ID: 36: PEGASPARGASE INDUCED SEVERE PANCREATITIS. FRIEND OR FOE?

2016 ◽  
Vol 64 (4) ◽  
pp. 942.1-942 ◽  
Author(s):  
N Vyas ◽  
H Alkhawam ◽  
R Sogomonian ◽  
RA Ching Companioni ◽  
M Tiba ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Abdominal Pain ◽  
Severe Acute Pancreatitis ◽  
Lymphoblastic Leukemia ◽  
Kidney Injury ◽  
Leukemic Cells ◽  
Drug Induced ◽  
Severe Pancreatitis ◽  
Elevated Liver Enzymes ◽  
Wide Range

IntroductionPegaspargase (Oncaspar) is a modified version of L-asparaginase conjugated with polyethylene glycol. In leukemic cells, asparaginase hydrolyzes L- asparagine to ammonia and L-aspartic acid leading to depletion of asparagine. Despite its potential benefits there are a wide range of side effects. One rare but potentially deadly complication is severe pancreatitis.CaseThe patient was a 24 year old Mexican male with a history of Acute T-Cell Lymphoblastic Leukemia (ALL) on recent chemotherapy including pegaspargase, admitted for abdominal pain, found to have acute pancreatitis secondary to hypertriglyceridemia. Heart rate was 127 bpm, chest revealed decreased air entry in right lung bases, and a distended severely tender abdomen. Laboratory tests were remarkable for elevated liver enzymes ALP 360 U/L, AST 310 U/L, GGT 216 U/L, ALT 44 U/L, LDH 829 U/L, elevated lipase 228 U/L, and hypertriglyceridemia >3,000 mg/dL. Abdominal CT showed pancreatitis with necrosis; peripancreatic, intraperitoneal and extensive retroperitoneal fluid. Subsequently his severe pancreatitis was associated with acute kidney injury and respiratory failure which is illustrated by his (BUN 22 Creatinine 2.16, and persistent hypoxia.) According to the Atlanta Classification, patient is classified under severe acute pancreatitis.DiscussionPegaspargase is used for treatment of ALL and is gaining in popularity over Asparaginase therapy due to it having fewer incidences of hypersensitivity reactions and because of its long half life (367 hrs) allowing dosing every 14 days as opposed to Asparaginase which is dosed daily. Pegaspargase definitely has its benefits but we can't lose sight of one of its rare, but potentially deadly complications, pancreatitis. In one study nine of the 50 patients (18%) with ALL treated with pegaspargase were diagnosed to have pancreatitis. In contrast, only one out of 52 (1.9%) ALL patients who received native E. coli L-asparaginase during the same time period developed pancreatitis. One proposed mechanism of this drug-induced pancreatitis is hypertriglyceridemia, which is seen in our case. It is suggested that apolipoprotein E polymorphism may influence the development of hyperlipidemia in ALL patients receiving pegaspargase therapy.We report a case to increase the awareness of higher incidence of pegaspargase-induced pancreatitis, which is a rare but potentially deadly complication. Clinicians should monitor triglycerides while on treatment and suspect pancreatitis if patient develops abdominal pain. If pancreatitis occurs, therapy should be stopped and not reinstituted. For patients with hypertriglyceridemia without pancreatitis discontinuation of therapy should be considered.Abstract ID: 36 Figure 1Impression: Severe acute pancreatitis. Significant interval worsening.

scholarly journals Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Tiffany J. Patton ◽  
Timothy A. Sentongo ◽  
Grace Z. Mak ◽  
Stacy A. Kahn
Keyword(s):  
Acute Pancreatitis ◽  
Abdominal Pain ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Pseudocyst ◽  
Fluid Collection ◽  
Initial Presentation ◽  
Metabolic Abnormalities ◽  
Pediatric Case ◽  
Severe Pancreatitis ◽  
Colonic Necrosis

Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis.

Clinical Profile and Outcomes in Patients with Acute Pancreatitis attending a Teaching Hospital at Gandaki Province, Nepal

2020 ◽  
Vol 16 (3) ◽  
Author(s):  
Subash Bhattarai ◽  
Merina Gyawali
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Age Groups ◽  
Data Entry ◽  
Kidney Injury ◽  
Severity Index ◽  
Clinical Profile ◽  
Cross Sectional ◽  
Systemic Complications ◽  
Keywords Alcohol

Background: Acute pancreatitis (AP) is inflammatory process of pancreas presenting with acute abdominal pain.The majority of patients have mild disease. Some patients develop local and systemic complications with increased morbidity and mortality. This study was undertaken to describe the clinical profile and outcomes in patients with acute pancreatitis.   Methods:  A cross-sectional hospital based study comprising of 62 consecutive patients with acute pancreatitis were enrolled between Jan 2019 to August 2020. Clinical profile at admission, complications and clinical outcomes including mortality were studied. Patients were classified into mild, moderately severe and severe acute pancreatitis based on revised Atlanta classification and modified CT severity index.  Data entry was done in Statistical Packages for the Social Sciences version 20. Results: The mean age of study subjects was 44±10.87 years with 43 (56%) males and 19 (44%) females (M:F=2.1:1). The commonest etiology of pancreatitis was alcohol (53.2%) followed by biliary pancreatitis (37.1%)  The most common presentation was abdominal pain (100%). The most common complication was pancreatic necrosis (21%) followed by acute kidney injury (19.4%) and pleural effusion (17.3%). Majority( 72.6%) was mild and 17.7% had severe acute pancreatitis. Mortality was seen in 6.5% patients. Mortality was observed in patients with persistent complications, organ failure, low serum calcium and high modified CT severity index.   Conclusions: Alcohol and gallstones were the two main etiologies of acute pancreatitis and were common in males, and in middle age groups. Majority presented with mild severity. Mortality was observed in some patients with severe acute pancreatitis.   Keywords: alcohol; biliary; CT severity index; mortality; outcome; pancreatitis          

scholarly journals Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Dania Lizet Quintanilla-Flores ◽  
Miguel Ángel Flores-Caballero ◽  
René Rodríguez-Gutiérrez ◽  
Héctor Eloy Tamez-Pérez ◽  
José Gerardo González-González
Keyword(s):  
Acute Pancreatitis ◽  
Abdominal Pain ◽  
Acute Lymphoblastic Leukemia ◽  
Diabetic Ketoacidosis ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Contrast Enhanced ◽  
Enhanced Computed Tomography ◽  
Hispanic Male ◽  
Contrast Enhanced Computed Tomography

Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

scholarly journals Comparison of BISAP score with Ranson’s score in predicting severe acute pancreatitis

2016 ◽  
Vol 18 (3) ◽  
pp. 44
Author(s):  
D Karki ◽  
T Tamang ◽  
D Maharjan ◽  
P Thapa ◽  
S Shrestha
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Scoring System ◽  
Laboratory Data ◽  
P Value ◽  
Severe Pancreatitis ◽  
Common Etiology ◽  
Sensitivity Specificity

Objectives: To compare BISAP score with Ranson’s scoring in predicting severity of acute pancreatitisMethods: Extensive demographic, radiographic, and laboratory data from consecutive patients with AP admitted to our institution was collected between March 2014 to March 2015. Ranson’s and BISAP score was calculated. Severity of pancreatitis was defined according to Atlanta classification. Sensitivity, Specificity, PPV, NPV of both the scoring system was calculated and compared.Results: A total of 42 patients with diagnosis of acute pancreatitis were included during the study period. 21(50%) were male and 21(50%) were female. Mean age is 49.52 ± 17.37.Most common etiology was biliary (45%) followed by alcohol (31%). 20 (48%) patients were categorized as severe pancreatitis according to Atlanta classification. 21 (50%) patients had a Ranson’s score of ≥3 and 19 (45.24%) patients had a BISAP score of ≥3. Both Ranson’s and BISAP scoring system was statistically significant in determining SAP ( p-value = 0.002). Sensitivity, specificity, PPV and NPV of Ranson’s and BISAP score was calculated to be 75%, 72.72%, 71.43%, 76.19% and 70%, 77.27%, 73.68%, 73.91%. respectively. The AUC for SAP by Ranson’s score is 0.7386 ; 95%CI (0.602 - 0.874) and BISAP score is 0.7364 ; 95% CI ( 0.599 - 0.872).Conclusions: Both Ranson’s and BISAP scoring system is similar in predicting SAP. However BISAP has the advantage due to its simplicity.

scholarly journals Ringer’s Lactate Prevents Early Organ Failure by Providing Extracellular Calcium

2020 ◽  
Vol 9 (1) ◽  
pp. 263 ◽  
Author(s):  
Biswajit Khatua ◽  
Jordan R. Yaron ◽  
Bara El-Kurdi ◽  
Sergiy Kostenko ◽  
Georgios I. Papachristou ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Organ Failure ◽  
Severe Acute Pancreatitis ◽  
Systemic Inflammation ◽  
Normal Saline ◽  
Meta Analysis ◽  
Extracellular Calcium ◽  
Severe Pancreatitis ◽  
Ringer’S Lactate

Objective: Ringer’s lactate may improve early systemic inflammation during critical illnesses like severe acute pancreatitis, which are associated with hypocalcemia. Ringer’s lactate is buffered and contains lactate and calcium. We, thus analyzed extracellular calcium or lactate’s effects on the mechanisms, intermediary markers, and organ failure in models mimicking human disease with nonesterified fatty acid (NEFA) elevation. Methods: Meta-analyses and experimental studies were performed. Experimentally, extracellular calcium and lactate were compared in their interaction with linoleic acid (LA; a NEFA increased in human severe pancreatitis), and its subsequent effects on mitochondrial depolarization and cytosolic calcium signaling resulting in cell injury. In vivo, the effect of LA was studied on organ failure, along with the effect of calcium or lactate (pH 7.4) on severe acute pancreatitis-associated organ failure. A meta-analysis of human randomized control trials comparing Ringer’s lactate to normal saline was done, focusing on necrosis and organ failure. Results: Calcium reacted ionically with LA and reduced lipotoxic necrosis. In vivo, LA induced organ failure and hypocalcemia. During severe pancreatitis, calcium supplementation in saline pH 7.4, unlike lactate, prevented hypocalcemia, increased NEFA saponification, reduced circulating NEFA and C-reactive protein, reduced pancreatic necrosis adjacent to fat necrosis, and normalized shock (carotid pulse distension) and blood urea nitrogen elevation on day 1. This, however, did not prevent the later increase in serum NEFA which caused delayed organ failure. Meta-analysis showed Ringer’s lactate reduced necrosis, but not organ failure, compared with normal saline. Conclusion: Hypocalcemia occurs due to excess NEFA binding calcium during a critical illness. Ringer’s lactate’s early benefits in systemic inflammation are by the calcium it provides reacting ionically with NEFA. This, however, does not prevent later organ failure from sustained NEFA generation. Future studies comparing calcium supplemented saline resuscitation to Ringer’s lactate may provide insights to this pathophysiology.

Role of Erythropoietin Receptor in t(12;21) Positive Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2792-2792
Author(s):  
Renate Panzer-Gruemayer ◽  
Gerd Krapf ◽  
Dominik Beck ◽  
Gerhard Fuka ◽  
Christian Bieglmayer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Erythropoietin Receptor ◽  
Molecular Signature ◽  
Leukemic Cells ◽  
Drug Induced ◽  
Induced Apoptosis

Abstract The chromosomal translocation t(12;21)(p13;q22) resulting in the TEL/AML1 (also known as ETV6/ RUNX1) fusion gene is the most frequent translocation in childhood B cell precursor (BCP) ALL. This type of ALL is characterized by a unique molecular signature, which includes the overexpression of the gene for the erythropoietin receptor (EpoR). So far, it is not known what causes the overexpression of the EpoR gene or whether it has any effect on the t(12;21) positive leukemia. We therefore aimed to evaluate potential mechanisms responsible for the upregulation of the EpoR in t(12;21) leukemias and to find out whether signalling via this receptor affects survival or proliferation of leukemic cells. In addition, we planned to explore signalling pathways linked to the respective effects and to elucidate relevant mechanisms that might be essential for cell survival. We first excluded the possibility that the EpoR expression is upregulated as a consequence of high Epo levels in the plasma that are induced by the patients’ low hemoglobin (Hb) levels. While Hb levels from patients with t(12;21)+ ALL were significantly lower compared to those with other subtypes of BCP ALL (median, 6,15g/dL and 7,9g/dL, respectively; p<0.001 Wilcoxon 2- sample test), which correlated with high Epo levels in the plasma, the extent of EpoR mRNA expression of leukemic cells was independent of the respective amount of Epo in the individual patient’s plasma. Next, the influence of Epo on t(12;21) + leukemic cell lines was evaluated and revealed a consistent time and dose dependent increase in proliferation (Epo concentrations 10, 50, 100U/ml for 72 hours) determined by 3H-Thymidine incorporation. This effect was abrogated upon addition of a blocking anti-EpoR antibody thereby confirming the specificity of EpoR signalling. Since Epo may have apoptosis-modulating potential in EpoR expressing malignant cells, we tested its influence on drug-induced apoptosis. For this purpose IC50 concentrations of drugs that are commonly used for the treatment of children with BCP ALL were used. A reduction of glucocorticoid (GC)-induced apoptosis by Epo was demonstrated in t(12;21)+ cell lines while no effect was seen in combination with other drugs or in t(12;21) negative cell lines. Preliminary data indicate that NF-kappa B as well as PI3K/Akt pathways are triggered by Epo, implying that they play a role in this rescue mechanism. Given that cell lines may have intrinsic changes, we are presently evaluating whether the observed results can also be reproduced in primary leukemic cells. In support of this assumption are results in a limited number of primary t(12;21)+ leukemias showing a superior survival (MTT assay) and reduced apoptosis rate to GC when cultured in the presence of Epo. These findings are in contrast to those in t(12;21) negative BCP ALLs. In conclusion, our data indicate that overexpression of EpoR in t(12;21) positive leukemias is not induced by low Hb, a feature that is generally observed in patients with this type of leukemia. Binding of Epo to its receptor in vitro leads to enhanced survival and negatively affects the sensitivity to GCs. Whether these findings have any implications on the treatment and care of patients with t(12;21)+ leukemia needs to be addressed in further studies. Financial support: OENB10720, FWF P17551-B14 and GENAU-CHILD Projekt GZ200.136/1 - VI/1/2005 to RPG.

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