A phase I study evaluating the effect of CDHP as a component of S-1 on the pharmacokinetics of 5-fluorouracil.

UNLABELLED: The purpose of this study was to investigate the effect of gimeracil (CDHP), a reversible dihydropyrimidine dehydrogenase (DPD) inhibitor, on the pharmacokinetics of 5-fluorouracil (5-FU) and other related metabolites by comparing the pharmacokinetic (PK) profile of S-1 (tegafur [FT] + CDHP + oteracil potassium [Oxo]) to that of FT alone. PATIENTS AND METHODS: Patients with advanced solid tumors received single oral doses of S-1 (50 mg) and FT (800 mg) on days 1 and 8 in a randomized crossover fashion. Plasma samples were collected on days 1, 2, 3, 8, 9 and 10. Single-dose PK parameters were determined for FT, 5-FU and α-fluoro-ß-alanine (FBAL). Following the single-dose crossover period, patients entered an extension phase and received treatment with S-1 b.i.d. for 14 days followed by a 7-day rest, repeated every 3 weeks. RESULTS: A total of 12 patients were enrolled; median age was 59 years and mean body surface area was 1.94 m(2). Following S-1 administration, 5-FU exposure was significantly greater (approximately 3-fold) compared to FT alone (p ≤ 0.0007 for AUC0-inf, AUC0-last, and C(max) of 5-FU) despite the 16-fold higher dose of FT administered alone compared to S-1, while plasma concentrations of FT and FBAL were significantly lower with S-1 (p < 0.0001 for all comparisons). Following both single- and multiple-dose administration of S-1, the average maximum DPD inhibition was observed at 4 h post-dose. The extent of inhibition was similar following single and multiple dosing. Following single- and multiple-dose administration of S-1, plasma concentrations of uracil returned to baseline levels within approximately 48 h of dosing, indicating reversibility of DPD inhibition by CDHP. CONCLUSION: Despite the differences in the FT dose administered, exposure to 5-FU was significantly greater following S-1 administration compared to FT administration. Conversely, exposure to FT and FBAL were significantly less following S-1 administration compared to FT administration. Thus, the DPD inhibitory action of CDHP contributes to a decrease in 5-FU catabolism and to significantly higher blood levels of 5-FU compared to FT alone.

Imaging of the thymus.

Technologic advances in imaging, particularly CT and MR imaging, have revolutionized the ability to noninvasively image the thymus. Increasing knowledge of the normal and pathologic states of the thymus has been accompanied by an increasing ability to depict morphologic alterations in this gland with fine spatial resolution and can even provide functional information. This article discusses the role of various imaging modalities in identifying suspected thymic disease, which historically required surgery to visualize. The role of imaging is best understood with an appreciation of the embryology, anatomy, and pathology of the thymus.

Pulmonary artery and aortic sarcomas: cross-sectional imaging.

Sarcomas of the major arteries are rare tumors often misdiagnosed due to nonspecific symptomatology. The authors present three cases of pulmonary artery and aortic sarcomas that were initially believed to be more common diseases. Modern imaging techniques including helical computed tomography (CT) and magnetic resonance imaging (MRI) are increasing the frequency of premortem diagnosis of these entities and aided surgical planning.

Pneumothorax and pneumomediastinum after laparoscopic surgery.

Pneumothorax, pneumomediastinum, pneumopericardium, and subcutaneous emphysema have been described as complications of laparoscopy. This study evaluates the incidence and significance of these extra alveolar collections of air. We found that pneumomediastinum with or without pneumothorax was not associated with significant morbidity and is more likely after laparoscopic fundoplication than other laparoscopic surgeries. The presence of pneumomediastinum after fundoplication is a normal finding. However, pneumothorax has clinical significance and should be considered pathological.

Detection of hepatocellular carcinoma in cirrhotic patients: sensitivity of CT and ultrasonography.

Patients with cirrhosis are at increased risk for the development of hepatocellular carcinoma. The heterogeneous hepatic parenchyma produced by cirrhosis makes detection of hepatomas more difficult. The purpose of this study was to determine the sensitivities of CT and ultrasonography for detecting hepatomas in cirrhotic patients. A retrospective analysis was performed of 733 patients who underwent liver transplantation at our institution. A study population of 21 patients was selected who met our inclusion criteria. The inclusion criteria required a pathologic diagnosis of hepatocellular carcinoma, pathologic evidence of cirrhosis, and contrast-enhanced CT and sonographic examinations performed within 1 week of each other. The sensitivities of CT and ultrasonography were determined by comparing the imaging findings with pathology findings from serially sectioned total hepatectomy specimens. A total of 40 hepatomas were detected pathologically in the 21 patients in our study population. CT identified 12 of 21 patients with hepatomas and detected 18 of 40 individual lesions (patient detection sensitivity = 57%, lesion detection sensitivity = 45%). Ultrasonography identified 14 of 21 patients with hepatomas and detected 21 of 40 individual lesions (patient detection sensitivity = 67%, lesion detection sensitivity = 51%). Combining the findings of CT and ultrasonography allowed identification of 17 of 21 patients with hepatomas and detection of 24 of 40 individual lesions (patient detection sensitivity = 80%, lesion detection sensitivity = 60%). We conclude that CT and ultrasonography have a low sensitivity for the detection of hepatocellular carcinoma in patients with cirrhosis.

Systemic venous enhancement patterns during dynamic abdominal CT.

In 25 patients we assessed the enhancement of abdominal venous structures during dynamic computed tomography (CT). The degree of venous enhancement demonstrated great variation. In six instances (out of 250 observations) a vessel was visually perceived as not enhancing and potentially thrombosed, including three gonadal veins. CT measurements were helpful in identifying enhancement, but were occasionally low enough that thrombosis remained a radiological consideration. The great variation in venous enhancement makes the diagnosis of thrombosis suspect, based on CT alone. Corroboration of this finding is suggested, when clinically relevant.

Excessive thoracic computed tomographic scanning in sarcoidosis.

BACKGROUND: The clinical value of computed tomographic (CT) scanning of the chest in the initial assessment of sarcoidosis was investigated. METHODS: One hundred consecutive patients referred to the sarcoidosis outpatient services of the Mount Sinai Medical Center, New York from 1990 to 1992 with a presumptive diagnosis of sarcoidosis were studied. The diagnosis was subsequently confirmed in all by a positive tissue biopsy sample or the Kveim-Siltzbach test. Clinical and laboratory data of each patient were reviewed. Chest radiographs were classified according to the classical stages of sarcoidosis. Thirty five of the 100 patients had a CT scan of the chest performed before presentation. The CT scans were compared with the presenting clinical data and standard chest radiographs in order to determine if they yielded useful additional information regarding diagnosis or treatment. RESULTS: The chest CT scan revealed no additional clinically relevant information compared with conventional chest radiographs in any of the 35 studies performed. In two patients mediastinal adenopathy was detected by CT scan which was not seen on standard radiographs. Two patients thought to exhibit hilar adenopathy and pulmonary infiltrations by standard radiography had no parenchymal disease on the CT scan. Bilateral parenchymal infiltrates were seen in one patient which were interpreted as unilateral infiltrates by standard radiographs. The variance between conventional radiographs and CT scans in these five patients was not clinically valuable. CONCLUSIONS: CT scans of the chest do not add clinically useful information to the standard chest radiographs in the initial assessment of sarcoidosis in patients presenting with the typical standard radiological patterns. CT scanning of the thorax is indicated in patients with proven or suspected sarcoidosis when the standard chest radiographs are normal or not typical of sarcoidosis, when signs or symptoms of upper airway obstruction are present, when the patient has haemoptysis, if there is a suspicion of a complicating second intrathoracic disease, or the patient is a candidate for lung transplantation.

Significance of distal false lumen after type A dissection repair.

Fifty-eight patients underwent repair of acute type A dissection between 1986 and 1992. Follow-up aortogram, computed tomographic scan with contrast, magnetic resonance imaging scan, or a combination of these tests was available in 38 patients with preoperatively patent distal false lumens. All distal anastomoses were constructed with the open technique during a period of circulatory arrest. There were 25 suture and 13 intraluminal graft anastomoses. Patency of the distal false lumen was found in 47.3%. Use of the intraluminal graft for the distal anastomosis decreased patency, although not significantly (4/13, 30% versus 14/25, 56%; p = 0.14). The direction of flow into the false lumen was antegrade in 11 of 24 (45.8%) of sutured anastomoses and 0 of 9 intraluminal graft anastomoses (p < 0.01). Actuarial survival at 5 years for patients with closed distal false lumen was 95% +/- 4.8% versus 76% +/- 15% for patients with patency of the distal false lumen (p = not significant). Event-free survival at 5 years for both groups was 84% +/- 8.3% (closed false lumen) and 63% +/- 13.5% (patency of distal false lumen; p = not significant). This experience indicates that in the treatment of acute type A dissections, operative strategy and anastomotic technique play a role in reducing the incidence of patency and related complications of the distal false lumen.

Seminoma of the testis presenting as an ulcerating mass of the duodenum.

Germ cell tumors (GCT) arising in the testes secondarily involve bowel in 5% of patients (1), and such involvement is usually via extension from adjacent metastatic lymphadenopathy. While this involvement often causes obstruction and gastrointestinal bleeding, radiologic identification of bowel ulceration has not been reported. We report an unusual case of small bowel invasion and ulceration, identified on CT examination, due to adenopathy resulting from testicular carcinoma.

Enzyme augmentation in moderate to life-threatening Gaucher disease.

Gaucher disease type 1 (GD type 1) is the most prevalent lysosomal storage disease and has its highest frequency in the Ashkenazi Jewish population. Deficiency of the enzyme, acid beta-glucosidase, results in the deposition of glucocerebroside primarily in macrophages. The accumulation of such "Gaucher cells" leads to visceromegaly, hepatic and bone marrow dysfunction, hypersplenism, and bony disease. Eleven GD type 1 patients, ages 4-52 y, with moderate to life-threatening manifestations, received 6-12 mo of enzyme augmentation with a macrophage-targeted acid beta-glucosidase preparation. Within 6 mo, substantial increases in Hb levels (mean = +30%) and platelet counts (mean = +39%) were observed. Hepatic and splenic volumes decreased by approximately 20% (range = 3-35%) and approximately 35% (20-52%), respectively. Hematologic and hepatic volume improvements were similar in the splenectomized (n = 4) and nonsplenectomized (n = 7) patient groups. In this patient population, no major differences were observed in the hematologic and visceral improvements with enzyme doses of 30, 50, or 60 IU/kg administered every 2 wk. Normal levels of acid beta-glucosidase activity were present in hepatic autopsy samples from one patient 11 d after enzyme infusion. In comparison, exogenous activity was absent from brain and lung specimens of the same patient. High levels (approximately 10-fold normal) were present in bone marrow samples from two patients obtained at 1 and 11 d after infusions. These studies demonstrate biochemical and clinical improvements by targeted enzyme augmentation in GD type 1, even in far advanced, life-threatening involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

CT manifestations of infectious mononucleosis.

A case of infectious mononucleosis (IM) which, on computed tomography (CT) scan, mimicked the morphologic features of lymphoma is reported. The CT findings in this case include generalized lymphadenopathy, splenomegaly, and focal low-attenuation splenic lesions in a fifty-three year old woman; these findings have not previously been described in patients with IM. This is most likely because IM is usually a clinical diagnosis confirmed by serologic testing. Imaging modalities such as CT scan have not routinely been utilized to support this diagnosis.

Carcinoid tumor of the lung presenting as a pleural mass: CT diagnosis.

Carcinoid tumors of the lung typically arise centrally within the tracheobronchial tree. We report a rare case of a carcinoid tumor presenting as a pleural mass. The classification and X-ray features are described.

Magnetic resonance findings in sarcoidosis of the thorax.

Fifteen patients with sarcoidosis underwent thoracic MRI examinations. The T2 signal intensity of lymphadenopathy varied, with no characteristic pattern noted. Three of four patients with bright lymph nodes on T2 images had stage I sarcoidosis, but low intensity nodes were also seen in stage I patients. Coronal images were complementary to axial images and better depicted subcarinal adenopathy. MRI does not distinguish the lymphadenopathy of sarcoidosis from other entities, but is useful for defining the anatomic extent of disease and differentiating pulmonary artery enlargement from adenopathy.

Shoulder subluxation as a complication of positioning during CT.

Previously unreported, we note the complication of anterior shoulder subluxation that occurred secondary to patient positioning during chest CT examination. Positioning a patient's arms abducted and externally rotated over the head can precipitate anterior shoulder subluxation in patients with anterior shoulder instability.

Localized fibrous pleural mesothelioma: CT findings.

The CT findings in 16 patients (20 examinations) with proven localized fibrous mesothelioma are described. These lesions proved to be large, uninvasive, sometimes heterogeneous, and enhancing solitary masses. These morphologic findings in an asymptomatic patient should be suggestive of this lesion.

Comparison of MRI and CT for study of renal and perirenal masses.

Accurate preoperative assessment of renal and perirenal tumors is crucial in determining the type of therapy and/or in planning the operative approach. Computed tomography has been used extensively to stage renal cancer by defining the extent of disease within and outside the kidney, demonstrating patency of the renal vein and inferior vena cava, and depicting sites of lymph node involvement. Recent studies have shown magnetic resonance imaging to be comparable or superior to computed tomography in staging renal carcinoma. Because of its multiplanar imaging capabilities, MRI has also proven useful in evaluating perirenal masses that may obstruct, displace, or invade the kidney. The advantages and limitations of MRI and CT are discussed and their current roles in the evaluation of renal and perirenal abnormalities are reviewed.

Residual dissection of the thoracic aorta after repair: MRI-angiographic correlation.

Thirteen patients' status post repair of thoracic aortic dissection were studied with both magnetic resonance and angiography. MRI was an accurate modality in identifying residual dissection when aortography was used as the gold standard. MRI can be used as a noninvasive modality for the follow-up of these patients.