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.

Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake.

PURPOSE: To assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared. PATIENTS AND METHODS: One hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites. RESULTS: In 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P < .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%. CONCLUSION: Lymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.

Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma.

PURPOSE: Low-grade non-Hodgkin's lymphoma (LGNHL) has traditionally been considered non-gallium-avid. The sensitivity of gallium 67 (67Ga) scintigraphy when using modern equipment and techniques in patients with LGNHL was investigated. MATERIALS AND METHODS: Fifty-seven consecutive patients with LGNHL underwent 67Ga scintigraphy at initial presentation (n = 40), when tumor progression occurred during treatment (n = 3), and at suspected disease recurrence after continuous clinical remission (CCR) (n = 14). Planar and tomographic images were obtained with either a very large field-of-view or a dual-head digital camera. Of 45 patients with Ga-avid LGNHL, 30 underwent 93 follow-up scans (one to six studies per patient). Scan findings were correlated with clinical and computed tomographic (CT) findings and with patient outcomes. RESULTS: 67Ga scintigraphy was positive in 45 of 57 patients (sensitivity, 79%) and in 113 of 164 disease sites (sensitivity, 69%). The sensitivity was higher in the more common types of LGNHL: follicular, predominantly small cleaved cell (FSC), and follicular, mixed small cleaved and large cell (FM) (84% and 91% in patients and 72% and 71% in disease sites, respectively). Sensitivity was lower in patients with mucosa-associated lymphoid tissue lymphoma (MALT) and small lymphocytic lymphoma (SL). Among 28 patients with disease recurrence after CCR (14 with and 14 without baseline studies), 67Ga scan was positive in 25, for a sensitivity of 89% for detection of disease recurrence. CONCLUSION: When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.

Gallium-67 uptake in a mass of benign transformation mimicking recurrence of nodular lymphocytic predominance Hodgkin's disease.

Gallium-67 is now widely used in the management of lymphoma patients. It is not, however, tumor-specific and reasons for uptake in nonmalignant and premalignant lesions associated with lymphoma should be recognized. Gallium-67 uptake in a mass of progressively transformed germinal centers and sarcoid-like reaction, mimicking recurrence in a 31-yr-old man with nodular lymphocytic predominance Hodgkin's disease, is described. Gallium-67 was taken up on two occasions and a recurrence was suspected. On the first occasion, abnormal uptake was present in axillary lymph nodes and on the second in mediastinal and parahilar lymph nodes. Histology of the lesions on both occasions showed progressively transformed germinal centers and sarcoid-like reaction but no evidence of Hodgkin's disease (HD). Bilateral parahilar abnormal uptake of 67Ga disappeared spontaneously without treatment after several months. The mass on CT regressed but did not disappear. This case demonstrates that the appearance of a new mass which takes up 67Ga in lymphocytic-predominance HD during a continuous clinical remission does not necessarily indicate recurrence and the need for treatment. It suggests that a biopsy should be performed to determine the nature of the lesion.

Gallium-67 scintigraphy in lymphoma with bone involvement.

UNLABELLED: Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium-99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment.

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.

Simultaneous operation for hydatid cysts of right lung and liver.

Hydatid disease is endemic in certain villages in Galilee, Israel. Most patients seen in our thoracic surgical department have only pulmonary cysts, but some of them have concomitant liver cysts. From 1963 until 1982, 10 patients who were referred for lung operations had echinococci removed from the liver through a right thoracotomy. Every patient with a suspected diagnosis of pulmonary hydatidosis had isotope and ultrasound scans of the liver. Liver cysts found adjacent to the right hemidiaphragm were removed at thoracotomy. Patients having liver cysts remote from the diaphragm were referred for laparotomy. There were no postoperative complications or deaths in this series. We advocate routine search for liver cysts in any surgical candidate with lung hydatids. Accessible liver cysts should be excised at the same thoracotomy. We did not find any mention of this approach in the literature available to us.

Application of a bedside whole blood D-dimer assay in the diagnosis of deep vein thrombosis.

Cross-linked fibrin degradation products have been used to detect venous thrombosis. While the sensitivity of plasma D-dimer measured by ELISA in the diagnosis of deep vein thrombosis (DVT) is high, the utility of ELISA methods is limited in a clinical setting. This study analysed the diagnostic value of a rapid D-dimer assay performed on whole blood samples (SimpliRed D-dimer) compared with latex and ELISA in 86 patients suspected of having DVT. SimpliRed D-dimer was positive in 47/50 of patients with DVT established by Doppler ultrasound (DU; sensitivity 94%). SimpliRed D-dimer was positive in 35/37 of patients with proximal DVT, nine out of nine with popliteal DVT and three out of four with superficial thrombophlebitis. The specificity of SimpliRed D-dimer in the diagnosis of DVT was 61%. The sensitivity of the SimpliRed D-dimer assay was at least comparable with the ELISA (87%) and superior to the latex assay (80%). The positive predictive value (77%), the negative predictive value (88%) and the overall accuracy (80%) of the SimpliRed assay were better than the ELISA and latex methods. It is concluded that SimpliRed D-dimer is a rapid useful assay for screening of patients suspected of having deep vein thrombosis.

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.

Duplex sonography in the diagnosis of portal vein thrombosis.

Portal vein thrombosis was readily diagnosed by pulsed duplex Doppler sonography in five patients. The cases represent different stages in the development of the thrombotic event, from partial or complete occlusion by an echogenic intraluminal thrombus to cavernous transformation of the portal vein. The unique ability of duplex scanning to demonstrate abnormal vascular structures and flow pattern is emphasised. This method should be the technique of choice in the diagnosis of portal vein thrombosis.

Late changes in veins after deep venous thrombosis: ultrasonographic findings.

In a prospective trial, 43 patients (45 legs) were re-examined by high resolution and continuous-wave Doppler ultrasonography 3-32 months after an acute episode of deep venous thrombosis (DVT). The veins were abnormal in 31 legs (69%). Abnormal veins were either narrowed with a highly echogenic lumen (thought to represent persistent occlusion) or with a relatively sonolucent lumen and thickened walls (thought to represent recanalized veins). Collateral veins were present. Some compression by probe could be achieved in partially occluded veins, but full collapsibility was absent. Continuous-wave Doppler studies were similar to those in acute DVT. In order to be able to diagnose new episodes of DVT in patients who have had DVT in the past, a baseline ultrasound study should be carried out approximately 6-12 months after an acute episode. In the absence of such a baseline study, contrast phlebography should be resorted to.

High-resolution real-time ultrasonography in the diagnosis of deep vein thrombosis.

The contribution of high-resolution real-time ultrasonography to the diagnosis of deep vein thrombosis (DVT) was evaluated in a prospective study performed on 96 patients. 45 patients were also examined with contrast venography and 79 with continuous wave Doppler ultrasound. The femoral and popliteal veins were examined for compressibility by pressure with the transducer probe, response to deep inspiration and Valsalva's manoeuvre and presence of an intraluminal mass. The contralateral veins were routinely screened for comparison. The diagnostic sensitivity versus phlebography was 87%, and the specificity 100% for the femoral vein. When including the popliteal vein the specificity was 91%. Real-time ultrasonography together with Doppler ultrasound examination is an effective non-invasive approach for the diagnosis of DVT. Phlebography can be avoided if these two examinations are unequivocally positive or negative for DVT.

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.

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.

Doppler ultrasound in the diagnosis of venous thrombosis.

Deep vein thrombosis (DVT) has known morbidity and mortality. New noninvasive techniques such as B-mode scanning and Doppler ultrasonography (duplex) are highly accurate in the diagnosis of this problem but are relatively expensive and time consuming. Continuous-wave Doppler, a precursor noninvasive technique, is simple, cheap, and easy to perform at the patient's bedside. To test the effectiveness of this technique the authors prospectively studied patients with clinical suspicion of DVT by Doppler ultrasound and compared the results with those from venography. During fourteen consecutive months, patients with a clinical suspicion of DVT underwent continuous-wave Doppler examination of both inferior limbs. Each case was diagnosed as positive, negative, or inconclusive. In addition, the patients underwent a questionnaire regarding risk factors, symptoms, and mean relevant physical findings. Doppler examination was blinded to venography results. A total of 116 patients with clinical suspicion of DVT were examined by Doppler ultrasound. Their mean age was fifty-five years (range: eighteen to eighty-eight). There were 57 men and 59 women, and from this group a total of 40 patients underwent both Doppler ultrasound examination and venography in the course of forty-eight consecutive hours. When cases with an inconclusive result were excluded, Doppler ultrasound showed a sensitivity of 89%, a specificity of 100%, and an accuracy of 94% for the diagnosis of DVT when compared with venography. When a similar analysis was done for the proximal named veins, continuous-wave Doppler examination showed a very high specificity and positive predictive value and a moderate sensitivity and negative predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Pattern analysis of temporal changes in the carotid artery diameter under normal and pathological conditions.

Age-related and temporal cyclic changes in the left and right common carotid arteries (CCA) diameters were studied in two groups of subjects: (i) 11 healthy normotensive subjects (ages 19-72 years), and (ii) eight hypertensive subjects (ages 59-85 years), with various degrees of stenosis in their ICA. Cross-sectional images of the left and right CCA were acquired via an ultrasonic system. Images were digitized, and the contour of the arterial wall for each frame was manually traced. Assuming a circular geometry, the arterial diameter was calculated. Averaging four to six consecutive heart beats yielded the typical patterns of temporal diameter changes for both the left and right CCA. For the group of normal subjects, a typical pattern of the temporal diameter changes with a consistent left vs right peak diameter delay (LRPDD), with the right CCA preceding the left, was observed. Plotting the normalized left vs right CCA diameters yielded a typical loop (DDloop) which changed in the counter-clockwise direction from systole to diastole. For the group of hypertensive subjects, the LRPDD decreased or became negative with the left CCA preceding the right if the stenosis degree exceeded 50% (p < 0.01). The DDloop changed from a counterclockwise to a clockwise direction. For the group of normal subjects, end diastolic, end systolic diameters and the elastic index of the CCA increased with age while the relative systolic change in diameter decreased with age. For the group of hypertensive subjects, the relative systolic change in diameter was smaller, compared to normals (7.8 +/- 1.2% vs 10.7 +/- 3.1%, respectively; p < 0.05). The elastic index for this group was significantly higher compared to the normal subjects (1.4 +/- 0.3 vs 0.6 +/- 0.2 x 10(5) dynes/cm2, respectively; p < 0.001). These findings imply that patterns of CCA temporal diameter changes can indicate the existence of a pathological state.

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.

[Ultrasonographic diagnosis of deep vein thrombosis of the leg].

142 patients with the clinical diagnosis of deep vein thrombosis (DVT) of the legs were examined by high resolution ultrasound. The deep and superficial femoral and popliteal veins were examined with 6.5 and 10 MHz transducers. 124 of the patients were also examined with continuous wave Doppler ultrasound and in 46 contrast phlebography was performed. The overall accuracy of ultrasound compared to phlebography was 90%. If only the deep femoral vein was considered, ultrasound and phlebography correlated in 100%. The ultrasonographic characteristics of DVT are increased echogenicity of the involved vein, absence of response to the Valsalva maneuver and non-collapsibility of the thrombosed vein on pressing with the transducer probe. High resolution ultrasonography should be the primary tool for the diagnosis of DVT.