High Uptake Group Research Articles

Subchondral Bone Condition and Intraoperative Grading of Cartilage Degeneration Underneath Patella Unrelated to the Clinical Outcome after TKA with Unresurfaced Patella.

The degree of cartilage degeneration assessed intraoperatively may not be sufficient as a criterion for patellar resurfacing in total knee arthroplasty (TKA). However, single-photon emission tomography/computed tomography (SPECT/CT) is useful for detecting osteoarthritic involvement deeper in the subchondral bone. The purpose of the study was to determine whether SPECT/CT reflected the cartilage lesion underneath the patella in patients with end-stage osteoarthritis (OA) and whether clinical outcomes after TKA without patellar resurfacing differed according to the severity of patellofemoral (PF) OA determined by visual assessment and SPECT/CT findings. This study included 206 knees which underwent TKA. The degree of cartilage degeneration was graded intraoperatively according to the International Cartilage Repair Society grading system. Subjects were classified into low and high uptake groups according to the degree of bone tracer uptake (BTU) on SPECT/CT in the PF joint. The Feller's patella score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were assessed preoperatively and postoperative 1 and 2 years. The increased BTU in the PF joint was associated with more severe degenerative cartilage changes underneath the patella (p < 0.001). The risk for the presence of denudated cartilage was greater in the high uptake group (odds ratio = 5.89). There was no association between clinical outcomes and visual grading of patellar cartilage degeneration or the degree of BTU on SPECT/CT. The visual assessment of the degree of cartilage degeneration underneath the patella and preoperative SPECT/CT evaluation of the PF joint were not predictive of clinical outcome after TKA with unresurfaced patella.

Physiologic colonic uptake of 18F-FDG on PET/CT predicts immunotherapy response and gut microbiome diversity in patients with advanced non-small cell lung cancer (NSCLC).

9600 Background: Immune checkpoint inhibitors (ICI) represent the backbone treatment of advanced non-small cell lung cancer (aNSCLC) patients. Emerging evidence suggests increased gut microbiome (GM) diversity is associated with favorable response. Conversely, antibiotic-induced dysbiosis may be associated with deleterious outcomes in patients receiving ICI in multiple retrospective studies and one prospective study. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics and could be a surrogate marker for GM diversity and therefore clinical response. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with outcomes and GM metagenomics in patients with advanced NSCLC. Methods: 71 patients with aNSCLC who underwent PET/CT prior to ICI were identified. For each patient, the colon was manually contoured, SUVmax was measured in each segment of the colon by a nuclear medicine specialist and average SUVmax was calculated for the whole colon. Patients were stratified in two groups according to median colon SUVmax (low vs high uptake). 18F-FDG physiologic colonic uptake was then compared to overall survival (OS), objective response (ORR), and progression-free survival (PFS). For patients with available stool samples (n = 10), GM composition was defined using metagenomics sequencing. Results: 71 patients (54% men, median age: 68 years) with aNSCLC were included in the study and ICI was the first line of therapy in 38% of those patients. The mean colon SUV for the low and high uptake groups were 1.41 (CI 95% 1.35-1.47) and 2.18 (CI 95% 1.90-2.46) respectively. The high uptake group had a higher proportion of non-responders (p = 0.033) and significant shorter PFS (4.1 months vs 11.3 months, p = 0.005). In the caecum, high uptake also correlated with numerically shorter OS (10.82 vs 27.56 months, p = 0.058) compared to low uptake group. Despite the low number of samples, metagenomics sequencing revealed that PLS-DA (Partial Least Squares Discriminant Analysis) for diversity was lower in the high SUV group (p = 0.008). Conclusions: Higher colon SUVmax on pre-ICI FDG PET/CT is associated with worse clinical outcomes and lower baseline GM diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a surrogate marker of GM diversity and predicts clinical outcomes.

Quantitative CD3 PET Imaging Predicts Tumor Growth Response to Anti-CTLA-4 Therapy.

A CD3 PET imaging agent targeting T cells was synthesized to test the role of such imaging as a predictive marker. The 89Zr-p-isothiocyanatobenzyl-deferoxamine-CD3 PET probe was assessed in a murine tumor xenograft model of anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy of colon cancer. Imaging on day 14 revealed 2 distinct groups of mice stratified by PET signal intensity. Although there was no significant difference in tumor volume on the day of imaging, in the high-uptake group subsequent measurements revealed significantly smaller tumors than in either the low-uptake group or the untreated controls. In contrast, there was no significant difference in the size of tumors between the low-uptake and untreated control mice. These findings indicate that high CD3 PET uptake in the anti-CTLA-4-treated mice correlated with subsequent reduced tumor volume and was a predictive biomarker of response.

Background Intestinal 18F-FDG Uptake Is Related to Serum Lipid Profile and Obesity in Breast Cancer Patients

BackgroundThis study investigated the relationships between background intestinal uptake on 18F–FDG PET and cardio-metabolic risk (CMR) factors.MethodsA total of 326 female patients that underwent 18F–FDG PET to determine the initial stage of breast cancer were enrolled. None of the patients had history of diabetes or hypertension. The background intestinal uptake on PET was visually graded (low vs. high uptake group) and quantitatively measured using the maximal standardized uptake value (SUVmax). SUVmax of 7 bowel segments (duodenum, jejunum, ileum, cecum, hepatic flexure, splenic flexure, and descending colon-sigmoid junction) were averaged for the total bowel (TB SUVmax). Age, body mass index (BMI), fasting blood glucose level (BST), triglyceride (TG), cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were the considered CMR factors. The relationships between background intestinal 18F–FDG uptake on PET and diverse CMR factors were analyzed.ResultsThe visual grades based on background intestinal 18F–FDG uptake classified 100 (30.7%) patients into the low uptake group, while 226 (69.3%) were classified into the high uptake group. Among CMR factors, age (p = 0.004), BMI (p<0.001), and TG (p<0.001) were significantly different according to visual grade of background intestinal 18F–FDG uptake. Quantitative TB SUVmax showed significant positive correlation with age (r = 0.203, p<0.001), BMI (r = 0.373, p<0.001), TG (r = 0.338, p<0.001), cholesterol (r = 0.148, p = 0.008), and LDL (r = 0.143, p = 0.024) and significant negative correlation with HDL (r = -0.147, p = 0.022). Multivariate analysis indicated that BMI and TG were independent factors in both visually graded background intestinal 18F–FDG uptake (p = 0.027 and p = 0.023, respectively) and quantitatively measured TB SUVmax (p = 0.006 and p = 0.004, respectively).ConclusionIncreased background intestinal 18F–FDG uptake on PET may suggest alteration of lipid metabolism and risk of cardio-metabolic disease in non-diabetic and non-hypertensive breast cancer patients.

Acceptability and feasibility of end‐of‐life care pathways in Australian residential aged care facilities

To investigate the acceptability and feasibility of using end-of-life (EOL) care pathways in residential aged care facilities (RACFs). Multistage action research approach involving interviews, surveys and prospective audits of deaths and EOL care pathway use among residents and staff of RACFs and associated general practitioners from 14 RACFs in Victoria and South Australia between April 2009 and July 2010. Introduction of EOL care pathways. Evidence of acceptability was determined by the rate of pathway use in RACFs and through feedback from RACF managers, staff and GPs. Evidence of feasibility was determined by reductions in transfers to hospital for symptom management before death, length of time on pathways, and whether care was consistent with best practice at EOL. The use of EOL care pathways across the RACFs fell into low-, moderate- and high-uptake groups (for 10%, 34% and 68% of all deaths at the facility, respectively). Feedback from RACF staff and GPs indicated that acceptability was critical to successful implementation. The use of EOL care pathways demonstrated improvements in care, sometimes over extended periods. There were fewer unnecessary admissions to hospital before death, although not all RACF staff and GPs were aware of the project. EOL care pathways are feasible strategies for delivering EOL care consistent with best practice. However, their introduction into Australian RACFs needs to include strategies to facilitate acceptability by RACF staff and GPs.

Relationship between Pretreatment FDG Uptake and Local Control after Stereotactic Body Radiotherapy in Stage I Non-small-cell Lung Cancer: The Preliminary Results

Relationship between pretreatment uptake of (18)F-fluoro-2-deoxy-d-glucose and local control after stereotactic body radiotherapy in stage I non-small-cell lung cancer was examined. Between June 2006 and June 2009, 90 clinically diagnosed stage I primary lung cancer in 86 patients were treated with stereotactic body radiotherapy in Shikoku Cancer Center. Among these, 51 tumors in 51 patients were evaluated by positron emission tomography using (18)F-fluoro-2-deoxy-d-glucose before treatment. Twenty-six tumors of histopathologically confirmed non-small-cell lung cancer were reviewed in this study. Tumors were divided into two groups by the threshold maximum standardized uptake value of 5.0 (high-uptake tumors, 9; low-uptake tumors, 17). One tumor with low uptake was pure ground-glass opacity. Typically, 48 Gy in four fractions was given at the isocenter. Follow-up time was 4-44 months (median, 21 months). Local failure-free rates at 15 months of the high-uptake group and the low-uptake group were 40% and 93% for all tumors (P= 0.0001), 0% and 91% for tumors 3 cm or less (P= 0.0004), 50% and 100% for tumors larger than 3 cm, and 40% and 89% for the mainly solid tumors (P= 0.0010). There were no statistically significant differences of local failure-free rates according to age, sex and tumor size (P= 0.4804, P= 0.4170 and P= 0.3638, respectively). High uptake of (18)F-fluoro-2-deoxy-d-glucose in a primary tumor was the significant unfavorable factor for local control after stereotactic body radiotherapy in stage I non-small-cell lung cancer.

FDG-PET for prediction of survival of patients with metastatic colorectal carcinoma

The current study focuses on the prognostic value of pretreatment metabolic activity in metastases as measured with [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), as an indicator of survival in colorectal cancer. In a prospective series of 152 patients with metastatic colorectal cancer, of whom 67 were treated with resection of metastases and 85 with chemotherapy, standardized uptake values (SUV) as measured with FDG-PET, were calculated prior to treatment. Survival probabilities were estimated by Cox proportional regression analysis. For Kaplan-Meier analysis SUV was stratified by the median value. Survival differences were assessed using the log-rank test. SUV in metastases was a significant predictor for overall survival (hazard ratio 1.17, 95% confidence interval 1.06-1.30, P = 0.002), independent of the subsequent treatment. According to the median value of the patient population a low (SUV <4.26) and high uptake group (SUV >4.26) was defined. The median survival and the 2- and 3-year survival rates were 32 months, 59% and 45%, respectively, in the low-uptake group and 19 months, 37% and 28%, respectively, in the high-uptake group (P = 0.017). A significant survival benefit was observed in patients with low FDG uptake in metastases of colorectal cancer.

Clinicopathologic and technical factors associated with the uptake of radiocolloid by sentinel nodes in patients with breast cancer.

Sentinel-node biopsy is becoming widely accepted in breast cancer treatment. Using the radioisotope technique, a lower risk of identification failure is related to the amount of radiocolloid in the sentinel nodes. The aim of this study was to identify the factors associated with the colloidal uptake of the sentinel nodes. Technetium-labeled colloid was injected peritumorally, with or without subdermal injection. According to the maximum radioactivity of the sentinel nodes, patients were divided into high (>/=100 counts/s) or low (<100 counts/s) uptake groups. The uptake was compared in relation to the clinicopathologic and technical features. The sentinel node was identified in 183 of 186 patients (98.4%), with 60 and 123 patients in the low- and high-uptake groups (mean: 39 and 1003 counts/s), respectively. Multivariate analysis showed that an age of 65 years or older and a sentinel-node size of 8 mm or more were significantly more predominant in the low-uptake group. Care must be taken when performing sentinel-node biopsy, especially for aged patients and for those with large sentinel nodes. The optimal technique should be determined on the basis of these results.

ANTI-CD45 MONOCLONAL ANTIBODY PERFUSION OF HUMAN RENAL ALLOGRAFTS PRIOR TO TRANSPLANTATION A SAFETY AND IMMUNOHISTOLOGICAL STUDY

The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.

Prognostic significance of in vitro thymidine uptake in patients with colorectal carcinoma.

In 127 patients with colorectal carcinoma, we measured thymidine uptake by tumor cells cultured in a semisolid medium and compared the influence of various parameters on survival by univariate and multivariate analysis. Fifty-four of the 127 carcinomas (42.5%) incorporated > 1,000 cpm of tritiated thymidine per culture dish and were designated as the high-uptake group, while the other tumors (57.5%, 73/127) were designated as the low-uptake group. There was no significant correlation between high or low thymidine uptake and most of the clinicopathological characteristics of the patients. Patients in the high-uptake had a poor prognosis and a 7-year survival rate of 32.6%, which was significantly different from the rate of 69.3% in the low-uptake group (P < 0.0005). Multivariate analysis showed that thymidine uptake was one of the variables strongly associated with survival in our study population. Thus, it is concluded that thymidine uptake by tumor cells has a high capacity of predicting prognosis, independent of its relationship to other variables. Furthermore, it seems to us that thymidine uptake can help in selecting those patients with colorectal carcinoma who are most likely to benefit from perioperative adjuvant therapy.

Thymidine uptake in vitro as a prognostic indicator for primary gastric cancer.

Prognostic significance of in vitro thymidine uptake by cancer cells remains unclear in patients with gastric cancer. In 173 patients with operable gastric cancer, the relations between thymidine uptake by gastric cancer cells in semi-solid media and their clinicopathologic features as well as their survival lengths were studied. There were significant correlations between in vitro thymidine uptake and such clinicopathologic features as lymph node metastasis (P = 0.00002), lymphatic invasion (P = 0.003), vessel invasion (P = 0.006), peritoneal metastasis (P = 0.010), depth of invasion (P = 0.011), and hepatic metastasis (P = 0.032). Ninety-five of 173 cancers (54.9%) that incorporated 1000 or more cpm in a single well were designated as being a high uptake group. Other gastric cancers (78 of 173; 45.1%) were designated as being a low uptake group. The overall survival rate of the patients was demonstrated to be significantly longer in the group with a low thymidine uptake than with a high uptake (P < 0.00001). The multivariate analysis showed that thymidine is one of the two variables that are the most highly correlated with the probability of patient death (P = 0.00044). These results indicated that in vitro thymidine uptake is an independent prognostic parameter for gastric cancer and may be useful for selecting patients who would benefit from more intensive therapy.

Patterns of care in a district general hospital psychiatric department.

A survey of all admissions of patients under the age of 65 during the first 6 years of a District General Psychiatric Department without mental-hospital support is reported. Three high-uptake groups of in-patients were defined; the long-stay (12 months or more), the medium-stay (6-12 months), and the revolving-door group (more than three admissions in any period of 12 months). Identifying characteristics which distinguish between these groups were examined. During a 7-year period there was no accumulation of long-stay patients, and a striking lack of schizophrenic patients who remained in hospital for more than 6 months or who had more than three admissions in any twelve-month period. This was not accounted for by drift of the high-uptake groups out of contact with the service, but may be related both to the style of service provision and to the socially cohesive nature of the area under study. Local variation should be given due importance when community services are being developed.

Measurement of Surface Temperature in Lung Cancer

We measured the surface temperature of the tumors in 27 patients with primary lung cancer, using a flexible bronchofiberscope and a thermometer made from chromel-constantan. The thermometer was inserted into the aspiration channel of the bronchofiberscope, and temperature was studied under bronchofiberscopic located in the central portion of the lung were higher than those of the carina of the trachea (P less than 0.01), truncus superior (P less than 0.01), or truncus inferior (P less than 0.05), and almost equal to those of the peripheral lung. Thus, lung cancer showed a significantly higher surface temperature. When 67Ga scintigraphy was performed in 22 patients with lung cancer, the temperature of the high-uptake group was higher than that of the low-uptake group.

Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls

Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O 1, O 2, O z, C 3 and C 4 to combined ear reference (A 1A 2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman-Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.