Nilay A. Shah and Jon Cardinal
Carcinomas of the biliary tract include those cancers arising in either the gallbladder or the bile duct. There will be an estimated 10,130 new cases of gallbladder and biliary tract cancers (excluding intrahepatic biliary tract cancer) in 2013 with 3,230 expected deaths resulting from these cancers. Gallbladder cancer is the most common biliary tract cancer, occurring nearly twice as often as cholangiocarcinomas. While the term cholangiocarcinoma was initially used to designate tumors of the intrahepatic bile ducts; it is now taken to refer to the entire spectrum of tumors arising in the intrahepatic, perihilar, and distal bile ducts. The epidemiology, clinical features, staging, and surgical treatment are distinct for carcinomas arising in the gallbladder and bile duct, therefore, these are describe separately. The palliative treatment options are similar and are discussed together at the end of the chapter.
CARCINOMA OF THE GALLBLADDER
Epidemiology
■Carcinoma of the gallbladder is the fifth most common GI malignancy.
■Women are affected two to six times more commonly than men and whites have a 50% greater incidence compared to black individuals.
■There is a prominent geographic variation in the incidence of gallbladder cancer. High rates are seen among Native Americans and in South American countries (particularly Chile). There is increased incidence in India, Pakistan, Japan, and Koreas as well. These populations share a high prevalence of cholelithiasis, which is a common risk factor.
■The United States is considered a low-incidence area. The age-adjusted incidence of carcinoma of the gallbladder is 1.2 per 100,000 population in the United States.
■The mean age at diagnosis is 65 years.
Etiology
■Cholelithiasis (gallstones): A history of gallstones appears to be one of the strongest risk factors for gallbladder cancer. Seventy to 90% of patients will have gallstones, whereas only 0.5% to 3% of patients with gallstones develop gallbladder cancer. The risk increases with an increase in the size and duration of the stones.
■Porcelain gallbladder: Extensive calcium deposition in the gallbladder wall was associated with cholecystitis in nearly all cases. Previously, the incidence of gallbladder cancer in patients with this condition was thought to range from 12.5% to 60%, although more recent data suggest the incidence is closer to 2% to 3%. Stippled, mucosal calcifications appear to be associated with a higher risk than diffuse intramural calcifications.
■Chronic infection: Carriers or those colonized with Salmonella typhi and Helicobacter pylori may be at increased risk of developing gallbladder cancer.
■Gallbladder polyps: Polyps >1 cm have the greatest malignancy potential and therefore are an indication for cholecystectomy.
■The anamolous pancreaticobiliary duct junction may contribute to the development of gallbladder cancer.
■Miscellaneous: Obesity, diabetes, medications (methyldopa, estrogens, isoniazid), and carcinogen exposure (radon, chemicals from the rubber industry, cigarettes) have also been associated with this disease.
Clinical Features
Early-stage disease may be asymptomatic or present with very nonspecific symptoms, including the following:
■Pain (82%)
■Weight loss (72%)
■Anorexia (74%)
■Nausea or vomiting (68%)
■Mass in the right upper quadrant (65%)
■Jaundice (44%)
■Abdominal distension (30%)
■Pruritus (20%)
■Incidental (15% to 20%)
■Courvoisier’s law states that if the gallbladder is enlarged and if the patient has painless jaundice, the cause is unlikely to be gallstones
Diagnosis
Three clinical scenarios exist in patients presenting with gallbladder cancer: final pathology after a routine laparoscopic cholecystectomy incidentally discovers gallbladder cancer; gallbladder cancer is suspected/diagnosed intraoperatively; or gallbladder cancer is suspected preoperatively.
■Of the three clinical scenarios listed above, the first is the most common with the majority of gallbladder cancers being diagnosed as an incidental finding during exploration of presumed benign disease. It is estimated that 1% to 2% of patients undergoing exploration for presumed benign disease will be found to have gallbladder cancer.
■Ultrasound is a useful modality in the preoperative workup for gallbladder pathology. In the case of gallbladder cancer, the ultrasonographic findings may include a thickened or calcified wall, a protruding mass, or a loss of gallbladder to liver interface; however, these may not be specific for gallbladder cancer.
■Endoscopic ultrasound (EUS) is more accurate than transabdominal ultrasound; it is useful in the differential diagnosis of polyps and in preoperative staging. EUS can accurately assess the depth of tumor invasion as well as define regional lymph node involvement.
■Triple-phase computerized tomography (CT) scan (liver protocol), which includes a noncontrasted phase, a hepatic arterial phase, and a portal venous phase, allows visualization of the extent of tumor growth, can aid in determining the nodal status as well as identifying distant metastases, and is particularly useful in determining the relationship of the tumor mass to the major hilar inflow structures which is an important preoperative determinant. This modality is less helpful is distinguishing benign from malignant polyps.
■Cholangiography: Magnetic resonance cholangiopancreatography (MRCP) is preferred to endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiopancreatography because it is a noninvasive modality. MRCP can provide information regarding the extent of disease and is able to differentiate a benign from malignant lesion/polyp. Furthermore, ERCP and PTC do not provide appropriate visualization of the gallbladder.
■Positron emission tomography (PET) scan’s role in the diagnosis of gallbladder cancer remains unclear at this time; however, it may be useful in detecting distant metastatic disease in patients previously determined to have resectable disease.
■Laboratory studies are generally not diagnostic. Elevated serum bilirubin or alkaline phosphatase can indicate a bile duct obstruction. Tumor markers such as carcinoembryonic antigen (CEA) or CA 19-9 can be elevated. CEA is specific for gallbladder cancer, but lacks sensitivity, whereas CA 19-9 has sensitivity and specificity that can approach 75%.
Pathology
■Adenocarcinoma accounts for close to 85% of cases. It is subcharacterized into papillary, tubular, mucinous, or signet cell type. Other histologies include anaplastic, squamous cell, small-cell neuroendocrine tumors, sarcoma, and lymphoma.
Staging
There are several staging systems available for gallbladder cancer. The original staging system developed by Nevin in 1976 is still widely used; however, the preferred classification scheme in the United States is the TNM staging system of the American Joint Committee on Cancer (AJCC).
■The AJCC TNM staging classification was recently updated in 2010. Please refer to the seventh edition of the Staging Manual for details. The Nevin staging, which is more commonly used in Europe, is provided in Table 6.1.
■The updated stage groupings were realigned to better correlate with resectability and prognosis.
Treatment
Surgery
■Surgical resection remains the only potentially curative therapy.
■The lack of a peritoneal lining on the side of the gallbladder that is attached to the liver represents an important anatomic consideration in the surgical management of gallbladder cancer. In a simple cholecystectomy, the surgeon dissects the plane between the muscularis of the gallbladder and the cystic plate, which is a fibrous lining that occupies the space between the gallbladder and the liver. For this reason, simple cholecystectomy is considered inadequate surgical therapy for all but the earliest stages of the disease.
■Factors determining resectability include the stage of the tumor as well as the location. Stage 0, I, and II tumors are potentially resectable with curative intent. Stage T3 tumors and above are generally considered difficult to resect.
■Patients noted to have T1a lesions may be observed post–simple cholecystectomy as long-term survival approaches 100%.
■Controversy exists about the proper management of patients with T1b lesions as some series show only a 50% 1-year survival following simple cholecystectomy, while others report cure rates of 90% to 100% at 5 years. It is generally agreed, however, that medically fit patients with T1b lesions should undergo extended cholecystectomy.
■Patients with T2 or greater lesions should undergo extended cholecystectomy after metastatic disease has been ruled out. Optimal resection (extended cholecystectomy) includes a cholecystectomy with en bloc hepatic resection and regional lymphadenectomy with or without bile duct excision. Achievement of R0 resection margins strongly correlates with long-term survival.
■The type of resection that is ultimately required to achieve an R0 resection can at times depend on the location of the tumor within the gallbladder. Tumors of the body and fundus may be manageable with a localized segment IV/V resection while those of the infundibulum may require division of inflow structures and consequently major hepatic resection with or without bile duct resection/reconstruction.
■Contraindications to surgery include distant metastases, extensive involvement of the porta hepatis causing jaundice, significant ascites, and encasement or occlusion of major vessels. Direct involvement of adjacent organs is not an absolute contraindication.
■However, biopsy should be avoided in patients who are surgical candidates are gallbladder cancer notoriously seeds biopsy tracks and can easily seed the peritoneal cavity.
Radiation
■In patients with unresectable tumors, available data suggest that tumor control is rarely achieved with RT.
■A number of reports have documented improvements in survival rates in cases of intraoperative or postoperative adjuvant radiotherapy. No prospective randomized controlled trials have been performed to address this issue. In 2003, however, Jarnigan and colleagues found that only 15% of patients had locoregional recurrence as their only site of recurrent disease which highlights the importance of effective, adjuvant systemic strategies.
Chemotherapy and Palliation
The benefits and options available for chemotherapy and palliation of carcinoma of the gallbladder are the same as those for cholangiocarcinoma which is discussed in the next section.
Survival
The various aspects of survival following treatment of gallbladder cancers according to stage are given in Table 6.2.
CARCINOMA OF THE BILE DUCTS (CHOLANGIOCARCINOMA)
Epidemiology
■Cholangiocarcinomas arise from the epithelial cells of either intrahepatic or extrahepatic bile ducts.
■Cholangiocarcinoma accounts for 3% of all GI malignancies. The reported incidence within the Unites States is one to two cases per 100,000 population.
■For some unclear reasons the incidence of intrahepatic cholangiocarcinoma has been steadily rising over the past two decades, while rates of extrahepatic cholangiocarcinomas have been declining.
■Incidence typically increases with age. Median age at diagnosis is between 50 and 70 years. However patients with primary sclerosing cholangitis (PSC) and those with choledochal cysts tend to present significantly earlier.
■In contrast to gallbladder cancer, cholangiocarcinomas are more common in males.
■Cholangiocarcinomas are subdivided into proximal extrahepatic (perihilar or Klatskin tumor; 50% to 60%), distal extrahepatic (20% to 25%), intrahepatic (peripheral tumor; 20% to 25%), and multifocal (5%) tumors.
■Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas, and perihilar cholangiocarcinoma is the most common type.
Etiology
A number of risk factors have been associated with the disease in some patients; however, no specific predisposing factors have been identified.
■Inflammatory conditions: PSC is associated with an annual risk of 0.6 to 1.5% per year and a 10% to 15% lifetime risk of developing cholangiocarcinoma. Ulcerative colitis and chronic intraductal gallstone disease also increase risk. Nearly 30% of cholangiocarcinomas are diagnosed in patients with coexistent ulcerative colitis and PSC.
■Bile duct abnormalities: Caroli disease (cystic dilatation of intrahepatic ducts), bile duct adenoma, biliary papillomatosis, and choledochal cysts increase risk. The overall incidence of cholangiocarcinoma in these patients can be as high as 28%.
■Infection: In Southeast Asia, the risk can be increased 25- to 50-fold by parasitic infestation from Opisthorchis viverrini and Clonorchis sinensis. These parasitic infections are more commonly associated with intrahepatic cholangiocarcinoma. An association with viral hepatitis has also been seen recently. A higher than expected rate of hepatitis C-associated cirrhosis was noted in patients with cholangiocarcinoma. An association with hepatitis B has also been suggested.
■Genetic: Lynch syndrome II and multiple biliary papillomatosis are associated with an increased risk of developing cholangiocarcinoma. Biliary papillomatosis should be considered a premalignant condition as one study noted that up to 83% will undergo malignant transformation. More recently, certain genetic polymorphisms (NKG2D) have been determined to be possible risk factors for developing cholangiocarcinoma.
■Miscellaneous: Smoking, toxic exposures, such as thorotrast (a radiologic contrast agent used in the 1960s), asbestos, radon, and nitrosamines are also known to increase the risk. Recently, patients with diabetes or a metabolic syndrome have been noted to have an increased risk of developing a cholangiocarcinoma as well.
Clinical Features
Cholangiocarcinomas usually become symptomatic when the biliary system becomes blocked.
■Extrahepatic cholangiocarcinoma usually presents with symptoms and signs of cholestasis (icterus, pale stools, dark urine, and pruritus or cholangitis, which includes pain, icterus, and fever). Laboratory studies will typically suggest biliary obstruction with elevated direct bilirubin and alkaline phosphatase.
■Intrahepatic cholangiocarcinoma may present as a mass, be asymptomatic, or produce vague symptoms such as pain, anorexia, weight loss, night sweats, and malaise. These patients are less likely to be jaundiced.
Diagnosis
Making a diagnosis of cholangiocarcinoma preoperatively can be challenging. The diagnosis is frequently based on the clinical scenario, serology, and radiographic findings but without histologic confirmation. This is an important issue because up to 33% of patients with imaging and symptoms suggestive of cholangiocarcinoma will have benign disease. Such a diagnosis in the absence of tissue should be made only after efforts are taken to prove the diagnosis by use of cytologic or pathologic evaluation.
■A cholestatic serologic picture may be seen as previously described. Liver function tests may be elevated, particularly with intrahepatic cholangiocarcinoma. Tumor markers such as CEA and CA-19-9 by themselves are neither sensitive nor specific enough to make a diagnosis. CEA level > 5.2 ng/mL had a sensitivity and specificity of 68% and 82%, respectively. Some tumors produce low levels or no CA 19-9. In one series, a level >180 units/mL had a sensitivity of 67%; however, the specificity was 98%.
■Ultrasonography is the first-line investigation for suspected cholangiocarcinoma, usually to confirm biliary duct dilatation, localize the site of obstruction, and to rule out cholelithiasis. This technique can often overlook masses and is poor at delineating anatomy.
■CT/MRI is recommended as part of the diagnostic workup of cholangiocarcinoma, intrahepatic tumors in particular. These imaging modalities can help determine tumor resectability by evaluating the tumor and the surrounding structures (major vessels, lymph nodes, presence of metastases).
■Cholangiography: MRCP is noninvasive and is considered a safer alternative to ERCP or PTC. MRCP provides excellent imaging of the intrahepatic and extrahepatic bile ducts and can create three dimensional imaging of the biliary tree and the vascular structures. This provides valuable information about disease extent and surgical options. Due to their ability to obtain brushings from as well as stent across strictures within the biliary tree, ERCP and/or PTC offer both diagnostic and therapeutic value in the workup and management of biliary obstruction; however, the diagnostic yield on cytology obtained from biliary brushings is notoriously suspect with sensitivities and specificities of roughly 50% being the norm.
■EUS may be useful in visualizing the extent of tumor and lymph node involvement of distal bile duct lesions. Its role in proximal bile duct lesions is less clear.
■PET scan is used to identify metastatic disease which could alter surgical management.
Pathology
■Adenocarcinomas account for 90% to 95% of tumors. The remainder is squamous cell carcinomas. They are graded as well, moderately and poorly differentiated, and are further divided into sclerosing, nodular, and papillary subtypes. Patients with papillary tumors present with earlier disease and have the highest resectability and cure rates; however, they are unfortunately the least common of the three subtypes.
■Immunohistochemical staining with cytokeratins 7 and 20 can help differentiate intrahepatic cholangiocarcinoma (CK7+, CK20–, CDX2–) from colorectal metastatic lesion (CDX2+, CK20+).
Staging
■The AJCC has developed the staging systems for cholangiocarcinomas. The TNM staging system is primarily based upon the extent of ductal involvement by the tumor.
■Previously, intrahepatic cholangiocarcinomas were staged identical to hepatocellular carcinoma. In the seventh edition of the AJCC Staging Manual, however, there is a new staging system independent of the one used for HCC. This revised system was validated by a study showing improved survival predictability correlating with the new TNM system.
■The seventh edition staging system for extrahepatic cholangiocarcinomas separates perihilar and distal bile duct tumors. These changes have improved the prognostic stratification of the TNM staging system. Please refer to the seventh edition AJCC Staging Manual for details.
■Cancers arising in the perihilar region have been also further classified according to their patterns of involvement of the hepatic ducts, the Bismuth-Corlette classification (Table 6.3).
Treatment
Surgery
Except in the case of distal common bile duct cancer, cholangiocarcinoma is a disease that, when managed surgically, often times requires major hepatic resection (segmentectomy, anatomic lobectomy, trisegmentectomy) with or without bile duct resection/reconstruction. Therefore, the general principles of such resection(s) should be reviewed.
From the standpoint of major hepatic resection, the surgical principles are simple and revolve primarily around leaving the patient with an adequate volume of a functioning liver remnant to sustain them postoperatively. This requires executing an operation that ensures both adequate inflow to (hepatic artery and portal vein) and outflow from (hepatic vein and bile duct) the remnant liver.
Generally speaking, roughly 75% of a patient’s liver volume can safely be resected; however, consideration must be given to the health of the background liver. Such consideration includes underlying chronic liver disease (hepatitis, prior alcohol use, steatosis/steatohepatitis) as well as any acute insults, which in the case of cholangiocarcinoma often times involves cholestasis. The former issues can limit the extent of resection that can safely be performed, while the latter often times necessitates preoperative delays while the cholestatic picture resolves.
If there is any concern about the adequacy of the planned future liver remnant, portal vein embolization on the side of the liver that is anticipated to be resected can be performed in an attempt to allow the contralateral side to hypertrophy preoperatively.
Intrahepatic Cholangiocarcinoma
■Surgery is the only potentially curative therapy for patients with intrahepatic cholangiocarcinoma; however, most patients present with advanced disease and are not surgical candidates.
■Multiple hepatic tumors, regional lymph node involvement, large tumor size, and vascular invasion predict poor recurrence-free survival postresection.
■The extent of surgery is dictated by what is necessary to obtain clear margins. R0 resection with 1 cm margins is the aim and is ultimately associated with significantly longer survival rates that can range from 30% to 67%.
■If microscopic positive tumor margins (R1) or residual local disease (R2) is noted after resection, patients should be evaluated for possible re-resection versus chemoradiation options.
■The role of routine nodal dissection in the management of intrahepatic cholangiocarcinoma is debated, although it is agreed upon that lymph node status dose carry prognostic significance.
■In laparotomy, thorough assessment of the intra-abdominal lymph node basins should be undertaken prior to hepatic resection, suspicious nodes should be biopsied, and attempts at resection should be aborted if nodal metastases are confirmed intraoperatively.
Distal Cholangiocarcinoma
■Primarily treated with a Whipple procedure (pancreaticoduodenectomy).
Perihilar Cholangiocarcinoma
■The main curative therapy for patients with extrahepatic perihilar cholangiocarcinoma is complete surgical resection.
■Surgery for extrahepatic hilar cholangiocarcinomas is based on the stage of disease, and the goal of surgical intervention is to obtain a tumor-free margin (Table 6.4).
■For patients with hilar cholangiocarcinoma, bile duct resection alone leads to high local recurrence rates. Hilar resection with lymphadenectomy and en bloc liver resection and biliary reconstruction are recommended for lesions in the extrahepatic biliary tree. Caudate resection is often required to achieve an R0 resection, particularly for tumors involving the left hepatic duct.
■Five-year survival rates range from 20% to 40% in patients treated with surgical resection for hilar cholangiocarcinoma.
■Liver transplantation is the only other potentially curative option for patients with extrahepatic cholangiocarcinoma and can only be recommended in highly select patients when combined with an intensive pretransplant regimen of chemo/radiation therapy.
Locoregional Therapies
■The role of local therapy (radiofrequency or cryoablation) in the management of intrahepatic cholangiocarcinoma is limited due to the often-large-size and multicentric nature of the tumor(s) at the time of their discovery.
■Regional approaches to intrahepatic cholangiocarcinoma are viable alternatives in cases where surgical resection is not possible. The approach with the most robust experience to date involves transarterial chemoembolization (TACE) with gemcitabine in combination with cisplatin, oxaliplatin, or mitomycin C. Selective internal radiation therapy (SIRT or Y90) is an option that lacks long-term follow-up data.
Adjuvant Chemotherapy and Chemoradiation
■The role of adjuvant therapy remains poorly defined. Due to the low incidence of biliary tract cancers, most trials represent single institution phase II trials. A large retrospective analysis using the SEER database revealed 2,325 patients in the surgical cohort from 1992 to 2002, of which only 17% received adjuvant chemoradiation.
■A phase III trial evaluated adjuvant chemotherapy in patients with resected pancreaticobiliary cancer. Fifty percent of these patients had gallbladder cancer of cholangiocarcinoma and they were randomly assigned to either 5-FU/mitomycin C or a control arm. Analysis revealed that adjuvant chemotherapy resulted in a significant improvement in the 5-year survival of only those patients with gallbladder cancer.
■Recommendations for fluoropyrimidine-based or gemcitabine-based chemotherapy or fluoropyrimidine-based chemoradiotherapy generally represent an extrapolation of data from studies in patients with advanced disease.
■No consensus recommendations for adjuvant therapy in individuals with intrahepatic cholangiocarcinoma and negative surgical margins with no involved lymph nodes.
Chemotherapy in Advanced-Stage Disease
■In patients with unresectable locally advanced disease or resected disease with positive margins there have been reports of improved survival with chemotherapy or combined-modality chemoradiotherapy. This survival benefit was first suggested in a trial comparing 5-FU, leucovorin, and etoposide to best supportive care.
■Definitive evidence from phase III studies to support this practice, however, remains lacking.
■A number of chemotherapy combinations as well as single agents have been evaluated in clinical studies. Examples of combinations that have demonstrated activity in phase II trials include gemcitabine and cisplatin, gemcitabine and capecitabine, gemcitabine and oxaliplatin, capecitabine and oxaliplatin, capecitabine and cisplatin, and 5-FU and cisplatin.
■Of the combinations listed above, the combination of gemcitabine with a platinum-based agent had the greatest benefit. A most recent study demonstrated that this combination significantly improved overall survival (11.7 months vs. 8.1 months) and progression-free survival (8.0 months vs. 5.0 months) compared to gemcitabine alone. Based on this study, gemcitabine and cisplatin are considered to be the standard of care.
Chemoradiation in Advanced Disease
■In locally advanced disease, radiation with or without chemotherapy may ameliorate painful symptoms and contribute toward biliary decompression and may even improve overall survival.
■The most extensively investigated and hence recommended agents to be used concurrently with radiation therapy have been 5-FU and capecitabine. Gemcitabine is not recommended for concurrent chemoradiation therapy.
■Treatments should be restricted to individuals without evidence of metastatic disease.
Targeted Therapy
■A phase 2 study has shown erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor, to have efficacy in a small study of previously treated and chemo-naive patients with biliary cancer.
■Erlotinib plus bevacizumab combination was addressed in a phase II study with 53 patients with advanced biliary tract cancer. Combination therapy resulted in a median response duration of 8.4 months, a median time to progression of 4.4 months, and a medial overall survival of 9.9 months. Stable disease was documented in 51%. Randomized trials will be needed for further evaluation of these agents in combination.
■GEMOX plus bevacizumab, GEMOX plus erlotinib, GEMOX plus cetuximab: These combinations of therapy were recently shown to be effective in separate phase II trials. They will need to be compared to GEMOX alone to determine the significance of the targeted therapy compared to the toxicity profile associated with them.
Palliation
■Patients with unresectable or metastatic disease may benefit from palliative surgery, radiation, chemotherapy, or a combination of these.
■Biliary drainage can be achieved by Roux-en-Y choledojejunostomy, bypass of the site of obstruction to left or right hepatic duct, or endoscopic or percutaneously placed stents (metal-wall stents have a larger diameter and are less prone to occlusion or migration and are preferably used in patients with a life expectancy of greater than 6 months and/or in those who have unresectable disease).
■Photodynamic therapy is another option for patients with locally advanced inoperable disease. This involves injecting a porphyrin photosensitizer and then endoscopically applying light to the tumor. Although the data are derived from small studies to support this practice, the survival benefit derived from photodynamic therapy appears impressive with one report showing an improvement in median survival of 14 months.
■Celiac plexus blockade may also ameliorate symptoms of pain in the patient with inoperable disease.
REVIEW QUESTIONS
1.A 53-year-old woman with a history of hypertension and hypothyroidism presented to the ER with complaints of right upper quadrant discomfort for the past 3 to 4 days. The pain is nonradiating and is described as dull in nature. She stated there was no correlation with her diet; however, the patient does admit to a decreased appetite over the past 2 weeks. She also noted an unintentional 12 lb weight loss over this same period of time. She is afebrile. Physical examination reveals tenderness to the right upper quadrant, no jaundice and ascites noted. Labs: WBC 8.6 thou/µL, hemoglobin 14.4 g/dL, Platelet count was 232 thou/mL, AST 28 units/L, ALT 41 units/L, total bilirubin 1.1 mg/dL, and alkaline phosphatase was 77 units/L. RUQ ultrasound revealed a thickened gallbladder wall. No evidence of cholelithiasis. The bile duct diameter was estimated to be 6 mm. The patient was initially sent home with a short course of antibiotics, however returned within 48 hours with worsening pain and persistent nausea. CT abdomen and pelvis was nonrevealing. MRCP revealed a small polyp within the posterior aspect of the gallbladder wall. The patient underwent a cholecystectomy the following morning. Few gallstones were noted within the gallbladder. A small polyp was seen at the posterior aspect of the gallbladder wall. Pathology revealed a well-differentiated adenocarcinoma consistent with gallbladder cancer. The tumor invaded the lamina propria; however, there was no evidence of muscle layer involvement. Tumor margins were negative. On review of prior CT scan, no lymph nodes were noted within the abdomen or pelvis. What is the next best step in the management of this patient?
A.Initiate chemotherapeutic treatment with gemcitabine/cisplatin
B.Observation
C.Intraoperative staging with possible extended cholecystectomy
D.Hospice discussion with patient and family
2.A 66-year-old man with no significant medical history is admitted to the hospital with right upper quadrant pain, low-grade fevers and worsening jaundice for the past 3 to 4 weeks. On further discussion, the patient states he has unintentionally lost 10 lbs over the same time period; however, he believes he has likely lost approximately 30 lbs over the past 3 months. Temperature: 37.9° C. Physical examination revealed a significantly jaundiced male who appeared to be in mild distress secondary to pain. No masses were appreciated in the abdomen or right upper quadrant in particular; however, the patient did display increased tenderness to palpation over the right upper quadrant and mid epigastric region. The remainder of the physical examination was unremarkable. Blood work revealed abnormal liver function tests. Alkaline phosphatase was elevated to 381 units/L. Total bilirubin was 7.2 mg/dL with direct bilirubin 6.6 mg/dL. AST and ALT were both at the upper limits of normal levels. WBC was mildly elevated to 12.0 thou/µL with a normal differential. CEA and CA 19-9 were normal. AFP was normal. RUQ units/S revealed the common bile duct to be dilated to 1.8 cm. There was no direct evidence of cholelithiasis. CT scan of the chest, abdomen, and pelvis confirmed the common bile duct dilatation but also revealed a distal ductal mass as the likely source of the obstruction. Imaging also revealed diffuse abdominal lymphadenopathy. An ERCP was performed and brush cytology from the distal portion of the common bile duct was consistent with a poorly differentiated adenocarcinoma. During laparoscopic staging, the tumor appeared to involve the head of the pancreas as well as the gallbladder. It also appeared to be wrapped around the base of the celiac axis. The tumor at this time was determined to be unresectable. A biliary stent was placed for symptomatic control. What is the next best step in the management of this patient?
A.Surveillance
B.Initiate single agent chemotherapy with gemcitabine
C.Begin combination chemotherapy with gemcitabine and cisplatin
D.Neoadjuvant chemoradiation with gemcitabine
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