Endoscopic cystogastrostomy: Still a viable option in children with symptomatic pancreatic fluid collection.

BACKGROUND/OBJECTIVES: Endoscopic transmural drainage is the preferred method of drainage of pancreatic fluid collections (PFCs) in adults; however, there is scant literature in children. We analyzed our experience of 33 endoscopic cystogastrostomies done in 29 children to find its efficacy and safety. METHODS: We retrospectively analyzed the prospectively collected database of 31 consecutive children (<18 years) who underwent endoscopic cystogastrostomy from June 2013 to December 2017. The procedure was done using the standard technique with an adult duodenoscope. Data related to clinical details, technical success, complications and follow-up were collected. RESULTS: The median age was 14 (3-17) years (22 males). Indications were early satiety in 28 (90%), vomiting in 15 (48%), and duodenal obstruction and infected pseudocyst in 2 children each. Etiology includes acute pancreatitis 22, post-traumatic 4 and chronic pancreatitis 5. The procedure was successful in 29 of 31 (93.5%) children with no mortality. Adverse events happened in four cases (12.9%); two infections, another with bleeding and another with pneumoperitonium, both of which resolved spontaneously. Incidents (minor bleeding) were noted in 6 (19%). Stents were removed in 26 (90%) after 12 (7-20) weeks and got spontaneously migrated out in 3 (10%) cases. Over a median follow-up of 26 (5-48) months, 26 (90%) had no recurrence of pseudocyst and 3 (10%) had recurrence of a small, asymptomatic pseudocyst. CONCLUSIONS: Endoscopic cystogastrostomy is a safe and effective method of draining bulging PFCs in children. The procedure carries acceptable morbidity with minimal recurrence. In younger children it may be the preferred method of drainage of PFCs.

Need for recognizing atypical manifestations of childhood sporadic acute viral hepatitis warranting differences in management.

Various atypical manifestations have been described in acute viral hepatitis (AVH). We evaluated the prevalence, clinical features, response to treatment and outcome of various atypical manifestations of AVH in children. Consecutive children (≤ 18 years) with AVH due to hepatitis A, B, or E were studied while patients with acute or acute on chronic liver failure were excluded. Diagnosis of atypical manifestations was based on standard criteria. A total of 477 children with AVH (median age 7.0 (5-11) years, 74% boys) were seen; 22% (n = 106) had atypical manifestations. Prolonged cholestasis was the most common (11%), followed by ascites (7%), intravascular hemolysis (3%), relapsing hepatitis (2%), acute pancreatitis (1.3%), and thrombocytopenia (0.7%). Atypical manifestations were more common in HAV as compared to HBV (30% vs. 3%, p = 0.00) and HEV (30% vs. 15%, p = 0.07). Prolonged cholestasis was significantly more common in older children (20% in > 10 years vs. 9% in 6-10 years ; p = 0.009 and 5% in 0-5 years of age [p < 0.000]). Ascites was more common in younger children, although not significant. All patients recovered with supportive treatment.Conclusions: Twenty-two percent of children with AVH have atypical manifestations, more often with HAV infection, and prolonged cholestasis is most common. Recognition of these manifestations ensures correct diagnosis and treatment. What is Known: • Acute viral hepatitis is a major public health problem in developing countries. • There is limited information about atypical manifestations which may lead to unnecessary investigations, delayed diagnosis and morbidity. What is New: • Atypical manifestations are common in children, seen most often with HAV infection, and prolonged cholestasis is most common. • Prompt recognition of these manifestations helps in early diagnosis, appropriate management, and preventing unnecessary investigations. • Ensure follow-up until complete recovery and not to miss underlying chronic liver disease.

Intussusception in celiac disease: Is it a common feature in children?

BACKGROUND AND AIM: There are sporadic reports of occurrence of intussusception in celiac disease (CD) but no systematic study yet. We prospectively studied the prevalence and natural history of intussusception in newly diagnosed CD. METHODS: From January 2010 to October 2013, 150 children, diagnosed to have CD on the basis of positive serology and duodenal biopsy, were recruited in this study. Abdominal ultrasonography was carried out before starting gluten-free diet (GFD) and repeated in those who had intussusception, on day 3 and then weekly till the resolution of intussusception. RESULTS: The median age was 72 (range, 16-204) months, and 79 (53%) were boys. Diarrhea was the presenting symptom in 119 (79%) cases. A total of 45 intussusceptions were detected in 37 (25%) children. Out of 45 intussusceptions, 95% involved small bowel. All but one had asymptomatic intussusception. On GFD, intussusception resolved spontaneously within 7 days in 65%, within 14 days in 84%, and within 28 days in 92% of cases, and none required surgical or hydrostatic reduction. On univariate analysis, younger age, low weight z score, presentation with diarrhea, abdominal distension, rickets, lower serum albumin, more severe villous atrophy, and refeeding syndrome were more common in children with intussusception. On multivariate analysis, abdominal distension and hypoalbuminemia were found to be significantly associated with intussusception. CONCLUSIONS: Intussusception is frequently (25%) seen in children with newly diagnosed CD, generally asymptomatic and resolves spontaneously on GFD. It is often associated with more severe disease. Children with CD and intussusception should not be subjected to surgical/radiological intervention.

Clinical profile and treatment outcome of chronic pancreatitis in children: a long-term follow-up study of 156 cases.

AIM: There is a paucity of literature in pediatric chronic pancreatitis (CP) and most information is derived from adult literature. We, therefore, analyzed our experience of CP to look for clinical profile and long-term outcome. METHODS: From January 2003 to December 2015, 156 consecutive children (≤18 years) diagnosed as CP were included. Their clinical profile, management, and follow-up data were retrieved. Genetic markers (PRSS1, SPINK1, and CFTR) were studied in 40 idiopathic cases. RESULTS: The median age of the patients was 13 [inter-quartile range (IQR): 10-14] years (93 males) and 134 (86%) were idiopathic. Genetic mutations were found in 22/40 (55%) idiopathic cases. All but two presented with pain abdomen (episodic pain in 93.6%) and symptom duration was 12 (IQR: 6-24) months. There were two subsets; calcific (CCP) 68 (43.5%) and non-calcific (NCCP) 88 (56.5%). In CCP group, significantly more children had Cambridge grade 5 magnetic resonance cholangiopancreatography changes, low weight Z-score, and had continuous pain more compared to NCCP group. Over a median follow-up of 23 (IQR: 8-45.5) months, more children in CCP group had complications. Endoscopic therapy (done for persistent pain in 40) relieved pain in 52.5% of cases while medical therapy did so in 36% of cases. CONCLUSION: Pediatric CP in Asia presents with episodic pain and genetic predisposition seems to be a major cause. There are two subsets; CCP and NCCP with former showing marked imaging changes, more often associated with malnutrition and complications. Endoscopic therapy for pain relief gives modest benefit but medical therapy is not encouraging.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

Hepatopulmonary Syndrome in children: a comparative study of non-cirrhotic vs. cirrhotic portal hypertension.

BACKGROUND & AIMS: Hepatopulmonary syndrome in children has not been extensively studied particularly in different subsets of portal hypertension. We prospectively studied hepatopulmonary syndrome in children with cirrhosis and extrahepatic portal venous obstruction. Their comparison might shed light on the pathogenesis of hepatopulmonary syndrome. METHODS: Between 1 to 18 years of age, 135 children with portal hypertension (cirrhosis 35, extrahepatic portal venous obstruction 100) were studied. Hepatopulmonary syndrome was diagnosed by the presence intrapulmonary shunt using transthoracic contrast echocardiography and hypoxia/orthodeoxia (in arterial blood gas examination). Comparative analyses were done for both the groups, and also intra- and intergroups with and without hepatopulmonary syndrome. RESULT: Of 135 children, hepatopulmonary syndrome occurred more frequently in cirrhosis (40%) than extrahepatic portal venous obstruction (13%) (P = 0.01). Cirrhotics with hepatopulmonary syndrome were symptomatic (85% vs. 14%, P < 0.001) and had longer disease duration [16(1-120) months vs. 28 (1-168) months, P = 0.01] as compared to cirrhotics without hepatopulmonary syndrome. Prevalence of hepatopulmonary syndrome among cirrhotics did not correlate with the severity of liver disease as assessed by both paediatric end-stage liver disease score and Child-Turcotte-Pugh score. Patients with extrahepatic portal venous obstruction and hepatopulmonary syndrome remain asymptomatic manifesting with clubbing alone (38%). CONCLUSIONS: Hepatopulmonary syndrome occurs more frequently in cirrhosis, a majority being symptomatic with more severity in comparison to extrahepatic portal venous obstruction having no symptoms and less severity. There seems to be a role of liver dysfunction besides portal hypertension as an added factor in the pathogenesis of hepatopulmonary syndrome.

Duodenal morphometry and small bowel permeability in children with portal hypertension.

OBJECTIVE: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out whether any association existed among structural changes, SIP, and nutritional status. METHOD: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n = 15 and extrahepatic portal venous obstruction n = 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake. RESULTS: Among children with PHT, 48% had PHTD defined as presence of villous atrophy (villous to crypt ratio < 2.5:1), dilated capillaries (capillary diameter > 16.8 µm, capillary area > 151 µm, capillary perimeter > 56 µm), and thickened muscularis mucosae (>22.2 µm). Lactulose excretion alone was increased in children with PHT as compared with healthy children (median %: 0.03, 0.02, and 0.01 for cirrhosis, extrahepatic portal venous obstruction, and controls, respectively [P < 0.01]) signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight, and triceps skin-fold thickness (<-2SD), whereas no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise, and PHTD in our patients had no correlation. CONCLUSIONS: PHT is often associated with duodenopathy. SIP does occur as a result of increased paracellular permeability. Factors of increased SIP, undernutrition, and PHTD do not have correlation in childhood PHT.

Serial evaluation of children with ALF with advanced MRI, serum proinflammatory cytokines, thiamine, and cognition assessment.

OBJECTIVES: This prospective, sequential study was done to understand changes in cerebral edema (CE) on magnetic resonance imaging and magnetic resonance spectroscopy, liver functions, and neurocognitive testing (NCT) in children with acute liver failure (ALF). METHODS: A total of 11 ALF and 8 healthy controls were evaluated with advanced magnetic resonance (MR) imaging, blood proinflammatory cytokines (PCs), thiamine levels, liver functions, and NCT. Reevaluation was done at 43.5 ±â€Š26.9 days (first follow-up, n = 8) and 157.3 ±â€Š52.3 days (second follow-up, n = 6) after discharge. RESULTS: At diagnosis, patients with ALF had vasogenic and cytotoxic CE, raised brain glutamine (23.2 ±â€Š3.4 vs. 15.3 ±â€Š2.7), and serum PCs (tumor necrosis factor [TNF]-α 40.1 ±â€Š8.9 vs. 7.2 ±â€Š2.7  pg/mL, interleukin [IL]-6 29.2 ±â€Š14.4 vs. 4.7 ±â€Š1.2  pg/mL). The mammillary bodies (MBs) were smaller, and brain choline (1.9 ±â€Š0.36 vs. 2.6 ±â€Š0.6) and blood thiamine (55.2 ±â€Š6.7 vs. 81.8 ±â€Š10.2  nmol/L) were lower than controls. At first follow-up, the brain glutamine and CE recovered. Brain choline and MBs volume showed improvement and thiamine levels normalized. Significant reduction in TNF-α and IL-6 was seen. The patients performed poorly on NCT, which normalized at second follow-up. Liver biochemistry and thiamine levels were normal and TNF-α and IL-6 showed further reduction at second follow-up. CONCLUSIONS: Patients with ALF have CE contributed by raised brain glutamine and PCs. MBs are small because of thiamine deficiency and show recovery in follow-up. CE and brain glutamine recover earlier than normalization of NCT and liver functions. Persistence of raised cytokines up to 6 months after insult suggests possible contribution from liver regeneration.

Management of extra hepatic portal venous obstruction (EHPVO): current strategies.

Extrahepatic portal venous obstruction (EHPVO) is the commonest cause of portal hypertension and variceal bleeding in children. Though mortality related to variceal bleeding is uncommon, morbidity due to massive splenomegaly with hypersplenism, growth failure, ectopic varices like rectal varices and portal biliopathy is significant. A significant proportion of cases in adults are due to procoagulant state but the same has not been documented in children. Studies in children have shown that hereditary or acquired coagulation disorders do not play a role in the pathogenesis of EHPVO in children. Regarding endotherapy for variceal bleeding, there is no doubt that band ligation is superior to sclerotherapy. Nevertheless, a combination of band ligation followed by sclerotherapy has shown to be superior to either modality in children with EHPVO. Growth retardation due to growth hormone resistance is common in children with EHPVO. Diminished portal blood flow results in decreased insulin delivery to the liver and thereby decreased production of insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). Improvement of growth after restoration of hepatic blood flow with mesenteric-left-portal bypass or Rex shunt, has been documented. Portal biliopathy is universal in adults and common in children but symptomatic cases are mainly in adults; thereby suggesting a progressive nature of the condition. Symptomatic biliary obstruction can be managed endoscopically but shunt surgery followed by biliary bypass (if necessary) seems to be the best management option. With the availability of the most physiological shunt (mesenteric-left-portal bypass or Rex) the management paradigm of EHPVO has changed from endotherapy to primary shunt surgery.

Diagnosis and Management of Gastroesophageal Reflux Disease in Children: Recommendations of Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics, Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN).

JUSTIFICATION: Gastroesophageal reflux (GER) related symptoms are a major cause of parental concern and referrals at all ages. These guidelines have been framed to inform pediatricians regarding current diagnosis and management of gastro-esophageal reflux disease (GERD). PROCESS: A group of experts from the pediatric gastroenterology sub-specialty chapter of Indian Academy of Pediatrics (ISPGHAN) discussed various issues relating to the subject online on 25 October, 2020. A consensus was reached on most aspects and a writing committee was constituted. This committee had three meetings for a detailed discussion. The statement was sent to the entire group and their approval obtained. OBJECTIVE: To formulate a consensus statement to enable proper diagnosis and management of GERD in children. RECOMMENDATIONS: GER is physiological in most infants and it improves as age advances. The pathological form, called GERD causes distressing symptoms that affect daily activities and may result in complications. The presentation would vary from regurgitation to severe symptoms due to esophageal or respiratory tract disease. In older children, esophagitis is the commonest manifestation of GERD. A careful history and clinical examination are adequate to make a diagnosis in most patients, but judicious investigations are necessary in a few. Upper gastro intestinal tract endoscopy may be required in those with esophageal manifestations, dysphagia and hematemesis. In children with extra-esophageal symptoms, MII-pH monitoring and scintigraphy are necessary. Empirical treatment with a Proton pump inhibitor (PPI) has not been proven useful in infants, but a four-week trial is recommended in older children without complications. While positioning and feed thickening have limited benefit in infants, life-style modifications are important in older children.

Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes.

BACKGROUND: To find out whether vitamin D levels are lower in children with newly diagnosed type 1 diabetes (T1D) as compared to non-diabetic subjects. METHODS: Plasma levels of vitamin D (25-OHD) were measured by high performance liquid chromatography (HPLC) in 50 children aged between 6 and 12 yr within a week of diagnosis of T1D, and in 50 healthy children. RESULTS: The mean levels of vitamin D were significantly lower in patients as compared to their controls [20.02 +/- 10.63 ng/mL (50.05 +/- 26.57 mmol/L) vs. 26.16 +/- 12.28 ng/mL (65.4 +/- 30.7 mmol/L), p-value 0.009]. Twenty-nine (58%) children in the study group were vitamin D deficient (25-OHD level < 20 ng/mL or < 50 mmol/L) as compared to only 16 (32%) in the control group. Overall, 43 (86%) diabetic and 38 (76%) healthy children were either vitamin D deficient or insufficient. CONCLUSION: These results suggest that vitamin D levels are low at the onset of T1D, and they strongly support the need for further clinical studies to prospectively evaluate the effect of vitamin D supplementation on T1D rates in this patient population.

Is acute recurrent pancreatitis in children a precursor of chronic pancreatitis? A long-term follow-up study of 93 cases.

BACKGROUND/AIMS: In view of paucity of literature we analyzed our experience of acute recurrent pancreatitis (ARP) to study clinical profile and long-term outcome. METHODS: Over 13 years, 93 consecutive children (≤18 years) diagnosed to have ARP were included in this study. Magnetic resonance cholangiopancreatography was done at baseline and on follow-up. Common mutations for serine-protease-inhibitor (SPINK1 N34S), protease inhibitor (PRSS1 R122S) and cystic fibrosis transmembrane conductance regulator (CFTR deltaF508, 5T) were studied in 22 idiopathic cases. RESULTS: The median age of the children with ARP was 13 (10-14.5) years, 53 were males. Etiology included biliary in 14 (15%), pancreas divisum in 6 (7%), others in 3 (3.5%) and idiopathic in the remaining 70 (75%). SPINK1 mutation was found in 10/22 (45%) cases. Over a median follow-up of 25.5 (8.25-48) months, 37 (42%) of 88 (5 lost to follow-up) developed chronic pancreatitis (CP). On multivariate analysis idiopathic etiology (p<0.03), presence of SPINK1 mutation (p=0.01), longer follow-up (p<0.001) were associated with progression to CP. CONCLUSIONS: Biliopancreatic structural/obstructive causes should always be looked for. It seems ARP is a precursor of CP and progression is associated with idiopathic etiology and presence of genetic mutations. Hence, patients with ARP should be kept on regular follow-up to detect CP.

A Report of 320 Cases of Childhood Pancreatitis: Increasing Incidence, Etiologic Categorization, Dynamics, Severity Assessment, and Outcome.

OBJECTIVES: Because there is paucity of data on natural history of pediatric pancreatitis, we studied prevalence, etiology, severity, and outcome of pancreatitis. METHODS: Over 12 years consecutive children with pancreatitis were included. Pancreatitis was classified as acute (AP), acute recurrent (ARP), and chronic pancreatitis (CP) as per standard definitions. RESULTS: The study group comprised of 320 children (age, 11.4 ± 3.5 years, 201 males); AP, 160 (50%); ARP, 67 (21%); and CP, 93 (29%). The number of cases increased progressively from 28 to 157 between first and last quarter, and there was a significant increase (r = 0.92, P < 0.001) in AP-related hospitalizations over the years. Half of AP were idiopathic, 69% had severe pancreatitis (6 died) and on follow-up (21.1 ± 20.9 months) 21.5% progressed to either ARP (n = 8) or CP (n = 24). Progression was significantly associated with idiopathic etiology. The majority of ARP (70%) and CP (88%) were idiopathic and on follow-up (23.2 ± 28.9 months) 22% of ARP developed CP. CONCLUSIONS: There was 7-fold increase in number of hospitalization due to pancreatitis over the years. Progression of AP to ARP/CP was noted in 21.5% and ARP to CP in 22%. Thus, a subset of pancreatitis seems to be a continuum of acute to ARP and CP.

Endoscopic management of bleeding gastric varices with N-butyl, 2-cyanoacrylate glue injection in children with non-cirrhotic portal hypertension.

Background and study aims: In view of the paucity of literature, we carried out this audit to evaluate the safety and efficacy of N- butyl, 2-cynoacrylate glue injection therapy in secondary prophylaxis of gastric varices in children. Patients and methods: Consecutive children (≤ 18 years) with non-cirrhotic portal hypertension who presented with bleeding from gastric varices and who had undergone cyanoacrylate glue injection therapy were included. They were evaluated for safety, efficacy and complications. Their long-term outcomes and follow-up were recorded. Results: Over 11 years, 28 children with median age 13 (range, 8 to 18) years (68 % boys), underwent cyanoacrylate glue injection for bleeding gastric varices. In 25 (89 %) cases, extrahepatic portal venous obstruction was the etiology and isolated gastric varices were the source of the bleeding. Primary and secondary gastric variceal bleeding was seen in 11 (39 %) and 17 (61 %) children, respectively. A total 36 sessions with median volume of 2 (range, 1 - 5) mL of glue injections were required (2 sessions in 8 children). Hemostasis was achieved in all and 57 % had gastric variceal obliteration. Two children had early (< 1 month) rebleeding and 2 children had late rebleeding. One child had gastric ulcer. Over a median follow-up of 24 (8 - 98) months, 14 children underwent surgery (12 porto-systemic shunt), 2 were lost to follow-up, 1 died and there was no recurrence of bleeding in the remaining 11. Conclusions: Cyanoacrylate glue injection is highly effective mode of secondary prophylaxis of bleeding gastric varices in children with non-cirrhotic portal hypertension. Rebleeding occurred in 14 % but treatment-related complications were uncommon. However, a large controlled clinical trial is required to confirm our findings.

Estimation of liver volume in the western Indian population.

BACKGROUND: A number of formulae to estimate standard liver volume (SLV) exist. However, studies have shown that only certain formulae are applicable to a particular patient population, whereas the other formulae have not been accurate in estimating the SLV. Aim of this study was to assess which formula is most accurate in estimating SLV in the western Indian population. METHODS: Data for donors of living donor liver transplantation from September 2014 to July 2015 was analyzed. Liver volumes were measured using computed tomography volumetry (CTV). SLV was calculated using formulae by the currently existing formulae. The mean SLV and CTV, percentage error in the SLV, and the correlation between SLV and CTV were calculated. RESULTS: Fifty-nine healthy subjects underwent donor hepatectomy [28 (47.5 %) males]. The mean age, mean body mass index (BMI), and mean body surface area (BSA) were 31.8 ± 8.8 years, 23.8 ± 3.7 kg/m(2), and 1.6 ± 0.4, respectively. Mean CTV was 1178 ± 246.8 mL. Difference between mean SLV and mean CTV ranged from -133.5 (±189) mL to 632.2 (±190.2) mL. Mean SLV was significantly different from CTV by all the formulae except Urata. Percentage of population whose SLV was within 15 % of the mean CTV ranged from 1.7 % to 67.8 %, with the highest percentage obtained by using Fu-Gui's formula. However, there was wide inter-individual variation on scatter plots between SLV and CTV by both these formulae. CONCLUSION: Currently existing formulae were not accurate in estimating SLV in our population.