Annals of Surgical Oncology 15(11):3132–3137

DOI: 10.1245/s10434-008-9917-y

A New Scoring System for Gallbladder

Cancer (Aiding Treatment Algorithm):
An Analysis of 335 Patients

Parul J. Shukla, MS, FRCS,1 Rakesh Neve, MS,1 Savio G. Barreto, MS,1
Rohini Hawaldar, BSc, DCM,2 Mandar S. Nadkarni, MS, DNB, MNAMS,1
K. M. Mohandas, MD, DNB,3 and Shailesh V. Shrikhande, MS, MD1

1
Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai 400 012, India
2
Clinical Research Secretariat, Tata Memorial Hospital, Parel, Mumbai 400 012, India
3
Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Parel, Mumbai 400 012, India

Background: There is currently no preoperative staging/scoring system available for gall-

bladder cancer. Unfortunately, in gallbladder cancer, patients manifest advanced stages of the
disease. There is need for a methodology that can aid accurate preoperative staging and the
subsequent treatment algorithm. We thus sought to validate a new scoring system, the Tata
Memorial Hospital Staging System (TMHSS), for gallbladder cancer.
Methods: TMHSS is based on the cumulative impact of specific features of computed
tomographic scan, presence or absence of jaundice, and serum cancer antigen 19–9 levels. This
scoring system was first proposed in 2004. Patients with gallbladder cancer were enrolled onto
the testing sample for TMHSS to ascertain its validity. A total of 335 consecutive patients with
gallbladder cancer who sought care at the Tata Memorial Hospital between May 1, 2005, and
December 31, 2006, were studied. Treatment was suggested on the basis of current existing
protocols. Each patient was assigned a TMHSS score, and the treatment decision taken was
compared with the algorithm generated for each individual score. Concurrence of the decision
taken with the score generated algorithm was tested by the Kendall tau-b test.
Results: Ordinal-by-ordinal analysis of the value of the test was .75, which showed excellent
concurrence and a statistically significant P value (P \ .0001).
Conclusion: TMHSS provides an excellent correlative treatment plan for patients with
gallbladder cancer. It has the potential to reduce unnecessary surgical explorations and to
direct patients to the ideal treatment strategy, thereby offering a degree of prognostication.
Key Words: Gallbladder—Scoring—Outcomes—Management—Cancer.

Gallbladder cancer remains a difficult malignancy
to treat, primarily because of the poor prognosis
associated with it.1 The only modality of treatment
offering a potential of long-term survival remains
radical surgery (except for T1a tumors).1,2 Chemo-
therapy and radiotherapy have limited applications
Published online May 6, 2008.
Address correspondence and reprint requests to: Parul J. Shukla,
MS, FRCS; E-mail: pjshukla@doctors.org.uk
Published by Springer Science+Business Media, LLC Ó 2008 The Society of
Surgical Oncology, Inc.
and modest benefits.3,4 In many patients who are
offered radical surgery, the disease is found to be too
extensive to permit adequate resection, which results
in patients undergoing an unnecessary surgical
exploration.5 It would be a great help if a preopera-
tive guide existed that facilitated clinical decision
making for patients with gallbladder cancer so such
exploration would be unnecessary.
The currently available staging systems for gall-
bladder cancer include the tumor, node, metastasis
staging system,6 the modified Nevin stating system,7

3132
 NEW SCORING SYSTEM FOR GALLBLADDER CANCER 3133

the Japanese Biliary Surgical Society System,8 and TABLE 1. Tata Memorial Hospital scoring system for
the Bartlett9 staging system. They are all based on gallbladder cancer
histopathological examination of a cholecystectomy Characteristic Score
specimen and do not have the potential to provide
CA 19-9 levels (U/mL) 1–4
useful preoperative information that would permit 0–30 1
management. 30–90 2
At the World Congress of the International Hep- 90–450 3
[450 4
ato-Pancreato-Biliary Association in 2004,10 we pro- Serum bilirubin levels (mg/dL) 0–2
posed a new scoring system, the Tata Memorial \3 0
Hospital Scoring System (TMHSS), for gallbladder [3 2
Computed tomographic scan featuresa 0–4
cancer, which is based on radiological, clinical, and Normal 0
biochemical features. The rationale behind this Gallbladder mass 1
system was to amalgamate the key features in the Liver infiltration 2
Medially placed mass/intrahepatic 3
investigative algorithm to streamline treatment biliary radicle dilatation
strategies; the objective is to predict resectability and Metastatic disease 4
offer prognostication. The inspiration for this scoring a
In the presence of more than one finding, the score remains that
system was the Child criteria,11 used widely in eval- of the finding with the highest value. Score calculated as A +
uating patients with liver disease that is being con- B + C (maximum score = 10).
sidered for surgical resection.
The aim of this study was to apply TMHSS in a Jaundice
large cohort of patients with gallbladder cancer to A total of 14 patients (11.2%) had serum bilirubin
validate it. levels of [ 3 mg/dL, and all of them had unresectable
disease. The median CA 19-9 levels in these patients
was 632.4 U/mL.
PATIENTS AND METHODS On the basis of these observations, TMHSS was
devised incorporating the CT findings, serum CA 19-
Training Sample 9 levels, and serum bilirubin. The total score for
TMHSS was intended to be up to a maximum of 10.
Between July 1, 2001, and December 31, 2004, the The CT findings were classified into five groups, from
data of all 124 patients with gallbladder cancer who 0 for normal CT to 4 for obvious metastasis; inter-
sought care at the Department of Gastrointestinal vening scores indicate gradual increments in invasive
Surgical Oncology, Tata Memorial Hospital, were pattern of disease on imaging. Any patient with liver
retrospectively analyzed. Careful attention was paid metastasis would automatically receive a score of 4.
to the group of patients presenting with gallbladder Serum CA 19-9 levels were classified into four groups
cancer, either for the first time or after undergoing a on the basis of the study conducted above. Because
cholecystectomy elsewhere and then being referred we had found that patients with a serum bilirubin
for a revision radical surgery. value [ 3 mg/dL were most likely to have inoperable
The investigations performed, especially serum disease, we assigned a score of 2 to a serum bilirubin
cancer antigen (CA) 19–9, serum bilirubin, and com- value of [ 3 mg/dL (Table 1).
puted tomographic (CT) scan, were carefully assessed
for correlation to outcomes of these patients, such as
radical surgery, palliative chemotherapy, endoscopic Testing Sample
retrograde cholangiopancreatography, and stenting, Between May 1, 2005, and December 31, 2006, all
or simply palliative care. These tests were noted to patients with gallbladder cancer who sought care at
correlate with outcome. Of the 124 patients, only 72 the Department of Gastrointestinal Surgical Oncol-
(58.06%) had disease amenable to resection. ogy, Tata Memorial Hospital, were included in the
testing sample in this study. Each of the patients was
CA 19-9 Levels thoroughly examined and investigated for confirma-
When the serum CA 19-9 values are [ 90 U/mL, tion of the diagnosis of the disease and estimation of
94% of patients had unresectable disease, and when the extent of the disease for further management.
the level rose to [ 450 U/mL, 100% of those patients Liver function tests, complete blood counts, CA 19-9
had unresectable disease. The normal range of CA levels, and CT scan were performed in all patients.
19-9 is 0 to 30 U/mL. The diagnosis was confirmed by histopathological

Ann. Surg. Oncol. Vol. 15, No. 11, 2008

3134 P. J. SHUKLA ET AL.
TABLE 2. Tata Memorial Hospital gallbladder cancer scoring system and its relationship to interpretation and managementa
Group Score Interpretation
A 0–3 Highly likely to be resectable
B 4–6 Maybe resectable
C 7–10 Highly likely to be unresectable
a
If evidence of metastatic disease appears on computed tomography (score = 4), it is treated as group C disease.
examination of the gallbladder or by guided fine-
needle aspiration cytology in patients with metastatic
or advanced disease.
Patients who had undergone a simple cholecystec-
tomy at another institution and who were referred to
our institution for radical surgery were also included
after we confirmed the diagnosis of the primary tu-
mor to be in the gallbladder. Variables such as age,
sex, clinical examination findings, levels of serum
bilirubin, serum transaminases, serum alkaline
phosphatase, CA 19-9, and hemoglobin, total and
differential white cell counts, prothrombin and acti-
vated partial thromboplastin times, chest X-rays, and
CT scan findings were recorded in all patients. The
follow-up protocol was tailored according to stage of
disease, treatment offered, and expected outcome.
Establishing a New Prognostic Score
We sought to construct a new prognostic model
based on the following principles: It is preferable to
have break points for continuous variables such as
serum bilirubin or CA 19-9 because their distribution
is wide, and a single break point may not be optimal.
Variables must be those commonly assessed in practice
to enable comparison between different institutions.
The model should not include established classifica-
tions because they may be modified in the future.
A total of 354 patients sought care at our depart-
ment from May 1, 2005, to December 31, 2006. Of
these patients, complete records were unavailable of
19, so the analysis was performed with data for 335
patients.
There were 227 women (67.8%) and 108 men
(32.2%) with a mean age of 51.2 ± 11.1 years (range,
18–81 years). All of the patients had received a
diagnosis of gallbladder cancer confirmed by either
histopathological examination of the resected speci-
mens (radical/revision radical surgery), review of
specimen slides from patients operated and not con-
sidered for surgical resection at the Tata Hospital, or
by fine-needle aspiration cytology of the gallbladder
mass under CT or ultrasound.
Treatment decisions were made on the basis of
patients’ complete clinical and imaging profile. The
Ann. Surg. Oncol. Vol. 15, No. 11, 2008
Management strategy
Surgery (staging laparoscopy—resection)
Neoadjuvant options/staging laparoscopy
Palliative options (palliative chemotherapy/stenting/symptomatic care)
patients were offered various treatments ranging from
simple cholecystectomy for T1a lesions (guided by
frozen section) and radical cholecystectomy for tu-
mors [ T1b, revision radical cholecystectomy for
patients with incidental gallbladder cancer who had
undergone surgery elsewhere, endoscopic retrograde
cholangiopancreatography and stenting for patients
with obstructive jaundice, palliative chemotherapy
for advanced disease, and symptomatic care for ad-
vanced malignancy with a poor general condition.
Patients were considered to have unresectable dis-
ease if they had evidence of liver metastases, perito-
neal metastases, noncontiguous organ involvement,
positive lymph node station involvement beyond N1
(N1 disease includes nodes on the cystic duct, portal
vein in the hepatoduodenal ligament, and the hilum
of the liver), and/or involvement of the hepatic artery
or the portal vein.
To analyze the outcomes of the score, we grouped
these patients into two categories. The first group
comprised patients to whom curative or potentially
curative treatment options, such as surgery, were
offered. The second group comprised patients to
whom palliative care was provided or to whom pal-
liative treatment options, such as stenting or pallia-
tive chemotherapy, were provided.
On the basis of our current existing protocols of
management, 109 (32.5%) patients underwent surgi-
cal exploration; 226 patients (67.5%) were underwent
palliative strategies of management. We then scored
each patient by TMHSS scheme (Table 2). On the
basis of the scoring system, 106 patients, 98 patients,
and 131 patients were classified into the groups A, B,
and C, respectively.
Statistical analysis was performed by SPSS version
14.0 (SPSS, Chicago, IL), and the Kendall tau-b test
was used to confirm the concurrence of the score with
the actual treatment given.
RESULTS
When we cross-tabulated the data, we compared
the distribution of the possible treatment modality
according to the scoring system with the actual
 NEW SCORING SYSTEM FOR GALLBLADDER CANCER 3135

TABLE 3. Data distribution of scores versus actual

treatment offered

Scorewise stage Total

Treatment number
provided Group A Group B Group C of patients
Curative
No. of patients 99 10 0 109
Percentage within 93.4% 10.2% 0.0% 32.5%
total score
Palliative
No. of patients 7 88 131 226
Percentage within 6.6% 89.8% 100% 67.5%
total score
Total 106 98 131 335

FIG. 2. Univariate linear correlation analysis between cancer

antigen 19-9 and the proposed scoring system.

to be .75, which showed excellent concurrence and a

significant P value (.0001).

DISCUSSION

Hawkins et al.5 have cited the importance of pre-

FIG. 1. Univariate linear correlation analysis between computed
tomographic scan and the proposed scoring system.
treatment given (Table 3). By Pearson correlation, we
determined the correlation of each of the factors in
the scoring system to the treatment group to be .827
for CT scan (Fig. 1), .821 for CA 19-9 (Fig. 2), and
.691 for serum bilirubin. Detailed examination of the
data revealed that serum bilirubin, which was high in
only 80 patients, had a 100% correlation with the
patient being offered palliative care (none of the pa-
tients with serum bilirubin [ 3 mg/dL could be of-
fered surgery).
By regression analysis with 95% confidence inter-
vals, we assessed the significance of each of these
scoring parameters. The CT score, serum bilirubin
scores, and the CA 19-9 scores were compared sep-
arately with the treatment provided. It was found
that all three components of the scoring system at-
tained statistical significance (P \ .0001), indicating
that none was more significant than the other. Ordi-
nal-by-ordinal analysis revealed the value of the test
operatively detecting patients who are unlikely to
benefit from a exploratory laparotomy. One of the
reasons for this is the increased postoperative mor-
bidity observed in patients with advanced disease.
Avoiding unnecessary surgeries reduces the unneces-
sary cost of investigations and hospitalization, and it
also allows patients and physicians to focus on pal-
liation and improving the patient’s quality of life.5
Jaundice has been noted by Oertli et al.12 to be
associated with advanced disease. The main causes
for hyperbilirubinemia in gallbladder cancer patients
are a medially placed tumor infiltrating into the porta
hepatis and a lymph nodal mass infiltrating or
encircling the common hepatic duct or the common
bile duct and causing obstruction. Biliary tree inva-
sion indicates aggressive tumor biology.5 As we
found in our scoring system analysis, all 80 patients
with bilirubin levels of [ 3 mg/dL had disease that
was ultimately suitable only for palliative treatment.
CA 19-9 has been routinely used a serum tumor
marker in gallbladder cancer as an adjunct to
ambiguous or indeterminate radiologic imaging.13
Ritts et al.14 noted 79.4% sensitivity and 79.2%
specificity when serum levels were [ 20 U/mL.
CT scanning has been widely used in the diagnosis
of gallbladder cancer to visualize the appearance of

Ann. Surg. Oncol. Vol. 15, No. 11, 2008

3136 P. J. SHUKLA ET AL.
the primary tumor (mass replacing the gallbladder,
wall thickening, intraluminal polyp), to study the
tumor’s extension into surrounding tissues, and to
stage the tumor.15–18 Some researchers, while study-
ing the sensitivity of conventional CT in gallbladder
cancer, found that despite the low-moderate sensi-
tivity in the detection of gallbladder cancer extension,
CT had a high positive predictive value in determin-
ing resectability and thus assisting treatment
planning, especially in advanced disease.19,20
Multidetector CT scans allow a faster examination
with lower collimation thickness and more reliable
volumetric reconstructions. This allows better detec-
tion of perivesicular tumor infiltration while mini-
mizing partial volume artifacts, thereby improving T
staging of the tumor.18,21,22
The existing protocols relating to gallbladder can-
cer focus on radical surgery for operable disease and
chemotherapy/chemoradiotherapy options for pa-
tients with inoperable disease. Although it is true that
in some cases the choice of therapy is straightfor-
ward, in many cases, this is not the case. Very often,
in patients found by imaging to have borderline
operable disease, the clinician is faced with the di-
lemma of whether surgery or some other modality of
treatment should be offered.
Here, we propose a new scoring system that takes
into account the important features of serum biliru-
bin, CA 19-9, and imaging characteristics useful in
prognostic assessment of patients with gallbladder
cancer. The score is easy to calculate and is based on
variables that are routinely assessed. We envisage
that this system—the first of its kind in gallbladder
cancer—will be useful in the clinical decision-making
process, thereby helping the treating surgeon in
deciding the patient’s chances for a curative resection.
At the present time, such a scoring system does not
exist. The existing staging systems for gallbladder
cancer rely primarily on the histopathological exam-
ination of the resected specimen. The proposed sys-
tem has a good discriminant ability, revealing patient
subgroups that are good candidates for surgery and
are likely to benefit from a radical attempt at resec-
tion. It also allows identification of a subgroup of
patients who seem to have a borderline chance of
resectability according to clinical investigation, but
who may benefit from exploratory laparotomy with
intent to cure. The final group of patients, with
clearly unresectable disease, are unlikely to be can-
didates for a curative resection.
We are hopeful that the proposed TMHSS will be
used and evaluated by other similar large-volume
centers and surgeons treating gallbladder cancer. The
Ann. Surg. Oncol. Vol. 15, No. 11, 2008
true test of this scoring system would be the confir-
mation of its validity in aiding treatment algorithms.
TMHSS complements the existing tumor, node,
metastasis and Nevin staging systems and provides a
practical, clinically based system. We believe that this
will be a valuable tool to guide surgeons in managing
gallbladder cancers.
REFERENCES
1. Balachandran P, Agarwal S, Krishnanin N, et al. Predictors of
long-tern survival in patients with gallbladder cancer. J Gas-
trointest Surg 2006; 10:848–54.
2. Foster JM, Hoshi H, Gibbs JF, et al. Gallbladder cancer:
defining the indications for primary radical resection and
radical re-resection. Ann Surg Oncol 2007; 14:833–40.
3. Todoroki T, Iwasaki K, Irii K, et al. Resection combined with
intraoperative radiotherapy (IORT) for stage IV (TNM) gall-
bladder carcinoma. World J Surg 1991; 15:357–62.
4. Pradeep R, Kaushik SP, Sikora SS, et al. Predictors of survival
in carcinoma of the gallbladder. Cancer 1995; 76:1145–9.
5. Hawkins WG, DeMatteo RP, Jarnagin WR, et al. Jaundice
predicts advanced disease and early mortality in patients with
Gallbladder Cancer. Ann Surg Oncol 2004; 11:310–5.
6. Wittekind C, Greene FL, Mutter RVP, et al. (2004) TNM
staging of gallbladder cancers. In: TNM Atlas. 5th edition. New
York: Springer. pp 124–34.
7. Donohue JH, Nagorney DM, Grant CS, et al. Carcinoma of
the gallbladder. Does radical resection improve outcome? Arch
Surg 1990; 125:237–41.
8. Onoyama H, Yamamoto M, Tseng A, et al. Extended chole-
cystectomy for carcinoma of the gallbladder. World J Surg
1995; 19:758–63.
9. Bartlett DL, Fong Y, Fortner JG, et al. Long-term results after
resection for gallbladder cancer. Ann Surg 1996; 224:639–46.
10. Shukla PJ, Nadkarni MS, Shrikhande SV. Proposal for a new
clinico-biochemical-radiological staging system for gallbladder
cancer (abstract). HPB 2004; 6(Suppl 1):97.
11. Child CG III, Turcotte JG. (1964) Surgery and portal hyper-
tension. In: Child CG III (ed). Major Problems in Clinical
Surgery. WB Saunders, Philadelphia. pp 11–85.
12. Oertli D, Herzog U, Tondelli P. Primary carcinoma of the
gallbladder: operative experience during a 16-year period. Eur
J Surg 1993; 159:415–20.
13. Bartlett DL, Fong Y. (2000) Tumour of the gallbladder. In:
Blumgart LH, Fong Y (eds). Surgery of the liver and biliary
tract. 3rd edition.WB Saunders, Philadelphia. pp 993–1016.
14. Ritts RE, Nagorney DM, Jacobson DA, et al. Comparison of
preoperative serum CA 19-9 levels with results of diagnostic
imaging modalities in patients undergoing laparotomy for
suspected pancreatic or gallbladder disease. Pancreas 1994;
9:707–16.
15. Franquet T, Montes M, Ruiz de Azua Y, et al. Primary gall-
bladder carcinoma: imaging findings in 50 patients with path-
ologic correlation. Gastrointest Radiol 1991; 16:143–8.
16. Tsuchiya Y. Early carcinoma of the gallbladder: macroscopic
features and US findings. Radiology 1991; 179:171–5.
17. Kumar A, Aggarwal S. Carcinoma of the gallbladder: CT
findings in 50 cases. Abdom Imaging 1994; 19:304–8.
18. Rodriguez-Fernandez A, Gomez-Rio M, Medina-Benitez A,
et al. Application of modern imaging methods in diagnosis of
gallbladder cancer. J Surg Oncol 2006; 93:650–64.
19. Ohtani T, Shirai Y, Tsukada K, et al. Spread of gallbladder
carcinoma: CT evaluation with pathologic correlation. Abdom
Imaging 1996; 21:195–220.
 NEW SCORING SYSTEM FOR GALLBLADDER CANCER 3137

20. Misra S, Chaturvedi A, Misra NC, et al. Carcinoma of the according to the TNM system in patients who underwent
gallbladder. Lancet Oncol 2003; 4:167–76. surgical resection. Am J Roentgenol 2002; 179:423–8.
21. Yoshimitsu K, Honda H, Shinozaki K, et al. Helical CT of the 22. Kim BS, Ha HK, Lee D, et al. Accuracy of CT in local staging
local spread of carcinoma of the gallbladder: evaluation of gallbladder carcinoma. Acta Radiol 2002; 43:71–6.

Ann. Surg. Oncol. Vol. 15, No. 11, 2008