Harrison X. Bai

Definitions of pediatric pancreatitis and survey of present clinical practices.

Objectives: There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis. Methods: Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice. Results: AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents’ future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria. Conclusions: INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.

What Have We Learned About Acute Pancreatitis in Children

Pediatric pancreatitis has received much attention during the past few years. Numerous reports have identified an increasing trend in the diagnosis of acute pancreatitis in children and key differences in disease presentation and management between infants and older children. The present review provides a brief, evidence-based focus on the latest progress in the clinical field. It also poses important questions for emerging multicenter registries to answer about the natural history and management of affected children with pancreatitis.

Novel Characterization of Drug-associated Pancreatitis in Children

Background and Objectives: Medications are a major cause of acute pancreatitis; however, little is known about their influence in children. Our primary aims were to identify common comorbidities and concomitant pancreatitis etiologies in children with drug-associated pancreatitis. Our secondary aims were to identify the most commonly associated drugs in the different age groups, evaluate management practices, and compare drug-associated cases with non–drug-associated cases. Patients and Methods: In the present study, we examined children (ages 0–20 years) admitted to Yale-New Haven Childrens Hospital with pancreatitis between 1994 and 2007. Results: Of a total of 271 pediatric cases, drugs were associated with pancreatitis in 25.6% (55). The 3 most common comorbidities in children with drug-associated pancreatitis were seizure disorders, acute lymphocytic leukemia, and Crohn disease. One third of drug-associated cases had an additional pancreatitis etiology. The most commonly associated drugs were valproic acid and corticosteroids. Compared with non–drug-associated cases, children with drug-associated cases were more likely to undergo CT scanning (54.5% vs 28.4%; P < 0.001), stay in the hospital longer (10 vs 4 days; P < 0.001), and transition to parenteral nutrition from a nil per os status (37.5% vs 21.2%; P < 0.05). There was a higher frequency of valproic acid–associated cases in children younger than 11 years (29.4% vs 9.5% in the 11- to 20-year-old age group). Conclusions: Our study underscores the importance of considering drugs as a cause and a contributor to pancreatitis in children, particularly valproic acid in young children.

The Association of Primary Hyperparathyroidism With Pancreatitis

The association between primary hyperparathyroidism (PHPT) and acute or chronic pancreatitis is controversial. For this reason, we conducted a review of the literature over the past 30 years to explore the relationship between these 2 disorders. Ten retrospective studies each with >50 patients diagnosed with PHPT were identified. With the notable exception of 2 studies, the rate of pancreatitis among patients with PHPT was higher than that reported in general among hospitalized patients without PHPT. A higher serum calcium level may contribute to pancreatitis in these cases, along with additional genetic or environmental insults. Hypercalcemia may predispose the pancreatic acinar cell to abnormal, sustained calcium levels, lead to premature pancreatic protease activation, and pancreatitis. Although there was only short-term follow-up, most reports cited that definitive treatment of PHPT by parathyroidectomy led to the resolution of pancreatitis attacks. The published cohorts of patients with PHPT and pancreatitis are subject to bias, because serum calcium screening was not universally performed among all control nonpancreatitis patients to evaluate for PHPT. However, the pooled clinical and experimental data suggest an association between PHPT and pancreatitis and implicate hypercalcemia. For clinicians, it is important to recognize pancreatitis in patients with PHPT and, conversely, to consider PHPT by checking serum calcium levels in patients, who present with an unexplained pancreatitis.

Risk Factors Associated with Biliary Pancreatitis in Children

Objectives: Little is known about risk factors for biliary pancreatitis in children. We characterized cases of pediatric biliary pancreatitis, compared biliary with nonbiliary cases, examined differences in presentation between younger and older children, and studied features distinguishing gallstone- from sludge-induced pancreatitis. Methods: We evaluated 76 episodes of biliary pancreatitis from 271 cases of acute pancreatitis in children admitted to a tertiary care hospital from 1994 to 2007. Results: Of the 76 cases, 55% had gallstones, 21% had sludge, and 24% had structural defects. Hispanic children had 2.85 (P = 0.01) and 5.59 (P = 0.003) times higher probability for biliary pancreatitis than white and black children, respectively. Median serum amylase and lipase in children with biliary pancreatitis were 64% and 49% higher, respectively, compared with other causes (P < 0.05). In multiple logistic regression, aspartate aminotransferase was an independent predictor of biliary pancreatitis (odds ratio 6.69, P = 0.001). When comparing gallstone- with sludge-induced causes, obesity was an independent predictor (38% more prevalent, P < 0.01) of gallstone cases. Conclusions: Hispanic ethnicity is a risk factor and aspartate aminotransferase is a biomarker for biliary pancreatitis over other causes. Furthermore, obesity can distinguish gallstone- from sludge-induced pancreatitis. These findings may spur prospective studies to determine the optimal evaluation and management of children with biliary pancreatitis.

ACR appropriateness criteria(®) ductal carcinoma in situ.

Abstract:  Ductal carcinoma in situ (DCIS) describes a wide spectrum of non‐invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole‐breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow‐up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole‐breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer‐reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Neuroimaging biomarkers of epileptogenesis

Much progress has been made in the field studying the process of epileptogenesis via neuroimaging techniques. Conventional imaging methods include magnetic resonance imaging with morphometric analysis, magnetic resonance spectroscopy and positron emission tomography. Newer network-based methods such as diffusion tensor imaging and functional magnetic resonance imaging with resting functional connectivity are being developed and applied to clinical use. This review provides a brief summary of the major human and animal studies in both partial and generalized epilepsies that demonstrate the potential of these imaging modalities to serve as biomarkers of epileptogenesis.

Calcium ameliorates diarrhea in immunocompromised children.

ABSTRACT Treatment of infectious diarrheas remains a challenge, particularly in immunocompromised patients in whom infections usually persist and resultant diarrhea is often severe and protracted. Children with infectious diarrhea who become dehydrated are normally treated with oral or intravenous rehydration therapy. Although rehydration therapy can replace the loss of fluid, it does not ameliorate diarrhea. Thus, during the last decades, there has been continuous effort to search for ways to safely stop diarrhea. Herein, we report 3 immunocompromised children who developed severe and/or protracted infectious diarrhea. Their diarrheas were successfully “halted” within 1 to 2 days following the administration of calcium.

Rhythmic 3–4 Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures

Absence seizures are transient episodes of impaired consciousness accompanied by 3-4 Hz spike-wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequencies of rodent (7-8 Hz) and human (3-4 Hz) spike-wave discharges. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3-4 Hz spike-wave seizures in the presence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike-wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different durations, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic-clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that the lack of fMRI decreases with spike-wave was not due to technical factors. These findings demonstrate that 3-4 Hz spike-wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation.

Multi-institutional experience of ductal carcinoma in situ in black vs white patients treated with breast-conserving surgery and whole breast radiation therapy

PURPOSE Given the paucity of data on racial disparities in ductal carcinoma in situ (DCIS), the data from a multi-institutional cohort of DCIS patients treated with breast-conserving surgery and whole breast radiation therapy (RT) were analyzed to determine whether racial disparities or differences exist. METHODS AND MATERIALS A total of 533 white and 76 black DCIS patients from 3 university-based cancer centers were uniformly treated with breast-conserving surgery and RT. All patient data were collected and analyzed as a function of race. RESULTS The median follow-up was 5.2 years. No significant racial differences were seen in tumor size, age at diagnosis, estrogen receptor status, necrosis, or grade (all P>.05). Of the treatment parameters, the RT dose delivered, boost, positive margin rates, frequency of hormone receptor status assessment, and receipt of hormonal therapy for the 2 cohorts did not significantly differ (all P>.05). The local relapse-free survival was similar at 5 years (96.1% and 98.1%, P=.399) and 10 years (92.8% vs 95.8%, P=.360), with no significant overall survival difference at 10 years (94.0% vs 88.9%, P=.290) between the white and black patients, respectively. On multivariate analysis, race was not an independent predictor of local relapse-free survival or overall survival when accounting for age, grade, and margin status. CONCLUSION In our large cohort of DCIS patients uniformly treated at 3 institutions with breast conservation without any apparent differences in treatment delivery parameters, we demonstrated that the clinical and pathologic features and local survival outcomes did not differ as a function of race. Our results suggest that when black patients with DCIS are appropriately selected for breast conservation and receive adjuvant RT without racial disparities in the treatment parameters, differences in the outcomes as a function of race do not exist.