Illustrative Case Series

Gall Bladder Cancer

By Jerome Yates, MD, Hematology/Immunology Unit, National Institute on Aging, NIH. Dr. Yates reports no financial relationships relevant to this field of study.

A 71-year-old retired police officer was admitted through the emergency room with right upper quadrant pain and low-grade fever. An ultrasound revealed gall bladder distension and calculi and he was taken to the operating room with a presumptive diagnosis of cholecystitis. Laparoscopic approach was converted to laparotomy when an inflammatory mass was discovered and a cholecystectomy was performed. At the time of surgery it was the impression that the changes were consistent with both chronic and acute cholecystitis. However, histopathology revealed an adenosquamous carcinoma within the fundus of the gall bladder with extension through the wall of the gall bladder and into adjacent liver.

Prior to the episode of abdominal pain that led to the emergency room visit he had been asymptomatic. His past medical history is essentially unremarkable. He has no known chronic illness and was taking no prescription drugs. He is a non-smoker and drinks approximately two beers a day. The physical examination (3 days post operatively) revealed him to robust and with minimal discomfort. His blood pressure was 150/90. There was no scleral icterus or palpable lymphadenopathy. The surgical site was healing nicely without evidence for infection. Laboratories revealed a normal complete blood count and serum electrolytes. Total bilirubin was normal. SGOT and ALT were mildly elevated but alkaline phosphatase was within normal limits. Chest/abdomen/pelvis CT scan revealed changes consistent with recent cholecystectomy but no evidence for residual mass or distant metastases.

CASE DISCUSSION

Although gall bladder cancer often presents at advanced stage it is not uncommon for it to be discovered as an incidental finding at the time of cholecystectomy for presumed cholecystitis. In the case presented, the general surgeon completed the cholecystectomy and it was not until pathology review that the resected mass was shown to harbor malignancy. Gall bladder tumors discovered incidentally, such as in this case, are not unusual. In fact, in one series of 435 patients with gall bladder surgery, 47% were diagnosed as an incidental finding during laparoscopic cholecystectomy.1 Nonetheless, the management from this point forward would follow the same principles as if the cancer had been discovered by diagnostic procedures short of surgery. Clearly the greatest chance for long-term survival is the surgical excision of residual cancer, and efforts are called for to determine if resection is possible. An immediate second surgical procedure may not be well tolerated, particularly by patients with comorbidities or functional impairment, and it is reassuring to note that briefly delaying the second operative procedure is not associated with a survival deficit compared with immediate resection.2

STAGING OF GALL BLADDER CANCER

In addition to the CT scan already obtained, further efforts should be considered to determine whether the patient would benefit from repeat laparotomy. As will be discussed below, the majority of patients for whom gall bladder cancer was discovered as an incidental finding after cholecystectomy are found to have residual disease upon repeat laparotomy. For patients who present with findings on imaging studies prior to surgery, laparoscopic staging has proven valuable in determining resectability of residual disease.3 The role for positron emission tomography (PET) scanning has not been established, but there is some evidence that it is useful in detecting the presence of metastatic gall bladder cancer4,5 and thus, it may prove useful in selecting appropriate candidates for re-resection.

SURGICAL MANAGEMENT

For patients with gall bladder cancer that presented as an incidental finding and with histology demonstrating invasion through the lamina propria into the muscular layer (such as in the current case in which the tumor actually penetrated into the adjacent liver [T3]), a second surgery is indicated providing there is no evidence for distant metastases.6 Such is warranted because a large subset will have residual disease. For example, in one compiled series from six hospitals including 115 patients for whom re-resection was undertaken, pathology from the re-resection specimen noted residual/additional disease in 46.4% of patients.7 As expected, T stage correlated with the extent of residual disease. For those with T1 disease, 0% had liver involvement and 12.5% had positive lymph nodes. In contrast, liver and lymph nodes were involved in 10.4% and 31.3% for those with T2 lesions and 31.3% and 36.4% for those with T3 lesions. In that series, attaining clear surgical margins was shown to strongly correlate with survival. In a retrospective analysis from a single institution (Memorial Sloan Kettering), 74% of patients who underwent surgical re-exploration following an incidental diagnosis of gall bladder cancer were found to have residual disease.1

For those who are considered to have potentially resectable disease, the operative procedure should include hepatic resection and lymphadenectomy with or without bile duct excision.8 This is a complex and risky procedure that should only be performed by surgical oncologists with appropriate training and experience.6

ADJUVANT MANAGEMENT

There are insufficient data from which to define standard management in the adjuvant setting. Nonetheless, treatment with a fluoropyrimidine with or without radiation would be a reasonable approach.6 For the patient under discussion, presuming apparent residual disease was resected at the second surgical procedure, and in light of the original pathology description of a T3 lesion, I personally would favor an aggressive adjuvant approach, acknowledging that the standard approach is yet to be established.

SUMMARY

Gall bladder cancer typically exhibits aggressive patterns of growth and spread and the prognosis is not good for patients who present with stage III/IV disease. For the patient under discussion, the critical next step is to determine the possibility for resection of residual disease. If preoperative imaging studies are negative and there is no other evidence for distant metastases, repeat laparotomy performed by an experienced hepatobiliary surgeon would offer the best chance for long-term survival. As mentioned, the decision to proceed thereafter to adjuvant treatment is a judgment call, not based on scientific evidence. In fact, if a clinical trial were available addressing the issue of adjuvant treatment in this setting and if the patient were willing to participate, I would favor that enrolment.

References

1. Duffy A, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008;98:485-489.

2. Fong Y, et al. Gallbladder cancer: Comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg 2000;232:557-569.

3. Agrawal S, et al. Laparoscopic staging in gallbladder cancer. Dig Surg 2005;22:440-445.

4. Corvera CU, et al. 18F-fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer. J Am Coll Surg 2008;206:57-65.

5. Petrowsky H, et al. Impact of integrated positron emission tomography and computed tomography on staging and management of gallbladder cancer and cholangiocarcinoma. J Hepatol 2006;45:43-50.

6. NCCN Guidelines: Version 1.2011: Gall Bladder Cancer. 2011.

7. Pawlik TM, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: Implications for re-resection. J Gastrointest Surg 2007;11:1478-1486; discussion 1486-1487.

8. Jensen EH, et al. A critical analysis of the surgical management of early-stage gallbladder cancer in the United States. J Gastrointest Surg 2009;13:722-727.