Histologic Findings in Persistent Hyperinsulinemic Hypoglycemia of Infancy: Australian Experience

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by hyperinsulinism and profound hypoglycemia, with most children requiring pancreatic resection. The histological classification of PHHI is controversial. Most authors acknowledge the existence of focal areas of islet cell proliferation (adenomatosis) in 30%–50% of cases and a diffuse disorganisation of islet architecture, termed “nesidiodysplasia,” in others. De Lonlay et al. reported that cases with adenomatosis are focal with normal remainder of pancreas and that focal and diffuse disease can be differentiated intraoperatively, on the basis of increased β-cell nuclear size found only in the diffusely abnormal pancreas. We have examined pancreatic histology in a blinded controlled study of PHHI patients. Pancreatic tissue was obtained at autopsy from 60 normal subjects (age 17 weeks gestation to 76 years) and from surgical specimens of 31 PHHI patients. Sections from PHHI subjects (n= 294 blocks) and control sections were stained with hematoxylin and eosin, insulin, glucagon, somatostatin, NSE, cytokeratin 19, and vimentin. Three sections from each PHHI patient were randomly chosen for further analysis. Age-matched control (n= 34) and PHHI sections (n= 66) were examined, with the identity of subjects concealed. A diagnosis of normal histology, adenomatosis, or diffuse nesidiodysplasia was recorded for each section. The presence of large β-cell nuclei (>19 μm), ductuloinsular complexes, and centroacinar cell proliferation was noted. Of a total of 65 subjects examined (34 control and 31 PHHI), 37 subjects were identified as normal on both sections examined. All the control cases were correctly identified as normal and none had large β-cell nuclei or centroacinar cell proliferation. Of 31 PHHI patients, 28 were identified as abnormal, either on the basis of abnormal architecture and/or abnormally large β-cell nuclei. Three patients were identified as normal in both sections. Fifteen of 31 patients had diffuse nesidiodysplasia only. Of 13 patients with areas of adenomatosis, 2 had resection of a nodule with adenomatosis present in most of the tissue removed at surgery. Nine patients had a diagnosis of adenomatosis in one section and a diagnosis of diffuse nesidiodysplasia in the other sections from nonadjacent pancreas. Only 2 of 31 PHHI cases had adenomatosis on one section examined and normal pancreas on the other section examined. Large β-cell nuclei were variably found in PHHI sections. Only 5 of 15 patients with diffuse nesidiodysplasia had large nuclei in both sections examined. Centroacinar cell proliferation was identified in 12 PHHI subjects, 6 with adenomatosis and diffuse nesidiodysplasia and 6 with diffuse changes only. It was patchy in distribution within sections and present in only one section in 7 of the 12 subjects. In summary, we have shown that a blinded observer could differentiate control and PHHI pancreatic tissue. Only 2 of 31 patients (6%) had focal adenomatosis with normal nonadjacent pancreas, the majority (24 of 31) had diffuse nesidiodysplasia affecting the remainder of their pancreas, with 38% (9 of 24) also having areas of adenomatosis. Large β-cell nuclei did not reliably identify those with diffuse disease in this study. There was evidence of significant ductal and centroacinar proliferation in 39% of PHHI cases, which was not observed in any of the controls. We have shown that PHHI subjects have a spectrum of pancreatic histological abnormalities, from no abnormality to diffuse subtle changes to florid adenomatosis. Patients could not be segregated into subtypes for different operative intervention despite the availability of full immunohistochemical staining. Received January 5, 2000; accepted June 22, 2000.     

婴幼儿持续性高胰岛素血症的术中冰冻诊断意义及病理分析

目的探讨婴幼儿持续性高胰岛素血症(persistent hyperinsulinemic hypoglycemia in infancy,PHHI)的病理分型以及术中冰冻病理对外科手术治疗方法选择的指导意义。方法2011年4月至2016年10月,复旦大学附属儿科医院共25例PHHI患儿经外科手术治疗,回顾性分析其相关临床资料、手术治疗经过及术后病理特征。结果25例患儿中男17例,女8例,年龄16 d至12个月,术前经内分泌科明确诊断患有PHHI,空腹血糖0.6~5.5 mmol/L,禁食实验胰岛素水平为3.1~50.1 mU/L。结合术前检查及术中冰冻结果,5例患儿诊断为局灶性病变,行胰腺病灶切除术,20例诊断为弥漫性病变,行胰腺次全切术。术后随访2~38个月,空腹血糖3.0~12.6 mmol/L,15例术后血糖恢复较好,1例仍有低血糖症状,需加用激素治疗,3例空腹时血糖偏低,进食后可恢复,另6例有术后高血糖症状,需药物治疗。1例术前疑诊为局灶性病变,行50%胰腺切除术后2周复发。术后病理检查有5例诊断为局灶型,1例为不典型型,余19例为弥漫型。结论对于内科治疗无效的PHHI以手术治疗为主,术前明确病理分型对手术方式的选择极为重要,术中快速冰冻切片结合术前辅助检查可以较为准确的指导手术方式。婴幼儿PHHI主要以弥漫型为主,但从术后病理区分弥漫型及局灶性仍存在困难,其中不典型型尚无明确的定义或分类,还有待在病理学方面进一步详细研究。     

Pancreatic arterial calcium stimulation in the diagnosis and localisation of persistent hyperinsulinemic hypoglycaemia of infancy

Background: Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is often resistant to medical therapy. Surgery is therefore necessary. It is due to focal adenomatous islet-cell hyperplasia treatable by partial pancreatectomy, or diffuse beta-cell hyperfunction, which requires near-total pancreatectomy. Pancreatic venous sampling (PVS) is the reference technique for the preoperative diagnosis and localization of focal forms of PHHI in the pancreas. However, hypoglycaemia is necessary to analyse the results and PVS is technically challenging. Pancreatic arterial calcium stimulation (PACS) is technically easier and does not require hypoglycaemia. Aim: To study the accuracy in the diagnosis and localization of PHHI. Materials and methods: PACS was performed in 12 patients and correlated with histology. Results: The accuracy of PACS is poor in diffuse lesions since only two of six cases were correctly identified by this test. Five of six focal lesions were correctly recognized and located. Conclusions: PACS is less accurate than PVS in PHHI. Currently, it should be performed only when PVS fails. Received: 15 December 2000 Accepted: 6 March 2001     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

Persistent hyperinsulinaemic hypoglycaemia in infancy

Persistent hyperinsulinaemic hypoglycaemia in infancy (PHHI) is a heterogeneous condition characterised by unregulated insulin secretion in response to a low blood glucose level. It is the most common cause of severe and persistent hypoglycaemia in neonates. It is extremely important to recognise this condition early and institute appropriate management to prevent significant brain injury leading to complications like epilepsy, cerebral palsy and neurological impairment. Histologically, PHHI is divided mainly into three types—diffuse, focal and atypical disease. Fluorine-18-l-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET/CT) scan allows differentiation between diffuse and focal diseases. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The molecular basis of PHHI involves defects in key genes (ABCC8, KCNJ11, GCK, SLC16A1, HADH, UCP2, HNF4A and GLUD1) that regulate insulin secretion. Focal lesions are cured by lesionectomy whereas diffuse disease (unresponsive to medical therapy) will require a near-total pancreatectomy with a risk of developing diabetes mellitus and pancreatic exocrine insufficiency. Open surgery is the traditional approach to pancreatic resection. However, recent advances in laparoscopic surgery have led to laparoscopic near-total pancreatectomy for diffuse lesions and laparoscopic distal pancreatectomy for focal lesions distal to the head of the pancreas.     

Congenital hyperinsulinism treated by surgical resection of the hyperplastic lesion which had been preoperatively diagnosed by 18F-DOPA PET examination in Japan: a nationwide survey

Purpose

Congenital hyperinsulinism is a rare disease, and the newly developed 18 fluoro-_L-dihydroxyphenylalanine-positron emission tomography (18F-DOPA PET) examination can detect hyperplastic lesions. Our purpose was to report the results of a nationwide survey on surgical treatment of congenital hyperinsulinism in Japan.

Methods

A questionnaire was sent to the 159 accredited and affiliated training institutes certified as pediatric surgical institutes by the Japanese Association of Pediatric Surgeons, asking if they had encountered patients who underwent surgical treatment for congenital hyperinsulinism after 18F-DOPA PET examination from 2000 to 2017. Six institutes answered that they had treated such cases, and the total number of cases was 14.

Results

18F-DOPA PET examination detected the focal lesion in 12 of the 14 cases. 18F-DOPA PET examination could accurately determine the site of the hyperplastic lesion in the pancreas in 11 (91.7%) of the 12 cases. All cases underwent surgical resection of the hyperplastic lesion at under 2 years of age.

Conclusion

Surgical resection of a focal hyperplastic lesion in the pancreas was a safe and effective treatment if the hyperplastic lesion was a focal lesion. However, it is necessary to check the exact distribution of the lesion by intraoperative pathologic examination of frozen sections.

     

保留睾丸手术治疗儿童睾丸畸胎瘤疗效观察

目的 评价保留睾丸手术治疗原发性儿童睾丸畸胎瘤的疗效.方法 对2001年1月～2007年9月收治29例原发性睾丸畸胎瘤患儿的临床资料进行回顾性分析.结果 29例患儿,均为单侧,平均发病年龄43.9个月(50 d～12岁).所有患儿均表现为患侧阴囊内无痛性肿块,且经术前B超证实.除1例50 d患儿的甲胎蛋白(AFP)超出正常范围外,其余28例的AFP检查结果均在正常范围内.29例患儿中21例(72%)行保留睾丸手术,其余8例因睾丸中无正常睾丸组织而行根治性睾丸切除术.所有病例术中冰冻与术后石蜡切片病理检查结果一致,均为睾丸畸胎瘤,其中成熟型27例,不成熟型2例(均行根治性睾丸切除).29例患儿术后随访至今,平均49.7个月(12～92个月).均未出现肿瘤复发、转移等并发症.21例保留睾丸组织的患儿术后B超随访患侧睾丸无萎缩.结论 原发性儿童睾丸畸胎瘤应首选考虑尽可能保留睾丸组织.治疗方法的选择有赖于术前AFP、B超以及术中对病变的评价、冰冻检查结果.     

The laparoscopic approach toward hyperinsulinism in children

Hyperinsulinemic hypoglycemia (HH) in children requiring surgery is rare. Early HH can be the result of focal or diffuse pancreatic pathology. A number of genetic abnormalities in early HH have been identified, but in the majority of patients no abnormality is found. The sporadic focal and diffuse forms as well the autosomal recessive form are particularly therapy-resistant and demand for early surgery. Preoperative discrimination between focal and diffuse disease in early HH is difficult. 18 F DOPA PET in combination with CT is promising as is laparoscopic exploration of the pancreas. Frozen section biopsy analysis has not been uniformly beneficial. If macroscopically no focal lesion is found, limited laparoscopic distal pancreatectomy provides tissue for definitive pathologic examination. Subsequent near total laparoscopic spleen-saving pancreatectomy surgery is not particularly difficult. Later HH may occur in the context of the MEN-1 syndrome and is then multifocal in nature. In MEN-1 patients, a distal spleen-saving pancreatectomy with enucleation of lesions in the head seems justified. Insulin-producing lesions in non-MEN-1 patients should be enucleated. There should always be a suspicion of malignancy. Also, in older children, surgery for hyperinsulinism should be performed laparoscopically.     

Study of the Regression Process in Cardiac Rhabdomyomas

Rhabdomyomas are the most common primary cardiac tumors in children, and have been shown to undergo spontaneous regression. The aim of our study was to investigate morphologically and immunohistochemically some mechanisms that may explain this clinical phenomenon. Eleven tumors from three term newborn girls who had physical and radiographic features pathognomonic of tuberous sclerosis were evaluated. Control specimens were left and right heart sections from five autopsies of age- and sex-matched patients who died of causes unrelated to the cardiovascular system. The tumors had been surgically excised from various regions in the heart, and all had similar “typical” histology. Histomorphologic evaluation with von Kossa and alizarin-red stains and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method were performed to evaluate cell calcifications, necrosis, and apoptosis. Ubiquitin immunohistochemical study was also conducted to evaluate intracytoplasmic protein degradation. In cardiac rhabdomyomas (CR), all myocytes with acidophilic cytoplasmic myofibrils showed strong intracytoplasmic ubiquitin immunoreactivity, compared with the occasional weak cytoplasmic and focal nuclear positivity in control heart sections. Calcified myocyte nuclei were commonly seen in CR tumoral and nontumoral rhabdomyocytes, whereas control nontumoral cardiac myocytes did not show any calcification. The incidence of TUNEL reactivity seen in CR (4.8 nuclei per 100 cardiac rhabdomyocyte nuclei) was higher than that seen in control heart sections (1.7 nuclei per 10⁶ cardiac myocytes, P < 0.005). The data led us to conclude that the cytoplasmic contents in CR were degraded via the ubiquitin pathway, and from our observation of increased TUNEL positivity, the rate of cell death in CR appeared increased. These findings may explain, to some extent, the mechanism of tumor regression. Received February 18, 2000; accepted October 25, 2000.     

Pancreatic exocrine and endocrine function after pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy.

AIM: To evaluate long term detailed pancreatic endocrine and exocrine function in children with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) after 85-95% pancreatectomy. METHODS: Six children with PHHI between 0.9 and 12.7 years after pancreatic resection underwent clinical and investigative follow up at 1.0 to 14.9 years of age. One child with PHHI who had not had pancreatectomy was also assessed. Standard endocrine assessment, pancreatic magnetic resonance imaging (MRI), and detailed direct and indirect tests of exocrine pancreatic function were performed. RESULTS: Pancreozymin-secretin stimulation test results were normal in only one child, borderline in two, and deficient in four, one of whom requires daily pancreatic enzyme supplements. Pancreolauryl tests performed in three children were borderline in two and abnormal in the other. Only one child had low faecal chymotrypsin values. One child developed insulin dependent diabetes at 9 years and two children at 1.0 and 13.3 years require diazoxide to maintain normoglycaemia. MRI showed no major regrowth of the pancreatic remnant after resection (n = 5). CONCLUSIONS: Clinical evidence of endocrine or exocrine dysfunction has developed in only two patients to date, but detailed pancreatic function testing suggests subclinical deficiency in all but one of our patients with PHHI. Although 95% pancreatectomy results in postoperative control of blood glucose, subclinical pancreatic insufficiency is present on long term follow up and development of diabetes mellitus and exocrine failure remain ongoing risks.     

Genotype-phenotype associations in patients with severe hyperinsulinism of infancy.

In hyperinsulinism of infancy (HI), unregulated insulin secretion causes hypoglycemia. Pancreatectomy may be required in severe cases, most of which result from a defect in the beta-cell KATP channel, encoded by ABCC8 and KCNJ11. Pancreatic histology may be classified as diffuse or focal disease (the latter associated with single paternal ABCC8 mutations), indicated by the presence of islet cell nuclear enlargement in areas of diffuse abnormality. We investigated genotype-phenotype associations in a heterogeneous Australian cohort. ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy. Ninety-eight control DNA samples were tested by single nucleotide polymorphism analysis. Eighteen ABCC8 mutations were identified, 10 novel. Eleven patients (4 compound heterozygote, 4 single mutation, 3 no mutation detected) had diffuse hyperinsulinism. Nine patients had focal hyperinsulinism (6 single paternal mutation, 2 single mutation of undetermined parental origin, 1 none found) with absence of islet cell nuclear enlargement outside the focal area, although centroacinar cell proliferation and/or nesidiodysplasia was present in 7 cases. Regeneration after near-total pancreatectomy was documented in 4 patients, with aggregates of endocrine tissue observed at subsequent operations in 3. Although the absence of enlarged islet cell nuclei is a useful discriminant of focal hyperinsulinism associated with a paternal ABCC8 mutation, further research is needed to understand the pathophysiology of other histological abnormalities in patients with HI, which may have implications for mechanisms of ductal and islet cell proliferation. Previous surgery should be taken into account when interpreting pancreatic histology.     

Morphologic analysis of focal and diffuse forms of congenital hyperinsulinism

Congenital hyperinsulinism is clinically characterized by an inappropriate insulin secretion resulting in recurrent severe hypoglycemia. Nesidioblastosis, the proliferation of islet cells budding off from ducts, has been considered for years as the histologic lesion responsible for the syndrome. In our morphologic studies, we demonstrate that nesidioblastosis is not specific of the disease, which is actually not a single entity. Indeed, we recognize the existence of 2 different forms-a diffuse form and a focal form-and demonstrate that they can be differentiated by morphologic criteria, even on frozen sections during surgery. This histologic distinction directs the therapeutic approach because the patients experiencing the focal form of the syndrome can be completely cured by a very limited pancreatectomy. Molecular findings confirmed the reliability of this histologic distinction, showing a specific background for each form.     

Duodenal heterotopic pancreas in a child

Background  Heterotopic pancreas is characterized by pancreatic tissue outside the pancreatic bed. However, duodenal heterotopic pancreas in children is rarely reported so far. We describe herein duodenal heterotopic pancreas in a child who suffered from chronic abdominal pain. Methods  An 8-year-old boy presented with upper abdominal pain and intermittent vomiting, without a history of melena, hematochezia, hematemesis, claycolored stools, jaundice, hepatitis or dyscrasia. No specific medication or change in position relieved the pain. Based on the elevated serum amylase levels, and the findings of CT, barium meal X-ray examination, magnetic resonance imaging, and upper gastrointestinal endoscopy, a duodenal mass was diagnosed initiatively. Intraoperative frozen section analysis was performed for the diagnosis. The mass was dissected. Results  Intraoperative frozen section analysis and routine pathological examination confirmed the diagnosis of duodenal heterotopic pancreas. The patient had an uneventful recovery and remained asymptomatic postoperatively during a follow-up period of 16 months. Conclusions  Heterotopic pancreas should be considered in children with a duodenal mass and abdominal pain. Intraoperative frozen section analysis is helpful in the diagnosis of the disease. Surgical treatment of the lesion should be performed to prevent bleeding, ulceration, outlet obstruction or malignant degeneration. Zheng LD and Tong QS contributed equally to this work     

Role of extramucosal seromuscular biopsy during preliminary fecal diversion in the management of Hirschsprung’s disease

The routine use of frozen section biopsy to identify distal ganglionic bowel in Hirschsprung’s disease is the accepted norm in well developed centres. With the aim of overcoming non-availability of frozen section biopsy and reducing the duration of definitive surgery, an alternative algorithm, based on extramucosal seromuscular biopsy at the time of preliminary fecal diversion and its examination by routine paraffin sections and staining,.was developed and used in 100 patients at our centre. This technique accurately marked the ganglionic colon for pull-through operation in 96.2% of cases with rectosigmoid transition zone and in 91.7% of those with transition zone in the descending colon, thus obviating the need for frozen section biopsy and saving nearly one hour during the pull-through surgery. However, in the more proximal varieties of Hirschsprung’s disease frozen section biopsy was still considered to be indispensable.     

Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism

OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.     

Histopathology of Congenital Hyperinsulinism: Retrospective Study with Genotype Correlations

The majority of the most severe cases of congenital hyperinsulinism (HI) are caused by defects in the -cell adenosine triphosphate (ATP)-sensitive potassium channel and usually require pancreatectomy to control blood sugar levels. In contrast to the recent advances in understanding the pathophysiology and genetic bases of HI, the histologic classification of this condition remains controversial. A recent proposal to classify the HI pancreata into diffuse and focal forms has drawn much interest because of its relative simplicity and its good correlation with the genetic abnormalities. We undertook a retrospective study to determine whether this classification scheme could be applied to 38 pancreata resected for HI at our institution. We also obtained leukocyte genomic DNA from 29 cases and screened the exons of ABCC8 and KCNJ11 genes for the presence of mutations. Nineteen cases (50.0%) were histologically classified as diffuse HI and 14 cases (36.8%) were categorized as focal form. The mutational analysis revealed that 14 of the 16 diffuse cases analyzed had either homozygous or compound heterozygous mutations of ABCC8 or KCNJ11 and 7 of 10 focal cases had only the paternally inherited mutations, consistent with the previous observations. Two patients (5.3%) had normal pancreatic histology but had persistent hypoglycemia postoperatively, leaving the possibility of residual focal lesion. Three of 38 cases (7.9%) did not fit well into either diffuse or focal category. Two cases differed from the described pattern for the diffuse form in that the nuclear enlargement was confined to a single area of the pancreas. The other case had a focal lesion but -cell nuclear enlargement was present in nonadjacent areas. Mutations for typical diffuse or focal HI were not identified in two of these three equivocal cases. We conclude from this study that nearly 90% of HI cases can be classified into either a diffuse or a focal form. However, a small percentage of cases represented a diagnostic challenge.     

Single incision laparoscopic 90 % pancreatectomy for the treatment of persistent hyperinsulinemic hypoglycemia of infancy

Single incision laparoscopic surgery as a surgical approach in treatment of pancreatic disease has recently been reported in adults. However, its application in persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in children is limited. In this article, we report single incision laparoscopic 90 % pancreatectomy for the treatment of persistent hyperinsulinemic hypoglycemia of infancy. Between July 2011 and February 2015, the single incision laparoscopic 90 % pancreatectomy was performed in three children with PHHI. All patients underwent ¹⁸F-FDOPA PET/CT before the surgeries. The scans showed diffuse physiologic ¹⁸F-FDOPA activity in entire pancreas. All patients were followed up. The levels of blood sugar and insulin were recorded postoperatively. The time required for surgery was 120–230 min, and blood loss was minimal. The hospital stay was 6 days. The duration of postoperative abdominal drainage was 4–5 days. The levels of fasting blood glucose after surgery were higher than those before surgery (4.38–8.9 vs. 0.54–1.8 mmol/L). The levels of fasting insulin after surgery were lower than those before surgery (2.4–5.5 vs. 14–33.3 uU/ml). The duration of follow-up was 4–46 months. During follow-up, the levels of blood glucose and insulin were normal in three patients. There was no recurrence of hypoglycemia after operation in all patients. Single incision laparoscopic 90 % pancreatectomy for children with PHHI is feasible and safe in well-selected cases in the experienced centers.     

Acetylcholinesterase Histochemistry and the Diagnosis of Hirschsprung's Disease: A 31/2—Year Experience

Using a modification of the histochemical acetylcholinesterase (ACE) reaction of Karnovsky and Roots, 154 suction rectal biopsies performed during the clinical investigation for Hirschsprung's disease were examined and compared to simultaneously obtained paraffin-embedded, hematoxylin-eosin (H&'E)-stained tissue. Serial paraffin sections were adequate to identify normal ganglia or to raise suspicion of Hirschsprung disease at initial biopsy in 129 of 154 (83%) cases. Interpretation of the ACE-stained tissue correlated exactly with this interpretation in 123 instances; 6 cases had uninterpretable ACE frozen sections. From this group of adequate paraffin sections, 18 patients with aganglionic megacolon were identified with the ACE preparation, relying primarily on a pattern of unusually thick and numerous nerve fibers within the muscularis mucosa.

Twenty-five paraffin-embedded specimens were deemed uninterpretable because of absent or insufficient submucosa or because of location. The ACE-stained section, however, correctly predicted the presence or absence of ganglia in 23 of these additional cases where the diagnosis could subsequently be confirmed either by repeat biopsy or repeated clinical follow-up examination of the patient. Using the ACE method alone, therefore, a diagnosis was obtainable at initial biopsy in 146 of 154 specimens (95%). This percentage was increased to 99% (152 of 154 specimens) if both ACE and paraffin sections were utilized. Recognition of the normal and abnormal patterns of nerve fiber staining in ACE preparations permits reliable, decisive interpretation of rectal suction biopsies in the evaluation of Hirschsprung's disease.     

Acetylcholinesterase histochemistry and the diagnosis of Hirschsprung's disease: a 31/2-year experience

Using a modification of the histochemical acetylcholinesterase (ACE) reaction of Karnovsky and Roots, 154 suction rectal biopsies performed during the clinical investigation for Hirschsprung's disease were examined and compared to simultaneously obtained paraffin-embedded, hematoxylin-eosin (H&E)-stained tissue. Serial paraffin sections were adequate to identify normal ganglia or to raise suspicion of Hirschsprung disease at initial biopsy in 129 of 154 (83%) cases. Interpretation of the ACE-stained tissue correlated exactly with this interpretation in 123 instances; 6 cases had uninterpretable ACE frozen sections. From this group of adequate paraffin sections, 18 patients with aganglionic megacolon were identified with the ACE preparation, relying primarily on a pattern of unusually thick and numerous nerve fibers within the muscularis mucosa. Twenty-five paraffin-embedded specimens were deemed uninterpretable because of absent or insufficient submucosa or because of location. The ACE-stained section, however, correctly predicted the presence or absence of ganglia in 23 of these additional cases where the diagnosis could subsequently be confirmed either by repeat biopsy or repeated clinical follow-up examination of the patient. Using the ACE method alone, therefore, a diagnosis was obtainable at initial biopsy in 146 of 154 specimens (95%). This percentage was increased to 99% (152 of 154 specimens) if both ACE and paraffin sections were utilized. Recognition of the normal and abnormal patterns of nerve fiber staining in ACE preparations permits reliable, decisive interpretation of rectal suction biopsies in the evaluation of Hirschsprung's disease.     

Persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis): a report from Kuwait

We report nine Bedouin children from Kuwait with persistent hyperinsulinaemic hypoglycaemia (PHHI) seen over a 13-year period in two regional hospitals. The incidence of PHHI in this inbred community is high (1:20,000); five of them came from two families. All the children presented with seizures associated with severe and recurrent hypoglycaemia, eight presenting in the neonatal period and one at the age of 2 months. One child died soon after birth. All the others received diazoxide initially, which achieved remission in one while two siblings remain dependent on the drug. Long-acting somatostatin analogue (octreotide) was successfully used in one child. Four children underwent pancreatectomy, two showed diffuse and two had localized nesidioblastosis. Two children achieved normal neurodevelopmental milestones, four suffered mental retardation of varying degrees and three died. Early diagnosis and prompt treatment are essential to avoid the neurological damage associated with hypoglycaemia. In some cases, this condition is due to an autosomal recessive pattern of inheritance and it is therefore important to offer genetic counselling to families with one or more affected siblings.