Usha A. Joseph

Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

BackgroundIt is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis.MethodsWe performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression.ResultsNo patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

Phase I evaluation of AT-125 single dose every three weeks

SummaryA Phase I trial of AT-125 was completed for the bolus dose every three week schedule. Dose limiting toxicity was primarily central nervous system (CNS) in the form of ataxia, confusion, hallucinations and dysarthria. Although this was most severe at doses of 150 mg/m2, lesser symptoms were reported at all dose levels. Nausea and vomiting were moderate to severe at higher doses. Myelosuppression did not occur. This schedule is not recommended for Phase II studies until methods are developed to reduce drug-related CNS toxicity.

Ventriculoperitoneal shunt catheter and cerebral spinal fluid infection initially detected by FDG PET/CT scan.

Whole body F-18 fluorodeoxyglucose (FDG) position emission tomography (PET) computed tomography (CT) in a 75-year-old woman with right lung cancer revealed linear increased FDG activity at the distal end of the ventriculoperitoneal (VP) shunt catheter in the pelvis and in the scalp reservoir. Culture of the later removed VP-shunt catheter demonstrated Gram-positive Staphylococcus. No increased FDG activity was identified in the cerebrospinal fluid (CSF) in the ventricles, probably due to interference from nearby cerebral cortex uptake. However, the sagittal images demonstrated mild intermittent linear FDG uptake in the spinal canal. The vertebral marrow FDG uptake obscured the mild CSF activity in spinal canal on the coronal or transaxial images. Sagittal projection images of the spinal canal are critical for PET/CT evaluation of suspected CSF infection.

Effect of Y-90 SIR-Spheres Therapy for Multiple Liver Metastases in a Variety of Tumors

Objective To evaluate the outcomes of patients receiving Y- 90 SIR-Spheres in patients with multiple liver metastases from different tumors. Methods: 29 consecutive patients with multiple liver metastases from colorectal (13), Islet cell tumors (9), carcinoid tumors (4) or non-small cell lung cancer (3) who were treated with Y-90 SIR-Spheres between March, 2003 and February, 2006 were included. Only patients who had follow-up radiological exams at our institution were included. Data regarding Y-90 SIR-Spheres dose, lobe of liver treated, and chemotherapy (CTx) administered were collected. Patients’ outcomes were evaluated based on radiological evidence of change in size and number of liver metastases. Results: The study population included 8 females and 21 males at a mean age of 60y. The mean Y-90 SIR-Spheres dose administered was 39.8 mCi. Both lobes of the liver, the right lobe only or the left lobe only were treated in 26, 2, 1 patients, respectively. Sixteen patients received Y-90 SIR-Spheres after CTx failure, 5 patients as adjuvant therapy after completion of CTx, 7 patients as concurrent therapy and one patient refused repeat CTx. The mean interval between the last CTx and Y-90 SIR-Spheres was 108 days. Four patients (14%) demonstrated radiological improvement and 9 (31%) were stable for a mean interval of 2.8 mo. after Y-90 SIR-Spheres infusion. Sixteen patients (55%) demonstrated continued progress of liver metastases. Conclusion: Y-90 SIR-Spheres therapy is useful in reducing or stabilizing multiple liver metastases from a variety of tumors.

Technetium-99m labeled red blood cells in the evaluation of hemangiosarcoma

Imaging with Tc-99m labeled red blood cells (RBC) is increasingly being used in the detection of acute gastrointestinal bleeding, especially in patients with intermittent bleeding. A patient is presented in whom the labeled RBC scan was helpful in the incidental discovery of a previously unsuspected probable angiosarcoma of the right femur and adjacent soft tissues of the right hip due to the “blood pool” or “blush effect” of the labeled cells. The labeled RBC scan also identified extravasation due to active gastrointestinal bleeding from a previously unknown angiosarcoma of the ascending colon. Thus, the Tc-99m labeled RBC scan was useful in simultaneously detecting extravasation and blood pool effect at two remote tumor sites in the same patient.

The impact of DaTscan in the diagnosis of Parkinson disease.

Purpose The aim of this study was to evaluate the impact of DaTscan in a heterogeneous group of patients with movement disorders as well as the degree of confidence in scan findings between different readers. Procedures A retrospective evaluation of consecutive patients who underwent DaTscan during 1 year was performed. The patients’ demographics, symptoms, duration, clinical diagnosis, and medications were collected. The scan findings were categorized by 2 blinded observers on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each of the caudate heads and putamina separately. A correlation of the scan findings with the clinical symptoms and diagnosis as well as interobserver agreement was performed. Disagreement was considered when a difference greater than 2 in more than 1 area of the basal ganglia was recorded. Descriptive statistics and &kgr; test for interobserver agreement were used for data analysis. Results Fifty-seven patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of Parkinson disease (PD) was certain in 26 and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). In 31 patients with uncertain diagnosis, 15 (48%) had markedly abnormal scans, 5 (16%) had mild abnormalities, and 11 (36%) had normal scans. Each of the sensitivity and positive predictive value of DaTscan in patients who had certain clinical diagnosis of PD (26 patients) is 92%. Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (&kgr; = 0.82). There was also a good correlation with laterality of symptoms in 32 (82%) of 39 positive studies. Conclusions Markedly abnormal DaTscan is confirmed as the diagnostic pattern for PD. This pattern helps confirm the diagnosis in patients with unclear clinical diagnosis. Good interobserver agreement is easily obtained in reading DaTscans.

Inguinal herniation of a bladder diverticulum on PET/CT and associated complications

Inguinal herniation of the urinary bladder is not routinely seen in clinical practice. Most patients are asymptomatic and are diagnosed incidentally on diagnostic imaging or during the course of surgical repairs. Bladder herniation has previously been reported on ultrasonography and computed tomography, but not on positron emission tomography (PET) imaging. We report an interesting case of bladder herniation and describe the findings observed by PET as well as the complications associated with this abnormality.

Functional Molecular Imaging in Hepatology

Functional Molecular Imaging in Hepatology is a well-written, informative, and useful e-book by knowledgeable, dedicated authors. The first chapter gives a good overview of the hepatic vascular anatomy, describing the dual blood supply of the liver (the hepatic artery and portal vein), the special hepatic outflow system (the hepatic veins), and the essential role of substance exchange between blood and the highly permeable hepatic sinusoids in maintaining metabolic homeostasis. The key dynamic interplay of the hepatic vascular components for metabolism of endogenous and exogenous substances is essential for maintaining proper liver function. Chapter 2 describes several methods that include intravascular tracers for dynamic PET measurement of total hepatic blood flow and perfusion of unit volume of liver tissue. Chapters 3 explains compartmental and microvascular models and describes research showing that, compared with compartmental models, the microvascular sinusoidal model of enzymatic elimination in vivo better explains the complex hepatic functions and in vivo effects of concentration gradients of substrates along capillaries. Chapter 4 discusses PET tracer use in measuring regional metabolism and in calculating the metabolic clearance of a mother substance based on clearance of its analog. Chapter 5, on hepatic glucose and fatty acid metabolism, describes methodologic advances in liver metabolism and clinical findings seen by PET imaging in metabolic diseases. Chapter 6, on biliary secretion, is a comprehensive, informative overview of the complex vital role played by the liver in preserving the balance of metabolic functions in the body. This chapter covers the detergent and detoxification role of bile; the protective role against colonic bacterial overgrowth; the role of biliary secretion, bile flow, and bile acids in normal digestion and disease; and cholesterol, triglyceride, and glucose and energy homeostasis. Ongoing medical research on quantification of liver metabolism and other medical challenges is also covered. Chapter 7 introduces us to metabolomic analysis, a new technology for rapid, accurate, and precise evaluation of a large number of metabolic responses to liver disease. Besides being used in basic research, this technology has clinical application in the diagnosis and prognosis of liver disease and in determining the biochemical consequences of drug treatment. Chapters 8–11 cover disease processes such as hepatocellular cancer, cholangiocarcinoma, liver metastases from colorectal cancer, and neuroendocrine tumors. The early diagnosis of hepatocellular cancer while the tumor is in a small, more curable stage using molecular imaging of specific metabolic pathways is beneficial compared with the traditional 4-phase contrast CT or dynamic contrastenhanced MR imaging. The authors discuss the improved diagnostic ability of 18F-FDG PET in detecting recurrent cholangiocarcinoma and distant metastasis and the role of 18F-FDG PET in colorectal cancer as the single best imaging modality for detecting intraand extrahepatic metastasis or evaluating early therapy response. The introduction of newer PET tracers for neuroendocrine tumor work-up is covered. This chapter discusses the fact that 18F-3,4-dihydroxyphenylalanine, a metabolism-based radiotracer, has limited use because of high production costs whereas the receptor-based compounds, 68Ga-DOTA peptides, are easier to use, are more economic, and localize better in well-differentiated neuroendocrine lesions than somatostatin receptor imaging agents. Also covered is the use of 18F-FDG in undifferentiated neuroendocrine tumors with higher glucose metabolism or tumors with low expression of somatostatin receptors, such as medullary cancer of the thyroid. Chapters 12–15 cover the neurologic effects of impaired hepatic function. Chapter 12 details the metabolic processes responsible for brain energy and ammonia metabolism. The effects of dysfunctional ammonia metabolism and toxic levels of ammonia in hepatic encephalopathy, brain energy metabolism, and amino acid metabolism are covered. Ongoing research tools to study these metabolic processes are discussed. Chapter 13 discusses the significant alterations in cerebral glucose utilization in cirrhosis with mild hepatic encephalopathy. 18F-FDG imaging shows decreased glucose utilization in the frontal cortex and anterior cingulate gyrus (which are involved in attention processes and motor performance), along with increased activity in the hippocampus, basal ganglia, and cerebellum. Chapter 14 discusses cerebral ammonia metabolism in liver failure, including the finding of no change in cerebral ammonia kinetics or in the permeability–surface area product for ammonia across the blood– brain barrier in cirrhotic patients with hepatic encephalopathy. The bulk of the evidence favors a correlation between metabolic trapping of ammonia and arterial blood ammonia concentration alone. Chapter 15 describes the relative merits of different MR techniques, including MR imaging and MR spectroscopy, and provides valuable insights into cerebral cell structure, water content, and metabolism in hepatic encephalopathy. The chapter also gives insight into neurologic dysfunction in liver diseases resulting from metal deposition (manganese, copper, and Wilson disease), hemochromatosis, and primary biliary cirrhosis and hepatitis C. As medical knowledge advances, its dissemination is taking novel approaches such as the e-book format, which will appeal to younger physicians who have grown up in the age of computers and the Internet. Some chapters, such as 2–4 and 12, are heavily biochemistry-oriented, requiring intense and dedicated concentration on the part of the reader to understand the many complex biochemical reactions covered. The clinically oriented chapters comprehensively cover useful information on hepatic function in health and disease and the toxic effects of ammonia and impaired hepatic function in hepatic encephalopathy. The effects of abnormal hepatic metabolism on functional molecular imaging are covered, as is future research using metabolic pathways and PET tracers. This textbook will be useful to hepatologists dealing with complex medical issues related to liver disease in their clinical practice. I also recommend the book to neurologists and to individuals involved in liver research.

The value of fused SPECT/CT in the evaluation of solitary skull lesion.

Aim: The aim of this study was to evaluate the role of single photon emission computed tomography and/or computed tomography (SPECT/CT) in differentiating metastatic from benign solitary skull lesions. Materials and Methods: Consecutive patients who had a SPECT/CT of the head subsequent to a whole-body bone scan (WBS) for the evaluation of a single skull lesion were selected. A single skull lesion on the WBS was further evaluated with SPECT/CT to characterize the lesion. The results of the SPECT/CT were correlated with other radiologic examinations performed within 2 weeks. An average follow-up interval after the SPECT/CT was 8.9 months to correlate with additional radiologic imaging studies and clinical information. Results: A total of 19 lesions in 19 patients were seen on the WBS and 2 additional lesions on the SPECT/CT. All lesions demonstrated focal increased tracer uptake. The SPECT/CT correctly identified 3 out of 3 metastatic lesions and 12 out of 17 benign lesions, that is 71% of lesions were correctly classifised as metastatic or benign lesions. Only 1 patient was classified incorrectly as metastatic lesion with SPECT/CT when it was proven benign by other imaging modalities and follow-up. The sensitivity, specificity, positive and negative predictive values of SPECT/CT images in identifying metastatic lesions were 100%, 92%, 75%, and 100%, respectively. Five lesions remained indeterminate even after the SPECT/CT interpretation and were confirmed benign by other imaging modalities. Conclusion: SPECT/CT can help identify benign versus metastatic solitary skull lesions in most of the patients with high sensitivity and specificity.

Scintigraphic assessment of pericardio-peritoneal window patency. Relevance to peritoneal dialysis.

To alleviate recurrent pericardial effusion secondary to systemic lupus erythematosus, pericardio-peritoneal window was performed. Subsequently, end stage renal disease developed and the patient required peritoneal dialysis. Patency of the pericardio-peritoneal window was demonstrated by intraperitoneal injection of Tc-99m SC through a Tenckhoff catheter, which prompted special counsel to the patient in order to prevent infectious pericarditis potentially complicating peritoneal dialysis induced-peritonitis.