PET in the management of urologic malignancies

FDG-PET has a limited role in diagnosis of prostate cancer mainly because of the low uptake of FDG in the tumor and normal excretion of FDG through urine. FDG-PET has shown some promise in the assessment of lymph nodes and bone metastases. There is a large degree of variability when FDG-PET is compared with bone scintigraphy. New C11-labeled radiotracers (acetate, choline, and methionine) have shown promising initial results but further studies are required to determine their role in such settings. These radiotracers provide a unique opportunity for dynamic, multitracer, and quantitative studies, which improve the sensitivity and specificity on PET in this population. Short half-lives and of C-11, however with the limits to their use requires an on-site cyclotron. Recent synthesis schemes with [18F]-labeling, however, may overcome this limitation. FDG-PET has a significant potential to assist with the diagnosis and management of testicular cancer. PET has been most useful in defining the presence or absence of disease in patients with residual masses. PET has shown promising results for the initial diagnosis of this cancer, but further for studies ar required to determine its role in the management of this malignancy. PET can be used in conjunction with conventional imaging techniques to diagnose retroperitoneal masses in patients with primary testicular cancer. FDG-PET has shown very encouraging results in a limited number of studies, and has also demonstrated a good sensitivity for initial staging. FDG-PET seems to be superior to conventional imaging modalities for detecting local disease and recurrence, and distant metastases.     

Normal variants in [18F]-fluorodeoxyglucose PET imaging

The number of fluorodeoxyglucose PET applications is increasing. In the process of reading fluorodeoxyglucose-PET scans, nuclear medicine physicians encounter a wide variety of normal findings, which must be recognized to determine the best management for patients. It is important to recognize and understand normal variants to avoid misinterpretation of more serious pathology. This article reviews different patterns of physiologic fluorodeoxyglucose uptake including changes with age.     

Investigation of thyroid, head, and neck cancers with PET

PET with [(18)F]-fluorodeoxyglucose (FDG) has been accepted as a useful imaging modality for the diagnosis of a variety of malignancies. This article discusses the use of FDG-PET in the management of patients with thyroid and head or neck cancers.     

Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors

OBJECTIVES/HYPOTHESIS: Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. STUDY DESIGN: We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. METHODS: Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. RESULTS: Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. CONCLUSIONS: We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer.     

Potential false-positive FDG PET imaging caused by subcutaneous radiotracer infiltration

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been useful in the management of a variety of malignancies with high accuracy. However, numerous nonmalignant lesions can also result in increased FDG accumulation and consequently may cause potential false-positive interpretation if the causes are not recognized. A single focus of FDG accumulation in the axilla can often easily be attributed to tracer infiltration when the injection was on the same side. However, multiple foci of FDG uptake can be similar to malignant lesions. A case is presented in which the follow-up study clarified the nature of multifocal increased FDG uptake in the axilla.     

Roles of positron emission tomography with fluorine-18-deoxyglucose in the detection of local recurrent and distant metastatic sarcoma

Sarcomas are a heterogeneous group of tumors comprising approximately 1% of all malignancies. Definitive treatment of sarcoma is surgical resection. However, after surgical removal, 40% to 60% of the patients will develop local or distant recurrence. Therefore, the early detection and treatment of recurrence is an important part of modern sarcoma therapy. Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) has been highly successful in detecting and staging a variety of malignancies. However, its use in the management of patients with sarcoma is less defined. The purpose of our study was to assess the potential roles of FDG-PET in the detection of local recurrence and distant metastases. In this retrospective study, the images of 33 FDG-PET scans, reports of 29 computed tomography (CT) scans, and 8 magnetic resonance imaging (MRI) scans from 28 patients were compared with surgical pathology or clinical follow up for at least 6 months. FDG-PET detected all 25 cases of local and distant recurrences with 100% sensitivity. CT was able to detect 18 of the 22 possible cases of recurrent disease, whereas MRI was able to detect 5 of 7 cases of recurrent disease. PET was particularly useful in patients with extensive histories of surgery and radiation therapy, precisely the setting in which CT and MRI have the lowest specificity and sensitivity. In conclusion, FDG-PET was a sensitive test to detect local and distant recurrences of sarcoma and this warrants further investigation.     

Rapid normalization of osseous FDG uptake following traumatic or surgical fractures

It is known that following a traumatic fracture or surgical intervention, bone scintigraphy reveals positive results for an extended period of time, posing a challenge when evaluating patients for possible malignancy or superimposed osteomyelitis. Previous reports indicate that acute fractures can also result in increased fluorine-18 fluorodeoxyglucose (FDG) accumulation and therefore cause difficulties when patients are evaluated for other indications by FDG-PET. The purpose of this study was to assess the pattern and time course of abnormal FDG uptake following traumatic or surgical fracture. A total of 1,517 consecutive patients who underwent whole-body FDG-PET imaging were retrospectively studied. A history of fractures or orthopedic intervention was obtained from an interview prior to scanning. The FDG-PET results were compared with the results of other imaging studies, including bone scans, radiographs, CT, and MRI, as well as surgical pathology reports. Thirty-seven patients with a known date of traumatic or surgical fracture were identified. Among these, 14 had fractures or surgery within 3 months prior to FDG-PET, while 23 had fractures or surgical intervention greater than 3 months prior to FDG-PET. FDG-PET showed no abnormally increased uptake at the known fracture or surgical sites in 30 of these patients. Notably, in the 23 patients with fractures more than 3 months old, all but one showed no abnormally increased uptake. Furthermore, the positive FDG uptake in this exception was a result of complicating osteomyelitis. In the 14 patients with a history of fracture less than 3 months old, only six had abnormally increased FDG uptake. Following traumatic or surgical fractures, FDG uptake is expected to be normal within 3 months unless the process is complicated by infection or malignancy.     

Use of ibritumomab tiuxetan anti-CD20 radioimmunotherapy in a non-Hodgkin's lymphoma patient previously treated with a yttrium-90-labeled anti-CD22 monoclonal antibody

Ibritumomab tiuxetan is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy-refractory CD20+ B-cell non-Hodgkin's lymphoma. Whereas chemotherapy agents can successfully be used multiple times in a given patient, there are few data on the repeated use of radioimmunotherapy in terms of efficacy or morbidity, and no reports as yet involving radioconjugates that target different antigens We report on a patient who was treated successfully with yttrium-90-labeled humanized anti-CD22 monoclonal antibody (90Y-epratuzumab). Upon relapse 3 years later, the patient was treated again with radioimmunotherapy consisting of 90Y-ibritumomab tiuxetan anti-CD20 monoclonal antibody, with a good response and acceptable bone marrow suppression. This case report demonstrates the potential for repeated treatments with radioimmunotherapy agents in patients with chemotherapy-refractory non-Hodgkin's lymphoma.     

Effect of renal transplantation on sperm quality and sex hormone levels

OBJECTIVE: To assess the effect of successful renal transplantation on semen variables, sexual function and sex hormone profiles in a clinical trial. PATIENTS AND METHODS: Thirty patients on haemodialysis underwent renal transplantation; before and after surgery, their sperm density, motility and morphology were analysed, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and testosterone levels measured and compared, and sexual function assessed using an abbreviated version of the International Index of Erectile Function (IIEF), with a successful outcome defined as a level of satisfaction of 4 or 5 on a 5-point scale. The paired t-test was used to assess the statistically significance of differences in all analyses. RESULTS: Sperm motility improved significantly (P < 0.001) but there were no significant changes in morphology or density (P = 0.33 and 0.068, respectively). Testosterone levels increased and FSH, LH and prolactin decreased significantly (P < 0.05) after renal transplantation. The IIEF showed that of the 30 patients, 14 were impotent before surgery and only six remained so afterward (P < 0.05). CONCLUSION: Although sperm morphology and density did not improve after renal transplantation, there were highly significant changes in sperm motility. Hormonal levels in patients on haemodialysis improved after transplantation and returned to nearly normal; sexual function was also significantly better. Further studies are needed to confirm these results.     

The role of hyperplasia in multiple parathyroid adenomas

BACKGROUND: Parathyroid adenoma is the most common cause of primary hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas have been reported to occur in as high as 11% of patients with pHPT. The significant incidence of multiple adenomas with histologic similarities to hyperplasia has raised the possibility that adenoma is a continuation of the hyperplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corresponding normal glandular tissue. Furthermore, we devised a scheme to definitively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable. METHODS: The study included three patients with a diagnosis of singular parathyroid adenoma and three with double parathyroid adenomas. Paraffin-embedded surgical specimens of both adenomas and normal glands were retrieved from each patient. Clonal analysis of the phosphoglycerolkinase (PGK) gene has suggested that parathyroid adenomas are monoclonal. Clonality of parathyroid adenomas and normal parathyroid glands was studied by polymerase chain reaction-based restriction fragment length polymorphic analysis for the PGK gene. Proliferative activity of the specimens was also analyzed using the immunohistochemical markers PCNA and Ki-67. RESULTS: All adenomas were monoclonal and all normal parathyroid glands were polyclonal for the PGK gene in both the single and double adenoma specimens. All adenomas stained positive for proliferative activity. In the three patients with singular adenoma, proliferative activity was not detected in the normal parathyroid tissue. However, in the double adenoma group, two of the three patients showed hyperproliferative activity in the normal glands. CONCLUSION: Proliferative activity consistent with hyperplasia was present in some normal glands of multiple adenoma patients. Our observation supports the theory that multiple adenomas may be a continuation of the hyperplasia state.