Multiple Primary Malignancy-Related Gallbladder Cancer - An Important Recommendation for the Early Detection of Gallbladder Cancer

Sep 23, 2026

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Gallbladder cancer often shows no early symptoms and becomes difficult to treat after clinical presentation, while risk-factor profiles beyond classic causes remain insufficient. This study retrospectively compares 22 patients with gallbladder cancer associated with multiple primary malignancies (MPM-positive) versus 16 without (MPM-negative), assessing clinical traits, major risk factors, tumor features, cancer-development sequence, and contrast-enhanced ultrasonography (CEUS). CEUS proved useful for both detection and qualitative diagnosis in all cases, and MPM-related disease frequently emerged as a second primary malignancy even without classical risks.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

Keywords

1. Introduction

Article Multiple Primary Malignancy-Related Gallbladder Cancer: An Important Recommendation for the Early Detection of Gallbladder Cancer Hiroko Naganuma 1, *, Hideaki Ishida 2, Naoki Matsumoto 3 and Masahiro Ogawa 3 Received: 22 December 2025 Revised: 8 February 2026 Accepted: 17 February 2026 Published: 19 February 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Gastroenterology, Yokote Municipal Hospital, Akita 013-8602, Japan 2 Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan; [minnnanous@gmail.com](minnnanous@gmail.com) 3 Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan; [matsumoto.naoki@nihon-u.ac.jp](matsumoto.naoki@nihon-u.ac.jp) (N.M.); [echo.m.ogawa0922@gmail.com](echo.m.ogawa0922@gmail.com) (M.O.) * [Correspondence: hiron@vesta.ocn.ne.jp](Correspondence: hiron@vesta.ocn.ne.jp) Abstract Background: Gallbladder cancer (GBC) is a highly lethal malignancy that is often asymptomatic in its early stages and difficult to treat once clinical symptoms appear. Although established risk factors include female sex, gallstones, and chronic biliary inflammation, other clinical contexts associated with GBC remain insufficiently characterized. Multiple primary malignancies (MPMs), in which more than one primary cancer develops in the same individual, have recently attracted attention; however, their relationship with GBChas only rarely been examined. In this study, we aimed to clarify the clinical features of MPMrelated GBC and explore its implications for early detection. Methods: We retrospectively compared 22 patients with GBC associated with other malignancies (MPM-positive GBC) and 16 patients with GBC alone (MPM-negative GBC) . Clinical characteristics, major risk factors, tumor presentation, and imaging findings were evaluated. Special attention was paid to the sequence of cancer development and the diagnostic utility of contrast-enhanced ultrasonography (CEUS). Results: In all MPM-positive cases, GBC occurred as a second primary malignancy, most commonly following gastrointestinal cancers (12/22) . Gallstones were significantly less frequent in the MPM-positive group than in the MPM-negative group (2/22 vs. 6/16) . The MPM-positive group showed a slight male predominance (12 males and 10 females) . Neither pancreaticobiliary maljunction nor porcelain gallbladder was identified in either group. CEUS was useful for both the detection and qualitative diagnosis of GBC in all patients. Conclusions: MPM-related GBC frequently develops as a second primary malignancy in patients with prior gastrointestinal cancer and may arise in the absence of classical risk factors. Careful long-term surveillance after cancer treatment is therefore essential for identifying second primary GBC at a potentially resectable stage. The combined use of ultrasonography and CEUS may facilitate earlier and more accurate diagnosis in this clinical setting. Keywords: gallbladder cancer; multiple primary malignancies; contrast-enhanced ultrasonography; risk factor; postoperative surveillance system 1. Introduction Gallbladder cancer (GBC) is a highly lethal neoplasm, with a five-year survival rate of less than 10%[1,2] . It is often asymptomatic in its early stages and becomes difficult to treat once symptoms appear; consequently, substantial improvement in prognosis has yet to be achieved [2,3] . Therefore, early detection remains a critical unmet need. Against this background, several established risk factors for GBC have been reported, including female sex [4], the presence of gallstones [5,6], pancreaticobiliary maljunction (PBM) [7,8], primary sclerosing cholangitis [9], porcelain gallbladder [10], and others [11,12] . Meanwhile, an inc

FAQs

What question does the study address about gallbladder cancer?

It clarifies the clinical features of gallbladder cancer related to multiple primary malignancies and explores implications for early detection.

How were MPM-positive and MPM-negative patients compared?

The study retrospectively compared 22 MPM-positive patients with 16 MPM-negative patients, evaluating clinical characteristics, major risk factors, tumor presentation, imaging findings, and the sequence of cancer development.

What role did contrast-enhanced ultrasonography (CEUS) play?

CEUS was useful for both detecting and providing qualitative diagnosis of gallbladder cancer across all patients.

Sep 23, 2026

Uploaded by Theodore