An update of lanreotide acetate for treatment of adults with carcinoid syndrome.

Carcinoid tumors are rare and usually slow-growing. Some patients with advanced metastatic disease however can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing. Many treatments including chemotherapy were tried unsuccessfully in the past to treat this syndrome. The symptoms of carcinoid syndrome are thought to be related to the ability of the tumors to produce serotonin. The discovery that the production of this hormone can be inhibited by somatostatin led to the development of somatostatin analogues octreotide and lanreotide, which differ from native somatostatin in that they have a longer half-life. These compounds have shown dramatic responses in symptom control and reduction of serotonin metabolites including urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of carcinoid tumors, the development of lanreotide as a treatment and future directions for the treatment of carcinoid syndrome.

Nonenhanced limited CT in children suspected of having appendicitis: prospective comparison of attending and resident interpretations.

PURPOSE: To prospectively compare resident and attending radiologic interpretations of nonenhanced limited computed tomographic (CT) scans obtained in children suspected of having appendicitis. MATERIALS AND METHODS: Seventy-five consecutive children underwent nonenhanced limited CT for suspected appendicitis. The scans were prospectively interpreted by a resident and an attending radiologist, each unaware of the other's interpretation. The probability that the findings indicated a diagnosis of appendicitis, level of certainty in the interpretation, and presence of an alternate diagnosis were statistically analyzed. RESULTS: Nineteen children (25%) had appendicitis. The area under the receiver operating characteristic curve was not significantly different between residents (0.97 +/- 0.02) and attendings (0.95 +/- 0.04). The percentage agreement between residents and attendings was 91% (kappa = 0.73 +/- 0.095). The average level of certainty tended to be higher for attendings (93% +/- 15) than residents (89% +/- 12). The sensitivity, specificity, and accuracy of resident interpretations were 63%, 96%, and 88%, respectively, compared with those of attending interpretations--95%, 98%, and 97%, respectively. Residents and attendings noted alternate diagnoses in 30% of children without appendicitis. CONCLUSION: A high level of agreement exists between resident and attending radiologists in the interpretation of nonenhanced limited CT scans in children suspected of having appendicitis. Residents, however, tend to be less confident in their interpretations.

Appendicitis and alternate diagnoses in children: findings on unenhanced limited helical CT.

The objective of this manuscript is to review and illustrate the findings of appendicitis, and of alternate diagnoses that may clinically or radiographically simulate appendicitis, on unenhanced limited CT in children. Potential pitfalls in unenhanced limited CT interpretation of pediatric patients will also be discussed.

In vivo visualization of pyloric mucosal hypertrophy in infants with hypertrophic pyloric stenosis: is there an etiologic role?

OBJECTIVE: Infantile hypertrophic pyloric stenosis (IHPS) is a common condition which presents in infants at 2-12 weeks of postnatal life, and whose cause remains obscure. Multiple associated abnormalities have been recognized within the external hypertrophied pyloric muscle layer, but the internal component of the pyloric mucosa has received scant attention in the literature to date. Our purpose in this study was to show that pyloric mucosal redundancy is a constant finding in infants with IHPS, to discuss its possible cause, and to explore the hypothesis of a relationship between pyloric mucosal redundancy and the development of IHPS. MATERIALS AND METHODS: We identified 102 consecutive infants with surgically confirmed IHPS and determined the thickness of the pyloric mucosa compared with the thickness of the surrounding hypertrophied muscle. Fifty-one infants who did not have pyloric stenosis served as controls. RESULTS: Mean mucosal thickness in patients with IHPS approximated mean muscle thickness, with a ratio of 0.89. In infants with IHPS, the pyloric mucosa constitutes approximately one third of the cross-sectional diameter of the pyloric mass and fills and obstructs the pyloric canal. CONCLUSION: Mucosal redundancy is a constant associated finding in IHPS. Although the origin of the redundancy and a cause-and-effect relationship are difficult to establish, our findings support the hypothesis that hypergastrinemia may be implicated in the pathogenesis of IHPS, and suggest that mucosal thickening could be implicated as one of the initiating factors in its development.

Unenhanced limited CT of the abdomen in the diagnosis of appendicitis in children: comparison with sonography.

OBJECTIVE: The purpose of this investigation is to determine the sensitivity, specificity, and accuracy of unenhanced limited CT of the abdomen in children with suspected appendicitis and compare these results with graded compression sonography. MATERIALS AND METHODS: Seventy-six children underwent unenhanced limited CT over a 11-month period for evaluation of suspected appendicitis. A historical cohort of 86 consecutive children who had undergone graded compression sonography was identified. Results were correlated with surgical, pathologic, chart, and clinical follow-up data. The sensitivity, specificity, accuracy, rate of alternate diagnosis, time to perform examinations, and charge at our institution were determined for unenhanced limited CT and sonography. RESULTS: Sensitivity, specificity, and accuracy for unenhanced limited CT were 97%, 100%, 99%, respectively, and were 100%, 88%, 91%, respectively, for sonography. Alternate diagnoses were suggested in 35% and 28% children without appendicitis who had unenhanced limited CT and sonography, respectively. Unenhanced limited CT required 5 min and sonography required 20-30 min to perform. The charge at our institution was $408 for unenhanced limited CT and $295 for sonography. CONCLUSIONS: CT can be performed rapidly in children without IV, oral, or rectal contrast medium. Unenhanced limited CT and sonography are highly sensitive, specific, and accurate in the evaluation of children with suspected appendicitis.

Pediatric renal masses: Wilms tumor and beyond.

A variety of pediatric renal masses may be differentiated from Wilms tumor on the basis of their clinical and imaging features. Wilms tumor is distinguished by vascular invasion and displacement of structures and is bilateral in approximately 10% of cases. Nephroblastomatosis occurs most often in neonates and is characterized by multiple bilateral subcapsular masses, often associated with Wilms tumors. Renal cell carcinoma is unusual in children except in association with von Hippel-Lindau syndrome and typically occurs in the 2nd decade. Mesoblastic nephroma is the primary consideration in a neonate with a solid renal mass. Multilocular cystic renal tumor is suggested by a large mass with multiple cysts and little solid tissue. Clear cell sarcoma is distinguished by frequent skeletal metastases, and rhabdoid tumor is distinguished by its association with brain neoplasms. Angiomyolipoma frequently contains fat and is associated with tuberous sclerosis. Renal medullary carcinoma occurs in patients with sickle cell trait or hemoglobin SC disease and manifests as an infiltrative mass with metastases. Ossifying renal tumor of infancy is differentiated from mesoblastic nephroma by the presence of ossified elements. Metanephric adenoma lacks specific features but is always well defined. Renal lymphoma is characterized by multiple homogeneous masses, often with associated adenopathy.

Appendicolith revealed on CT in children with suspected appendicitis: how specific is it in the diagnosis of appendicitis?

OBJECTIVE: The purpose of this study was to determine the sensitivity, specificity, and positive and negative predictive values of a diagnosis of appendicitis when CT without enteric contrast material reveals an appendicolith in children with suspected appendicitis. MATERIALS AND METHODS: A retrospective review of children who underwent abdominal CT for suspected appendicitis over a 25-month period was performed to identify patients with an appendicolith. An age-matched group of patients examined for trauma served as controls. RESULTS: CT was performed in 104 children. Appendicitis was present in 60 (58%) of 104 children; 39 (65%) of 60 had an appendicolith. Appendicitis was not present in 44 (42%) of 104; six (14%) of 44 had an appendicolith. An appendicolith detected on CT had a sensitivity of 65% and a specificity of 86% for the radiologist diagnosing appendicitis. An appendicolith had a positive predictive value of 74% and a negative predictive value of 26%. Among the control population, two (3%) of 74 children had an appendicolith. This number was statistically significant compared with children in the study group with an appendicolith and abdominal pain, but without appendicitis (p = 0.02). CONCLUSION: Although an appendicolith is significantly associated with appendicitis, the detection of an isolated appendicolith on CT is not sufficiently specific to be the sole basis for the diagnosis of acute appendicitis.

Scurvy presenting as painful gait with bruising in a young boy.

A case of scurvy occurred in an apparently well-nourished 5-year-old boy with normal growth parameters. Only after the diagnosis of scurvy was raised on clinical grounds did we discover the peculiar dietary habits that were responsible for his deficiency of ascorbic acid. His case is a reminder to the clinician that nutritionally based disease may occur in any socioeconomic setting and that nutritional screening remains an important part of every child's general health care.

A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.

Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.

Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.

OBJECTIVE: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy. METHODS: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy. RESULTS: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07). CONCLUSION: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Pelvic examination, tumor marker level, and gray-scale and Doppler sonography in the prediction of pelvic cancer.

OBJECTIVE: To determine the ability of pelvic examination, tumor marker assessment, and transvaginal ultrasonography, with selected use of Doppler ultrasonography, to predict pelvic malignancy. METHODS: Two hundred twenty-six women scheduled for operative removal of a pelvic mass were entered in the study prospectively. Each woman underwent pelvic examination, tumor marker assessment, and transvaginal ultrasonography preoperatively. Women whose gray-scale findings were suspicious for malignancy underwent Doppler ultrasonography. Suspicious findings included masses that were fixed or irregular on pelvic examination; CA 125 level greater than 35 U/mL; elevations in serum lactic dehydrogenase, alpha-fetoprotein, or hCG; and the presence of a substantial solid component on gray-scale ultrasonography. Suspicious Doppler findings included intratumoral color flow, pulsatility index less than 1.0, or resistance index 0.4 or lower. The findings were correlated with the presence of malignancy. RESULTS: If all three indicators (examination, tumor marker assessment, and gray-scale ultrasound findings) were nonsuspicious, 99% of premenopausal women and 100% of postmenopausal women had benign masses. If all three indicators were suspicious, 77% of premenopausal women and 83% of postmenopausal women had malignant tumors. Logistic regression identified ultrasound impression and tumor size to be significant predictors of malignancy in premenopausal women, whereas CA 125 level and ultrasound impression were significant in postmenopausal women. In patients with suspicious gray-scale findings, recategorization based on Doppler findings resulted in inferior diagnostic indices. CONCLUSIONS: Ultrasonographic tumor size and appearance are the best predictors of pelvic malignancy in premenopausal women, whereas CA 125 level and ultrasonographic appearance are the best predictors in postmenopausal women. Neither color nor spectral Doppler is useful in this setting.

Radiologic studies in acute fatty liver of pregnancy. A review of the literature and 19 new cases.

OBJECTIVE: Radiologic findings thought to be characteristic of acute fatty liver of pregnancy have been described in a limited number of cases. We describe wide experience with liver imaging of this disease. STUDY DESIGN: A retrospective review was performed on charts from 1982 to 1994 to identify those patients with acute fatty liver of pregnancy who had radiologic studies. RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were identified, for an incidence of 1/6,692 births. Nineteen patients underwent at least one imaging study, and seven had more than one. Findings consistent with fatty infiltration of the liver are found in 3/11 patients with ultrasound, 5/10 with computed tomography (CT) and 0/5 with magnetic resonance imaging (MRI). Three patients with normal ultrasound scans subsequently had evidence of fatty filtration on CT scan. CONCLUSION: Detection of fat in the liver of patients with acute fatty liver of pregnancy with current imaging techniques is limited and did not contribute to the management of patients in this series. Further studies are necessary to define to role of MRI--in particular, spectroscopy.

Hemoperitoneum in a newborn secondary to antenatal hemorrhage into a retroperitoneal lymphangioma.

Hemoperitoneum in the newborn is an uncommon event, occurring most often in the setting of traumatic delivery. Hemoperitoneum resulting from antenatal hemorrhage into an abdominal mass is rare. We present a case of neonatal hemoperitoneum secondary to antenatal hemorrhage into a retroperitoneal lymphangioma. The differential diagnosis of neonatal hemoperitoneum is discussed.

Traumatic epididymitis: evaluation with color Doppler sonography.

OBJECTIVE: We performed this study to determine whether scrotal trauma can cause hyperemia of the epididymis. This diagnosis is helpful because traumatic epididymitis can be treated conservatively. MATERIALS AND METHODS: We retrospectively reviewed color Doppler and gray-scale sonograms of five patients who had suffered trauma to the scrotum that resulted in epididymal hyperemia, which we called traumatic epididymitis. We also reviewed the presentation and management of each patient. RESULTS: Color Doppler sonography revealed focal (one patient) and diffuse (four patients) hyperemia. Gray-scale images revealed epididymal enlargement in all patients. These findings were indistinguishable from those of infectious epididymitis by sonography. One patient also had hyperemia of the testis. Four of the five patients were managed conservatively; the other underwent surgical exploration for a coexisting testicular rupture. CONCLUSION: Careful evaluation of the epididymis with both gray-scale and color Doppler sonography should be part of every sonographic survey of the scrotum for blunt trauma. Traumatic epididymitis, which may be noted on color Doppler images, should not be confused with infectious epididymitis. Surgery is not necessary unless another injury requires it.

Color Doppler sonography of adnexal torsion.

The purpose of this study was to describe the color Doppler sonographic findings in adnexal torsion that distinguish viable from nonviable ovaries. We present the color Doppler sonographic features in 13 patients with surgically proved adnexal torsion that help determine whether or not the ovaries were viable or nonviable at the time of surgery. Eleven combined ovarian and tubal torsions and two isolated tubal torsions were studied. In 10 cases the ovaries were considered nonviable at the time of surgery and in three cases they were considered viable. Of the nonviable group, six showed absent arterial and venous flow centrally, but two had low velocity (< 5 cm/s) arterial flow peripherally in the region of the adnexal branch of the uterine artery or in the main ovarian artery, and two demonstrated absent or reversed diastolic arterial flow. None of the nonviable ovaries showed venous flow centrally. In contrast, all of the viable ovaries demonstrated venous flow centrally, and two had peripheral and central arterial flow. Although the CDS findings in adnexal torsion are variable, ovarian viability may be predicted if central venous flow is present.

Differentiation of benign and malignant adnexal masses: relative value of gray-scale, color Doppler, and spectral Doppler sonography.

OBJECTIVE: The purpose of this study was to evaluate prospectively the relative usefulness of color Doppler, spectral Doppler, and gray-scale sonography in differentiating benign from malignant adnexal masses. SUBJECTS AND METHODS: A total of 170 adnexal masses in 161 patients were classified prospectively as suggestive of or not suggestive of malignant tumor on the basis of gray-scale morphology, internal flow versus peripheral or no flow, and spectral Doppler pulsatility, as measured by a pulsatility index (PI) threshold of 1.0 and a resistive index (RI) threshold of 0.4. RESULTS: Surgical pathology revealed 123 benign masses and 46 malignant masses. One malignant mass was confirmed by cytologic evaluation of ascitic fluid. On gray-scale analysis, 46 of the 47 malignant masses were classified as suggestive of tumor, and 76 of the 123 benign masses were classified as not suggestive of tumor (sensitivity, 98%; specificity, 62%; negative predictive value [NPV], 99%; and positive predictive value [PPV], 50%). The use of internal color flow as a predictor of malignant tumor yielded a sensitivity of 77%, a specificity of 69%, an NPV of 89%, and a PPV of 49%. The PI and RI values were significantly lower (p < .0001) in malignant masses than in benign masses, although the values overlapped considerably. For a PI of less than 1.0, sensitivity was 67%, specificity was 66%, NPV was 83%, and PPV was 46%. For an RI of less than 0.4, sensitivity was 24%, specificity was 90%, NPV was 73%, and PPV was 50%. CONCLUSION: In our series, a gray-scale prediction of benignity was reliable (NPV = 99%), and a prediction of malignancy was unreliable (PPV = 50%). Internal color flow was not useful as a predictor of malignancy (PPV = 49%). Although the absence of internal or peripheral color flow suggested benignity (NPV = 94%), only 17 (16 benign) of the masses (about 10%) had no flow. Spectral Doppler analysis with RI and PI was not useful, as no reliable discriminatory value with both high sensitivity and high specificity could be found for either parameter because of the overlap in values obtained for benign and malignant masses.

Hypertrophic pyloric stenosis in the infant without a palpable olive: accuracy of sonographic diagnosis.

PURPOSE: To evaluate the accuracy of sonography for both diagnosis and exclusion of pyloric stenosis in the infant with nonbilious vomiting without a palpable olive and to clarify the relationship between infant age and size and the dimensions of the hypertrophic pylorus. MATERIALS AND METHODS: The sonograms of 152 infants with suspected pyloric stenosis were evaluated. The prospective diagnoses were categorized as pyloric stenosis, normal pylorus, and pylorospasm with potential to progress to pyloric stenosis. Positive findings were confirmed at surgery; negative findings were confirmed by means of chart review. RESULTS: Sensitivity, specificity, and accuracy of sonography in determination of appropriate surgical referral were 100%. A significant (P < .05) correlation was found between the size of the hypertrophied muscle and the age of the patient at initial examination. CONCLUSION: Sonography is highly sensitive and, in this patient population, highly specific, and by virtue of direct visualization of the pyloric muscle, it is the method of choice for both diagnosis and exclusion of pyloric stenosis.