Eugene Libson

Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.

PURPOSEnThe purpose of our studies was to define the maximal-tolerated dose of liposomal doxorubicin (DOX-SL; Liposome Technology Inc, Menlo Park, CA), a doxorubicin formulation of polyethyleneglycol-coated liposomes, characterize the toxicities associated with this formulation, and evaluate any indication of antitumor activity within a phase I setting.nnnPATIENTS AND METHODSnTwo separate phase I studies were conducted following the initial human pharmacokinetic testing at one of the sites (Hadassah). The starting dose of 20 mg/m2 at the University of Southern California was just below the dose without toxicity in the pharmacokinetic study. At Hadassah, the phase I starting dose was just above their earlier safe single doses, 60 mg/m2. Both studies involved cohorts of at least three patients and redosing every 3 to 4 weeks. To determine the recommended dose for phase II trials, an additional level of 50 mg/m2 every 3 weeks was explored, and the level of 60 mg/m2 every 4 weeks was expanded.nnnRESULTSnA total of 56 patients receiving 281 courses of DOX-SL was accrued and evaluated for toxicity. Hand-foot (H-F) syndrome and stomatitis are the two main dose-limiting factors of DOX-SL. Stomatitis was dose-limiting for high single doses of DOX-SL greater than 70 mg/m2. Skin toxicity manifested primarily as H-F syndrome was dose-limiting for repetitive dosing, but acceptable at either 50 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Attenuation of acute subjective symptoms and lack of alopecia were generally observed. Patients with carcinomas of the breast, ovary, prostate, and head and neck were among those showing objective antitumor responses or improvement based, in part, on blood levels of tumor markers.nnnCONCLUSIONnThe toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences, resembles that of prolonged continuous infusion. This finding, as well as the antitumor activity observed, supports wide phase II testing of DOX-SL in solid tumors.

Image-guided core-needle biopsy in malignant lymphoma: experience with 100 patients that suggests the technique is reliable.

PURPOSEnIn an initial evaluation of 1,500 computed tomography (CT)-guided core-needle biopsies performed at our institute during the period from 1989 to 1994, we encountered 100 patients with the diagnosis of lymphoma. Here, we review the clinical impact of 109 image-guided needle biopsies in these 100 patients with non-Hodgkins lymphoma (NHL) and Hodgkins disease (HD).nnnPATIENTS AND METHODSnNHL was diagnosed in 71 patients, and 29 had HD. Among the NHL patients, 17 (24%) had proven lymphoma diagnosed before the biopsy was performed; in 54 (76%) core-needle biopsy was performed as the first diagnostic procedure. Of 29 HD patients, nine (31%) were already established cases of HD, and in 20 (69%) core-needle biopsy was the first diagnostic procedure attempted. Most of the biopsies were performed under CT control using a 20- or 18-gauge Turner biopsy needle.nnnRESULTSnEighty-six patients received therapy based on the results of the needle biopsy alone. Fourteen patients received therapy after undergoing surgical biopsy for a suspected diagnosis of lymphoma, which could not be established with certainty on the basis of an earlier core-needle biopsy alone. In 78% of the patients, the needle biopsy saved a further surgical procedure that may have been difficult to perform because of the primary location of the tumor.nnnCONCLUSIONnFrom our experience in this study, image-guided core-needle biopsies provide sufficient information for the diagnosis of and subsequent therapeutic decision to treat most cases of lymphoma.

CLINICAL STUDIES OF LIPOSOME-ENCAPSULATED DOXORUBICIN

Initial clinical studies with doxorubicin entrapped in the bilayer of phosphatidylglycerol-rich liposomes were hindered by the avid reticuloendothelial system (RES) uptake and by drug leakage from circulating liposomes. In contrast, recent tests of a doxorubicin formulation of polyethyleneglycol-coated liposomes (Doxil) in cancer patients indicate that the drug pharmacokinetic properties are significantly altered, with a prolonged distribution half-life of approximately 2 days. Plasma fractionation studies show that nearly all the drug measured in plasma is in liposome-encapsulated form. The dose of Doxil has been escalated from 25 to 60 mg/m2. Stomatitis is the most significant toxicity, and skin toxicity, in the form of hand-foot syndrome, may complicate the repeated administration of Doxil. A number of objective antitumor responses in a variety of malignancies have been observed, indicating that Doxil is an active antitumor compound. Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin.

Metastatic tumours of bones of the hand and foot

Metastases in the bones of the hands and feet are rate. The literature relating to these tumours has been reviewed, and 43 new cases are reported. In the comulative total of cases, metastases to the hand outnumber those to the foot 2:1 (196 cases as against 94). Bronchial carcinoma is the most common neoplasm metastasising to the hand. Subdiaphragmatic neoplasms such as gastrointestinal, vesical, renal and uterine malignancies, metastasise more frequently to the foot. A possible explanation for this latter finding is the retrograde spead of tumour emboli from the vertebral venous plexus down incompetent leg veins.

Critical Analysis of the Performance of Double-Contrast Barium Enema for Detecting Colorectal Polyps ≥ 6 mm in the Era of CT Colonography

OBJECTIVEnThe purpose of our study was to perform a meta-analysis comparing the performance of double-contrast barium enema (DCBE) with CT colonography (CTC) for the detection of colorectal polyps > or = 6 mm using endoscopy as the gold standard.nnnMATERIALS AND METHODSnProspective DCBE and CTC studies were identified. Percentages of polyps and of patients with polyps > or = 10 mm and 6-9 mm were abstracted. The performance of DCBE versus CTC was determined by separately evaluating each techniques performance versus that of endoscopy, and contrasting the techniques. The I-squared statistic and Fishers exact test were used for heterogeneity, the Cochran-Mantel-Haenszel and the Kruskal-Wallis tests for correlation, and the A(z) test for comparing pooled weighted estimates of performance.nnnRESULTSnEleven studies of DCBE (5,995 patients, 1,548 polyps) and 30 studies of CTC (6,573 patients, 2,348 polyps) fulfilled inclusion criteria. For polyps > or = 10 mm, a 0.121-per-patient sensitivity difference favored CTC (p < 0.0001; DCBE, 0.702 [95% CI, 0.687-0.715]; CTC, 0.823 [0.809-0.836]). For polyps > or = 10 mm, a 0.031-per-polyp sensitivity difference favored CTC (p < 0.0001; DCBE, 0.715 [0.703-0.726]; CTC, 0.746 [0.735-0.757]). For polyps > or = 10 mm, a specificity difference of 0.104 favored CTC (p = 0.001; DCBE, 0.850 [0.847-0.855]; CTC, 0.954 [0.952-0.955]). DCBE was also significantly less sensitive for 6- to 9-mm polyps (p < 0.001).nnnCONCLUSIONnDCBE has statistically lower sensitivity and specificity than CTC for detecting colorectal polyps > or = 6 mm.

Incidence and Management of Complex Fibroadenomas

OBJECTIVEnComplex fibroadenomas are a fibroadenoma subtype harboring one or more complex features. We sought to evaluate the incidence of complex fibroadenoma on biopsy and to propose decision criteria for managing patients with these breast lesions.nnnMATERIALS AND METHODSnComplex fibroadenomas were diagnosed in 63 of 401 fibroadenomas (15.7%) found at consecutive percutaneous needle or excisional surgical biopsy. We evaluated the clinical and imaging presentations of complex fibroadenomas; compared pathology at core and excisional biopsy; and contrasted age, pathology, and size of complex and simple fibroadenomas using the Students t test.nnnRESULTSnPatients with complex lesions were 18.5 years older (median age, 47 years; range, 21-69 years) than patients with noncomplex fibroadenomas (median age, 28.5 years; range, 12-86 years) (p < 0.001). Complex fibroadenomas were half the size (average, 1.3 cm; range, 0.5-2.6 cm) of noncomplex fibroadenomas (average, 2.5 cm; range, 0.5-7.5 cm) (p < 0.001). Only one malignancy, an invasive lobular carcinoma, was found in 63 complex fibroadenomas (1.6%). This patient had atypical lobular hyperplasia at core needle biopsy.nnnCONCLUSIONnApproximately 16% of fibroadenomas are complex. Complex fibroadenomas are smaller and appear at an older age. At a mean follow-up of 2 years, we found a low incidence of malignancy in complex fibroadenomas. Women with complex fibroadenomas may therefore be managed with a conservative approach, similar to the approach now recommended for women with simple fibroadenomas.

Parasitic ovarian dermoid tumor of the omentum-A review of the literature and report of two new cases

Two cases of a parasitic omental teratoma which originated from an ovarian dermoid that underwent torsion, autoamputation and omental reimplantation are presented. A review of the literature revealed 23 additional cases of omental teratoma which occurred mostly in females. In some cases, the mature teratoma of the omentum showed histological evidence of ovarian stroma, and was associated with a dermoid tumor of the remaining contralateral ovary. It is generally believed that autoamputation and reimplantation of an ovarian dermoid cyst is the most common etiology of omental teratomas. Abdominal pain is the main presenting symptom of these tumors, and on physical examination a mobile abdominal or pelvic mass is often found. Both ultrasonography with colour flow Doppler and CT-scan are helpful in the diagnosis of dermoid tumors, but the correct diagnosis of omental localisation is extremely difficult. Mature omental teratomas may be treated by simple resection. The immature teratomas of the greater omentum, however, are potentially malignant tumors requiring postoperative chemotherapy and radiotherapy.

CT-guided core-needle biopsy in the diagnosis of mediastinal lymphoma.

Abstract. The advent of radiologic guidance techniques for percutaneous biopsy has changed the approach to the routine diagnosis of mediastinal lymphoma. The aim of the present study was to evaluate the diagnostic accuracy of CT-guided percutaneous core-needle biopsy (PCNB) in the clinical management of patients with mediastinal lymphoma. The results of 49 CT-guided PCNB of mediastinal lymphoma performed under local anesthesia in 42 ambulatory patients were analyzed. A positive diagnosis of lymphoma was obtained in 30 of 42 patients, with an overall success rate of 71.5 %. The technique was equally successful in the diagnosis of Hodgkins and non-Hodgkins lymphoma. There were no major complications. Percutaneous CT-guided CNB of mediastinal lymphoma is a quick, safe, accurate, and efficient alternative to open biopsy in the evaluation of mediastinal lymphoma, mainly at presentation. It should become the preferred initial diagnostic procedure for obtaining histologic samples in patients with suspected mediastinal lymphoma.

Sonographic features of horseshoe kidney: review of 34 patients.

Horseshoe kidney is a difficult sonographic diagnosis, especially if the isthmus is not seen. The purposes of this report are to review the sonographic images in 34 patients with proven horseshoe kidney, to discuss the limitations of ultrasonography in demonstrating the anomaly, and to identify features that would alert the examiner to the possibility of a horseshoe kidney. Among 34 patients, the isthmus was noted in 27. Of the 67 kidneys studied, 52 (78%) were judged to be low‐lying, and in 24 (36%) the sonographic images suggested malrotation with anteriorly pointing pelvis. Additional sonographic features seen in the 67 kidneys included a bent or curved configuration of the kidney in the long axis (58%), tapering and elongation of the lower pole (60%), and a poorly defined inferior border of the kidney (84%). These features should suggest the presence of a horseshoe kidney and direct the examiner to search for the isthmus.

The periosteal sunburst reaction to bone metastases

The periosteal sunburst reaction is an unusual response to metastatic bone tumours. Fifty such cases are reported in the literature, and 20 additional cases are reported in this study. The most common primary tumour showing this response is prostatic carcinoma, and the majority of cases are associated with osteoblastic metastases. Twenty percent of sunburst metastases occur in bones distal to the elbow and knee, a much higher prevalence than is found overall in bone metastases.