Adjunctive High-Definition Transcranial Direct Current Stimulation in Brain Glutamate-Glutamine and γ-Aminobutyric Acid, Withdrawal and Craving During Early Abstinence Among Patients With Opioid Use Disorder on Buprenorphine-Naloxone: A Proton Magnetic Resonance Spectroscopy-Based Pilot Study.

OBJECTIVE: Our study aimed to (1) examine the effect of adjunctive high-definition transcranial direct current stimulation (HD-tDCS) in craving and withdrawal among patients with opioid use disorder on buprenorphine-naloxone, and (2) examine effect of HD-tDCS changes in glutamate-glutamine and γ-aminobutyric acid (GABA) at the left dorsolateral prefrontal cortex (DLPFC) among patients with opioid use disorder on buprenorphine-naloxone. METHODS: This was a pilot randomized double-blind, sham-controlled parallel-group study. A total of 28 patients on buprenorphine-naloxone (6/1.5 mg/d) were randomly allocated into 2 groups for active and sham HD-tDCS stimulation. High-definition transcranial direct current stimulation was administered twice daily for consecutive 5 days, from days 2 to 6. The Clinical Opiate Withdrawal Scale (COWS), the Desire for Drug Questionnaire (DDQ), the Obsessive-Compulsive Drug Use Scale (OCDUS), and glutamate-glutamine and GABA at DLPFC via proton magnetic resonance spectroscopy were measured at baseline and on day 7. RESULTS: Both active and sham groups had comparable changes in DDQ, OCDUS (except 2 subcomponents), COWS, and glutamate-glutamine and GABA at DLPFC. In the active HD-tDCS group, statistically significant reductions were observed in DDQ, OCDUS, and COWS but not in glutamate-glutamine and GABA. CONCLUSIONS: The adjunctive active HD-tDCS group showed comparable changes in craving and withdrawal, and glutamate-glutamine and GABA at DLPFC compared with sham HD-tDCS. Craving and withdrawal but not glutamate-glutamine and GABA at DLPFC decreased significantly with adjunctive HD-tDCS. Future studies with larger sample size and online assessment of glutamate-glutamine and GABA would enhance our knowledge.

Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617.

PURPOSE: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. METHODS: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. RESULTS: This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4-4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8-0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2-4.4), ALP (HR 1.1; 95% CI, 1-1.2) and LDH (HR 1.2; 95% CI, 1-1.5) as biomarkers prognostic of overall survival. CONCLUSIONS: In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

Prostate-specific membrane antigen PET/computed tomography for staging prostate cancer.

PURPOSE OF REVIEW: Molecular imaging with PET/CT targeting the prostate-specific membrane antigen (PSMA) receptor is increasingly utilized in men with prostate cancer (PCa), with clinical indications now expanding beyond biochemical recurrence. PSMA PET/CT often detects sub-centimetre size pathologic nodes and low-volume bone marrow disease that are occult on conventional imaging when the lesion does not cause sclerosis or osteoblastic reaction in surrounding bone. This review focuses on recent evidence for PSMA PET/CT in initial disease staging. RECENT FINDINGS: Several recent studies including a large randomized trial have evaluated the clinical impact of PSMA PET/CT in initial staging of PCa. PSMA PET/CT is more sensitive and accurate than the conventional imaging standard of CT and bone scan. Change in treatment plan or modality of therapy occurs frequently when PSMA PET/CT forms part of the diagnostic algorithm. Hybrid PET/MRI also has potential utility, particularly in evaluating pelvic disease, but evidence base remains very limited. SUMMARY: PSMA PET/CT has emerged as a new standard in primary staging of PCa. Reimbursement by national funding bodies and incorporation into international clinical guidelines is anticipated within the next few years.

Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series.

PURPOSE: Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. METHODS: Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. RESULTS: Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 109/L, range 3-75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19-94), but from t-MN diagnosis was only 13 months (1-56), with death due primarily to haematological disease progression. CONCLUSIONS: The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.

Comparison of objective criteria and expert visual interpretation to classify benign and malignant hilar and mediastinal nodes on 18-F FDG PET/CT.

BACKGROUND AND OBJECTIVE: There is widespread adoption of FDG-PET/CT in staging of lung cancer, but no universally accepted criteria for classifying thoracic nodes as malignant. Previous studies show high negative predictive values, but reporting criteria and positive predictive values varies. Using Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) results as gold standard, we evaluated objective FDG-PET/CT criteria for interpreting mediastinal and hilar nodes and compared this to expert visual interpretation (EVI). METHODS: A retrospective review of all patients with lung cancer who had both FDG-PET/CT and EBUS-TBNA from 2008 to 2010 was performed. Scan interpretation was blinded to histology. Patients from 2008/2009 were used for the prediction set. The validation set analysed patients from 2010. Objective FDG-PET/CT criteria were SUVmax lymph node (SUVmaxLN), ratio SUVmaxLN/SUVmax primary lung malignancy, ratio SUVmaxLN/SUVaverage liver, ratio SUVmaxLN/SUVmax liver and ratio SUVmaxLN/SUVmax blood pool. A nuclear medicine physician reviewed all scans and classified nodal stations as benign or malignant. RESULTS: Eighty-seven malignant lymph nodes and 41 benign nodes were in the prediction set. All objective FDG-PET/CT criteria analysed were significantly higher in the malignant group (P < 0.0001). EVI correctly classified 122/128 nodes (95.3%). Thirty-four malignant nodes and 19 benign nodes were in the validation set. The new proposed cut-off values of the objective criteria from the prediction set correctly classified 44/53 (83.0%) nodes: 28/34 (82.4%) malignant nodes and 16/19 (84.2%) benign nodes. EVI had 91% accuracy: 33/34 (97.1%) malignant nodes and 15/19 (79.0%) benign nodes. CONCLUSIONS: Objective analysis of 18-F FDG PET/CT can differentiate between malignant and benign nodes but is not superior to EVI.

Lung Involvement Patterns in COVID-19: CT Scan Insights and Prognostic Implications From a Tertiary Care Center in Southern India.

Background COVID-19, caused by the SARS-CoV-2 virus, has presented an unparalleled challenge and a profound learning curve globally. Among the myriad of investigative tools, CT scans of the chest have become instrumental in assessing the magnitude of lung involvement in the pathogenesis of this disease. Objectives This study aimed to evaluate the distribution and patterns of lung involvement depicted in the CT chest scans of COVID-19 patients admitted to a specialized tertiary care center located in a southern state of India. Methods With clearance secured from the Institutional Ethics Committee, an analytical cross-sectional study was conducted. It encompassed CT chest images from all symptomatic COVID-19 patients within the designated study center during the specified study timeline. Subsequent data analysis ensued. Results Among the 1066 COVID-19 patients evaluated, ground-glass opacities (GGO) were the predominant lung involvement pattern. Distinct patterns, such as GGOs combined with solid consolidation or atelectasis, were noted, with the highest mortality linked to GGOs paired with pneumomediastinum (PM). Data underscored a direct correlation between the extent of lung involvement and patient prognosis, with specific lung regions, namely the right apical, right posterior, right superior basal, left superior lingular, and left inferior lingular segments, showing frequent involvement. Conclusion Amidst the pandemic, our study emphasizes that ground-glass opacities on CT scans are robust indicators of COVID-19 in RT-PCR-positive patients. Early identification can enhance patient management, with findings highlighting a strong link between lung involvement and prognosis. This insight aids in refining patient triage, while further research is warranted to delve deeper into variations in lung involvement and guide treatment advancements.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Actinium-225 Prostate-specific Membrane Antigen Theranostics: Will α Beat ß?

Optimisation of prostate-specific membrane antigen (PSMA) based radioligand therapy (RLT) requires a focus on prospective trials.

A role of PSMA PET/CT in multimodality imaging approach in adenoid cystic carcinoma.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Mechanistic Insights for Optimizing PSMA Radioligand Therapy.

PSMA radioligand therapy is a promising new class of therapy for prostate cancer. Heterogeneity of PSMA expression is an important factor explaining variability in clinical results. The ability to visualize the target with theranostics provides unique mechanistic insights. Potential clinically applicable strategies to improve patient selection and optimize therapeutic efficacy are discussed.See related article by Current et al., p. 2946.

Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial.

AIM: The purpose of this randomized clinical trial was to evaluate the intensity and duration of postoperative pain after pulpectomy of primary teeth using three preparation techniques. MATERIALS AND METHODS: A total of 60 patients were randomly allocated to three groups of 20 patients each, according to the root canal instrumentation techniques used. In group I, the teeth were prepared using manual NiTi K flex files till size 35. In group II, the teeth were prepared using NiTi K flex files till size 35 in reciprocating motion. In group III, the teeth were prepared using Kedo-S pediatric rotary files. After root canal preparation, the canals were obturated with endoflas paste and were restored permanently with composite filling material. The intensity and duration of postoperative pain were evaluated after 6, 12, 24, 48, and 72 hours, using a four-point pain-intensity scale. RESULTS: There was a statistically significant difference among the groups, wherein the postoperative pain was more in NiTi K flex files used in reciprocating motion followed by manual NiTi K flex files and Kedo-S pediatric rotary files. CONCLUSION: Postoperative pain was more with NiTi K flex files in reciprocating motion and was less with Kedo-S rotary files after root canal preparation in primary maxillary molars. HOW TO CITE THIS ARTICLE: Jeevanandan G, Ravindran V, Subramanian EMG, et al. Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2020;13(1):21-26.

Efficacy of Peptide Receptor Radionuclide Therapy for Esthesioneuroblastoma.

Esthesioneuroblastoma is rare, with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in esthesioneuroblastoma from 2 referral centers. Methods: Using PRRT databases at 2 European Neuroendocrine Tumor Society Centers of Excellence, cases were sought between 2004 and 2018 of patients who had PRRT with recurrent or metastatic esthesioneuroblastoma deemed unsuitable for further conventional therapies. Evaluations of survival and of response using a composite reference standard were performed. Results: Of 7 patients, 4 had partial response, 2 had disease stabilization, and one had early progression. Possible side effects include worsening cerebrospinal fluid leaks. Median progression-free survival was 17 mo (range, 0-30 mo), and median overall survival was 32 mo (range, 4-53 mo). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic esthesioneuroblastoma warranting larger cohort studies incorporating measures of quality of life.

The segmental distribution and clinical significance of colorectal fluorodeoxyglucose uptake incidentally detected on PET-CT.

BACKGROUND: Unexpected focal colorectal fluorodeoxyglucose (FDG) uptake is becoming a common clinical dilemma with the increasing utilization of positron emission tomography (PET). These findings may subsequently reveal malignant or premalignant pathology. AIM: In addition to reporting the prevalence of clinically significant colonic pathology associated with unexpected focal FDG uptake, this study analysed the correlation between pathological colonic segments with those reported on the FDG-PET scan. METHODS: The reports of 2071 consecutive PET-computed tomography (PET-CT) scans performed in a calendar year were reviewed. Information regarding subsequent patient investigation and management was collected from medical records. The segments harbouring foci of unexpected bowel FDG uptake were compared against the eventual outcome(s) of the endoscopic and pathological investigations. RESULTS: Among the 62 individual patients represented, 37 (60%) were investigated further. Clinically unsuspected neoplasms were found in 68% of those investigated, including 10 diagnosed with carcinoma. In addition, an unknown bowel lymphoma and 19 colonic adenomas were discovered. The positive predictive value for pathology was higher in the proximal colon than the distal colon. The segments in which the pathological findings were identified correlated well with those reported as abnormal on PET-CT. CONCLUSION: Unexpected bowel FDG uptake on PET-CT is associated with a high incidence of neoplastic pathology. In particular, focal FDG uptake in the proximal colon is associated with a high positive predictive value for neoplasm. The location of pathology is strongly concordant with endoscopic findings.

Setting the stage: Contemporary staging of non-melanomatous skin cancer and implementation of the new American Joint Committee on cancer eighth edition staging manual.

Non-melanomatous skin cancer (NMSC) generally refers to basal cell and squamous cell carcinoma of the skin. The majority of patients are curatively treated with simple excision. Only few present with locally advanced disease or have evidence of high-risk features, placing them at an elevated risk of relapse. In such cases, further investigations may guide the multidisciplinary management plan. There are no universally agreed on indications for recommending additional staging investigations, due to a lack of prospective data reporting their impact on patient outcomes. Some generally agreed upon indications are discussed in this review article. Most commonly, computed tomography (CT) and magnetic resonance imaging (MR) are used in cases of locally advanced NMSC for staging purposes and surgical planning. While Positron Emission Tomography (PET)/CT and sentinel lymph node biopsy have shown utility, data is lacking to establish their roles in the staging algorithm. An updated NMSC system was included in The American Joint Committee for Cancer eighth edition staging manual (AJCC8). Under AJCC8 the majority of patients with regional disease are upstaged by the presence of extranodal extension, however, this updated system appears to provide limited prognostic discrimination between the nodal categories and the overall TNM stages. This review article will explore the contemporary role of staging investigations, including evolving technologies, and review the changes implemented in AJCC8. It will also discuss the implications of the AJCC8 decision to assign patients with p16-positive cervical nodal SCC with an unknown primary to the oropharyngeal staging system, with particular relevance to clinicians working in areas of high NMSC incidence.

Preoperative Positron Emission Tomography for Node-Positive Head and Neck Cutaneous Squamous Cell Carcinoma.

Objectives Surgery is the primary treatment modality for node-positive cutaneous squamous cell carcinoma of the head and neck with no distant disease (HNcSCC-M0). The role of preoperative positron emission tomography/computed tomography (PET/CT) scan for these patients is unclear. We compared preoperative PET/CT with final histopathology among patients undergoing lymphadenectomy and/or parotidectomy for HNcSCC-M0. Study Design Case series with chart review. Setting Single Australian center. Subjects and Methods Investigation included disease parameters and preoperative CT and PET/CT findings of 64 patients with node-positive HNcSCC without distant metastatic disease. Fisher's exact test was used to test for a difference in the proportion of patients with chronic lymphocytic leukemia between the false- and true-negative PET/CT subgroups. Results Of 64 patients who underwent PET/CT prior to surgery for node-positive HNcSCC-M0, 56 underwent a neck dissection and 30, a parotidectomy. Of these, 13 neck dissections and 2 parotidectomies were performed in the absence of FDG-avid (18F-fludeoxyglucose) nodes in these nodal fields. The PET/CT positive predictive value of the neck was 91.1%. The negative predictive values in the neck and parotid regions were 60%. Of the false-negative subgroup, 66.7% had chronic lymphocytic leukemia, compared with 11.1% of the true-negative subgroup ( P = .09). Based on PET/CT findings, surgical plans according to preoperative CT were changed for 6.25% of patients. Conclusion Use of PET/CT for surgical candidates with node-positive HNcSCC-M0 has high specificity and positive predictive value with relatively low sensitivity and negative predictive value. A statistical trend toward a higher rate of chronic lymphocytic leukemia among patients with false-negative results is suggested.

Focal Inflammatory Myositis on 18F-FDG PET/CT.

Focal myositis is a rare benign inflammatory pseudotumor that can mimic malignancy, clinically and on imaging. A 34-year-old man presented with a 3-week history of sudden-onset, nontender, left upper neck mass that was nonresolving with antibiotics. Anatomical imaging was concerning for a sarcoma of the sternocleidomastoid muscle with possible regional nodal metastases and surrounding inflammatory change. F-FDG PET/CT showed marked FDG uptake extending around the anterior border of the sternocleidomastoid muscle with no FDG-avid local nodal disease. Core biopsy of the sternocleidomastoid muscle and adjacent node revealed inflammatory changes. A diagnosis of focal inflammatory myositis was made.