Gemcitabine Hydrochloride in Treating Patients With Locally Advanced Pancreatic Cancer

Inclusion Criteria: * Histologically or cytology proven pancreatic ductal carcinoma * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0,1 or 2 * Absolute neutrophil count (ANC) \>= 1500 * Platelets (PLT) \>= 100,000 * Hemoglobin (HgB) \> 9.0 g/dL * Total bilirubin \< 2.0 x upper limit of normal (ULN) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 5 x ULN * Creatinine =\< 1.5 mg/dL * Negative pregnancy test done =\< 14 days prior to registration, for women of childbearing potential only * Provide informed written consent * Imaging, a combination of at least two of the following (computed tomography \[CT\], magnetic resonance imaging \[MRI\], endoscopic ultrasound \[EUS\]) staging the pancreatic mass as "locally advanced" * EUS clinically indicated for staging, and/or celiac neurolysis * Resection declined by surgical staff based on designation of LAPC * Willing to provide blood samples * Willing to receive their standard multimodality therapy at Mayo Clinic, Rochester * Willing to return to Mayo Clinic, Rochester during the observation phase Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * Any prior treatment (chemotherapy, radiation) for pancreatic cancer * Other active malignancy =\< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer * History of myocardial infarction =\< 168 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias * Prior pancreatic surgery * Pancreatic tumor histology other than carcinoma (e.g. islet cell, lymphoma, etc.)