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The new European Society of Thoracic Imaging (ESTI) nodule management recommendations for low-dose CT lung cancer screening emphasize lesion aggressiveness, size, and morphology, while building on previous guidance.

A team led by Prof. Mathias Prokop, chair of radiology at Radboud University Center, Nijmegen, the Netherlands, and Dr. Annemiek Snoeckx, chair of radiology at Antwerp University Hospital in Belgium, published the new guidance on 1 July in European Radiology. They noted that ESTI sought a balance between mitigating the number of follow-up visits, the possibility of overtreatment, and reducing the risk of a major stage shift in developing its recommendations.

Flowchart for management of new nodules. New nodules that had been missed or not reported on previous scans are managed according to the same rules as nodules found at baseline.Courtesy Prokop, Snoeckx, ESTI; European Radiology.

The guidelines emphasize categorizing by the size of the solid nodule or the solid part of a subsolid or cystic nodule. Volume is the recommended method for measurement; the authors stated that measurements taken with calipers are substantially less accurate and reproducible than volumetric measurements. However, manual diameter measurements are recommended as backup if segmentation at volumetry is found to be inaccurate and cannot be corrected. The authors gave specific guidelines for both methods of measuring, as well as for calculating the repeatability coefficient.

Additionally, volume-doubling time (VDT) is recommended here as the preferred measure for the growth rate of the tumor; the aggressiveness of the nodule is estimated from this VDT or from yearly diameter change. However, the authors cautioned that the calculation of the growth rate is affected by measurement variability, with larger error margins in cases of shorter follow-up periods and slower growth.

Furthermore, the VDT has been shown to vary among types, with solid nodules growing faster than either partially solid or nonsolid nodules. Therefore, the guidelines set the growth thresholds for stages in order that rapidly growing nodules could be identified while still small, and unnecessary follow-up could be avoided for those that are slow-growing, for which a conservative approach is generally recommended.

Likewise, as the authors stated that rapid growth is associated with aggressiveness in tumors, stage shift is also more likely in rapidly growing tumors and after longer intervals between follow-up visits, and with nodules closer in size to the next stage. Larger nodule size increases the risk for lymphatic and distant metastases, and if those metastases develop, or if a tumor stage T1a (<1 cm) at baseline develops into a tumor stage ≥T1c (≥2 cm) during follow-up, a major stage shift has occurred, according to these guidelines.

The guidelines are structured to provide management for nodules according to type, size, and morphology. They underscore again that subsolid and cystic nodules are generally less aggressive and a more conservative approach with long-term surveillance is appropriate; furthermore, new nonsolid nodules are usually infectious, and even when premalignant, are slow-growing. However, the authors also added that the development of a solid component in these nodules indicates invasiveness.

Growth with solid nodules may be variable; while rapid growth is a measure of aggressiveness, the guidelines also caution that malignant nodules may be slow-growing. For this reason, the authors added an absolute growth threshold of 5 mm: Should a slow-growing lesion increase in diameter by at least 5 mm, the decision should be made to weigh possible overtreatment against the risk from the cancer. Through this standard, the ESTI aims at “avoiding stage-shift in patients with a good life expectancy while reducing aggressive management in patients who might not profit from it.”

Overtreatment is most likely to occur with slow-growing tumors, which are unlikely to metastasize, or in patients with comorbidities that are much more likely to affect their survival than the lung tumor, according to the authors.

For follow-up intervals, the ESTI team states that “[t]he nodule with the shortest follow-up interval determines participants’ management”; benign nodules should have no effect on management. Furthermore, while nodule management is based on malignancy risk, it should always take into account the lesion’s projected aggressiveness to avoid overdiagnosis and overtreatment, as well as to minimize the amount of follow-up a patient must undergo. Regular lung cancer screening should be performed at one-year intervals, the authors wrote.

Read the new ESTI recommendations here.

Scientists from Cincinnati Children’s and colleagues based in Japan report achieving a major step forward in organoid technology–producing liver tissue that grows its own internal blood vessels.

This significant advance could lead to new ways to help people living with hemophilia and other coagulation disorders while also taking another step closer to producing transplantable repair tissues for people with damaged livers.

The study, led by Takanori Takebe, MD, PhD, director for commercial innovation at the Cincinnati Children’s Center for Stem Cell and Organoid Research and Medicine  (CuSTOM), was published online June 25, 2025,  in Nature Biomedical Engineering. Co-authors included experts from the Institute of Science Tokyo, the Ichan School of Medicine at Mount Sinai, and Takeda Pharmaceutical Co., which also provided funding for the study.

“Our research represents a significant step forward in understanding and replicating the complex cellular interactions that occur in liver development. The ability to generate functional sinusoidal vessels opens up new possibilities for modeling a wide range of human biology and disease, and treating coagulation disorders and beyond,” Takebe says.

What are organoids?

For more than 15 years, researchers at Cincinnati Children’s and many other institutions have been working to grow human organ tissue in the laboratory. Such tissues already have become important tools for medical research and may soon become sophisticated enough to be used directly to help repair damaged organs.

The complex process involves placing induced pluripotent stem cells (iPSCs) in special gels designed to prompt the stem cells to grow into specific tissue types. The stem cells can be generic or come from specific individuals with health conditions and can be gene-edited before beginning the process.

Cincinnati Children’s has been a leader in organoid research since 2010 when experts here developed the first functional intestinal organoid grown from iPSCs. Since then, CuSTOM has grown and evolved to include 37 labs across 16 research divisions, where teams are improving organoid technology and using organoids to shed new light on a wide range of diseases and conditions.

Overcoming a challenge

Until recently, the size of lab-grown organoids has been fundamentally limited because they have not included important tissues that connect organs to the rest of the body; such as nerves and blood vessels.

This study recounts how the research team overcame the blood vessel obstacle. The experiments involved required nearly a decade to complete.

Ultimately, the project succeeded at differentiating human pluripotent stem cells into CD32b+ liver sinusoidal endothelial progenitors (iLSEP). Then the team used an inverted multilayered air-liquid interface (IMALI) culture system to support the iLSEP cells as they self-organized into hepatic endoderm, septum mesenchyme, arterial, and sinusoidal quadruple progenitors.

The advantage of using the iLSEP progenitor cells as building blocks is that they are specific to the liver. Some other studies seeking to add vascularization to organoids have depended upon “fully committed” arterial endothelial cells. These vessels may not function inside an organ as well as progenitor cells from that organ.

Location and timing also were crucial to achieving the initial vessel formation.

“The success occurred in part because the different cell types were grown as neighbors that naturally communicated with each other to take their next development steps,” says the study’s first author Norikazu Saiki, PhD, of the Institute of Science Tokyo.

Key findings from the research include:

• Development of Fully Functional Human Vessels: The new method produced “perfused blood vessels with functional sinusoid-like features,” which means the vessels were fully open and included the pulsing cell types needed to help blood move through.
• Correction of Coagulation Disorders: The advanced organoids also generated the correct cell types needed to produce four types of blood coagulation factors, including Factor VIII, which is missing among people with hemophilia A. In mice that mimic hemophilia, the study showed that organoid-derived Factor VIII rescued them from severe bleeding.
• Potential Application Beyond Liver Organoids: By developing IMALI culture methods for allowing multiple cell types to self-organize naturally, the new technology may open a possibility to grow organ-specific vesselsin other types of organoids.

Big Step Closer to Improved Treatments for Hemophilia, Liver Failure

In the U.S. an estimated 33,000 males live with hemophilia. Most have hemophilia A (factor VIII deficiency), while a smaller group has hemophilia B (factor IX deficiency).

The condition can cause repeated bleeding within joints that can lead to chronic pain and mobility limitations. Hemophilia makes surgery risky and other wounds harder to heal. It also can lead to seizures and paralysis when bleeding affects the brain.

Hemophilia is treated by injecting commercially prepared concentrates to replace the missing coagulation factors. However, human blood contains a dozen different clotting factors and there are no available human protein sources for missing coagulation factors V or XI. Also, about 20% of people with hemophilia A develop inhibitors to standard treatment products.

“These advanced liver organoids can secrete these coagulation factors. If they can be produced at scale, they could become a viable treatment source that would benefit people who have developed inhibitors or are not indicated for gene therapy,” Takebe says.

Meanwhile, people experiencing acute or chronic liver failure also do not produce adequate supplies of coagulation factors, placing them at higher risk of bleeding complications during surgery. A factor-secreting organoid ‘factory’ also could help these patients.

Longer-term, increasingly sophisticated liver organoids may eventually supply repair tissues that can help diseased livers heal themselves.

Reference: Saiki N, Nio Y, Yoneyama Y, et al. Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids. Nat Biomed Eng. 2025. doi: 10.1038/s41551-025-01416-6

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A new study, published recently in Nature Communications, offers the first-ever map of which parts of Chikungunya virus trigger the strongest response from the body’s T cells. 

With this map in hand, researchers are closer to developing Chikungunya vaccines or therapies that harness T cells to strike specific targets, or “epitopes,” to halt infection. The new study also offers important clues for understanding why many people experience chronic, severe joint pain for years after clearing the virus.