Left-sided congenital diaphragmatic hernia and liver-up: time to revise simplistic views?

Pelizzo, Gloria; Finazzo, Francesca; Vitaliti, Marcello Savino; Bellieni, Carlo V.; Calcaterra, Valeria

doi:10.1080/14767058.2019.1702948

Cited by 3 publications

(8 citation statements)

References 17 publications

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“…According to the dual‐hit hypothesis, pulmonary injury in the case of CDH is explained by two developmental insults: one affecting both lungs before diaphragm development during the organogenesis stages and the other affecting mostly the ipsilateral lung after defective diaphragm development secondary to herniation of the abdominal viscera. In our study, the variability of lung weight on the contralateral side, in addition to differences in birthweights, 4–7,16–18 could support the effect of a first hit, but also the variability of the diaphragmatic hole surgically created has influence in the different severities of pulmonary hypoplasia and size found. The differences observed in the growth of internal organs between left and right CDH suggest multisystemic involvement 23 and remodeling related to a second hit (as the fetus attempts to adapt).…”

Section: Discussionsupporting

confidence: 62%

“…Abnormal lung development, which accompanies this condition, is considered the most crucial clinically relevant characteristic. However, the role of structural problems in other internal organs, such as the liver and heart, should not be underestimated on CDH prognosis 13,16–18 …”

Section: Discussionmentioning

confidence: 99%

“…The hypothesis that reduced mRNA expression levels are responsible for the morphological changes affecting the function of liver lipid droplet expression has been postulated 16–20 . However, the role of hemodynamic changes on metabolic impairment of the hepatic cellular component should be not excluded.…”

Section: Discussionmentioning

confidence: 99%

“…Anatomically, the position of the hepatic and portal veins is consistent with the orientation of the liver parenchyma within the abdominal cavity. When the liver herniates into the thorax, the hepatic and portal vein orientations are altered, thus influencing hemodynamics 16–18 …”

Section: Discussionmentioning

confidence: 99%

“…However, the role of structural problems in other internal organs, such as the liver and heart, should not be underestimated on CDH prognosis. 13,[16][17][18] Liver involvement, including its position, has been reported to have prognostic value in CDH prenatal and postnatal assessment. It is a useful prenatal prognostic factor when associated with other markers, including intrathoracic stomach, lung-to-head ratio (LHR), observed to expected LHR, percentage predicted lung volumes, and total lung volume.…”

Section: Discussionmentioning

confidence: 99%

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Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Pelizzo

Peiró

Villanacci

et al. 2022

Congenital Anomalies

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To date, fetal liver implication is not a well-understood phenomenon in congenital diaphragmatic hernia (CDH). We evaluated the fetal morphologic changes on liver growth after surgical procedure in CDH experimental model. A diaphragmatic defect at gestational day E25 and tracheal occlusion (TO) at E27 were surgically created in rabbit fetuses. Five experimental groups were assessed: control group, left CDH, right CDH, CDH + TO, and TO alone. Body and organ growth were measured. For histological evaluation of the CDH effect, liver sections were collected. Left-CDH group had livers with increased leukocyte infiltration in comparison with controls (p = 0.02). Increased capillary sinusoid congestion and hepatocyte vacuolation were greater in left-CDH compared with the right-CDH group (p = 0.05). Capillary sinusoid congestion and interstitial edema were more evident in the left-CDH compared with CDH + TO group (p = 0.05). Increases in sinusoid congestion, hepatocyte vacuolation, and interstitial edema were also greater in the CDH + TO compared with controls (p ≤ 0.02). Intrathoracic liver weight was higher in right-CDH compared with left-CDH group (p < 0.001). Total lung weights (TLW) were significantly lower in both left-CDH compared with controls (p < 0.001), CDH + TO (p = 0.01), and TO (p < 0.01) and in right-CDH compared with CDH + TO (p < 0.01) and TO (p < 0.01).Decreased kidney and heart weights were also recorded. Hemodynamics and structural fetal liver changes in laterality were noted in CDH model. Regulation of intrathoracic liver weights seems to be disturbed by the absence of diaphragmic contact.Pulmonary injury is supported by the effect of a first hit, while the growth of internal organs suggests a multisystemic remodeling related to the fetal adaptation.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Pelizzo

Peiró

Villanacci

et al. 2022

Congenital Anomalies

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The quantitative lung index: the left lung

Kontopoulos

Quintero

Chmait

et al. 2020

The Journal of Maternal-Fetal & Neonatal Medicine

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The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia

Ott

Scorletti

et al. 2022

Front. Pediatr.

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ObjectiveLiver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth.MethodsClinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth.ResultsData was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost.ConclusionRight-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.

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Left-sided congenital diaphragmatic hernia and liver-up: time to revise simplistic views?

Cited by 3 publications

References 17 publications

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

The quantitative lung index: the left lung

The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia

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