Alec Goldenberg

MEIS1 and HOXA7 genes in human acute myeloid leukemia

Co-activation of Meisl with Hoxa7 or Hoxa9 homeobox genes by retroviral gene insertion has recently been reported to be leukemogenic in murine myeloid leukemia. In this study we determined their expression in human leukemia. Most human myeloid leukemia cell lines co-expressed MEIS1 with HOXA7 and HOXA9. Among patients with acute leukemia, 50% of AML patients expressed MEIS1, while the majority of ALL patients were negative. A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7. In unadjusted models, poorer response to chemotherapy was associated with expression of HOXA7 regardless of MEIS1 status and older patients were more likely to express either gene.

MR-guided needle aspiration biopsies of hepatic masses using a closed bore magnet.

PURPOSE Our purpose was to assess the efficacy of MR-guided biopsies with a conventional superconducting MR scanner and describe the techniques used to achieve successful results. METHOD Fourteen biopsies were completed under MR guidance in 11 patients. Seven patients with previously detected lesions were referred for biopsy under MR guidance when hepatic lesions were identified by MRI but not with prebiopsy noncontrast CT or ultrasound (US). Additionally referred for MR-guided biopsy were four patients in whom previous CT- or US-guided biopsies of focal lesions were nondiagnostic. A 22 gauge MR-compatible needle was used in each case. Lesions ranged in size from 8 to 32 mm. Eleven lesions (eight patients) were suspected of being hepatomas, and three lesions (three patients) were suspected of being metastases. RESULTS Thirteen of 14 MR-guided biopsies (93%) were diagnostic. Hepatocellular carcinoma was confirmed in 6 of 11 lesions suspected of representing hepatoma. One lesion, in a patient treated with chemoembolization, demonstrated necrotic material. One lesion yielded nondiagnostic material despite repeated visualization of the needle tip in the target lesion. Three lesions demonstrated metastatic carcinoma. Benign hepatocytes were detected in three biopsy specimens. Seven of the lesions that were successfully biopsied measured < 2.5 cm in diameter. CONCLUSION With use of a closed bore 1.5 T system, diagnostic MR-guided needle aspiration biopsies of hepatic masses and subcomponents, including small lesions (< 2.5 cm), can be successfully obtained.

B-cell lymphoma presenting as infiltrative renal disease.

Acute renal failure is rarely the presenting manifestation of non-Hodgkins lymphoma. Of the reported cases of renal insufficiency secondary to diffuse renal infiltration with lymphoma, few have presented with acute renal failure. We present a patient with acute renal failure secondary to diffuse bilateral renal infiltration by a B-cell non-Hodgkins lymphoma. The findings of an elevated serum lactate dehydrogenase (LDH), lymphopenia, and homogenous bilateral renal enlargement on computed tomographic (CT) imaging were important in suggesting the diagnosis of primary renal lymphoma. Renal biopsy with immunohistochemical and ultrastructural analysis was instrumental in confirming this diagnosis.

Plasmacytoma of the breast: A report of two cases diagnosed by aspiration biopsy

BACKGROUND Extramedullary plasmacytoma of the breast is an uncommon neoplasm, occurring either as a solitary tumor or as evidence of disseminated multiple myeloma. CASE Two cases of plasmacytoma of the breast were diagnosed by fine needle aspiration cytology. Aspiration smears showed a dispersed population of plasmacytoid cells with eccentric nuclei, abundant cytoplasm and the characteristic paranuclear hof. CONCLUSION The clinical, cytologic and immunophenotypic features of plasmacytoma are characteristic, and the importance of distinguishing these neoplasms from primary mammary tumors is important to avoid unnecessary surgery.

Treating hepatocellular carcinoma progression following first-line sorafenib: therapeutic options and clinical observations

Despite the established efficacy of sorafenib in advanced hepatocellular carcinoma (HCC), a significant number of sorafenib-treated patients experience disease progression. Current guidelines recommend either best supportive care or clinical trial enrollment for this population. As such, there remains an unmet need for tolerable, life-prolonging strategies in the second-line setting. New information regarding the molecular pathogenesis of resistance to antiangiogenic therapy and positive post-progression experience with antiangiogenics in other tumor types has led to trials investigating the effect of continued use of sorafenib, alone or combined with other agents. Trials investigating the effect of switching from sorafenib to alternate antiangiogenic agents, phosphatidylinositol 3 kinase/AKT/mammalian target of rapamycin inhibitors, or cMet inhibitors are also underway. As these data emerge, clinicians may consider a new paradigm for managing advanced HCC. This article briefly reviews the mechanisms of disease resistance to antiangiogenic therapy as a vehicle for discussing clinical strategies to prolong survival in patients with advanced HCC that are currently employed at our institutions or are under investigation. Key ongoing trials investigating the use of molecularly targeted therapies in patients with progressive disease are also highlighted.

Dysplastic nodules and hepatocellular carcinoma: sensitivity of digital subtraction hepatic arteriography with whole liver explant correlation.

Purpose The purpose of this work was to determine the sensitivity of hepatic digital subtraction arteriography (DSA) for the detection of hepatocellular carcinoma (HCC) and dysplastic nodules (DNs) when compared with pathological findings from whole liver explants. Method Twenty-one patients 30–72 years old (mean 54 years) with cirrhosis and known or clinically suspected HCC (20 prior to chemoembolization) underwent hepatic DSA with subsequent transplantation within 80 days (mean 32 days). The prospective DSA report was compared with pathologic findings from explanted livers. Results Overall, DSA detected 31 of 95 HCC lesions for a sensitivity of 33%. Of these 31 lesions, 28 were hypervascular and 3 were hypovascular. DSA detected all six HCCs measuring >5 cm, all six HCCs measuring 3–5 cm, and all five HCCs 2–3 cm, resulting in a sensitivity of 100% (17/17) for HCC >2 cm. DSA detected 7 of 18 HCCs measuring 1–2 cm (sensitivity 39%) and 7 of 60 HCCs ⩽1 cm (sensitivity 12%). Overall sensitivity for DSA in detection of HCC ⩽2 cm was 18% (14/78 lesions). None of 17 DNs (0.2–1.5 cm in size) was identified on DSA. Conclusion DSA is insensitive to small HCC (⩽2 cm), carcinomatosis arising within nodules, and DN.

Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry

Background: Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets. Methods: Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physicians discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected. Results: In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade ≥3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged. Conclusions: The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE.

A Multicenter Evaluation of Utility of Chest Computed Tomography and Bone Scans in Liver Transplant Candidates With Stages I and II Hepatoma

Objective:To determine utility of practice of chest computed tomography (CCT) and bone scan (BS) in patients with early-stage hepatoma evaluated for transplantation (LT). Summary Background Data:Consensus-based policy mandates routine CCT and BS in LT candidates with hepatoma. No data exist either to support or refute this policy. Methods:From January 1999 to December 2002, stages I and II hepatoma patients evaluated at 4 centers were included. Scan interpretation was positive, indeterminate, or negative. Outcomes of evaluation and transplantation were compared between groups based on scans. Total charges incurred were derived from mean of charges at the centers. Results:One hundred seventeen stages I and II patients were evaluated. None had positive scans, 78 had negative, 29 had at least 1 indeterminate, and 10 did not have 1 or both scans. Twelve patients were declined listing, 6 from progression of hepatoma but none from CCT or BS findings. Two listed patients were delisted for progression of the hepatoma. Proportion of patients listed, transplanted, clinical and pathologic stage of hepatoma, and recurrence after LT were similar in groups with negative and indeterminate scans. Indeterminate scans led to 6 invasive procedures, 1 patient died of complications of a mediastinal biopsy, and none of the 6 showed metastases. Charges of

Phase I study of doxorubicin, ICRF-187 and granulocyte/macrophage-colony-stimulating factor

2933 were generated per patient evaluated. Conclusions:Positive yield of routine CCT and BS in patients with hepatoma is very low despite substantial charges and potential complications. CCT and BS performed only when clinically indicated will be a more cost-effective and safer approach.

Encapsulated Anaplastic Thyroid Carcinoma Transformed from Follicular Carcinoma: A Case Report

SummaryA group of 16 patients with advanced malignancy were entered on a phase I trial of escalating doses of doxorubicin with ICRF-187 for cardioprotection and granulocyte/macrophage-colony-stimulating factor (GMCSF) for bone marrow protection. Patients received intravenous ICRF-187 (dose ratio 20∶1 ICRF-187: doxorubicin) 30 min prior to doxorubicin. GMCSF at a dose of 15 μg kg−1 day−1 was self-administered subcutaneously on days 3–14 of the cycle. Doxorubicin was administered every 21 days. Substantial hematological and non-hematological toxicity was seen. Fever, malaise, and pulmonary symptoms, thought to be due to GMCSF, were not eliminated by reduction in the GMCSF dose to 10 or 5 μg kg−1 day−1. Severe hematological toxicity was seen despite GMCSF administration and it was not possible to escalate the doxorubicin dose above 72 mg/m2 with this combination. Dose escalation of doxorubicin may be more feasible with the use of other growth factors or growth factor combinations.