Gallbladder Cancer

Cancer that arises in the gallbladder is uncommon. In patients whose superficial cancer is discovered on pathological examination of tissue after gallbladder removal for other reasons, the disease is often cured without further therapy. Even in patients who present with symptoms, the tumor is rarely diagnosed preoperatively. In such cases, the tumor often cannot be removed completely by surgery and is incurable, although palliative measures may benefit these patients. Cholelithiasis is an associated finding in the majority of cases, but fewer than 1% of patients with cholelithiasis develop this cancer. The most common symptoms caused by gallbladder cancers are jaundice, pain, and fever.

These patients often do poorly.: Those patients who have cancer confined to the gallbladder wall that can be completely resected represent a minority of cases of gallbladder cancer. Patients with cancers confined to the mucosa have 5-year survival rates of nearly 100%..Patients with muscular invasion or beyond have a survival of less than 15%. Regional lymphatics and lymph nodes should be removed along with the gallbladder in such patients.

The most common presenting complaint was abdominal pain, followed by jaundice and weight loss. Surgery was performed in 61 patients and of these patients, only two had accurate preoperative diagnosis which was made by ultrasonography. Twelve of the 13 patients who were treated medically had the disease diagnosed at autopsy. One of the 13 patients had the diagnosis of gallbladder cancer by the findings of ultrasonography and abdominal computed tomography (CT) scanning. The resectability of the surgically managed group was 36.1%, and the majority of patients with advanced tumors (82.2%) were deemed unresectable. The most common histologic type was adenocarcinoma. Liver was the organ most commonly invaded (76.5%) by direct extension and/or metastases, followed by regional lymph nodes (52.9%). The overall 5-year survival rate was 5.4%. A high index of suspicion of the disease, intraoperative examination of gallbladder specimen, and earlier, more aggressive surgical treatment may improve patient survival..
Some patients may benefit from postoperative radiation as noted below:

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Hepatogastroenterology 1999 May-Jun;46(27):1578-84

Gallbladder cancer: role of radiation therapy.

Houry S, Haccart V, Huguier M, Schlienger M

Department of Surgery, Tenon Hospital, University Paris VI, France.

BACKGROUND/AIMS: Gallbladder carcinoma is characterized by late diagnosis, ineffective treatment and poor prognosis. These tumors were usually considered to be radioresistant. So far, the role of radiotherapy has not been adequately evaluated. The aim of this report is to assess the value of radiotherapy in carcinoma of the gallbladder. METHODOLOGY: We reviewed all publications concerning the role of radiation therapy in gallbladder carcinoma. External radiation therapy, intra-operative radiation therapy, and brachytherapy were evaluated in two groups in which the prognosis is quite different; a group operated on, with apparent complete resection of the tumor, and a palliative surgery group. RESULTS: It appears that gallbladder carcinomas are not as radioresistant as was formerly thought. Local control of the tumor and reduction of tumor size was reported in several publications. Collected data showed a slight improvement of survival after adjuvant or palliative radiotherapy, especially in the advanced stage of gallbladder carcinomas. It appears preferable to give a "boost" (15 Gy) to the gross lesion or residual lesion at operation (intra-operative irradiation or brachytherapy), and deliver an additional 45-50 Gy post-operatively. CONCLUSIONS: The results published encourage further trials in well defined populations. Radiotherapy seems to be a safe procedure, morbidity is minimal, and a slight effect on survival is observed after curative or palliative surgical procedures.

Trop Gastroenterol 1996 Jan-Mar;17(1):22-5

Role of radiation therapy in carcinoma of the gall bladder--a preliminary indian experience.

Mehta A, Bahadur AK, Aranya RC, Jain AK

Department of Radiotherapy, L.N.J.P. Hospital and M.A.M.C., New Delhi, India.

Carcinoma of the gall bladder has a poor prognosis despite surgical resection of the tumour. We prospectively enrolled 21 patients with histologically proven adenocarcinoma of the gall bladder, who were stage III or beyond for post operative radiotherapy. Six month survival was 67% (14 of 21 patients) while one year survival was 33% (7 out of 21 patients) and five year survival was 23% (5 of 21 patients). Those patients who had residual disease or were considered inoperable at surgery had no improvement in survival. The 1 year and 5 year survival in these patients was encouraging with radiotherapy in the present open labelled study of radiotherapy in patients with carcinoma of the gall bladder.

Hepatogastroenterology 1999 May-Jun;46(27):1585-91

Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer.

Todoroki T, Kawamoto T, Otsuka M, Koike N, Yoshida S, Takada Y, Adachi S, Kashiwagi H, Fukao K, Ohara K

Department of Surgery and Radiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Japan. todorov@md.tsukuba.ac.jp

BACKGROUND/AIMS: The efficacy of combining resection and radiation in the management of advanced gallbladder cancer has not yet been defined. In this study, effects of combining radiation therapy on survival, local control and the pattern of recurrences were analyzed as a retrospective review. METHODOLOGY: From October 1976 to May 1996, 85 patients with stage IV (pTNM) gallbladder cancer underwent various aggressive resection modalities in our institute, including 34 liver resections, 30 hepatopancreaticoduodenectomies. Intra-operative, external or intracavitary radiation therapy was supplemented to resection in 47 patients. RESULTS: The 30-day operative mortality rate was 5.9% and the overall 5-year survival rate of stage IV disease patients was 6.3%; 3 patients are living well more than 6 years after surgery. Adjuvant radiotherapy yielded a significantly (p=0.0023) higher 5-year survival rate (8.9%) than resection alone (2.9%). The local control rate was significantly (p=0.0467) higher in the adjuvant radiation group than in the resection alone group (59.1% vs. 36.1%). However, there was no statistical difference in the frequency of distant metastasis between the two groups. Significant improvement (p=0.0028) of long-term survival was exhibited when radiation was used appropriately on patients with microscopic residues only. Those with macroscopic or without microscopic residues failed to improve. The 5-year survival rate and median survival time of patients receiving adjuvant radiation therapy for microscopic residues were 17.2% and 463 days, respectively. CONCLUSIONS: Adjuvant radiation therapy following aggressive resection, in certain circumstances, improves prognosis with acceptable operative mortality for stage IV gallbladder cancer.

Am J Surg 1976 Dec;132(6):703-6

Primary carcinoma of the gallbladder. The role of adjunctive therapy in its treatment.

Treadwell TA, Hardin WJ

Of forty-three patients with carcinoma of the gallbladder discovered ih a twenty-five year period (during which 10,349 patients were diagnosed as having cholelithiasis), eighteen patients (42 per cent) had no obvious tumor outside of the gallbladder at the time of operation, nineteen patients (44 per cent) had local spread of the disease, and six patients (14 per cent) had abdominal carcinomatosis or distant metastasis. In the twenty-one patients who underwent surgical therapy for cure of their disease, the five year survival rate was 33 per cent. The more extensive surgical procedures (other than cholecystectomy alone) did not significantly increase survival. Neither the duration of the symptoms nor the pathologic type of the tumor altered the eventual outcome. No patients with tumor outside the gallbladder at the time of operation survived longer than two years. Compared to those who did not receive it, the fifteen patients treated postoperatively with adjunctive therapy (radiation therapy or chemotherapy or both) lived longer and also were significantly better palliated when tumor outside of the gallbladder was found at the time of operation. From these findings, the routine use of adjunctive therapy is recommended in all patients with disease outside of the gallbladder and serious consideration should be given to its use in all patients found to have carcinoma of the gallbladder.

Strahlenther Onkol 1996 Sep;172(9):496-500

Primary carcinoma of the gallbladder: role of external beam radiation therapy in patients with locally advanced tumor.

Uno T, Itami J, Aruga M, Araki H, Tani M, Kobori O

Department of Radiation Therapy, International Medical Center of Japan, Tokyo, Japan.

BACKGROUND/AIM: Several reports have demonstrated that occasional long-term survival might be obtained with external beam radiation therapy in patients with gallbladder cancer. However, there are few reports which evaluate the local effect of irradiation. The aim of our study was to investigate the local effect of radiation therapy. and to evaluate its role for locally advanced gallbladder cancer. PATIENTS AND METHODS: Twenty-two patients with locally advanced gallbladder cancer were treated with high-dose external beam radiation therapy. Tumor resection was performed in 5 patients, palliative surgery in 5, and the remaining 12 patients were treated by radiation therapy alone. RESULTS: Overall survival was 36% at 1 year, 18% at 3 years and 14% at 5 years. All but 2 patients developed local recurrence and died of disease at 1 to 99 months after radiation therapy. Among 17 patients who had not undergone tumor resection, partial response was obtained in 4 patients and no response in 13. Survival times in patients who achieved partial response were 14, 26, 47 and 99 months, whereas those of no response were 1 to 12 months with a mean of 4.8 months. Survival between these 2 groups (partial vs. no response) showed significant difference (p = 0.0008, logrank test). CONCLUSION: It is concluded that high-dose external beam radiation therapy could improve survival in some patients with unresectable gallbladder cancer.

Radiat Med 1991 Nov-Dec;9(6):241-3

High-dose-rate intraluminal brachytherapy for postoperative residual tumor of gallbladder carcinoma: a case report.

Kurisu K, Hishikawa Y, Taniguchi M, Kamikonya N, Miura T, Kanno H, Okamoto E

Department of Radiology, Hyogo College of Medicine, Japan.

The case of a patient with gallbladder carcinoma who had a postoperative residual tumor treated with high-dose-rate intraluminal brachytherapy (HDRIBT) and external radiotherapy (ERT) is presented. HDRIBT (20 Gy/2 fr) was performed at one point 10 mm from the 60Co source on 27 and 34 days after simple cholecystectomy. ERT (30 Gy/15 fr) was also given two weeks after HDRIBT. Following radiotherapy, she has been alive and well without signs of recurrence for one year and ten months as of this writing. HDRIBT combined with ERT is recommended for the treatment of post-operative residual tumors of advanced gallbladder carcinomas.

Radiat Med 1983 Oct-Dec;1(4):326-9

Radiotherapy of carcinoma of the gallbladder.

Hishikawa Y, Tanaka S, Miura T

Thirteen patients with carcinoma of the gallbladder were treated with radiation therapy using Cobalt-60 or 10 MV X-ray. The total dosage ranged from 16 Gy to 54 Gy. Eight patients were treated for palliation, three patients had post-operative irradiation and two patients were treated for recurrence after surgery. Palliation was achieved in six of the eight patients (75%). The results of our series of tests together with other reports suggest radiotherapy can contribute to palliation and post-operative irradiation as an adjunctive treatment.

Indian J Pathol Microbiol 1989 Jul;32(3):146-51

Primary carcinoma of gall bladder--a review of thirty six cases.

Kaul V, Wani NA, Paljor YD

Majority of patients were found to be middle aged females (24 out of 36 cases). Most common presenting symptom was abdominal pain and duration of symptoms was two months or less in majority of cases. Gall stones were found in 55.5% cases. Diagnosis of primary gall bladder carcinoma was an incidental histopathological finding in 22% patients. Well differentiated adenocarcinoma was found to be the commonest type of malignancy (77.7%). 33% cases had widespread metastatic disease at the time of operation and liver was the commonest site of invasion (47.2%). Follow up records of 21 out of 36 patients available show only two patients to be alive till date with more than two year follow up and in both these cases carcinoma was an incidental histopathological diagnosis at cholecystectomy. Rest of the patients had died within 5-6 months after surgery. This reinforces the poor outcome for primary gall bladder carcinoma patients irrespective of treatment unless diagnosed and treated at a very early stage. Long term survival can be expected in incidentally found carcinoma at cholecystectomy.