients with hormone refractory prostate cancer and elevated Chromogranin A (CgA) serum values were treated with estramustine for 15 months. The results were evaluated by analyzing clinical data and the serially measured total PSA and Chromogranin A serotest concentration, as well as bone scan recordings. In responders to therapy a sharp decline in CgA level was recorded as well as a slight decrease in the number of metastatic lesions in the bone. However, in 6- and 12-month nonresponders, supranormal serum CgA concentrations were measured (mean 305 +/- 122 ng/ml/ and 284 +/- 101 ng/ml, respectively). Statistical significance was found between neither of these groups (p > 0.05). Mean bone lesions data were practically identical in nonresponding groups (9.6 and 9.5) but were much lower in the respective responders (4.9 and 4.1). Twelve patients were found to be nonresponders 3 months after therapy initiation (12 out of 34, 35.3%). From the remaining 22 studied subjects a positive response patients continued in 17 patients during the next 3 months or overall in a six-month period (17 out of 34, 50%, or 17 out of 22, 77.3% from 3-month responders). After 9 months of therapy, 15 responding, patients were found (15 out of 34, 44.1%, or 15 out of 17, 88.2% from 6-month responders) while, after a full year of estramustine administration, 8 patients responded to therapy (8 out of 34, 23.5%, or 8 out of 15, 53.3% from responders after 9 months of treatment). Finally, after 15 months of treatment, only 3 responding patients found (3 out of 34, 8.8% or 3 out of 8, 37.5% from responders after 12 months of treatment). Mean response periods after 12 and 15 months of estramustine treatment were 5.5 and 5.7 months, respectively. In conclusion, the reported results indicate a 12-15 month responding period for estramustine therapy in patients with a slight initial elevation in CgA serotest (up to 150 ng/ml) and less than 10 metastatic osseous lesions. Thus, serum CgA assessment has definitely found a role in monitoring PC patients with NE positive stage D3 disease. This specially holds true as the population of aged men is rapidly increasing, posing a great challenge to urologists and oncologists in treating difficult-to-manage hormone-independent prostatic carcinoma.

Serum chromogranin A in monitoring metastatic prostate cancer patients.

In a number of studies the important role of neuroendocrine structures during the development of aggressive prostate cancer has been reported. We have recorded serum Chromogranin A and PSA values (CIS biointernational, France) in responders and nonresponders to both hormone therapy (Mab) and chemohormonal treatment (Estracyt) using (BPH) subjects as controls. In BPH patients (12 subjects) the mean CgA serotest value (+/- SD) was 23.3 + 13.9 ng/ml (range 7.2-55.9). In responders (24) and nonresponders (14) to Mab, respective values were 39.5 + 18.3 (7.6-78.4) and 214.8 + 250.3 (9.9-1084.3), while in responders (19) and nonresponders (12) to Estracyt, the mean CgA level was 47.6 +/- 22.7 (4.4-101.2) and 366.7 +/- 291.4 (82.0-925.7). In all patients osseous metastates were detected. Statistical P-values were > 0.05 in the correlation between both responders to hormonal therapy and Estracyt (P = 0.194) and nonresponders to these two therapies (P = 0.179). All other recorded P-values were < 0.01. In some nonresponders to Estracyt (3/12) the normal total PSA value together with %FPSA well below 20 indicated contribution of anaplastic tumor. Cessation of Estracyt therapy in 4/14 responders caused the sharp elevation of CgA serotest level. Accordingly, Estracyt may control the activity of CgA positive structure(s). In accordance with these preliminary data, we advocate the CgA serotest assessment in candidates for hormonal therapy as well as during follow-up of pharmacological treatment.

Free and total serum PSA values in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer and BPH. Is F/T PSA a potential probe for dormant and manifest cancer?

Free and total PSA serum concentrations were retrospectively measured in 106 subjects: 45 patients with intraepithelial prostatic neoplasia (PIN), 30 subjects with benign prostatic hypertrophy (BPH) and 31 subjects with untreated prostatic carcinoma. The (F/T) x 100 PSA value is recorded in subjects with the elevated total PSA level (> 4 ng/ml). PIN patients were divided into two groups: a low grade PIN (PIN 1) and high grade PIN (PIN II-III) patients. The mean (F/T) x 100 PSA value in low grade PIN patients was 27.9 +/- 16.2 (range 17.1-41.2, median 25.1) and has been numerically similar to the respective value in BPH subjects (29.1 +/- 13.2, 15.8-48.0, 27.7). These parameters differed markedly (P < 0.01) from the mean (F/T) x 100 PSA value in high grade PIN patients (16.9 +/- 9.0, range 9.9-24.9, median 16.5). The later values were in turn comparable (P > > 0.05) with the respective value measured in untreated prostate cancer patients (14.4 +/- 10.8, 6.6-21.4, 12.6). Hence, values derived from the measurement of free and total serum PSA level may distinguish low grade PIN that prevailingly remains latent disease from high grade PIN that is in most cases not only early prostatic carcinoma but that is often a precursor of an aggressive neoplasm. The published literature is incoherent regarding the influence of tumor spread on F/T PSA level. The cutoff point that divides BPH from cancer may depend on tumor stage. We have not investigated F/T PSA values related to different stages and grades of prostate cancer. The cutoff point of (F/T) x 100 PSA in our study that divides malignant from benign prostate, or latent from manifest cancer, was tentatively assigned as 18 with a specificity of 91% and selectivity of 69%. Our data are based on the application of the CIS assay that, according to the literature, gives higher F-PSA % compared to other respective kits.

Analysis of NK cell activity, lymphocyte reactivity to mitogens and serotest PSA and TPS values in patients with primary and disseminated prostate cancer, PIN and BPH.

In a total of 59 prostate cancer (PCa) patients, 9 patients with PIN. 29 subjects with BPH and 26 healthy men serum TPS and PSA values were measured together with NK cell activity, number and proportion of CD16+ cells, and reactivity of lymphocytes to mitogens (Con A. PHA and PWM). NK activity data indicate highly significant differences between both of patients with local tumor and those with disseminated disease (P < 0.01) and b) responders and nonresponding patients to hormonal therapy (P < 0.01). The number and proportion of CD16+ cells is lowest in BPH patients in comparison with controls and PCa patients. Since benign enlargement is attributed mainly to stromal cell proliferation in the absence of cell death in this compartment, gene expressions which control these events may participate in the surprisingly low CD16+ cell proportion. The reactivity of lymphocytes to mitogens (PHA. Con A and PWM) showed lower numerical values in all categories of PCa and BPH patients when compared with healthy men. The reactivity of T and B lymphocytes reported herein as immunological responses to mitogens (PHA. Con A and PWM) was performed 4-6 months after the beginning of therapy. Our data fit in well with those previously reported. Numerically lowest respective reactivity parameters to all mitogens were assessed in PIN subjects. Reported results show the specific significance of the changes in NK cell activity in regard with both metastatic extention of PCa and tumor response to therapy. These alterations match in their reliability changes with tumor marker values related to prostate cancer activity (TPS) and tumor differentiation (PSA). Lymphocyte reactivity to mitogens (Con A. PHA. PWM) may help in a subclinical discrimination between BPH and PIN patients that is still an important goal of clinical urology.

Immunohistochemical staining and serotest markers during development of a sarcomatoid and small cell prostate tumor.

Prostate cancer with marked neuroendocrine (NE) differentiation belongs to the hormone resistant carcinomas. We report the development of TSH-secreting small cell prostate cancer (SCPC) from high grade adenocarcinoma (Gleason score 8) with an elevated number of chromogranin A positive cells located in benign structures adjacent to the cancer. Conversion to SCPC was followed-up during 4 years. The initial adenocarcinoma exerted a stronger positivity for PAP than for PSA (respective staining indexes, Sls, 2.2 and 1.8, maximum staining 3.0). In the developed SCPC, 2 cell subpopulations that were derived from epithelial cells were found (positive stain for EMA and CEA, respectively) and from one of them originated CEA-positive liver metastases. Blood CEA and NSE levels were elevated in SCPC (284 ng/ml and 24.5 ng/ml). However, blood TPS level which reflects proliferation of epithelial cells was within the normal range. The development of a << pure >> sarcomatoid prostatic tumor from adenocarcinoma with 2 areas of similar differentiation grades (Gleason score 7 and 9-10) that initially differ in staining for PSA and PAP (SIs for PSA were 1.2 and 0.02 and for PAP were 1.6 and 0.02, respectively) was followed-up during 4 years of treatment with Estracyt. Adenocarcinoma tissue specimens was slightly CEA-positive. The disappearance of lower grade adenocarcinoma during treatment was accompanied by the development of sarcomatoid areas that were 100% vimentin positive. In the last year of follow-up the primary tumor was composed only of vimentin positive sarcomatoid cells with a slight positivity for Chromogranin A, NSE and ACTH. In parallel, normal serum PSA and PAP values and elevated CEA and NSE serotests (12.6 ng/ml and 24.7 ng/ml, respectively) were found. Blood TPS level was at the upper limit of the normal range. Scintigraphy revealed extensive liver metastases. The recorded data indicate (i) extremely poor prognoses associated with high grade adenocarcinomas that demonstrate stronger immunohistochemical positivity for PAP than that for PSA (ii), chromogranin A positive cells in benign structures adjacent to the cancer as a possible paracrine promoter of SCPC from poorly differentiated adenocarcinoma, and (iii) a high degree of heterogeneity of both SCPC and sarcomatoid prostatic neoplasms with some evidence for definite links (EMA and CEA) to secretory epithelial cells.

Serum TPS, PSA, and PAP values in relapsing stage D2 adenocarcinoma of the prostate.

Serum tissue polypeptide-specific antigen (TPS), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) concentrations were serially measured in 31 prostate cancer patients with bone metastases who had relapsed following hormonal therapy. Of these subjects 7 had well-differentiated cancer (G1), 13 patients were assessed to have moderately differentiated tumor (G2) while in 11 subjects poorly differentiated tumor (C13) was found. With increasing tumor grade (G1 to G3), a proportional increase in mean TPS value was found while the increase in respective PAP serotest values was not linear. Simultaneously measured mean PSA values showed a curved effect. Both PSA and PAP serotest concentrations depend on the respective hormone-dependent gene expressions that gradually decrease with tumor dedifferentiation. Therefore, in progressive hormonally treated stage D2 prostate cancer patients an androgen-independent TPS serotest seems to be a useful clinical addition for monitoring protocols. The combined use of TPS, PSA, and PAP seems to give a better reflection of tumor status. According to the bone scan data metastatic tumor mass in G3 carcinomas was virtually equal to cancer burden in G2 tumors. Hence, the marked elevation of TPS serotest values in G3 adenocarcinomas could not be attributed to greater tumor mass but was most likely due to an increase in proliferation rate. Some authors have recently proposed cytokeratins 8, 18, and 19 to be the origin of TPS serum findings. However, cytokeratin content has been proven to be lower in G3 tumors than in better-differentiated neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

A more objective staging of advanced prostate cancer--routine recognition of malignant endocrine structures: the assessment of serum TPS, PSA, and NSE values.

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogeneous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2 patients, with a small number of bone lesions (> or = 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (> 3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors.

Serial measurements of tissue polypeptide specific antigen (TPS), PSA, PAP and CEA serotest values in treated patients with primary and metastatic prostate cancer.

Blood tissue polypeptide specific antigen (TPS) concentration was serially measured by IRMA radioimmunodetective procedure in hormonally treated prostate cancer patients with Stage Do-D1 tumor (20 subjects free of bone lesions) and Stage D2 disease (20 subjects with bone metastases). Monoclonal antibody against the principle M3-TPA epitope was used in this TPS assay. Serum TPS values were compared with respective blood prostate specific antigen (PSA), prostatic acid phosphatase (PAP), carcinoembryonic antigen (CEA) and testosterone levels in a retrospective manner. A control group included healthy men, patients with benign prostatic hypertrophy (BPH), subjects with inflammation of the prostate, and men with diabetes. PSA is reported to be a quantitative calibration for prostate cancer load in untreated patients, especially during early stages of the disease. In hormonally treated, advanced, and dedifferentiated prostatic carcinoma this serotest fails to reflect properly both tumor status and response to treatment. In Stage Do-D1 patients TPS concentrations remain normal or become slightly elevated even during local tumor progression. This finding is in accord with the slow proliferation of nonaggressive primary tumors. Circulating TPS concentrations are elevated in progressive metastatic patients, in the majority of Stage D2 subjects with stable disease and even in some of these patients during partial tumor remission. This latter result may be attributed not only to the heterogeneity of the advanced prostatic cancer but also to the actual tumor response to treatment, since serum PSA level fails to reflect properly the outcome of hormonal treatment. There is some evidence that an abrupt elevation in serum TPA level in such patients is a consequence of NK cell-mediated lysis of circulating tumor cells, thus giving rise to a simultaneous and rapid delivery of intracellular TPS into the bloodstream. Prostatic inflammation elevates TPS concentrations only slightly, while diabetes, even during a proper treatment, raises TPS concentration more intensely. In patients with BPH normal or slightly increased TPS values were measured. The results ot these preliminary investigations seem to open the way for further prospective studies.

Comparison between NK cell activity and prostate cancer stage and grade in untreated patients: correlation with tumor markers and hormonal serotest data.

NK cell activity was measured in 24 patients with untreated prostate cancer (11 subjects with localized disease, D0, and 13 patients with stage D tumor) and 10 healthy controls. In these same subjects serum prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, prolactin and cortisol concentrations were assessed. The data obtained were correlated with both tumor spread (localized vs disseminated disease) and grade (well-differentiated cancer, G1, vs moderately and poorly differentiated carcinoma, G2 and G3). In patients with stage D0 cancer mean NK activity (33.0 +/- 10.6) was virtually identical with the mean value recorded in healthy men (34.5 +/- 7.1), while in subjects with stage D1-D2 disease NK activity was significantly reduced (11.9 +/- 7.1). These findings correspond with our data on treated subjects, in whom NK activity level was found to correlate well with the presence of tumor cells in the circulation. In subjects free of malignant tumors but with a chronic disease (diabetes, arthritis, severe rheumatic disorders) mean NK activity was clearly reduced (5.7 +/- 1.5). The use of NK activity data as a probe for tumor metastases was found to be statistically as reliable as was the application of the PSA serotest (but not serum PAP concentrations). None of the measured hormonal parameters correlated well with tumor stage. Both testosterone and prolactin serum concentrations were found to be lower in the G2 and G3 cancer group than in well-differentiated (G1) tumors, in accordance with the published literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of cell proliferation marker (TPS), natural killer (NK) activity and tumor load serotest (PSA) in untreated and treated prostatic tumors.

Tissue polypeptide specific antigen (TPS) is a new tumor proliferation serotest marker. The respective radioimmunodetective procedure is based on the application of monoclonal antibodies raised against one the principle epitopes of tissue polypeptide antigen (TPA). TPS is useful tool for the identification of proliferative epithelial cells and is negative in all non-epithelial tissues such as lymph nodes, bone marrow, carcino-sarcomic and neuroendocrine prostatic tumors. In previous studies we have shown the clinical usefulness of this serotest in serial measurements during prostate cancer monitoring. In this study serum prostatic specific antigen (PSA) concentrations and natural killer (NK) cell activity data were compared with serum TPS values in a wide spectrum of prostate cancer condition (99 patients), benign prostatic hypertrophy (BPH, 40 patients), atypical prostate (12 subjects) and in 8 healthy men. Measured parameters reflect different aspects of the disease. Blood PSA concentrations and TPS serotest values were found to denote the status of disseminated prostate cancer with nearly equal significance, while PSA appears to be a more appropriate tumor marker in early stages of the disease. In atypical prostate a nonsignificant elevation of both PSA and TPA values were recorded when compared with BPH. In parallel, a pronounced and sharp drop in NK activity data was assessed resembling closely respective data in progressive Stage D2 patients. TPS serotest clearly detects cancer progression in treated and untreated patients (P < 0.01) while being less efficient in distinguishing between tumor stabilization and partial remission (p > 0.05). In this respect NK activity data serve as a sensitive probe for the presence of epithelial tumor cells in the circulation even during stabilization of the disease. According to the reported results we advocate the application of the TPS serotest as a useful addition in monitoring progressive patients with advanced prostatic carcinoma.

NK cell activity in treated prostate cancer patients as a probe for circulating tumor cells: hormone regulatory effects in vivo.

Natural killer (NK) cell activity was studied together with tumor marker serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin concentrations in treated prostate cancer patients. NK cell activity data were correlated with tumor stage (stage D0 + D1 versus stage D2) and showed statistically insignificant differences. Both tumor progression and stabilization of metastatic disease, triggered by the application of more appropriate therapy in progressive subjects, yielded low NK activity data. By contrast, normal NK activity was found during both partial remission of stage D2 tumor and stabilization of the same disease, after an initial period of tumor remission. Differences between NK activity data from the aforementioned two groups are statistically significant (P less than 0.01). In subjects examined, the application of NK activity assay to those with advanced disease reflected changes in the outcome of the treatment more closely than it did routine tumor marker assessment. The activity of NK cells seems unaffected by changes in basal blood estradiol, cortisol, testosterone, and prolactin concentrations that occur during therapy with pharmacological agents (estradiol, cyproterone acetate, diethylstilbestrol, and flutamide) and during surgical castration. The reported NK activity recordings in treated prostate cancer patients might be indicative of the presence of tumor cells in the circulation. If this holds true, the measurement of NK activity would appear to furnish urological oncology with a new tool for early, rapid recognition of progressive metastatic tumors.

Plasma osteocalcin values and related hormonal parameters in patients subjected to a variety of prostate anticancer agents.

Circulating osteocalcin (OC) and cortisol levels were measured in blood samples from 93 patients with dissaminated prostate cancer. Among these subjects 79 had not responded to therapy, while 14 had responded to a variety of anticancer treatment strategies (orchiectomy, cyproterone acetate (CPA), flutamide, Buserelin, diethylstilbestrol (DES), Estracyt, and polyestradiol phosphate). The control group consisted of 19 patients with benign prostatic hypertrophy. In the majority of these patients blood adrenocorticotropic hormone (ACTH), estradiol human growth hormone (hGH), and thyroid stimulating hormone (TSH) levels were also assessed. In nonresponders to therapy with DES and Estracyt subnormal circulating OC levels were measured, while normal OC values were found in nonresponders to other treatment strategies. In patient given Estracyt highly elevated estradiol levels were recorded. Subnormal and/or low-normal estradiol concentrations were found in patients subjected to CPA and DES. Elevated blood cortisol levels were assessed in subjects treated with DES and Estracyt while at the same time either subnormal and low-normal plasma ACTH concentrations were measured in these same patients. Accordingly, the decline observed in OC concentration seems to be a consequence of the well-established inhibitory effect of glucorticoids on osteoblast activity. The decline in blood cortisol levels obtained after administration of dexamethasone in patients given DES and Estracyt may be attributed both to possible changes in catabolic pathways and to the contribution of the negative neuroendocrinological feedback.

Investigation on serum neurone-specific enolase in prostate cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay.

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

[Bacteriological analysis of the cervical canal in uterine cervix insufficiency]. / Bakterioloska analiza cervikalnog kanala kod insuficijencije grla maternice.

A bacteriological analysis was made of pyogenic agents from the cervical canal of 260 pregnant women with cervical incompetency, in whom the cerclage of the cervix was performed. Pyogenic agents were found in 139 (53.5%) pregnancies. The most frequently isolated pathogenic agent was Enterococcus--in 19.2% of all pregnant women and in 36.0% in those with a pathologic swab. E. coli was isolated in 16.5% of all pregnant women and in 30.9% of those with the pathologic swab. A significantly higher number of pathologic swabs were found in women with colpitis and the cleanliness 3 degree of the vaginal discharge and without colpitis (6.4%). In pregnant women with a pathologic swab, in spite of the cervical cerclage, spontaneous abortions and premature deliveries were significantly more frequent (8.2% and 16.4% respectively) than in pregnant women with a sterile swab (1.8% and 6.1% respectively).

Correlation between bone scans and serum levels of osteocalcin, prostate-specific antigen, and prostatic acid phosphatase in monitoring patients with disseminated cancer of the prostate.

Response of prostatic cancer bone metastases to therapy (androgen withdrawal and Estracyt) was studied in 43 patients by applying scintiscanning and radioimmunodetective measurement of serum osteocalcin (OC) values. The prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) concentrations, as sensitive probes for the overall tumor spread, were used in parallel in a monitoring procedure. A significant rise in OC levels to values elevated from a pretreatment normal level has been found in patients with a partial osseous tumor remission, and this may be easily distinguished from normal and/or subnormal OC level in bony tumor progression (P less than 0.01) and during stabilization in metastatic spread (P less than 0.01). On these bases, differences between disease progression and the "no change" response category could not be statistically recognized (P greater than 0.05). A sharp increase in circulating OC level has been recorded 1 months after the beginning of the treatment leading to bone remodeling processes and precedes improvements in scintiscan appearance. Blood OC concentration seems also to be of utility 1) in distinguishing scintigraphic flare phenomenon from a slight bone scan progression and 2) when related to scans with regions of both disease improvement and worsening. Furthermore, serum OC concentration can frequently be measured through a noninvasive procedure, thus serving as a significant addition to bone scintigraphy.

Unoccupied prolactin binding components of the benign and malignant human prostate in a subclinical and clinical procedure.

Optimal conditions for the quantitation of free prolactin binding components of human prostatic tissue obtained by TURP were studied by applying gamma receptor assay. The radioligand used was 125I-prolactin. Significantly greater heat stability of the prostate membrane prolactin binding sites, when compared to that of androgen cytoplasmic receptors, was confirmed. The saturability and specificity of the prolactin binding components was demonstrated by the results of both Scatchard plot analysis and displacement studies. Free prolactin receptors were found in none of the poorly differentiated (G3) prostatic tumors examined, and only in 62.5% of medium differentiated (G2) prostatic malignancies. The majority of tissue specimens coming from patients with either BPH or well differentiated prostatic tumor (G1) contain measureable amounts of free prolactin membrane binding components. In the present study we report also the case in which the change in tumor differentiation toward a higher grade (G2 to G1, provoked by the successful chemohormonal treatment) is accompanied with the appearance of previously absent free prolactin binding components. In histologically proven BPH tissue specimens free prolactin receptor negative status has been found in most patients with a slight increase in serum PAP values, while receptor rich status was detected in the majority of those with elevated PSA concentrations. We believe therefore that the prolactin receptor values, when used as part of the multivariable analysis, may participate in further delineation of the role of prolactin in the development of prostate cancer, but may also play a role in a subclinical prediction related to the conversion of either an adenoma or a latent adenocarcinoma to the clinically manifest prostatic malignancy.