LETTER OF MEDICAL NECESSITY FOR HEREDITARY PANCREATITIS GENETIC TESTING

Date: Date of service/claim

To: Utilization Review Department

Insurance Company Name, Address, City, State

Re: Patient Name, DOB, ID #

ICD-9 Codes: (list codes)

This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage of medically-indicated genetic testing for hereditary pancreatitis predisposition to be performed by Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-approved and CLIA-certified laboratory located at 7 Argonaut, Aliso Viejo, CA 92656. Significant aspects of my patient’s personal and/or family medical history are below:

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Based on my patient’s recurrent attacks of acute pancreatitis, an underlying genetic cause is suspected. Additionally, results of routine tests already performed suggest a diagnosis of hereditary pancreatitis.However, the only way to confirm this diagnosis is to perform genetic testing on my patient.

There are currently at least 4 genes that have been identified as significant risk factors in recurrent acute and/or chronic pancreatitis. These include: the cystic fibrosis transmembrane conductance regulator gene, CFTR; the cationic trypsinogen gene, PRSS1; the pancreatic secretory trypsin inhibitor gene, SPINK1; and the chymotrypsin C gene, CTRC.

Confirmation of the diagnosis through molecular genetic testing will directly impact my patient’s care and management. An accurate diagnosis of the underlying cause of the pancreatitis will identify the most appropriate medical management, based on the gene mutations that are identified. Mutations in different genes will indicate a different course of treatment as follows:

PRSS1 mutations that alter either of the calcium regulatory regions markedly increase sensitivity to calcium-mediated activation or enzyme survival. Therefore, strategies to minimize the rise in intra-acinar cell calcium concentrations are warranted. These include minimizing stimulation of the acinar cells by giving digestive enzymes and possibly gastric acid suppression and optimizing acinar cell calcium regulation by reducing intracellular stress with antioxidants, alcohol avoidance, and attention to metabolic factors like serum calcium levels. Additionally, individuals with PRSS1 mutations can develop an inflammatory milieu at high risk for the accumulation of oncogenic mutations, causing an increased lifetime risk to develop pancreatic cancer. Identifying these mutations could allow for an aggressive cancer surveillance plan to be implemented [1].

CFTR mutations markedly reduce the ability to flush digestive enzymes out of the pancreatic duct. Therefore, strategies to reduce the risk of damage within the pancreatic duct focus on maximizing fluid flow through the duct. This may include avoiding gastric acid suppression in order to increase release of secretin, and using high-quality, acid-resistant digestive enzyme supplements such as Creon®.

Utilizing this testing, a significant number of patients will actually be diagnosed with a form of cystic fibrosis (CF); it is then unlikely that these strategies will be effective. However, these patients should be triaged immediately for CF care, which would change medical management regarding pulmonary functions.

Heterozygous mutations in SPINK1 and CTRC have been linked to worsening of the pancreatitis phenotype, and to markedly increasing the risk of pancreatitis with most CFTR mutations. Strategies to minimize the effects of these mutations must therefore be linked to limiting the effect of trypsinogen mutations or CFTR mutations.

Additionally, symptoms of pancreatitis may be due to sphincter of Oddi dysfunction, typically diagnosed by endoscopic sphincterotomy. Unfortunately, this invasive and costly procedure may actually induce pancreatitis in up to 20% of individuals [2, 3]. Confirming an inherited cause for my patient’s pancreatitis through genetic testing would help eliminate this likelihood by sparing my patient this procedure.

A positive test result would provide a definitive cause for my patient’s pancreatitis and would ensure this patient is being treated appropriately, depending on the gene involved. As such, I am ordering this genetic test as medically necessary care, and affirm that my patient has provided informed consent for genetic testing. I am specifying Ambry Genetics because this laboratory has highly sensitive and cost-effective testing for hereditary pancreatitis, along with the largest database of tested patients to ensure the most accurate and informative test interpretation.

I recommend that you support this request for coverage of diagnostic genetic testing for hereditary pancreatitis predisposition for my patient. Genetic testing can take up to five weeks to complete and the laboratory will not bill until testing is concluded. Therefore, we are requesting that the authorization be valid for 2 months.

Thank you for your time and please don’t hesitate to contact me with any questions.

Sincerely,

Ordering Clinician Name (Signature Provided on Test Requisition Form)

(MD/DO, Clinical Nurse Specialist, Nurse-Midwives, Nurse Practitioner, Physician Assistant, Genetic Counselor*)

*Authorized clinician requirements vary by state

Test Details

CPT codes: 81223x1, 81224x1, 81404x2, 81479x1, 81222x1

Laboratory: Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-accredited and
CLIA-certified laboratory located at 7 Argonaut, Aliso Viejo, CA 92656

References:

1. Weiss, F.U., Pancreatic cancer risk in hereditary pancreatitis. Front Physiol, 2014. 5: p. 70.

2. Fogel, E.L., et al., Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone. Endoscopy, 2002. 34(4): p. 280-5.

3. Cotton, P.B., et al., Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc, 2009. 70(1): p. 80-8.