Dual diagnoses: Gallstone ileus and squamous cell carcinoma of the gallbladder

Surgical Rounds®, November 2007, Volume 0, Issue 0

Sonny S. Wang, Chief Resident in General Surgery, Department of Surgery; Philip J. Katzman, Associate Professor of Pathology and Laboratory Medicine, Department of Pathology; Luke O. Schoeniger, Associate Professor of Surgery and Oncology, Department of Surgery, Division of Surgical Oncology, University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY

Sonny S. Wang, MD

Chief Resident in

General Surgery

Department of Surgery

Philip J. Katzman, MD

Associate Professor of

Pathology and

Laboratory Medicine

Department of Pathology

Luke O. Schoeniger, MD, PhD

Assistant Professor of

Surgery and Oncology

Department of Surgery

Division of Surgical

Oncology

University of Rochester

Medical Center

Strong Memorial Hospital

Rochester, NY

Introduction: Gallstone ileus is a rare cause of nonstrangulated bowel obstruction. It results when there is fistulization between the gallbladder and the gastrointestinal tract, and it is usually found in patients with a history of cholecystitis. Squamous cell carcinoma of the gallbladder (SCCG) is rarer than gallstone ileus and has a poorer prognosis than the more common adenocarcinoma of the gallbladder.

Results and discussion: This paper describes the case of a 75-year-old woman who presented to the hospital with signs and symptoms of gallstone ileus and a liver mass. The patient underwent a one-stage procedure consisting of enterolithotomy, cholecystectomy, and cholecystoduodenal fistula excision and repair. A wedge resection of the liver mass was also performed.

Conclusion: Pathology identified two nodules of tumor in the body and neck of the patient's gallbladder as SCCG; the hepatic lesion was determined to be either metastasis or direct extension of the gallbladder tumor. The presence of large gallstones, which this patient was known to have, is considered a risk factor for SCCG. Although there is some controversy over treating such patients with a one-step procedure, the patient in this case had a positive outcome.

Gallstone ileus reportedly accounts for 25% of nonstrangulated bowel obstructions in patients older than 65 years.1 This rare mechanical bowel obstruction is seen in less than 1% of patients identified as having gallstones.1 It is atypical to find gallstone ileus in the setting of squamous cell carcinoma of the gallbladder (SCCG). SCCG is an aggressive tumor that makes up only 1% to 12% of all gallbladder cancers and generally has a poorer outcome than adenocarcinoma of the gallbladder.2 We were able to diagnose our patient's gallstone ileus preoperatively, and a postoperative pathology examination identified the SCCG.

A 75-year-old African American woman presented to the hospital with a 3-day history of colicky midepigastric abdominal pain, which was accompanied by intermittent nausea and abdominal distention. She reported no recent emesis, fever, or chills, and had continued to pass flatus until 24 hours before her presentation. The patient's abdomen was tender to palpation at the right- to mid-periumbilical region. Her history was notable for a poor appetite and an unintentional 50-lb weight loss over the previous 4 years. Her medical history was significant for cholelithiasis, congestive heart failure, type 2 diabetes mellitus, and an open appendectomy in the distant past.

On physical examination, the patient had stable vital signs, with a temperature of 37.6°C, heart rate of 95 beats per minute, blood pressure of 116/50 mm Hg, and respiratory rate of 18 breaths per minute. No clinical jaundice was observed. Significant laboratory values included a white blood cell count of 17.1 x 109/L (normal, 4.5—11.0 x 109/L), hematocrit of 28% (normal, 35%—45%), platelet count of 442 x 109/L (normal, 150?450 x 109/L), blood urea nitrogen of 7.85 mmol/L (normal, 2.9—8.2 mmol/L), creatinine of 124 ?mol/L (normal, 53—106 ?mol/L), total bilirubin of 6.84 ?mol/L (normal, 5—21 ?mol/L), aspartate aminotransferase of 14 U/L (normal, 20?48 U/L), alanine aminotransferase of 15 U/L (normal, 10—40 U/L), and alkaline phosphatase of 81 U/L (normal, 50—120 U/L).

Ultrasonography of the right upper quadrant demonstrated gallstones, a thickened gallbladder wall, intrahepatic ductal dilatation, and a dilated common bile duct that measured 1.8 cm. Computed tomography (CT) scanning of the patient's abdomen and pelvis confirmed the ultrasonography findings (Figure 1). A right hepatic lobe lesion that measured 3.7 x 2.1 cm was also seen; this lesion was not observed on a CT scan taken 4 months earlier. A large gallstone in the distal ileum was visualized, and a diagnosis of gallstone ileus was made.

The patient underwent an exploratory laparotomy for gallstone ileus. After entering the abdomen, we palpated a large gallstone in the distal ileum, which was removed through a proximal enterotomy. The stone was faceted. We biopsied the liver mass (segment V), and this revealed poorly differentiated adenosquamous carcinoma. The gallbladder appeared chronically inflamed, and we observed additional residual, large gallstones, but no gross mass was palpated. The intraoperative differential diagnosis included a primary hepatic malignancy because we observed no evidence of any masses, ascites, or lymphadenopathy outside of the liver. We thought that the patient's cholecystoduodenal fistula was attributable to gallstones and chronic cholecystitis and did not suspect gallbladder cancer.

Our patient remained hemodynamically stable during the entire operation, which allowed us to perform a one-stage procedure consisting of enterolithotomy, cholecystectomy, and cholecystoduodenal fistula excision and repair. A wedge resection of the liver mass was also performed. On running the entire small intestine, we found another large gallstone in her proximal jejunum, which was removed through a separate enterotomy. The patient lost less than 200 cc of blood and was extubated after the surgery was completed.

Pathology found two nodules of tumor, whose greatest dimensions were 4.5 cm and 1.0 cm, respectively, in the body and neck of the gallbladder (Figure 2A). The liver lesion, which was 4.5 cm at its greatest dimension, could represent metastasis or direct extension of the gallbladder tumors (Figure 2A). Two multifaceted gallstones were present in the gallbladder (Figure 2B). Microscopically, the gallbladder lesion was a poorly differentiated SCCG, with invasion into the gallbladder subserosa and angiolymphatic system, which may have resulted from squamous metaplasia (Figure 3).

The poor differentiation of our patient's tumor lends itself to scrutiny of being a mixed adenosquamous-cell carcinoma. Early descriptions of SCCG were of the well-differentiated keratinizing variety.3 The identification, however, of squamous metaplasia, dysplasia, or carcinoma in situ associated with SCCG, as it was in this case, was useful in making this rare diagnosis and excludes the more common adenocarcinoma.4

Postoperatively, the patient received a short course of perioperative antibiotic to prevent intra-abdominal infection, and her postoperative pain was managed through patient-controlled analgesia. She received total parenteral nutrition until postoperative day 7, when an upper gastrointestinal study revealed no leak at the duodenal repair and her diet was advanced. A postoperative chest CT scan revealed no radiographic evidence of pulmonary metastases. The patient was discharged from the hospital on postoperative day 14. Although her recovery from surgery was uneventful, she died from hypercalcemia 7 months later. None of her follow-up bone scans or CT scans had demonstrated recurrence, osseous or otherwise.

Discussion

Gallbladder cancer is the fifth most common gastrointestinal malignancy in the United States. The incidence increases after the fifth decade of life, with a reported incidence of 1.2 cases per 100,000 persons annually.5 Adenocarcinoma is the most common gallbladder malignancy, and SCCG accounts for very few cases. The presence of large gallstones is known to be a risk factor for developing gallbladder cancer.

Squamous cell carcinoma of the gallbladder

Most literature records SCCG as accounting for approximately 1% of all gallbladder malignancies.6-8 To date, more than 146 cases of SCCG have been reported in the English-language literature.4 The majority of these rare tumors occur in older women, with a female predominance of 3:1.2

SCCG is an invasive and aggressive tumor that has a high incidence of local infiltration and hepatic metastases. Patients with these tumors are considered to have a worse prognosis than those with adenocarcinoma of the gallbladder. Some researchers have suggested that this histological tumor may arise from squamous differentiation of adenocarcinoma of the gallbladder.

Surgical treatment of SCCG consists of cholecystectomy with wedge resection of adjacent liver tissue or direct liver resection combined with regional lymphadenectomy and skeletonization of the hepatic hilum. Radiotherapy and chemotherapy are considered palliative treatments. Prognosis without radical surgery is poor, with patients surviving an average of 6 months.2,9 Oohashi and colleagues retrospectively reviewed 29 gallbladder cancer cases, of which 28 involved adenosquamous carcinoma and 1 involved SCCG.10 Based on their analysis, patients who underwent radical cholecystectomy with extended resection and regional lymphadenectomy had an increase in median survival to 18 months. Residual tumor status was their only significant independent prognostic factor.

Gallstone ileus

Gallstone ileus is a fistulization between the gallbladder and the gastrointestinal tract. It is usually found in patients who have a history of cholecystitis. Stones larger than 2.5 cm may lodge in the distal ileum (60.5%), jejunum (16.1%), stomach (14.2%), colon (4.1%), or duodenum (3.5%).1 Patients usually present with a "tumbling" course of intermittent bowel obstruction as the stone passes slowly into the distal bowel and becomes lodged at the terminal ileum. Gastric outlet obstruction may also occur when a large gallstone passes into the duodenal bulb through a biliogastric or bilioduodenal fistula. This has been described as Bouveret's syndrome. Endoscopic lithotripsy with stone extraction has been reportedly successful at treating Bouveret's syndrome.11 Our patient's large gallstones predisposed her to getting gallbladder cancer. The combination of gallstones and gallbladder cancer likely led to chronic cholecystitis and the development of gallstone ileus.

Enterolithotomy is the standard operative treatment for gallstone ileus. There is controversy over whether cholecystectomy and the resultant duodenal fistula repair are beneficial. Comorbidities and hemodynamic instability at the time of surgery, which are often found in patients with this disease, force surgeons to operate quickly.12 In the largest retrospective review to date, consisting of 1,001 patients, Reisner and Cohen promoted simple enterolithotomy as a safe and effective management for gallstone ileus.1 Their study found that recurrence of gallstone ileus after enterolithotomy was less than 5%, and only 10% of their patients required reoperation for biliary tract symptoms. Concerns over recurrent cholecystitis, cholangitis, gallstone ileus, and the risk for gallbladder cancer have resulted in controversy among proponents of a one-stage procedure consisting of enterolithotomy, cholecystectomy, and cholecystoenteric fistula repair. Tan and associates retrospectively compared 19 patients who were treated urgently for gallstone ileus and found that in their one-stage surgical group (n=12), patients had lower American Society of Anesthesiology grades, no preoperative hypotension or shock, and no mortality.13 This study, however, still recommended enterolithotomy as the surgery of choice because it is less demanding technically, requires less operative time, and has no delayed complications from a remnant fistula. Rodriguez-Sanjuan and colleagues retrospectively reviewed 35 patients with gallstone ileus and concluded that a one-stage procedure resulted in slightly higher morbidity, mortality, and reoperation rates.14 Their study could not support a one-stage procedure as an operation of choice for patients with gallstone ileus, but they suggested it might be acceptable for low-risk patients. A retrospective review of 34 patients treated for gallstone ileus found that all three patients who underwent one-stage procedures survived.15 In our patient's case, the presence of a faceted stone, which was extracted by enterolithotomy, suggested the need to search for other stones and to perform a cholecystectomy for residual cholelithiasis.

Conclusion

Our patient's case was unconventional because she presented with gallstone ileus and underlying metastatic SCCG. Despite her advanced age and comorbidities, she tolerated a one-stage procedure well. This case adds to the body of literature confirming successful management using a one-stage procedure of gallstone ileus in the setting of SCCG.

Disclosure

The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article and attest that the data meet the requirements for informed consent and for the Institutional Review Boards.

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