Controlling precocious puberty--surgical excision of hypothalamic hamartoma causing precocious puberty

Among the causes of precocious puberty, hypothalamic hamartoma comprises a small percentage. However, the frequency of precocious puberty in the presence of hypothalamic hamartoma is quite high. Recently, results of surgery in 14 cases of hypothalamic hamartoma were reported. Precocious puberty completely subsided in three cases and slight improvement was achieved in another three cases. We performed surgery in four patients with hypothalamic hamartomas, with the goal of decreasing the symptoms of precocious puberty. The patients were two females (aged 1 yr, 3 mo and 6 mo) and two males (aged 3 yr, 7 mo and 1 yr, 9 mo). The main symptoms were precocious puberty and mental retardation of varying degrees. The males had excessive growth of body and external genitalia, while the females had genital bleeding and premature breast development. In each case, computed tomographic scans disclosed a round, isodense mass in the interpeduncular cistern, attached to the base of the hypothalamus. Contrast enhancement was negative. Endocrinologically, in case 1, testosterone was 92.6 ng/ml, FSH was 16 mIU/ml, and LH was 2.2 mIU/ml. Although LH was within normal limits, it overresponded to LH-RH stimulation. In case 2, estrogen was 13.5 ng/day, LH was 5.2 mIU/ml, FSH was 5.3 mIU/ml, and LH showed an exaggerated response to LH-RH stimulation. In case 3, testosterone was 362 ng/ml, LH was 8.8 mIU/ml, FSH was 4.8 mIU/ml, and LH showed an abnormally high response to LH-RH stimulation. In case 4, LH was 18.4 mIU/ml, FSH was 12.0 mIU/ml, and both hormones were stimulated abnormally strongly by LH-RH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic hamartoma with precocious puberty--a case report

A case of hypothalamic hamartoma with precocious puberty is presented and the literature of reported cases is reviewed. An 8-year-old boy was admitted to our hospital because of precocious puberty and mental retardation. His genital development was Tanner's stage 4 and pubic hair was Tanner's stage 3. Bone age was 11 years. Plain CT showed an isodense mass in the suprasellar cistern which was not enhanced following contrast administration. Metrizamide CT cisternography showed a filling defect in the suprasellar cistern. Endocrinological evaluation revealed high levels of serum luteinizing hormone (LH) and testosterone with a marked response of LH to LH-RH injection. A left frontotemporal craniotomy was performed and the tumor was partially removed. The tumor was gray, firm and well-circumscribed with poor vascularity. Postoperatively, a right oculomotor palsy and transient diabetes insipidus developed. He was discharged ambulatory one month later. Serum LH and testosterone returned to normal and the response of LH to LH-RH injection became normal. Hamartoma was diagnosed on histological examination. Electron micrographic study showed numerous dense granules with approximately 0.1 mu in diameter, in which Judge proved LH-RH by immunofluorescent study in 1977. Our case supports the hypothesis that hypothalamic hamartoma may cause precocious puberty by autonomous secretion of LH-RH and we consider that neurosurgical treatment is recommended.     

Pubertas praecox and hypothalamic hamartoma

Summary Precocious puberty of cerebral origin is classified into pseudoprecocious puberty and true precocious puberty. Pseudoprecocious puberty is caused by HCG secreting tumours. True precocious puberty is caused by various hypothalamic diseases. Among them, hypothalamic hamartoma is the most common cause. Precocious puberty is caused by elevated blood pituitary gonadotropin concentration, secondary to the elevated hypothalamic LHRH secretion. The hypothalamic hamartoma is not infrequently associated with laughing (gelastic) seizures as well as convulsions. Diagnosis of a hypothalamic hamartoma is easily made by CT. Although the hypothalamic hamartoma is difficult to operate on, the value of surgery is stressed for treatment of precocious puberty. This is also confirmed by recent reports.     

Microsurgical treatment for hypothalamic hamartoma in children with precocious puberty

BACKGROUND: We review the surgical treatment of hypothalamic hamartoma causing precocious puberty. METHODS: Six children (three girls and three boys) with precocious puberty secondary to hypothalamic hamartoma were recruited for our study. The mean age of the patients was 30 months old (range 13 months to 5 years), and the mean age of the onset of puberty was 7.3 months. All patients were treated by microsurgery. RESULTS: All patients had higher then normal stature, body weight, bone growth, and serum levels of sexual hormones. The boys presented with mature external genitalia, pubic hair, frequent erection, and acne, while the girls presented with growth of breasts and menarche. Magnetic resonance image (MRI) revealed an isointense mass below the tuber cinereum extending into the supersellar and interpeduncular cistern, ranging from 4 to 12 mm in diameter, consistent with pedunculate hamartoma. The hamartoma was removed completely via a right pterional approach. The symptoms and signs of precocious puberty resolved completely, and sexual hormone levels decreased to the pre-pubertal range in all six patients without any postoperative complications. CONCLUSION: We report a series of six children with hypothalamic hamartoma-induced precocious puberty who underwent microsurgical treatment. All of them recovered completely to their age-appropriate state. Microsurgery is a good choice of treatment for pedunculate hypothalamic hamartoma.     

The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma.

OBJECT: Hypothalamic hamartoma is generally diagnosed based on its magnetic resonance (MR) imaging characteristics and the patient's clinical symptoms, but the relationship between the neuroradiological findings and clinical presentation has never been fully investigated. In this retrospective study the authors sought to determine this relationship. METHODS: The authors classified 11 cases of hypothalamic hamartoma into two categories based on the MR findings. Seven cases were the "parahypothalamic type," in which the hamartoma is only attached to the floor of the third ventricle or suspended from the floor by a peduncle. Four cases were the "intrahypothalamic type," in which the hamartoma involved or was enveloped by the hypothalamus and the tumor distorted the third ventricle. Six patients with the parahypothalamic type exhibited precocious puberty, which was controlled by a luteinizing hormone-releasing hormone analog, and one patient was asymptomatic. No seizures or mental retardation were observed in this group. All patients with the intrahypothalamic type had medically intractable seizures, and precocious puberty was seen in one. Severe mental retardation and behavioral disorders including aggressiveness were seen in two patients. The seizures were controlled in only one patient, in whom stereotactically targeted irradiation of the lesion was performed. This topology/symptom relationship was reconfirmed in a review of 61 reported cases of hamartoma, in which the MR findings were clearly described. The parahypothalamic type is generally associated with precocious puberty but is unaccompanied by seizures or developmental delay, whereas the intrahypothalamic type is generally associated with seizures. Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. CONCLUSIONS: Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.     

Hypothalamic hamartoma successfully treated by operation. Case report

An 18-month-old boy was diagnosed as having a hypothalamic hamartoma. When he was 1 year old, he developed precocious puberty, and at 18 months old, endocrinological tests revealed abnormally high follicle-stimulating hormone, luteinizing hormone, and testosterone levels. The center of the hamartoma was subtotally excised, as confirmed on the postoperative computerized tomography scan. Precocious puberty subsided after the operation.     

Treatments of hamartoma with neuroendoscopic surgery and stereotactic radiosurgery: a case report.

Hypothalamic hamartoma is a non-neoplastic tumor manifesting as gelastic seizure, precocious puberty, and abnormal behavior. Treatment of it is very complicated due to its location. We report a case of hypothalamic hamartoma treated by neuroendoscopic surgery and stereotactic radiosurgery. A 5-year-old girl presented with violent behavior, precocious puberty, gelastic seizure and atonic seizure. She was diagnosed with hypothalamic hamartoma by CT and magnetic resonance imaging at 11 months of age. Tumor size did not change, but tumor intensity had changed on the MR image at 5 years of age. Magnetic resonance spectroscopy revealed decreased N-acetylaspartate and increased choline and creatine in the tumor. After neuroendoscopic biopsy, she underwent linear accelerator stereotactic radiosurgery. But her symptoms remained unchanged for 6 months. She then underwent partial resection and laser coagulation of the tumor by a neuroendoscopic approach. After the procedure, the frequency of her seizures was remarkably decreased, and her violent behavior improved. The transventricular neuroendoscopic approach to the hypothalamus is less invasive than the radical surgery. Neuroendoscopic surgery can be one of the treatments of choice for hypothalamic hamartoma.     

Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty

We have studied a 3 1/12-year-old boy who presented with a hypothalamic mass and precocious puberty. His history suggested a course of isosexual precocity progressing from birth. Gelastic seizures also began at an early age. Endocrine evaluation revealed normal thyroid-stimulating hormone and growth hormone secretion, elevated basal and stimulated prolactin concentrations, and luteinizing hormone responses to sequential intravenous injections of gonadotropin-releasing hormone (GnRH) that were pubertal in pattern and magnitude. A needle biopsy of the mass recovered tissue that contained neurons histologically similar to those found in the normal hypothalamus, and the mass was characterized as a hypothalamic hamartoma. Immunohistochemical staining of this tissue with anti-GnRH antiserum demonstrated positive staining for GnRH immunoreactivity in neurons. This suggests a neurosecretory pathogenesis for the precocious puberty found in patients with hamartomas in the hypothalamic region.     

Hypothalamic hamartoma: the role of surgery

A hypothalamic hamartoma associated with true precocious puberty in a 7-month-old girl is hereby reported. Hormonal studies disclosed elevated serum levels of luteinizing hormone (LH) and follicle stimulating hormone, both of which responded well to LH-releasing hormone stimulation. Following a subtotal removal of the tumor, the clinical manifestations of precocious puberty as well as associated endocrinological abnormalities returned to normal. The role of surgery for this lesion, which appears to be safe when a planned microsurgical course is employed, is discussed.     

A case of hypothalamic astrocytoma with precocious puberty]

A case of hypothalamic astrocytoma with precocious puberty is presented. In July 1989, a 2-year-old girl was admitted to our hospital because of vaginal bleeding and enlargement of breasts. Breast development was Tanner's stage 3 and no pubic hair was present. Endocrinological evaluation revealed a slightly high level of LH, but the responses of LH and FSH to LH-RH test resulted in exceedingly high values similar to those in adults. Plain CT scan showed an isodense mass in the suprasellar cistern which was not enhanced following administration of contrast medium. MR imaging revealed the precise location of the mass attached to the posterior hypothalamus between the pituitary stalk and the mamillary bodies in sagittal view. The signal intensity of the mass was homogenous and isointense relative to the gray matter on T1 weighted image. But on T2 weighted image, it showed high signal intensity compared with the normal brain parenchyma. A right fronto-temporal craniotomy was performed and the tumor was partially removed. Histological examination disclosed moderate hypercellularity of glial cells but no neurons were visible. This appeared to be astrocytoma grade II. In the literature, CT and MRI behaviour of hypothalamic hamartomas are almost similar to our case. Therefore we think it is not possible at the present time to differentiate a low grade astrocytoma from hamartoma when using CT and MRI alone. In this case, the mechanism of development of precocious puberty seemed to be due to hypothalamic compression by the tumor.     

Syringocystadenoma papilliferum on the breast: An unusual location

Introduction

Syringocystadenoma papilliferum (SCAP), otherwise known as naevus syringocystadenomatosus papilliferus, is a skin hamartoma originating from apocrine or exocrine sweat glands [1], microscopically characterized by papillary invaginations lined by bi-layered epithelium and decapitation secretion rich in plasmacytes [3].

Case Report

A 29-year-old female presented with a cluster of large fleshy, irregular, sessile, moist, pinkish tumours located over her left breast, with pain, itching, discharge and bleeding upon friction with undergarments.

Discussion

SCAP is an uncommon skin tumour usually seen in children or adolescents as a firm plaque of skincoloured to pinkish-brown hairless grouped nodules or a solitary nodule. Verrucous, papillary, hyperkeratotic, fleshy transformations are often seen in puberty [4,5]. Uncommon sites, such as the buttock, vulva, scrotum, pinna, eyelid, outer ear canal, postoperative scar, thigh, axilla, arms, lower limb, inguinal and perineal regions, have also been reported [6–9].

Conclusion

SCAP is a rare adnexal tumour commonly arising in association with congenital Sebaceous Naevus of Jadassohn. A watchful alertness is mandatory as adulthood malignancies can occur in more than one-third of this deceptively docile tumour.     

Precocious puberty due to a hypothalamic hamartoma.

A case of precocious puberty due to a hypothalamic hamartoma is presented. Concentrations of plasma LH and FSH, testosterone and its derivatives were found to be elevated. Circadian rhythms of LH were also observed. After removal of the mass, plasma LH and FHS concentrations declined to nearly half the preoperative levels.     

Precocious puberty and hypothalamic hamartoma. Report on a new case with ultrastructural data

A new case of hypothalamic hamartoma associated with precocious puberty is presented. After reviewing the literature, 23 other cases appeared. The ultrastructural study of the present case revealed common features with other hamartomatous lesions of the central nervous system and with the gangliogliomas. The data suggest that these lesions are morphologically organized in a very similar manner despite their very different growing potential.     

Suprasellar arachnoid cyst associated with precocious puberty: report of an operated case and review of the literature]

The pathogenesis remains unknown in the majority of patients with precocious puberty, and yet infrequently such causative cerebral lesions as hypothalamic hamartomas are associated with sexual precocity. We reported a rare case of suprasellar arachnoid cyst in an infant presenting with precocious puberty, which eventually disappeared after a cyst-peritoneal shunt. It was believed that the mass effect of the arachnoid cyst upon the hypothalamus was, at least in part, responsible for development of precocious puberty. The role of surgical decompression of the cyst was also discussed. A one-year-old girl was admitted to the hospital for evaluation of genital bleeding which had persisted on and off for two months. The height, 80cm, and the weight, 12.4kg, exceeded by far the two standard deviations from the mean level of the normal population. In addition she had the development of breast tissue as classified Tanner's Stage II, and both pubic and axillary hair. The bone age by skeletal survey of the hand was rated as 3 years. Endocrinological examination showed that serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol had increased for her age, to levels equivalent to those for females at puberty. An LH-RH test revealed an excessive LH reaction. There were no definite neurological deficits. CT and MRI demonstrated the presence of a large arachnoid cyst involving the suprasellar region as well as the right middle and posterior fossa. After the patient underwent a cyst-peritoneal shunt, the cyst decreased in size and such symptoms as genital bleeding and breast growth disappeared. Serum levels of her LH and FSH also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stereotactic radiofrequency ablation for sessile hypothalamic hamartoma with an image fusion technique

Summary ¶Background. Radiosurgery has been advocated as a primary treatment for hypothalamic hamartoma (HH), but it has a risk of damaging the surrounding structures and does not have an immediate effect for refractory epilepsy, endocrinological and mental disorders. Method. We report on a 13-year-old boy with a large and sessile HH who presented with intractable seizures, precocious puberty and aggressiveness. Stereotactic radiofrequency ablation (SRA) combined with an image fusion technique was performed to make a maximum ablative lesion within the HH via multiple trajectories. Findings. After surgery, we observed rapid cessation of the gelastic seizures and aggressiveness. The ophthalmological function did not get worse, and the hypothalamopituitary function improved. Interpretation. SRA in combination with an image fusion technique is a viable alternative treatment for HH, because it provides precise preoperative simulation and immediate improvement of symptoms can be obtained.Published online July 31, 2003     

Hypothalamic protein kinase C regulates glucose production

OBJECTIVE—A selective rise in hypothalamic lipid metabolism and the subsequent activation of SUR1/Kir6.2 ATP-sensitive K⁺ (K_ATP) channels inhibit hepatic glucose production. The mechanisms that link the ability of hypothalamic lipid metabolism to the activation of K_ATP channels remain unknown.RESEARCH DESIGN AND METHODS—To examine whether hypothalamic protein kinase C (PKC) mediates the ability of central nervous system lipids to activate K_ATP channels and regulate glucose production in normal rodents, we first activated hypothalamic PKC in the absence or presence of K_ATP channel inhibition. We then inhibited hypothalamic PKC in the presence of lipids. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of hypothalamic administrations on glucose metabolism in vivo.RESULTS—We first reported that direct activation of hypothalamic PKC via direct hypothalamic delivery of PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) suppressed glucose production. Coadministration of hypothalamic PKC-δ inhibitor rottlerin with OAG prevented the ability of OAG to activate PKC-δ and lower glucose production. Furthermore, hypothalamic dominant-negative Kir6.2 expression or the delivery of the K_ATP channel blocker glibenclamide abolished the glucose production-lowering effects of OAG. Finally, inhibition of hypothalamic PKC eliminated the ability of lipids to lower glucose production.CONCLUSIONS—These studies indicate that hypothalamic PKC activation is sufficient and necessary for lowering glucose production.The hypothalamus senses nutrients and hormones to regulate energy and glucose homeostasis (1–9), but the associated central nervous system (CNS) sensing mechanisms remain unclear. A selective increase in long-chain fatty acyl-coenzyme A (LCFA-CoA) level in the hypothalamus leads to the activation of SUR1/Kir6.2-containing ATP-sensitive K⁺ (K_ATP) channels and lowers glucose production (10). In contrast, an elevation of LCFA-CoA level in the liver actually increases glucose production during hyperinsulinemia (1). These observations led us to hypothesize that lipid-sensing mechanisms share similar biochemical (i.e., LCFA-CoA accumulation) but have opposing physiological mechanisms (i.e., glucose production regulation) in operation (1).In the peripheral tissues such as the liver and muscle, an elevation of lipids (especially the long-chain fatty acids [LCFAs]) activates the novel isoforms of protein kinase C (PKC) (i.e., -δ, -ɛ, and -θ) to induce insulin resistance during hyperinsulinemic-euglycemic clamps (11–16). Although novel isoforms of PKC (especially -δ and -ɛ) are expressed in the brain (17), it is currently unknown whether LCFAs activate hypothalamic, novel isoforms of PKC to regulate glucose production. It has been reported that activation of PKC leads to phosphorylation of the conserved threonine residue (T180) in the pore-forming subunit Kir6.2 of the K_ATP channels in the pancreatic β-cells (18). These channels are expressed in both β-cells and neurons (18,19), and direct activation of the hypothalamic K_ATP channels has been shown to lower glucose production (19). Both the PKC-induced K_ATP channel activation (18) and hypothalamic K_ATP channels’ regulation of glucose production (19) are blocked by pretreatment with the K_ATP channel blocker glibenclamide (18,19). It is possible that the mechanism of activation of K_ATP channels in the β-cells by PKC is also found in the hypothalamus.Based on these independent yet parallel findings, we tested the hypothesis that activation of hypothalamic PKC is sufficient and necessary for CNS lipid-sensing mechanisms to lower glucose production and regulate glucose homeostasis (Fig. 1A).Open in a separate windowFIG. 1.Hypothalamic PKC activation lowers glucose production. A: Working hypothesis: lipids activate hypothalamic PKC to phosphorylate and activate the hypothalamic Kir6.2/SUR1-containing K_ATP channels to lower glucose production. Direct MBH administration of PKC activator OAG increased glucose infusion rate (B) and lowered glucose production (C) during the clamps. MBH OAG coinfused with general PKC inhibitor BIM (n = 5), specific PKC-δ inhibitor Rot (n = 6), or K_ATP channel blocker glibenclamide (n = 5) or in MBH DN Kir6.2 AAA-injected rats (n = 5) failed to increase glucose infusion rate (B) and lower glucose production (C). D: Glucose uptake was comparable in all groups. MBH vehicle (VEH) (n = 6) consisted of MBH saline (n = 3) and MBH 5% DMSO (n = 3). MBH OAG (n = 7) consisted of MBH OAG in normal rats (n = 4) and in MBH GFP-injected rats (n = 3). *P < 0.001 (ANOVA) and P < 0.01 vs. other individual groups.     

Penile apoptosis in association with p53 under lack of testosterone

It is known that testosterone deficiency induces apoptosis in the prostate and that p53 protein is involved in this apoptosis. Therefore, p53 protein may also be involved in apoptosis induction in a testosterone-deficient state in the penis. In this study, we investigated whether castration and chemical castration induce apoptosis at penile tissue in rats, and whether p53 protein is involved in this apoptosis. Male SD rats aged 8 weeks were divided into four groups: 1) the Control group; 2) the Castration group; 3) the Estrogen group, in which rats received estradiol 17-(-D-glucuronide) injection of 500 g/body/day; and 4) the LH-RH group, in which rats received LH-RH analogue (leuprorelin acetate) injection of 2 mg/kg. The rats were sacrificed after treatment on days 1, 3, 5, 14, and 28 by cervical dislocation. Apoptotic cells and p53 protein-positive cells were observed on the 5th day after treatment and thereafter in all castration, estrogen, and LH-RH groups. These findings showed that both castration and chemical castration induced p53 protein in vascular endotherial cells in the corpus cavernosus during the process of losing testosterone. It was also suggested that in such states, apoptosis is induced in vascular endotherial cells in the corpus cavernosus.     

Linkage between O6-methylguanine-DNA methyltransferase (O6-MT) activity and cellular resistance to antitumour nitrosoureas in cultured rat brain tumour cell strains

Summary We have examined O⁶-methylguanine-DNA methyltransferase (O⁶-MT) activity of rat brain tumour cell strains with reference to cellular resistance to antitumour nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (nimustine, ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy--D-glucopyranoside (ramustine, MCNU). The values of O⁶-MT activity were 52 and 160 fmol/mg protein extract in 9 L and C 6 rat brain tumour cells, respectively; while HeLa S 3 cells, as a methyl excision repair positive (Mer⁺) cell strain, revealed a rather high value of 488 fmol/mg. 9 L cells indicative of a low O⁶-MT activity showed 13 M for ACNU and 18 M for MCNU at a 10% survival dose (SD₁₀), determined by a clonogenic cell assay as an index of cellular resistance. In contrast to this, C 6 cells revealed a SD₁₀ value of 67 M and 36 M for ACNU and MCNU, respectively, indicating higher resistance than 9 L cells. HeLa S 3 cells showed the highest SD₁₀ value as follows: 84 M for ACNU and 73 M for MCNU. The relationship between the O⁶-MT activity and the cellular resistance was almost linear, with relatively resistant cell lines exhibiting the higher levels of the O⁶-MT activity. This correlation between the O⁶-MT activity and the cellular resistance to nitrosoureas as ACNU and MCNU was not observed among other antitumour drugs, which included bleomycin (BUM), neocarzinostatin (NCS),cis-diamminedichloroplatinum (II) (CDDP), and etoposide (VP-16) in clinical use for brain tumour chemotherapy. This indicates that O⁶-MT activity can be an indicator of cellular resistance to antitumour nitrosoureas in the chemotherapy of brain tumours.     

Intraoperative use of high-field MRI in hypothalamic hamartomas associated with epilepsy: clinico-pathological presentation of five adult patients

Background

Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity.

Methods

We present a series of five adult patients with drug-resistant epilepsy who had been operated on for HH using neuronavigation and intraoperative 1.5-T magnetic resonance imaging (MRI). In this retrospective investigation, we compared our surgical strategy and postoperative results to existing series.

Results

During surgery, we identified remnant HH in the first intraoperative MRI control scan in three out of five patients. After re-segmentation of the residual lesion using neuronavigation, complete resection was achieved in two of the three patients as confirmed by final intraoperative and late follow-up MRI, raising the rate of total resections to four out of five patients. Two patients died during the observation period. One patient suffered from a permanent third nerve palsy and one from a transient monoparesis of the left arm. New endocrinological disturbances included diabetes insipidus centralis in two and secondary hypothyroidism and hypogonadism in one patient. Four out of five patients had favourable seizure control (Engel I or II) after 64.8 (34–83) months of mean follow-up.

Conclusions

Neuronavigation and intraoperative MRI are valuable tools to encounter difficulties while performing surgery in patients with HHs. Intraoperative resection control increases the amount of maximum resection.     

Biliary atresia,the next generation: a review of liver function,social activity,and sexual development in the late postoperative period

Purpose: The current study aimed to establish the management for biliary atresia (BA) patients in the late postoperative period. Methods: Of 165 BA patients operated on in the authors' department, 44 patients (16 boys, 28 girls) with a follow-up period of more than 15 years were reviewed retrospectively. Results: Forty-one of 44 patients (93.2%) currently are employed or highly educated, 7 are married, whereas 2 (4.5%) died, and 10 (22.7%) required liver transplantation after puberty. Four babies have been born from BA parents without congenital anomalies. Four girls conceived 5 times and delivered 3 newborns weighing 2,330 to 2,474 g including one delivered after transplantation. Maternal portal hypertension uniformly deteriorated during pregnancy, and one pregnancy was terminated. Menstrual disorder correlated significantly with the biochemical data related to liver function at puberty such as serum choline esterase (266 [plusmn] 70.4 in 19 normal patients v 159 [plusmn] 34.3 IU/L in 9 abnormal patients, P = .00057), asparate aminotransferase (42 [plusmn] 30.8 v 96.0 [plusmn] 63.6 IU/L; P = .0031), and serum albumin (4.6 [plusmn] 0.4 v 3.9 [plusmn] 0.6 g/dL; P = .013). Conclusions: The long-term survivors of Kasai's operation, with or without liver transplantation, have reached the next generation. Transgenerational follow-up and management including conception and perinatal care should be required for BA patients.