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.

Granulocyte colony stimulating factor in decompensated cirrhosis, acute alcoholic hepatitis, and acute-on-chronic liver failure: A comprehensive meta-analysis of randomized controlled trials.

BACKGROUND: GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis. METHODS: Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes. RESULTS: In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90. CONCLUSION: G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

Utility of the New Faster Compressed SENSE MRCP at 3 Tesla MRI in Children with Pancreatitis.

OBJECTIVE: To compare the acquisition time, diagnostic efficacy, and image quality of the newer compressed SENSE 3D MRCP (CS-3D MRCP) with conventional 3D MRCP (C-3D MRCP) in children with pancreatitis. METHODS: A total of 24 children (2-17 y) diagnosed with pancreatitis were included in this study. The children underwent CS-3D MRCP and C-3D MRCP sequences. C-3D MRCP and CS-3D MRCP images were evaluated for the acquisition time duration, visualization of the pancreaticobiliary ducts, background suppression, image quality degradation by artifacts, and overall image quality by the two radiologists independently. Paired sample t-test was used to compare the acquisition time, the McNemar test for the image quality features, and the kappa coefficient was used for interobserver agreement. RESULTS: A two-fold decrease in the acquisition time of CS-3D MRCP (~148 ± 61 s) was seen, compared to C-3D MRCP (~310 ± 98 s), p < 0.001. The median scores for overall image quality on CS-3D MRCP and C-3D MRCP, respectively, were 2.05 ± 0.52 and 2.21 ± 0.53 (p = 0.18) for both radiologists. No significant difference was seen for the visibility of ducts, background suppression, and artifacts between the two radiologists, with substantial to almost perfect agreement seen for the different findings. CONCLUSION: The application of compressed SENSE 3D MRCP in children with pancreatitis results in a two-fold reduction in acquisition time with acceptable image quality. This may help in reducing the need for long sedation in children requiring anesthesia support for the MRCP and potentially help in reducing motion artifacts.

Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial.

OBJECTIVE: Pediatric irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with variable response to various therapeutic agents. Psyllium has been proven to be effective in adults; however, there is no study in children. The objective of this study is to evaluate the efficacy of psyllium husk as compared to placebo in pediatric IBS patients. METHODS: In this double-blind randomized controlled trial, 43 children were assigned to psyllium arm (Group A) and 38 into placebo arm (Group B). Severity is assessed at baseline and after 4 weeks of treatment using IBS severity scoring scale (IBS-SSS) and classified into mild, moderate, and severe categories. Categorical data was compared with chi-square test and paired categorical variable was compared with McNemer test. RESULTS: Mean ages (±SD; in years) of Groups A and B were 9.87 (2.7) and 9.82 (3.17), respectively, with median duration of illness of 12 months. At baseline, type, severity, and parameters (IBS-SSS) of IBS were equally distributed in 2 groups. There was a significant reduction in median interquartile range (IQR) of total IBS-SSS in psyllium versus placebo [75 (42.5-140) vs 225 (185-270); P < 0.001] at 4 weeks. Similarly 43.9% in Group A versus 9.7% in Group B attained remission [IBS-SSS < 75 ( P < 0.0001)]. The mean difference in IBS-SSS between Group A and Group B was -122.85 with risk ratio of 0.64 (95% CI; 0.42-0.83; P = 0.001) and absolute risk reduction of 32% (NNT = 3). CONCLUSIONS: Psyllium husk is effective for the therapy of pediatric IBS when compared with placebo in short term.

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.

Shear wave elastography of the spleen using elastography point quantification: stiffness values in healthy children.

PURPOSE: To evaluate the shear wave elastography (SWE) values of the spleen in healthy children using Elastography Point Quantification (ElastPQ). METHODS: In this IRB approved prospective study, spleen stiffness was measured in 146 healthy children (2-15 years) using ElastPQ. SWE values were recorded in upper pole, mid pole, and lower pole of the spleen in all the children. RESULTS: The mean (± SD) SWE values of the spleen in children in ≤ 5 years age group, > 5-10 years age group, and > 10-15 years age group were 5.6 (± 4.2) kPa, 6.5 (± 3.2) kPa, and 5.9 (± 3.6) kPa, respectively. No statistically significant difference was seen in SWE values of the spleen between these three groups (p > 0.5). The mean (± SD) SWE values in ≤ 10 years and > 10 years age group were 6.1 (± 3.6) kPa and 5.9 (± 2.6) kPa, respectively. No statistically significant difference was seen in SWE values of the spleen between these two groups (p > 0.5). There was no significant difference in the SWE values for boys and girls. Statistically significant difference was seen between the mean SWE values in the two groups based on the median splenic length, which was 5.5 (± 3.8) kPa in the group with a length of ≤ 7.6 cm and 6.7 (± 2.8) kPa in the group with a length of > 7.6 cm. CONCLUSION: SWE values of the spleen in healthy children do not correlate with age, and no significant difference is there in the SWE values for boys and girls. There was a statistically significant difference in the SWE values of the spleen while comparing the groups based on the median splenic length.

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.

Gallbladder motility in children with celiac disease before and after gluten-free diet.

BACKGROUND: Gallbladder (GB) hypomotility has been reported in adults with celiac disease (CD), but there is no literature on GB dysfunction in children with CD. We aimed to study GB motility in children with CD, before and after a gluten-free diet (GFD), using ultrasonography (USG) and technetium-99 labeled mebrofenin hepatobiliary scintigraphy (HBS). METHODS: Children with newly diagnosed CD were enrolled and evaluated for GB ejection fraction (GBEF) using HBS and USG. Those with reduced GBEF on initial HBS were again evaluated after 6 months of strict GFD and the results were compared. RESULTS: Of the 50 children with CD (mean age 9±2.1 years, 54% boys), 16% (n=8) had a low GBEF at baseline (19±13%). These children had a significantly greater delay in diagnosis compared to those with normal GBEF (6.5±2.0 vs. 2.3±1.2 years, P<0.001). A significant improvement in GBEF was noted on HBS post GFD (74±12%1 vs. 9±13%, P<0.001). GBEF also improved significantly as assessed by USG parameters after GFD (P<0.001). The fasting GB volume decreased (5.7±1.4 vs. 10.2±2.6, P=0.002), with a significant improvement in percentage postprandial GB volume change (52±10.5% vs. 24±16.5%, P=0.007) compared to baseline pre-GFD values. Orocecal transit time was also increased in children with reduced GBEF. CONCLUSIONS: GB function is impaired in at least 16% of children with CD at diagnosis and is reversible with GFD. GB dysfunction is significantly associated with a delayed diagnosis and may be a part of general gastrointestinal dysmotility.

Necrotizing Enterocolitis Following Pediatric Living Donor Liver Transplant.

Necrotizing enterocolitis is one of the most common and worrying diseases in neonates, commonly shown in premature neonates, and is associated with significant mortality and morbidity. Necrotizing enterocolitis is characterized by intestinal mucosal injury that can progress to transmural bowel necrosis, and radiologically it can present with either pneumatosis intestinalis or portal venous gas. It is postulated to develop in an immunocompromised host in the setting of bacterial colonization, usually after administration of non-breast milk feed. Cow's milk allergy association with necrotizing enterocolitis has not been well determined, and the pathophysiology is still not clear. Necrotizing enterocolitis is very rare following living donor liver transplant. In our case, a 6-year-old boy who was doing well in the postoperative period had sudden worsening of general condition after he was started on milk feed. On evaluation and reexploration, he was diagnosed with necrotizing enterocolitis and later succumbed to death.

Pulmonary thromboembolism: A rare complication of amoebic liver abscess in a child.

Amoebic liver abscess is common in children in developing countries due to lack of hygiene and sanitary conditions. Inferior vena cava thrombosis is a rare complication of this disease, with only a few cases reported in the literature, where this thrombus led to pulmonary thromboembolism. We report the case of a 7-year-old child with amoebic liver abscess who developed pulmonary thromboembolism and was promptly diagnosed and managed.

Clinical Characteristics of Children With Celiac Disease Not Responding to Hepatitis B Vaccination in India.

The immunological response to hepatitis B virus (HBV) vaccine may be suboptimal in children with celiac disease (CD), but the reasons for this are not well defined. Objectives: This study was undertaken to assess the immune response to HBV vaccine in CD children and to explore the possible factors affecting the immune response. Methods: The study population consisted of 3 groups-50 newly diagnosed CD children (group 1), 50 previously diagnosed CD children who were on gluten free diet (GFD) >3 months (group 2), and 100 age and gender matched healthy controls (group 3). The patient characteristics were recorded, and the blood samples were analyzed for HBsAg and anti-HBs titers. The nonresponders were given a booster dose of HBV vaccine and reevaluated after 6 weeks. Results: Positive anti-HBs response was found in 46% in newly diagnosed CD children, 60% in CD children on GFD, and 83% in healthy controls (P < 0.001). The immune response to HBV vaccine in CD children was inferior to that in healthy children (53% vs 83%, P < 0.001). The immune response was found to be significantly affected by age at diagnosis, delay in diagnosis, type of presentation, and compliance to GFD. 44 out of 45 (97.77%) nonresponders from CD group seroconverted after a single booster dose. Conclusion: Early diagnosis and good compliance to GFD may improve the immune response to HBV vaccine in CD children. Single additional booster dose is sufficient to attain optimal immune response.

Coinfection with Hymenolepis nana and Hymenolepis diminuta infection in a child from North India: A rare case report.

Hymenolepiasis is considered the most common tapeworm infection throughout the world infecting 50-75 million people. Hymenolepis diminuta infection is not commonly reported in human beings as compared to Hymenolepis nana because it is primarily a parasite of rats and mice. There are few case reports of H. diminuta in the Indian population. To the best of our knowledge, not a single case of coinfection with H. nana and H. diminuta has been reported from India. We present here a rare case report of coinfection of H. nana and H. diminuta in a 4-year-old male child from a semirural area of India who presented with acute and severe colitis.

Role of Granulocyte Colony Stimulating Factor on the Short-Term Outcome of Children with Acute on Chronic Liver Failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) results in very high mortality in children. We aimed to evaluate the role of granulocyte colony-stimulating factor (GCSF) on short-term outcome of children with ACLF in a nontransplant unit. METHODS: Children (aged > 1 year) diagnosed with ACLF over a 15 month period were randomised. Group A was given GCSF therapy along with standard medical care (SMC - details in supplementary data) and group B was given only SMC. The outcome was evaluated as survival at 30 and 60 days of therapy. RESULT: Thirty-one children with ACLF were enrolled, with a mean age of 6.92 ± 4.3yrs. A total of 15 patients were randomised to group A and 16 to group B. The overall mortality was 54.83%. The intervention group showed survival rates of 80%, 66.67% and 53.3%, whereas the control group had survival rates of 43.75%, 37.5% and 37.5% at 14, 30 and 60 days, respectively. A significant survival benefit was noted on day 14 (p = 0.043) of therapy in group A with significant difference in Child-Turcotte-Pugh (CTP) and pediatric end-stage liver disease (PELD) scores in the two groups. After an initial rise in group A, the granulocyte counts fell to become comparable in the two groups by day 30 and 60, indicating that the effect of GCSF therapy wears off over time. There was no significant difference in the overall survival, median/mean CTP, PELD and MCS (Modified Cliff sequential organ failure assesment (SOFA)) scores on day 30 and 60. Mean (%) CD 34 + cells level showed a rise on day 7 in group A but was statistically insignificant. CONCLUSION: The present study shows that GCSF therapy at 5 mcg/kg/day for 5 days seems to be ineffective in improving the survival outcome on day 30 and 60 of therapy. Studies with larger number of children enrolled and longer duration of therapy are required. (CTRI/2017/11/010420).

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.

Abdominal tuberculosis in children: A real-world experience of 218 cases from an endemic region.

BACKGROUND AND AIM: Abdominal tuberculosis (ATB) in children poses a diagnostic challenge because of its nonspecific clinical features, which often delay the diagnosis. Our aim was to present our real-world experience and provide an insight into the presentation, pattern of distribution, and diagnosis of the disease. METHODS: A retrospective review was conducted of case records of all children ≤12 years of age diagnosed with ATB from January 2007 to January 2018. Clinical details and investigations were recorded and analyzed. RESULTS: A total of 218 children (110 boys), with a median age of 10 (0.25-12) years, were included. There was a median delay of 4 (0.5-36) months in establishing the diagnosis. Abdominal pain, fever, and loss of weight were the most common presenting features, with the triad of symptoms present in 54%. Multiple intra-abdominal sites were involved in 118 (54%) patients, with a combination of the gastrointestinal tract (I) and abdominal lymph nodes (L) being the most common (53/118). Among children with single-site involvement (n = 100), the most commonly involved was L in 39 (39%), followed by I in 35(35%). Loss of weight was more common in children with involvement of multiple sites (85/118 vs 60/100, P = 0.03). Overall, a confirmed diagnosis was possible in 94 participants (43.1%). Suggestive imaging had the highest diagnostic yield of 85%. Nine (4.1%) patients needed surgical management. CONCLUSION: A triad of abdominal pain, fever, and weight loss is suggestive of ATB. Multiple intra-abdominal sites are frequently involved. Microbiological confirmation is possible in only one-third of the cases.

Role of noninvasive tools for prediction of clinically evident portal hypertension in children.

BACKGROUND: Noninvasive tools (NITs) for predicting varices in children with portal hypertension (PHTN) are infrequently used. METHODS: Eighty-five consecutive, treatment-naïve children with PHTN and 97 controls were enrolled study from July 2017 to November 2018. Each case was evaluated by esophagogastroduodenoscopy (EGD) and various NITs: platelet spleen size Z (PSZ), clinical prediction rule (CPR), King's variceal prediction rule (KVaPS), Splenic stiffness (SSM) and liver stiffness measurement (LSM) by point shear wave elastrography (pSWE). RESULTS: Had PHTN due to extra hepatic portal vein obstruction (EHPVO) and 70% due to cirrhosis [chronic liver disease (CLD)]. Sixty-five percent of PHTN cases had varices. Children with varices had lower platelet counts, lower albumin and larger spleens. SSM and LSM were significantly higher in cases as compared with controls. SSM was significantly higher in cases with varices than those without. SSM and LSM, at cutoffs of 3.8 and 3.2 kPa, respectively, discriminated PHTN cases from controls with an area under the curve (AUROC) of 0.67 (0.59-0.74). Both SSM and LSM predicted varices in CLD, but in EHPVO, only SSM predicted varices. SSM of 5.2 and 12.8 kPa, in CLD and EHPVO subgroups, respectively, had AUROC of 0.73 and 0.94 for variceal prediction. Blood-based NITs performed better in the CLD subgroup: aspartate aminotransferase platelet ratio index, CPR and KVPS predicted severity of PHTN with AUROC of 0.81, 0.92 and 0.93, respectively. CONCLUSIONS: Blood-based NITs outperform elastography for prediction of PHTN/varices in children with CLD. SSM by pSWE is a better predictor of varices than LSM, especially in the EHPVO subgroup.

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.