Patient must be >= 18 years of age

Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
* NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible

Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization

Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
* No radiographic evidence of distant disease (M1 disease)
* No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
* No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
* No evidence of new-onset ascites
* Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes ‘localized resectable’ disease are allowable

Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study

Patient must have the ability to understand and the willingness to sign a written informed consent document or, have legally authorized representative provide authorization to participate

Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to randomization)

Platelets >= 100,000/mcL (obtained =< 28 days prior to randomization)

Total bilirubin =< institutional upper limit of normal (ULN) except in patients with Gilbert’s syndrome. Patients with Gilbert’s syndrome are eligible if direct bilirubin < 1.5 x ULN of the direct bilirubin (obtained =< 28 days prior to randomization)

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 28 days prior to randomization)

Serum creatinine =< institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 (Based on Cockcroft Gault estimation) (obtained =< 28 days prior to randomization)

Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial

For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better

PRIMARY OBJECTIVE:
I. To determine the difference in overall survival (OS) for patients given neoadjuvant gemcitabine hydrochloride (gemcitabine) and cisplatin prior to re-resection followed by adjuvant gemcitabine and cisplatin compared to patients who receive only adjuvant gemcitabine and cisplatin after re-resection for incidental gallbladder cancer (IGBC).

SECONDARY OBJECTIVES:
I. To compare the incidence of residual disease at the time of re-resection between patients with IGBC who receive perioperative chemotherapy prior to re-resection and those who receive only adjuvant chemotherapy after re-resection.
II. To assess the clinical effect of preoperative chemotherapy compared to upfront re-resection on resectability among 3 cohorts: all enrolled patients, all patients who undergo staging laparoscopy, and all patients who undergo laparotomy.
III. To determine the difference in progression-free survival (PFS) for patients with IGBC who receive perioperative chemotherapy prior to and after re-resection compared to patients who receive only adjuvant chemotherapy after re-resection.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Within 4 weeks of randomization, patients undergo surgery to remove part of the liver, the lymph nodes around the liver, and possibly the bile ducts. Within 16 weeks after completion of surgery, patients then receive gemcitabine intravenously (IV) over 30 minutes and cisplatin IV over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) and magnetic resonance imaging (MRI) on study. 

ARM II: Patients receive gemcitabine IV over 30 minutes and cisplatin over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Approximately 4-8 weeks after completion of chemotherapy, patients whose disease has not spread to other places in the body (metastasized) undergo surgery as in Arm I. Patients with successful surgery then resume treatment with gemcitabine IV and cisplatin IV on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT and MRI during baseline and on study.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 1 year after surgery or until disease recurrence, whichever comes first, for up to 5 years.