Faculty Bibliography

PURPOSE: To determine the clinical and biologic effects of bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Adults with organ-confined HCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease were eligible. Patients received bevacizumab 5 mg/kg (n = 12) or 10 mg/kg (n = 34) every 2 weeks until disease progression or treatment-limiting toxicity. The primary objective was to determine whether bevacizumab improved the 6-month progression-free survival (PFS) rate from 40% to 60%. Secondary end points included determining the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay. RESULTS: The study included 46 patients, of whom six had objective responses (13%; 95% CI, 3% to 23%), and 65% were progression free at 6 months. Median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. Bevacizumab was associated with significant reductions in tumor enhancement by dynamic contrast-enhanced magnetic resonance imaging and reductions in circulating VEGF-A and stromal-derived factor-1 levels. Functional angiogenic activity was associated with VEGF-A levels in patient plasma. CONCLUSION: We observed significant clinical and biologic activity for bevacizumab in nonmetastatic HCC and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients

Introduction: Quantifying cellularity is an integral component of bone marrow examinations. Estimates of marrow cellularity may influence the diagnostic interpretation of bone marrow samples. The accuracy of cellularity estimates may be influenced by the variable distribution of cellular elements within the marrow space. To better understand the degree of heterogeneity of bone marrow cellularity, we undertook a study to quantify the variable distribution of bone marrow cells in bone marrow core biopsies. Method: 8 gauge bone marrow core biopsies of 20 patients were retrospectively reviewed by 2 hematopathologists (SI,CL). The specimens were recovered from the posterior superior iliac crest using standard technique with 8G Snarecoil biopsy needles by 3 operators (KH, PK, GD). The percent cellularity was determined in sequential 0.2 X 0.4 cm portions of the core biopsies by each of the hematopathologists. Cellularities were recorded in 10% increments. Results: The mean age of the patients was 73.2 1.8 years. There were 12 males and 8 females. 5 patients had monoclonal gammopathies. Anemia, multiple myeloma and thrombocytopenia were each diagnosed in three patients. 2 patients demonstrated myelodysplasia and 1 patient each had acute leukemia, leukocytosis, non-Hodgkin's lymphoma and thrombocytosis. The mean white blood cell count, hemoglobin and platelet count were 8.7 (range 3.842.8), 12.2 (range 10.115.3), and 233 (range 91226), respectively. The mean length of the core biopsies was 1.78 0.09 cm (range 1.43.3) and the median number of 0.2 x 0.4 cm portions examined per core biopsy was 8 (range 512). In total, 165 portions were examined by each hematopathologist independently. The cellularity of 12 and 11 portions could not be determined by each of the hematopathologists, respectively, as a result of biopsy artifacts. No core biopsy showed a consistent cellularity within the examined portions, each core demonstrating a range of cellularities. Only 2/20 and 1/20 of the core biopsies, as examined by each hematopathologist, respectively, demonstrated 2 consistent cellularities. A median of 4 different cellularities were identified in each core. The mean range of cellularities of each core's portions was 43 4.6 %, and 46.5 4.9 %, as determined by the 2 hematopathologists, respectively, which was statistically equivalent (paired t-test p=0.349)

Recently, donation after cardiac death (DCD) has been encouraged in order to expand the donor pool. We present a case of anaplastic T-cell lymphoma transmitted to four recipients of solid organ transplants from a DCD donor suspected of having bacterial meningitis. On brain biopsy, the donor was found to have anaplastic central nervous system T-cell lymphoma, and the recipient of the donor's pancreas, liver and kidneys were found to have involvement of T-cell lymphoma. The transplanted kidneys and pancreas were excised from the respective recipients, and the kidney and pancreas recipients responded well to chemotherapy. The liver recipient underwent three cycles of chemotherapy, but later died due to complications of severe tumor burden. We recommend transplanting organs from donors with suspected bacterial meningitis only after identification of the infectious organism. In cases of lymphoma transmission, excision of the graft may be the only chance at long-term survival

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 $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