Prognostic value of connexin43 expression in patients with clinically localized prostate cancer.

Connexins (Cxs) are a family of transmembrane proteins that build cell-to-cell channels in gap junctions. Gap junctions composed of Cxs have an essential role in intercellular communication, adhesion and cell differentiation. Several studies investigated the role of connexin43 (Cx43) in different carcinomas; however, none investigated its prognostic role in prostate cancer. Cx43 expression and relationship with established prognostic features were assessed in a cohort of 102 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Cx43 expression in prostate cancer was significantly associated with established features indicative of worse prognosis, such as follow-up time (P < 0.001) and preoperative PSA (P < 0.007). Patients with lower Cx43 expressions in tumours have shorter follow-up time, which indicated shorter disease-free survival and higher preoperative PSA values. Furthermore, tumours with positive surgical margins (P < 0.001) showed significantly lower Cx43 expression compared with tumours without this feature. In univariate (P < 0.001) and multivariate (P = 0.014) analyses, decreased Cx43 expression was found to be a significant predictor of biochemical recurrence free-survival. Study results show the association of decreased Cx43 expression with prostate cancer progression. Moreover, Cx43 could serve as an additional prognostic marker and used together with traditional prognostic markers might help in further stratifying the risk of disease progression in patients with prostate cancer.

Expression and prognostic role of syndecan-2 in prostate cancer.

Syndecans are a four-member family of transmembrane heparan sulphate proteoglycans that have different functions in cell signalling, adhesion, cytoskeleton organization, migration, proliferation, and angiogenesis. Several studies investigated the role of syndecan-2 (SDC2) in different carcinomas; however, only one being focused on SDC2 in prostate cancer. SDC2 expression and relationship with established prognostic features were assessed in a cohort of 86 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. SDC2 expression was present in the majority of prostate cancers and absent in only 11.6% of cases. SDC2 expression was also recorded in cells of prostatic intraepithelial neoplasia, whereas normal prostatic epithelial tissue and stroma did not express SDC2. SDC2 overexpression in prostate cancer was significantly associated with established features indicative of worse prognosis such as higher preoperative PSA (P=0.011), higher Gleason score (P<0.001), positive surgical margins (P<0.003), and extraprostatic extension of disease (P<0.003). Moreover, expression of SDC2 was also associated with biochemical disease progression on univariate analysis (P<0.001). Study results supported the potential role of SDC2 in prostatic carcinogenesis and cancer progression. Moreover, SDC2 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression in patients with prostate cancer.

Aggressiveness of inflammation in histological prostatitis--correlation with total and free prostate specific antigen levels in men with biochemical criteria for prostate biopsy.

BACKGROUND AND AIMS: Although prostatitis can contribute to the lack of prostate specific antigen (tPSA) specificity, there is disagreement concerning the effect of histological inflammation on free PSA (fPSA). We investigated the correlation between aggressiveness of histological inflammation and tPSA, fPSA and f/tPSA in patients without detectable prostate cancer (PC). METHODS: The study included 106 patients with tPSA <10 ng/mL, without clinical prostatitis and with biopsy negative for PC. The inflammation in prostate biopsies was scored for aggressiveness using the four-point scale reported by Irani. The patients were divided into two groups of less aggressive and more aggressive inflammation and compared by use of regression analysis. RESULTS: The median tPSA, fPSA and f/tPSA levels were 6.39 ng/mL, 1.1 ng/mL and 16% in the less aggressive inflammation group and 7.3 ng/mL, 0.79 ng/mL and 10.7% in the more aggressive inflammation group, respectively. There was no significant between-group difference in tPSA levels (P=0.16), however, statistically significant between-group differences were recorded in fPSA and f/tPSA levels (P<0.001 both). Spearman's analysis yielded a significant negative correlation of inflammation aggressiveness with fPSA (r=-0.34; P<0.001) and f/tPSA (r=-0.45; P<0.001). Free PSA and f/tPSA were lower in the group with more aggressive inflammation. CONCLUSIONS: Histological inflammation has a high prevalence in cancer-free prostate biopsy specimens and exerts similar effects on fPSA and f/tPSA levels as PC. Our study suggests histological prostatitis to be an important cause of decreased fPSA and f/tPSA values; therefore, when it is identified, antibiotic or anti-inflammatory therapy should be introduced to reduce the percentage of men with a continuing indication for prostate biopsy.

Holistic approach to analysis of medical data: cancer of the corpus uteri.

Besides the information regarding his/her disease, each hospitalized cancer patient also provides the variety of data regarding his/her psychological, cultural, social, economical, genetic, constitutional and medical background. The aim of this study was to introduce a holistic approach to analysis of medical data, in this case clinical data regarding cancer of the corpus uteri. Such approach requires the collection of data regarding different aspects of the cancer patient, and after the satisfactory sample size is obtained (which should be at least five times greater than the number of examined patient characteristics), the performance of factor analysis. In this study, the authors have processed the data regarding 25 characteristics of 928 corpus uteri cancer patients treated between 1980 and 1990 at the Department for Gynecological Oncology of the University Hospital for Gynecology and Obstetrics, Zagreb, Croatia. In factor analysis, the principal components were rotated after the initial extraction (the authors recommended the use of oblimin rotation) in order to obtain better ground for interpretation of the obtained results. The next step in this approach was the stepwise exclusion of characteristics with smallest communalities according to Kaiser-Meyer-Olkin criteria, and retaining the characteristics and components with the most significant impact on the explained system variance. When the number of principal components and initial analyzed characteristics was reduced to 3-4 and 7-10, respectively, the ultimate interpretations and conclusions were made. This approach outlined some clusters of correlations between medical data which are difficult to identify using other statistical procedures, primarily the impacts of various socioeconomic and hereditary-constitutional variables on overall survival.

Blinded comparison of cranial CT and MR in closed head injury evaluation.

PURPOSE: To compare CT and MR in the evaluation of acute head injury. METHODS: One hundred seven consecutive patients who were referred to the emergency department and underwent both MR and CT cranial examinations within 48 hours were retrospectively reviewed. The films were interpreted by two neuroradiologists blinded to all patient information. RESULTS: The sensitivity of MR was significantly higher than that of CT for the detection of contusion, shearing injury, subdural and epidural hematoma, and sinus involvement. The sensitivity of CT was significantly higher than that of MR for the evaluation of fracture. The sensitivities of MR and CT were statistically equivalent for the detection of superficial soft-tissue injury. The overall sensitivity of MR for the detection of abnormalities in acute head trauma was 96.4%, and for CT was 63.4%. CONCLUSIONS: CT and MR are complementary studies in the evaluation of acute head trauma. MR is necessary to define or exclude contusions, deep shearing injury, and extraaxial fluid collections in acute head trauma.

Adult "congenital" bilateral occlusion of the foramina of Monro.

Bilateral occlusion of the foramina of Monro was detected and treated in a hydrocephalic adult who developed rapid striking recent memory loss. She was treated by midline windowing of the third ventricle into the dilated lateral ventricles at a location 2 cm posterior to the occluded foramina of Monro. No inflammation was present. A biopsy specimen showed no evidence of malignancy. A reservoir was placed for long-term measurement of intraventricular pressure. Ten-year follow-up with pressure measurements, serial computed tomography scans, and magnetic resonance imaging showed no evidence of tumor.

Comparison of CT, low-field-strength MR imaging, and high-field-strength MR imaging. Work in progress.

To assess objectively the sensitivity and specificity of low-field-strength (0.064 T) magnetic resonance (MR) imaging, a prospective blind study of 280 examinations was performed to compare low-field-strength MR imaging with computed tomography (CT) and with high-field-strength (1.5-T) MR imaging of the cranium. The sensitivity (defined as the true-positive rate) with high-field MR imaging was superior to that with low-field MR imaging and CT in helping detect overall abnormalities. Sensitivities were generally similar over a broad range of specific cranial central nervous system diseases. Low-field and high-field MR imaging were equivalent in the blind diagnoses of neoplasms and white matter disease, whereas low-field MR and CT were equivalent in the blind diagnoses of contusion, subdural and epidural hematoma, sinus disease, normality, and abnormality. The specificities with low-field MR imaging and CT were substantially better than those with high-field MR imaging.

Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis.

The authors investigated whether identification of corpus callosal (CC) involvement might increase the specificity of magnetic resonance (MR) imaging in differentiating multiple sclerosis (MS) from other periventricular white matter diseases (PWDs). They prospectively evaluated 42 patients with MS and 127 control patients with other PWDs. Ninety-three percent of the MS patients demonstrated confluent and/or focal lesions involving the callosal-septal interface (CSI). These lesions characteristically involved the inferior aspect of the callosum and radiated from the ventricular surface into the overlying callosum. CSI lesions were optimally demonstrated on sagittal long repetition time (TR)/short echo time (TE) images and frequently (45% of cases) went undetected on axial images. Only 2.4% of the control patients had lesions of the CC. The authors conclude that midsagittal long TR/short TE images are highly sensitive and specific for MS and that callosal involvement in MS is more common than previously reported.

Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter.

Two types of high-signal intensity abnormalities are frequently found bilaterally in the cerebral white matter of brains of elderly patients on T2-weighted magnetic resonance imaging (MRI) scans. One is located in the immediate periventricular region; the other, in the deep subcortical white matter (centrum semiovale). The diagnostic implications of this second type continue to be uncertain. To determine the neuropathologic correlates of these lesions, the brains from seven elderly patients were fixed in buffered formaldehyde solution, subjected to MRI scanning, and examined neuropathologically. Variable degrees of bilateral periventricular (subependymal) sharply defined areas of high-signal intensity were found in all the brains, and the larger of these showed corresponding areas of myelin pallor with gliosis and dilated perivascular spaces. Discrete bilateral patches of high-signal intensity were found in the centrum semiovale in five patients. Myelin and axon stains showed varying degrees of diffuse white matter pallor in many areas examined, both with and without these areas of high-signal intensity on MRI scans. Neither the myelin nor the axon stains showed discrete white matter abnormalities that corresponded to the MRI findings. We believe that these changes, so commonly found on MRI scans in the elderly, reflect actual changes in the white matter but that their nature and clinical significance need to be elucidated.

Multicenter study of gadopentetate dimeglumine as an MR contrast agent: evaluation in patients with spinal tumors.

In an open-label, multicenter study, the efficacy and safety of gadopentetate dimeglumine (0.1 mmol/kg) administered IV as an MR imaging contrast agent were evaluated in 113 patients with symptoms of spinal tumors. The examinations were performed with a variety of imagers at different field strengths. Scans with short and long TRs were obtained in all patients before and after IV administration of the contrast medium. Contrast enhancement was seen in 77% of patients. No enhancement was seen in 23%, but this absence was useful diagnostic information in all cases. In 66% of the cases, additional information regarding location, size, configuration, and/or characterization of the lesion was obtained from postcontrast scans. The investigators made a change from referral diagnosis to postinjection diagnosis in 30% of the cases. Postinjection images provided additional information in 96% (43/45) of intradural extramedullary and intramedullary tumors; it also provided additional information in 20 (53%) of 38 cases of extradural tumor. Gadopentetate dimeglumine demonstrated a high level of safety and tolerance, as evidenced by the lack of clinically significant trends toward abnormal changes from baseline evaluations for physical and neurologic examinations, vital signs, and hematologic and blood chemistry parameters and by the low prevalence and mild nature of adverse reactions. Gadopentetate dimeglumine was found to be efficacious in the evaluation of suspected spinal tumors. High levels of safety and tolerance were demonstrated.

CT infusion scanning for the detection of cerebral aneurysms.

Computerized tomography (CT) infusion scanning can confirm the presence or absence of an aneurysm as a cause of spontaneous intracerebral hemorrhage. Eight patients who presented with spontaneous hemorrhage were examined using this technique. In five patients the CT scan showed an aneurysm which was later confirmed by angiography or surgery; angiography confirmed the absence of an aneurysm in the remaining three patients. This method is an easy effective way to detect whether an aneurysm is the cause of spontaneous intracerebral hemorrhage.

MR imaging of periventricular leukomalacia in childhood.

Eight children with clinical and radiologic abnormalities consistent with periventricular leukomalacia were investigated with MR imaging of the brain that employed both inversion-recovery and T2-weighted spin-echo imaging sequences. The more precise delineation of white and gray matter on inversion-recovery images as compared with CT allows a detailed demonstration of the anatomic features of periventricular leukomalacia; specifically, a reduced quantity of white matter in the periventricular region and centrum semiovale and, in more severe cases, cavitated infarcts that replace the immediate periventricular white matter. The T2-weighted spin-echo and short inversion time inversion-recovery images demonstrated abnormally increased signal in white matter that appeared normal on CT scans and only minimally abnormal on conventional inversion-recovery images. These abnormalities most probably represent white matter gliosis that extends beyond the immediate periventricular regions. MR recognition of cerebral white matter abnormalities associated with periventricular leukomalacia may confirm the clinical suspicion of this diagnosis in children with spastic diplegia or quadriplegia.

Gadolinium-DTPA-enhanced MR imaging of spinal neoplasms: preliminary investigation and comparison with unenhanced spin-echo and STIR sequences.

Unenhanced T1- and T2-weighted spin-echo, short inversion time inversion recovery (STIR), and gadolinium-DTPA (Gd-DTPA)-enhanced spin-echo and STIR imaging techniques were used in 20 patients as part of a multicenter study to assess the safety and efficacy of Gd-DTPA in spinal imaging. Five patients had normal MR scans. Of those with lesions, both Gd-DTPA-enhanced T1-weighted spin-echo and unenhanced STIR scans improved detection and evaluation of spinal tumors over conventional spin-echo methods, particularly T2-weighted spin echo, by providing higher tissue contrast in shorter imaging times. The Gd-DTPA-enhanced T1-weighted spin-echo scans were most helpful in evaluating intradural tumors, whereas STIR sequences were most effective for extradural tumors and bone metastases. In most cases, Gd-DTPA-enhanced T1-weighted spin-echo scans best delineated tumor margins, and the enhancement was helpful in suggesting a cellular or active nature of the lesions. In some cases, the enhancement resulted in a more homogeneous and thus less abnormal-appearing marrow in vertebrae involved by tumor; therefore, a precontrast T1-weighted spin-echo scan is necessary in all patients who are to be studied with Gd-DTPA. A combined approach that uses T1-weighted spin-echo, Gd-DTPA-enhanced T1-weighted spin-echo, and STIR images currently appears optimal for MR imaging of spinal neoplasms. T2-weighted spin-echo images add information only in occasional cases.

Early diagnosis of spinal metastases by CT and MR studies.

Fifteen patients with known metastatic or high-risk primary cancer, normal neurologic examinations, and new abnormalities on 99mTc bone scan were evaluated with spinal CT and magnetic resonance (MR) imaging. Four patients underwent CT metrizamide myelography. Spinal CT and MR agreed in 14 of 15 patients demonstrating spinal metastases in 12 patients and benign disease in two. In one patient spinal CT was normal, but MR showed altered marrow signal consistent with metastatic disease. Epidural tumor was demonstrated by CT metrizamide myelography in four cases, all correctly identified by MR. Further evaluation of spinal MR in this setting is warranted.

CT diagnosis of toxic brain injury in cyanide poisoning: considerations for forensic medicine.

Two deaths occurred after ingestion of cyanide-containing Extra-Strength Excedrin capsules. Cranial CT scans obtained within 3 hr of each patient's collapse showed diffuse cerebral swelling and loss of gray-white differentiation. Most diffuse cerebral insults (hypoxia, ischemia) do not show such changes so soon after injury. The early onset of diffuse cerebral edema with loss of gray-white differentiation may be a clue to the diagnosis of acute cyanide poisoning.

CT of acquired hyperopia with choroidal folds.

Seven patients with an ophthalmologic diagnosis of acquired hyperopia with choroidal folds were evaluated by high-resolution axial CT of the orbits. Coronal, oblique coronal, and parasagittal reformations were obtained and the thickness of the optic nerve and morphologic appearance of the globes were assessed by measurement and subjective appearance. Flattening of the globe, which caused the globe to assume an ellipsoid shape, was seen in all 11 affected eyes. Mild to moderate optic nerve enlargement was also demonstrated in most patients. In six of 11 affected eyes a visible space was noted between the optic nerve and its sheath, implying expansion of the subarachnoid perineural compartment. These findings were not demonstrated in a control group of five patients scanned in a similar manner. Scans of a phantom revealed no evidence of CT-generated distortion. These findings may help to identify hyperopia with choroidal folds as a benign disease and eventually help to establish its cause.

Poor prediction of positive computed tomographic scans by clinical criteria in symptomatic pediatric head trauma.

A retrospective study of 98 children who received CT scanning for head trauma was conducted to determine whether clinical signs would accurately identify patients needing CT scans. The clinical findings of Glasgow Coma Scale score of 12 or less, altered consciousness on admission, and focal abnormalities on neurologic examination were each significantly associated with abnormal findings on CT scans (P less than .01). However, 31% of the 51 patients with Glasgow Coma Scale scores greater than 12 had abnormal CT scan findings. No clinical findings, alone or in combination, accurately identified all patients with abnormal findings on CT scans.