High Fluorodeoxyglucose Uptake Research Articles

Immunoglobulin G4-Related Hypertrophic Pachymeningitis Presenting with Multiple Lower Cranial Nerve Palsies

Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ condition that infrequently exhibits neurological involvement. Here, we describe a case of IgG4-related hypertrophic pachymeningitis with multiple lower cranial nerve palsies. A 65-year-old man presented with a 5-month history of hoarseness and dysphagia. A neurologic examination revealed multiple lower cranial nerve palsies. Brain magnetic resonance imaging indicated diffuse dural involvement along the left tentorium and temporal fossa. Serum IgG and IgG4 levels were found to be elevated. Ethmoid polyp biopsy revealed chronic inflammation with moderate lymphoplasmacytic and some eosinophilic infiltration. Up to 60 IgG4-positive cells were observed per high-power field, and the measured IgG4/IgG ratio was approximately 10% to 20%. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography indicated abnormally high FDG uptake in the left posterior fossa, tentorium, and left temporal fossa, with additional involvement of the lung, iliac artery, and renal artery. Based on these findings, we diagnosed the patient with IgG4-related hypertrophic pachymeningitis and successfully treated the condition with steroids and rituximab. IgG4-RD should be differentiated from distinct conditions presenting with multiple cranial nerve palsies accompanied by pachymeningitis.

Cardiac cavernous hemangioma with high fluorodeoxyglucose uptake on preoperative positron emission tomography/computed tomography: a case report

BackgroundReports on cardiac hemangioma detection by F-18-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) are extremely rare.Case presentationHere we describe a case of a 61-year-old man with hemangioma. CT revealed a tumor with a size of 60 mm. Magnetic resonance imaging showed high signal intensity on T2-weighted images. Hemangioma was initially suspected. However, PET/CT showed high FDG absorption, which led us to suspect a malignant tumor. The tumor was resected, and a cavernous hemangioma diagnosis was made by postoperative histopathological examination.ConclusionsThis case may serve as a reference for clinicians to become more aware of the potential application of FDG PET/CT for cardiac hemangioma detection.

Incidental Diagnosis of Prostate Cancer by 18F-FDG PET-CT Imaging in a Patient During Post-operative Evaluation for Cecal Cancer

Incidental high fluorine-18 FDG (fluorodeoxyglucose) uptake in well-differentiated prostate cancer is rare. We reported the case of a 75-year-old man who underwent a whole-body FDG PET-CT (positron emission tomography with computed tomography) scan for post-operative evaluation of caecal cancer and demonstrated no evidence of recurrence. However, a focal hypermetabolic lesion was detected in the right lateral lobe of the prostate. The patient’s prostatic biopsy from the right lobe revealed well-differentiated adenocarcinoma with a Gleason score of six and a raised serum PSA level. Incidental, focally intense FDG uptake in the prostate gland should be considered for further investigations to confirm the presence of prostate cancer. Bangladesh J. Nuclear Med. 26(1): 51-53, 2023

High-Grade Endometrioid Stromal Sarcoma of the Ovary: Malignant Transformation of Ovarian Mature Cystic Teratoma

We report an extremely rare case of ovarian high-grade endometrioid stromal sarcoma arising from a mature cystic teratoma with clinicopathologic features, and then we briefly review the pertinent literature. A 62-year-old nulliparous woman presented with lower abdominal pain that had begun 6 months earlier. Magnetic resonance imaging showed two adnexal masses with fat components, which suggested that they were mature cystic teratomas. The eccentric thick rim of the left mass showed irregular invasion of the uterus, which was suggestive of malignancy. Positron emission tomography/computed tomography demonstrated high fluorodeoxyglucose uptake in the corresponding area. The patient underwent debulking cytoreductive surgery. The diagnosis was of an International Federation of Obstetrics and Gynecology stage IIIC high-grade endometrioid stromal sarcoma arising from a mature cystic teratoma. After surgery, the patient received adjuvant chemotherapy with three courses of doxorubicin regimen. The cancer recurred 3 months after surgery, and the patient died of progressive disease. It might be helpful for clinicians to be aware of this rare disease and the poor prognosis when it is at an advanced stage.

PET/CT-Based Characterization of 18F-FDG Uptake in Various Tissues Reveals Novel Potential Contributions to Coronary Artery Disease in Psoriatic Arthritis

Background and ObjectivesPsoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies.MethodsIn this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity.ResultsCompared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003).InterpretationTogether, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA.

T Stage and Pretreatment Standardized Uptake Values Predict Tumor Recurrence With 5-Fraction SABR in Early-Stage Non-Small Cell Lung Cancer

PurposeFive-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. MethodsNinety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. ResultsOf 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. ConclusionsFive-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.

The effect of additional acarbose on metformin-associated artificially high 18F-Fluorodeoxyglucose uptake in positron emission tomography/computed tomography.

Metformin causes diffuse and intense fluorodeoxyglucose (FDG) uptake more frequently in the colon and less frequently in the small intestine. In this study, we aimed to investigate the effect of simultaneous use of acarbose and metformin on FDG uptake in positron emission tomography/computed tomography (PET/CT), which has not been investigated previously. Totally 145 patients with amedian age of 65years (range: 18-80years), who underwent FDG PET/CT in the Department of Nuclear Medicine of Erciyes University Medical School between 2018 and 2021, were involved in the study. The patients undergoing PET/CT were categorized as metformin plus acarbose users (group MA), metformin users (group M), and control subjects without diabetes (group C). The maximum and mean standard uptake values (SUVmax and SUVmean) of FDG uptake of the all intestine segments were measured separately. The number of participants in each group was 35, 51 and 59 in group MA, group M and group C, respectively. The FDG uptake of all intestine was significantly higher in group MA and group M than in group C. The FDG uptake of ascending, transverse, descending, and sigmoid colon was significantly lower in group MA than in group M. The FDG uptake of the small intestine was not different between group MA and group M. The FDG uptake of the rectum was lower in group MA than group M and it was significant for SUVmean, but not significant for SUVmax. The addition of acarbose to metformin therapy decreased SUV and artificially high FDG uptake in the colon and may be an alternative recommendation to discontinuing metformin in patients going to PET/CT imaging.

The feasibility of dose escalation using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) with FDG PET/CT guided in esophageal cancer.

Previous studies show that dose escalation for gross tumor volume (GTV) improves local control of esophageal cancer (EC). However, optimal boosting remains uncertain. Recently, functional imaging guidance to achieve dose escalation in high-risk areas of tumors has been proposed. This study evaluated the feasibility of dose escalation in tumor regions with high fluorodeoxyglucose (FDG) uptake using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT). GTVPET was defined as a high FDG uptake region with 50% SUVmax threshold for dose escalation. IMRT and IMPT plans were generated for three boosting modes: plan 50.4 (50.4 Gy in clinical target volume, CTV), plan 63 (50.4 Gy in CTV, 63 Gy in GTV), plan 70 (50.4 Gy in CTV, 63 Gy in GTV, and 70 Gy in GTVPET). Eleven patients with squamous cell carcinoma were evaluated. Dose parameters for heart, lung, and spinal cord were compared based on the dose-volume histogram (DVH). Paired t-test was performed on the doses to organs-at-risk (OARs) among plan 50.4, plan 63, and plan 70 for IMRT and IMPT. Dosimetric parameters for IMRT for heart, lung, and spinal cord increased significantly for plan 63 and some parameters even exceeded dose limits for OARs. Further dose escalation in GTV-PET did not increase dosimetric parameters significantly. Most dosimetric parameters of OARs in IMPT exhibited no statistical change compared with plan 50.4, and doses to OARs were far less than dose constraints. Dose escalation by IMRT may lead to increased risk of radiation-related injury. Further dose escalation in high FDG uptake regions did not increase doses to OARs. This dose escalation is ideal for achieving better outcomes for EC treatment.

Changes in glucose metabolism of the brain after immunochemotherapy in patients with diffuse large B-Cell lymphoma on fluorodeoxyglucose positron emission tomography/computed tomography

Objective: Mild cognitive impairment seen after chemotherapy is called chemo brain. Neuropsychological tests mainly diagnose chemo brain, but morphological or functional imaging modalities may also contribute to the diagnosis. This study aimed to examine the change in brain fluorodeoxyglucose (FDG) uptake after immunochemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). Materials and Methods: FDG positron emission tomography/computed tomography images performed for both staging and treatment response evaluation of patients treated with R-CHOP for DLBCL were retrospectively analyzed. It was investigated whether the FDG uptake of the brain decreased after the treatment. Results: There was no significant decrease in FDG uptake in the brain regions of 40 patients treated with R-CHOP compared to pretreatment. There was no significant change in brain FDG uptake after treatment between Ann Arbor Stage 1 or Stage 2 patients and Ann Arbor Stage 3 or Stage 4 patients compared to pretreatment. There was no significant change in brain FDG uptake after treatment compared to pretreatment between patients with Deauville score (DS) 1–3 and patients with DS 4 or 5 according to treatment responses. Patients with the most hypermetabolic lesion SUVmax >30.5 had significantly decreased posttreatment SUVmean in the right basal ganglia, left and right central regions, left cingulate and paracingulate cortices, right striatum, left and right frontal cortices, left occipital cortex, left and right parietal cortices, left and right precunei, and right temporal cortex. Conclusion: FDG uptake decreased in many brain regions after R-CHOP in patients with DLBCL whose lesions showed high FDG uptake.

Primary lower-limb arterial stent infection managed with resection and In situ bovine pericardial revascularization

Peripheral arterial stent infection is a rare but morbid condition. We present the case of a patient with primary stent infection of his superficial femoral artery (SFA) and popliteal artery, managed with surgical explant and in situ reconstruction using rifampicin-soaked bovine pericardial tube graft. A 69-year-old man presented with a 3-day history of left groin pain. He had had stents placed into his SFA and popliteal artery in 6 months prior. Duplex ultrasound demonstrated a pseudoaneurysm of the common femoral artery (CFA), with ying-yang flow. A computed tomography angiogram confirmed this pseudoaneurysm, which had a thick rind of nonenhancing soft tissue. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus. The patient was taken to the operating theater, and the CFA, profunda femoris artery, and SFA were exposed. After heparinization and clamp control, the pseudoaneurysm was incised, which revealed that the proximal SFA had been completely eroded. All infected tissues were resected. In situ arterial reconstruction was undertaken using a rifampicin-soaked bovine pericardium tube graft. A subsequent positron emission tomography scan revealed high fluorodeoxyglucose uptake around the patients remaining distal SFA and popliteal artery stents. These were explanted in the same manner described above. There is limited evidence regarding the prevention of infection when placing peripheral arterial stents. The Society of Interventional Radiology does not recommend routine prophylactic antibiotics when placing peripheral stents. In situ reconstruction using bovine pericardium is a well-described technique in the management of aortic graft infections, but there is limited experience in its use in a peripheral setting.

"WHAT AN IMPOSTER!" LIPOMATOUS HYPERTROPHY OF THE ATRIAL SEPTUM: A DIAGNOSTIC CHALLENGE IN CARDIAC IMAGING

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Lipomatous hypertrophy of the atrial septum (LHAS) is a rare, non-neoplastic fatty infiltration of the inter-atrial septum that spares the fossa ovalis. It is best differentiated from other cardiac tumors with transesophageal echocardiogram (TEE) and cardiac computed tomographic (CT) or magnetic resonance (MR) imaging. CASE PRESENTATION: A 52-year-old woman with diabetes, hypertension and a chronic tobacco smoker, presented with complaints of shortness of breath. An electrocardiogram showed non-specific ST-T wave changes. A TTE revealed an ejection fraction of 60% and a well-encapsulated mass in the right atrium; the differential diagnosis of the mass included entities such as atrial myxoma. Further evaluation with a TEE demonstrated a large, sessile, immobile mass in the right atrium with a characteristic dumbbell shaped thickening of the atrial septum, thus raising the possibility of lipomatous hypertrophy of the atrial septum (LHAS). Cardiac MRI confirmed the distinctive hour-glass shaped mass in the intra-atrial septum, with characteristic sparing of the fossa ovalis. There was no contrast enhancement and lacked signal on fat suppression sequences confirming benign LHAS. DISCUSSION: LHAS is a rare, non-neoplastic abnormality of the heart. Unlike other cardiac tumors such as myxomas and papillary fibroelastomas which require surgical intervention, LHAS is a benign finding. It is thought to be an infiltration of brown adipose tissue into the myocytes of the interatrial septum. Most cases remain clinically silent and are detected incidentally during echocardiography, surgery or autopsy. Echocardiography, where a TEE is more sensitive than a TTE, and cardiac MRIs demonstrate a characteristic dumbbell or hour-glass shaped appearance. Tailored MRI sequences with lack of gadolinium enhancement and fat suppression imaging, differentiate it from other intracardiac neoplasms, including myxomas. Moreover, positron emission tomography (PET) scans will show high fluorodeoxyglucose (FDG) uptake by the brown adipose tissue that may further aid in diagnosis. Rare complications of LHAS include SVC syndrome, sick-sinus syndrome and other life-threatening arrhythmias that may warrant surgical intervention. CONCLUSIONS: LHAS is an uncommon cardiac anomaly. The utility of TEE and cardiac MRI, in this case, aids in defining the benign nature of LHAS. REFERENCE #1: Nadra I. Lipomatous hypertrophy of the ineratrial septum; a commonly misdiagnosed mass often leading to unnecessary cardiac surgery. Heart. 2004;90(12):66. REFERENCE #2: Heyer C, Kagel T, Lemburg S, Bauer T, Nicolas V. Lipomatous hypertrophy of the interatrial septum. Chest. 2003;124(6):2068–2073. doi: 10.1378/chest.124.6.2068. DISCLOSURES: No relevant relationships by Adhiraj Bhattacharya, source=Web Response No relevant relationships by Rizwan Khan, source=Web Response No relevant relationships by Michael Maysky, source=Web Response

Hippocampal glucose uptake as a surrogate of metabolic change of microglia in Alzheimer\u2019s disease

BackgroundDynamically altered microglia play an important role in the progression of Alzheimer’s disease (AD). Here, we found a close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake on [18F]fluorodeoxyglucose (FDG) PET.MethodsWe used an AD animal model, 5xFAD, to analyze hippocampal glucose metabolism using both animal FDG PET and ex vivo FDG uptake test. Cells of the hippocampus were isolated to perform single-cell RNA-sequencing (scRNA-seq). The molecular features of cells associated with glucose metabolism were analyzed at a single-cell level. In order to apply our findings to human brain imaging study, brain FDG PET data obtained from the Alzheimer’s Disease Neuroimaging Initiative were analyzed. FDG uptake in the hippocampus was compared according to the diagnosis, AD, mild cognitive impairment, and controls. The correlation analysis between hippocampal FDG uptake and soluble TREM2 in cerebrospinal fluid was performed.ResultsIn the animal study, 8- and 12-month-old 5xFAD mice showed higher FDG uptake in the hippocampus than wild-type mice. Cellular FDG uptake tests showed that FDG activity in hippocampal microglia was increased in the AD model, while FDG activity in non-microglial cells of the hippocampus was not different between the AD model and wild-type. scRNA-seq data showed that changes in glucose metabolism signatures including glucose transporters, glycolysis and oxidative phosphorylation, mainly occurred in microglia. A subset of microglia with higher glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. In the human imaging study, we found a positive association between soluble TREM2 and hippocampal FDG uptake. FDG uptake in the hippocampus at the baseline scan predicted mild cognitive impairment conversion to AD.ConclusionsWe identified the reconfiguration of microglial glucose metabolism in the hippocampus of AD, which could be evaluated by FDG PET as a feasible surrogate imaging biomarker for microglia-mediated inflammation.

PET/CT and contrast-enhanced CT imaging findings in benign solitary schwannomas

ObjectivesImaging features of positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT and pathological changes in benign solitary schwannoma were retrospectively analyzed, and the factors associated with high uptake of fluorodeoxyglucose (FDG) were examined. MethodsThe PET/CT, contrast-enhanced CT, and pathological results of 58 cases of benign solitary schwannomas confirmed by surgery or biopsy were retrospectively analyzed. The association of each variable with the maximum standardized uptake value (SUVmax) was evaluated. ResultsThe SUVmax of the 58 benign schwannoma cases was 4.1 ± 2.1 (1.5–11.1). When the locations of schwannomas were divided into gastrointestinal system/heart/abdominal and pelvic cavities/thoracic wall (type-1 locations) and other sites (type-2 locations), the schwannoma location was significantly correlated with the SUVmax (r = 0.538, p = 0.000). The SUVmax values were 5.8 ± 2.4 and 3.3 ± 1.5, respectively (p = 0.000). Peritumoral lymphoid cuffs were observed in 7 cases, 4 of which were tumors of gastrointestinal origin, accounting for 80 % of the gastrointestinal schwannomas (4/5). The presence of peritumoral lymphoid cuffs was significantly correlated with the SUVmax (r = 0.456, p = 0.000). The location of the schwannoma was significantly correlated with the presence of peritumoral lymphoid cuffs (r = 0.640, p = 0.000). We found that a peritumoral lymphoid cuff is strongly correlated with the presence of regional lymphadenopathy. Among the 7 cases showing peritumoral lymphoid cuffs, 5 cases had the presence of peritumoral enlarged lymph nodes. The degree of enhancement was significantly correlated with the SUVmax (r = 0.556, p = 0.000). ConclusionsBenign schwannomas originating from the gastrointestinal system/heart/abdominal location and showing the presence of peritumoral lymphoid cuffs or moderate and significant enhancement on contrast-enhanced CT were significantly associated with high FDG uptake. An accurate understanding of the factors associated with high FDG uptake can help reduce the misdiagnosis rate.

Characterization of 18F-fluorodeoxyglucose metabolic spatial distribution improves the differential diagnosis of indeterminate pulmonary nodules and masses with high fluorodeoxyglucose uptake.

The aim of this study was to investigate the value of visual assessment of 18F-fluorodeoxyglucose (18F-FDG) metabolic spatial distribution (V-FMSD) in the diagnosis of indeterminate pulmonary nodules and masses with high 18F-FDG uptake. A total of 301 patients with indeterminate pulmonary nodules or masses who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging were retrospectively studied. The characteristics of 18F-FDG metabolic spatial distribution (FMSD) in the proximal and distal regions of the lesions were visually analyzed using a 5-point scoring system. The sensitivity, specificity, accuracy, and area under receiver operating characteristic curve (AUC) were compared between V-FMSD and conventional PET/CT methods for the diagnosis of hypermetabolic indeterminate pulmonary nodules and masses. The V-FMSD results showed that 180 (92.8%) malignant lesions had a score of ≥3 and 78 (72.9%) benign lesions had a score of ≤2. This indicated that the FMSD in the proximal region of malignant lesions was significantly higher than that of the distal region, and the FMSD in the proximal region of benign lesions was significantly lower than that of the distal region. V-FMSD had a specificity of 72.9%, which was markedly higher than those of the maximum standard uptake value (SUVmax; 0%, P<0.001) and the retention index (RI; 26.2%, P<0.001). The AUC of V-FMSD was 0.886, which was significantly larger than those of the SUVmax (0.626, P<0.001), RI (0.670, P<0.001), and PET/CT (0.788, P<0.05). Our study found that pulmonary benign and malignant lesions have distinct FMSD characteristics. V-FMSD can therefore be used as a novel auxiliary marker to improve the diagnostic accuracy of hypermetabolic indeterminate pulmonary nodules and masses.

P84.20 VATS Right Upper Lobectomy for Advanced Non-Small Cell Lung Cancer After ALK-Tyrosine Kinase Inhibitor Administration.

Surgical resection is not generally indicated, but systemic chemotherapy or several molecular-targeted agents are selected as main treatments for advanced lung cancer. But as for the molecular-targeted agents, most patients eventually experience tumor progression due to acquired resistance. The role of residual or recurrent tumor resection after the treatment is unclear. A 65 year-old man was referred to our hospital due to abnormal radiographic image. Chest CT revealed a 50mm solid mass in the right upper lobe. The tumor involved hilar lymph node and extended to the junction of upper lobar bronchus. MRI revealed a 20mm brain metastasis in the left parietal lobe. He was initially diagnosed with cT2bN1M1b StageIVA EGFR(-) adenocarcinoma by transbronchial lung biopsy. Then, brain metastasis was removed surgically. He was finally diagnosed with ALK-rearranged adenocarcinoma from tissue of brain metastasis. Alectinib (600mg/day) was started as the first-line therapy. After 14 months of alectinib therapy, chest CT revealed remarkable reduction of the tumor and other two new lesions in the right upper lobe. One was a 10mm nodule close to the scar of primary tumor, which had not found at chest CT from three months ago. The other was a 15mm nodule apart from the scar, which existed before the alectinib treatment and had got larger gradually. PET-CT revealed the high fluorodeoxyglucose (FDG) uptake of only two new lesions. We performed complete VATS right upper lobectomy and mediastinal lymph node dissection for treatment and diagnosis. Histopathlogical diagnoses: No residual viable cell was found in the primary lesion. The lesion close to the scar of the primary lesion was adenocarcinoma (ALK-rearranged), which was thought to be a recurrent lesion because of resemblance to brain metastasis in pathological tissue. The lesion apart from the main lesion was pT1bN0M0 StageIB squamous cell carcinoma, which was thought to be primary lung cancer. Alectinib was continued after the operation, and chest CT shows no sign of recurrence so far. We experienced a VATS right upper lobectomy for advanced non-small cell lung cancer after ALK-tyrosine kinase inhibitor administration.

Prognostic implications of dual tracer PET/CT: PSMA ligand and [18F]FDG PET/CT in patients undergoing [177Lu]PSMA radioligand therapy

BackgroundProstate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [18F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT.Materials and methodsThis bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patients, the pattern of PSMA ligand and FDG uptake was visually assessed. Patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA−) lesions were compared to patients without any FDG+/PSMA− lesions. A log-rank analysis was used to assess the difference in OS between subgroups.ResultsMedian OS was 11 ± 1.8 months (95% CI 7.4–14.6). A significantly lower OS (p < 0.001) was found in patients with at least one FDG+/PSMA− lesion at baseline PET/CTs (n = 18) with a median OS of 6.0 ± 0.5 months (95% CI: 5.0–7.0 months). In comparison, patients without any FDG+/PSMA− lesions (n = 36) had a median OS of 16.0 ± 2.5 months (95% CI: 11.2–20.8 months).ConclusionFDG+/PSMA− lesions are a negative predictor of overall survival in patients with mCRPC undergoing RLT. However, it remains to be determined if patients with FDG+/PSMA− lesions should be excluded from PSMA RLT.

Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer

ObjectivesAccumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients. Materials and methodsThis randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m2) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes. ResultsMetformin group showed no significant difference in the risk of progression and death compared to control group (progression: hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 − 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67–1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose (FDG) uptake on baseline PET image than non-SqCC NSCLC (P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12−0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18–0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatment in metformin group compared to control group (P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment. ConclusionsAddition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.

Extraordinarily long-inactive solitary fibrous tumor transformed to produce big insulin-like growth factor-2, leading to hypoglycemia and rapid liposarcoma growth: a case report

BackgroundA high-molecular-weight form of insulin-like growth factor-2 (IGF-2), known as “big” IGF-2, is occasionally produced by various tumor types, leading to hypoglycemia. Although solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, it has been estimated that 4–6% of SFT patients develop hypoglycemia due to circulating big IGF-2. The mean time elapsed from tumor detection until the onset of hypoglycemia is reportedly less than one year (8.5 ± 1.9 months).Case presentationA 68-year-old man was hospitalized for exacerbation of recurring hypoglycemic episodes. He had been diagnosed with an SFT 17 years before the onset of hypoglycemia, and the SFT had already been very large at that time. The tumor, which was non-resectable and refractory to chemotherapies, had slowly increased in size since the initial diagnosis. Half a year before the hypoglycemic episodes manifested, another tumor, adjacent to the left kidney, was newly identified. Fluorodeoxyglucose positron emission tomography-computed tomography scanning, revealed the left peri-renal tumor to show much higher fluorodeoxyglucose uptake than the preexisting SFT, suggesting that it was unlikely to be a metastasis from the SFT. Abundant serum big IGF-2 was detected by western immunoblot analysis, indicating it to be the cause of the hypoglycemia. Since the 17 years between SFT detection and the onset of IGF-2-induced hypoglycemia was an extremely long period as compared with those in previous reports, we initially suspected that the new, peri-renal tumor had produced big IGF-2, but transcatheter arterial embolization of its feeding arteries did not suppress hypoglycemia. Notably, by measuring the tumor volume doubling time, the peri-renal tumor growth was shown to be markedly accelerated in parallel with exacerbation of the hypoglycemia. The patient died of heart failure 21 months after the onset of hypoglycemia. Unexpectedly, autopsy revealed that big IGF-2 had been produced only by the preexisting SFT, not the peri-renal tumor, and that the peri-renal tumor was a dedifferentiated liposarcoma.ConclusionsWe should keep in mind that even a long-inactive SFT can undergo transformation to produce big IGF-2, which then acts on both insulin and IGF-1 receptors, possibly leading to both hypoglycemia and the development/growth of another tumor, respectively.

Discontinuation of metformin to prevent metformin-induced high colonic FDG uptake: is 48\xa0h sufficient?

ObjectiveIn this retrospective, single-center observational study, we investigated whether discontinuing metformin for at least 48 h prevents metformin-induced [18F]fluorodeoxyglucose (FDG) uptake in all segments of the colon.MethodsPatients with type 2 diabetes who were using metformin before undergoing an FDG PET/CT scan were included. Two groups were created: patients who discontinued metformin for less than 48 h (< 48 h group) and patients who discontinued metformin for between 48 and 72 h (≥ 48 h group). A control group comprised non-diabetic patients who were not using metformin before undergoing an FDG PET/CT. We visually scored the uptake of FDG in four segments of the colon—the ascendens, transversum, descendens, and rectosigmoid—using a four-point scale (1–4) and considered scores of 3 or 4 to be clinically significant.ResultsColonic FDG uptake in the ≥ 48 h group (n = 23) was higher than uptake in the control group (n = 96) in the colon descendens [odds ratio (OR) 14.0; 95% confidence interval (CI) 4.8–40.9; p value: 0.001] and rectosigmoid (OR 11.3; 95% CI 4.0–31.9; p value: 0.001), and there was no difference in the colon ascendens and transversum. Colonic FDG uptake in the < 48 h group (n = 25) was higher than uptake in the ≥ 48 h group (n = 23) in the colon transversum (OR 4.8; 95% CI 1.3–18.5; p value: 0.022) and rectosigmoid (p value: 0.023), and there was no difference in the colon ascendens and descendens.ConclusionsDiscontinuing metformin for 48 h before undergoing an FDG PET/CT still gives a high uptake in the distal parts of the colon when compared with non-diabetic patients who are not using metformin. Discontinuing metformin for 48 h seems to be useful for scanning the more proximal segments of the colon.

Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in amyotrophic lateral sclerosis

BackgroundWe recently reported that enhanced [18F]-fluorodeoxyglucose (FDG) uptake in skeletal muscles predicts disease aggressiveness in patients with amyotrophic lateral sclerosis (ALS). The present experimental study aimed to assess whether this predictive potential reflects the link between FDG uptake and redox stress that has been previously reported in different tissues and disease models.MethodsThe study included 15 SOD1G93A mice (as experimental ALS model) and 15 wildtype mice (around 120 days old). Mice were submitted to micro-PET imaging. Enzymatic pathways and response to oxidative stress were evaluated in harvested quadriceps and hearts by biochemical, immunohistochemical, and immunofluorescence analysis. Colocalization between the endoplasmic reticulum (ER) and the fluorescent FDG analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) was performed in fresh skeletal muscle sections. Finally, mitochondrial ultrastructure and bioenergetics were evaluated in harvested quadriceps and hearts.ResultsFDG retention was significantly higher in hindlimb skeletal muscles of symptomatic SOD1G93A mice with respect to control ones. This difference was not explained by any acceleration in glucose degradation through glycolysis or cytosolic pentose phosphate pathway (PPP). Similarly, it was independent of inflammatory infiltration. Rather, the high FDG retention in SOD1G93A skeletal muscle was associated with an accelerated generation of reactive oxygen species. This redox stress selectively involved the ER and the local PPP triggered by hexose-6P-dehydrogenase. ER involvement was confirmed by the colocalization of the 2-NBDG with a vital ER tracker. The oxidative damage in transgenic skeletal muscle was associated with a severe impairment in the crosstalk between ER and mitochondria combined with alterations in mitochondrial ultrastructure and fusion/fission balance. The expected respiratory damage was confirmed by a deceleration in ATP synthesis and oxygen consumption rate. These same abnormalities were represented to a markedly lower degree in the myocardium, as a sample of non-voluntary striated muscle.ConclusionSkeletal muscle of SOD1G93A mice reproduces the increased FDG uptake observed in ALS patients. This finding reflects the selective activation of the ER-PPP in response to significant redox stress associated with alterations of mitochondrial ultrastructure, networking, and connection with the ER itself. This scenario is less severe in cardiomyocytes suggesting a relevant role for either communication with synaptic plaque or contraction dynamics.