Comparative study of high-resolution multifrequency ultrasound of the plantar skin in patients with various types of hereditary palmoplantar keratoderma.

BACKGROUND: High-variable-frequency ultrasound is used as an imaging tool for various cutaneous disorders. We utilized this tool in pachyonychia congenita (PC) patients, who typically present with plantar hyperkeratosis and often severely debilitating pain, compared to patients with epidermolytic palmoplantar keratoderma (EPPK) and mal de Meleda (MDM). OBJECTIVE: To ascertain the feasibility of ultrasound technology for the diagnosis of PC. METHODS: The study included a total of 16 patients, 7 with PC, 5 with EPPK and 4 with MDM, who underwent ultrasound examination of the plantar skin with high-resolution multifrequency ultrasound equipment. RESULTS: Ultrasound scans performed over the proximal and distal plantar foot calluses in PC patients demonstrated hyperechoic dots and lines within the epidermis compatible with hyperkeratosis, engorged varicose veins in the dermis and an anechoic layer interposed between the epidermis and the dermis, corresponding to blister fluid below the calluses. In contrast to PC patients, patients with MDM and EPPK demonstrated no blisters. CONCLUSION: PC patients, as opposed to a group of patients with MDM and EPPK, displayed subepidermal blistering beneath their calluses. This finding may help in the diagnosis of PC and in partially explaining plantar pain as part of PC symptomatology.

Do we need a cancer screening in patients with idiopathic deep vein thrombosis?

AIM: To review the literature concerning the need for a cancer screening battery to diagnose a hidden cancer in patients presenting with idiopathic venous thromboembolism (VTE). MATERIALS AND METHODS: Data from computerized database programs (Medline, Ovid) was retrieved. A review of the literature regarding studies on cancer screening in patients with idiopathic VTE was performed and our own policy included. RESULTS: Patients with VTE have a higher rate of malignancy which may still be undiagnosed. During follow-up of patients with idiopathic VTE, the incidence of cancer increases and is more likely associated with a worse prognosis. Limited diagnostic work-up in patients with idiopathic VTE allows the diagnosis of a hidden malignancy in about half of the cases with a sensitivity of 48 %. Extensive screening of cancer with idiopathic VTE allows less of a delay and earlier stage at diagnosis with a 93 % sensitivity. However, reduced cancer-related mortality is not statistically significant. A two-fold fatal PE and more than 3-fold fatal bleeding are registered in VTE patients with hidden cancer compared to patients without cancer. The major risk factors for hidden cancer are old age, anemia, idiopathic and bilateral deep vein thrombosis. CONCLUSION: There is no consensus regarding the benefit of extensive screening in patients presenting with idiopathic VTE. Clear diagnostic work-up guidelines are not yet available. A cost-effective diagnostic algorithm for cancer screening in patients with idiopathic VTE is needed.

Immuno-chemotherapy in metastatic renal cell carcinoma: long-term results from the rambam and linn medical centers, Haifa, Israel.

Nephrectomy, immuno-chemotherapy and resection of residual disease have been the treatment of choice for patients with metastatic renal cell carcinoma during the past decades. The aim of this study was to report the long-term results of this treatment approach. Sixty-two patients with metastatic renal cell carcinoma participated in a Phase II study. At diagnosis, 32 patients had localized disease, 30 had metastatic disease and 53 underwent nephrectomy. Metastatic sites were lungs, lymph nodes, bones and liver. Immuno-chemotherapy consisted of: interleukin-2, interferon alpha, 5-fluorouracil and vinblastine. All patients were evaluated for toxicity and response to treatment. CR was achieved in 4 patients and PR in 14. Seven patients, with maximum response to immuno-chemotherapy underwent resection of residual tumor and reached CR. Therefore, CR was achieved in 11 patients (18%) with a median survival of +67 months. Flu-like symptoms were the common side effects. Performance status and histology type significantly affected survival. Nephrectomy, immuno-chemotherapy and resection of residual disease are recommended for patients with metastatic renal cell carcinoma.

Computerised analysis of liver texture with correlation to needle biopsy.

AIM: To assist in tissue characterisation for the non-invasive diagnosis of diffuse fatty liver infiltration by providing quantitative indices of ultrasonic (US) backscatter with correlation to histology. METHODS AND MATERIALS: US images from patients referred to US-guided liver needle biopsy (LNB) for persistently elevated liver enzymes or serologically positive markers for viral hepatitis were recorded. The histopathological reports were reviewed. Steatosis, inflammation and degree of fibrosis were scored from 0 (normal) to 3 (severe). Patients with level 3 steatosis without inflammation or fibrosis were selected. US images from twenty-four healthy subjects served as control. Four textural indices were calculated for a selected ROI corresponding to the biopsy site. Sensitivity and specificity of discrimination between the two groups were evaluated. RESULTS: Fatty and healthy livers formed two distinct clusters. However, in all parametric subspaces there was a slight overlap between the groups with a few numbers of cases located across the dichotomy line.The sensitivity for all the indices was high (90 - 100 %). The specificity for each of the indices was moderate. The co-occurrence local homogeneity index yielded the highest specificity (88.5 %), with a sensitivity equivalent to two of the other indices (90 %). CONCLUSIONS: Highly accurate "ultrasonic biopsy" may be obtained for severe fatty liver. The described indices can serve as a tool in US computer- aided diagnosis (CAD) of diffuse parenchymal liver disease, in particular for severe steatosis of the liver.

Prevalence and characteristics of pain induced by percutaneous liver biopsy.

UNLABELLED: Percutaneous needle liver biopsy is an important procedure for the diagnosis and evaluation of liver disease and is frequently associated with pain. In this prospective study, we investigated the prevalence and characteristics of this pain syndrome. Fifty-four subjects, who underwent liver biopsy under ultrasound guidance, received 5 mg of diazepam orally 1 h before the procedure and local infiltration with 10 mL of 2% lidocaine just before needle insertion. Outcome measures included the visual analog scale for measuring pain intensity over 24 h, pain localization on a body scheme, and the Spielberger questionnaire for measuring anxiety levels. Forty-seven (84%) of the 54 respondents reported pain 30 min after the biopsy (visual analog scale, 4.2 +/- 0.5; mean +/- SEM), and 21 (39%) reported pain at the 24-h time point. Biopsy site pain was reported by 9 subjects, right shoulder pain by 14, and pain at both sites by 24. Higher pain intensities were reported by women and by subjects with higher anxiety levels. This study indicates that liver biopsy is a painful condition in most patients. Mild anxiolytic treatment plus local anesthetic infiltration seem to produce insufficient analgesia, thus indicating that a more profound analgesic treatment is required for better control of this pain. IMPLICATIONS: Percutaneous liver biopsy is a painful procedure in most patients. Mild anxiolytic treatment plus local anesthetic infiltration seem to produce insufficient analgesia. A more profound analgesic treatment is required for better control of this pain.

Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans.

The beneficial health effects attributed to the consumption of fruit and vegetables are related, at least in part, to their antioxidant activity. Of special interest is the inverse relationship between the intake of dietary nutrients rich in polyphenols and cardiovascular diseases. This effect is attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate polyphenols can protect LDL against cell-mediated oxidation via two pathways, including either direct interaction of the polyphenols with the lipoprotein and/or an indirect effect through accumulation of polyphenols in arterial macrophages. Pomegranate polyphenols were shown to reduce the capacity of macrophages to oxidatively modify LDL, due to their interaction with LDL to inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen species and also due to accumulation of polyphenols in arterial macrophages; hence, the inhibition of macrophage lipid peroxidation and the formation of lipid peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. These antioxidative and antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice. Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atherosclerotic lesions and this may be attributed to the protection of LDL against oxidation.

Etoposide, doxorubicin and cisplatin alternating with 5-fluorouracil, doxorubicin and high-dose methotrexate in patients with advanced adenocarcinoma of the stomach or the gastroesophageal junction.

Both the etoposide, doxorubicin, cisplatin (EAP) and 5-fluorouracil, doxorubicin, high-dose methotrexate (FAMTX) schedules have been reported to be active in advanced gastric cancer. Since these regimens include non-cross resistant agents, a regimen that consists of EAP alternating with FAMTX may have an advantage over each regimen alone. We undertook a phase II trial to evaluate EAP/FAMTX in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction. Of the 56 patients treated, an objective response was observed in 34%, including complete response in 7%. Median response duration was 8 months and median survival for the entire group was 9 months. The main toxicity was myelosuppression. Hospitalization for granulocytopenic fever was required in 32% of patients and 34% required red blood cells (RBC) transfusion. Non-hematological toxicity was moderate. There were three drug-related deaths associated with granulocytopenic fever. We conclude that the alternating EAP/FAMTX regimen is associated with occasional lethal events and has no obvious advantage over either regimen alone.

Impact of intraoperative sonography on resection and cryoablation of liver tumors.

PURPOSE: We retrospectively analyzed the impact of intraoperative sonography (IOUS) on the management of patients referred for resection of liver tumors. METHODS: Forty patients underwent IOUS with a 7-MHz curved-array sector transducer; in selected cases, a 5-MHz linear-array transducer attached to a color Doppler unit was also used. The number, size, and location of tumors on IOUS, including tumor proximity to or invasion of major vessels or invasion of the diaphragm, were compared to findings on preoperative imaging studies. The effect of these findings on surgical management was assessed. Unresectable lesions were treated by cryoablation under ultrasound guidance. RESULTS: IOUS detected preoperatively unsuspected lesions in 7 patients (18%). Metastases suspected on CT arterial portography were ruled out in 2 patients (5%), and indeterminate lesions were diagnosed as cysts by IOUS in 2 other patients (5%). Vascular proximity or vascular or diaphragmatic invasion detected by IOUS rendered lesions unresectable in 4 patients (10%). Cryoablation under IOUS guidance and monitoring was attempted in 11 patients (28%) and performed successfully in 10. CONCLUSIONS: IOUS changed the management in 38% of patients and guided cryoablation in 28% of patients. IOUS performed by an experienced sonologist is invaluable for the accurate assessment of liver tumor resectability; the detection of additional, preoperatively unknown lesions; and the guidance of cryoablation of unresectable tumors.

The new technology of combined transmission and emission tomography in evaluation of endocrine neoplasms.

UNLABELLED: The clinical value of a novel technology of combined transmission and emission tomography (TET) was assessed in patients with endocrine tumors. METHODS: TET technology, which combines simultaneous acquisition of SPECT and CT images, using the same imaging device, allows correct fusion of images of both modalities. TET was performed on 27 patients with known or suspected endocrine tumors. The radiopharmaceuticals used for the emission part of the study were chosen according to the tumor type: (111)In-octreotide for patients with neuroendocrine tumors (n = 10), (99m)Tc-sestamibi for patients with primary hyperparathyroidism (n = 8), (131)I for patients with thyroid cancer (n = 4), and (123)I-metaiodobenzylguanidine and (75)Se-cholesterol for patients with adrenal masses (n = 3 and n = 2, respectively). The additional information provided by TET compared with scintigraphy was assessed for both image interpretation and clinical utility. RESULTS: TET did not provide any additional data in 16 patients (59%), including 5 patients with normal scintigraphy. In 11 patients (41%) with abnormal SPECT findings, TET improved image interpretation by providing a better anatomic localization of SPECT-detected lesions. It showed unsuspected bone involvement in 4 patients, it identified the organs involved and the relationship of the lesions to neighboring structures in 5 patients, and it differentiated physiologic uptake from tumor uptake in 2 patients. TET provided additional information of clinical value in 9 patients (33%). It assisted in better planning of surgery in 2 patients with neuroendocrine tumors and in 2 patients with ectopic parathyroid adenomas. It changed the treatment approach in 2 patients with neuroendocrine tumors and 1 patient with thyroid carcinoma, and it altered prognosis in 2 patients with thyroid malignancy. CONCLUSION: TET enhances the already unique role of nuclear medicine procedures in the assessment and management of patients with endocrine neoplasms.

Late recurrence of combined hepatocellular carcinoma and hepatoblastoma in a child: case report and review of the literature.

We report on a case of late relapse of hepatocellular carcinoma in a child suffering from combined hepatoblastoma and hepatocellular carcinoma, stage IV. This is a rare event, as it has been accepted that a 5-year period free of any signs of disease in children suffering from malignant hepatic tumors is sufficient to classify such patients as survivors. In our patient, recurrence of the hepatocellular carcinoma component was diagnosed more than five years after the initial diagnosis. This case illustrates the need for more prolonged follow-ups for such children.

The effect of low-dose interleukin-2-based immunotherapy on salivary function and composition in patients with metastatic renal cell carcinoma.

One of the side-effects accompanying low-dose recombinant interleukin-2 (rIL-2)-based immunotherapy is salivary hypofunction. We evaluated the functional and compositional whole salivary profile at both resting and stimulated conditions in 10 renal cell carcinoma patients who received prolonged low-dose rIL-2-based immunotherapy. Following the termination of 4 weeks of the combined administration of rIL-2 and recombinant interferon-alpha (rIFN-alpha), we found significant reductions of salivary flow rates at resting condition, accompanied by significant multiple compositional alterations, including increases in calcium, magnesium and phosphate concentrations, and significant reductions in total protein concentration. In contrast, no flow rate reduction was noted under stimulated condition, and the only significant altered compositional component was the phosphate. We recommend salivary-supporting therapies and anticariogenic treatments for patients undergoing low-dose rIL-2-based immunotherapy.

Color-coded duplex ultrasound compared to CT angiography for detection and quantification of carotid artery stenosis.

OBJECTIVE: The purpose of this study was to compare findings on color-coded duplex ultrasound and CT angiography for grading internal carotid artery stenosis, and to investigate whether both these imaging modalities are necessary for an accurate diagnosis of carotid stenosis in the pre-surgical assessment of the internal carotid artery. PATIENTS AND METHODS: We examined 92 internal carotid arteries from 46 randomly chosen patients with suspected carotid stenosis by color-coded duplex ultrasound and by three-dimensional CT angiography (CTA). This retrospective study adhered to international guidelines with gradings of mild, moderate, severe, and occlusive carotid disease. RESULTS: The study demonstrated agreement between the degree of stenosis found on color-coded duplex ultrasound and that found on CTA in 78% of cases overall and in 79% of patients requiring surgical intervention. When compared to CTA, color-coded duplex ultrasound yielded a sensitivity of 78.9% and a specificity of 96.3%. Although findings on color-coded duplex ultrasound and CTA were comparable, disagreement affecting treatment decision occurred in 10:92 arteries. CONCLUSION: CTA was not found to be beneficial for patients exhibiting mild stenosis on color-coded duplex ultrasound, as none of the mild groupings found by sonography were interpreted as severe or occluded by CTA. However, CTA may be an important adjunct to color-coded duplex ultrasound regarding the categories of moderate, severe and occluded when carotid endarterectomy is considered.

Comparing thyroid ultrasonography to thyroid function in long-term survivors of childhood lymphoma.

BACKGROUND: We studied the value of thyroid ultrasonography as a follow-up tool in survivors of childhood lymphomas and correlated morphologic abnormalities with thyroid function tests. PROCEDURE: A prospective follow-up study of 45 long-term survivors of histology-proved childhood lymphomas was performed. Mean age at diagnosis was 9.1 years (range 2.1-16.4 years) and mean follow-up duration 10.9 years (range 3.9-22.2 years). RESULTS: Among the 26 survivors of Hodgkin disease (HD) who received mantle field irradiation, 14 (54%) had abnormal ultrasonograms. Elevated thyroid-stimulating hormone (TSH) concentrations were found in 14 (54%), and 6 of them (42%) had normal thyroid functions. Six of twelve patients with normal ultrasonograms had abnormal thyroid function, and 5 of 11 patients with normal function had abnormal sonograms. Among the 19 non-HD survivors who did not receive radiotherapy, 18 (95%) had both normal sonograms and normal function. Thus thyroid gland abnormalities were detected in 54% of HD survivors after mantle field irradiation. No correlation between the abnormalities detected on ultrasonography and serum levels of TSH and thyroid hormones were found. CONCLUSIONS: Both ultrasound and thyroid function tests independently provide clinically useful information; the former examines gland morphologogy and the latter evaluates hormonal changes associated with thyroid disease. The high frequency of thyroid abnormalities detected by ultrasonography suggests that periodic thyroid ultrasonography is advisable in the follow-up of patients treated with mantle irradiation to screen for morphologic changes that may presage malignant transformation.

Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy.

PURPOSE: To evaluate use of gallium 67 scintigraphy early during chemotherapy to predict the outcome in patients with aggressive non-Hodgkin lymphoma. MATERIALS AND METHODS: Among 118 patients, 67Ga scintigraphy was performed after one cycle of chemotherapy in 51 patients, after a median of 3.5 cycles in 97 patients, and both in 30 patients. Computed tomography (CT) was performed after a median of 3.5 cycles of treatment in 87 patients. The failure-free survival was compared between patients with positive or negative 67Ga or CT scans by using the log-rank test. Multivariate analysis helped determine the relation between 67Ga scintigraphic and CT findings and the outcome. RESULTS: The differences in failure-free survival between patients with positive versus negative 67Ga scans after one cycle of treatment (P < .001) and at midtreatment (P < .001) were significant. There was no statistically significant difference in failure-free survival between patients with positive versus negative CT findings during treatment. In multivariate analysis, 67Ga scintigraphy after one cycle (P < .045) and at midtreatment (P < .006) was an independent factor associated with outcome. CONCLUSION: Gallium 67 scintigraphic findings after one cycle of chemotherapy and at midtreatment are predictive of outcome in patients with aggressive non-Hodgkin lymphoma. CT findings are not predictive. Early 67Ga scintigraphy during chemotherapy is a good indicator of patients who may benefit from a change to a more aggressive treatment. A future study is necessary to investigate the potential effect of early change of treatment.

October 17, 2000 8:30-8:45. The New Technology of Combined Transmission and Emission F-18 FDG Tomography (FDG-TET) in the Diagnosis and Management of Cancer Patients.

The purpose of the study was to evaluate a new technology of simultaneous transmission and F-18 FDG emission tomography (FDG-TET) in tumor imaging and its impact on patient management.Emission and transmission devices were installed on the same gantry. 167 patients with histologically proven malignancy were evaluated at diagnosis or during follow up. Eight mCi of FDG were injected for PET and a low dose X-ray tube was used for CT. The FDG and CT were first interpreted independently, without knowledge of findings in other imaging modality. Subsequently fusion images were analyzed.FDG-TET changed the interpretation of PET or CT in 75 patients (45%). In 60 patients TET allowed for correct localization of lesions on the PET studies. In 15 patients, FDG uptake was found in sites of physiologic activity. In 12 patients lesions previously missed on CT were retrospectively identified. In 21 patients, TET detected 34 previously unknown sites of disease.FDG-TET changed the clinical management of 29 patients (17%). The stage of disease was changed in 9 patients. Early diagnosis of recurrence was made in 8 patients. Seven patients were referred for previously unplanned surgery. In 6 patients surgery was cancelled. Fifteen patients received additional chemo- or radiotherapy.Diagnosis of cancer on CT is based on a change in size or attenuation of a mass. PET shows the metabolic status of a lesion but lacks anatomical landmarks. FDG-TET improves the diagnostic accuracy in cancer and may have a significant impact on patient management.

Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of chemotherapy.

PURPOSE: To investigate gallium 67 scintigraphy performed early during treatment as a means to predict outcome and thus to optimize treatment of Hodgkin disease (HD) in the future. MATERIALS AND METHODS: Ninety-eight patients with HD were examined. Thirty-one patients underwent 67Ga scintigraphy after one chemotherapy cycle and 83 patients after a mean 3.5 cycles (range, 2-5 cycles). Sixteen patients underwent 67Ga scintigraphy both after one cycle and at midtreatment. Patients underwent whole-body scintigraphy and single photon emission computed tomography of the torso. Torso computed tomography (CT) was performed after a mean 3.5 cycles (range, 2-6 cycles). Failure-free survival was compared between patients with positive and patients with negative test findings (Kaplan-Meier method), and the significance of the difference was calculated. The association of failure-free survival with various prognostic clinical factors before treatment was compared (log-rank test univariate analysis). RESULTS: Failure-free survival differed significantly (P < .002) between patients with positive and patients with negative 67Ga scintigrams after one chemotherapy cycle but not at midtreatment. Failure-free survival was not significantly different between patients with positive and patients with negative CT scans at midtreatment. Twenty-two (92%) of 24 patients with negative 67Ga scintigrams after one cycle and 64 (82%) of 78 patients with negative scintigrams at midtreatment remained in complete response. In four (57%) of seven patients with positive 67Ga scintigrams after one cycle, treatment failed. CONCLUSION: 67Ga scintigraphy after one cycle of chemotherapy is a good early predictor of outcome of HD.

Celiac artery aneurysm: diagnosis by color Doppler sonography and three-dimensional CT angiography.

Celiac artery aneurysms are rare vascular lesions that are sometimes found incidentally during abdominal imaging. Their significance is in their potential to rupture, which can lead to death. We present the case of a celiac artery aneurysm diagnosed by color Doppler sonography and 3-dimensional CT angiography.

Clinical implication of VEGF serum levels in cirrhotic patients with or without portal hypertension.

AIM:To determine whether serum vascular endothelial growth factor (VEGF) levels correlates with the severity of liver cirrhosis and whether portal hypertension impacts on the expression of serum VEGF protein.METHODS:Fifty-three patients (mean age 56 ± 2 years) with HCV (n = 26), HBV (n = 13), and cryptogenic liver cirrhosis (n = 14) (Child-Pugh's class A: 24, B: 19 and C: 12) and normal renal function constitute the patient population, who were all diagnosed by clinical, histological and radiological findings. Six healthy people and six patients with acute hepatitis served as controls. Severity of liver disease was evaluated by the CP score. Serum levels of IGF-1 and VEGF were measured by radioimmunoassay and ELISA,respectively.Portal hypertension was assessed using pulsed Doppler ultrasound. RESULTS:The mean serum VEGF levels in all cirrhotic patients (73 ± 58) were significantly lower than those of healthy controls (360 ± 217, P < 0.01) and acute hepatitis (1123 ± 1261, P < 0.01) respectively. No significant difference in median serum VEGF levels were noted among the different Child-Pugh's classes (class A: median, 49.4ng/L, range, 21ng/L-260ng/L, Class B: median 59.9ng/L; range 21-92, and Class C: median 69; range 20ng/L-247ng/L). A significant correlation was noted between serum VEGF and two accurate parameters of portal hypertension: portal blood flow velocity (r = 0.6) and spleen size (r = 0.55). No correlation was found between VEGF serum levels and serum albumin, IGF-1, platelets count and aminotrasnferases (r = 0.2, r = 0.1, r = 0.2 and r = 0.2, respectively).CONCLUSION:Circulating VEGF level in patients with liver cirrhosis could not serve as an indicator of the progression of chronic liver disease but rather, they may reflect increased portal hypertension or decreased hepatic regenerative activity or the combination of both.