Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. PATIENTS AND METHODS: In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. RESULTS: In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. CONCLUSION: This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

FAPI PET uptake patterns after invasive medical interventions: a single center retrospective analysis.

PURPOSE: Fibroblast activation protein (FAP)-inhibitor (FAPI)-PET tracers allow imaging of the FAP-expressing cancer associated fibroblasts (CAF) and also the normal activated fibroblasts (NAF) involved in inflammation/fibrosis that may be present after invasive medical interventions. We evaluated [68Ga]Ga-FAPI-46 uptake patterns post-medical/invasive non-systemic interventions. METHODS: This single-center retrospective analysis was conducted in 79 consecutive patients who underwent [68Ga]Ga-FAPI-46 PET/CT. Investigators reviewed prior patient medical/invasive interventions (surgery, endoscopy, biopsy, radiotherapy, foreign body placement (FBP) defined as implanted medical/surgical material present at time of scan) and characterized the anatomically corresponding FAPI uptake intensity both visually (positive if above surrounding background) and quantitatively (SUVmax). Interventions with missing data/images or confounders of [68Ga]Ga-FAPI-46 uptake (partial volume effect, other cause of increased uptake) were excluded. Available correlative FDG, DOTATATE and PSMA PET/CTs were analyzed when available. RESULTS: 163 medical/invasive interventions (mostly surgeries (49%), endoscopies (18%) and non-surgical biopsies (10%)) in 60 subjects were included for analysis. 43/163 (26%) involved FBP. FAPI uptake occurred in 24/163 (15%) of interventions (average SUVmax 3.2 (mild), range 1.5-5.1). The median time-interval post-intervention to FAPI-PET was 47.5 months and was shorter when FAPI uptake was present (median 9.5 months) than when absent (median 60.1 months; p = 0.001). Cut-off time beyond which no FAPI uptake would be present post-intervention without FBP was 8.2 months, with a sensitivity, specificity, positive predictive value and negative predictive value of 82, 90, 99 and 31% respectively. No optimal cutoff point could be determined when considering interventions with FBP. No significant difference was detected between frequency of [68Ga]Ga-FAPI-46 and [18F]FDG uptake in intervention sites. Compared to [68Ga]Ga-PSMA-11, [68Ga]Ga-FAPI-46 revealed more frequent and intense post-interventional tracer uptake. CONCLUSION: [68Ga]Ga-FAPI-46 uptake from medical/invasive interventions without FBP appears to be time dependent, nearly always absent beyond 8 months post-intervention, but frequently present for years with FBP.

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Efficacy of cell proliferation imaging with 4DST PET/CT for predicting the prognosis of patients with esophageal cancer: a comparison study with FDG PET/CT.

PURPOSE: 4'-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer used for cell proliferation imaging. The aim of this study was to evaluate the prediction of prognosis with pretreatment 4DST PET/CT compared to fluorodeoxyglucose (FDG) PET/CT in patients with esophageal cancer. METHODS: In this prospective study, we analyzed 46 patients (68.2 ± 10.0 years old) with pathologically proven esophageal squamous cell cancer who underwent pretreatment 4DST and FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion proliferation (TLP) were measured for FDG and 4DST PET. The study endpoints were progression-free survival (PFS) and overall survival (OS). Patients' clinical backgrounds, including age, histological type, clinical stage, and surgical treatment, were adjusted using the Cox proportional-hazards model. RESULTS: In the follow-up period (median 18.8 (interquartile range: 10.1-29.0) months), 26 and 19 patients showed disease progression and cancer-related death, respectively. After adjusting for clinical variables, only the 4DST parameters (SUVmax (p = 0.001) and TLP (p = 0.022)) were statistically significant for predicting PFS. FDG MTV (p = 0.031), 4DST SUVmax (p = 0.022), and TLP (p = 0.023) were statistically significant for predicting OS. Of the PET parameters, 4DST SUVmax yielded the highest adjusted hazard ratio for both PFS (4.88, 95% confidence intervals (CI): 1.83-12.97) and OS (4.19, 95% CI: 1.23-14.20). CONCLUSION: Higher accumulation of 4DST in the primary tumor may lead to shorter OS and PFS. 4DST PET/CT is useful for predicting prognosis and may outperform FDG PET/CT.

Clinical and radiological findings of silent hypoxia among COVID-19 patients.

The aim of this study was to describe the clinical and radiological findings of COVID-19 patients with "silent hypoxia," who had no dyspnea on admission even though their oximetry saturation was less than 94%. This retrospective cohort study included all COVID-19 patients (n = 270) at a large tertiary care hospital between January 31 and August 31, 2020. Clinical and radiological characteristics of patients who met our criteria of "silent hypoxia", which included those who reported no dyspnea even though oximetry saturation was <94%, were extracted. Eight patients (3.0%) met the criteria for "silent hypoxia." The median age was 61 years (interquartile range [IQR]: 48.8-72.3), and five (62.5%) were men. All patients had consolidation on CT and showed a moderate to high COVID-19 CT severity score (median: 13.5, IQR: 10.8-15.3). The median FIO2 of the maximum oxygen required was 55 (IQR: 28-70)%. Two patients (25.0%) were intubated, and one patient (12.5%) underwent extracorporeal membrane oxygenation. Some COVID-19 patients with "silent hypoxia" may develop severe disease. Close and accurate monitoring of patients using arterial blood gas and pulse oximetry is necessary, regardless of their symptoms.

Pseudomyxoma peritonei: visceral scalloping on CT is a predictor of recurrence after complete cytoreductive surgery.

OBJECTIVES: Pseudomyxoma peritonei (PMP) is characterized by peritoneal dissemination of gelatinous ascites following rupture of a mucinous tumor. Treatment by cytoreductive surgery (CRS) has improved its prognosis. Although visceral scalloping, notably liver scalloping, on computed tomography (CT) is a typical feature of PMP, its prognostic value remains unknown. We aimed to investigate the efficacy of liver scalloping in predicting recurrence in PMP patients. METHODS: Among 159 consecutive patients with PMP who had contrast-enhanced CT between September 2012 and December 2018, 64 treatment-naïve patients who subsequently underwent CRS with complete resection (i.e., completeness of cytoreduction score (CC)-0 or CC-1), were included in analysis. Presence of liver scalloping and maximum thickness of mucin deposition at the liver surface were evaluated on CT. Disease-free survival (DFS) was determined based on the combination of postoperative CT features and tumor marker values. RESULTS: Median follow-up was 24.3 months. CT revealed liver scalloping in 40/64 (63.4%) patients. Kaplan-Meier analysis showed significantly shorter DFS in patients with scalloping than in those without (p = 0.001; hazard ratio, 4.3). In patients with scalloping, greater mucin deposition (thickness ≥ 20 mm) significantly correlated with poorer DFS (p = 0.042). In multivariate Cox proportional hazards regression including CC status, pathologic type, and tumor markers, the presence of scalloping independently and significantly correlated with DFS (p = 0.031). CONCLUSIONS: Liver scalloping was an independent predictor even after adjusting for clinical covariates. The presence of liver scalloping can lead to a high recurrence rate after CRS. KEY POINTS: • The presence of liver scalloping is a prognostic factor independent of histological grade and tumor markers. • Greater mucin deposition (thickness ≥ 20 mm at the liver surface) is associated with higher recurrence rates in patients with liver scalloping.

Significance of 11C-PIB PET/CT in cardiac amyloidosis compared with 99mTc-aprotinin scintigraphy: A pilot study.

BACKGROUND: This study was to investigate the significance of 11C-Pittsburgh B (PIB) PET/CT in patients with suspected cardiac amyloidosis compared with 99mTc-aprotinin scintigraphy. METHODS: Thirteen consecutive patients with suspected cardiac amyloidosis were considered for enrolment in this prospective pilot study. Participants were scheduled to undergo a series of 11C-PIB PET/CT and 99mTc-aprotinin within a 2-month period. Finally, we evaluated nine cases who underwent both imaging modalities, and compared imaging results with clinical and pathological results and prognosis. RESULTS: Six of the 9 patients who underwent both imaging modalities were diagnosed with amyloidosis, of whom 3 patients were diagnosed with cardiac amyloidosis from endomyocardial biopsy. These 3 patients with positive 11C-PIB uptake at the left ventricle wall showed worsening of cardiac function progressing in the short term or death caused by acute exacerbation of chronic heart failure. Six of 8 patients with positive uptake on 99mTc-aprotinin presented with amyloid deposition in the left ventricle wall, but symptoms remained stable if results of 11C-PIB were not positive. CONCLUSION: In a small sample of subjects, the present study showed that 11C-PIB accumulation in myocardium indicated cardiac amyloidosis with poor prognosis. Uptake of 11C-PIB may be related to progressive amyloid deposition to the heart and can predict patient prognosis.

Correction to: Performance of 99mTc-aprotinin scintigraphy for diagnosing light chain (AL) cardiac amyloidosis confirmed by endomyocardial biopsy.

This prospective study was conducted according to the principles outlined within the Declaration of Helsinki, and approved by the Ethics Review Board of National Center for Global Health and Medicine (NCGM-G-00839-01, NCGM-G-00839-02).

Performance of 99mTc-aprotinin scintigraphy for diagnosing light chain (AL) cardiac amyloidosis confirmed by endomyocardial biopsy.

BACKGROUND: Light chain (AL) cardiac amyloidosis is associated with a poor prognosis. Diagnosing at an early stage is critical for treatment and the management of cardiac complication. PURPOSE: We aimed to evaluate the diagnostic performance of 99mTc-aprotinin images in patients with AL cardiac amyloidosis. METHODS AND RESULTS: 99mTc-aprotinin scintigraphy and endomyocardial biopsy were performed in 10 patients with suspected amyloidosis. Endomyocardial biopsy showed amyloid deposits in 5 of 10 patients. 99mTc-aprotinin (planer image) was positive in 4 of 5 patients who had amyloid deposits in endomyocardial biopsy. On the other hand, all 5 patients without amyloid deposits were negative in planer image. 99mTc-aprotinin (SPECT/CT image) was positive in all 5 patients who had amyloid deposits. CONCLUSIONS: 99mTc-aprotinin scintigraphy is valuable for the non-invasive diagnosis of AL cardiac amyloidosis.

Radionuclide Imaging of Cardiac Amyloidosis and Sarcoidosis: Roles and Characteristics of Various Tracers.

Amyloidosis and sarcoidosis are systemic diseases that affect multiple organ systems. Accurate diagnosis of cardiac amyloidosis and sarcoidosis is particularly important because cardiac involvement can be fatal. Amyloidosis is characterized by the deposition of amyloid fibrils, and cardiac amyloidosis is classified into amyloid immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) types. Radionuclide tracers for amyloidosis include (a) bone tracers, (b) amyloid-directed molecules, and (c) PET amyloid agents. Bone tracers are particularly sensitive in detection of ATTR type amyloidosis, whereas PET amyloid agents show a higher affinity for the AL type. In sarcoidosis, gallium 67 (67Ga) citrate scintigraphy and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET are pivotal to diagnosis of cardiac sarcoidosis, and 18F-FDG PET/CT has particularly high efficacy in detection of sarcoidosis and monitoring of response to therapy. A major limitation of 18F-FDG is physiologic uptake in the myocardium, which can remain in approximately 20% of patients even after elaborate preparation (eg, prolonged fasting >12-18 hours, modification to a high-fat and low-carbohydrate diet, and injection of unfractionated heparin). This limitation has led to a search for potential new tracers. Recently introduced tracers that show promise include those used in somatostatin receptor imaging and cellular proliferation imaging, which provide detectability as high as that for 18F-FDG without requiring dietary restrictions and have potential for monitoring disease activity. ©RSNA, 2020.

Fluorodeoxyglucose PET/CT of Arthritis in Rheumatic Diseases: A Pictorial Review.

Rheumatic diseases are various painful conditions that affect joints, bones, cartilage, tendons, ligaments, and muscles. Arthritis is a typical condition of rheumatic disease. Although rheumatoid arthritis is a representative rheumatic disease, various diseases other than rheumatoid arthritis can also affect joints, and differential diagnosis of rheumatic diseases is often difficult owing to the similar clinical manifestations. However, accurate diagnosis is crucial for an appropriate treatment strategy. The utility of fluorine 18 fluorodeoxyglucose (FDG) PET/CT has been established, and it is widely used for assessing malignancies. In addition to accumulating in tumor cells, FDG also accumulates in inflammatory tissue, allowing FDG PET/CT to demonstrate arthritis. PET/CT allows evaluation of whole-body articular and extra-articular lesions in one examination, representing a key advantage over US and MRI, which allow assessment of only a few regions because of their limited field of view. Although FDG PET/CT is sensitive for detecting inflammatory lesions, the uptake itself is nonspecific; therefore, knowledge of characteristic uptake patterns is necessary to narrow the differential diagnosis in rheumatic disease. Furthermore, pathognomonic extra-articular findings such as vasculitis, skin lesions, lymphadenopathy, and chondritis play an important role in achieving accurate diagnosis. The authors present the FDG PET/CT appearances of (a) rheumatoid arthritis and allied disorders (polymyalgia rheumatica, remitting seronegative symmetrical synovitis with pitting edema, adult-onset Still disease), (b) spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease arthritis, SAPHO [synovitis, acne, pustulosis, hyperostosis, and osteitis] syndrome, chronic recurrent multifocal osteomyelitis), and (c) miscellaneous systemic disorders with arthropathy (relapsing polychondritis, multicentric reticulohistiocytosis, amyloidosis, sarcoidosis, hemophilia). ©RSNA, 2020.

Impact of a modified peritoneal cancer index using FDG-PET/CT (PET-PCI) in predicting tumor grade and progression-free survival in patients with pseudomyxoma peritonei.

OBJECTIVES: The peritoneal cancer index (PCI) is widely used for assessing pseudomyxoma peritonei (PMP) in surgery. The aim of this study was to evaluate the utility of a modified PCI using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT (PET-PCI) for predicting pathologic grade and progression-free survival (PFS) in patients with PMP. METHODS: Thirty-five patients who underwent 18F-FDG-PET/CT before cytoreductive surgery and/or hyperthermic intraperitoneal chemotherapy were enrolled. PET-PCI was determined by summing up the visually scored 18F-FDG uptake of PMP lesions in 13 specific abdominal-pelvic regions. Uptake score was defined as 0, no lesion or lesion without uptake; 1, slight uptake less than or equivalent to mediastinal blood pool; 2, moderate uptake above mediastinal but below or equal to liver; and 3, intense uptake moderately to markedly higher than liver. SUVmax of the lesion was also evaluated. RESULTS: Pathologic diagnosis revealed 19 patients with low-grade PMP and 16 patients with high-grade PMP. Patients with high-grade PMP showed significantly higher PET-PCI and SUVmax than patients with low-grade PMP (PET-PCI 14.8 vs. 8.7, p = 0.007; SUVmax 3.6 vs. 2.6, p = 0.013). Using a cutoff PET-PCI of 12, Kaplan-Meier analyses showed a significant difference in PFS between patients with high and low PET-PCI (p < 0.001; hazard ratio (HR), 12.4). For SUVmax, the optimal cutoff was 2.7 and the correlation with PFS was also significant (p = 0.008; HR, 4.7). In multivariate Cox proportional-hazards regression, PET-PCI was independently and significantly correlated with PFS. CONCLUSIONS: PET-PCI can reflect histopathologic features and appears useful for predicting recurrence in patients with PMP. KEY POINTS: • Peritoneal cancer index using 18F-FDG-PET/CT (PET-PCI) has great potential for predicting progression-free survival in patients with pseudomyxoma peritonei. • PET-PCI provides higher prognostic performance than maximum standardized uptake value (SUVmax). • PET-PCI shows high correlation with histopathologic grade of pseudomyxoma peritonei.

Histological analysis of vasculopathy associated with pulmonary hypertension in combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis or emphysema alone.

AIMS: To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema (CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis (IPF) alone and emphysema alone. METHODS AND RESULTS: We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups (P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular (P = 0.004) and arteriolar (P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. CONCLUSIONS: These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases.

Characterizing Normal Variant [68Ga]Ga-FAPI-46 Uptake in the Epididymis.

The biodistribution of fibroblast activation protein inhibitor (FAPI) PET tracers includes the kidneys, bladder, uterus, breast, muscles, and bone marrow. We describe its occasional uptake patterns in the epididymis. Methods: Epididymal [68Ga]Ga-FAPI-46 uptake was retrospectively analyzed in 55 PET/CT studies of 55 men. Uptake intensity (SUV), pattern (diffuse, focal, or multifocal), laterality, and location (epididymal head with or without body/tail) were analyzed. Electronic medical records were reviewed to determine the presence of epididymis-related disease. Results: Epididymal [68Ga]Ga-FAPI-46 uptake was observed in 8 of 55 (15%) subjects, with bilateral epididymal head uptake in all cases and epididymal body/tail uptake in 6 of 8 (75%) cases, 5 of 6 (83%) bilaterally and 1 of 6 (17%) unilaterally. The average SUVmax was greater in the epididymal heads than in the epididymal bodies/tails, with an SUVmax of 4.1 versus 3.0 (P < 0.001). No subject had epididymal disease related to the uptake. Conclusion: [68Ga]Ga-FAPI-46 uptake in the epididymis occurs occasionally and does not appear related to epididymal disease.

Visual and whole-body quantitative analyses of 68 Ga-DOTATATE PET/CT for prognosis of outcome after PRRT with 177Lu-DOTATATE.

BACKGROUND: Somatostatin receptors (SSTR) represent an ideal target for nuclear theranostics applications in neuroendocrine tumors (NET). Studies suggest that high uptake on SSTR-PET is associated with response to SSTR peptide receptor radionuclide therapy (PRRT). The purpose of this study was to evaluate the role of baseline whole-body (WB) 68 Ga-DOTATATE PET/CT (SSTR-PET) quantitative parameters, and the presence of NET lesions without uptake on SSTR-PET, as outcome prognosticator in patients with NET treated with PRRT. METHODS: Patients with NET who underwent at least 4 177Lu-DOTATATE PRRT cycles between 07/2016 and 03/2021 were included in this retrospective analysis if they fulfilled the following inclusion criteria: SSTR-PET within 6 months of 1st PRRT cycle, follow-up CT and/or MRI performed > 6 months after the 4th cycle of PRRT. The SSTR-PET analysis consisted of a visual and a quantitative analysis done independently by two board-certified physicians. The visual analysis assessed the presence of NET lesions visible on the SSTR-PET co-registered CT. The quantitative analysis consisted in contouring all SSTR-avid lesions on SSTR-PET and extracting WB quantitative parameters: SUVmean (WB-SUVmean), SUVmax of the lesion with highest uptake (H-SUVmax), and tumor volume (WB-TV). WB-SSTR-PET parameters and the presence of SSTR-PET-negative lesions were correlated to radiologic response (assessed by RECIST 1.1 criteria) and progression-free survival (PFS). Fisher's exact test, Mann-Whitney's U test and Kaplan-Meier curves with Cox-regression analysis were used for the statistical analysis. RESULTS: Forty patients (F/M: 21/19; 34/40 with gastro-entero-pancreatic (GEP) NET, 6/40 with non-GEP NET) were included in the analysis. The median follow-up period after the 4th PRRT cycle was 25.7 months (range 15.2-59.1). Fourteen/40 (35%) patients showed radiologic response (RECIST PR). PFS event was observed in 17/40 (42.5%) patients. Thirteen/40 (32.5%) patients had SSTR-PET-negative lesions at baseline. Higher WB-SUVmean and H-SUVmax were associated with better response (p = 0.015 and 0.005, respectively). The presence of SSTR-PET-negative lesions and lower WB-SUVmean were associated with shorter PFS (p = 0.026 and 0.008, respectively). CONCLUSION: Visual and quantitative analyses of baseline SSTR-PET can yield valuable information to prognosticate outcomes after 177Lu-DOTATATE PRRT.