Sarcopenia does not affect liver regeneration and postoperative course after a major hepatectomy. A prospective study on 125 patients using CT volumetry and HIDA scintigraphy.

BACKGROUND & OBJECTIVES: Sarcopenia is a morbi-mortality risk factor in digestive surgery, though its impact after major hepatectomy (MH) remains unknown. This prospective pilot study investigated whether volume and function of a regenerating liver is influenced by body composition. METHODS: From 2011 to 2016, 125 consecutive patients had computed tomography and 99mTc-labelled-mebrofenin SPECT-scintigraphy before and after MH at day 7 and 1 month for measurements of liver volumes and functions. L3 vertebra muscle mass identified sarcopenia. Primary endpoint was the impact of sarcopenia on regeneration capacities (i.e. volume/function changes and post-hepatectomy liver failure (PHLF) rate). Secondary endpoint was 3-month morbi-mortality. RESULTS: Sarcopenic patients (SP; N = 69) were significantly older than non-sarcopenic (NSP), with lower BMI and more malignancies, but with comparable liver function/volume at baseline. Postoperatively, SP showed higher rates of ISGLS_PHLF (24.6 % vs 10.9 %; p = 0.05) but with comparable rates of severe morbidity (23.2 % vs 16.4 %; p = 0.35), overall (8.7 % vs 3.6 %; p = 0.3) and PHLF-related mortality (8,7 % vs 1.8 %; p = 0.075). After matching on the extent of resection or using propensity score, regeneration and PHLF rates were similar. CONCLUSION: This prospective study using first sequential SPECT-scintigraphy showed that sarcopenia by itself does not affect liver regeneration capacities and short-term postoperative course after MH.

Giant cell arteritis-related cerebrovascular ischemic events: a French retrospective study of 271 patients, systematic review of the literature and meta-analysis.

BACKGROUND: Cerebrovascular ischemic events (CIE) are among the most severe complications of giant cell arteritis (GCA). Heterogeneity between different studies in the definition of GCA-related CIE leads to uncertainty regarding their real prevalence. The aim of our study was to evaluate the prevalence and describe the characteristics of GCA-related CIE in a well-phenotyped cohort completed by a meta-analysis of the existing literature. METHODS: In this retrospective study performed in the Lille University Hospital, all consecutive patients with GCA according to American College of Rheumatology (ACR) diagnostic criteria were included from January 1, 2010, to December 31, 2020. A systematic review of the literature using MEDLINE and EMBASE was performed. Cohort studies of unselected GCA patients reporting CIE were included in the meta-analysis. We calculated the pooled summary estimate of GCA-related CIE prevalence. RESULTS: A total of 271 GCA patients (89 males, mean age 72 ± 9 years) were included in the study. Among them, 14 (5.2%) presented with GCA-related CIE including 8 in the vertebrobasilar territory, 5 in the carotid territory, and 1 patient having multifocal ischemic and hemorrhagic strokes related to intra-cranial vasculitis. Fourteen studies were included in the meta-analysis, representing a total population of 3553 patients. The pooled prevalence of GCA-related CIE was 4% (95% CI 3-6, I2 = 68%). Lower body mass index (BMI), vertebral artery thrombosis on Doppler US (17% vs 0.8%, p = 0.012), vertebral arteries involvement (50% vs 3.4%, p < 0.001) and intracranial arteries involvement (50% vs 1.8%, p < 0.001) on computed tomography angiography (CTA) and/or magnetic resonance angiography (MRA), and axillary arteries involvement on positron emission computed tomography (PET/CT) (55% vs 20%, p = 0.016) were more frequent in GCA patients with CIE in our population. CONCLUSIONS: The pooled prevalence of GCA-related CIE was 4%. Our cohort identified an association between GCA-related CIE, lower BMI, and vertebral, intracranial, and axillary arteries involvement on various imaging modalities.

Evaluation of a convolution neural network for baseline total tumor metabolic volume on [18F]FDG PET in diffuse large B cell lymphoma.

OBJECTIVES: New PET data-processing tools allow for automatic lesion selection and segmentation by a convolution neural network using artificial intelligence (AI) to obtain total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) routinely at the clinical workstation. Our objective was to evaluate an AI implemented in a new version of commercial software to verify reproducibility of results and time savings in a daily workflow. METHODS: Using the software to obtain TMTV and TLG, two nuclear physicians applied five methods to retrospectively analyze data for 51 patients. Methods 1 and 2 were fully automated with exclusion of lesions ≤ 0.5 mL and ≤ 0.1 mL, respectively. Methods 3 and 4 were fully automated with physician review. Method 5 was semi-automated and used as reference. Time and number of clicks to complete the measurement were recorded for each method. Inter-instrument and inter-observer variation was assessed by the intra-class coefficient (ICC) and Bland-Altman plots. RESULTS: Between methods 3 and 5, for the main user, the ICC was 0.99 for TMTV and 1.0 for TLG. Between the two users applying method 3, ICC was 0.97 for TMTV and 0.99 for TLG. Mean processing time (± standard deviation) was 20 s ± 9.0 for method 1, 178 s ± 125.7 for method 3, and 326 s ± 188.6 for method 5 (p < 0.05). CONCLUSION: AI-enabled lesion detection software offers an automated, fast, reliable, and consistently performing tool for obtaining TMTV and TLG in a daily workflow. KEY POINTS: • Our study shows that artificial intelligence lesion detection software is an automated, fast, reliable, and consistently performing tool for obtaining total metabolic tumor volume and total lesion glycolysis in a daily workflow.

Complete pathological response following chemotherapy and radiotherapy in two cases of advanced anaplastic thyroid carcinoma.

Introduction: Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets. Case presentation: Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair-gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages. Conclusion: We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.

Pituitary adenoma & nuclear medicine: Recent outcomes and ongoing developments.

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

18F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study.

BACKGROUND: Interstitial lung disease is a common complication of systemic sclerosis (SSc-ILD), and it remains difficult to accurately predict its course. Progressing ILD could be more metabolically active, suggesting that the 18F-FDG tracer could be a tool in the managing of SSc-ILD. METHODS: In our center, SSc patients and controls (non-Hodgkin lymphoma cured after first-line regimen) who had received a PET/CT were screened retrospectively. The FDG uptake (visual intensity, pattern, SUVmax) was systematically recorded in > 30 regions of interest (ROIs) linked to SSc in a blind reviewing by 2 independent nuclear medicine physicians using a standardized form. RESULTS: Among the 545 SSc patients followed up in our center, 36, including 22 SSc-ILDs, had a PET/CT, whose indication was cancer screening in most cases. The mean ± SD age was 57.9 ± 13.0 years with 20/36 females. Fourteen patients had a disease duration of less than 2 years. A third had anti-centromere antibodies and 27.8% had anti-topoisomerase antibodies. Pulmonary FDG uptakes were higher in SSc patients than in controls (n = 89), especially in those with ILD compared with those without ILD. Pulmonary FDG uptakes were positively correlated with the ILD severity (fibrosis extent, %FVC, and %DLCO). No significant difference was found in the FDG uptakes from extrathoracic ROIs. Progressing SSc-ILDs within the 2 years after PET/CT (n = 9) had significant higher pulmonary FDG uptakes at baseline than stable SSc-ILDs (n = 13). CONCLUSION: PET/CT could be a useful tool in the assessment of the severity and the prediction of pulmonary function outcome of SSc-ILD.

Quantitative dual isotope 123iodine/99mTc-MIBI scintigraphy: A new approach to rule out malignancy in thyroid nodules.

BACKGROUND: The aim of this study was to evaluate the role of dual isotope 123Iodine/99mTc-MIBI thyroid scintigraphy (IMS) in discriminating between malignant and benign lesions in indeterminate nodules using quantitative analysis methods. METHODS: Thirty-five consecutive patients with thyroid nodules of indeterminate or non-diagnostic cytology and cold on 123Iodine scintigraphy (10 Bethesda I, 24 Bethesda III-IV, 1 in which cytology was impossible) underwent IMS between 2017 and 2019 with uptake quantification at two time points ahead of thyroidectomy: early and late. Images were analyzed by two blinded physicians. RESULTS: Twelve nodules were malignant and 23 benign on histopathology. Mean uptake values were lower in benign than in malignant nodules at both time points: early, 8.7±4.1 versus 12.9±3.5 (P=0.005); and late, 5.3±2.7 versus 7.7±1.1 (P=0.008). Interobserver reproducibility was excellent. The intraclass correlation coefficient was 0.86 in benign and 0.92 in malignant lesions for early uptake result (ER) and 0.94 and 0.85 respectively for late uptake result (LR). The optimal LR cut-off  to exclude a diagnosis of malignancy was set at 5.9 . The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off were, respectively, 100%, 65.2%, 60%, 100% and 77.1%. CONCLUSION: Despite some study limitations, quantitative analysis of 99mTc-MIBI thyroid scintigraphy had a good reproducibility, which could help to rule out malignancy in non-diagnostic or indeterminate thyroid nodules and thereby reducing the number of patients undergoing unnecessary surgery when LR is below 5.9.

The Impact of Modern Chemotherapy and Chemotherapy-Associated Liver Injuries (CALI) on Liver Function: Value of 99mTc-Labelled-Mebrofenin SPECT-Hepatobiliary Scintigraphy.

BACKGROUND: Chemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS). METHODS: From 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (≥ 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (≤ 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues. RESULTS: Among 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis ≥ 30% significantly compromised function, as well as NAS, especially grades 2-5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis ≥ 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS. CONCLUSIONS: In this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction through steatosis or NAS.

Imaging for Metastasis in Prostate Cancer: A Review of the Literature.

Background: Initial staging and assessment of treatment activity in metastatic prostate cancer (PCa) patients is controversial. Indications for the various available imaging modalities are not well-established due to rapid advancements in imaging and treatment. Methods: We conducted a critical literature review of the main imaging abnormalities that suggest a diagnosis of metastasis in localized and locally advanced PCa or in cases of biological relapse. We also assessed the role of the various imaging modalities available in routine clinical practice for the detection of metastases and response to treatment in metastatic PCa patients. Results: In published clinical trials, the most commonly used imaging modalities for the detection and evaluation of therapeutic response are bone scan, abdominopelvic computed tomography (CT), and pelvic and bone magnetic resonance imaging (MRI). For the detection and follow-up of metastases during treatment, modern imaging techniques i.e., choline-positron emission tomography (PET), fluciclovine-PET, or Prostate-specific membrane antigen (PSMA)-PET provide better sensitivity and specificity. This is particularly the case of fluciclovine-PET and PSMA-PET in cases of biochemical recurrence with low values of prostate specific antigen. Conclusions: In routine clinical practice, conventional imaging still have a role, and communication between imagers and clinicians should be encouraged. Present and future clinical trials should use modern imaging methods to clarify their usage.

Prognostic value of the metabolic bulk volume in patients with diffuse large B-cell lymphoma on baseline 18F-FDG PET-CT.

We retrospectively investigated the prognostic value of the metabolic bulk volume (MBV), defined as the metabolic volume of the largest lesion, in 106 patients with diffuse large B-cell lymphoma who underwent baseline 18FDG PET-CT. Semi-automatically segmented (41% SUVmax) total metabolic tumor volume (TMTV) and MBV underwent receiver operating characteristic analysis, identifying optimal thresholds of 147 cm3 for the TMTV and 41.5 cm3 for the MBV. A low TMTV and a low MBV were significantly associated with longer progression-free survival (PFS) and overall survival (OS). According to Cox multivariate analysis, the TMTV and MBV were independent predictors, respectively, for PFS (HR = 3.501), and OS (HR = 7.242). The TMTV and MBV classification were discordant in 18.9% of patients with a 5-year PFS rate of 100% for patients with low MBV/high TMTV and 74% for high MBV/low TMTV. The baseline MBV can be an efficient tool for the risk stratification of aggressive lymphoma.

Asymmetric kinetics of volume and function of the remnant liver after major hepatectomy as a key for postoperative outcome - A case-matched study.

BACKGROUND: The kinetics of remnant liver (RL) function is unknown after major hepatectomy (MH), especially in case of post-hepatectomy liver failure (PHLF). This study investigated the change in RL function after MH using 99mTc-labelled-mebrofenin SPECT-scintigraphy and its correlation with RL volume and PHLF. METHODS: From 2011 to 2015, 125 patients undergoing MH had volumetric assessment by CT and functional SPECT-scintigraphy preoperatively and at day 7 (POD7) and 1 month (1M). RL volume and function changes were compared in (i) overall population and (ii) 17 patients with vs. 42 without PHLF (ISGLS) matched on preoperative RL function. RESULTS: Increase in RL function correlated poorly with volume increase at POD7 (r = 0.035, p = 0.43) and 1M (r = 0.394, p < 0.0001). Overall, function increase on POD7 (+38.8%) was lower than volume (+49.4%), but comparable at 1M (+78.8% vs. +73%). PHLF patients showed lower function increase on POD7 (+2.1% [-89%-77.8%] vs. +50% [-39%-218%]; p = 0.006). At 1M, 4 PHLF patients died with no function increase despite significant volumetric gain. CONCLUSIONS: We first showed via sequential SPECT-scintigraphy that RL function increase after MH is slower than volume increase. A poor kinetic of function was correlated with PHLF as early as POD7, contrasting with substantial volume gain in PHLF patients.

Laparoscopic Partial ALPPS: Much Better Than ALPPS!

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has emerged as an alternative for patients with bilobar colorectal liver metastasis deemed unresectable due to inadequate future remnant liver (FRL). Nevertheless, high morbidity and mortality rates have been reported. In this setting, including hepatobiliary scintigraphy in the clinical and surgical management of patients offered ALPPS has been advocated to both assess eligibility for ALPPS stagel and suitable time for ALPPS stage2. Recently, it was stated that partial ALPPS with a liver split restricted to 50% of the transection line (or up to the middle hepatic vein in case of right extended hepatectomy) and a shortened stagel allows improving the postoperative course without precluding the inter-stages FRL hypertrophy. We describe a case series of p-ALPPS with stagel performed laparoscopically, including sequential assessments of the FRL volumes and functions via pre-stagel and pre-stage2 computed tomography volumetry and HIDA SPECT-scintigraphy. In five patients, laparoscopic p-ALPPS was associated with rapid and significant gain of remnant functional volume - much better than previously observed for ALPPS - facilitating early stage2 without inflammatory adherences. In conclusion, laparoscopic p-ALPPS is feasible and seems less aggressive than the original ALPPS technique with total transection. It may be an interesting alternative to the classical portal vein embolization (PVE) and two-stage hepatectomy strategy.

High 18F-FDG Avidity of Low-Grade Esthesioneuroblastoma.

Esthesioneuroblastoma is a rare neuroectodermic tumor of the olfactory tract. An F-FDG PET/CT was performed in a 75-year-old woman with cervical lymphadenopathy. It demonstrated focal intense uptake (SUVmax, 72 g/mL) in an occult sphenoclival tumor. Anatomopathological examination of the lymphadenopathy and the primary tumor biopsy revealed well-differentiated esthesioneuroblastoma. Explaining the paradox between tumor differentiation and PET findings, immunohistochemistry showed low Ki-67 but overexpression of GLUT-1 suggesting an activation of hypoxia pathways. Unlike many solid tumors, FDG avidity is not correlated with histological grade in esthesioneuroblastoma. The tumor biology may clarify the discrepancy between metabolic activity and cellular mitotic processes.

Contribution of hepatobiliary scintigraphy in assessing ALPPS most suited timing.

To reduce post-hepatectomy liver failure (PHLF), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently developed for patients with a limited future remnant liver (FRL). Nevertheless, high morbi-mortality rates have been reported . The current study aimed to analyze the kinetics of FRL function in patients who were offered ALPPS. Serial SPECT (99 m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) was performed in all patients before and after surgery as well as at inter-stage to quantitatively assess hepatic function [total liver (TL) and FRL]. Patients were offered ALPPS for colorectal liver metastases (CLMs) (n = 6) and gallbladder carcinoma (n = 1). The data of delta of function or volume, expressed as (postoperative FRL - preoperative FRL/preoperative FRL) were compared to those derived from HBS of patients referred to the university hospital of Lille for one-stage major hepatectomy (n = 93). Additionally, the intrinsic liver function (i.e. function per unit of volume) was used to assess the regeneration rate. All but one patient had an anticipated FRL to body weight ratio (FRLBWR) ≤0.5%. Inter-stages HBS showed a progressive attenuation of the functional value of the excluded hepatic segments in favour of the FRL for all patients. Overall, there was a drop of total liver function contrasting with subnormal passive biochemical tests. Notably, the increase in FRL function between ALPPS stages [+12.5% (4.2-28.6%)] was lower than the volumetric gain [+42.6% (18.3-110.2%)] and inferior to that observed after one-stage major hepatectomy [+41.7% (-38.6 to +158.33%)]. This resulted in a drop of the FRL intrinsic liver function in ALPPS patients, of whom one died from PHLF. Our study enhances the importance of assessing liver function along with volume during ALPPS procedure and supports HBS as a suitable and reliable method, including a valuable contribution to determine most appropriate stage 2 surgical timing.

FDG PET/CT allowing detection and follow-up of tumor cell transplantation.

After detection of small cell lung cancer in a 67-year-old patient who had donated a kidney 7 months earlier, the graft recipient underwent FDG-PET/CT to determine the presence/absence of tumor cell transmission. It showed abnormal increased uptake of the renal graft, associated with hypermetabolic lymph nodes and hepatic, pulmonary and bone lesions. Emergency graft resection was performed 5 days after PET/CT, permitting immunosuppressive therapy withdrawal. Pathologic examination of the kidney showed parenchymal infiltration by tumor cells compatible with small cell lung cancer. Thereafter, pathologists proved that the recipient's and donor's tumor cells matched using microsatellite markers. FDG-PET/CT was performed in the follow-up and showed progression in the donor despite chemotherapy and radiotherapy. He died a few months later. However, FDG-PET/CT showed a complete metabolic response after only 3 courses of chemotherapy in the recipient.

Is STAPLE algorithm confident to assess segmentation methods in PET imaging?

Accurate tumor segmentation in [18F]-fluorodeoxyglucose positron emission tomography is crucial for tumor response assessment and target volume definition in radiation therapy. Evaluation of segmentation methods from clinical data without ground truth is usually based on physicians' manual delineations. In this context, the simultaneous truth and performance level estimation (STAPLE) algorithm could be useful to manage the multi-observers variability. In this paper, we evaluated how this algorithm could accurately estimate the ground truth in PET imaging. Complete evaluation study using different criteria was performed on simulated data. The STAPLE algorithm was applied to manual and automatic segmentation results. A specific configuration of the implementation provided by the Computational Radiology Laboratory was used. Consensus obtained by the STAPLE algorithm from manual delineations appeared to be more accurate than manual delineations themselves (80% of overlap). An improvement of the accuracy was also observed when applying the STAPLE algorithm to automatic segmentations results. The STAPLE algorithm, with the configuration used in this paper, is more appropriate than manual delineations alone or automatic segmentations results alone to estimate the ground truth in PET imaging. Therefore, it might be preferred to assess the accuracy of tumor segmentation methods in PET imaging.