Wahid T. Hanna

Time Course of Early Response to Chemotherapy in Non–Small Cell Lung Cancer Patients with 18F-FDG PET/CT

PET and 18F-FDG have the potential to follow the early metabolic response to chemotherapy in patients with non–small cell lung cancer and to predict success or failure of the therapy. Methods: We studied 16 patients with non–small cell lung cancer as they followed 2 courses of docetaxel and carboplatin. Each patient was studied weekly for 7 wk, and tissue activity was assessed by the amount of radioactivity retained 90 min after the intravenous injection of 18F-FDG. In a prospective analysis, the linear least-squares method was used to evaluate the time course of metabolic activity in tumor and liver, bone marrow, and unaffected lung tissues; a metabolic response was defined as a response in which the slope of the regression was negative and significantly different from zero. Our hypothesis was that patients who exhibited a tumor metabolic response would survive longer than those who did not. In a retrospective examination of our data, we grouped our patients into those who survived <6 mo and those who survived longer and calculated the difference in the standardized uptake value (SUV) between day 7 and subsequent time points to determine the most appropriate timing of 2 PET studies in predicting response to therapy. Results: Fifteen of 16 patients completed the study. In the prospective study, 8 patients were classified as nonresponders as the slope of the regression of tumor SUV versus time was not different from zero; they all died within 35 wk of the end of their study. Seven patients were classified as responders; 5 survived and 2 died, one at 25 wk and the other at 76 wk. In the retrospective study, a decrease of 0.5 SUV between studies performed at 1 and 3 wk after the initiation of chemotherapy was predictive of those patients who survived >6 mo and in whom chemotherapy was presumably successful. Conclusion: Patients with non–small cell lung cancer who had a positive outcome, as exhibited by prolonged survival, were those who showed a tumor metabolic response assessed using weekly 18F-FDG PET studies. 18F-FDG PET studies performed at 1 and 3 wk after the initiation of chemotherapy allowed prediction of the response to therapy.

Alterations of serum and urinary carnitine profiles in cancer patients: hypothesis of possible significance.

The present study examined the serum and urinary carnitine concentrations of 21 cancer patients with metastatic disease and 13 healthy age-matched controls by taking three consecutive samples during an 8-week period. The serum concentrations of all fractions of carnitine were significantly lower in the female cancer patients than in the female controls. The concentrations of urinary carnitine fractions were relatively higher in the total cancer population; however, only acid-insoluble acylcarnitine (AIAC) was statistically significant. The renal clearance of acid-soluble acylcarnitine (ASAC) and AIAC was significantly greater in cancer subjects than in controls. Significant inverse relationships were established between the ASAC and AIAC clearances and their respective serum concentrations. The renal tubular reabsorption of AIAC was significantly less in cancer patients than in control subjects as indicated by the fractional excretion of carnitine. The increased clearance of acylcarnitine and excretion of large amounts of AIAC are proposed to be a response to chemotherapy and represent a loss of energy to the cancer patient.

Primary angiosarcoma of the spleen: A case report and review of the literature

We describe a 47-year-old man with shoulder pain, multiple bony lesions, and a 1-cm lesion in the spleen. T-1 facetectomy revealed a poorly differentiated malignant neoplasm. Several months after chemotherapy, multiple splenic lesions were found by computed tomography and liver-spleen scan. A splenectomy showed a malignant spindle-cell neoplasm forming irregular vascular spaces. Tumor cells were positive for factor VIII-related antigen and vimentin. This patient died of extensive metastases from this primary angiosarcoma of the spleen. Splenic angiosarcoma is a rare neoplasm that often has a cryptic presentation and a dismal prognosis.

Prevalence of Hepatitis A Antibodies in Hemophiliacs: Preliminary Results from the Southeastern Delta Hepatitis Study

The University of North Carolina at Chapel Hill. N.C., Vanderbilt University, Nashville, Tenn., University of Tennessee at Knoxville, Tenn., Medical College of Georgia, Augusta, Ga., Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C., and Tulane University of Louisiana, New Orleans, La., USA: University of Calgary, Aka., Canada Prevalence of Hepatitis A Antibodies in Hemophiliacs: Preliminary Results from the

Psychogenic purpura (autoerythrocyte sensitization).

A 41-year-old woman has had a long history of repeated episodes of recurrent painful ecchymotic lesions. Results of coagulation tests were normal other than a slight decrease in antithrombin III. Skin tests were positive in response to the patients own washed red cells. Light and electron microscopy of both the spontaneous and the induced lesions showed nonspecific changes but failed to reveal immunologic vasculitis. Psychologic evaluation showed hysterical and masochistic traits, depression, anxiety, and inability to deal appropriately with hostile impulses. Placebo was successful on several occasions in controlling or modifying the severity of the ecchymotic lesions.

Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma

This non‐comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab‐chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21‐d cycles of: bortezomib 1·6 mg/m2 (days 1, 8), rituximab 375 mg/m2 (day 1), cyclophosphamide 1000 mg/m2 (day 1) and prednisone 100 mg (days 1–5; VR‐CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR‐CP, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 (day 1; VR‐CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR‐CP, the response rate was 77%, with a 27% complete response rate. After a median follow‐up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression‐free survival was 21·9 and 14·9 months, respectively. Common drug‐related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR‐CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug‐related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR‐CP was active and well tolerated in patients with relapsed/refractory FL.

Radioimmunoassay of fragment E-related neoantigen: validation studies and clinical application

Summary. Measurement of fibrinogen‐fibrin degradation products (FDP) levels in plasma may provide a direct index of plasmin action, and increased levels of FDP would indicate coagulopathy. We have established an E‐neoantigen radioimmunoassay (Eneo RIA) that can determine normal and pathological plasma levels of E‐related FDP. The assay employs rabbit antiserum produced against fragment E derived from a plasmin digest of fibrinogen and subsequently absorbed with fibrinogen. The absorbed antiserum contains antibodies which are equally reactive with fibrinogen derived E (Fg‐E) and fibrin derived E (Fb‐E) but not with fibrinogen at 1 mg/ml. The Eneo RIA was validated by assay parallelism and by recovery experiments. Plasma Eneo immunoreactivities in 14 normals were 4–22 ng/ml (mean 12.7 ng/ml). Plasma Eneo levels in 23 of 24 patients with neoplastic and haematological diseases were elevated above normal (range 27–2027 ng/ml). Unusually high Eneo values were observed with three patients whose diseases were complicated by either disseminated intravascular coagulation (DIC) or deep vein thrombosis. After heparin therapy, the Eneo level of a patient with chronic DIC declined. A pathological plasma was eluted from a Sephadex G‐200 column and Eneo immunoreactivity was determined on the eluates. The gel filtration pattern of Eneo indicates that E‐related FDP is a family of plasmic fragments derived from crosslinked fibrin.

Factors affecting the appearance of a pre-peak during crossed immunoelectrophoresis of factor VIII related antigen

Abstract Conditions were examined which elicit “pre-peak” formation during crossed immunoelectrophoresis (CIEP) of normal, human factor VIII related antigen (FVIII:RAg). Pre-peak artifacts could be induced by sample handling conditions leading to cryoprecipitate, platelets or platelet fragments in the plasma. Under conditions not promoting pre-peak artifacts, only 25% of the hemophilic samples tested showed pre-peaks. No other abnormality tested produced pre-peaks with the exception of samples from recently infused patients. Pre-peaks appear, therefore, to be of limited predictive value.

Decreased antithrombin iii level associated with failure of anticoagulation

A 67-year-old man with adenocarcinoma of the colon had recurrent pulmonary emboli. The patients level of serum antithrombin III was found to be below normal. Heparin therapy led to further reduction, resulting in failure of adequate anticoagulation. The patient subsequently died of massive pulmonary emboli despite heparin therapy. We believe the antithrombin III level should be routinely determined for patients receiving heparin therapy.

Spurious polycythemia and renal malignancy.

We have described a 19-year-old woman with polycythemia. Based on a normal red cell mass and decreased plasma volume, spurious polycythemia was diagnosed. CT scan of the abdomen revealed a 4 cm mass in the right kidney. Upon right nephrectomy, the mass was found to be an unusual neoplasm of the renal tubular epithelium. Four weeks postoperatively, both the hemoglobin and hematocrit values were normal.