The primary objective of this study is to assess the safety, tolerability and toxicity of preoperative HBOT in patients undergoing a pancreaticoduodenal resection for premalignant and malignant tumors of the common bile duct, periampullary and duodenum.

Patients diagnosed with premalignant and malignant tumors of the common bile duct, periampullary and duodenum will be screened for eligibility within 4 weeks of their scheduled surgery. Initiation of therapy is defined as the first day of HBOT for patients receiving HBOT therapy (Arm A) and the day of surgery for patients not receiving HBOT (Arm B). Patients will be considered "enrolled into study" once the consent form has been signed, all screening procedures have been undertaken and all the eligibility criteria are met. The fifty eligible patients will be randomized in a 1:1 ratio the same day of the screening process. The eligible subjects undergoing HBOT will be treated with up to 2.4 Atmospheres Absolute (ATA) of oxygen (O2), for a maximum of 90 minutes each day with or without air breaks, as deemed necessary by the investigator, for two days. Patients who are deemed ineligible will receive the same standard of care without any exceptions. The start day of the week to commence HBOT will be Monday through Wednesday, as the second and final day of HBOT treatment will be the day in which the patient undergoes pancreaticoduodenectomy. The subjects who complete the HBOT regimen must undergo subsequent pancreaticoduodenectomy within five hours of termination of HBOT. If there is more than a five hour delay from completion of the HBOT to commencement of operation, the subject will be considered "off study treatment". However, "off study treatment" patients will continue to be followed up every six months for the first thirty months, and annually thereafter. During the postoperative period, clinical data and questionnaire forms will be collected on day 1, day 3, day 5, and one month (± 2 weeks) during the first year. As for secondary objectives, the investigators will collect clinical data from patients during their follow up visits in the office, by contacting them on the phone, or by mailing them the protocol specific questionnaires every 6 months for 5 years.

Inclusion Criteria:

• All patients diagnosed via endoscopic ultrasound (EUS) and fine needle aspiration (FNA) or CT-guided biopsy with periampullary adenocarcinoma, duodenal cancer, premalignant lesions of the pancreas (pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm) and cholangiocarcinoma (Klatskin tumor) undergoing pancreaticoduodenectomy
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
• One or more comorbidities:

Diabetes Mellitus Chronic Obstructive Pulmonary Disease Cardiac Disease: history of angina, myocardial infarction, previous percutaneous cardiac intervention, or cardiac surgery, dysrhythmia Peripheral Vascular Disease: history of revascularization or amputation, rest pain, or gangrene Neurological Disease: history of stroke with or without residual deficit, seizure disorder, transient ischemic attack, hemiplegia, paraplegia, or impaired sensorium Dyspnea Bleeding Disorder Metabolic Disease (e.g. BMI ≥ 35) Renal Insufficiency Hepatic Insufficiency Another comorbidity that in the opinion of the investigator makes the patient compromised

• Nutritionally depleted. Albumin level ≤ 3.5 grams/deciliter (g/dL)
• Adequate organ function defined as:

Absolute neutrophil count >1,500 / (microliter) mcL Platelets >100,000 / mcL Total bilirubin <2.5 time upper limits of normal Aspartate aminotransferase (AST) / Alanine transaminase (ALT) <2.5 times institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >60 mL/min/ per Cockcroft-Gault equation for patients with creatinine levels above institutional normal

- Signed informed consent

Exclusion Criteria:

• History of asthma. There is some evidence that the administration of some bronchodilators may increase the incidence of gas embolism to the brain through pulmonary vasodilation.
• Congenital spherocytosis. Increased risk of massive hemolysis.
• High grade fever at time of screening (more than 38.5 degree Celsius tend to lower the seizure threshold due to oxygen toxicity and may result in the delay of relatively routine therapy
• Optic neuritis.
• Upper respiratory tract infection and viral infection (relative contra-indications due to the difficulty such patients may have in clearing their ears and sinuses.
• Pregnancy.
• Emphysema with carbon dioxide retention.
• Viral infection. There are controversial clinical evidences whether the hyperbaric oxygen therapy (HBOT) can be helpful in eliminating viral infections or otherwise viral infections may be considerably worsened after HBOT.
• Cisplatin therapy (some evidence that this drug retards wound healing when combined with HBOT).
• Disulphiram therapy. Evidence suggests that this drug blocks the production of superoxide dismutase. This may severely affect the body's ability to neutralize oxygen free radicals.
• Doxorubicin therapy. This chemotherapeutic agent becomes increasingly toxic under pressure. Animal studies suggest at least a one-week break between last dose and first treatment of HBOT.
• Claustrophobia. Some degree of confinement anxiety has been reported.