"IN-SITU" CARCINOMA OF THE GALLBLADDER: A SEER PERSPECTIVE Open Access

Abstract

ABSTRACT

"IN-SITU" CARCINOMA OF THE GALLBLADDER: A SEER PERSPECTIVE

By KAJAL NILESH PATEL

Background: The etiology of gallbladder cancer remains unknown, treatment options are limited and prognosis dismal. Diagnosis of gallbladder carcinomas (GBCs) is often made incidentally and at later stages. While non-papillary (flat) carcinomas represent the most common histologic group (>75%) of this neoplasm, papillary (tumoral) variants have been recognized as a distinct morphologic variant. The distinct biologic behavior of the papillary GBC is thought to confer survival benefits.

Purpose: To conduct an analysis of GBC incidence, risk factors and survival with a primary focus histology and on the earliest (in-situ) stage.

Design: Retrospective analysis of primary GBC cases identified in the Surveillance Epidemiology and End Results (SEER) program from 1973-2010.

Methods: We examined cancer trends using Joinpoint regression. Kaplan-Meier and Cox proportional hazards regression methods were used to estimate clinical and demographic survival differences.

Results: Women, non-Hispanic whites and individuals 60 years of age or older represented >50% of cases. GBC in the distant stage was diagnosed roughly 9 times more than in-situ. Papillary tumors accounted for 5.6% of all GBC, but represented over 20% of in-situ cases.. Survival of all GBC cases was inversely related to age and stage, and non-papillary histology. Incidence of in-situ disease has not changed appreciably since 1973, while 5 and 10-year survival estimates for GBC at this stage were 87% and 79%, respectively.

Conclusion: We found that in situ GBC survival was lower than previously reported. The relatively low survival of in-situ disease suggests under-staging with missed invasive or more advanced carcinomas. In addition, deaths during the long-term follow-up period provide evidence of the occurrence of a field-effect/field defect phenomenon in the biliary tree. These findings indicate the need for reviewing the entire gallbladder specimen with non-invasive GBC findings to rule out more advanced disease. Relatively stable GBC in-situ rates indicate lack of earlier cancer detection mechanisms.

Table of Contents

TABLE OF CONTENTS

1. INTRODUCTION
Introduction ................................................................................................................. 1
Overview ..................................................................................................................... 1

The Gallbladder: Organ, Structure & Histology ......................................................... 1
Risk Factors for GBC .................................................................................................. 2

GBC Clinical Features & Pathology ........................................................................... 3
Molecular Pathology of GBC ..................................................................................... 3
GBC Staging & Challenges ........................................................................................ 4
Epidemiology ............................................................................................................. 6
Gallbladder Carcinoma In-situ (CIS): What's special? ............................................. 7
Trends in GBC ............................................................................................................ 7
Relevance .................................................................................................................... 8

2. MATERIALS & METHODS
Materials and Methods ................................................................................................ 9-12

3. RESULTS
Results ........................................................................................................................ 13-16

4. DISCUSSION
Discussion ................................................................................................................... 17-22
Conclusion ................................................................................................................... 22

5. REFERENCES
References .................................................................................................................. 23-33

6. TABLES & FIGURES
Table 1: Demographic Characteristics of Patients with Gallbladder Tumors by Decade
Table 2: Clinicopathologic Characteristics of Gallbladder Tumors by Decade

Table 3: The Histopathologic Characteristics of Gallbladder Tumors by Stage

Table 4: Age-Adjusted Incidence Rates & Incidence Rate Ratios of Gallbladder Tumors by Sex, Race & Stage

Figure 1 (A-D): Trends in Observed Incidence of Gallbladder Tumors

Table 5: The 5 and 10-year Survival of Patients with Gallbladder Tumors by Sex, Race, Marital status, Histology & Stage

Figure 2 (A-C): Survival Rates for all GBCIS, Overall and by Histology

Figure 3 (A-E): Kaplan-Meier (K-M) Survival Curves for GBC cases

Table 6: 10-year Survival Cox Multivariate Regression Parameters for all GBC cases
Table 7: Cause-specific Death Classification of all GBC Tumors by Stage

7. APPENDIX: TABLES & FIGURES

Table A: AJCC Staging System

Table 1: Carcinoma In-situ: Demographic Characteristics of Patients with GBC by Decade

Table 2: Localized: Demographic Characteristics of Patients with GBC by Decade

Table 3: Regional: Demographic Characteristics of Patients with GBC by Decade

Table 4: Distant: Demographic Characteristics of Patients with GBC by Decade

Table 5: Unstaged: Demographic Characteristics of Patients with GBC by Decade

Table 6: The Histopathologic Characteristics of Gallbladder Tumors for each Stage by Year of Diagnosis

Table 7: Cox Multivariate Regression Parameters for GBC In-situ cases

Figure 1 (A-F): Trends in Observed Incidence of GBC Tumors by Stage

Figure 2 (A-F): Trends in Observed Incidence of GBC Tumors by Race & Gender

Figure 3 (A-F): Trends in 5 & 10-year Relative Survival for all GBC & GBCIS tumors

Figure 4 (A-F): Trends in 5 & 10-year Relative Survival of GBC by Gender & Race/Ethnicity

Figure 5: Relative Survival GBC cases by Histologic type & Stage at Diagnosis

Figure 6 (A-F): K-M Survival Curves for patients with GBC by Demographic Characteristics.

Figure 7 (A-F): K-M Survival Curves for patients with GBCIS

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Pathology Health Sciences, Oncology
Keyword	SEER GALLBLADDER CARCINOMA IN-SITU
Committee Chair / Thesis Advisor	Goodman, Michael, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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