Safety and Efficacy of 177 Lu-DOTATATE in Children and Young Adult Population : A Single-Center Experience.

PURPOSE: This single-center retrospective study explores the safety and efficacy of 177 Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs). PATIENTS AND METHODS: This study is a retrospective analysis of all children and young adult patients (≤29 years) with advanced inoperable/metastatic epithelial or nonepithelial NETs who were administered a median of 4 cycles of 177 Lu-DOTATATE therapy and low-dose oral capecitabine as a radiosensitizer every 8-12 weeks, except 2 patients who received CAPTEM chemotherapy. The radiological response was assessed using RECIST 1.1 on interim and end-of-treatment 68 Ga-DOTANOC PET/CT. The primary endpoint was objective response rate, whereas disease control rate, toxicity profile, progression-free survival, and overall survival were secondary endpoints. RESULTS: Nineteen biopsy-proven NET patients (median age, 22 ± 10 years) with 8 of them adolescents (10-18 years) and the remaining young adults (19-29 years) were included. Fourteen patients had gastroenteropancreatic neuroendocrine tumor (pancreas being most common primary site), whereas the rest had non-gastroenteropancreatic neuroendocrine tumor. A total of 65 cycles of 177 Lu-DOTATATE (range, 1-6 cycles) were administered with a median cumulative activity of 600 mCi (range, 100-1000 mCi). The objective response rate and disease control rate were 41% and 94%, respectively. Grade 1 and 2 adverse events were observed in 14 (74%) and 5 (26%) of 19 patients, respectively. In a total of 8 events (42%), 4 events each of disease progression and death occurred during a median follow-up of 80.1 months with an estimated 5-year progression-free survival and overall survival of 54% (95% confidence interval, 30-78) and 63% (95% confidence interval, 39-87), respectively. CONCLUSIONS: 177 Lu-DOTATATE appears safe and effective in children and young adults with metastatic/inoperable NETs. Large prospective trials are required to validate these results.

Hyaline cartilage at the portal plate and gallbladder in biliary atresia.

Biliary atresia (BA) is a fibro-obliterative cholestatic disease of infancy. The presence of cartilage in the resected tissue is an uncommon finding. We documented the presence of both mature and immature hyaline cartilage in the portal plate and the wall of the gallbladder in a 2-month-old girl infant with BA who had undergone Kasai portoenterostomy. The presence of cartilage could be part of a heterotopia or an uncommon connective tissue metaplasia. The presence of immature cartilage with the merging of the perichondrium with the soft tissue highlights a metaplastic etiology in the index case.

Neoadjuvant Peptide Receptor Radionuclide Therapy in a Rare Case of Pediatric Primary Hepatic Gastrinoma.

ABSTRACT: Gastrinomas with predilection for the adult male population are located in the gastrinoma triangle (>90%). Primary hepatic gastrinoma especially in pediatric population is very rare. Peptide receptor radionuclide therapy has shown benefit in metastatic gastroenteropancreatic neuroendocrine tumors (NETs) with an increasing interest in expanding its role as neoadjuvant treatment modality to improve the surgical candidature in inoperable NETs. There is currently no literature supporting its role in the pediatric NET patients. We present a rare case of a young boy with primary hepatic gastrinoma where 177Lu-based peptide receptor radionuclide therapy in the neoadjuvant setting contributed to his final disease-free status.

Hyaline cartilage at the portal plate and gallbladder in biliary atresia

ABSTRACT Biliary atresia (BA) is a fibro-obliterative cholestatic disease of infancy. The presence of cartilage in the resected tissue is an uncommon finding. We documented the presence of both mature and immature hyaline cartilage in the portal plate and the wall of the gallbladder in a 2-month-old girl infant with BA who had undergone Kasai portoenterostomy. The presence of cartilage could be part of a heterotopia or an uncommon connective tissue metaplasia. The presence of immature cartilage with the merging of the perichondrium with the soft tissue highlights a metaplastic etiology in the index case.

Carnitine-acylcarnitine translocase deficiency: a case report with autopsy

ABSTRACT Fatty acid oxidation defects are a heterogeneous group of disorders related to the mitochondrial fatty acid oxidation pathway. Carnitine acylcarnitine translocase (CACT) is an enzyme responsible for the unidirectional transport of acylcarnitine across the inner mitochondrial membrane. This enzyme plays a crucial role in the oxidation of fatty acids. The autopsy pathology of the CACT deficiency is described in only a few cases. We describe the autopsy pathology of a child with CACT deficiency dominantly in the form of microvesicular steatosis of the hepatocytes, renal proximal tubular epithelia, cardiac myocytes, and rhabdomyocytes. The diagnosis was further confirmed on whole exome sequencing with compound heterozygous variants in the exon 1 (c.82G>T, p.Gly28Cys; likely pathogenic) and exon 5 (c.535G>A, p.Asp179Asn; uncertain significance) of the SLC25A20 gene. This case elucidates the histopathology of the liver and the detailed autopsy of a case of CACT deficiency from India.

Clinical spectrum & changing presentation of celiac disease in Indian children.

Background & objectives: Celiac disease (CD) is a genetic immune mediated disorder characterised by gluten intolerance. This single centre study, from north India was aimed to assess the clinical, serological and histological profile of CD in a large cohort of children and the changing trends in its presentation. Methods: A review of clinical details of CD children diagnosed between 2000 and 2019 and currently on follow up was performed. Information on demography, symptoms, associated conditions, serology, biopsy findings and gluten-free diet were analyzed. Results: The mean age (±standard deviation) of 891 children included in the study, at onset and at diagnosis was 4.0±2.7 and 6.2±3.1 yr, respectively. Growth faltering, abdominal pain, abdominal distension and diarrhoea were presenting symptoms in 70, 64.2, 61.2 and 58.2 per cent, respectively. A positive family history of CD was present in 14 per cent and autoimmune conditions in 12.3 per cent of children. Thyroid disorders were seen in 8.5 per cent of children and Type 1 diabetes mellitus (T1DM) in 5.7 per cent. The duration of breastfeeding had a weak positive correlation with age at onset and diagnosis of CD (P<0.001). Non-classical CD was significantly more common in children aged >10 yr and in those presenting after 2010 (P<0.01). T1DM and hypothyroidism occurred more frequently in non-compliant children. Interpretation & conclusions: This was the largest single centre study, pertaining to the presentation and follow up of CD in children. Infants and young children were more likely to present with classical symptoms of diarrhoea, abdominal distension and growth failure while older children presented with non-classical CD. There was a trend towards non-classical forms of CD in recent years.

Role of Serology, Dietary Assessment, and Fecal Gluten Immunogenic Peptides for Predicting Histologic Recovery in Children with Celiac Disease.

BACKGROUND: A strict lifelong gluten-free diet (GFD) remains the only treatment of celiac disease (CD). Adherence to gluten-free diet is best reflected by mucosal healing. Noninvasive tools capable of predicting mucosal recovery in CD patients need to be identified. AIMS: To compare the ability of various modalities used to assess compliance to GFD, for predicting persistent mucosal damage in children with CD. METHODS: A prospective, single-center, observational study on children with CD on a GFD was conducted between January 2020 and April 2021. Children with CD on GFD were consecutively enrolled and various modalities used to assess adherence to GFD were compared. RESULTS: One hundred and fifty children (Mean age 12.2 ± 3.6 years, 58% Boys) on GFD (Mean duration 6 ± 3.1 years) were enrolled in the study. Persistent mucosal damage was seen in 88% of the enrolled. Fecal gluten immunogenic peptide (GIP) was positive in 87.8% (129/147). Antibodies to tissue transglutaminase (TGA-IgA) and/or deamidated gliadin peptide (DGP) were positive in 32% (48/150) whereas antibody to synthetic neoepitopes of TGA-IgA was positive in 24.8% (37/149). Non-compliance as assessed by local questionnaire, Biagi score, and dietitian detailed interview were 62.7%, 60%, and 75.3%, respectively. Serology had the highest specificity (83%) and fecal GIP had the highest sensitivity (89%). On logistic regression analysis, only non-compliance by Biagi score predicted poor mucosal recovery. CONCLUSION: Fecal GIP may be sensitive to detect only "one-point dietary transgression." None of the existing modalities used to assess compliance to GFD accurately predict persistent mucosal damage. A subset of patients may develop gluten tolerance.

Unusual manifestations of Peutz-Jegher's syndrome in children.

PeutzJegher's syndrome (PJS) is a rare, autosomal dominant disease, characterized by gastrointestinal (GI) polyps and perioral hyperpigmentation along with the increased risk of certain malignancies. In children, the most common presentation is recurrent intussusception due to polyps. These polyps can involve any part of the GI tract and can present with a variety of clinical presentations. Usually, these polyps can be removed endoscopically but often require surgical excision also. In this report, we discuss two children of PJS with uncommon presentations, one presented with retrograde intussusception and another with gastric outlet obstruction. The first child underwent laparoscopy and another required open surgery with intraoperative enteroscopy.

Portal Cavernoma Cholangiopathy in Children: An Evaluation Using Magnetic Resonance Cholangiography and Endoscopic Ultrasound.

BACKGROUND: Portal cavernoma cholangiopathy (PCC) refers to abnormalities of the extra- and intrahepatic bile ducts in patients with portal cavernoma. The literature on PCC in children is very scarce. This study aimed at characterizing PCC in children with extrahepatic portal venous obstruction (EHPVO) using endoscopic ultrasound (EUS) and magnetic resonance cholangiography/portovenography (MRC/MRPV). METHODS: A total of 53 consecutive children diagnosed with EHPVO were prospectively evaluated for PCC using MRC/MRPV and EUS. Chandra classification was used for type of involvement and Llop classification for grading of severity. RESULTS: All 53 children (100%) had PCC changes on MRC/EUS, but none were symptomatic. Extrahepatic ducts (EHDs) and intrahepatic ducts were involved in majority (85%), and 58.5% had severe changes. Periductal thickening/irregularity (71%) was the commonest change in intrahepatic ducts, whereas irregular contour of the duct with scalloping (68%); common bile duct (CBD) angulation (62.3%) were the frequent changes in the EHDs. Increased CBD angulation predisposed to CBD strictures (P = 0.004). Both left and right branches of portal vein were replaced by collaterals in all children. Among the EUS biliary changes, para-pericholedochal, intrapancreatic, and intramural gall bladder collaterals had significant association with severity, with higher frequency of occurrence in children with the most severe Llop Grade. CONCLUSIONS: PCC develops early in the disease course of EHPVO, in children, but is asymptomatic despite severe changes. EUS biliary changes are more likely to be observed with increasing severity of PCC.

Pancreatic ascites and Pleural Effusion in Children: Clinical Profile, Management and Outcomes.

BACKGROUND: Pancreatic ascites (PA) and pleural effusion (PPE) are rarely encountered in children. They develop due to disruption of the pancreatic duct (PD) or leakage from an associated pancreatic fluid collection (PFC). The literature on childhood PA/PPE and its management is scarce. METHODS: A retrospective review of children with PA/PPE diagnosed and managed at our center over the last 4 years was performed. The clinical, biochemical, radiological and management profiles were analyzed. Conservative management included nil per oral, octreotide and drainage using either percutaneous catheter or repeated paracentesis. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) and transpapillary stenting. RESULTS: Of the 214 children with pancreatitis, 15 (7%) had PA/PPE. Median age was 9 years with a third under 2 years. Median ascitic fluid amylase was 8840 U/L and all had elevated protein (>2.5 g/dl) and low serum ascites-albumin gradient ascites (<1.1). While PA/PPE was the first manifestation of underlying chronic pancreatitis (CP) in 10 children (67%), trauma was seen in 4 (26%) and hypertriglyceridemia in 1 (7%). On imaging, PD disruption could be identified in 10 (67%) children. ERCP and stenting was done in 10 children. Conservative management alone (n = 4) and endotherapy (n = 10) was successful in 93% with only one requiring surgery. The younger children (n = 4), were managed conservatively and only 1 of them required surgery. Resolution of PA/PPE was achieved in all with no recurrences. CONCLUSIONS: Conservative management and ERCP plus transpapillary stenting results in resolution of majority of pediatric PA/PPE. Children presenting with PA/PPE needs to be evaluated for CP.

Robotic Excision of Choledochal Cyst with Hepaticoduodenostomy (HD): Report of HD Technique, Initial Experience, and Early Outcome.

INTRODUCTION: Minimal access surgical approach to choledochal cyst (CC) is becoming a standard of care in pediatric age group. Robotic-assisted excision of CC is increasingly being practiced at centers which have access to the system. We present our experience and technique of hepaticoduodenostomy (HD). Over all initial experience, short-term outcomes and complications are also presented and discussed. MATERIALS AND METHODS: Patients with CC and undergoing robotic excision were retrospectively studied. Patients with active cholangitis, liver dysfunction, and perforated CC were excluded for robotic procedures. All included patients were preoperatively evaluated as per the defined protocol. They underwent excision of CC with HD. The duodenal anastomosis was done after limited mobilization and emphasis was laid on anastomosing the distal D2 part to the common hepatic duct. This prevents bile reflux into stomach. The follow-up evaluation was done for these patients. Hepatobiliary iminodiacetic acid (HIDA) scan for duodenogastric reflux (DGR) was done only if patients reported symptoms related to it. RESULTS: A total of 19 patients (10 females) were studied. The mean age was 84 months. Type 1b was present in 12 patients and the rest were type IVb. Complete cyst excision with HD was done in all patients except conversion to open in one patient. The mean surgical time was 170 ± 40 minutes with console time of 140 ± 20 minutes. Median follow-up duration is 2.5 years (range: 3.5-0.5 years). HIDA scan was done in five patients who had reported epigastric pain. Of these five, one patient had a positive DGR. He is on conservative management. CONCLUSION: Robot-assisted CC excision with HD is feasible as proven by the outcome of 19 patients presented in this series. HD is to be done away from pylorus in distal part of down curving D2. This particular step prevents DGR and is the most important point of technique in doing HD. The presented series is the first report of robotic excision of CC with HD. The robot is a facilitator for complex and difficult operations as CC excision and HD.

An Infant with Severe Anemia and Hypoalbuminemia.

We discuss the case of a two-month-old girl admitted with complaints of progressive pallor, generalized body swelling and pale colored stool since the neonatal period. On examination, severe pallor, chubby cheeks and moderate hepatomegaly were noted. Investigations revealed isolated anemia, transaminitis, conjugated hyperbilirubinemia, prolonged prothrombin time and hyperlipidemia. She died due to severe sepsis, shock, and pulmonary hemorrhage. An autopsy revealed characteristic histopathology findings of cystic fibrosis in the liver, lungs, and pancreas. Genetic analysis performed on autopsy tissue was positive for F508del compound heterozygous (WT/F508del) mutation, confirming the diagnosis of cystic fibrosis.

Paediatric acute pancreatitis: Clinical profile and natural history of collections.

BACKGROUND & AIMS: Acute Pancreatitis (AP) tends to have a benign course in children. However there is a paucity of information with respect to severity of AP in children, the categorization of collections viz., walled off necrosis (WON)& pseudocyst and their natural history & outcomes. METHODS: A retrospective medical record review of 187 children with pancreatitis diagnosed and managed at our centre was performed. RESULTS: 101 children (59% boys, Median age 9yrs) had AP of which 37.6%, 60.4% and 2% had mild, moderately severe and severe AP. 61.4%(62) had PFC at diagnosis; 34%(21) acute pancreatic fluid collections (APFC) and 66%(41) acute necrotic collections (ANC). 52.3%(11of21) of APFC evolved into pseudocysts & 68.2%(28of41) of ANC into WON's. Drainage was required in 31%(12of39) of persisting collections, more frequently in children with traumatic AP. Percutaneous catheter drainage (PCD) was done in 6 children and endoscopic ultrasound (EUS) guided cystogastrostomy with placement of plastic or self expanding metal stents (SEMS) in 6 children. CONCLUSIONS: Moderately severe AP is common in hospitalized children with AP with PFC developing in 61.4%, majority being APFC. 48% of APFC and 32% of ANC will resolve and the rest evolve into pseudocyst or WON. Spontaneous resolution is more likely in children with non -traumatic AP having pseudocysts rather than WON's.

An interesting cause of chronic abdominal pain in a child.

We encountered an eight-year-old boy who was subsequently diagnosed with a retroperitoneal ganglioneuroma. In view of the rarity of this tumour and its presentation, we are prompted to report this case.

Management of Primary Lymph Nodal Gastrinoma With Liver Metastases Resulting in Zollinger-Ellison Syndrome.

Primary lymph node gastrinoma has been defined as gastrin-producing tumor present in lymph nodes and predominantly found in well-defined anatomical region known as gastrinoma triangle. They are usually localized preoperatively with imaging, and their surgical resection results in long-term relief. The authors report a case of unresectable primary lymph nodal gastrinoma with liver metastases in a 14-year-old adolescent boy with proven histopathology detected on Ga-DOTANOC whole-body PET/CT scan followed by preoperative multiple Lu-DOTATATE cycles for cytoreduction. Subsequent surgical resection of residual mass resulted in complete response with a follow-up of around 4 years in this unusual case of Zollinger-Ellison syndrome.

Bertiella studeri Infection-A Rare Cause of Chronic Abdominal Pain in a Child from North India.

Bertiella is a common parasite seen in non-human primates. It is rarely seen in humans. We present the case of a 2-year-old child with bertiellosis. He had recurrent abdominal pain, and worm fragments were found in stool, which were refractory to albendazole therapy.

Co-infection of Sarcina and Giardia in a child.

We present a case of 3-year-old boy who presented with vomiting and chronic diarrhoea, and the duodenal biopsy showed the presence of both Giardia and Sarcina. The clinical and pathological significance of Sarcina remains unknown in human beings and its co-existence with Giardia has not been reported.

Approach to a child with upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is a potentially life threatening medical emergency requiring an appropriate diagnostic and therapeutic approach. Therefore, the primary focus in a child with UGIB is resuscitation and stabilization followed by a diagnostic evaluation. The differential diagnosis of UGIB in children is determined by age and severity of bleed. In infants and toddlers mucosal bleed (gastritis and stress ulcers) is a common cause. In children above 2 y variceal bleeding due to Extra-Hepatic Portal Venous Obstruction (EHPVO) is the commonest cause of significant UGIB in developing countries as against peptic ulcer in the developed countries. Upper gastrointestinal endoscopy is the most accurate and useful diagnostic tool to evaluate UGIB in children. Parenteral vitamin K (infants, 1-2 mg/dose; children, 5-10 mg) and parenteral Proton Pump Inhibitors (PPI's), should be administered empirically in case of a major UGIB. Octreotide infusion is useful in control of significant UGIB due to variceal hemorrhage. A temporarily placed, Sengstaken-Blakemore tube can be life saving if pharmacologic/ endoscopic methods fail to control variceal bleeding. Therapy in patients having mucosal bleed is directed at neutralization and/or prevention of gastric acid release; High dose Proton Pump Inhibitors (PPIs, Pantoprazole) are more efficacious than H2 receptor antagonists for this purpose.

An autopsy case of infantile GM1 gangliosidosis with adrenal calcification.

We describe an autopsy case of a 1-year-old male baby presenting with failure to gain milestones, floppiness, and reddish skin lesions since birth. Fundoscopic examination revealed bilateral cherry-red spots in the macula. The baby died of respiratory failure and autopsy revealed numerous ballooned neurons and astrocytes with cytoplasmic storage material seen throughout central white matter, basal ganglia, cerebellum, choroid plexus, and brain stem. There was neuronal degeneration with loss of myelin in central white matter with axonal degeneration as well. The storage material was weakly positive with PAS and oil red-O stains. Ultrastructurally, multilayered lamellated bodies were seen within the ballooned neurons. Biochemical analysis of lysosomal enzymes done in leucocytes revealed ß-galactosidase deficiency that is consistent with GM1 gangliosidosis. Extensive visceral deposition of similar material was also seen. Remarkably, both adrenals revealed extensive medullary calcification, which has not been reported in this lysosomal storage disorder, to the best of our knowledge.