Karen P. Holdeman

Predictive value and diagnostic accuracy of F-18-fluoro-deoxy-glucose positron emission tomography treated grade 1 and 2 follicular lymphoma

F-18-fluoro-deoxy-glucose positron emission tomography (PET) is a powerful tool for the imaging of aggressive B-cell lymphomas. In contrast, there is relatively little data on PET in follicular lymphoma grade 1 (FL-1) and grade 2 (FL-2). In this manuscript, we present our findings utilizing PET in treated FL-1 and FL-2. A retrospective review of patients who underwent PET examinations at our institution produced 95 PET examinations among 31 patients with FL-1 and FL-2. PET was obtained at initial staging, mid-induction and post-treatment. Results were compared with clinical follow-up. PET had high sensitivity (95%) and specificity (88%) for lesion detection in treated FL-1 and FL-2. Abnormal foci in FL-1 and FL-2 had similar intensities. Post-induction PET positive patients had shorter mean progression free survivals compared with PET negative patients (p-value ≤0.001), post-salvage PET positive trended toward shorter mean response duration compared with negative patients (p-value: 0.09). Our results indicate that PET is accurate in the diagnostic assessment of treated FL-1 and FL-2 and, post-treatment PET positive patients are likely to relapse prior to PET negative patients.

Sarcoidosis mimicking recurrent lymphoma

A 63-year-old woman became tired, unable to carry out all of her usual activities and had the onset of drenching night sweats in January of 2007. While in the woods feeding deer, she became confused and fell down a hill. She was taken to an emergency room where she was found to have hypercalcemia, renal failure, and retroperitoneal lymphadenopathy. A biopsy of the retroperitoneal lymphadenopathy showed diffuse large B-cell lymphoma. Further evaluation revealed no enlarged supradiaphragmatic lymph nodes, a negative bone marrow biopsy, and an elevated LDH. She was treated with fluids, furosemide, and CHOP plus rituximab in the beginning of March 2007. A restaging evaluation after four cycles of chemotherapy showed a creatinine of 1.0 mg/DL, calcium of 8.7 mg/DL, and LDH of 359 IU/L (maximum normal 618 IU/L). An FDG PET/CT scan showed no evidence of residual lymphoma. The patient received her fifth and sixth cycles of CHOP plus rituximab. In March 2008, she was seen in routine follow-up. She was able to carry out her usual activities, did not complain of being tired, and did not have fevers, drenching night sweats, or weight loss. However, at that time, her calcium was 12.1 mg/DL and LDH 280 IU/L (maximum normal 618 IU/L). Except for some swelling of her eyelids, there were no new physical findings. Because of concern about recurrent lymphoma, an FDG PET/CT scan was performed. (Image 1 is a maximum intensity projection PET image showing focal FDG uptake in multiple lymph nodes of the mediastinum, bilateral hila, and porta hepatis with a maximum SUV of 9.1) Although it appeared that the patient had relapsed, a decision was made to not institute therapy without histological proof of recurrent lymphoma. A biopsy of a mediastinal lymph node and of lacrimal glands showed granulomatous infiltration with occasional multinucleated giant cells consistent with sarcoidosis. (Image 2 shows a lacrimal gland with a noncaseating granuloma H&E stain, 2003). Treatment was instituted with prednisone at a dose of 40 mg. daily. The eye swelling resolved and the serum calcium and the FDG PET/CT scan normalized. As of November 2011, the patient has remained in remission from lymphoma for more than 4 years, and her sarcoidosis and hypercalcemia have never recurred. This patient illustrates the danger of initiating therapy for recurrent lymphoma in a patient in initial complete remission based on abnormal imaging studies when no biopsy has been performed. Whether salvage chemotherapy and an autotransplant (i.e., the standard therapy for recurrent diffuse large B-cell lymphoma) might have cured the patient’s sarcoidosis is unknown, but it would have been unnecessary and dangerous. It is our policy to never treat a patient who achieves a complete remission without biopsy proof of recurrence. Over the last 30 years, this has led to avoiding further chemotherapy or radiation in patients with follicular hyperplasia, other malignancies, infections, and sarcoidosis. PET scans represent an important advance in evaluating patients with lymphoma. They are more accurate than CT scans in identifying active disease, and a negative PET scan at the completion of therapy is the best evidence of a

On the safety of 5-[125I]iodo-2′-deoxyuridine. Preclinical evaluation in swine

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.

Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease

Our aim was to evaluate gastric emptying and orocecal transit in patients with end-stage liver disease and portal hypertension undergoing evaluation for liver transplantation. Although gastric emptying half-times for both liquid and solid emptying were similar in patients with chronic liver disease and control subjects, orocecal transit, as measured by a scintigraphic technique, was significantly prolonged in the patients with liver disease (transit time, minutes, mean +/- SEM, patients versus controls: 127 +/- 10.5 versus 80 +/- 9.5, P < .003). Serum levels of progesterone and estradiol were similar in patients and controls. We conclude that small intestinal transit is delayed in patients with advanced liver disease and portal hypertension and may contribute to gastrointestinal symptoms and promote sepsis of enteric origin in this patient population.

Delayed Gastric Emptying of Both the Liquid and Solid Components of a Meal in Chronic Liver Disease

OBJECTIVES To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. METHODS We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). RESULTS Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. CONTROLS 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. CONCLUSIONS Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.