Brian P. Mullan

Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): Temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause-specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient-years. The 25-year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40-year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10-year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10-year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near-total thyroidectomy and conservative nodal excision.

The Incidence, Prevalence, and Outcomes of Patients With Gastroparesis in Olmsted County, Minnesota, From 1996 to 2006

BACKGROUND & AIMS The epidemiology of gastroparesis is unknown. We aimed to determine the incidence, prevalence, and outcome of gastroparesis in the community. METHODS Using the Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with potential gastroparesis. The complete medical records were reviewed by a gastroenterologist. Three diagnostic definitions were used: (1) definite gastroparesis, delayed gastric emptying by standard scintigraphy and typical symptoms for more than 3 months; (2) probable gastroparesis, typical symptoms and food retention on endoscopy or upper gastrointestinal study; (3) possible gastroparesis, typical symptoms alone or delayed gastric emptying by scintigraphy without gastrointestinal symptoms. Poisson regression was used to assess the association of incidence rates with age, sex, and calendar period. RESULTS Among 3604 potential cases of gastroparesis, 83 met diagnostic criteria for definite gastroparesis, 127 definite plus probable gastroparesis, and 222 any of the 3 definitions of gastroparesis. The age-adjusted (to the 2000 US white population) incidence per 100,000 person-years of definite gastroparesis for the years 1996-2006 was 2.4 (95% confidence interval [CI], 1.2-3.8) for men and 9.8 (95% CI, 7.5-12.1) for women. The age-adjusted prevalence of definite gastroparesis per 100,000 persons on January 1, 2007, was 9.6 (95% CI, 1.8-17.4) for men and 37.8 (95% CI, 23.3-52.4) for women. Overall survival was significantly lower than the age- and sex-specific expected survival computed from the Minnesota white population (P<.05). CONCLUSIONS Gastroparesis is an uncommon condition in the community but is associated with a poor outcome.

Subtraction peri-ictal SPECT is predictive of extratemporal epilepsy surgery outcome

&NA; Article abstract Objectives To determine whether localization of extratemporal epilepsy with subtraction ictal SPECT coregistered with MRI (SISCOM) is predictive of outcome after resective epilepsy surgery, whether SISCOM images provide prognostically important information compared with standard tests, and whether blood flow change on SISCOM images is useful in determining site and extent of excision required. Background The value of SISCOM in predicting surgical outcome for extratemporal epilepsy is unknown, especially if MRI findings are nonlocalizing. Methods SISCOM images in 36 consecutive patients were classified by blinded reviewers as “localizing and concordant with site of surgery,” “localizing but nonconcordant with site of surgery,” or “nonlocalizing.” SISCOM images were coregistered with postoperative MRI, and reviewers visually determined whether cerebral cortex underlying the SISCOM focus had been completely resected, partially resected, or not resected. Results Twenty-four patients (66.7%) had localizing SISCOM, including 13 (76.5%) of those without a focal MRI lesion. Eleven of 19 patients (57.9%) with localizing SISCOM concordant with the surgical site, compared with 3 of 17 (17.6%) with nonlocalizing or nonconcordant SISCOM, had an excellent outcome (p < 0.05). With logistic regression analysis, SISCOM findings were predictive of postsurgical outcome, independently of MRI or scalp ictal EEG findings (p < 0.05). The extent of resection of the cortical region of the SISCOM focus was significantly associated with the rate of excellent outcome (100% with complete resection, 60% with partial resection, and 20% with nonresection, p < 0.05). Conclusion SISCOM images may be useful in guiding the location and extent of resection in extratemporal epilepsy surgery.

Gastric Accommodation and Emptying in Evaluation of Patients With Upper Gastrointestinal Symptoms

BACKGROUND & AIMS Endoscopy-negative dyspepsia is a common symptom that often is difficult to define in pathophysiologic terms. The aim of this study was to assess the frequency of disordered gastric accommodation and emptying in patients referred with unexplained upper gastrointestinal symptoms. METHODS A computerized diagnostic index was used to identify all patients, 18-70 years old, who underwent single-photon emission computed tomography (SPECT) to assess gastric accommodation at Mayo Clinic Rochester over a 3-year period. Demographics, clinical features, and results of diagnostic testing, including scintigraphic gastric emptying, were extracted from the electronic record. RESULTS A total of 214 patients were identified; the primary clinical diagnoses were functional dyspepsia, postfundoplication syndromes, rumination syndrome, and diabetic dyspepsia. Gastric accommodation was impaired in 43% of the whole group: 47% of functional dyspepsia, 44% of postfundoplication syndromes, and 33% of diabetic dyspepsia. Delayed gastric emptying was most prevalent in diabetic dyspepsia, and was accelerated in postfundoplication syndromes groups. Thirty-seven percent of patients had abnormal gastric emptying. The highest prevalence of delayed gastric emptying was in the diabetic dyspepsia and accelerated gastric emptying in postfundoplication syndromes groups. Twenty-five percent of patients with normal gastric emptying had impaired accommodation. Upper-gastrointestinal symptoms were not different in groups based on gastric accommodation or emptying results. CONCLUSIONS Impaired gastric accommodation is common in patients with unexplained dyspepsia. Symptoms alone cannot predict physiologic disturbances. These noninvasive tests identify single or combined pathophysiologic disturbances and may help to identify subgroups of patients as candidates for more selective pharmacotherapy in the future.

Subtraction ictal SPET co-registered to mri in partial epilepsy : Description and technical validation of the method with phantom and patient studies

Computer-aided subtraction of the co-registered and normalized interictal from the ictal single photon emission tomography (SPET) scan, followed by co-registration to the magnetic resonance image, may improve the utility of ictal SPET in the localization of partial epilepsy. This paper describes and technically validates our method. The SPET to SPET co-registration was tested using six sequential 99Tcm brain phantom SPET images of different known positions (15 matches). The registration error was determined by multiplying the calculated match transformation matrix by the inverse of the known transformation matrix. The ‘worst case’ co-registration error was less that one voxel diameter in all cases (median 3.2 mm, range 1.2–4.8 mm). For interictal to ictal SPET registrations in 10 consecutive intractable partial epilepsy patients, a similar root mean square distance (RMSD) between corresponding points on the matched scans was found as for the phantom studies (median 2.2 vs 2.6 mm). The appropriateness of our normalization was studied by comparing the pixel intensity distributions between the matched scans, and by analysing the subtraction pixel intensity distribution. The pixel intensity distribution for both the normalized phantom, and paired normalized patient studies, were closely matched to each other except for the extreme values, which in clinical situations likely represent regions of ictal activation or depression. The subtraction image intensity distributions were symmetrically centred on zero for all values up to at least within the 5th to 95th centile range, confirming good normalization for the ‘non-activated’ pixels. Also, a linear relationship was demonstrated between the measured pixel intensity on the phantom scans and the true changes in 99Tcm activity based on its decay constant. The results of this study demonstrate that our method produces accurate SPET to SPET co-registration, and appropriate SPET normalization, thereby allowing a valid ictal subtraction image to be derived.

Development of a test to measure gastric accommodation in humans

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of (99m)Tc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 +/- 11 (SE) ml and mean postprandial volume was 690 +/- 32 ml (P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Comparison of 18F-FDG and PiB PET in Cognitive Impairment

The purpose of this study was to compare the diagnostic accuracy of glucose metabolism and amyloid deposition as demonstrated by 18F-FDG and Pittsburg Compound B (PiB) PET to evaluate subjects with cognitive impairment. Methods: Subjects were selected from existing participants in the Mayo Alzheimers Disease Research Center or Alzheimers Disease Patient Registry programs. A total of 20 healthy controls and 17 amnestic mild cognitive impairment (aMCI), 6 nonamnestic mild cognitive impairment (naMCI), and 13 Alzheimer disease (AD) subjects were imaged with both PiB and 18F-FDG PET between March 2006 and August 2007. Global measures for PiB and 18F-FDG PET uptake, normalized to cerebellum for PiB and pons for 18F-FDG, were compared. Partial-volume correction, standardized uptake value (SUV), and cortical ratio methods of image analysis were also evaluated in an attempt to optimize the analysis for each test. Results: Significant discrimination (P < 0.05) between controls and AD, naMCI and aMCI, naMCI and AD, and aMCI and AD by PiB PET measurements was observed. The paired groupwise comparisons of the global measures demonstrated that PiB PET versus 18F-FDG PET showed similar significant group separation, with only PiB showing significant separation of naMCI and aMCI subjects. Conclusion: PiB PET and 18F-FDG PET have similar diagnostic accuracy in early cognitive impairment. However, significantly better group discrimination in naMCI and aMCI subjects by PiB, compared with 18F-FDG, was seen and may suggest early amyloid deposition before cerebral metabolic disruption in this group.

Characterization of the Solitary Pulmonary Nodule: 18F-FDG PET Versus Nodule-Enhancement CT

OBJECTIVE The purpose of this study was to directly compare nodule-enhancement CT and 18F-FDG PET in the characterization of indeterminate solitary pulmonary nodules (SPNs) greater than 7 mm in size. MATERIALS AND METHODS Examinations from patients undergoing both nodule-enhancement CT and 18F-FDG PET to characterize the same indeterminate SPN were reviewed. For nodule-enhancement CT, an SPN was considered malignant when it showed an unenhanced to peak contrast-enhanced increase in attenuation greater than 15 H. Fluorine-18-FDG PET studies were blindly reinterpreted by two qualified nuclear radiologists. SPNs qualitatively showing hypermetabolic activity greater than the mediastinal blood pool were interpreted as malignant. These interpretations were compared with the original prospective clinical readings and to semiquantitative standardized uptake value (SUV) analysis. Results were compared with pathologic and clinical follow-up. RESULTS Forty-two pulmonary nodules were examined. Twenty-five (60%) were malignant, and 17 (40%) were benign. Nodule-enhancement CT was positive in all 25 malignant nodules and in 12 benign nodules, with sensitivity and specificity of 100% and 29%, respectively, and with a positive predictive value (PPV) and negative predictive value (NPV) of 68% and 100%, respectively. Qualitative 18F-FDG PET interpretations were positive in 24 of the 25 malignant nodules and in four benign nodules. Fluorine-18-FDG PET was considered negative in one malignant nodule and in 13 of the 17 benign nodules. This correlates with a sensitivity and specificity of 96% and 76%, respectively, and with a PPV and NPV of 86% and 93%, respectively. Original prospective 18F-FDG PET and semiquantitative SUV analysis showed sensitivity, specificity, PPV, and NPV of 88%, 76%, 85%, and 81% and 84%, 82%, 88%, and 78%, respectively. CONCLUSION Due to its much higher specificity and only slightly reduced sensitivity, 18F-FDG PET is preferable to nodule-enhancement CT in evaluating indeterminate pulmonary nodules. However, nodule-enhancement CT remains useful due to its high NPV, convenience, and lower cost. Qualitative 18F-FDG PET interpretation provided the best balance of sensitivity and specificity when compared with original prospective interpretation or SUV analysis.

Comparison of positron emission tomography, computed tomography, and endoscopic ultrasound in the initial staging of patients with esophageal cancer

IntroductionImprovement in esophageal cancer staging is needed. Positron emission tomography (PET), computed tomography (CT), and endoscopic ultrasound (EUS) in the staging of esophageal carcinoma were compared.MethodsPET, CT, and EUS were performed and interpreted prospectively in 75 patients with newly diagnosed esophageal cancer. Either tissue confirmation or fine needle aspiration (FNA) was used as the gold standard of disease. Sensitivity and specificity for tumor, nodal, and metastatic (TNM) disease for each test were determined. TNM categorizations from each test were used to assign patients to subgroups corresponding to the three treatment plans that patients could theoretically receive, and these were then compared.ResultsLocal tumor staging (T) was done correctly by CT and PET in 42% and by EUS in 71% of patients (P value > 0.14). The sensitivity and specificity for nodal involvement (N) by modality were 84% and 67% for CT, 86% and 67% for EUS, and 82% and 60% for PET (P value > 0.38). The sensitivity and specificity for distant metastasis were 81% and 82% for CT, 73% and 86% for EUS, and 81% and 91% for PET (P value > 0.25). Treatment assignment was done correctly by CT in 65%, by EUS in 75%, and by PET in 70% of patients (P value > 0.34).ConclusionsEUS had superior T staging ability over PET and CT in our study group. The tests showed similar performance in nodal staging and there was a trend toward improved distant disease staging with CT or PET over EUS. Assignment to treatment groups in relation to TNM staging tended to be better by EUS. Each test contributed unique patient staging information on an individual basis.

The value of quantifying 18F-FDG uptake in thyroid nodules found incidentally on whole-body PET-CT.

ObjectiveTo determine if quantification of [18F]fluorodeoxyglucose (18F-FDG) uptake in a thyroid nodule found incidentally on whole-body 18F-FDG positron emission tomography–computed tomography (PET–CT) can be used to discriminate between malignant and benign aetiology. MethodsA retrospective review of all patients with focally high uptake in the thyroid as an incidental finding on 18F-FDG PET–CT from May 2003 through May 2006. The uptake in the nodules was quantified using the maximum standardized uptake value (SUVmax). The aetiology was determined by cytology and/or ultrasound, or on histopathology. ResultsIncidental focally high uptake was found in 79/7347 patients (1.1%). In 31/48 patients with adequate follow-up, a benign aetiology was determined. Median SUVmax for the benign group was 5.6, range 2.5–53. Malignancy was confirmed in 15/48 patients. The malignancies were papillary thyroid carcinoma in 12, metastasis from squamous cell carcinoma in one, and lymphoma in two. Median SUVmax for the malignant lesions was 6.4, range 3.5–16. Cytology suspicious for follicular carcinoma was found in 2/48 patients. No statistical difference (P=0.12) was found among the SUVmax between the benign and malignant groups. ConclusionFocally high uptake of 18F-FDG in the thyroid as an incidental finding occurred in 1.1% of the patients. Malignancy was confirmed or was suspicious in 17/48 (35%) of the patients that had adequate follow-up. There was no significant difference in the SUVmax between benign and malignant nodules.