Sonohysterography for evaluation of the endometrium in women treated with tamoxifen.

OBJECTIVE: This study was performed to evaluate sonohysterography for the diagnosis of endometrial abnormalities in women treated with tamoxifen. MATERIALS AND METHODS: Fifty sonohysterograms were obtained in 48 consecutive tamoxifen-treated women. All women were postmenopausal and had been undergoing tamoxifen therapy for a mean of 2.6 years. Forty-six sonohysterograms (92%) were completed and four were unsuccessful. Sonohysterogram findings were correlated with prior endometrial biopsy results for 23 sonohysterograms (46%) that were preceded by endometrial biopsy. Sonohysterogram findings were also compared with histopathology results, available for 38 sonohysterograms (76%) that were followed by hysteroscopy with dilatation and curettage. RESULTS: Sonohysterography revealed 31 endometrial polyps (62%), six thickened endometria (12%), five normal endometria (10%), and four subendometrial cysts (8%). Surgery was avoided when seven sonohysterograms (14%) revealed normal endometria or subendometrial cysts. In the group with histopathologic correlation, 23 of 28 polyps were confirmed and two of five thickened endometria were shown to represent endometrial hyperplasia. Twelve (63%) of 19 sonohysterograms with prior normal endometrial biopsy findings had abnormalities on sonohysterography, including 10 polyps and two thickened endometria. CONCLUSION: Sonohysterography aids the diagnosis of endometrial abnormalities in tamoxifen-treated women even if prior endometrial biopsies have negative findings. In 14% of cases, visualization of a normal endometrium on sonohysterography obviated surgery.

Testicular microlithiasis: what is its association with testicular cancer?

PURPOSE: To determine the prevalence of testicular microlithiasis in patients who were referred for scrotal ultrasonography (US) at a tertiary care cancer center and to evaluate the association between microlithiasis and cancer. MATERIALS AND METHODS: Testicular sonograms obtained in 528 men were retrospectively reviewed to identify patients with US findings suggestive of microlithiasis, intratesticular masses, and intratesticular heterogeneous changes. The association of US findings with medical records and with histopathologic findings that were available in 95 patients was evaluated. Statistical analysis was performed to determine the relationship of testicular cancer, intratesticular mass, and microlithiasis. RESULTS: Forty-eight (9%) of the 528 patients had microlithiasis; 13 of these (27%) had testicular cancers. Of the 480 patients without microlithiasis, 38 (8%) had testicular cancer. Ninety patients had an intratesticular mass, of whom 23 (26%) had microlithiasis. Forty-three (12 with microlithiasis) patients with a mass had testicular cancer, 43 (10 with microlithiasis) had benign findings or nontesticular malignant histopathologic findings, and four (one with microlithiasis) had no pathologic findings. CONCLUSION: Intratesticular microlithiasis is highly associated with confirmed testicular cancer, as well as with US evidence of testicular mass.

Pancreatic ultrasonography.

Pancreatic abnormalities usually are detected on US when it is used for screening patients with abdominal pain and for assessment of the gallbladder and bile ducts. Pancreatic visualization is limited by bowel gas, but with experienced sonographers and newer techniques, including harmonic imaging and oral contrast US, diagnosis of pancreatic abnormalities has significantly improved compared with earlier reports. Appropriate initial diagnosis by US can tailor further investigation, and US-guided biopsy may establish definitive diagnosis.

What is the yield of intraoperative ultrasonography during partial hepatectomy for malignant disease?

BACKGROUND: Previous studies have shown that intraoperative ultrasonography (IOUS) during hepatic resection for malignancy changes the operative plan or identifies occult unresectable disease in a large proportion of patients. This study was undertaken to reassess the yield of IOUS in light of recent improvements in preoperative staging. STUDY DESIGN: Patients with potentially resectable primary or metastatic hepatic malignancies subjected to exploration, bimanual palpation of the liver, and IOUS were evaluated prospectively. Intraoperative findings were recorded, and preoperative imaging studies were reanalyzed by radiologists blinded to the intraoperative findings. The extent of disease based on preoperative imaging was compared with the intraoperative findings. RESULTS: From October 1997 until November 1998, 111 patients were evaluated. At exploration, a total of 77 new findings or findings different than suggested on the imaging studies were identified in 61 patients (55%), the most common of which was additional hepatic tumors (n = 37). Thirty-five of 77 (45%) new findings were identified by IOUS alone and 10 (13%) by palpation alone; the remainder were identified by both palpation and IOUS. Forty-seven of 61 patients (77%) underwent a complete resection despite new intraoperative findings, with a modification (n = 28) or no change (n = 19) in the planned operation. Twenty-one patients (19%) had new findings identified only on IOUS. Thirteen of these patients underwent resection with no change in the operative plan, six underwent a modified resection and two were considered to have unresectable disease based solely on the findings of IOUS. CONCLUSIONS: In patients with hepatic malignancies submitted to a potentially curative resection, new intraoperative findings or findings different than suggested on preoperative imaging studies are common. But resection with no change in the operative plan or a modified resection is still possible in the majority of patients despite such findings. The findings on IOUS alone rarely lead to a change in the operative plan.

Lower extremity venous sonography in the high-risk cancer population: one leg or two?

OBJECTIVE: We correlated the diagnostic yield of unilateral and bilateral lower extremity venous sonograms in a high-risk cancer population with the clinical indication for the examination. MATERIALS AND METHODS: Reports from 433 bilateral and 619 unilateral lower extremity Doppler sonograms obtained over an 18-month period in patients with cancer were retrospectively reviewed, and clinical indication and findings were determined. RESULTS: Overall, 228 (22%) of 1052 examinations revealed deep venous thrombosis (DVT): 83 (19%) of 433 bilateral and 145 (23%) of 619 unilateral. Among studies performed for unilateral symptoms (pain, edema, or postorthopedic procedure), 23% (135/581) of unilateral and 27% (44/162) of bilateral studies revealed DVT. Among these 44 bilateral studies with positive findings performed for unilateral symptoms, there were 30 DVT in the symptomatic side, 12 bilaterally, and two in the asymptomatic side alone. Ten percent (11/110) of the bilateral studies performed for bilateral symmetric symptoms revealed DVT. Among studies performed for bilateral asymmetric symptoms, 13% (1/8) of the unilateral and 8% (2/25) of the bilateral studies revealed DVT; both bilateral studies showed positive findings in the more symptomatic side. Among studies performed for suspected or proven pulmonary embolus, 20% (23/113) of bilateral and 54% (7/13) of unilateral studies had positive findings. CONCLUSION: In a high-risk cancer population, the incidence of DVT in patients with unilateral symptoms is more than twice that of patients with bilateral symptoms. Because DVT isolated to an asymptomatic lower extremity is rare (1%), bilateral sonographic examination is generally unnecessary with unilateral lower extremity symptoms.

Diagnostic imaging approaches and relationship to hepatobiliary cancer staging and therapy.

Diagnostic imaging plays an essential role in management of hepatobiliary tumors. High resolution images provided by computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) allow detection of tumor within the liver. CT arterial portography remains the standard for detection of small lesions in the range of 1.5 cm, but noninvasive techniques such as contrast-enhanced helical CT and MR hold promise for comparable lesion detection. MRI provides lesion characterization for differentiation of benign and malignant tumors. Lesion characterization has been further improved by faster CT and MR techniques that allow imaging in both arterial and portal venous phases for characterization of lesions based on the rate and pattern of enhancement. Functional imaging such as 2-fluoro-2-deoxy-D-glucose-positron-emission tomography (FDG-PET) is increasingly utilized for detection of intrahepatic tumor and extrahepatic disease. Accuracy of FDG-PET for extrahepatic disease is better than conventional imaging and has been shown to change management in a significant number of patients. Imaging is also invaluable for surgical planning. Segmental anatomy is well shown by CT, MRI, and US. CT or MR angiography with newer 3D techniques delineate vascular variants and areas of encasement or occlusion by tumor. Biliary involvement at the hilus may be shown by US and MR cholangiography. Imaging detection of vascular involvement, bile duct extension, and lobar atrophy may alter the surgical approach.

Adnexal masses in women with breast cancer: US findings with clinical and histopathologic correlation.

PURPOSE: To correlate ultrasonographic (US), clinical, and histopathologic findings in patients with breast cancer who underwent surgery for adnexal masses evident at US. MATERIALS AND METHODS: A database search yielded 54 patients with breast cancer and with adnexal masses at US and histopathologic examinations. Clinical, US, and histopathologic findings were correlated. RESULTS: Forty (74%) patients had benign adnexal masses, and 14 (26%) had malignant masses; three patients had both benign and malignant ovarian masses. Seven patients had primary ovarian cancer, and seven had breast metastases to the ovary. All breast metastases to the ovary were bilateral solid masses at histopathologic examination and occurred in women with stage IV breast carcinoma at the time of US. Eleven ovaries with breast metastases were solid at US. The remaining three ovaries with breast metastases had cystic components at US because of hemorrhage or coexistent benign ovarian cysts. Four of seven patients with primary ovarian carcinoma had bilateral ovarian tumors, and seven of 11 ovarian carcinomas were predominantly cystic at US. No patient with primary ovarian carcinoma had stage IV breast cancer. CONCLUSION: In this small series, half the ovarian malignancies in patients with breast cancer were primary ovarian carcinomas and half were breast metastases to the ovary. Breast metastases to the ovary most frequently are bilateral solid masses at US and are associated with stage IV disease at the time of US.

Abnormal testis at US in patients after orchiectomy for testicular neoplasm.

PURPOSE: To categorize ultrasonographic (US) intratesticular abnormalities in patients after orchiectomy for testicular neoplasm and to correlate US, clinical, and histopathologic findings. MATERIALS AND METHODS: Two hundred thirty-five testicular US examinations were performed in 171 patients who previously underwent orchiectomy for testicular neoplasm. Abnormalities were identified in 28 patients. The abnormalities were described as masses, heterogeneous changes, or macrocalcification. US findings were correlated with histopathologic findings in specimens obtained at surgery in 18 patients; follow-up to determine clinical outcome was obtained from the review of medical records in the remaining 10 patients. RESULTS: Testicular US revealed intratesticular mass in 15, heterogeneous changes in 11, and macrocalcification in two patients. Eighteen patients had histopathologic correlation; 13 had testicular cancer. At US, 10 of the 15 (67%) patients with a mass and only three of the 11 (27%) with heterogeneous changes had cancer. All 10 patients without surgical correlation had clinical follow-up of 2(1/2)-7 years (mean, 3.95 years), with no evidence of disease. CONCLUSION: Intratesticular mass always is a concern, and heterogeneous changes are less worrisome, but in all patients, rigorous follow-up is recommended to rule out malignancy.

Hepatic sonography: comparison of tissue harmonic and standard sonography techniques.

OBJECTIVE: This study was performed to compare tissue harmonic sonography of the liver with conventional sonography of the liver. SUBJECTS AND METHODS: Forty-eight patients underwent tissue harmonic and conventional sonography of the liver, using a randomized imaging sequence. Imaging parameters were standardized, but gain varied. Techniques were compared using predetermined impact analysis categories. If a finding was revealed by only one sonographic technique, additional confirmation was obtained by another imaging technique or by surgery. In a separate image quality analysis, masked images were reviewed by two experienced radiologists to evaluate fluid-solid differentiation, near-field, far-field, and overall image quality. Rankings were correlated with field of view of images and body habitus of patients as determined by body mass index. RESULTS: Tissue harmonic sonography provided the same information as conventional sonography in 34 patients (71%) and added information in 14 patients (29%). The findings from tissue harmonic sonography resulted in altered treatment in five patients (10%). Eight patients (17%) had lesions revealed by tissue harmonic sonography only. Four patients (8%) had inadequate far-field visualization by both techniques. Both observers ranked tissue harmonic sonography the same as or better than standard sonography in 46 patients (96%) for fluid-solid differentiation, in 46 patients (96%) for near-field image quality, and in 45 patients (94%) for overall image quality. For far-field image quality, one observer ranked tissue harmonic sonography the same as or better than conventional sonography in 40 patients (83%), and the second observer, in 41 patients (85%). Image quality ratings showed no correlation with body habitus of the patients or field of view of images. CONCLUSION: Tissue harmonic sonography of the liver provides more information and better image quality than does conventional sonography of the liver.

The role of herpes simplex virus ICP27 in the regulation of UL24 gene expression by differential polyadenylation.

Herpes simplex virus specifies two sets of transcripts from the UL24 gene, short transcripts (e.g., 1.4 kb), processed at the UL24 poly(A) site, and long transcripts (e.g., 5.6 kb), processed at the UL26 poly(A) site. The 1.4- and 5.6-kb transcripts initiate from the same promoter but are expressed with early and late kinetics, respectively. Measurements of transcript levels following actinomycin D treatment of infected cells revealed that the 1.4- and 5.6-kb UL24 transcripts have similar stabilities, consistent with UL24 transcript kinetics being regulated by differential polyadenylation rather than by differential stabilities. Although the UL24 poly(A) site, which gives rise to short transcripts, is encountered first during processing, long transcripts processed at the UL26 site are equally or more abundant; thus, operationally, the UL24 site is weak. Using a series of viral ICP27 mutants, we investigated whether ICP27, which has been suggested to stimulate the usage of weak poly(A) sites, stimulates 1.4-kb transcript accumulation. We found that accumulation of 1.4-kb transcripts did not require ICP27 during viral infection. Rather, ICP27 was required for full expression of 5.6-kb transcripts, and the decrease in 5. 6-kb transcripts relative to 1.4-kb transcripts was not due solely to reduced DNA synthesis. Our results indicate that temporal expression of UL24 transcripts can be regulated by differential polyadenylation and that although ICP27 is not required for processing at the operationally weak UL24 poly(A) site, it does modulate 5.6-kb transcript levels at a step subsequent to transcriptional initiation.

Laparoscopic ultrasound enhances standard laparoscopy in the staging of pancreatic cancer.

OBJECTIVE: To define the role of laparoscopic ultrasound (LUS) in the staging of pancreatic tumors. SUMMARY BACKGROUND DATA: Laparoscopy has recently been established as a valuable tool in the staging of pancreatic cancer. It has been suggested that the addition of LUS to standard laparoscopy could improve the accuracy of this procedure. METHODS: A prospective evaluation of 90 patients with pancreatic tumors undergoing laparoscopy and LUS was performed over a 27-month period. LUS equipped with an articulated curved and linear array transducer (6 to 10 MHz) was used. All patients underwent rigorous laparoscopic examination. Clinical, surgical, and pathologic data were collected. RESULTS: The median age was 65 years (range 43 to 85 years). Sixty-four patients had tumors in the head, 19 in the body, and 3 in the tail of the pancreas. Four patients had ampullary tumors. LUS was able to image the primary tumor (98%), portal vein (97%), superior mesenteric vein (94%), hepatic artery (93%), and superior mesenteric artery (93%) in these patients. LUS was particularly helpful in determining venous involvement (42%) and arterial involvement (38%) by the tumor. This resulted in a change in surgical treatment for 13 (14%) of the 90 patients in whom standard laparoscopic examination was equivocal. CONCLUSIONS: LUS is useful in evaluating the primary tumor and peripancreatic vascular anatomy. When standard laparoscopic findings are equivocal, LUS allowed accurate determination of resectability. Supplementing laparoscopy with LUS offers improved assessment and preoperative staging of pancreatic cancer.

Deep venous thrombosis after orthopedic surgery in adult cancer patients.

BACKGROUND AND OBJECTIVES: Patients with cancer and patients undergoing major orthopedic procedures are two groups at risk of deep venous thrombosis (DVT). The objective was to determine the rate of venous thromboembolic disease in patients with a malignant neoplasm and major orthopaedic surgery of the lower limb. METHODS: The study included 169 patients. All patients were given knee-high intermittent pneumatic compression devices for prophylaxis. Postoperative surveillance for thrombosis was performed on all patients with venous duplex doppler ultrasonography. RESULTS: Proximal DVT occurred in 24 of 169 patients (14.2%). One patient (0.6%) developed a symptomatic, nonfatal pulmonary embolus (PE). The development of DVT was not associated with age, sex, type of surgery, type of neoplasm, location, or pathologic fracture. The addition of anticoagulant medication such as warfarin did not significantly reduce the rate of DVT in a subset of 54 patients. In three patients, the DVT occurred only in the contralateral limb, and in four patients, there were bilateral DVTs. CONCLUSIONS: When intermittent compression boots were used for prophylaxis in conjunction with ultrasound screening, the risk of proximal DVT was substantial (14.2%), but the rate of symptomatic PE was low (0.6%).

Gallbladder cancer: can ultrasonography evaluate extent of disease?

This study reviews the spectrum of sonographic findings in patients with gallbladder cancer, attempts to determine if sonography can identify patients with potentially resectable disease, and emphasizes the limitations of ultrasonography in the evaluation of -gallbladder cancer. Thirty-five consecutive patients with histologically proven gallbladder carcinoma who had preoperative abdominal ultrasonography and surgery were identified. Involvement of the gallbladder and gallbladder fossa, metastases, bile ducts, portal vein, and adjacent lymph nodes was assessed sonographically. The extent of disease and staging as revealed by sonography was compared to operative and surgical pathologic findings. Masses in the gallbladder or gallbladder fossa were present at surgery in 26 patients; 22 (85%) of these masses were shown by sonography. Sonography identified six (67%) of nine cases of pathologically confirmed liver metastases, 11 (79%) of 14 cases of bile duct involvement, and two (67%) of three cases of portal venous involvement by tumor. Sonography revealed lymph node metastases in only five (36%) of 14 patients. None of the 12 cases with peritoneal metastases was identified sonographically. By surgical staging 16 (46%) patients had potentially resectable disease (stage III or less), and 19 (54%) patients had unresectable stage IV disease. Sonography correctly identified 15 (94%) of 16 patients with potentially resectable disease and seven (37%) of 19 patients with advanced disease. Twelve patients with advanced disease were under-staged: nine had peritoneal metastases, two had liver metastases, and one had celiac adenopathy, which was not shown by sonography. In conclusion, sonography is reliable in the detection of a primary gallbladder mass or of local extension of tumor into the liver. However, sonographic findings do not accurately reflect the full extent of disease, and sonography is particularly limited in the diagnoses of metastases to the peritoneum and lymph nodes.

Tumor involvement in hepatic veins: comparison of MR imaging and US for preoperative assessment.

PURPOSE: To compare use of magnetic resonance (MR) imaging and ultrasonography (US) for diagnosis of vascular involvement by tumor at the hepatic vein confluence. MATERIALS AND METHODS: Thirty-seven consecutive patients with tumors at the hepatic vein confluence were prospectively evaluated with spin-echo and gradient-echo MR imaging and gray-scale and Doppler US. Encasement, thrombosis, occlusion, and nonvisualization were considered to be evidence of vascular involvement. Imaging results were compared with surgical and pathologic examination findings in 27 patients who underwent resection. RESULTS: Sixteen hepatic veins (nine right, four middle, three left) were seen to be involved at surgery. Twelve of 16 involved veins were identified at MR imaging (75% sensitivity, 98% specificity, 92% positive predictive value, 94% negative predictive value). Thirteen of 16 involved veins were detected at US (81% sensitivity, 97% specificity, and 87% positive and 95% negative predictive values). There was one false-positive diagnosis of inferior vena cava involvement at both MR imaging and US. Ten patients had unresectable disease. One patient had motion artifact on MR images; in the remaining nine patients, MR imaging and US yielded identical findings at 26 of 27 hepatic vein sites. CONCLUSION: MR imaging and US provide comparable results for assessment of hepatic vein involvement by tumor.

Laparoscopic sonography of peripancreatic tumors: preliminary experience.

OBJECTIVE: This study was performed to evaluate the use of laparoscopic sonography in patients with suspected peripancreatic tumors and to assess the impact of laparoscopic sonography on patient management. SUBJECTS AND METHODS: In a prospective study, 24 patients with suspected pancreatic malignancy underwent CT, laparoscopy, and laparoscopic sonography. The pancreas, peripancreatic vasculature, liver, and porta hepatis were evaluated in each patient. Metastases (hepatic, peritoneal, or nodal), extrapancreatic extension of tumor, or vascular encasement was considered evidence of unresectable disease. Histopathology was the standard of reference; unresectable disease was confirmed by biopsy. At the completion of the laparoscopic sonography, each examination was scored according to impact analysis categories that had been prospectively established. RESULTS: Peripancreatic vasculature was adequately shown by laparoscopic sonography in 22 patients (92%), of whom 12 patients had histopathologic evidence of vascular encasement. All 12 cases of vascular encasement were revealed by laparoscopic sonography, and 10 of 12 cases of vascular encasement were revealed by CT. Liver lesions were seen in eight patients (33%). One hemangioma was shown solely by laparoscopic sonography; the other seven liver lesions were revealed by CT, laparoscopy, or both. In six patients (25%), laparoscopic sonography was used to guide biopsy of lesions that were not seen by laparoscopy. Impact analysis showed that laparoscopic sonography provided additional information in eight patients (33%) and altered management in four patients (17%). Of those patients for whom laparoscopic sonography altered management, three patients underwent successful resection after laparoscopic sonography two of these patients had suspected vascular encasement on CT but laparoscopic sonography revealed normal vessels, and the third patient had CT evidence of a liver lesion that was shown to be a cyst on laparoscopic sonography. A fourth patient was spared laparotomy when laparoscopic sonography revealed unsuspected vascular encasement. CONCLUSION: Preliminary experience suggests that laparoscopic sonography may aid diagnosis and alter management in patients with suspected pancreatic neoplasms.

Mammographic findings after stereotactic 14-gauge vacuum biopsy.

PURPOSE: To evaluate mammographic findings after stereotactic 14-gauge vacuum biopsy. MATERIALS AND METHODS: Retrospective review was performed of results at stereotactic 14-gauge vacuum biopsy in 108 lesions in 100 women. The median number of specimens obtained per lesion was 12 (mean, 14; range, 1-50). In all cases, mammography was performed immediately after vacuum biopsy. Pre- and postbiopsy mammograms were reviewed. RESULTS: Postbiopsy mammograms depicted air at the biopsy site in 78 (72%) of 108 lesions and hematoma in 65 (60%) of 108 lesions. Of 55 lesions depicted as calcifications, postbiopsy mammograms depicted a decrease in the number of calcifications in 45 (82%), including nine cases in which all calcifications were removed. No residual lesion was identified on postbiopsy mammograms in 14 (13%) of 108 lesions; 11 (58%) of 19 mammographic lesions that measured 0.5 cm or less in maximal dimension were completely removed. Nineteen patients underwent a needle localization procedure, at a median 14 days (range, 6-51 days) after vacuum biopsy. In one patient a hematoma was depicted at mammography 10 days after biopsy; in the remaining 18 (95%) patients, mammograms obtained during needle localization depicted no hematoma or air. CONCLUSION: Air and hematoma were often present on mammograms immediately after stereotactic vacuum biopsy, but these changes resolved rapidly. Stereotactic vacuum biopsy provided wide sampling of calcifications and allowed complete removal of the mammographic lesion in some cases.

Cholangiocarcinoma at the hepatic hilus: sonographic findings.

OBJECTIVE: This study was performed to characterize sonographic findings in patients with cholangiocarcinoma at the hepatic hilus and to compare those sonographic findings with surgical and pathologic findings. MATERIALS AND METHODS: Thirty-nine consecutive patients with hilar cholangiocarcinoma (Klatskin tumor) had preoperative color and spectral Doppler sonography and had surgical-pathologic correlation. Biliary drainage catheters were present in 24 patients (62%). In all patients, we evaluated presence of bile duct mass, level of bile duct involvement, patency of portal veins, and hepatic mass lesions. RESULTS: Ductal masses were revealed by sonography in 34 patients (87%). Masses were isoechoic in 22 patients (65%), hypoechoic in seven (21%), and hyperechoic in five (15%). The masses included nodular mural thickening in 19 patients (56%), infiltrative lesions in nine (26%), and intraductal polypoid masses in six (18%). The extent of bile duct involvement was revealed sonographically in 34 cases (87%) by the distribution of bile duct obstruction, the location of a ductal mass, or both. Portal vein involvement by tumor was shown sonographically in 20 patients (51%); 13 patients had occluded portal veins, and seven had encased portal veins without occlusion. Twenty-one portal veins in 16 patients were found to be involved at surgery; sonography showed 18 (86%) of 21 involved portal veins. Hepatic masses were present at surgery in six patients; four of these masses were malignant and two were benign. Sonography revealed five of the six masses and failed to reveal metastases in one patient who had pneumobilia from a biliary drainage catheter. CONCLUSION: Although Klatskin tumors are usually isoechoic, they can be revealed by sonography, and their morphology can be characterized. The extent of bile duct involvement may be shown on sonograms by the location of tumor and the distribution of bile duct obstruction. Portal vein involvement is frequent, and hepatic metastases are uncommon.

Identification of a competitive translation determinant in the 3' untranslated region of alfalfa mosaic virus coat protein mRNA.

We report that the competitive translational activity of alfalfa mosaic virus coat protein mRNA (CP RNA), a nonadenylated mRNA, is determined in part by the 3' untranslated region (UTR). Competitive translation was characterized both in vitro, with cotranslation assays, and in vivo, with microinjected Xenopus laevis oocytes. In wheat germ extracts, coat protein synthesis was constant when a fixed amount of full-length CP RNA was cotranslated with increasing concentrations of competitor globin mRNA. However, translation of CP RNA lacking the 3' UTR decreased significantly under competitive conditions. RNA stabilities were equivalent. In X. laevis oocytes, which are translationally saturated and are an inherently competitive translational environment, full-length CP RNA assembled into large polysomes and coat protein synthesis was readily detectable. Alternatively, CP RNA lacking the 3' UTR sedimented as small polysomes, and little coat protein was detected. Again, RNA stabilities were equivalent. Site-directed mutagenesis was used to localize RNA sequences or structures required for competitive translation. Since the CP RNA 3' UTR has an unusually large number of AUG nucleotide triplets, two AUG-containing sites were altered in full-length RNA prior to oocyte injections. Nucleotide substitutions at the sequence GAUG, 20 nucleotides downstream of the coat protein termination codon, specifically reduced full-length CP RNA translation, while similar substitutions at the next AUG triplet had little effect on translation. The competitive influence of the 3' UTR could be explained by RNA-protein interactions that affect translation initiation or by ribosome reinitiation at downstream AUG codons, which would increase the number of ribosomes committed to coat protein synthesis.

Endometrial thickness in tamoxifen-treated patients: correlation with clinical and pathologic findings.

OBJECTIVE: This study was performed to evaluate sonographic measurements of endometrial thickness in postmenopausal breast cancer patients being treated with tamoxifen and to correlate endometrial thickness with pathology, symptoms, and duration of tamoxifen treatment. MATERIALS AND METHODS: Pelvic sonograms and medical records of 91 postmenopausal breast cancer patients being treated with tamoxifen were retrospectively reviewed. Histologic results were available in 46 patients (51%). Endometrial thickness was measured in anteroposterior dimension and was considered normal when less than 8 mm. Endometrial thickness was then correlated with histopathologic findings, symptoms, and duration of tamoxifen treatment. RESULTS: Forty-seven examinations (52%) showed endometrial thickness of less than 8 mm and 44 examinations (48%) showed endometrial thickness of 8 mm or more. Endometrial biopsy was performed in 10 women (21%) in whom the endometrial thickness was less than 8 mm, revealing seven normal endometria, one endometrial polyp, and two insufficient samples. Endometrial biopsy was performed in 36 women (82%) in whom endometrial thickness was 8 mm or more, revealing three cases with more than one diagnosis. In this group, diagnoses included 14 normal endometria, 12 endometrial polyps, four endocervical polyps, three hyperplasias, two endometrial cancers, one papillary syncytial metaplasia, one cystic change, one inflammatory debris, and one insufficient sample. Postmenopausal bleeding prompted 20 studies, 12 of which revealed endometrial thickness of 8 mm or more. We found no difference in endometrial thickness of patients who had bleeding versus those who had no bleeding. Endometrial thickness increased with the duration of tamoxifen treatment. Seventy-three women being treated with tamoxifen for less than 5 years had a median endometrial thickness of 5 mm, and 44% of biopsies yielded abnormal results. Eighteen women receiving tamoxifen 5 years or longer had a median endometrial thickness of 14 mm, and 58% of endometrial biopsies in this group were abnormal. The two endometrial cancers occurred in women who were treated with tamoxifen for 6 years. Correlation between duration of tamoxifen use and endometrial thickness was significant (p < .026). CONCLUSION: The majority of women being treated with tamoxifen were asymptomatic, but 48% of sonograms revealed an endometrial thickness of 8 mm or more. Endometrial polyps, the most common abnormality, were diagnosed in 33% of biopsies performed for endometrial thickness of 8 mm or more. Endometrial thickness showed no correlation with symptoms, but we found a statistically significant correlation between increased endometrial thickness and duration of tamoxifen treatment that was longer than 5 years.

When the common femoral vein is revealed as flattened on spectral Doppler sonography: is it a reliable sign for diagnosis of proximal venous obstruction?

OBJECTIVE: The purpose of the study was to determine if a monophasic waveform with no response to Valsalva's maneuver in the common femoral vein on spectral Doppler sonography is reliable for the diagnosis of proximal venous obstruction. SUBJECTS AND METHODS: In a prospective study from January 1993 through October 1995, 37 of 2138 cancer patients examined with duplex Doppler sonography exhibited monophasic flow in the common femoral vein on spectral Doppler imaging and no response to Valsalva's maneuver. These 37 patients were further evaluated with an abdominal and pelvic CT scan with IV contrast medium (n = 23), with sonography (n = 8), with MR imaging (n = 4), with venography (n = 1), or by both venography and CT (n = 1) to determine the cause of monophasic flow in the common femoral vein and lack of response to Valsalva's maneuver. All follow-up imaging studies were obtained from 0 to 30 days after initial duplex Doppler sonography. RESULTS: All patients with monophasic flow in the common femoral vein on spectral Doppler imaging and no response to Valsalva's maneuver had proximal venous extrinsic compression or deep venous thrombosis. Twenty-nine (78%) of 37 patients had extrinsic compression. Such compression was caused by pelvic masses in 15 (41%) of 37 patients, enlarged nodes in eight patients (22%), and postsurgical changes in six patients (16%). The remaining eight patients (22%) had proximal deep venous thrombosis. CONCLUSION: On spectral Doppler sonography, monophasic waveform with no response to Valsalva's maneuver in the common femoral vein is a dependable sign for the diagnosis of proximal extrinsic compression or deep venous thrombosis. If such a waveform is identified, further investigation is warranted.