The central challenge the researchers set out to address is deceptively simple: when a patient is diagnosed with gastric cancer that appears advanced on scans, how reliable is that initial assessment, and what does it actually predict for survival? In Japan, where many tumors that look advanced on imaging turn out to be early-stage disease obscured by inflammatory changes, clinicians have long struggled to identify which patients genuinely benefit from neoadjuvant chemotherapy, or chemotherapy given before surgery. Traditionally, decisions about postoperative chemotherapy have rested on pathological staging, the detailed examination of the removed tumor and lymph nodes. But that approach requires surgery first, leaving no opportunity to shrink the tumor beforehand. With evidence accumulating that perioperative chemotherapy improves survival in resectable advanced disease, the need for trustworthy clinical staging, performed entirely before the operating room, has become urgent.

JCOG1302A was designed as a prospective, multicenter observational study to test exactly how well endoscopy and computed tomography could classify tumor depth and nodal spread. Between July 2013 and November 2014, 1,275 patients were enrolled across 53 specialized Japanese institutions. Each underwent staging with multidetector-row CT using prespecified imaging criteria: localized wall thickening with a smooth serosal surface indicated T2 disease, diffuse thickening with a smooth surface indicated T3, and irregular or nodular serosal change or invasion of surrounding fat signaled T4a, while loss of the fat plane between tumor and adjacent organs defined T4b. Lymph nodes with a short axis of at least 8 millimeters or a long axis of at least 10 millimeters were called metastatic. The earlier analysis found that a striking share of patients clinically labeled T2 or T3 without nodal involvement actually harbored pathologically Stage I disease, contamination that ranged from 50.4 percent in cT2N0 down to just 3.0 percent in cT4aN(+).

That earlier work led the investigators to conclude that patients with clinical T3 disease plus detectable nodes, and those with any T4 disease, were the optimal candidates for preoperative chemotherapy, a conclusion that directly shaped the ongoing Phase III trial JCOG1509. But a critical piece was missing: no study had ever described long-term survival stratified by prospectively determined clinical stage. The new follow-up analysis, JCOG1302A2, collected additional survival data on the original cohort. After excluding patients who did not undergo surgery, those found ineligible, and 83 patients lost to follow-up, 1,176 patients formed the analytical population. The group was overwhelmingly treated with the Japanese standard of gastrectomy plus D2 lymph node dissection, performed in 98 percent of patients, and roughly half received adjuvant chemotherapy, most commonly the oral agent S-1 alone.

The survival data revealed a clean, stepwise gradient across both clinical dimensions. Five-year overall survival was 82.1 percent for clinical T2 tumors, 72.7 percent for T3, 60.0 percent for T4a, and 40.0 percent for the small T4b group. Nodal status told a parallel story: 78.0 percent for node-negative disease, 70.6 percent for cN1, 59.1 percent for cN2, and 28.4 percent for cN3. In statistical models measuring the risk of death over time, clinical T4a carried nearly two and a half times the mortality hazard of T2, while cN3 disease carried almost five times the hazard of cN0. When both dimensions were combined, the picture sharpened further. The most favorable group, comprising cT2N0, cT2N(+), and cT3N0, all achieved five-year survival near or above 77 percent, with cT2N0 topping the chart at 83.5 percent.

Perhaps the most consequential finding concerns the middle of the distribution. Patients with cT3N(+) disease and those with cT4aN0 disease showed nearly identical, intermediate survival, around 68.0 and 66.8 percent at five years respectively, and both carried roughly double the mortality risk of the cT2N0 reference group. Meanwhile, cT4aN(+) patients fared worst among the sizable subgroups, at 57.7 percent. Notably, cT3N0 disease did not show a statistically significant increase in risk compared with cT2N0, suggesting that node-negative T3 tumors, at least when staged by rigorous CT criteria, behave more like earlier disease than like truly advanced cancer. This three-tier risk architecture, favorable, intermediate, and poor, gives clinicians a practical framework for matching treatment intensity to genuine baseline risk.

The results also carry a pointed message about the TNM staging system itself. In the eighth edition of the TNM classification, clinical T3 and T4a tumors are grouped together, despite the acknowledged difficulty of distinguishing them on imaging. The Japanese data, with clearly separated survival curves between the two categories, suggest this merging may obscure clinically meaningful differences. The finding echoes the exploratory radiological sub-analysis of the PRODIGY trial, in which clinical T4 disease, with minimal contamination by pathological Stage I, was identified as the subgroup deriving the greatest benefit from neoadjuvant chemotherapy. Together, these results argue that T3 and T4a disease, when carefully distinguished by multidetector CT, warrant separate consideration in treatment planning and in the design of future clinical trials.

The study’s authors are careful to frame the work as prognostic rather than therapeutic. Because the analysis was observational, it did not directly test whether neoadjuvant chemotherapy improves survival in any subgroup, and the choice and regimen of postoperative chemotherapy were left to treating physicians, varying across patients and institutions. Most patients with Stage III disease received S-1 monotherapy, since the JACCRO GC-07 trial demonstrating the superiority of adding docetaxel had not yet reported when the cohort was treated. Adjuvant chemotherapy use also differed across clinical subgroups, from 34.5 percent in cT2N0 to 65.1 percent in cT4aN(+), a variation that may have influenced the observed outcomes. The cohort excluded scirrhous tumors, bulky nodal disease, and paraaortic metastases, so the findings cannot be generalized to those populations, and all patients were treated at specialized Japanese centers.

Even with those caveats, the timing of this evidence is significant. The Pan-Asian adapted ESMO Clinical Practice Guidelines now emphasize that perioperative chemotherapy should be considered only for selected patients with resectable locally advanced gastric cancer, and the recent MATTERHORN trial has shown that perioperative chemo-immunotherapy can improve outcomes, albeit with greater toxicity and cost. Against that backdrop, knowing which clinically defined groups face the highest baseline mortality risk, and which do well with surgery and standard adjuvant therapy alone, becomes essential for balancing benefit against burden. The data suggest that patients with cT2N0 and cT3N0 disease, who achieved roughly 80 percent five-year survival with upfront surgery, may have little to gain from intensified perioperative regimens, while those with cT3N(+), cT4aN0, cT4aN(+), and cT4b disease represent the higher-risk subgroups in whom such strategies deserve priority investigation.

For a disease that remains one of the world’s leading causes of cancer death, the study delivers something the field has lacked: a prospectively validated, clinically applicable survival map drawn entirely from information available before treatment. It validates the diagnostic criteria used in JCOG1302A, confirms that clinical T and N categories carry genuine prognostic weight, and provides the reference outcomes against which the ongoing JCOG1509 trial and the coming wave of perioperative chemo-immunotherapy studies will be judged. As treatment intensifies, the humble CT scan, applied with disciplined, standardized criteria, may prove to be the most important tool for ensuring that the right patients receive the right therapy at the right time.

Subject of Research: Long-term survival stratified by prospectively determined clinical staging in locally advanced gastric cancer

Article Title: Survival Results by the Prospectively Determined Clinical Staging for Locally Advanced Gastric Cancer: A Follow‐Up Study of JCOG1302A

Article References: Hayashi, T., Kato, R., Mitome, N., Ogawa, R., Fukagawa, T., Katai, H., Nunobe, S., Tokunaga, M., Bando, E., Ito, Y., Yamada, T., Nomura, T., Makino, S., Kinoshita, T., Hara, H., Aizawa, M., Boku, N., Kurokawa, Y., Terashima, M., & Yoshikawa, T. (2026). Survival Results by the Prospectively Determined Clinical Staging for Locally Advanced Gastric Cancer: A Follow‐Up Study of JCOG1302A. Annals of Gastroenterological Surgery, Article ags3.70293. https://doi.org/10.1002/ags3.70293

Image Credits: AI Generated

DOI: 10.1002/ags3.70293

Keywords: gastric cancer, clinical staging, neoadjuvant chemotherapy, JCOG1302A, overall survival, CT imaging, D2 lymphadenectomy, TNM classification, perioperative treatment, oncology, prognosis, Japan Clinical Oncology Group

The 2015 edition of the LeishVet review emerged at a time when interest in feline leishmaniosis was growing but the evidence base remained thin. The disease, caused primarily by the protozoan parasite Leishmania infantum and transmitted by phlebotomine sand flies, had been documented in cats across endemic regions, yet most of what clinicians knew came from isolated case reports. In the intervening decade, the landscape has shifted considerably. Veterinary awareness of the disease has increased, diagnostic support has become more widely available, and a steady stream of prevalence studies, clinical descriptions and treatment reports has accumulated in the literature.

Despite this progress, the authors are candid about the limitations of the current evidence. Knowledge of feline leishmaniosis still derives largely from case reports and small case series, with fewer analytical studies and a lower overall level of evidence than is available for canine leishmaniosis. Dogs remain the principal reservoir host of L. infantum and the model species for most leishmaniosis research, meaning that extrapolation from canine data to feline patients must be made cautiously. It is precisely this gap that the updated review seeks to address, combining key international publications with the clinical expertise and structured consensus of the expert panel.

To make the guidance as usable as possible, the panel organized the review around a series of questions covering the aspects of the disease most relevant to practitioners. These span the etiology of the infection, its transmission dynamics, its epidemiology including geographical distribution and risk factors, the immunology of the host-parasite relationship in cats, the range of clinical presentations and clinicopathological findings, the role of coinfections and comorbidities, diagnosis, prognosis based on clinical staging, treatment, monitoring and prevention. Each answer is supported by visual aids, including tables, figures and algorithms designed to guide clinical decision-making at the point of care.

The review focuses primarily on L. infantum infection and disease in domestic cats, reflecting the fact that this species is by far the most frequently diagnosed cause of leishmaniosis in felines. However, the panel also devoted two specific questions to topics that extend beyond the household cat. One addresses infection in wild felids, providing support for veterinary specialists working in wildlife and zoo medicine, where leishmaniosis has increasingly been recognized. The other considers Leishmania species other than L. infantum, an issue of growing relevance as globalization moves animals, vectors and pathogens across borders and presents practitioners with new diagnostic challenges.

Supporting the epidemiological sections of the review are two extensive supplementary tables compiled from data published between 2015 and 2025. The first covers the prevalence of Leishmania infection in cats in Old World countries, and the second covers the New World, drawing on both serological and molecular detection techniques. These tables catalogue the sampling periods, the characteristics of the studied cat populations and the variables associated with test positivity, and in nearly all cases the species involved was confirmed or presumed to be L. infantum. Together they represent one of the most complete pictures to date of how widely the parasite circulates among cats across both hemispheres.

On the diagnostic front, the review reflects the expanded toolkit now available to clinicians. Serological methods such as the indirect fluorescent antibody test, enzyme-linked immunosorbent assay and the direct agglutination test can detect antibody responses, while molecular techniques, including quantitative real-time polymerase chain reaction, allow parasite DNA to be detected and quantified in tissue and blood samples. Cytology, histopathology and immunohistochemistry remain important for demonstrating amastigote forms in lesions. The panel’s recommendations emphasize how these tools should be interpreted in combination, since infection and clinical disease are not the same thing, and cats can carry the parasite without showing signs of illness.

Coinfections and comorbidities receive particular attention in the updated guidance, reflecting the complex clinical reality of feline medicine. Retroviral infections with feline immunodeficiency virus and feline leukaemia virus, chronic kidney disease and immune-mediated conditions such as immune-mediated hemolytic anemia and feline chronic gingivostomatitis can all complicate the picture in a cat infected with L. infantum. The review also incorporates modern monitoring parameters relevant to feline patients, including urinary protein-to-creatinine ratios and symmetric dimethylarginine, which are used in staging and tracking chronic kidney disease under the International Renal Interest Society framework. These considerations matter because treatment decisions and prognosis in cats must account for the whole patient, not just the parasite.

Treatment and prevention recommendations are likewise updated in light of the past decade’s experience. Therapeutic options discussed in the context of feline leishmaniosis include allopurinol, meglumine antimoniate and miltefosine, the drugs that form the backbone of therapy in canine leishmaniosis, with the panel weighing their use against the specific pharmacological and safety considerations that apply to cats. Clinical staging is presented as the basis for formulating a prognosis and tailoring monitoring plans, mirroring the staged approach long used in canine medicine. Prevention advice addresses reducing exposure to sand fly vectors, an approach that becomes increasingly important as the geographic footprint of leishmaniosis expands.

The publication of this update comes at a moment when the boundaries of leishmaniosis are shifting. Climate change, animal movement and urbanization are altering the distribution of sand fly vectors and bringing previously unaffected populations of both dogs and cats into contact with L. infantum. For practitioners in endemic areas, the message of the review is that feline leishmaniosis should no longer be treated as a rare curiosity but as a differential diagnosis in cats with compatible clinical signs. For those in emerging areas, the review provides a framework for recognizing a disease they may never have been taught to look for. By consolidating a decade of scattered evidence into structured, consensus-based recommendations, the LeishVet panel has given veterinary medicine its clearest roadmap yet for understanding, diagnosing and managing leishmaniosis in one of its most overlooked hosts.

Subject of Research: Updated veterinary recommendations for the diagnosis, treatment and prevention of feline leishmaniosis caused by Leishmania infantum

Article Title: LeishVet update and current recommendations on feline leishmaniosis

Article References: Pennisi, M. G., Baneth, G., Bourdeau, P., Cardoso, L., Miró, G., Ordeix, L., Solano-Gallego, L., & Oliva, G. (2026). LeishVet update and current recommendations on feline leishmaniosis. Parasites & Vectors, 19(1), Article 421. https://doi.org/10.1186/s13071-026-07642-4

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07642-4

Keywords: feline leishmaniosis, Leishmania infantum, LeishVet, cats, sand flies, veterinary parasitology, diagnosis, clinical staging, treatment, prevention, wild felids, coinfections

The most widely cited monument to Yahr’s career is the 1967 paper he co-authored with Margaret Hoehn, titled Parkinsonism: Onset, Progression and Mortality, published in the journal Neurology. That paper introduced what became known as the Hoehn and Yahr scale, a five-stage classification of Parkinson’s disease severity based on the degree of functional impairment. Stage one describes unilateral involvement, typically with minimal or no functional impairment; stage two marks bilateral disease without impairment of balance; stage three adds postural instability, producing mild to moderate functional disability while the patient remains physically independent; stage four denotes severe disability, with the patient still able to walk or stand unassisted; and stage five describes the wheelchair-bound or bedridden state unless aid is constantly provided. The elegance of the system lay in its simplicity: a bedside observation, requiring no instrumentation, that captured the trajectory of the illness in a single ordinal number.

The technical rationale behind the scale reflected the clinical realities of the pre-levodopa era. Hoehn and Yahr analyzed a large cohort of patients with parkinsonism, documenting the natural history of onset, the pattern of symptom progression, and mortality relative to the general population. Their data demonstrated that disability accumulated in a broadly predictable sequence, beginning asymmetrically and progressing to bilateral involvement, and that mortality in parkinsonian patients was significantly elevated compared with matched controls. By anchoring disease severity to observable motor signs rather than subjective impressions, the scale provided the first widely reproducible endpoint for clinical research. More than five decades later, modified versions of the scale remain embedded in the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale and in the regulatory frameworks used to approve new Parkinson’s therapies.

Yahr’s second great contribution was his role in bringing levodopa into mainstream clinical practice. The pharmacological groundwork had been laid by others: Arvid Carlsson had established dopamine as a neurotransmitter in the brain and shown that reserpine-induced parkinsonism in animals could be reversed by levodopa, work that later earned him a Nobel Prize; Oleh Hornykiewicz had demonstrated that dopamine concentrations were profoundly depleted in the striata of deceased Parkinson’s patients; and George Cotzias had pioneered high-dose oral levodopa regimens. A 2015 review in Movement Disorders by Andrew Lees, Eduardo Tolosa and C. Warren Olanow grouped Yahr alongside Carlsson, Hornykiewicz and Cotzias as the four pioneers of levodopa treatment, a designation that underscores how central he was to translating laboratory dopamine biology into bedside therapy.

The decisive clinical paper came in 1969, when Yahr, together with Roger Duvoisin, M. J. Schear, R. E. Barrett and Margaret Hoehn, published Treatment of Parkinsonism with Levodopa in the Archives of Neurology. The study reported the results of levodopa administration in a substantial series of parkinsonian patients and documented striking improvements in the cardinal motor features of the disease, including bradykinesia, rigidity and tremor. The paper was among the first large, systematically documented demonstrations, conducted at a major American academic center, that restoring dopaminergic tone could produce clinically meaningful benefit in Parkinson’s disease. Its publication helped catalyze the rapid adoption of levodopa, often combined with a peripheral dopa-decarboxylase inhibitor to reduce nausea and cardiovascular side effects, as the standard of care, a position the drug still holds as the most effective symptomatic treatment available.

The impact of that therapeutic shift is difficult to overstate. Before levodopa, a diagnosis of Parkinson’s disease carried a grim prognosis; Hoehn and Yahr’s own 1967 mortality data showed that patients died at markedly elevated rates compared with the general population, often after years of progressive immobility, aspiration and institutionalization. After levodopa, life expectancy and quality of life improved substantially, and the management of the disease shifted from palliative custodial care to long-term pharmacological treatment with attention to motor complications such as wearing-off and dyskinesia. The 1998 reprint of the Hoehn and Yahr paper in Neurology, appearing in a series honoring classic papers, attested to the enduring relevance of the original work even as the therapeutic landscape it helped create had transformed the disease course it once described.

The new biographical article also situates Yahr within the institutional history of American neurology. He spent the core of his career in New York, where he built one of the leading movement disorders programs of his era and trained generations of neurologists who went on to shape the field. His department became a proving ground for systematic clinical investigation in parkinsonism, combining careful bedside phenomenology with emerging quantitative methods and the first generation of controlled therapeutic trials. The tribute’s authors, based at the Federal University of Paraná and the Federal University of Paraíba in Brazil, are themselves movement disorders specialists, and their article forms part of a broader historiographical effort to preserve the intellectual genealogy of a subspecialty that only consolidated as a distinct field in the second half of the twentieth century.

Contemporaries marked Yahr’s passing in 2004 with obituaries and tributes in the leading medical journals. The British Medical Journal published an obituary by F. Charatan, and the Journal of Neural Transmission carried a tribute by Peter Riederer, Emmanuel Hirsch, Moussa Youdim and Donald Calne, honoring his scientific achievements and his personal influence on colleagues across three continents. Such coordinated commemoration reflected the breadth of his network: Yahr’s collaborators and trainees populated departments of neurology throughout the United States and beyond, and his editorial work and society leadership helped professionalize the study of movement disorders at a time when the field was transitioning from descriptive neurology to mechanism-driven neuroscience.

From a modern vantage point, the methodological contributions of the Hoehn and Yahr era reveal both their power and their limits. The original scale is a rating of motor disability, insensitive to the non-motor dimensions of Parkinson’s disease, including autonomic dysfunction, cognitive decline, sleep disturbance and neuropsychiatric symptoms, which contemporary research has moved to the center of the field. Modern clinical trials increasingly rely on continuous digital monitoring, biomarkers such as alpha-synuclein seed amplification assays, and composite endpoints that capture disease heterogeneity far beyond a five-stage ordinal ranking. Yet the conceptual move that Hoehn and Yahr made, namely that Parkinson’s disease must be measured against its natural history with standardized, reproducible instruments, remains the epistemological foundation on which all subsequent scales, from the UPDRS to the MDS criteria for prodromal and diagnosed disease, were built.

The story of Melvin Yahr is ultimately a story about the speed at which clinical neuroscience can change when rigorous observation meets a mechanistic breakthrough. Within roughly a decade of Carlsson’s dopamine experiments, a dopamine precursor was in routine clinical use, and within the same decade a severity scale had been devised that made the disease legible to science. The Journal of Neurology’s decision to devote a Pioneers in Neurology article to Yahr, published in 2026, more than two decades after his death, testifies to how completely his twin legacies, the staging of Parkinson’s disease and the levodopa revolution, have been absorbed into the everyday grammar of neurology. Every clinician who assigns a patient a Hoehn and Yahr stage, and every patient who takes a levodopa tablet, is exercising a legacy forged in the New York clinics of the 1960s by a physician who insisted that parkinsonism be measured, quantified and treated.

Subject of Research: Historical biography of neurologist Melvin Yahr and his contributions to Parkinson's disease staging and levodopa treatment

Article Title: Melvin Yahr (1917–2004)

Article References: Teive, H. A. G., Coutinho, L., Meira, A. T., & Camargo, C. H. F. (2026). Melvin Yahr (1917–2004). Journal of Neurology, 273(10), Article 637. https://doi.org/10.1007/s00415-026-14184-3

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14184-3

Keywords: Melvin Yahr, Parkinson's disease, Hoehn and Yahr scale, levodopa, movement disorders, neurology history, dopamine, clinical staging, Journal of Neurology, biographical research, basal ganglia, pioneers in neurology

The concept of oligometastatic disease sits at one of the most consequential fault lines in modern oncology. It describes an intermediate state in which cancer has spread beyond the primary organ but only to a small number of sites, conventionally defined in this study as three or fewer metastatic lesions. Unlike widespread metastatic disease, which is managed with systemic therapy aimed at control rather than cure, oligometastatic prostate cancer may be amenable to metastasis-directed therapies such as stereotactic body radiotherapy or surgery targeting individual lesions. Randomized trials including STOMP and ORIOLE have suggested that ablating these limited deposits can delay progression, and trials such as ARTO and RADIOSA have explored combining such approaches with hormonal therapy. But every one of these strategies depends on one thing: knowing exactly which patients truly have only a handful of metastases. That is where the accuracy of the staging scan becomes decisive.

PSMA-PET works on a fundamentally different principle from conventional imaging. Rather than relying on anatomical changes, such as an enlarged lymph node or a bone lesion visible on a scintigram, it uses a radioactive tracer that binds to prostate-specific membrane antigen, a molecule abundantly expressed on the surface of most prostate cancer cells. When injected intravenously, the labeled ligand accumulates in PSMA-expressing tissue, and the PET scanner maps this molecular signal across the whole body, typically fused with computed tomography for anatomical correlation. The result is a functional image that can reveal metastases only a few millimeters in size, long before they distort anatomy enough to be caught by CT or bone scan. Joint procedure guidelines from the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging, along with standardized reporting frameworks such as E-PSMA and PROMISE version 2, have progressively codified how these scans should be acquired and interpreted.

To test how this translates into everyday clinical practice, the researchers assembled a retrospective cohort of 497 patients with intermediate- to high-risk prostate cancer drawn from multiple centers. Of these, 255 men had undergone both PSMA-PET and conventional imaging within a four-month window, satisfying the strict inclusion criteria for the primary analysis. The primary endpoint was the detection rate of oligometastatic disease, defined as three or fewer metastatic sites, under each modality. The secondary endpoint examined whether the PSMA-PET findings altered the intended clinical management, as judged by a retrospective multidisciplinary review of each case.

The numbers tell a clear story. PSMA-PET identified oligometastatic disease in 11.4 percent of the analyzed patients, or 29 of 255 men, compared with just 6.7 percent, or 17 of 255, using conventional imaging, a difference that reached statistical significance with a p-value of 0.040. In other words, for every hundred men staged with conventional scans alone, roughly five who actually harbored limited metastatic disease would have been misclassified as having localized cancer. The molecular technique also detected more patients with multimetastatic disease, meaning widespread spread beyond the oligometastatic threshold. This pattern of reclassification, in which a more sensitive test shifts patients into more advanced disease categories, is what epidemiologists call stage migration, and it has profound implications for how clinical statistics and treatment decisions are framed.

Perhaps the most clinically resonant finding concerned treatment planning. When a multidisciplinary panel re-reviewed each case in light of the PSMA-PET results, the intended management changed in 36.5 percent of patients, or 93 of the 255 studied. These changes split roughly evenly into major and minor categories, each accounting for about 18 percent of the cohort. A major change typically meant a fundamental shift in therapeutic strategy, for example abandoning a planned curative treatment such as radical surgery or radiotherapy in favor of systemic therapy once previously invisible metastases came to light. Minor changes included adjustments within a general strategy, such as modifying the radiation field or adding hormonal therapy. The authors are careful to note that these figures reflect the intended treatment plan rather than the treatment actually delivered, an important distinction given the retrospective design.

The study’s authors are equally candid about its limitations, and understanding them is essential to interpreting the results correctly. Because the analysis was retrospective, there was no independent reference standard, such as histopathological confirmation of every detected lesion, against which the two imaging modalities could be judged. No central review of the images was performed, meaning scans were interpreted at the originating institutions under routine conditions. Crucially, no patient follow-up was available, so the study cannot say whether the additional detections by PSMA-PET translate into longer survival or better disease control. The authors explicitly state that their findings demonstrate increased detection and reclassification, not proven improvements in diagnostic accuracy or outcomes. This is a common and honest caveat in the stage migration literature: a more sensitive test will always find more disease, but only longitudinal data can confirm that finding it earlier and more completely helps patients live longer.

Even with those caveats, the results align with a growing body of prospective evidence. The landmark proPSMA trial, published in The Lancet in 2020, randomized men with high-risk prostate cancer to PSMA-PET or conventional imaging before curative-intent treatment and found superior accuracy for the molecular approach. Subsequent work has shown that PSMA-PET-guided staging is potentially cost-effective in European and American health systems, and diagnostic accuracy studies have confirmed high sensitivity for pelvic nodal metastases prior to radical prostatectomy. On the therapeutic side, the same PSMA target has been exploited for treatment, most notably with lutetium-177-PSMA-617 radioligand therapy, which improved survival in metastatic castration-resistant prostate cancer in a landmark New England Journal of Medicine trial. The imaging and therapeutic applications of PSMA thus form a theranostic pipeline in which the molecule that reveals the cancer also becomes the vehicle for destroying it.

Why does accurate identification of oligometastatic disease matter so much right now? Because the treatment landscape for advanced prostate cancer is fragmenting into increasingly tailored options. Men with de novo metastatic hormone-sensitive disease benefit from intensification strategies, including androgen deprivation therapy combined with docetaxel or androgen receptor pathway inhibitors such as abiraterone and darolutamide, as established by trials including CHAARTED, LATITUDE, PEACE-1 and ARASENS. Men with limited metastatic disease, by contrast, may be candidates for metastasis-directed therapy, potentially avoiding or deferring systemic side effects. The boundary between these populations is exactly where PSMA-PET is drawing a sharper line. If conventional imaging leaves oligometastatic patients hidden within the localized cohort, they may receive curative-intent local therapy that cannot address their occult spread. If it leaves them hidden within the multimetastatic cohort, they may receive systemic therapy forgoing potentially curative ablative treatment. Either misclassification carries a cost.

The practical consequence of this study is likely to be a strengthening of the case for PSMA-PET as the default staging modality for intermediate- and high-risk prostate cancer, a position already reflected in contemporary European Association of Urology guidelines. For patients, the message is that the type of staging scan they receive can genuinely determine which treatment pathway they are offered. For clinicians and trialists, the stage migration documented here means that historical survival statistics, which were built on conventional imaging cohorts, cannot be directly compared with outcomes in PSMA-PET-era populations, since the same label now describes patients with different underlying disease burdens. Future prospective studies with long-term follow-up will need to establish whether reclassifying these men improves survival. What this real-world analysis establishes today is simpler but consequential: the scans that medicine relied on for decades were missing metastatic disease in a meaningful fraction of men, and a molecular imaging technique that sees what those scans cannot is already changing the plan of care for more than one in three patients.

Subject of Research: The role of PSMA-PET in detecting oligometastatic prostate cancer and driving stage migration compared with conventional imaging

Article Title: Stage migration in prostate cancer: the role of PSMA-PET in identifying oligometastatic disease

Article References: Mattana, F., Luzzago, S., Dragonetti, V., Kasivisvanathan, V., Conlon, S., Castellucci, P., Farolfi, A., Miszczyk, M., Techmański, T., Rajwa, P., Shariat, S. F., Zattoni, F., Reitano, G., Briganti, A., Montorsi, F., Frassoni, S., Bagnardi, V., Gandaglia, G., & Ceci, F. (2026). Stage migration in prostate cancer: the role of PSMA-PET in identifying oligometastatic disease. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08166-w

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08166-w

Keywords: prostate cancer, PSMA-PET, oligometastatic disease, stage migration, nuclear medicine, cancer staging, metastasis-directed therapy, conventional imaging, molecular imaging, stereotactic body radiotherapy, theranostics, clinical staging

The research, led by Lucy Hyam of King’s College London with colleagues including Karina L Allen and Ulrike Schmidt, was grounded in a critical realist perspective, a philosophical stance that treats participants’ accounts as windows onto real underlying causal mechanisms rather than as mere opinion. Between interviews and focus groups, the team gathered data from 21 participants: ten people with lived experience of an eating disorder, two carers and nine clinicians. The material was analysed using Fryer’s critical realist approach to thematic analysis, in which themes are developed not simply as descriptive labels but as nuanced causal explanations of how participants understood illness development, progression, treatment and recovery. This is a methodologically demanding form of qualitative analysis, seeking to model the mechanisms that drive phenomena rather than only cataloguing what was said.

Five superordinate themes emerged from the analysis. The first concerned clinical staging itself, framed by the authors as seeking structure in a fluid illness. The second captured how eating disorders take hold and hold on, a phrase that conveys the process by which restrictive, bingeing or compensatory behaviours consolidate from early, seemingly controllable habits into entrenched patterns that feel inseparable from a person’s identity. The third theme addressed the wider forces shaping illness trajectories, including social, relational and systemic influences. The fourth examined how healthcare experiences themselves influence illness progression, an unexpected but clinically significant finding, and the fifth focused on recovery as building life beyond the eating disorder, a conception of recovery that extends beyond symptom remission toward restored social and personal functioning.

On the central question of validity, the study found broad support: staging, participants suggested, could largely be interpreted as an accurate framework for conceptualising eating disorders. Many recognised the value of a model that communicates where someone sits along the course of illness and what might be expected next. Yet this endorsement came with a consistent and important caveat. Across all three participant groups, eating disorders were described as following a non-linear trajectory. People described periods of improvement followed by relapse, shifts between different patterns of disordered eating, and partial recoveries that did not follow a neat progression from mild to severe. Participants worried that staging systems, if applied rigidly, could impose an artificial order on a fundamentally fluctuating illness, potentially locking patients into a fixed clinical narrative.

This tension between structure and fluidity goes to the heart of why staging in psychiatry is contested. In oncology, staging is anchored in measurable anatomy, such as tumour size and spread, and a stage once assigned rarely reverses. In eating disorders, the proposed anchors are behavioural and psychological, including the duration and severity of restriction or bingeing, physical complications, and the degree to which the illness dominates identity and daily life. The present study identified candidate stage-defining features that resonate with this, with participants pointing to changes in habits, identity and physical health, and shifts in symptoms over time. Such markers align with the general thrust of emerging staging models in eating disorders, which typically distinguish an early or at-risk phase, in which behaviours are intermittent and self-esteem remains tied to sources outside the illness, from later stages in which behaviours become habitual, medically dangerous and central to a person’s sense of self.

The causal emphasis of the critical realist analysis produced one of the study’s most consequential findings: illness progression was felt to be strongly influenced by gaps in treatment and delays in accessing care. Participants identified multiple barriers to early intervention in eating disorders, a familiar problem given the well-documented pattern of long delays between symptom onset and first contact with specialist services. If the course of illness can be reshaped by the health system itself, then stages are not purely properties of the disease but partly artefacts of service provision. This reframes staging from a descriptive exercise into something with real accountability attached: a delayed referral or a demoralising episode of care can, in effect, move a person from an early to a later stage.

That insight connects directly to the fourth theme, in which harmful treatment experiences were seen as shaping both illness progression and the stages people pass through. Participants suggested that negative encounters with healthcare, such as dismissive responses, rigid protocols or care experienced as shaming, could entrench the illness or deter help-seeking, whereas personalised and compassionate care was described as vital across all participant groups. Combined with the study’s conclusion that early intervention is crucial to prevent illness progression, this implies that any staging system for eating disorders must be paired with services capable of acting on it promptly and humanely. The authors’ related research environment, including programmes such as FREED, a service designed to deliver rapid early intervention for first-episode eating disorders, reflects precisely this ambition of closing the gap between onset and treatment.

The overall conclusion of the study is a preference for staging approaches that are flexible and person-centred, capable of accommodating individual differences, non-linear trajectories and what the authors call stage-modifying factors, meaning influences such as treatment access and healthcare experience that can accelerate, delay or reverse progression between stages. In staging terminology, modifiers act as caveats that adjust the interpretation of the primary stage; in eating disorders, participants’ accounts suggest these modifiers may be as consequential as the stage itself. This has practical implications for how any future staging model is built and implemented: it should be explicit that regression is possible, that transitions between diagnostic patterns are common, and that a person’s stage is a dynamic clinical summary rather than a permanent label.

For clinicians, the study offers a usable framework for conversations with patients about where they are in their illness and what might change that course, while the findings caution against letting a stage number eclipse the individual. For researchers, the study demonstrates the value of stakeholder input, drawing on those with lived experience, carers and clinicians, in informing the development and refinement of clinical staging models, a process that has often been driven by expert consensus alone. The authors argue that incorporating these perspectives may increase both the acceptability and the perceived validity of staging among the people it is ultimately designed to help. Given that eating disorders carry among the highest mortality and burden of any psychiatric condition, and that early intervention is repeatedly shown to improve prognosis, a staging model that survives contact with lived reality could help target scarce treatment resources where they matter most: at the earliest, most modifiable point in the illness.

The study, conducted at King’s College London with the South London and Maudsley NHS Foundation Trust, received ethical approval from the King’s College London Research Ethics Office and was published open access, reflecting growing recognition that the future of eating disorder care depends on models shaped jointly by science and by the people who live with the illness every day.

Subject of Research: Clinical staging frameworks for eating disorders explored through qualitative interviews with patients, carers and clinicians

Article Title: Clinical staging in eating disorders: qualitative insights from those with lived experience, carers, and clinicians

Article References: Hyam, L., Karabıçak, I., Elsheikh, A., Carnegie, A., Allen, K. L., & Schmidt, U. (2026). Clinical staging in eating disorders: qualitative insights from those with lived experience, carers, and clinicians. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01775-8

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01775-8

Keywords: eating disorders, clinical staging, qualitative research, anorexia nervosa, early intervention, recovery, mental health services, thematic analysis, carers, illness trajectory, person-centred care, Journal of Eating Disorders

The review, published in the Journal of Perinatology by a large international team led from Trinity College Dublin, set out to answer a focused question: how do randomised controlled trials, the most rigorous experiments in medicine, actually diagnose and stage NEC? The question matters because a trial is only as good as its outcome measures. If two trials use different definitions of the same disease, their results cannot be cleanly compared or combined in meta-analyses, and regulators and clinicians are left guessing about whether a treatment that appears to work in one setting will work in another.

NEC is a significant cause of morbidity and mortality for preterm neonates, and its stakes have only risen as survival at earlier gestational ages improves. Whole-population surveillance in England has documented the scale of severe disease across neonatal networks, and reviews of contemporary outcomes continue to report substantial mortality among infants who require surgery. The disease is understood to involve a destructive interplay between an immature intestinal barrier, an unstable and often dysbiotic gut microbiome, inflammation mediated in part by innate immune receptors such as toll-like receptor 4, and haemodynamic fragility of the preterm mesentery. Risk factors described in the literature include enteral feeding practices, the protective association of early human milk, maternal smoking, and even in-utero exposures such as indomethacin tocolysis.

Against this complicated biological backdrop sits a diagnostic framework born in 1978. In that year, Bell and colleagues published a staging system for neonatal necrotizing enterocolitis in the Annals of Surgery, designed to guide therapeutic decisions based on clinical staging. The scheme stratified suspected disease from stage one, or suspected NEC with nonspecific systemic signs, through stage two, in which radiographic findings such as pneumatosis intestinalis, gas trapped within the bowel wall, confirm the diagnosis, to stage three, advanced disease with perforation or profound systemic collapse. Walsh and Kliegman refined the criteria in 1986, producing the modified Bell’s staging that generations of neonatologists have since memorised.

Herein lies the conceptual tension that the Dublin-led review interrogates. As the authors point out, Bell’s criteria were never intended as a case definition of NEC. They were a staging tool, created for an era when the sickest infants were often older and more mature than the micro-preemies cared for today. With the survival of neonates at earlier gestations, the clinical phenotype of intestinal injury has shifted, and researchers have repeatedly questioned whether a single framework can capture what is now a heterogeneous spectrum of disease. Some have argued that spontaneous intestinal perforation, a condition with different pathology and outcomes, has been inappropriately lumped together with classic NEC in older trials, muddying the interpretation of surgical studies comparing laparotomy with peritoneal drainage.

To map how trials actually define the disease, the team performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the PRISMA guidelines that standardise how such evidence syntheses are conducted and reported. They searched PubMed to identify randomised controlled trials published in the last twenty years that used NEC in the study title and included NEC either as a primary outcome or as an inclusion criterion. This dual requirement ensured that every trial analysed genuinely placed NEC at the centre of its scientific question rather than treating it as a passing safety mention.

The screening funnel distilled a large body of literature into a focused evidence base. The initial search identified fifty-six randomised controlled trials, of which thirty-six proceeded to full-text analysis. The headline finding was striking in its consistency: thirty-three of the thirty-six trials used Bell’s criteria or the modified Bell’s criteria to define NEC, while only three trials deployed unique, author-created definitions. In other words, when researchers design the most rigorous experiments on NEC prevention and treatment, the overwhelming majority still anchor their case ascertainment to a staging framework conceived before the advent of modern neonatal intensive care as it exists today.

What does that anchoring mean in practice? Bell’s staging relies on a combination of nonspecific systemic signs, abdominal findings, radiographic evidence such as pneumatosis intestinalis or portal venous gas, and, at the severe end, surgical or autopsy confirmation. Its strengths are real: it is universally recognised, cheap to apply, and requires no specialised laboratory infrastructure. But its weaknesses are equally well documented. Interobserver agreement on stage one disease is notoriously poor, the criteria were never gestational-age adjusted, and they predate the biomarker and imaging revolution now reshaping neonatal diagnostics. Recent work has evaluated neutrophil CD64 as a surveillance marker, explored data-driven diagnostic algorithms integrating clinical and laboratory features, and compared abdominal ultrasonography with plain radiography for detecting disease and predicting severity.

The review’s authors situate their findings within a broader reform movement. A gestational age-specific case definition developed by the UK Neonatal Collaborative has been proposed to capture disease more accurately across the preterm spectrum, and the Vermont Oxford Network maintains its own surveillance definitions, as do the CDC’s NHSN surveillance criteria. Critical evaluations of current definitions have concluded that the field’s diagnostic heterogeneity impedes both research and drug development, with regulatory scientists arguing that a consensus case definition is a prerequisite for any licensed therapy for NEC. The authors of the new review conclude that while the consistent use of Bell’s and modified Bell’s criteria in trials is itself informative, international consensus on further modification of the definition would greatly contribute to both research and clinical practice, allowing greater consistency in staging and therefore optimal management.

The trials catalogued in the review span the full range of neonatal intervention research: prophylactic and therapeutic probiotics including Bifidobacterium breve and Lactobacillus strains, bovine lactoferrin, synbiotics, oral glutamine, enteral L-arginine, docosahexaenoic acid supplementation, bovine colostrum and oropharyngeal colostrum administration, donor human milk fortification, early versus delayed minimal enteral feeding, maternal dietary manipulation, early caffeine treatment and erythropoietin. Each of these trials judged success or failure largely through the lens of a 1978 staging system. If the field can converge on a modern, gestational-age-aware, biologically informed definition, one that perhaps integrates imaging advances, biomarkers and patient-centred research priorities championed by families through organisations such as the NEC Society, the resulting consistency could sharpen future trials, accelerate regulatory approval of preventives and treatments, and ultimately help clinicians identify, stage and treat this devastating disease more reliably.

Subject of Research: How necrotizing enterocolitis is defined and staged in randomised controlled trials involving preterm neonates

Article Title: Definitions of neonatal Necrotizing Enterocolitis (NEC) in randomised controlled trials: a systematic review

Article References: Ballantine, R. S., Campbell, E., Croitoru, O., Jackson, E., Lyne, E. J., McGoldrick, C., Murphy, S. M., Oganezova, K., Shukla, T., Yogesan, S. S., Trayer, J., Stewart, P., Carroll, S., Branagan, A., Roche, E., Tabassum, S., Abrahamsson, T., Embleton, N., Berrington, J., … Molloy, E. J. (2026). Definitions of neonatal Necrotizing Enterocolitis (NEC) in randomised controlled trials: a systematic review. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02905-5

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02905-5

Keywords: necrotizing enterocolitis, Bell's criteria, preterm infants, randomised controlled trials, systematic review, neonatology, clinical staging, PRISMA, gut microbiome, neonatal mortality, case definition, Journal of Perinatology