Relationship between Eating Alone and Handgrip Strength in Korean Older Adults.

Sarcopenia is defined as an age-related decline in muscle mass, muscle strength, and physical performance. Eating alone has been linked to various health issues in older adults. This study investigated the relationship between eating alone and handgrip strength (HGS) in older adults using data from 7278 individuals (≥65 years) who participated in the 2014-2019 Korea National Health and Nutrition Examination Survey. HGS was measured using a digital grip strength dynamometer, relative HGS was calculated by dividing HGS by body mass index, and dynapenia was defined as an HGS < 28 kg for men and <18 kg for women. Multivariable logistic regression analysis showed that women who ate two meals alone were more likely to exhibit dynapenia than those who never ate alone (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.03-1.77). If the groups that never ate alone or ate one meal alone were combined as the reference group, the probability of dynapenia was higher in the combined groups that ate two or three meals alone (OR, 1.25; 95% CI, 1.04-1.50). No association was observed between eating alone and dynapenia in men. This suggests that eating alone is a modifiable related factor of dynapenia in older women.

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer.

BACKGROUND: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). AIM: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT. METHODS: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT. RESULTS: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes. CONCLUSION: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

Efficacy of preoperative lymphoscintigraphy in predicting surgical outcomes of lymphaticovenous anastomosis in lower extremity lymphedema: Clinical correlations in gynecological cancer-related lymphedema.

BACKGROUND: Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA. METHODS: A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA. RESULTS: Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes. CONCLUSION: The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.

The effects of low-dose radiation therapy in patients with mild-to-moderate Alzheimer's dementia: an interim analysis of a pilot study.

PURPOSE: We aimed to determine whether low-dose radiotherapy (LDRT) is effective in patients with Alzheimer disease (AD). MATERIALS AND METHODS: We included patients according to the following criteria: probable Alzheimer's dementia according to the New Diagnostic Criteria for Alzheimer's Disease; confirmation of amyloid plaque deposits on baseline amyloid positron emission tomography (PET); a Korean Mini-Mental State Examination 2nd edition (K-MMSE-2) score of 13-26; and a Global Clinical Dementia Rating (CDR) score of 0.5-2 points. LDRT was performed six times at 0.5 Gy each. Post-treatment cognitive function tests and PET-CT examinations were performed to evaluate efficacy. The medication for AD treatment was maintained throughout the study period. RESULTS: At 6 months after LDRT, neurological improvement was seen in 20% of patients. Patient #2 showed improvement in all domains of the Seoul Neuropsychological Screening Battery II (SNSB-II). Moreover, the K-MMSE-2 and Geriatric Depression Score-Short Form scores improved from 20 to 23 and from 8 to 2, respectively. For patient #3, the CDR score (sum of box score) improved from 1 (4.0) to 1 (3.5) at 3 months follow-up. Moreover, the Z scores for language and related functions, memory, and frontal executive function improved to -2.56, -1.86, and -1.32, respectively at the 6-month follow-up. Two patients complained of mild nausea and mild hair loss during LDRT, which improved after treatment. CONCLUSION: One of the five patients with AD treated with LDRT experienced a temporary improvement in SNSB-II. LDRT is tolerable in patients with AD. We are currently under follow-up and will conduct cognitive function tests after 12 months after LDRT. A large-scale randomized controlled trial with a longer follow-up period is warranted to determine the effect of LDRT on patients with AD.

Salivary Gland Uptake on 18F-FP-CIT PET as a New Biomarker in Patients With Parkinsonism.

OBJECTIVE: 18F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on 18F-FP-CIT PET as a new biomarker in patients with parkinsonism. MATERIALS AND METHODS: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed 18F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. RESULTS: The SUVR in early 18F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). CONCLUSION: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early 18F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase 18F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

In vivo tissue pharmacokinetics of ERBB2-specific binding oligonucleotide-based drugs by PET imaging.

Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer-drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image-based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine-18-labeled aptamers with erb-b2 receptor tyrosine kinase 2 (ERBB2)-specific binding were synthesized by base-pair hybridization using a complementary oligonucleotide platform. To investigate the PKs and properties of in vivo tissue, usefulness of in vivo PET imaging in the development of an oligonucleotide-based drug as an assessment tool was evaluated in normal and tumor xenografted mice. ERBB2-cODN-idT-APs-[18 F]F ([18 F]1), injected intravenously showed significant and rapid uptake in most tissues except for the initial brain and muscle; the uptake was highest in the heart, followed by kidneys, liver, lungs, gall bladder, spleen, and stomach. The main route of excretion was through the renal tract ~77.8%, whereas about 8.3% was through the biliary tract of the total dose. The estimated effective dose for an adult woman was 0.00189 mGy/MBq, which might be safe. ERBB2-positive tumor could be well visualized in the KPL4 xenograft animal model by in vivo PET imaging. Consequently, the distribution in each organ including ERBB2 expression could be well determined and quantified by PET with fluorine-18-labeled aptamers. In vivo PK parameters such as terminal half-life, time to maximum concentration, area under the curve, and maximum concentration, were also successfully estimated. These results suggest that image-based PET with radioisotope-labeled aptamers could be provide valuable information on properties of oligonucleotide-based drugs in drug discovery of targeted therapeutics against various diseases.

Clinical Impact of SPECT/CT in Evaluation of Abdominothoracic Fistula.

ABSTRACT: Abdominothoracic fistula is rarely observed but can be life-threatening. Pleuroperitoneal communication, known to occur in 1.6% of all patients who undergo continuous ambulatory peritoneal dialysis, is an uncommon but well-recognized complication. The most common symptoms are dyspnea and right-sided pleural effusion. A biliopleural fistula is well-described as a complication of radiofrequency ablation and transcatheter arterial chemoembolization of hepatic lesions. It is important to diagnose the cause of pleural effusion early for proper treatment because if the abdominothoracic fistula effusion amount is not large, appropriate diagnosis may be difficult. Here, we introduce 2 cases showing the usefulness of SPECT/CT in evaluating pleuroperitoneal and biliopleural fistulas.

Potential Utility of SPECT/CT for Early Detection of Spontaneous Osteonecrosis of the Knee.

ABSTRACT: Spontaneous osteonecrosis of the knee (SONK) is the most common phenotype of osteonecrosis of knee joints in older adults. Early diagnosis with appropriate management is crucial for improving the prognosis of the SONK. We present SONK in bone scintigraphy and SPECT/CT in 65-year-old man with sudden worsening knee pain and normal radiographs. SPECT/CT revealed intense uptake in subchondral area of left femoral medial condyle, which can be differed from progressed osteoarthritic change of the knee joints suspected on planar scintigraphy. Subsequently performed MRI showed characteristic finding of SONK. Total knee replacement arthroplasty was performed with final histological diagnosis of SONK.

Feasibility of 18F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

Imaging techniques for diagnosing muscle atrophy and sarcopenia remain insufficient, although various advanced diagnostic methods have been established. We explored the feasibility of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) for evaluating skeletal muscle atrophy, as an imaging technique that tracks choline level changes in muscles. Cell uptake in L6 cells by 18F-FCH was performed in a complete medium containing serum (untreated group, UN) and a serum-free medium (starved group, ST). Small-animal-dedicated PET/CT imaging with 18F-FCH was examined in in-vivo models with rats that were starved for 2 days to cause muscle atrophy. After the hind limbs were dissected, starvation-induced in-vivo models were anatomically confirmed by reverse-transcription polymerase chain reaction to evaluate the expression levels of the atrophy markers muscle RING-finger protein-1 (MuRF-1) and atrogin-1. 18F-FCH uptake was lower in the starvation-induced cells than in the untreated group, and in-vivo PET uptake also revealed a similar tendency (the average standardized uptake value (SUVmean) = 0.26 ± 0.06 versus 0.37 ± 0.07, respectively). Furthermore, the expression levels of MuRF-1 and atrogin-1 mRNA were significantly increased in the starvation-induced muscle atrophy of rats compared to the untreated group. 18F-FCH PET/CT may be a promising tool for diagnosing skeletal muscle atrophy.

Clinical Usefulness of 18 F-FET PET in a Pediatric Patient With Suspected Demyelinating Disease.

ABSTRACT: An 11-year-old boy who presented with headache and progressive right-sided weakness exhibited cortical swelling in the parafalcine area of both frontoparietal high convexity and splenium portion of corpus callosum on brain MRI. This suggested the possibility of encephalopathy, but required differential diagnosis from brain tumor. 18 F-FET ( O -(2-[ 18 F]fluoroethyl)- l -tyrosine) PET/CT identified increased uptake along the parafalcine area of the frontoparietal lobes and the splenium portion of the corpus callosum. The relatively low target-to-background ratios were more indicative of inflammatory changes such as demyelinating disease. The patient recovered after empirical steroid and immunoglobulin treatment. Clinically, the patient was diagnosed with acute disseminated encephalomyelitis.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

Efficacy of voxel-based dosimetry map for predicting response to trans-arterial radioembolization therapy for hepatocellular carcinoma: a pilot study.

OBJECTIVE: Typical clinical dosimetry models for trans-arterial radioembolization (TARE) assume uniform dose distribution in each tissue compartment. We performed simple voxel-based dosimetry using post-treatment 90Y PET following TARE with 90Y-resin microspheres and investigated its prognostic value in a pilot cohort. METHOD: Ten patients with 14 hepatocellular carcinoma lesions who underwent TARE with 90Y-resin microspheres were retrospectively included. The partition model-based expected target tumor dose (TDp) was calculated using a pretreatment 99mTc-macroaggregated albumin scan. From post-treatment 90Y-microsphere PET and voxel-wise S-value kernels, voxel-based dose maps were produced and the absorbed dose of each lesion (TDv) was calculated. Heterogeneity of intratumoral absorbed doses was assessed using the SD and coefficient of variation of voxel doses. The response of each lesion was determined based on contrast-enhanced MRI or CT, or both. Lesion responses were classified as local control success or failure. Prognostic values of dosimetry parameters and clinicopathological factors were evaluated in terms of progression-free survival (PFS) of each lesion. RESULTS: TDv was significantly different between local control success and failure groups, whereas tumor size, TDp and intratumoral dose heterogeneity were not. Univariate survival analysis identified serum aspartate transaminase level ≥40 IU/L, tumor size ≥66 mm and TDv <81 Gy as significant prognostic factors for PFS. However, only TDv was an independent predictive factor in the multivariate analysis (P = 0.022). There was a significant correlation between TDv and PFS (P = 0.009; r = 0.669). CONCLUSIONS: In TARE, voxel-based dose index TDv can be estimated on post-treatment 90Y PET using a simple method. TDv was a more effective prognostic factor for TARE than TDp and clinicopathologic factors in this pilot study. Further studies are warranted on the role of voxel-based dose and dose distribution in TARE.

Cases of high lying azygos arch and its embryological consideration.

PURPOSE: This study aimed to report cases of high-lying azygos arch and discuss the embryological basis of its development by a thorough evaluation of the anatomical features assessed using computed tomography (CT) images. METHODS: This study was approved by our institutional review board. We retrospectively reviewed chest CT images between November 2011 and November 2018. To determine high-lying azygos arch, we set the upper margin of the T4 vertebral body as the reference level. Regarding the embryological development of high-lying azygos arch, we retrospectively reviewed the CT images of 105 patients with tracheal bronchus to identify the location of the azygos arch. RESULTS: We noted that on three cases CT images, the azygos arch was located higher than the upper margin of the right main bronchus, and drained into the proximal superior vena cava (SVC) at a level higher than the conventional T4 or T5 vertebral level. All 105 patients with right tracheal bronchus showed azygos arch above the tracheal bronchus. CONCLUSION: This variation in the location of the azygos arch can mimic pathological lesion on plain radiographs, and, therefore, it is important to be aware of high-lying azygos arch. Our findings show that the azygos arch may have possibly migrated downward during embryological development.

Prognosis prediction of pancreatic cancer after curative intent surgery using imaging parameters derived from F-18 fluorodeoxyglucose positron emission tomography/computed tomography.

Imaging parameters including metabolic or textural parameters during F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are being used for evaluation of malignancy. However, their utility for prognosis prediction has not been thoroughly investigated. Here, we evaluated the prognosis prediction ability of imaging parameters from preoperative FDGPET/CT in operable pancreatic cancer patients.Sixty pancreatic cancer patients (male:female = 36:24, age = 67.2 ±â€Š10.5 years) who had undergone FDGPET/CT before the curative intent surgery were enrolled. Clinico-pathologic parameters, metabolic parameters from FDGPET/CT; maximal standard uptake value (SUVmax), glucose-incorporated SUVmax (GI-SUVmax), metabolic tumor volume, total-lesion glycolysis, and 53 textural parameters derived from imaging analysis software (MaZda version 4.6) were compared with overall survival.All the patients underwent curative resection. Mean and standard deviation of overall follow-up duration was 16.12 ±â€Š9.81months. Among them, 39 patients had died at 13.46 ±â€Š8.82 months after operation, whereas 21 patients survived with the follow-up duration of 18.56 ±â€Š9.97 months. In the univariate analysis, Tumor diameter ≥4 cm (P = .003), Preoperative Carbohydrate antigen 19-9 ≥37 U/mL (P = .034), number of metastatic lymph node (P = .048) and GI-SUVmax (P = .004) were significant parameters for decreased overall survival. Among the textural parameters, kurtosis3D (P = .052), and skewness3D (P = .064) were potentially significant predictors in the univariate analysis. However, in multivariate analysis only GI-SUVmax (P = .026) and combined operation (P = .001) were significant independent predictors of overall survival.The current research result indicates that metabolic parameter (GI-SUVmax) from FDGPET/CT, and combined operation could predict the overall survival of surgically resected pancreatic cancer patients. Other metabolic or textural imaging parameters were not significant predictors for overall survival of localized pancreatic cancer.

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in descending necrotizing mediastinitis and cervical vertebral osteomyelitis in a cancer patient: A case report.

RATIONALE: A deep neck infection (DNI) with descending necrotizing mediastinitis (DNM) has great clinical importance because of its high morbidity and mortality, particularly when associated with predisposing underlying disease. With the expanding clinical use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), it may be necessary to perform FDG PET/CT for immediate diagnosis and treatment of DNM. To the best of our knowledge, this is the first case report of DNI with DNM diagnosed based on FDG PET/CT findings. PATIENT CONCERNS: A 65-year-old man who underwent chemotherapy for stage IV lung cancer complained of sore throat, fever, and mild pain in the right upper arm for 4 days before admission. DIAGNOSES: FDG PET/CT revealed retropharyngeal abscess with acute osteomyelitis of the vertebral bodies of C4 and C5 and DNM. In blood and sputum cultures, Klebsiella pneumoniae was isolated. DNI with DNM was diagnosed based on contrast-enhanced neck and chest CT. INTERVENTIONS AND OUTCOME: Because of his underlying condition, antibiotic therapy with ceftriaxone and ciprofloxacin was started. There was initial improvement, but the patient died after 2 weeks from sepsis and multiorgan failure. LESSONS: The findings of DNI with DNM on FDG PET/CT were as follows: as an acute infection, DNM showed more severe uptake relative to the average maximum standardized uptake value of brown fat or physiologic muscle; showed the prevertebral uptake pattern rather than the paravertebral uptake pattern of brown fat; and showed continuous patterns of hypermetabolic lesions from the retropharyngeal/parapharyngeal space to the thoracic prevertebral space.

Coexistence of lung adenocarcinoma and pulmonary tuberculosis within a single lesion: A rare case report.

RATIONALE: Pulmonary tuberculosis and lung adenocarcinoma are highly prevalent pulmonary diseases associated with high mortality. However, the coexistence of lung cancer and pulmonary tuberculosis is rare. Further, the morphological features of lung cancer with coexisting pulmonary tuberculosis are similar to that of lung cancer without pulmonary tuberculosis, even though the lesion is predominantly cavity. For these reasons, the diagnosis in patients with coexisting lung cancer and pulmonary tuberculosis could be delayed until the advanced stage, and therefore, prognosis in these patients is worse compared with that of lung cancer patients without coexisting pulmonary tuberculosis. Therefore, early diagnosis of the condition is essential for initiating timely and suitable treatment. PATIENT CONCERNS: A 67-year-old man was detected abnormal finding on chest CT performed outside the hospital during health screening without significant symptom. DIAGNOSES: Chest CT revealed a 3.2, irregular, enhancing cavitary mass in right lower lobe of lung and PET-CT revealed significant uptake of 18 FDG by the cavitary mass, which was suggestive of lung cancer. Pathology results confirmed a diagnosis of coexisting lung adenocarcinoma and tuberculosis. INTERVENTIONS AND OUTCOME: The patient underwent a right lower lobectomy. No significant complications occurred in a 24 month post-surgery follow-up period LESSONS:: Although rare, the coexistence of lung adenocarcinoma and tuberculosis within a single lesion can occur. Therefore, early diagnosis of such a lesion is essential to improve the prognosis in affected patients.

Ipsilateral Hyperhidrosis: Atypical Symptom of Small Lung Adenocarcinoma Evaluated by 18F-FDG PET-CT.

A 45-year-old male visited our clinic due to right palmar anhidrosis and contralateral hyperhidrosis. Chest computed tomography (CT) showed a solitary pulmonary nodule with mediastinal lymph node enlargement, but a cause for atypical palmar anhidrosis was not identified. Subsequent fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed (PET/CT) revealed a localized pleural metastasis at the right apex with direct invasion of the paravertebral sympathetic chain. The pleural metastasis, which was not seen on chest CT, evoked ipsilateral anhidrosis independent of a mass effect or direct invasion by the primary lung tumor. 18F-FDG PET/CT can be helpful in identifying the cause of atypical symptoms in patient with small sized lung cancer.

Prognostic value of metabolic tumour volume on baseline 18F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic volumetric parameters as a quantitative index on pre-treatment 18F-FDG PET/CT in addition to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 103 consecutive patients with DLBCL and baseline FDG PET/CT were retrospectively evaluated. Quantitative metabolic parameters, including total metabolic tumour volume (TMTV) using a standardized uptake value (SUV) of ≥2.5 as the threshold, were estimated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values for the metabolic parameters. The relationships between study variables and patient survival were tested using Cox regression analysis. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: Median follow-up was 34 months. In patients with a low TMTV (<249 cm3), the 3-year progression free survival (PFS) rate was 83% and the overall survival (OS) rate was 92%, in contrast to 41% and 57%, respectively, in those with a high TMTV (≥249 cm3). In univariate analysis, a high TMTV and NCCN-IPI ≥4 were associated with inferior PFS and OS (P < 0.0001 for all), as was a high total lesion glycolysis (P = 0.004 and P = 0.005, respectively). In multivariate analysis, TMTV and NCCN-IPI were independent predictors of PFS (hazard ratio, HR, 3.11, 95% confidence interval, CI, 1.37-7.07, P = 0.007, and HR 3.42, 95% CI 1.36-8.59, P = 0.009, respectively) and OS (HR 3.41, 95% CI 1.24-9.38, P = 0.017, and HR 5.06, 95% CI 1.46-17.60, P = 0.014, respectively). TMTV was able to separate patients with a high-risk NCCN-IPI of ≥4 (n = 62) into two groups with significantly different outcomes; patients with low TMTV (n = 16) had a 3-year PFS rate of 75% and an OS rate of 88%, while those with a high TMTV had a 3-year PFS rate of 32% and an OS rate of 47% (χ2 = 7.92, P = 0.005, and χ2 = 8.26, P = 0.004, respectively). However, regardless of TMTV, patients with a low-risk NCCN-IPI of <4 (n = 41) had excellent outcomes (3-year PFS and OS rates of 85% and 95%, respectively). CONCLUSION: Pretreatment TMTV was an independent predictor of survival in patients with DLBCL. Importantly, TMTV had an additive prognostic value in patients with a high-risk NCCN-IPI. Thus, the combination of baseline TMTV with NCCN-IPI may improve the prognostication and may be helpful guide the decision for intensive therapy and clinical trials, especially in DLBCL patients with a high-risk NCCN-IPI.

Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis.

Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here, we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in patients with non-small cell lung cancer (NSCLC). We found a strong correlation between CD68 TAM immunostaining and PET 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of patients with NSCLC. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 patients with NSCLC from The Cancer Genome Atlas database. TAM secreted TNFα to promote tumor cell glycolysis, whereas increased AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T-cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies, which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies, including immunotherapy. SIGNIFICANCE: These findings show that tumor-associated macrophages can significantly modulate tumor metabolism, hindering the efficacy of anticancer therapies, including anti-PD-L1 immunotherapy.

Prophylactic Temporary Occlusion of the Cystic Artery Using a Fibered Detachable Coil During 90Y Radioembolization.

PURPOSE: To address the feasibility of prophylactic temporary occlusion of the cystic artery using a detachable coil during 90Y radioembolization. MATERIALS AND METHODS: From January 2012 to October 2016, nine patients underwent temporary occlusion of the cystic artery during 90Y radioembolization. Based on the planning hepatic angiography, a detachable coil was deployed into the cystic artery, which arose from a more distal level (e.g., right anterior hepatic artery) than its usual origin, but the proximal 1 cm was left inside the microcatheter. 90Y microspheres were infused proximal to the cystic artery where the 99mTc-MAA had been infused, and then the coil was retrieved. Afterward, the patients underwent PET/CT imaging. Medical records were reviewed, and the differences in the uptake of 99mTc-MAA and 90Y microspheres in the gallbladder were evaluated using Wilcoxon's signed-rank test. RESULTS: Temporary placement of a detachable coil was feasible in all cases. On the angiograms obtained after detachable coil placement, the distal cystic artery and gallbladder were partially identifiable in eight of the nine (88.8%) patients, but fully restored after the removal of the coils in all cases. The proportional uptake of 99mTc-MAA (mean, 4.35%) and 90Y (mean, 0.90%) in the gallbladder was significantly different due to the temporary occlusion of the cystic artery (p = 0.004). No clinical complications were identified for three months after the procedure. CONCLUSION: Temporary occlusion of the cystic artery using a detachable coil appeared to be feasible and effective in reducing 90Y uptake in the gallbladder.