To examine pathophysiology of parameatal urethral cyst (PUC) with comparison between the surgical excision group and the spontaneous resolution group.
We retrospectively reviewed all patients ...diagnosed with PUC and aged ≤15 years. Initially, all the patients received observation without any treatment. The indication of surgical excision was family preference. The patients were analyzed according to their sex, age, symptoms, clinical course, and pathological examination findings.
Among the 54 boys visited our hospital for PUC. The median age at presentation was 35 (IQR: 12-50) months, including 7 (13.0%) neonates cases. In total, 38 (70.4%) patients were underwent surgical excision, 12 (22.2%) had spontaneous resolution during observation, 1 (1.9%) had observation without resolution, and 3 (5.6%) were lost to follow-up. The median size of PUC at the first visit was significantly larger in the surgical excision group (5 mm median, IQR 3-5) than in the spontaneous resolution group (1.5 mm median, IQR 1-2.5) (P <.0001). In this study, PUC ≥5 mm in diameter did not have spontaneous resolution.
This is the largest study of PUC conducted at a single institute. This study indicated that 22% of PUCs had spontaneous resolution, and PUCs <5 mm had potential for spontaneous resolution. The results recommend an observation of at least 5.5 months for patients with asymptomatic PUC <5 mm. By contrast, we recommend the surgical excision for symptomatic PUC ≥5 mm according to the family preference.
Hirschsprung's disease (HSCR) is caused by incomplete colonization of enteric neural crest-derived cell (ENCC) in the bowel, the failure of ENCCs to proliferate, differentiate, and migrate leads to ...an absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. Various animal models of HSCR have been important in the understanding of the anatomy and pathophysiology of the disease and in the discovery of genes involved in HSCR. Four types of HSCR animal models have been developed: teratogen-induced, surgically created, naturally occurring models, and knockout models. Mutations in several genes affect enteric nervous system (ENS) development and can have pleiotropic effects on this system. Furthermore, certain animal models are informative regarding how such molecules control the development and functional differentiation of the ENS. In this article, we summarize recent advances in this field and highlight opportunities for new discoveries.
Purpose
Cell therapy is a promising approach to treat enteric neuropathies such as Hirschsprung disease (HD). Recent studies have reported that enteric neurons derived from stem cells (ENCCs) can be ...grafted into the HD colon. Thus, we investigated the migration and generation of enteric neurospheres from
SOX10
-VENUS
+
mice after transplantation into control or
Ednrb
KO mice, which are a model of HD.
Methods
Single-cell suspensions were isolated from the fetal guts of
SOX10
-VENUS
+
mice E13.5 and dissociated. These cells were cultured for 7 days under non-adherent conditions to generate neurospheres, which were co-cultured with dissociated control or
SOX10
-VENUS
−
Ednrb
KO mouse gut on E13.5. 4 days later, these cells were fixed and the expression of the neuronal marker, Tuj1, was evaluated.
Results
Transplanted neurospheres had undergone abundant neuronal migration and differentiation of ENCCs in the control gut compared with the HD gut. The average length and intersections were significantly decreased in HD colon compared with controls (
p
< 0.05), and a similar pattern was observed in the HD small intestine (
p
< 0.05).
Conclusions
We demonstrated that transplanted ENCCs did not differentiate properly in HD gut. These results highlight the importance of the neuronal environment in the recipient gut for enteric nervous system development.
Semaphorins are guidance cues for developing neurons, implicated in the determination of the migratory pathway of neural crest-derived neural precursors during enteric nervous system development. ...Recently, it has been reported that Semaphorin 3A (SEMA3A) expression is up-regulated in the aganglionic colon in Hirschsprung disease (HD) patients, suggesting that increased SEMA3A expression may be a risk factor for HD. Thus, the aim of our study was to determine the expression of SEMA3A using Sox10-Venus mice gut.
We harvested the gut on postnatal day 2 (P2). SOX10-Venus+/EDNRB−/− mice were compared with SOX10-Venus+/EDNRB+/+ mice as controls. QRT-PCR was performed to determine gene expression of SEMA3A (n=8). Fluorescent immunohistochemistry was performed to assess protein distribution.
On P2, gene expression levels of SEMA3A were significantly increased in the HD group compared to controls in the proximal and distal colon (p<0.05). Laser scanning microscopy revealed SEMA3A expression was localized within the submucosa and muscle layer of the gut in both HD and controls. In HD, SEMA3A was highly expressed in the proximal and distal colon.
In the present study, we demonstrated that SEMA3A expression is increased in the EDNRB−/− HD model on P2, suggesting that SEMA3A may interfere with ENCC migration, resulting in an absence of enteric neurons.
A modified pull-through (PT) distinguished by complete full-thickness removal of the posterior rectal cuff, initially developed as an open procedure in 1980, has been performed with laparoscopic ...assistance since 1997. Postoperative bowel dysfunction improved when the anatomic landmark for PT surgery was revised from the dentate line (DL) to the anorectal (or Herrmann's) line (ARL) in 2007. A 40-year (1980-2019) review of 153 consecutive rectal/rectosigmoid type Hirschsprung's disease (HD) patients is presented.
Data for postoperative bowel dysfunction and Hirschsprung-associated enterocolitis (HAEC) classified according to the American Pediatric Surgical Association (APSA) scale were obtained retrospectively.
PT was open (
= 43) and laparoscopic (
= 110). Dissection was DL (
= 57) and ARL (
= 96). Over 40 years, 5/153 patients (3.3%) had postoperative obstructive symptoms (POS), and 10/153 patients (6.5%) had 13 episodes of postoperative HAEC; APSA grades were: I (
= 4); II (
= 8); and III: (
= 1) presenting with explosive diarrhea (10/13; 76.9%), fever (10/13; 76.9%), abdominal distension (9/13; 69.2%), or bloody stools/shock (1/13 with grade III; 7.7%). The grade III case had histologically-proven transitional zone PT. Postoperative HAEC developed in 3/5 (60.0%) POS+ patients and 7/148 (4.7%) POS- patients (
= .002). Symptom duration and treatment were not correlated with APSA grades.
Complete full-thickness posterior rectal cuff excision and using the ARL reduced postoperative HAEC significantly in this series. Despite being anatomically distinct, the DL is inadequate as a precise landmark for PT surgery because it lacks functional relevance. The APSA scale could benefit from timely review to improve its clinical and prognostic value.
Purpose
Laminin, an extracellular matrix molecule, is essential for normal development of the nervous system. The alpha1 subunit of laminin-1 (LAMA1) has been reported to promote neurites and ...outgrowth and is expressed only during embryogenesis. Previously, we developed a
Sox10
transgenic version of the Endothelin receptor-B (
Ednrb
) mouse to visualize Enteric neural crest-derived cell (ENCC)s with a green fluorescent protein, Venus. We designed this study to investigate the expression of LAMA1 using
Sox10-
VENUS mice gut.
Methods
We harvested the gut on days 13.5 (E13.5) and 15.5 (E15.5) of gestation.
Sox10
-VENUS
+
/
Ednrb
−/−
mice (
n
= 8) were compared with
Sox10
-VENUS
+
/
Ednrb
+/+
mice (
n
= 8) as controls. Gene expression of LAMA1 was analysed by real-time RT-PCR. Fluorescent immunohistochemistry was performed to assess protein distribution.
Results
The relative mRNA expression levels of LAMA1 were significantly increased in HD in the proximal and distal colon on E15.5 compared to controls (
p
< 0.05), whereas there were no significant differences on E13.5. LAMA1 was expressed in the serosa, submucosa and basal lamina in the gut, and was markedly increased in the proximal and distal colon of HD on E15.5.
Conclusions
Altered LAMA1 expression in the aganglionic region may contribute to impaired ENCC migration, resulting in HD. These data could help in understanding the pathophysiologic interactions between LAMA1 and ENCC migration.
Aim
Detailed implications of age at laparoscopic transanal pull-through (LTAPT) on postoperative bowel function (POBF) in Hirschsprung’s disease (HD) are somewhat obscure because of a spectrum of ...factors.
Methods
Age at surgery was used to categorize 106 consecutive postoperative HD cases treated by our modified LTAPT (JLTPAT) between 1997 and 2015; group A: < 3 months old (
n
= 31); group B: 3–11 months old (
n
= 44); group C: 1–3 years old (
n
= 19); and group D: ≥ 4 years old (
n
= 12). POBF was assessed by reviewing outpatient records 1, 3, 5, 7, and 10 years after JLTAPT prospectively and scoring each of 5 criteria on a scale of 0–2; best score = 10.
Results
Only operative time was statistically longer in group D versus groups A, B, and C. Differences in gender ratios, blood loss, duration of follow-up, and POBF scores were not statistically significant. Mean POBF scores over time were: group A: 6.8, 7.6, 8.4, 8.6, and 8.4; group B: 7.1, 7.8, 8.3, 8.5, and 9.0; group C: 6.9, 7.9, 8.1, 8.3, and 8.6; group D: 7.0, 7.4, 8.2, 8.1, and 8.5, respectively.
Conclusion
Age at JLTAPT was not correlated with POBF in HD.
Purpose
Hirschsprung’s disease (HD) is caused by a failure of enteric neural crest-derived cells (ENCC) to colonize the bowel, resulting in an absence of the enteric nervous system (ENS). Previously, ...we developed a
Sox10
transgenic version of the Endothelin receptor-B (
Ednrb
) mouse to visualize ENCC with the green fluorescent protein, Venus. The aim of this study was to isolate
Sox10
-Venus
+
cells, which are differentiated neurons and glial cells in the ENS, and analyze these cells using
Sox10
-Venus mice gut.
Methods
The mid-and hindgut of
Sox10
-Venus
+
/
Ednrb
+
/
+
and
Sox10
-Venus
+
/
Ednrb
−
/
−
at E13.5 and E15.5 were dissected and cells were dissociated.
Sox10
-Venus
+
cells were then isolated. Expression of PGP9.5 and GFAP were evaluated neurospheres using laser scanning microscopy.
Results
7 days after incubation,
Sox10
-Venus
+
cells colonized the neurosphere. There were no significant differences in PGP9.5 expressions on E13.5 and E15.5. GFAP was significantly increased in HD compared to controls on E15.5 (
P
< 0.05).
Conclusions
Our results suggest increased glial differentiation causes an imbalance in ENCC lineages, leading to a disruption of normal ENS development in this HD model. Isolation of ENCC provides an opportunity to investigate the ENS with purity and might be a useful tool for modeling cell therapy approaches to HD.
Dysgerminoma is a malignant ovarian germ cell tumor, and unlike sex-cord stromal tumors, endocrine manifestation is considered rare. Here, we report the first case of dysgerminoma presenting ...precocious puberty. The patient is a 7-year-old girl who presented with a breast development in Tanner stage 3. Serum estradiol (E2) was markedly elevated while luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were suppressed below the detection limit. Microscopically, the right ovarian mass displayed nests of large polygonal cells and fibrous septa which were focally concentrated by theca-like plump spindle cells. Immunohistochemistry revealed that the spindle cells expressed various steroidogenic enzymes involved in estrogen biosynthesis including P450 aromatase. The tumor was diagnosed with pure dysgerminoma with estrogen-producing functioning stroma. After the operation, serum E2 declined below the detection limit; LH and FSH returned within the normal range. This case demonstrates that even a conventional dysgerminoma can present endocrine manifestation through functioning stroma.
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