Nuclear medicine is an integral part of medical practice in Nepal. This article reports on the current infrastructure, human resources, training, and research related to nuclear medicine in Nepal. A questionnaire was sent to all nuclear medicine services in Nepal to collect data on the number and types of imaging devices, staffing, and procedures conducted in 2025. In addition, nuclear medicine-related publications were extracted from relevant research portals. Nepal, a lower middle-income country of 30 million inhabitants, has nine nuclear medicine departments equipped with four single-photon emission computed tomography (SPECT), two SPECT/CT (computed tomography), and three positron emission tomography/CT (PET/CT) scanners. In 2025, nearly 200 scans per month were performed at each center with a gamma camera, whereas ∼100 PET/CT cases per month were performed at centers equipped with PET/CT scanners. A total of approximately 50 radionuclide therapy cases per month, mainly comprising I-131 therapies, were performed at centers with gamma cameras. Staff members include 9 MD nuclear medicine physicians, 3 MSc nuclear medicine technologists, 20 radiological technologists involved in nuclear medicine services, and a few staff nurses, although resources are unevenly distributed. Research output has increased substantially since 2020, often in collaboration with international institutions. Nepal has a relatively advanced nuclear medicine infrastructure supported by public investment, government regulation, international collaboration, and education. However, challenges remain in service expansion, workforce shortages, research development, and equitable access. If these challenges are addressed, Nepal could serve as a compelling model for improving nuclear medicine services in least-developed countries.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.
We aimed to investigate the early side effects of recombinant human thyroid-stimulating hormone (rhTSH)-aided radioactive iodine (RAI) administration in an unselected cohort of patients with differentiated thyroid cancer (DTC) in the real-world setting. During follow-up (at 6 weeks, 6 months, and 12 months post-RAI) of patients with DTC who received rhTSH-aided RAI, we used a standardized questionnaire to collect patient-reported side effects of RAI. We investigated the factors that impact the occurrence of RAI-associated side effects. A total of 111 patients with a female predominance (66.7%) and a mean age of 51.1 ± 16.0 years were included, including 13 patients (11.7%) who had previously received RAI. The predominant tumor histology was papillary thyroid cancer, with 91.0% of patients having stage I/II disease. At 6-week follow-up, loss of taste/smell, nausea, salivary gland pain or swelling, dry mouth, and neck pain were reported by 45.9, 37.8, 30.6, 36.9, and 20.7% of patients, respectively. In most patients, these side effects lasted for less than 1 week. At 6-month post-RAI, 13 patients reported lingering RAI-associated side effects, including 4 and 3 patients who reported dry mouth and dry eyes, respectively. A 12-month post-RAI, one patient each reported dry eyes, watery eyes, and fatigue as RAI side effects. Women were at higher risk of neck pain, while young patients were more likely to experience nausea ( p  < 0.05). rhTSH-aided RAI administration in DTC patients is associated with tolerable side effects, most of which resolved within weeks of treatment.
Congenital anomalies of the kidney and urinary tract (CAKUT) result from embryonic developmental defects and are usually not isolated. We evaluate the functional status of the kidney with Tc-99m renal scintigraphy in CAKUT patients associated with a rare complex systemic syndrome/sequence. We retrospectively screened 788 Tc-99m EC (ethylenedicysteine) and 187 Tc-99m DMSA (dimercaptosuccinic acid) renal scintigraphies performed between January 2022 and November 2024. Patients were selected based on the presence of congenital systemic syndrome and CAKUT. The Kruskal-Wallis test was used to compare grading of functional impairment of kidneys across different systemic syndromes. The Mann-Whitney U-test was used to compare the functional impairment of the kidney for continuous variables. A total of 38 patients (23 males, 15 females, mean age: 6.7 ± 6.7, range 0.03-33 years) of congenital systemic syndrome with associated CAKUT were identified. The most common systemic syndrome was anorectal malformation in 15 patients (39.5%). A few patients had features of more than one syndrome. The most common CAKUT was an orthotopic or ectopic nonfunctioning kidney in 15 patients (39.5%). The Tc-99m renal scintigraphies showed abnormal findings in 31 patients and normal findings in 7 patients. The proportion of abnormal findings was 81.6% (95% confidence interval: 65.7-92.3%). The difference in proportion of abnormal findings of renal scintigraphy across different syndromes was not statistically significant (Fisher's exact test, p  = 0.128). The Kruskal-Wallis H-test revealed significant differences in the grading of functional impairment of kidneys across different systemic syndromes, H(16) = 27.24, p  = 0.039. The Mann-Whitney U-test revealed significant difference ( p  = 0.007) in serum creatinine of normal Tc-99m scintigraphy (mean = 0.49, n  = 7) and abnormal Tc-99m scintigraphy (mean =1.25, n  = 31), U = 36.5, z  = 2.71, r  = 1.65. However, there was no significant difference ( p  = 0.097) in the age of patients who showed normal and abnormal Tc-99m scintigraphies. A complex systemic syndrome may have occult CAKUT that remains silent initially but presents as a complicated case later. Thus, these patients need functional evaluation with Tc-99m EC and Tc-99m DMSA scintigraphies for early diagnosis of renal anomaly and timely management and follow-up, especially after surgical intervention, to avoid future complications.
The pace of surgical innovation appears ever faster. Innovation is being freed from the design constraints of the opposable digits of a surgeon's hand through the use of programmable binary digits. Surgeons must be the drivers of change and central to the application of innovations. We should collaborate with industry, engineers and scientists to think out of the box but must consider also expense, environmental impact, equity, and ethics. But we should not be blinded by shiny technology: innovation without impact is mere noise. The ultimate considerations are the diagnosis and management of surgical disease, of improving the care of our patients. Expert surgeons, scientists and engineers across the world were identified and invited to describe areas of innovation within surgery. They were given free rein to review their areas of expertise and to discuss both current and future applications of technology within surgical care. The Commission spans multiple surgical specialties and scientific domains. It reviews translational genomics, including the role of ctDNA, alongside microbiomic and proteomic applications in improving the diagnosis, treatment and monitoring of surgical disease. Applications to enhance surgical procedures are described, from medical micro/nanorobots for minimally invasive interventions, sensory-enriched surgery with visual optimization and molecular image-guidance to intelligent and semiautomated instruments. The expansion and broad influence of artificial intelligence in surgical writing, training and simulation, diagnosis and robotics is widely described. The role of surgical innovation and technology in driving personalized care for benign and malignant surgical disease from genomic profiling to bespoke surgical and non-surgical treatment pathways and surveillance is considered. The future of surgery is poised to become more precise, personalized, and effective. Collaboration with engineers, data scientists, and industry partners not only represents an exciting opportunity for surgeons to participate in team science but is critical to focus innovation goals on optimizing patient care and outcomes.
Sphincter of Oddi dysfunction (SOD) can lead to increased intra-biliary-pancreatic duct pressure,manifesting as persistent biliary pain or recurrent pancreatitis. Currently,the diagnosis and treatment of SOD still face numerous challenges. Previously,the method of guiding endoscopic sphincterotomy based on the results of sphincter of Oddi manometry was only effective for some patients with modified Milwaukee type Ⅱ SOD,and it was associated with multiple complications,raising concerns about its safety. The main reason for this is the complex pathophysiology of SOD. Research on SOD has mainly focused on biliary manometry,and the evidence is mostly derived from early animal experiments. Therefore,further real-world research related to SOD should be strengthened to explore the overall regulatory mechanisms of sphincter of Oddi involving the gastrointestinal tract,biliary-pancreatic system,nervous system,and hormone endocrine system. Additionally,clinical collaboration across specialties such as endoscopy,imaging,nuclear medicine,and digestive surgery should be enhanced,with the aim of finding more convenient,safe,and minimally invasive methods for the diagnosis and treatment of SOD. Oddi括约肌功能障碍（SOD）可导致胆胰管内压升高，表现为持续的胆源性疼痛或反复发作的胰腺炎。目前，SOD的诊治仍面临诸多困难。既往根据Oddi括约肌压力测定（SOM）结果指导的内镜下乳头括约肌切开术（EST）仅对部分改良Milwaukee Ⅱ型SOD患者有效，且术后并发症较多。究其原因，主要是SOD的病理生理机制复杂，现有关于SOD的研究主要聚焦于胆道测压，且证据多来自于早年的动物实验。因此，应进一步应加强SOD相关的真实世界研究，探索胃肠道、胆胰系统、神经系统、内分泌系统对于Oddi括约肌的整体调控机制；并加强消化内镜科、影像科、核医学科及消化外科医师的临床协作，以期寻找到更便捷、安全和微创的SOD诊治方法。.
Radiomics has shown potential for quantitative characterization of tumors in molecular imaging; however, its clinical translation in theranostic 1 7 7Lu SPECT/CT remains limited due to poor robustness of extracted features to reconstruction variability and partial volume effects. Establishing reproducible radiomics biomarkers across correction strategies is therefore a prerequisite for reliable clinical modeling and treatment monitoring. This study aimed to evaluate radiomics feature reproducibility, defined as the stability of feature values across different partial volume correction (PVC) strategies and reconstruction settings, in clinical 1 7 7Lu SPECT/CT imaging. In addition, we explored two volumetric shape-based indices, the metastasis-to-liver ratio (MLR) and metastasis-to-spare liver ratio (MSLR), as surrogate markers of hepatic metastatic burden in the theranostic treatment setting. In 13 patients (40 scans) treated with 177Lu, 837 radiomics features were extracted from 11 abdominal regions and metastases on SPECT/CT using original and wavelet-decomposed images across four bin widths (50-200). Two post-reconstruction PVC methods, namely Richardson-Lucy (RL) and Reblurred Van Cittert (RVC), were applied. Feature reproducibility was quantified using two complementary metrics: the intraclass correlation coefficient (ICC) to assess feature-level stability across PVC strategies, and the concordance correlation coefficient (CCC) to evaluate pairwise agreement and systematic bias among reconstruction methods. Visual image quality assessments were independently performed by two experienced nuclear medicine specialists in a blinded setting. Exploratory metastatic tumor burden was assessed descriptively using 3D shape-based MLR and MSLR indices. Low-frequency wavelet decomposition (LLL-wavelet) and original features showed the highest reproducibility (ICC ≥ 0.90 in >95% of liver and metastasis features at BW50), whereas high-frequency features and larger bin widths demonstrated reduced stability. CCC analysis revealed excellent agreement between RL and RVC (≥0.95 in major organs at BW50-100), while agreement with uncorrected SPECT (no PVC) was consistently lower, especially for high-frequency features. RL achieved higher visual scores in sharpness and contrast (p < 0.01), with good inter-reader agreement supporting the consistency of these assessments. MLR/MSLR demonstrated inter-patient variability and were explored descriptively as indices of metastatic liver burden. Reproducibility in theranostic SPECT radiomics is highly feature- and organ-dependent and is further influenced by scanner-specific factors and reconstruction protocols, which remain critical for real-world clinical translation. RL and RVC showed stronger mutual agreements than each with uncorrected SPECT. Importantly, only RVC translated visual improvements into enhanced feature-level reproducibility, while RL provided the most consistent overall balance of reproducibility and image quality, supporting its role as the preferred PVC strategy for clinical and modeling applications. Robust radiomics feature selection as well as standardized reproducible PVC strategies are essential to generate methodological harmonization for future clinical translation and to support integration of radiomics analyses into personalized SPECT theranostics.
Intratumoral heterogeneity is a primary driver of treatment resistance in many malignancies, including esophageal cancer. While Fluorine-18 Fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) is a standard tool for staging and response assessment in the esophageal malignancy, the qualitative visual assessment of primary tumor and metastases is limited by interobserver variability. The purpose of this study is to determine if the non-invasive imaging biomarkers on F-18 FDG PET can reliably distinguish the two primary histological subtypes of esophageal malignancy namely squamous cell carcinoma (SCC) and adenocarcinoma (AC). This is a retrospective study approved by the institutional ethical committee, and conducted in histopathologically proven cases of esophageal malignancy of either squamous cell or AC subtypes, who underwent baseline staging F-18 FDG PET/CT as per the standard guidelines. The metabolic parameters namely tumoral maximum standardized uptake value (SUVmax), total lesional glycolysis (TLG), metabolic tumor volume (MTV) and metabolic ratio of tumor to liver (standardized uptake ratio [SUR]) were calculated and compared between the two histological subtypes using Mann - Whitney U test. A p -value of less than 0.05 was considered statistically significant. Out of 59 patients (M:F = 33:26) included in the study, 40 had squamous cell subtype and 19 had AC. Median age was 57 years (range: 30-83), and the median SUVmax, SUR, MTV, and TLG of AC group was 10.89 g/mL, 3.86, 9.98 mL, and 55.8 g/mL, while that of squamous group was 13.88 g/mL, 5.6, 13.52 mL, and 108.4 g/mL, respectively. There was significant difference noted in the tumoral SUVmax ( p  = 0 .043) , SUR ( p  = 0 .019 ), and TLG ( p  = 0 .032 ) between the two groups, with higher metabolic values observed in the squamous group. MTV ( p  = 0 .224 ) between the two groups was insignificant. This study demonstrates that quantitative parameters on F-18 FDG PET are effective non-invasive biomarkers for differentiating the histological subtypes of esophageal malignancy. The squamous cell subtype exhibits significantly higher metabolism and total lesion glycolysis than AC.
68 Ga- and 18 F-labeled prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) agents have advanced prostate cancer (PC) imaging. 64 Cu-SAR-bisPSMA may offer several advantages for imaging of PC over standard-of-care PSMA PET agents due to its sarcophagine chelator, bivalent structure and longer half-life of 64 Cu (12.7h vs. <2h for 68 Ga and 18 F), which may lead to detection of additional and smaller lesions. This study determined the administered activity (AA) of 64 Cu-SAR-bisPSMA required to achieve diagnostic-quality imaging for clinical use. The PROPELLER trial (CLP03; NCT04839367) enrolled 30 men with untreated, histopathology-confirmed, primary PC with intermediate- to high-risk features. Participants received an intravenous injection of 64 Cu-SAR-bisPSMA at 100, 150, or 200 MBq, followed by whole-body PET/computed tomography 2 to 4 hours post-injection. Images were anonymized, randomized, and reviewed by two blinded central readers using the three-point Image Utility Classification Score. For intra-individual comparisons, a subset of images acquired at 200 MBq were digitally reconstructed to simulate 100 and 150 MBq acquisitions on the same scanner; these were randomized and then evaluated by a blinded reader. They were ranked from best image to worst image and scored with a 4-item, 5-point Likert Image Quality Score (maximum 20 points). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also measured. Mean Image Utility Classification Score was the highest in the 200 MBq 64 Cu-SAR-bisPSMA cohort compared with the 100 and 150 MBq cohorts (1.44, 1.17, and 0.92, respectively). For the intra-individual comparisons, images corresponding to 200 MBq were ranked as having the best image quality with a statistically significant difference in image quality ranking between AAs ( p  = 0.0025). The mean Image Quality Score was highest at 200 MBq of 64 Cu-SAR-bisPSMA (16.0 ± standard deviation 1.10) versus 150 MBq (12.2 ± 1.17) and 100 MBq (10.3 ± 1.63). Quantitatively, 200 MBq of 64 Cu-SAR-bisPSMA had the greatest SNR in both the liver and prostate and the highest CNR for liver relative to the gluteus muscle. An AA of 200 MBq was identified as the optimal AA for 64 Cu-SAR-bisPSMA PET, yielding improved image quality across both qualitative and quantitative metrics compared with 150 and 100 MBq. These findings support the selection of 200 MBq for clinical studies evaluating 64 Cu-SAR-bisPSMA as an imaging agent for PC. NCT04839367, Registered 2021-04-07.
Gallbladder carcinoma (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed at a locally advanced stage. Accurate risk stratification is crucial for optimizing treatment, yet conventional imaging and staging systems have limitations. This study aimed to evaluate the prognostic value of metabolic and volumetric parameters from 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in patients with locally advanced GBC. This retrospective study included 32 patients with biopsy-confirmed, locally advanced GBC who underwent baseline 18 F-FDG PET/CT. The standard uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for both primary tumors and nodal metastases. A univariate Cox proportional hazards model was used to assess the association between these volumetric metabolic PET parameters and progression-free survival (PFS) and overall survival (OS). The multivariate Cox model was used to test the independence of significant univariate prognostic factors. In the univariate analysis of volumetric metabolic PET parameters of primary tumors, higher pSUVmean (hazard ratio [HR]: 1.39, p  = 0.04), pTLG2.5 (per 100 units; HR: 1.01, p  = 0.02), pMTV40 (HR: 1.00, p  = 0.02), and pTLG40 (per 100 units; HR: 1.09, p  = 0.01) were all significantly associated with worse OS. Similar significant associations were found for PFS. Notably, the conventional metric of pSUVmax was not a significant predictor of either PFS ( p  = 0.11) or OS ( p  = 0.25). On multivariate analysis, pTLG40 remained an independent predictor of survival. Furthermore, none of the volumetric metabolic PET parameters derived from nodal metastases showed a significant association with survival outcomes. Volumetric metabolic PET parameters, particularly TLG and MTV, which reflect the total metabolic burden of the primary tumor, may offer greater prognostic utility in locally advanced GBC compared with the conventional SUVmax. These parameters should be considered for integration into prognostic models to enhance patient risk stratification and guide personalized therapeutic strategies.
The EXTREME regimen (cetuximab with cisplatin/carboplatin and 5-fluorouracil) has long been a standard first-line treatment for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), particularly in patients ineligible for immunotherapy. However, real-world evidence remains limited, especially in regions with delayed access to novel therapies. We conducted a retrospective, multicenter study of 217 patients with R/M HNSCC treated with cetuximab-based chemotherapy at six Croatian oncology centers between 2016 and 2022, prior to reimbursement of pembrolizumab. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rates, and safety. The majority (91%) received the EXTREME regimen. Median OS was 14 months (95% CI, 12-17), and median PFS was 6.2 months (95% CI, 6.0-7.2). Objective response rate was 21%, and disease control rate was 63%. Cetuximab-induced rash correlated with longer PFS. Grade ≥ 3 toxicity occurred in 18.9% of patients. No treatment-related deaths were observed. In routine clinical practice, cetuximab combined with platinum-based chemotherapy remains an effective and well-tolerated first-line treatment for R/M HNSCC, particularly in patients who are ineligible for immunotherapy or with PD-L1-negative tumors. These findings support its continued use in appropriately selected patients.
Myocardial perfusion imaging (MPI) aids in evaluating the left ventricular function and therefore helps in risk stratification and prognosis. The purpose of this study was to evaluate the clinical impact of three cardiac software packages (Emory Cardiac Toolbox, Cardiogam, and Myovation Evolution) at 1-year follow-up. This prospective investigation involved 370 patients who underwent myocardial perfusion scintigraphy. Participants were stratified into three groups based on left ventricular ejection fraction determined by two-dimensional echocardiography. Among these, 294 patients were available for follow-up at 1 year. Semiquantitative parameters (summed rest score [SRS], summed stress score [SSS], summed difference score [SDS]) and quantitative parameters (defect extent [DE], transient ischemic dilatation [TID], ejection fraction [EF], end-diastolic volume [EDV], end-systolic volume [ESV], and stroke volume [SV]) derived from each software platform (ECTb, Cgam, and ME) were used to evaluate their diagnostic performance in predicting major adverse cardiac events (MACE) using receiver operating characteristic curve analysis in patients during 1-year follow-up. Among the 294 participants available for follow-up, 6% ( n  = 17) developed MACE at 1 year and 88% ( n  = 15) belonged to the high-risk group. Follow-up analysis indicated that all three software packages could predict 1-year cardiac events with varying cut-off values, sensitivities, and specificities. Cut-off values for SRS (ECTb) was ≥4 (area under the curve [AUC], 0.82), while for Cgam it was ≥11 (AUC 0.8), DE (REST) (ECTb) was ≥6% (AUC 0.82), and Cgam value ≥4.18% (AUC 0.81), EF (REST) was ≤44% (AUC 0.82), ≤68% (AUC 0.84) and ≤35% (AUC 0.83) for ECTb, Cgam, and ME, respectively, EDV (REST) was ≥137 mL for both ECTb (AUC 0.83) and Cgam (AUC 0.85) while for ME it was ≥116 mL (AUC 0.8), ESV (REST) was ≥91 mL (AUC 0.83), ≥55 mL (AUC 0.86) and ≥78 mL (AUC 0.82) for ECTb, Cgam, and ME, respectively. Majority of the MACE occurred in the group with high-risk characteristics. All three software packages demonstrated the ability to predict 1-year cardiac events, albeit with varying parameter cut-off values, sensitivities, and specificities.
There is little information on non-thyroid cancer risks, including haematological malignancies (HM), among the residents of most contaminated regions after the Chernobyl (Chornobyl) nuclear power plant accident. We studied the incidence of lymphoma, multiple myeloma and leukaemia in relation to the raion-average age-specific cumulative absorbed red bone marrow (RBM) dose among the residents of Gomel and Mogilev oblasts in Belarus, which were highly contaminated. The follow-up period was 40 years (1978-2018). HM cases and population size data were received from the Belarusian national cancer registry and the state department of statistics. Our ecological study included 7328 lymphoma, 9476 leukaemia and 2003 multiple myeloma incident cases and 90.8 million person-years in people who were born before the accident and have attained age <80 years old. The mean (median) RBM dose accumulated by December 31, 2018 was 14.2 (6.4) mGy. We found no evidence of increased risks of Hodgkin and non-Hodgkin lymphoma, multiple myeloma or total leukaemia associated with two-year lagged raion-average cumulative RBM dose after adjustment for sex, attained age, urban/rural status and calendar period effects. There was a suggestion of an elevated relative risk of myeloid leukaemia per 100 mGy after exclusion of Gomel and Mogilev cities. Little evidence was found on interaction between selected factors, except sex, and RBM dose for each study outcome. Studies with individually reconstructed cumulative absorbed RBM doses are warranted to provide more insight on dose-effect relationships between HM risk, specifically leukaemia, and protracted environmental exposure at a low dose range.
Radiation-induced oral mucositis (RIOM) is a common and debilitating complication of radiotherapy in oral cancer patients, significantly impairing quality of life and potentially interrupting treatment. This study evaluated the therapeutic efficacy of N-acetylcysteine (NAC) nano-spray in managing RIOM, with particular emphasis on mucositis severity, quality of life, and serum gastrin-17 levels. In this randomized clinical study, 40 oral cancer patients undergoing radiotherapy were allocated in a 1:1 ratio to receive either NAC nano-spray (n = 20) or conventional therapy (n = 20) for six weeks. Mucositis severity was assessed using the World Health Organization (WHO) Oral Mucositis Severity Scale, and quality of life was evaluated using the Oral Health Impact Profile (OHIP-14). Serum gastrin-17 levels were measured before and after treatment. Patients treated with NAC nano-spray demonstrated a significant reduction in WHO mucositis grades and significantly improved OHIP-14 scores compared with the control group (p < 0.05). Additionally, a significant increase in serum gastrin-17 levels was observed in the NAC group relative to conventional therapy (p < 0.05). These effects were evident during radiotherapy and at the end of treatment. N-acetylcysteine nano-spray appears to be an effective therapeutic option for the management of RIOM, reducing mucositis severity and improving quality of life in oral cancer patients. The trial was registered at Clinical Trials .gov on 24/7/2025, registration number: (NCT07082621).
Association of [ 99m Tc]Tc-pyrophosphate (PYP) uptake with survival of cardiac amyloidosis (CA) is still unknown. This study aimed to describe the scintigraphic findings of CA suspected cases and determine the prognostic value of scintigraphy. Between September 2020 and December 2023, all [ 99m Tc]Tc-PYP scintigraphy images of CA suspected cases were evaluated retrospectively. The scintigraphy images were obtained 1 and 3 hours after intravenous injection of 740 MBq [ 99m Tc]Tc-PYP. The quantitative and semiquantitative results of scintigraphy were analyzed, and their correlation with survival was evaluated. Among the 268 cases (147 females, 121 males; median age: 65), 12 (4.5%) were diagnosed with transthyretin (ATTR) CA and 19 (7.1%) with light chain (AL) CA. The median follow-up time was 386 days. ATTR CA cases exhibited significantly higher [ 99m Tc]Tc-PYP uptake than AL CA and non-CA cases. The 1- and 3-hour heart-to-contralateral lung ratios were positively highly correlated with each other, and SPECT/CT (single-photon computed tomography/computed tomography) imaging reduced equivocal results from 82 to 37%. Eight of the AL CA cases (42.1%), 1 ATTR CA case (8.3%), and 15 of non-CA cases (6%) died on follow-up. Median survival was 22 days in ATTR CA, 201 days in AL CA, and 105 days in non-CA deceased cases. Survival analysis indicated significantly lower survival in non-CA cases compared with ATTR CA and AL CA. [ 99m Tc]Tc-PYP scintigraphy is highly sensitive and specific for detecting ATTR CA and differentiating from AL CA. Even in the absence of a diagnosis of CA, the fact that survival may be short in cases with high uptake on scintigraphy should be considered in the follow-up of these cases.
Depression and anxiety are often undertreated in patients with cancer, and brief, robust screening measures are needed. The objective was to assess the sensitivity and specificity of the Edmonton Symptom Assessment System-Revised (ESAS-r) anxiety and depression items against the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item scale (GAD-7) (reference measures). We conducted a analysis of baseline data from the evaluation of a real-world patient-reported outcome measure (PROM) screening program. Patients with cancer completed the ESAS-r, PHQ-9, and GAD-7. Receiver operating characteristic analysis assessed ESAS-r depression and anxiety item accuracy by calculating area under the curve (AUC) and 95% confidence intervals (95% CI). Youden's index guided suggested screening cutoffs. Analyses were conducted for the entire sample, followed by exploratory analyses stratified by sex, age, income, and education. Of 375 eligible participants, 177 with complete data were included. The AUCs were excellent against the reference measures: 0.81 (95% CI: 0.73-0.90) for depression and 0.83 (95% CI: 0.70-0.96) for anxiety. Optimal cutoffs were ≥ 2 for depression (sensitivity: 0.83, specificity: 0.66) and ≥ 4 for anxiety (sensitivity: 0.83, specificity: 0.79), with low positive predictive values (0.32 and 0.31, respectively). Exploratory stratified analyses suggested comparable performance across subgroups, anxiety prevalence in males (2%) was too low for meaningful analysis. The AUCs for the depression and anxiety ESAS-r items were excellent, at 0.81 and 0.83, respectively. Findings support ESAS-r-D ≥ 2 and ESAS-r-A ≥ 4 as thresholds to identify those in need of further assessment, but professional judgment and previous findings should also be considered.
68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11) was approved by the U.S. Food and Drug Administration as the first prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging drug for patients with prostate cancer. However, the utility of 68 Ga-PSMA-HBED-CC may be limited due to PET/CT or PET/MR accessibility and 68 GaCl 3 availability produced from 68 Ge/ 68 Ga generator or cyclotron. Thus, in-house preparation of 99m Tc-PSMA-HBED-CC was developed as an alternative to 68 Ga-PSMA-HBED-CC to be ubiquitous and affordable in the worldwide population. A solution of 99m Tc-pertechnetate was added to PSMA-HBED-CC and 4% SnCl 2 ·2H 2 O in a 10-mL sterile vial. The mixture was heated at 100°C for 15 minutes and then allowed to cool to room temperature. Labeling conditions were optimized to maximize the radiochemical yield of 99m Tc-PSMA-HBED-CC. The chelation completeness was monitored using instant thin layer chromatography, and the stability of 99m Tc-PSMA-HBED-CC was subsequently evaluated. The radiolabeling of 99m Tc-PSMA-HBED-CC was successful using the appropriate amount of 10 µg PSMA-HBED-CC 3 µg SnCl 2 ·2H 2 O and 99m Tc-pertechnetate 370 MBq at 100°C for 15 minutes, yielded the best result in high radiochemical yield (71.49 ± 2.42%), radiochemical purity (98.29 ± 2.65%), and specific activity of 37.84 ± 1.47 GBq/µmol. 99m Tc-PSMA-HBED-CC is stable with radiochemical purity of more than 95% within 4 hours at room temperature. A new labeling method of 99m Tc-PSMA-HBED-CC was developed. Quality control parameters of 99m Tc-PSMA-HBED-CC met the criteria in accordance with the European Pharmacopoeia.
Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide. Accurate detection of lymph node metastases plays a crucial role in determining disease stage and guiding treatment decisions. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET/magnetic resonance imaging (MRI) are advanced imaging modalities widely used in clinical practice. The study aimed to compare the diagnostic accuracy of [ 18 F]FDG PET/CT and [ 18 F]FDG PET/MRI in detecting lymph node metastases in CRC patients. A comprehensive literature search was conducted across PubMed, Embase, and Web of Science databases to identify relevant studies published up to February 2025. Inclusion criteria encompassed studies evaluating the diagnostic performance of [ 18 F]FDG PET/CT and [ 18 F]FDG PET/MRI for detecting lymph node metastases in CRC patients. Sensitivity and specificity were analyzed using the DerSimonian and Laird random-effects model, with results adjusted by the Freeman-Tukey double arcsine transformation. The quality of the included studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. This meta-analysis incorporated 24 studies with a cumulative total of 3,369 patients. The findings revealed that [ 18 F]FDG PET/CT exhibited significantly lower sensitivity (0.75 vs. 0.93, p  = 0.0096) and a lower AUC value (0.81 vs. 0.96) compared with [ 18 F]FDG PET/MRI in detecting lymph node metastases among CRC patients. Both [ 18 F]FDG PET/CT and [ 18 F]FDG PET/MRI demonstrated similar specificity (0.77 vs. 0.88, p  = 0.1892). Furthermore, the funnel plot asymmetry test indicated no significant publication bias across any of the outcomes (Egger's test: all p  > 0.05). Our meta-analysis demonstrated that [ 18 F]FDG PET/MRI has higher sensitivity and comparable specificity to [ 18 F]FDG PET/CT in detecting lymph node metastases in CRC patients, suggesting its potential superiority for preoperative staging and postoperative surveillance. However, the limited number of direct head-to-head studies (only two) underscores the need for larger, prospective studies to validate these findings and assess their impact on clinical decision-making and patient outcomes.
This article aims to assess the presence of skeletal and soft tissue infections before or after treatment and to assess treatment response in Ga-68 citrate positron emission tomography/computed tomography (PET/CT) scan positive patients. A prospective study was conducted for 43 patients. The eligibility criteria included those patients clinically suspected of infections who underwent a Ga-68 citrate PET/CT. Exclusion criteria were pregnancy and lactation. Patients with suspicion of infection or treatment failure underwent a Ga-68 citrate PET/CT between January 2020 and November 2021. Among these, eight patients underwent a follow-up scan posttreatment to assess their treatment response. The Institutional Review Board (IRB No.12511) approved the study. Forty-three patients underwent a diagnostic Ga-68 citrate PET/CT scan. The scan interpretation was based on visual comparison of uptake of Ga-68 citrate in the region of interest, which was compared with the normal side/adjacent soft tissue/blood pool. The semiquantitative parameter maximum standardized uptake value was retrospectively analyzed as well. PET/CT findings were correlated with tissue diagnosis, clinical symptoms, biochemical parameters like C-reactive protein (CRP), erythrocyte sedimentation rate, and total leukocyte count, and other imaging modalities with a statistically significant association with CRP ( p  = 0.001). Tissue diagnosis was considered the gold standard and out of the 43 patients included in the study, 27 had a tissue diagnosis. Sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated at 100, 87.5, 100, 95, and 96.3%, respectively. Ga-68 citrate is a promising tool to assess the presence of bone and soft tissue infections before or after treatment.