P2109 - Acute Pancreatitis Secondary to Tamoxifen-Induced Hypertriglyceridemia: A Systematic Review

Tuesday, October 26, 2021

10:30 AM – 4:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Zahra Akhtar, MBBS

University of Texas Medical Branch, Galveston
Galveston, TX, United States

Zahra Akhtar, MBBS¹, Muhammad Kashif Amin, MD², Muhammad Hassan Naeem Goraya, MBBS³, Faisal Inayat, MBBS⁴, Hassam Ali, MD⁵, Junaid Rasul Awan, MBBS⁶, Nadeem Hussain, MD⁴, Gul Nawaz, MD⁷, Zahid I. Tarar, MD⁸, Rahul Pamarthy, MD⁵, Muhammad Adnan Zaman, MD⁹
¹University of Texas Medical Branch, Galveston, Galveston, TX; ²Texas Tech University Health Sciences Center, Amarillo, TX; ³Services Institute of Medical Sciences, Lahore, Punjab, Pakistan; ⁴Allama Iqbal Medical College, Lahore, Punjab, Pakistan; ⁵East Carolina University, Greenville, NC; ⁶University Hospital Limerick, Limerick, Limerick, Ireland; ⁷Marshfield Clinic, Marshfield, WI; ⁸University of Missouri School of Medicine, Columbia, MO; ⁹Wexham Park Hospital, Slough, England, United Kingdom

Introduction: The association of severe lipaemia and tamoxifen was first reported by Brun et al. in 1986. Since then, hypertriglyceridemia (HTG) remains a rare side effect of this drug but may be life-threatening if it causes pancreatitis. To our knowledge, this is the first systematic review performed to investigate cases of acute pancreatitis (AP) with tamoxifen-induced HTG as the mechanism of injury.

Methods: A systematic search of MEDLINE, Embase, Scopus, and Cochrane was conducted for English-only articles, published between inception and June 15, 2021. Abstracts from major gastroenterology scientific meetings and bibliography lists were also reviewed. Search terms “pancreatitis” and ‘‘acute pancreatitis’’, were combined using the Boolean operators ‘AND’ and ‘OR’ with the terms “tamoxifen” and ‘’hypertriglyceridemia’’, with all permutations. AP was defined by meeting 2 of 3 Revised Atlanta Classification criteria. Tamoxifen-related hypertriglyceridemic AP was characterized by active use of tamoxifen, an elevated level of serum TGs, and exclusion of plausible causes of AP (alcohol, biliary, drugs, and hereditary). Two authors independently reviewed each article for eligibility. The search yielded a total of 213 results. However, 11 articles fulfilled the inclusion criteria. Another 3 case reports were excluded as they failed to meet the criteria for AP diagnosis.

Results: A total of 11 case reports only (level of clinical evidence: IV) of AP following tamoxifen-related HTG were identified, dating from 1987 to 2019 (Table 1). The mean age of patients was 46.63 years (range: 36-55 years), with 9/11 cases under age 50. Tamoxifen dose was 20 mg/day. The mean onset delay was 15.63 months (range: 7-48 months). AP was categorized as mild (n = 4), moderately severe (n = 4), and severe (n = 3). A positive rechallenge was reported in only one patient. All had favorable outcomes, but one patient died following hepatic failure.

Discussion: Tamoxifen-associated increased production of TGs causes blockage of the endogenous pancreatic capillaries, culminating in an inflammatory response in the pancreas (Figure 1). This systematic review provides a summary of data on this rare association between AP and tamoxifen therapy. Clinicians should remain cognizant of this important adverse effect. It is crucial to monitor serum lipids up to 4 years and beyond for patients on tamoxifen. The inclusion of tamoxifen as an etiology of AP may reclassify idiopathic AP cases. Further studies are warranted to evaluate this duo.

Figure: Figure 1: Contrast-enhanced computed tomography abdomen at the level of the pancreas in a patient who was under therapy with tamoxifen. The pancreas appears to be slightly enlarged, with a non-enhancing pancreatic body area, suggestive of acute necrotizing pancreatitis. Peripancreatic fluid collection is also present.

Authors	Age	Clinical presentation	Tamoxifen dosage (mg/day)	Serum amylase (IU/L)	Serum TGs (mg/dL)	Onset delay (months)	Treatment	Clinical outcome
Noguchi et al.	36	Acute pancreatitis	20	NA	3673	7	Hemodialysis, plasma exchange	Died
Elisaf et al.	53	Epigastric discomfort, nausea, vomiting	20	1600	5200	8	IV fluids, meperidine, gemfibrozil	Recovered
Lin et al.	43	Abdominal pain, nausea, vomiting	NA	1727	1005	24	Meperidine, promethazine	Recovered
Alagozlu et al.	46	Abdominal pain, nausea, vomiting, anorexia	20	1557	920	12	IV calcium gluconate, IV fluids, meperidine, insulin infusion, gemfibrozil	Recovered
Sakhri et al.	44	Acute respiratory distress syndrome	20	750	1180	12	Intubation, mechanical ventilation in ICU	Recovered
Kim et al.	40	Epigastric discomfort, nausea, vomiting	20	1119	3241	3	Morphine, demerol, fenofibrate, gabexate, imipenem, insulin infusion	Recovered
Singh et al.	50	Abdominal pain, vomiting	20	778	4568	3	IV fluids, analgesics, atorvastatin,	Recovered
Kataria et al.	50	Abdominal pain, vomiting	20	350	1050	1	intravenous pantoprazole, tramadol	Recovered
Kochar et al.	48	Epigastric pain, nausea	20	NA	2611	48	Gemfibrozil	Recovered
Yoneyama et al.	48	Epigastralgia, vomiting	20	221	2569	6	Bulk fluid replacement, antibiotics, and O₂ therapy	Recovered
Tey et al.	55	Acute epigastric pain	20	221	3,883	48	IV fluids, tramadol, IV insulin infusion, oral fenofibrate, nicotinic acid, and atorvastatin	Recovered

Table: Table 1. Summary of the data regarding acute pancreatitis secondary to tamoxifen therapy-associated hypertriglyceridemia.

Disclosures:
Zahra Akhtar indicated no relevant financial relationships.
Muhammad Kashif Amin indicated no relevant financial relationships.
Muhammad Hassan Naeem Goraya indicated no relevant financial relationships.
Faisal Inayat indicated no relevant financial relationships.
Hassam Ali indicated no relevant financial relationships.
Junaid Rasul Awan indicated no relevant financial relationships.
Nadeem Hussain indicated no relevant financial relationships.
Gul Nawaz indicated no relevant financial relationships.
Zahid I. Tarar indicated no relevant financial relationships.
Rahul Pamarthy indicated no relevant financial relationships.
Muhammad Adnan Zaman indicated no relevant financial relationships.

Zahra Akhtar, MBBS¹, Muhammad Kashif Amin, MD², Muhammad Hassan Naeem Goraya, MBBS³, Faisal Inayat, MBBS⁴, Hassam Ali, MD⁵, Junaid Rasul Awan, MBBS⁶, Nadeem Hussain, MD⁴, Gul Nawaz, MD⁷, Zahid I. Tarar, MD⁸, Rahul Pamarthy, MD⁵, Muhammad Adnan Zaman, MD⁹. P2109 - Acute Pancreatitis Secondary to Tamoxifen-Induced Hypertriglyceridemia: A Systematic Review, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.