Hepatobiliary scintigraphy and gamma-GT levels in the differential diagnosis of extrahepatic biliary atresia.

AIM: The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as the cause of cholestasis in neonates with prolonged jaundice and thus accelerate the decision for surgical intervention, which is critical for prognosis. METHODS: We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They were referred because of direct hyperbilirubinemia and jaundice persisting beyond the 2nd postnatal week. They had received phenobarbitone premedication prior to scintigraphy. Dynamic images for 30 min and then static images (if required) at 1, 2 and 24 h postinjection were acquired. Images were evaluated visually and semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared (Mann-Whitney U test) between infants with EHBA (Group A) and infants without (Group B). The L/H ratios were correlated with age in each group and with gamma-GT in the entire population. RESULTS: A total of 7/21 infants were classified in Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A. The correlation between L/H ratio and age was negative in EHBA and positive in non-atretic infants. The gamma-GT levels were inversely correlated with the L/H ratios in the entire population, being significantly higher in Group A. CONCLUSION: In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA scintigraphy and the L/H ratio index seem to give useful information in the differential diagnosis of EHBA, especially when associated with markedly elevated serum gamma-GT levels.

Multiple meningiomas.

A 57-year-old woman with hyperthyroid ophthalmopathy underwent somatostatin receptor scintigraphy with In-111 pentetreotide. She also reported migraine-type headaches over the previous 3 months, without any other obvious neurologic symptoms and signs. The study revealed an increased uptake of the radiopharmaceutical in both periorbital areas and the right lobe of the thyroid gland. Multiple foci of marked tracer uptake were also detected in the right half of the head. A brain MRI scan subsequently revealed multiple lesions consistent with meningiomas on the surface of the right cerebral hemisphere.

Palliative treatment of painful disseminated bone metastases with 186Rhenium-HEDP in patients with lung cancer.

AIM: The aim of this study was to determine if patients with lung cancer and metastatic bone pain due to disseminated secondary bone disease, can benefit from the treatment with (186)Re-HEDP and to discuss the criteria useful for selecting those patients. METHODS: Twenty-four patients were included in this study and they received 1295 MBq (186)Re-HEDP. All patients underwent (99m)Tc-MDP bone scan before treatment from which the bone scan index (BSI) was determined (mean=18.7+/-17.1%). Most patients underwent CT scan of the painful areas from which the osteolytic element of their bone lesions as well as possible infiltration of the soft tissues was determined. Patients with predominantly osteolytic metastases at the sites considered to be the origin of pain in the CT scan, were excluded. All patients were under analgesic therapy, 22/24 were taking opiates. Pain was estimated by the visual analogue scale (VAS) before the application of (186)Re-HEDP and over the following 8 weeks. The possible myelotoxicity of (186)Re was assessed. RESULTS: The mean VAS score was 6.9+/-2.5 before the application and 3.2+/-2.6 after therapy. Pain relief was obtained in 23/24 patients. Sixty-two percent of the patients exhibited clinically significant pain relief of at least 3 VAS score. The dosage of opiates was decreased in 77% of the patients and could be discontinued in 4 of them. Myelotoxicity was observed in 1 patient. Ninety-one percent of our patients showed improvement in the parameters that assess the quality of life. CONCLUSION: The application of a standard dose of (186)Re-HEDP in patients with lung cancer and painful disseminated bone metastases has a satisfactory pain alleviating effect. The easy application and very low myelotoxicity are important factors in this group of patients. A better analgesic effect of the (186)Re-HEDP application can be expected if combined estimation of the (99m)Tc-MDP bone scan and the CT scan is used.

Reverse of the differential uptake intensity of Tc-99m MIBI and Tc-99m V-DMSA by multiple myeloma lesions in response to therapy.

PURPOSE: The objective of this study was to compare the uptake changes of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) and Tc-99m pentavalent dimercaptosuccinic acid (V-DMSA) in multiple myeloma (MM) lesions in response to high-dose chemotherapy (HDC). MATERIALS AND METHODS: The authors compared Tc-99m MIBI and Tc-99m V-DMSA scans before and after HDC in a patient with focal MM lesions without amyloidosis who had received previous standard chemotherapy as well. RESULTS: HDC had the effect of eliminating all Tc-99m MIBI uptake in the lesions. Tc-99m V-DMSA uptake was increased in lesions presenting significant initial Tc-99m MIBI uptake. In 1 particular lesion that demonstrated this phenomenon, magnetic resonance showed necrosis of the area of MM. CONCLUSION: The authors consider that the effect of increasing Tc-99m V-DMSA uptake in the absence of an increase in viable plasma cells possibly reflects the treatment-generated inflammatory and fibrotic changes and not necessarily viable tumor tissue. Exclusive focal Tc-99m V-DMSA uptake in this clinical setting could be considered as a sign of effectively treated lesions and not a sign of deterioration.

Treatment of industrial oily wastewaters by wet oxidation.

In the present work, the homogeneous wet oxidation (WO) of an oily wastewater (COD approximately 11,000 mg l(-1)), composed mainly of alcohols and phenolic compounds, was studied in a high-pressure agitated autoclave reactor in the temperature range of 180-260 degrees C and oxygen pressure 1 MPa. Temperature was found to have a significant impact on the oxidation of the contaminants in the wastewater. Among the compounds contained in the wastewater, ethylene glycol showed great resistance to wet oxidation. Temperatures above 240 degrees C were required for its effective degradation. Organic acids, mainly acetic acid, were the intermediate products of the wet oxidation process and their conversion to carbon dioxide was very slow. A generalised model based on a parallel reaction scheme was used to interpret the experimental data obtained. The activation energies obtained were in the range of 90-130 kJ mol(-1).

Uptake and washout of 99mTcV-dimercaptosuccinic acid and 99mTc-sestamibi in the assessment of histological type and grade in breast cancer.

This study was performed to investigate the relationship between histological type and grade, with the uptake and washout of 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi, 99mTc-MIBI) and 99mTcV-dimercaptosuccinic acid (99mTcV-DMSA) in breast cancer. Forty-five patients with histologically proven breast cancer had previously been referred for 99mTcV-DMSA and/or 99mTc-MIBI scintimammography. Twenty-five of them underwent both 99mTcV-DMSA and 99mTc-MIBI scintigraphy in a double phase study. Lateral prone and anterior supine images were acquired at 15 and 60 min after administration of 740-925 MBq of each radiotracer. Uptake ratios and retention index were calculated and correlated with histology and grade of malignancy. Histology showed eight different histotypes: 77.7% were infiltrating ductal or lobular carcinomas. Mammography was definitely positive in 32/45, indeterminate in 10 and negative in three cases (sensitivity 71%). 99mTcV-DMSA was true positive in 37/40 (sensitivity 92.5%) and 99mTc-MIBI in 28/30 (sensitivity 93.3%) breast cancers. Uptake ratios were significantly higher in ductal than in lobular carcinomas on 99mTcV-DMSA and 99mTc-MIBI scintigrams at early and delayed phases. Grade II carcinomas had significantly lower values of retention index (rapid washout) than grade III carcinomas. This finding was statistically significant only on 99mTc-MIBI scans and was observed in ductal and lobular carcinomas. The retention index did not show any significant difference between ductal and lobular carcinomas. Uptake ratios were also not statistically different between grade II and III cancers. It is concluded that 99mTc-MIBI and 99mTcV-DMSA uptake in breast cancer is probably related to histological type and may distinguish ductal from lobular carcinomas. To a certain degree, the washout rate may reflect the histological grade, but since grade is not the only factor influencing this phenomenon it should be explored further in conjunction with other parameters by multivariate analysis in order to clarify eventual indirect correlations.

99mTc-(V)DMSA scintimammography in the assessment of breast lesions: comparative study with 99mTc-MIBI.

The purpose of this study was to evaluate and compare the diagnostic accuracy of pentavalent technetium-99m dimercaptosuccinic acid [99mTc-(V)DMSA] and 99mTc-methoxyisobutylisonitrile (MIBI) in the detection of primary breast cancer and metastatic lymph node involvement, and in the clarification of cases with indeterminate mammograms. Forty-one women (mean age+/-SD 55+/-7 years) referred for a suspicious breast lesion on physical examination and/or an abnormal mammogram underwent MIBI and (V)DMSA scintimammography (SMM) at separate sessions (48-h interval). Lateral prone and anterior supine images were obtained at 10 and 60 min after administration of 740-925 MBq of each tracer, in the arm contralateral to the breast lesion. The ipsilateral axillary region was also included in the field of view. The results of SMM and mammography were compared with histological findings. Breast cancer was histologically confirmed in 26 patients (mean diameter+/-SD 2.87+/-1.5 cm). Benign lesions were found in 15 patients (mean diameter+/-SD 2.04+/-2.7 cm). Mammography was definitely positive in 23/26 patients with breast cancer and indeterminate in 3/26 (sensitivity 88.4%). In benign lesions, mammography was true negative in 5/15 cases and indeterminate in 10/15 (specificity 33.3%). Both MIBI and (V)DMSA SMM detected 23/26 breast cancers (sensitivity 88.4%) and were true negative in 14/15 (specificity 93.3%). T/B ratios for breast cancer in MIBI and (V)DMSA scans were similar, and significantly higher than for benign lesions. MIBI correctly diagnosed 12/13 and (V)DMSA 11/13 cases in which the findings of mammography were indeterminate. In addition, (V)DMSA detected seven of eight cases of in situ ductal carcinoma (DCIS) associated with infiltrating carcinomas, while MIBI detected only two of these eight cases. (V)DSMA was also diffusely concentrated in benign lesions complicated by epithelial hyperplasia. Metastatic lymph node involvement was successfully imaged in 15/19 patients with metastatic disease by both agents (sensitivity 78.9%), while true-negative scans were observed in 19/22 (specificity 86.3%) patients with benign or malignant tumours without lymph node metastases. Linear regression analysis revealed a high coefficient of correlation between the (V)DMSA and the MIBI T/B ratios (r=0.8 P<0.001). We conclude that both (V)DMSA and MIBI show an excellent ability to detect breast cancer and its lymph node metastases. (V)DMSA also has a tendency to be diffusely and more intensely localised than MIBI in pre-invasive lesions, such as DCIS or epitheliosis, which are at risk of developing into malignancies. (V)DMSA could therefore provide a useful tool in the diagnosis of such lesions and possibly modify a predefined surgical plan. Finally, we believe that both tracers could offer an alternative method for elucidating nondiagnostic mammograms.

Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: an immunocytochemical study.

In discriminating benign and malignant origins of cytologically suspicious effusion smears a panel of antibodies against carcinoembryonic antigen (CEA), Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One hundred and thirty seven effusions were studied of which 107 had a malignant and 30 a benign aetiology as determined by clinical and histological examination. Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious. Staining for F was positive in all effusions of benign and 3 of malignant origin. MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of benign origin. Positive CEA was observed in 43% of effusions of malignant origin and in 10 of benign origin. The combination of MOC-31 positivity measured the sensitivity and specificity of the cytological examination in cases where the cytological examination result was suspicious as did F positivity improve the sensitivity for a benign origin of the effusion. Positivity or negativity for CEA is less valuable than the other parameters.

Scintimammographic findings of in situ ductal breast carcinoma in a double-phase study with Tc-99m(V) DMSA and Tc-99m MIBI value of Tc-99m(V) DMSA.

The authors present a case of in situ ductal carcinoma of the breast (DCIS) with no associated mass in a 46-year-old woman examined with Tc-99m MIBI and Tc-99m(V) DMSA scans, which were acquired in separate sessions 10 minutes and 60 minutes after injection. Histologic analysis revealed a small (<1 cm) infiltrating ductal carcinoma located within the DCIS. Mammography showed a cluster of microcalcifications on a very dense parenchymal background. Tc-99m(V) DMSA was characterized as positive for DCIS, especially in the delayed image. Tc-99m MIBI failed to identify the lesions previously noted. In conclusion, Tc-99m(V) DMSA scintimammography seems to have an advantage and could improve the detection of nonpalpable in situ breast carcinomas.

Prognostic significance of p53, bcl-2 and EGFR in carcinoma of the endometrium.

OBJECTIVE: To evaluate the part played by several parameters in the prognosis of patients with endometrial carcinoma. STUDY DESIGN: Eighty imprint smears from fresh endometrial tumor specimens were studied immunocytochemically for the expression of p53, bcl-2 and epidermal growth factor receptor. Also, the presence of estrogen receptor (ER) and progesterone receptor (PR) in the tumor tissue was measured. The data obtained were related to survival, and associations were sought between the parameters studied. RESULTS: Strong associations were found between advanced stage, high grade, lymph node metastases at diagnosis, nonendometrioid histology and p53 expression with poor survival. Bcl-2 expression was associated with good five-year survival. ER expression was associated marginally with good five-year survival, but PR expression was not. A strong association was found between p53 and advanced disease, stage and lymph node metastases at diagnosis. An association between EGFR positivity and survival was not found. CONCLUSION: p53 Expression of uterine tumors is an independent and strong indicator of poor prognosis. Even patients with stage I and II disease at surgery who have p53-positive tumors must be considered at high risk.

Cold thyroid nodule as the sole manifestation of Rosai-Dorfman disease with mild lymphadenopathy, coexisting with chronic autoimmune thyroiditis.

A case of thyroid Rosai-Dorfman disease (RDD) without apparent lymphadenopathy in a 49-year-old woman with underlying euthyroid chronic autoimmune thyroiditis, as indicated by high thyroid autoantibodies titers, is presented. The initial presentation was that of a cold, hypoechogenic nodule of left thyroid lobe which increased in size during the two years of follow up, together with new ultrasonographic findings of the right lobe. No biochemical abnormalities were found apart from mild hypercalcemia. A near total thyroidectomy was performed. Histologically, the left lobe nodule as well as the right lobe lesions consisted of typical RDD cellular population, with the pathognomonic phenomenon of emperipolesis. Infiltration to the periphery of the gland was observed and three adjacent lymph nodes were also involved. The uninvolved thyroid parenchyma showed changes compatible with chronic autoimmune thyroiditis. No other localizations or systemic manifestations of RDD were revealed. Normocalcemia was restored promptly and the patient remains free of clinically overt disease one year post-operatively.

p53 and bcl-2 protein expression in non-small-cell lung carcinoma.

The diagnostic significance of p53 and bcl-2 proteins in epithelial non-small-cell lung cancers was examined, and the relationship between these proteins expression and other disease parameters, including stage of the disease and tumor differentiation, were studied. We analyzed p53 and bcl-2 proteins expression in 60 imprint smears of freshly resected lung tumors (37 squamous and 23 adenocarcinomas) using the immunocytochemical technique. There were seven patients with stage I disease, 24 with stage II, 23 with stage IIIa, and six with stage IIIb disease, according to the International Staging System classification. Sixteen of the tumors were bcl-2 positive and 25 were p53 positive. Twenty tumors were negative for both bcl-2 and p53 (33.3%). Statistical analysis showed no association between the incidence of p53 or bcl-2 positivity. Adenocarcinoma or squamous carcinoma analysis showed significant associations between p53 positivity and poor differentiation and advanced disease stage as well as bcl-2 and early disease stage and well-differentiated tumors. There was also an association between the stage of the disease and the degree of differentiation of the tumors. In conclusion, bcl-2 positivity must be considered a good prognostic sign. On the other hand, p53 positivity seems to indicate, even in tumors at a relatively early stage, that a serious aggressive tumor which will not be easily eradicated is present.

Expression of p53, bcl-2 and heat shock protein (hsp72) in malignant and benign ovarian tumours.

The occurrence of p53, bcl-2 and heat shock protein (HSP) expression in ovarian tumours was examined and the correlation was investigated between the expression of these proteins and other disease parameters, including FIGO stage, histological subtype, tumour differentiation and steroid hormone receptor status. We analysed p53, bcl-2 and HSP expression in 100 smears of patients with epithelial ovarian carcinomas, 16 smears of patients with borderline malignancy and 20 smears of patients with benign ovarian neoplasms by using immunocytochemical techniques. There were 29 patients with stage I disease, 24 with stage II disease, 40 with stage III disease and seven with stage IV disease according to the FIGO classification. The sensitivities and specificities of bcl-2, p53 and HSP for malignancy were 53% and 40%, 43% and 80%, and 37% and 90%, respectively. HSP was statistically significantly associated with malignant rather than benign tumours. Significant association was also observed between bcl-2 and p53, and p53 and HSP. The association of HSP with malignant tumours is confined to the premenopausal group of patients and in this group by itself there is also a significant association between p53 and malignancy. HSP and p53 were associated with undifferentiated carcinomas, bcl-2 and p53 expression is reduced as disease stage progresses in serous carcinomas and bcl-2 expression is increased as disease progresses in endometrioid carcinomas. There was no significant association between bcl-2 and ER/PR status. In conclusion, HSP has a high specificity for malignant ovarian tumours, bcl-2 and p53 have only moderate to low sensitivity and specificity. Changes in the frequency of bcl-2 and p53 overexpression between FIGO I and FIGO III stage disease of different ovarian carcinomas indicate a different role of these substances in cellular survival mechanisms in different carcinomas. bcl-2 probably is associated with cell proliferation but not with differentiation.

Expression of cathepsin D and pS2 in imprint smears of breast carcinoma.

The aim of this study was to add to existing information on the effects of certain tumour markers expressed by breast cancers on tumour malignancy as evidenced by size of primary and occurrence of lymph node invasion. One hundred freshly resected breast cancers were examined by immunocytochemical staining of imprint smears for Cathepsin D and pS2. Oestrogen receptor (ER) and progesterone receptor (PR) were tested for by dextrose-coated charcoal (DCC) assay and the results correlated with tumour size, histology and presence or absence of lymph node metastases at the time of surgery using chi(2) analysis. A significant positive correlation was demonstrated between Cathepsin D positivity and ER, PR and pS2 positivity. In tumours < 2 cm in diameter at surgery a positive correlation was observed between Cathepsin D positivity and the presence of lymph node metastases. The findings support the hypothesis that Cathepsin D may promote early metastasis, possibly by its proteolytic activity.

Cathepsin D immunoreactivity in ovarian cancer: correlation with prognostic factors.

In view of the somewhat inconclusive nature of the reports of the role of Cathepsin D (Cath D) in ovarian carcinoma and its relationship with various other parameters of malignancy the present study was performed to aid in the further clarification of this role. One hundred freshly resected primary ovarian carcinomas of various histological types were studied for ER, PR and Cath D status and the results examined with respect to menopausal status, histology, size and lymph node invasion. In our series Cath D positivity was more frequent in serous than in other types of ovarian cancer but this Cath D positivity was not related to the frequency of lymph node invasion regardless of the size of the tumor. Nor was any association observed between Cath D positivity and ER or PR status of the tumors or the menopausal state of the patients. The reported prognostic value of Cath D, ER and PR is discussed as well as the distinction between tumor invasion by lymphatic channels and direct interstitial infiltration. It was concluded that Cath D may not play a role in the former mode but, as might be expected from its proteolytic properties, in local spread by means of tissue destruction.

99mTc Tetrofosmin imaging in breast tumours.

Eighty-five women, 18 to 80 years of age, with palpable breast lumps were studied 1-4 days before surgery in order to evaluate 99mTc Tetrofosmin imaging for the detection of malignant breast tumours. Intravenous injection of 99mTc Tetrofosmin was followed by 3 min planar images at 5-60 min postinjection. In the latter 57 patients, planar imaging was preceded by a dynamic study of 20x5 sec images. The myocardium was always included in the field of the left breast. Count rates in suspicious areas were compared with normal tissue areas in the same and the opposite breast and with myocardial counts. Data analysis showed that 77 of the 85 scan results were in agreement with the histological findings; six scans were false negative and two false positive for malignancy. The sensitivity of the method was 90.32% and the specificity 91.30%, with a positive predictive value of 96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may play an important role in the detection of breast malignancies.

Primary malignant melanoma of the conjunctiva of the upper eyelid. A case report.

BACKGROUND: Malignant melanoma of the conjunctiva is rare. The nomenclature and clinical and pathologic features of cutaneous and conjunctival melanomas are different. CASE: A 62-year-old male presented with a history of slight bleeding of the upper conjunctiva for the previous six months. On clinical examination the ophthalmologist observed a smooth, partly nodular, pigmented lesion on the conjunctiva under the left eyelid, 1.5 cm in diameter. Fine needle aspiration (FNA) biopsy of the mass showed tumor cells dispersed as single cells with eccentric, round nuclei; coarsely granular chromatin; prominent nucleoli; and dense cytoplasm with occasional brownish pigmentation as well as small aggregates of spindle-shaped neoplastic cells with hyperchromatic nuclei and no cytoplasmic pigment. CONCLUSION: FNA cytology is a simple and efficient method of making the diagnosis of malignant melanoma in conjunctival masses. Careful correlation with the clinical history and histologic findings is often necessary for confirmation of the diagnosis.

Immunocytochemical detection of P-glycoprotein in the management of malignant effusions.

P-glycoprotein (P-gp), a cell membrane protein, has been found in multidrug-resistant cancer cells. A total of 104 smears from patients with breast-cancer-associated pleural effusions and ovarian-cancer-related peritoneal effusions were studied for P-gp with the antibody C-219 and the avidin-biotin-immunoperoxidase method. Samples were taken before and 3 and 7 days after intracavitary bleomycin therapy and reaccumulation of effusion was assessed at 30 days. Smears that were P-gp-negative by the 7th day were associated with a good 30-day response to bleomycin in the majority of cases, while P-gp-positive smears were associated with a significant reaccumulation of fluid at 30 days. P-gp status is a valuable prognostic indicator of response to intracavitary bleomycin treatment in effusions from breast or ovarian cancer.