Detection of incidental colorectal tumours with 18F‐labelled 2‐fluoro‐2‐deoxyglucose positron emission tomography/computed tomography scans: results of a prospective study

Aim This study assessed the clinical significance of incidental colorectal 2‐fluoro‐2‐deoxyglucose (FDG) uptake using ¹⁸F‐FDG positron emission tomography/computed tomography (PET/CT) scans and evaluated the importance of colonoscopy when incidental colorectal FDG uptake was observed. Method A prospective study was designed and conducted at a single institution over a 2‐year period. In patients undergoing PET/CT scans, all with FDG uptake in the colorectum were assigned to have colonoscopy and biopsy. The value of PET/CT scanning was studied by comparison with the colonoscopy and biopsy results. Results Among 10 978 PET/CT scans, one or more focal uptakes of FDG in the colorectum were observed in 148 (1.35%) patients. In 136 valid patients, malignant colorectal tumours and polyps were found in 23.5% and 20.5%, respectively,, while the colon in the other 56% was normal. A higher false‐positive rate was found in the right colon compared with the distal colorectum (66.2%vs 36.7%, P = 0.004). A significant increase of the maximum standardized uptake (SUVmax) value was found among normal, polyps and cancer groups. Multivariate analysis revealed that SUVmax was the risk factor for predicting colorectal cancer or polyps and FDG uptake in the right colon was a negative predictive factor for finding cancers or polyps. Conclusions Our study proves the necessity of colonoscopy when incidental FDG uptake is found on PET/CT imaging. The false‐positive FDG uptake is more commonly observed in the right colon. Although the SUVmax value is higher in cancer patients, a high SUVmax value does not necessarily result in malignancies.     

Significance of 18F‐fluorodeoxyglucose positron‐emission tomography/computed tomography for the postoperative surveillance of advanced renal cell carcinoma

OBJECTIVES

To evaluate the role of ¹⁸F‐fluorodeoxyglucose (FDG) positron‐emission tomography (PET)/computed tomography (CT) for the surveillance of patients with renal cell carcinoma (RCC) who have a high risk of local recurrence or distant metastasis, by comparing the results with those of conventional imaging methods.

PATIENTS AND METHODS

Sixty‐three patients with RCC had conventional imaging studies and FDG PET/CT during the follow‐up after surgical treatment. Their pathological stages were T2 in 28 patients, T3a in 14, T3b in 19 and T4 in two; lymph‐node or distant metastases were present in 12 patients. Suspicious recurrent or metastatic lesions were confirmed by histopathology or by clinical follow‐up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of conventional surveillance methods and FDG PET/CT were analysed. The difference in the accuracy of FDG PET/CT by nuclear grade and histological subtype of tumours was also assessed.

RESULTS

The FDG PET/CT accurately classified the presence of a recurrence or metastasis in 56 (89%) patients. FDG PET/CT had an 89.5% sensitivity, 83.3% specificity, 77.3% positive predictive value, 92.6% negative predictive value, and 85.7% accuracy in detecting recurrence or metastasis, which was not significantly different from the results with conventional methods. Moreover, the accuracy of the FDG PET/CT by nuclear grade and histological subtypes was not significantly different.

CONCLUSION

For the surveillance of high‐risk RCC, FDG PET/CT had results that were as good as conventional methods and were not influenced by the nuclear grades of cancer cells. In addition, it was possible to examine all organ systems in one procedure, and there was no need for contrast agents, that can damage renal function. Therefore, FDG PET/CT might replace conventional methods.     

The value of 18F‐FDG PET/CT in diagnosing and localising deep sternal wound infection to guide surgical debridement

Deep sternal wound infection (DSWI) is a severe complication in patients after open heart surgery (OHS). But there is a lack of appropriate imaging tool to detect the infection sites, which may lead to incomplete debridement. The present study aims to investigate the value of ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG PET/CT) in comparison with CT scan in diagnosing and localising DSWI. A total of 102 patients with DSWI after OHS were retrospectively collected from January 2012 to December 2017 in our hospital. All the patients had surgical debridements for DSWI with pretreatment imaging of either ¹⁸F‐FDG PET/CT or CT scan. The sensitivity, specificity, and accuracy of localising infection sites were compared between PET/CT and CT groups, with surgical, microbiological, and histopathological findings as the gold standard. The length of hospital stays and the rate of recurrence were also compared. Ten patients in the PET/CT group had a follow‐up PET/CT scan after debridement, and the correlations between the changes of PET/CT findings and surgical outcomes were analysed. ¹⁸F‐FDG PET/CT is more accurate than CT in diagnosing and localising DSWI after OHS, which leads to a more successful surgical debridement with a lower rate of recurrence and a shorter length of hospital stay. In addition, follow‐up PET/CT after debridement could evaluate the treatment effect.     

Evaluation of fluorodeoxyglucose positron‐emission tomography with computed tomography for staging of urothelial carcinoma

Study Type – Diagnostic (case series)
Level of Evidence 4

OBJECTIVE

To investigate the role of ¹⁸F‐fluorodeoxyglusose positron‐emission tomography (FDG‐PET), combined with computed tomography (CT) and forced diuresis, in the staging and follow‐up of urothelial carcinoma (UC).

PATIENTS AND METHODS

We recruited 44 patients with muscle‐invasive urothelial bladder cancer (UBC) before radical cystectomy (RC), 19 under follow‐up after RC and seven after systemic chemotherapy. For those who had RC, histopathology was used as the reference standard to compare the sensitivity and specificity of FDG‐PET/CT and standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36 patients with ≥6 months of follow‐up imaging were considered to describe the progression of UC and extrapelvic positive FDG‐PET/CT images.

RESULTS

For the detection of primary UBC, FDG‐PET/CT was slightly more sensitive than CT (85% vs 77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis FDG‐PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for both imaging techniques. In 20 patients, extrapelvic FDG‐PET/CT images showed suspected disease at the first evaluation. UC progressed in nine of the 10 patients who had synchronous multiple PET‐positive retroperitoneal or mediastinal lymph nodes, and in only two of the nine with unique hyperactive lesions in the lung. FDG‐PET/CT also detected a pT1G3 UC of the renal pelvis and all bone metastases detected by bone scintigraphy.

CONCLUSIONS

FDG‐PET/CT could replace standard CT and bone scintigraphy in the presurgical staging and monitoring of patients with UC after surgery or chemotherapy.     

Clinical significance of incidental focal colorectal 18F‐fluorodeoxyglucose uptake: our experience and a review of the literature

Aim The aims of the present study were: (i) to evaluate the focal incidental colorectal uptake of ¹⁸F‐fluorodeoxyglucose ([¹⁸F]FDG) and to correlate it with colonoscopy and histological findings; (ii) to evaluate the relationship between the presence/absence of neoplastic disease and clinical data and the anatomical site of [¹⁸F]FDG uptake; and (iii) to compare our results with those reported for incidental colorectal uptake of [¹⁸F]FDG in the literature and those obtained from various screening programmes for colorectal cancer. Method The database of 6000 patients referred for [¹⁸F]FDG positron emission tomography/computed tomography (PET‐CT) to our centre was retrospectively reviewed for incidental colorectal uptake of [¹⁸F]FDG. Patients with focal uptake were selected and the aetiology of PET findings was verified with a subsequent colonoscopy and histopathological analysis when available. Results Incidental colorectal uptake of [¹⁸F]FDG was seen in 144 (2.4%) patients, of whom 64 (1.1%) had focal uptake; 48 out of these 64 patients underwent colonoscopy, which showed malignant tumours in 12 (25%), premalignant lesions in 19 (40%), non‐neoplastic lesions in six (12%) and lesions not confirmed by colonoscopy in 11 (23%). Our data agreed with previously published data. Statistical analysis did not show any significant relationship between the presence/absence of neoplastic disease and patient sex or age, type of primary disease and anatomical site of [¹⁸F]FDG uptake. Comparing our data with various screening programmes, a significant difference was found only with series in which colonoscopy was performed in patients at high risk for colorectal cancer. Conclusion Focal incidental colorectal uptake of [¹⁸F]FDG is observed in about 1% of PET/CT studies and carries a high risk of neoplastic disease. A PET‐CT report should suggest colonoscopy when abnormal findings are reported.     

Diagnostic Performance of CT Attenuation Values of Focal 18F‐FDG Avid Breast Lesions Detected on Whole‐Body PET‐CT in Postoperative Breast Cancer Patients

To assess whether CT attenuation values help in differentiating benign from malignant etiology of focal ¹⁸F‐FDG avid breast lesions detected on whole‐body PET/CT exam in postoperative breast cancer patients. Institutional review board approval and waived informed consent were obtained for this HIPAA‐compliant retrospective study. Between January 2009 and July 2011, a total of 85 patients had 97 focal ¹⁸F‐FDG avid breast lesions on whole‐body PET/CT. Of these, 54 (56%) lesions were biopsy‐proven primary invasive breast carcinoma that had not undergone treatment at the time of PET/CT, 35 (36%) were benign lesions, and 8 were locally recurrent breast carcinoma. Mean attenuation values were retrospectively measured in Hounsfield units (HU) for the correlative lesion on the CT portion of the exam. Receiver‐operating characteristic curves (ROC) were calculated to determine the optimal cutoff values of HU that would best discriminate between benign and malignant lesions. Interobserver agreement for measured mean attenuation values was assessed by calculating the intraclass correlation coefficient (ICC). Mean HU for the benign lesions group and the local recurrence lesions group was ?11.0 ± 30.3 versus 32.9 ± 6.87 (p < 0.0002). ROC curve analysis comparing benign breast lesions to local recurrence lesions found an optimal cutoff value of 17 HU (area under curve = 0.982, p < 0.0001, Sensitivity = 100%, Specificity = 89%). ICC with regard to interobserver agreement in measuring the mean HU of the benign lesions was 0.84 (95% confidence interval 0.64–0.93) and for the malignant lesions was 0.88 (95% confidence interval 0.77–0.94). A CT attenuation threshold value of less than 17 HU suggests benign etiology of focal ¹⁸FDG avid breast lesions in postoperative breast cancer patients. If confirmed by additional studies, these findings may provide additional information to guide the treating physician regarding decisions for supplementary imaging or the need to biopsy.     

Tumor localization and biochemical response to cure in tumor‐induced osteomalacia

Tumor‐induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor‐23 (FGF23)‐secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and postoperative biochemical changes in 31 subjects with TIO. All had failed either initial localization, or relocalization (in case of recurrence or metastases) at outside institutions. Functional imaging with ¹¹¹Indium‐octreotide with single photon emission computed tomography (octreo‐SPECT or SPECT/CT), and ¹⁸fluorodeoxyglucose positron emission tomography/CT (FDG‐PET/CT) were performed, followed by anatomic imaging (CT, MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20 of 31 subjects (64.5%). Nineteen of 20 subjects underwent octreo‐SPECT imaging, and 16 of 20 FDG‐PET/CT imaging. Eighteen of 19 (95%) were positive on octreo‐SPECT, and 14 of 16 (88%) on FDG‐PET/CT. Twelve of 20 subjects underwent VS; 10 of 12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were as follows: sensitivity = 0.95, specificity = 0.64, PPV = 0.82, and NPV = 0.88 for octreo‐SPECT; sensitivity = 0.88, specificity = 0.36, PPV = 0.62, and NPV = 0.50 for FDG‐PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease‐free at last follow‐up. Serum phosphorus returned to normal in all subjects within 1 to 5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C‐terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25‐dihydroxyvitamin D₃ (1,25D) rose and exceeded the normal range. In this systematic approach to tumor localization in TIO, octreo‐SPECT was more sensitive and specific, but in many cases FDG‐PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation.     

Combined 18F‐fluorocholine and 18F‐fluoride positron emission tomography/computed tomography imaging for staging of high‐risk prostate cancer

Study Type – Diagnosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Positron emission tomography/computed tomography (PET/CT) with choline and fluoride for the detection of metastases in patients with prostate cancer have each been evaluated, with mixed results. Choline PET/CT has been evaluated against pelvic lymphadenectomy, generally with a low sensitivity but a high specificity; however, the study populations have been heterogenous. Fluoride PET/CT has been evaluated against other imaging methods, such as bone scan, single photon emission CT and MRI, and has been shown to have high specificity as well as sensitivity for bone metastases, but there are no studies with biopsy verification. This is the first study that evaluates the clinical use of both choline and fluoride PET/CT on the same patients in a well‐defined population of patients with high‐risk prostate cancer.

OBJECTIVE

• ? To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both ¹⁸F‐fluorocholine and ¹⁸F‐fluoride as markers, add clinically relevant information for patients with prostate cancer who have high‐risk tumours and a normal or inconclusive planar bone scan.

PATIENTS AND METHODS

• ? Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8–10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a ¹⁸F‐fluorocholine and a ¹⁸F‐fluoride PET/CT.
• ? None of the patients received hormonal therapy before the staging procedures were completed.

RESULTS

• ? For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases.
• ? ¹⁸F‐fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%).
• ? ¹⁸F‐fluoride PET/CT was suggestive for bone metastases in 37 patients (41%).
• ? In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non‐curative.
• ? Of the patients with positive scans, 74% had Gleason score 8–10 tumours. Of the patients with Gleason score 8–10 tumours, 64% had positive scans.

CONCLUSIONS

• ? PET/CT scans with ¹⁸F‐fluorocholine and ¹⁸F‐fluoride commonly detect metastases in patients with high‐risk prostate cancer and a negative or inconclusive bone scan.
• ? For 20% of the patients the results of the PET/CT scans changed the treatment plan.

     

Predicting neo‐adjuvant chemotherapy response and progression‐free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F‐18 FDG PET/CT and diffusion‐weighted MR imaging

Predicting response to neo‐adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion‐weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co‐occurrence matrix, the voxel‐alignment matrix, neighborhood intensity difference matrix, intensity size‐zone matrix (ISZM), normalized gray‐level co‐occurrence matrix (NGLCM), neighboring gray‐level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression‐free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow‐up period of 17.3 months, 14 patients experienced recurrence. High‐intensity zone emphasis (HIZE) and high‐intensity short‐zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence.     

Fluorodeoxyglucose F18 Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F¹⁸ (¹⁸F‐FDG), thus ¹⁸F‐FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 ¹⁸F‐FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 ± 18 minutes after administration of 3.2 ± 0.2 MBq/kg of ¹⁸F‐FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, and 2.2 ± 1.2 for the normal, borderline, AR, and other groups, respectively. One‐way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r² = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, ¹⁸F‐FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs with suspected AR.     

The Role of Preoperative [18F]Fluorodeoxyglucose Positron Emission Tomography in Predicting Early Recurrence After Curative Resection of Hepatocellular Carcinomas

Purpose  

¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan reflects tumor differentiation and predicts clinical outcome in patients with hepatocellular carcinoma (HCC). We investigated the correlation of PET scans with tumor differentiation and early tumor recurrence (time-to-recurrence <1 year).     

Incidental focal colonic lesions found on 18Fluorodeoxyglucose positron emission tomography/computed tomography scan: further support for a national guideline on definitive management

Aim ¹⁸Fluorodeoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) is an established part of staging in a wide variety of malignancies. Incidental abnormal uptake of ¹⁸FDG of unknown significance is frequently encountered. Therefore, we investigated patients with abnormal colonic uptake of ¹⁸FDG, determined by PET/CT images, using colonoscopy. Method The radiology reports of all patients referred to a tertiary referral centre for a PET/CT scan were reviewed retrospectively. Patients with abnormal colonic uptake of ¹⁸FDG were identified and the PET/CT findings were correlated with colonoscopic findings. Results Of 555 consecutive patients identified over a 26‐month period, 53 had abnormal colonic uptake of ¹⁸FDG, as determined by PET/CT images. Twenty‐nine were not investigated following discussion in a specialist multidisciplinary (MDT) meeting, according to local protocol. Twenty out of 24 patients investigated by endoscopy had a colonic lesion correlating to the site identified on the PET/CT image: 16 patients had tubulovillous adenomas (nine of which were > 10 mm), two had invasive adenocarcinomas, two had diverticular disease and one had collagenous colitis; no colonic lesion was detected in three. These findings were incidental and not related to the primary diagnosis for which the scan was being performed. Accordingly, a positive predictive value of 83% is associated with the finding of abnormal uptake of ¹⁸FDG on PET/CT images. Conclusion Incidental abnormal colonic uptake of ¹⁸FDG, determined by a PET/CT scan requires definitive colonic investigation in patients suitable for further treatment because significant colonic pathology is frequently identified. The benefit of this approach should be discussed in specialist MDT meetings and tailored to each patient; however, national guidelines for management are required.     

Living donor liver transplantation or resection for Child‐Pugh A hepatocellular carcinoma patients with multiple nodules meeting the Milan criteria

The optimum primary treatment strategy for early hepatocellular carcinoma (HCC) patients with multiple nodules remains unclear. We aimed to compare the outcomes of living donor liver transplantation (LDLT) with that of liver resection (LR) for early Child‐Pugh A HCC patients with multiple nodules meeting the Milan criteria. From January 2007 to July 2012, 67 of 375 patients with early HCC in our centre fulfilled the inclusion criteria (group LDLT, n = 34 versus group LR, n = 33). Patient and tumour characteristics, operative data, postoperative course and outcomes were analysed retrospectively. The postoperative mortality and rate of major complications were similar in both groups. The 5‐year overall survival (OS; 76.5% vs. 51.2%, P = 0.046) and recurrence‐free survival (RFS; 72.0% vs. 19.8%, P = 0.000) were better in group LDLT than that in group LR. The 5‐year OS and RFS were similar between patients with tumours located in the same lobe (TSL) and those in the different lobes (TDL) after LDLT, whereas the 5‐year RFS was better in patients with tumours in TSL (30.6% vs. 0%, P = 0.012) after LR. In conclusion, primary LDLT might be the optimum treatment for early HCC patients with multiple nodules meeting the Milan criteria.     

The clinical advances of fluorine‐2‐D‐deoxyglucose – positron emission tomography/computed tomography in urological cancers

Fluorine‐18 labeled fluorine‐2‐D‐deoxyglucose (FDG) is the most frequently used positron emission tomography (PET) probe but it has certain limitations when used in urological cancers. The introduction of co‐registered PET and computed tomography (PET/CT) represents a major advance in technology and FDG‐PET/CT has now become the new standard. The diagnostic performance of FDG‐PET and PET/CT depends on the metabolic activity of tumor tissue, which is generally low in primary renal cell and prostate cancers and often in their metastatic deposits. In contrast, both seminomatous and nonseminomatous germ cell tumors are characterized by upregulated glucose metabolism with subsequently increased FDG uptake in tumor sites. Generally, the metabolic activity provides accurate information regarding the presence of a viable tumor, except in patients with residual mature teratoma. Although bladder cancer demonstrates sufficiently increased FDG uptake, primary tumors are difficult to identify due to the renal excretion of FDG. The accuracy of FDG‐PET/CT in metabolically active metastases is generally higher compared to conventional CT except for identifying small lung deposits. With disease progression and subsequent de‐differentiation of prostate cancer, castrate resistant disease is more likely to present with lesions that have increased glucose metabolism.     

Whole-Body [18F]FDG PET in the Management of Metastatic Brain Tumours

Summary Background To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [¹⁸F]FDG was performed in 20 consecutive patients. Methods  All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [¹⁸F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. Results  Metastatic brain tumours were diagnosed on whole-body [¹⁸F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [¹⁸F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [¹⁸F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewing's sarcoma, and cavernous angioma.  Patients felt no discomfort during the whole-body [¹⁸F]FDG PET procedure and there were no complications. The false negative rate in [¹⁸F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [¹⁸F]FDG PET or conventional work-up. Conclusion  It is suggested that whole-body [¹⁸F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.     

Expanded living‐donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5‐5‐500 rule ‐ a retrospective study

Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living‐donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5‐year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha‐fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5‐5‐500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa‐fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5‐year recurrence rate of 7.3% (5.2–9.3) and a 19% increase in the number of eligible patients. In addition, the 5‐5‐500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria – the 5‐5‐500 rule – might provide rational expansion for LDLT candidates with HCC.     

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([¹⁸F]FDG) and [¹⁸F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [¹⁸F]FDG, for detecting inflammatory processes, or [¹⁸F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV_mean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [¹⁸F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [¹⁸F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [¹⁸F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.     

Prognostic Value of Preoperative Metabolic Tumor Volume and Total Lesion Glycolysis in Patients with Epithelial Ovarian Cancer

Purpose

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) uptake on PET/CT images. The purpose of this study was to investigate the relationship between functional tumor parameters (MTV and TLG) and clinical outcomes in patients with epithelial ovarian cancer (EOC).

Methods

Fifty-five patients with EOC who had undergone [¹⁸F]FDG PET/CT before surgical staging were included in this retrospectively study. For each patient, we determined the highest (SUV_max and SUV_avg), the cumulative TLG, and the sum of all MTV, and compared their predictive value of recurrence and the effects of pretreatment functional tumor activity on progression-free interval (PFI).

Results

The median duration of PFI was 11 (range 3?C43) months, and 20 patients (36.4%) experienced recurrence. Poor outcome was associated with higher values for both the MTV (P?=?0.022, hazard ratio 5.571, 95% confidence interval 1.279?C24.272) and the TLG (P?=?0.037, hazard ratio 2.967, 95% confidence interval 1.065?C8.265). The Kaplan?CMeier survival graphs showed a significant difference in PFI between the groups categorized by MTV and TLG, respectively (P?=?0.01 for MTV, P?=?0.0287 for TLG, log rank test).

Conclusions

Pretreatment metabolic parameters such as MTV and TLG showed statistically significant association with recurrence in patients with EOC. These values can be useful quantitative criteria for disease prognostication in patients with EOC before treatment.     

Comparison of 18F‐FDG PET/CT and 68Ga‐DOTATATE PET/CT in the Targeted Imaging of Culprit Tumors Causing Osteomalacia

ObjectiveTo assess and compare the performance of fluorine‐18‐labeled fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG‐PET/ CT) and gallium‐68‐labeled tetraazacyclododecanetetraacetic acid‐DPhe1‐Tyr3‐octreotate (⁶⁸Ga‐ DOTATATE) PET/CT in the targeted imaging of culprit tumors causing osteomalacia.MethodsThis was a clinical retrospective analysis. We analyzed 13 patients (five men, eight women; mean age, 49 years; range, 19–55 years) with suspicion of tumor‐induced osteomalacia (TIO) between March 2017 and October 2019. All patients underwent two functional imaging methods to locate the culprittumors. Studies were performed on a PET/CT scanner. The injection doses of ¹⁸F‐ FDG and ⁶⁸Ga‐DOTATATE were 0.5mCi/kg and approximately 5.0mCi, respectively. In the two scans, the whole body was captured from head to toe 45 to 60 min after intravenous tracer injection. ⁶⁸Ga‐DOTATATE PET/CT and ¹⁸F‐FDG PET/CT imaging results locate culprit tumors according to the following criteria: (i) abnormal foci uptake concentration was observed locally, and the uptake level was higher than the background level of the right lobe of the liver; (ii) combined CT showed or did not have obvious abnormal density changes; and (iii) non‐specific ingestion lesions due to fracture, arthritis, necrosis of femoral head are excluded. Compared with the results of pathological examination and clinical follow‐up, the sensitivity, specificity and accuracy of ⁶⁸Ga‐DOTATATE PET/CT imaging and ¹⁸F‐FDG PET/CT imaging for TIO were analyzed.ResultsAll patients had symptoms of osteomalacia and hypophosphatemia. The lag time (symptoms to PET diagnosis) ranged from 2 to 12 years. There were eight cases of TIO patients and five cases of non‐TIO patients confirmed by surgery, pathology and follow‐up. Among the eight TIO patients, there were six cases (75.0%) of PMTs, one case (12.5%) of giant cell tumor, one case (12.5%) of hemangiopericutoma. Most (n = 6, 75.0%) of the confirmed tumors in our patient population were in the lower extremities, followed by craniofacial regions (n = 1, 12.5%), and torso (n = 1, 12.5%), respectively. Among the five non‐TIO patients, there were two cases of Fanconi syndrome, one case of rickets, and two cases of sporadic osteomalacia hypophosphorus. The culprit tumors could be located either in the bone (n = 5, 62.5%) or the soft tissue (n = 3, 37.5%). ¹⁸F‐FDG PET/CT was able to localize the tumor in six (6/13, 46.1%) patients. ⁶⁸Ga‐DOTATATE PET/CT detected tumor in 8 (83.3%) of 13 patients. The sensitivity of ⁶⁸Ga‐DOTATATE PET/CT imaging and ¹⁸F‐FDG PET/CT imaging in the evaluation of TIO in our patient population were 100% (8/8) vs 75% (6/8). The specificity of the two different methods was 80% (4/5). The overall accuracy was 92.3% (12/13) vs 76.9% (10/13).Conclusions ⁶⁸Ga‐DOTATATE PET/CT is very effective in assessing hypophosphatemia patients with TIO typical symptoms compared with ¹⁸F‐FDG. Therefore, in clinically suspected cases of hypophosphatemic osteomalacia, ⁶⁸Ga‐DOTATATE PET/CT should be preferred as an imaging modality investigation to avoid delay in the treatment of this disease.     

Diagnostic yield of 18F‐FDG PET/CT imaging and urinary CXCL9/creatinine levels in kidney allograft subclinical rejection

Subclinical kidney allograft acute rejection (SCR) corresponds to “the unexpected histological evidence of acute rejection in a stable patient.” SCR detection relies on surveillance biopsy. Noninvasive approaches may help avoid biopsy‐associated complications. From November 2015 to January 2018, we prospectively performed positron emission tomography/computed tomography (PET/CT) after injection of F¹⁸‐fluorodeoxyglucose (¹⁸F‐FDG) in adult kidney transplant recipients with surveillance biopsy at ~3 months posttransplantation. The Banff‐2017 classification was used. The ratio of the mean standard uptake value (mSUVR) between kidney cortex and psoas muscle was measured. Urinary levels of CXCL‐9 were concomitantly quantified. Our 92‐patient cohort was categorized upon histology: normal (n = 70), borderline (n = 16), and SCR (n = 6). No clinical or biological difference was observed between groups. The mSUVR reached 1.87 ± 0.55, 1.94 ± 0.35, and 2.41 ± 0.54 in normal, borderline, and SCR groups, respectively. A significant difference in mSUVR was found among groups. Furthermore, mSUVR was significantly higher in the SCR vs normal group. The area under the receiver operating characteristic curve (AUC) was 0.79, with 83% sensitivity using an mSUVR threshold of 2.4. The AUC of urinary CXCL‐9/creatinine ratios comparatively reached 0.79. The mSUVR positively correlated with ti and acute composite Banff scores. ¹⁸F‐FDG‐PET/CT helps noninvasively exclude SCR, with a negative predictive value of 98%. External validations are required.