Journal of the Royal Society of Medicine Volume 84 February 1991

Adenocarcinoma of the gallbladder- a 5 of outcome in Newcastle upon Tyne



P Burgess MD FRCS P D Murphy PhD FRCS M B Clague MD FRCS Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE

Department of Surgery,

Keywords: gallbladder; adenocarcinoma; in situ carcinoma

Summary Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were detected after routine cholecystectomy. Laparotomy was performed in 21 patients (72%) of which only 14 patients had a cholecystectomy performed. Mean survival after surgery was 6.6 months with only one patient alive after 5 years. Metastatic disease was present in 72% of patients. The poor prognosis of carcinoma of the gallbladder reflects its late diagnosis and early metastasis to distant sites. Improvement in survival will depend upon early detection of in situ lesions and identification of at risk patients. Introduction Carcinoma of the gallbladder, the fourth commonest upper gastrointestinal malignancy, is associated with a poor prognosis due to late diagnosis. Early identification of in situ lesions is due to providence at elective cholecystectomy. The majority ofpatients are elderly, presenting with obstructive jaundice of short duration. Operative procedures are often palliative and may not significantly affect the disease outcome in the majority of patients.

Methods All patients diagnosed histologically as having carcinoma of the gallbladder during the 5-year period 1980-1985 were identified via Regional Health Authority compilations of Hospital Activity Analysis returns from the three main hospitals serving Newcastle upon Tyne Health District. Case notes were retrieved and the presentation and management of the patients reviewed. Results

During the 5 year period studied, 29 patienta were identified (18 female, 11 male) as having had carcinoma of the gallbladder. Patients had a mean age of 74 years (range 49-90 years) at time of diagnosis. Presentation was varied, but symptom duration prior to diagnosis was short with a mean of 6 weeks. Eighteen patients (62%) presented with jaundice, 11 patients (38%) had a palpable mass, only eight (28%) had abdominal pain on diagnosis. A correct preoperative diagnosis was made in only two patients (7%), both by ultrasonographic examination. In eight patients (28%) the diagnosis was only confirmed after postmortem examination.

Of the 29 patients, 21 (72%) underwent laparotomy (Table 1). Two patients were found to have carcinoma of the gallbladder after elective cholecystectomy for cholelithiasis. Cholecystectomy was performed in 14 patients (67%). A biliary by-pass procedure was necessary in eight patients (38%). Eight patients had no operative procedure performed in whom the diagnosis was confirmed by subsequent postmortem examination. There was a high incidence of metastatic disease in the group. Twenty-one patients (72%) had metastatic carcinoma confirmed at operation or postmortem. In 51% of patients, tumour spread was restricted to liver and local lymph nodes. In 21% of patients there was widespread distant metastases to pancreas, lung and adrenal glands. One patient presented with acute spinal cord compression due to metastatic deposits of the dorsal spine. Two patients had cutaneous metastases at the time of diagnosis. Preoperative investigation was by ultrasound examination in 16 patients, computerized axial tomography was performed in four patients. In only 10 patients (34%) were gall stones identified as being coincidentally present with the tumour. Endoscopic retrograde cholangiopancreatography (ERCP) was attempted in four patients. Overall survival after diagnosis is shown in Table 2. The mean value was 4.3 months for all patients and 6.6 months for those undergoing surgery. Histology of the primary tumour was shown to be an adenocarcinoma in 28 patients. One patient had a non-keratinizing squamous cell tumour. There appeared to be no correlation between the degree of differentiation of the primary tumour and the presence of metastases or subsequent survival. However, the single patient identified as having an in situ mucosal lesion, was still alive after 5 years. Only one patient received adjuvant radiotherapy postoperatively, in whom a preoperative diagnosis of gallbladder cancer had been made on ultrasound examination. In this case, survival following diagnosis was 15 months. Subsequent postmortem examination revealed widespread metastases, including adrenal gland deposits. Review of haematological investigations performed on admission showed an erythrocyte sedimentation rate (ESR) had been estimated on 17 patients at the time of diagnosis. Of th:ese 13 (76%) had values over 40 mm/h and in four (23%) the ESR was over 90 mm/h. Both patients who had been found to have carcinoma of the gallbladder after routine elective cholecystectomy had ESR values over 40 mm/h preoperatively.


020084-03/$02.00/0 © 1991 The Royal Society of


Journal of the Royal Society of Medicine Volume 84 February 1991 Table 1. Carcinoma of gallbladder - operative procedures performed

Patient 1 2 3 4 5

6t 7

8tt 9 10* 11* 12 13$

14" 15* 16 17 18* 19 20t 21

Survival from -date of diagnosis

Age (years) Procedure 81 70 60 79 84 55 71 74 74 73 75 90 67 56 75 74 82 80 73 49 74

Cholecysto-jejunostomy None Cholecystectomy Cholecystectomy+T-Tube drainage Cholecystectomy+T-Tube drainage Cholecystectomy, choledochoduodenostomy Cholecystectomy+stenting of common bile duct Gastroenterostomy Cholecystectomy+stenting of common bile duct T-Tube drainage of common bile duct only Cholecystectomy, choledochoduodenostomy Ileo-colic anastomosis Cholecystectomy+wedge resection of liver Cholecystectomy Liver biopsy Cholecystectomy, choledochoduodenostomy Cholecystectomy Biopsy only Cholecystectomy+T-Tube drainage Cholecystectomy Cholecystectomy

1 month 1 month 5 months 1 month 2 weeks 19 months 9 months ;3 weeks 2 months 3 months 6 months 1 month 1 month Alive at 5 years 1 month 3 years 1 month 2 weeks 4 months 5 months 15 months

tElective cholecystectomy for gall stones ttPresented with pyloric stenosis *ERCP performed prior to surgery $Asymptomatic gallbladder carcinoma detected at abdomino-perineal resection for rectal tumour "In situ carcinoma in gallbladder removed for pancreatitis Table 2. Survival after diagnosis of carcinoma of the gallbladder Survival 3 6 1 5

months months year years

Patients alive 10 6 4 1

(34%) (21%) (14%) (3%)

Mean survival: 4.3 months

Discussion Survival after diagnosis of carcinoma of the gallbladder is extremely poor unless the primary lesion is confined to the mucosa. Similar survival rates to this study have been reported' with post-resection 5-year survival rates less than 5% unless the tumour is confined to the mucosa, when a 64% 5-year survival can be expected. Cumulative survival rates of 42.6% at 5 years have been reported2 and advocation of 'second look' procedures when apparent curative resections are undertaken. Advanced carcinoma however, is generally associated with poor survival. Few 5-year survivors have been reported3. Previous reports suggest some success in preoperative diagnosis with ultrasound examination but the investigation has a poor sensitivity rate of 44% or less4.

Identification of lesions still confined to the mucosa appears to be difficult. There is evidence that polyps within the gallbladder may be premalignant, as identified either by ultrasound or oral cholecystographic examination. Koga et aL5 identified 40 polyps in 411 consecutive cholecystectomy specimens of which eight were malignant. If larger

than 1 cm, there was an associated risk of malignancy of 88%. In patients over 60 years of age there was a 75% chance of an identified polyp being malignant. Prevention of late presentation of the disease may be achieved by early cholecystectomy in women presenting with cholelithiasis over the age of 50 years6. In hispanic women, the incidence of carcinoma of the gallbladder appears high in younger age


Prognosis for individual patients with apparent local disease may be indicated by the mucopolysaccharide content of the tumour8. In vitro tissue culture of tumour cells can be achieved in 30% of cases and may be used as a future model to test efficacy of chemotherapeutic agents on the tumour9. For the majority of patients, surgery would appear to offer only palliative relief of obstructive jaundice or local symptoms. Only pre-malignant in situ lesions can be treated adequately with cholecystectomy alone. In such cases, radical resection is recommended where possible, including wedge resection of the gallbladder bed and portal vein reconstruction when dissection is necessary at the porta hepatis'0. There is probably a place for routine adjuvant local radiotherapy in addition to surgery, although the tumour is not particularly radiosensitive". In this study, where presentation of the disease was late, surgical intervention was not associated with any significant improvement in survival compared to untreated patients. The outcome of carcinoma of the gallbladder is influenced by its late presentation, often in elderly patients with obstructive jaundice. Metastatic spread occurs early in the disease, but if resected whilst an in situ lesion there is a good prognosis. Early detection of carcinoma of the gallbladder is unlikely to improve unless 'at risk' patients



Journal of the Royal Society of Medicine Volume 84 February 1991

are identified. Cholecystectomy should be considered for female patients over 60 years of age if a mucosal polyp is identified, particularly if found to be larger than 1 cm in size. Patients with gallbladder disease in whom an elevated ESR is detected may also represent a high-risk group. References 1 Johnson LA, Lavin PT, Dayal YY, et al. Gall bladder adenocarcinoma: the prognostic significance of histologic grade. J Surg Oncol 1987;34:16-18 2 Tsunoda T, Tsuchiya R, Harada N, Izawa K, Yamaguchi T, Yamamoto K, Motoshima K, Tomioka T, Matsuo S, Eto T. The surgical treatment of carcinoma of the gall bladder - rationale of the second-look operation for inapparent carcinoma. Jpn J Surg 1987;17:478-86 3 Athlin LE, Domellof LK, Bergman FO. Advanced gall bladder carcinoma: a case report and review of the literature. Eur J Surg Oncol 1987;13:449-53 4 Hederstrom E, Forsberg L. Ultrasonography in carcinoma of the gall bladder. Diagnostic difficulties and pitfalls. Acta Radiol 1987;28:715-18

5 Koga A, Watanabe K, Fukuyama T, Takiguchi S, Nakayama F. Diagnosis and operative indications for polypoid lesions of the gall bladder. Arch Surg 1988; 123:26-9 6 Isman H, Bourgeon R. A curative surgical approach to gall bladder carcinoma in its early stages. Ital J Surg Sci 1986;16:117-22 7 Whetstone MR, Saltzstein EC, Mercer LC. Demographic characteristics of gall bladder cancer in an area endemic for biliary calculi. Am J Surg 1986;152:728-30 8 Johnson LA, Lavin PT, Dayal YY, et al. Gall bladder carcinoma: prognostic significance of tumour acid mucopolysaccharide content. J Surg Oncol 1986;33: 243-5 9 Harris GJ, Von Hoff DD. Drug sensitivity testing of carcinoma of the gall bladder and biliary tree in a human tumour cloning assay. Cancer Drug Deliv 1986;3:197-204 10 Sakaguchi S, Nakamura S. Surgery of the portal vein in resection of cancer of the hepatic hilus. Surgery 1986;99:344-9

(Accepted 25 June 1990. Correspondence to Mr PD Murphy)

Adenocarcinoma of the gallbladder--a 5 year review of outcome in Newcastle upon Tyne.

Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. ...
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