New High-Risk Pediatric Liver Cancer Identified

Until recently, nearly all pediatric liver cancers were classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC). However, pediatric pathologists observed that some liver tumors have histological features that do not easily fit either of these two carcinoma models. These cancers are less likely to respond to chemotherapy, and patient outcomes are poor.

First author Dr. Pavel Sumazin, associate professor of pediatrics at Baylor College of Medicine and Texas Children’s Cancer and Hematology Center, and his colleagues looked to better characterize this high-risk cancer, reporting their findings in the Journal of Hepatology.

The researchers examined the molecular profiles of the tumors, including genetic alterations and gene expression profiles. They found that these profiles do not fit into the HB or HCC molecular categories. Instead, these tumors exhibited recurring molecular features that have been observed in both HBs and HCCs. They designated these tumors as hepatoblastomas with hepatocellular carcinoma features (HBCs).

The team also examined HBC treatments and outcomes and found that they tended to be more resistant to standard chemotherapy and have poor outcomes when not treated with more aggressive surgical approaches, including transplantation. Based on their findings, the team proposed a diagnostic algorithm to stratify HBCs and guide specialized treatment.

“Our findings highlight the importance of molecular testing to accurately classify these tumors to optimize treatment recommendations at the time of initial diagnosis,” said Dr. Dolores López-Terrada, corresponding author of the paper, professor of pathology, immunology, and pediatrics at Baylor, and chief of the division of genomic medicine at Texas Children’s. “Our analysis suggested that children with HBCs may benefit from treatment strategies that differ from the guidelines for patients with hepatoblastoma and hepatocellular carcinoma.”

Drug Combo for Obesity and Diabetes More Effective Than Single Therapy?

Canadian and German researchers are teaming up to identify new drug combinations to treat people with obesity and type 2 diabetes. The goal is to develop personalized prescriptions that are more effective than single drugs and that can potentially replace more invasive treatments, such as bariatric surgery, especially for children.

“As a pediatric endocrinologist, I can tell you we’re seeing more and more type 2 diabetes in kids and adolescents, and it seems to be a more aggressive form than adult-onset diabetes, so we do need better therapies to achieve even greater efficacy and degree of weight loss,” said Dr. Andrea Haqq, a professor in the University of Alberta (U of A) Faculty of Medicine & Dentistry.

The researchers recently published a paper that examines the potential of several drugs that control incretins. These metabolic hormones stimulate the body to produce insulin and use it effectively. They also suppress appetite to control blood sugars and reduce weight. The researchers conclude that combining the drugs has several advantages, including higher effectiveness in at least some patients and fewer side effects.

Even a 5% weight loss is considered clinically meaningful, and patients in some of the combination drug trials are achieving 10% or 15%, said Dr. Haqq, who is a member of the Alberta Diabetes Institute and the Women and Children’s Health Research Institute. Dr. Haqq’s laboratory is collaborating with that of Timo Müller, director of the Institute for Diabetes and Obesity at the Helmholtz Diabetes Center and a researcher with the German Center for Diabetes Research in Münich.

As part of the collaboration with the Müller team, first author Qiming Tan, a PhD candidate in the U of A Faculty of Medicine & Dentistry, will study for a term in Germany and a German student will join Dr. Haqq’s laboratory.

Dr. Haqq and Ms. Tan recommend further research to identify why some individuals respond differently to the drugs. Some racial and ethnic groups bear a disproportionate burden of obesity and type 2 diabetes, they said, so more participants from these groups are needed in trials. Further studies should also focus on how differences in biological sex affect drug efficacy and safety.

In addition to drug combinations, the researchers are looking for nonpharmacologic solutions, such as how adding fiber to a person’s diet can slow weight gain and improve the effectiveness of existing diabetes medications.

Some Children With Cerebral Palsy Scoliosis May Not Need Pelvic Surgery

A new Michigan Medicine study finds that some children with cerebral palsy and scoliosis do not require pelvic fixation when undergoing growing rod treatment, potentially avoiding several complications.

Using data from around 20 health systems, researchers analyzed nearly 100 pediatric patients with cerebral palsy and scoliosis treated with growth-friendly implants, in which expandable rods are inserted into the back to help control the spinal curvature while still allowing the spine to grow. They found that for children with a pelvic tilt and lower lumbar spine tilt of less than 10 degrees, the pelvis did not need to be included when inserting growing rods. The results are published in Spine Deformity.

“Inserting screws into the pelvis to anchor the growing rods is not benign; screws in that area tend to be more prominent,” said G. Ying Li, MD, lead author of the paper and pediatric orthopaedic surgeon at University of Michigan Health C.S. Mott Children’s Hospital.

“Prominent screws can be painful and can also cause overlying skin breakdown, leading to infection. In the past, there has also been a high rate of these screws failing. For these reasons, understanding which kids have enough of a tilt in their pelvis and lower lumbar spine to benefit from anchoring the rods into the pelvis is important.”

Children with cerebral palsy have abnormal nerve and muscle control, and many of them are wheelchair users. When they develop scoliosis, the curve in their spine tends to be longer and more sweeping than those without the condition. The curve may extend into the pelvis, affecting standing and sitting balance and causing pressure that can make sitting more painful or lead to skin breakdown.

Patients treated with growing rods require more than one surgery, and most children eventually need a spinal fusion. Growth-friendly treatment is already associated with more complications than a single spinal fusion. For patients with cerebral palsy who have a small enough pelvic tilt, Dr. Li said, it is beneficial to avoid inserting screws into the pelvis in the early stages of growth-friendly treatment.

“Even though we did see some children with growing rods anchored to the spine who later needed to have the rods anchored to the pelvis, we inserted those pelvic screws when kids were undergoing their final spinal fusion procedure,” she said.

“These findings provide fellow surgeons with more information to help patients avoid complications while still correcting a curve that can impact quality of life, pain, and lung development for children with cerebral palsy.”

Middle Ear Fluid Common in Children on Ventilators

Babies and toddlers who need a tracheostomy—a tube surgically inserted into their windpipe to help relieve breathing problems—are at a high risk of accumulating fluid behind their eardrum when on a ventilator. That is the conclusion of a study published in the International Journal of Pediatric Otorhinolaryngology by UT Southwestern head and neck surgeons. This buildup of fluid, called a middle ear effusion (MEE), can put them at risk for ear infections, hearing loss, and delays in speech and language development.

“The majority of the time that these children are being cared for, the focus is on more pressing lung and heart concerns,” said study leader Stephen R. Chorney, MD, MPH, assistant professor of otolaryngology—head & neck surgery at UTSW and Pediatric Otolaryngologist at Children’s Health. “But our study suggests we should also be mindful of things that might appear more trivial, like ear effusions, because they can impact communication skills and developmental milestones in a vulnerable population of kids.”

Many young children who require a tracheostomy were born prematurely with underdeveloped lungs or narrow airways. In these cases, doctors may attach a mechanical ventilator—a form of life support to help a child breathe—to the tracheostomy tube.

MEE is a common problem for all young children. Nearly one in 10 kids has ear tubes placed to help clear this fluid, treat infections, and reduce hearing loss. Dr. Chorney and his colleagues suspected, based on their own observations, that tracheostomy-dependent children on a ventilator might be at a higher risk of MEE.

The study followed 94 children who received a tracheostomy before age 2 years at Children’s Medical Center Dallas between 2015 and 2020. On average, the children underwent tracheostomy at age 5 months and would then periodically obtain hearing tests to determine the presence of MEE. In the 2 years following their tracheostomy, 74% of children requiring mechanical ventilation developed at least one MEE, while only 31% of those not on the ventilator developed a MEE. When controlling for age, diagnosis of craniofacial syndrome, and results of newborn hearing tests, mechanical ventilation predicted the presence of a MEE. Further, among all children with a tracheostomy, 80% of MEEs persisted for at least several months between multiple hearing exams.

“This information allows us to have an objective reference point when communicating with parents,” said Dr. Chorney. “We know that this is a common phenomenon, and we might consider ear tubes in some of these children.”

Since placing ear tubes requires general anesthesia, some children with a tracheostomy on ventilator support might not be good candidates for the procedure, and the new data help clinicians weigh risks and benefits. In future studies, Dr. Chorney would like to explore the impact of MEEs on hearing and communication in this population.

“What we would hope is that if we’re more vigilant with screening for and addressing MEEs in these children, positive outcomes on speech and language development can be achieved,” he said. “But we need more data on that.”

Some Epilepsy Surgery May Risk Chronic Headaches

Surgeons who observe persistent fluid buildup after disconnecting epileptic and healthy brain areas should think twice before installing low-pressure nonprogrammable drainage shunts, according to a study coauthored by Rutgers pediatric and epilepsy neurosurgeon Yasunori Nagahama that found chronic headaches could result from these procedures.

The study in Operative Neurosurgery followed 70 children who underwent a connection-severing surgery, known as functional hemispherotomy for intractable epilepsy, between 1994 and 2018 to see if inserting permanent drainage shunts after surgery increased the brain’s tendency to shift across the skull after surgery.

Hemispherotomy often eliminates seizures in juvenile patients whose epilepsy affects one side (or hemisphere) of the brain by removing some tissue and severing connections between the healthy and overactive hemispheres. However, tissue removal reduces local pressure, causing the remaining brain tissue to shift toward the low-pressure zone. This shift can cause persistent headaches and other problems.

The study is the first to examine whether shunts, which allow excess cerebrospinal fluid to drain into the abdominal cavity, increase brain shift and, if so, whether certain types of shunts increase it more than others.

The study’s initial measurements of average midline brain shift were comparable in shunted and nonshunted patients, but final measurements were 16.3 millimeters in shunted kids and 9.7 millimeters in nonshunted kids. Further investigation by Dr. Nagahama and colleagues from the University of California, Los Angeles, suggests insufficient pressure in some shunt opening valves created the increased brain shift.

Patients whose shunts required above-average pressure to open their valves and drain fluid fared comparably to nonshunted patients. Patients whose shunts had below-average valve opening pressure experienced an average brain shift of 18.7 millimeters. Researchers also found that nonprogrammable shunt valves were associated with elevated brain shift—18.9 millimeters—while programmable valves were not.

“The finding that shunts as a whole increase midline brain shift is interesting but not actionable,” said Dr. Nagahama, the director of pediatric epilepsy surgery at Rutgers University’s Robert Wood Johnson Medical School. “You have to install shunts when there’s chronic cerebrospinal fluid buildup.”

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