Insulin therapy and biliary tract cancer: insights from real-world data

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Abstract

Objective

The association between insulin therapy and the risk of biliary tract cancer (BTC) is uncertain. We aimed to assess this risk in type 2 diabetic patients.

Methods

Using electronic medical data from the Shanghai Hospital Link database, 202,557 patients with type 2 diabetes (164,997 insulin never-users and 37,560 insulin ever-users) were identified in this study between January 1, 2013, and December 31, 2016, with follow-up until December 31, 2019. By propensity score matching, an ever-user was matched with a never-user. Cox proportional hazards regression analysis was used to estimate risk ratios (HRs) and 95% CIs for three subtypes of BTC (intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC)).

Results

At a mean follow-up of 5.33 years, 143 cases of BTC were observed. The crude incidence rates (per 100,000 person-years) of ECC, ICC, and GBC in ever-users:never-users were 10.22:3.63, 2.04:2.04, and 8.17:6.01, respectively. Insulin therapy was associated with an increased risk of ECC (HR, 4.10; 95% CI, 1.54–10.92; P = 0.005) compared to patients who never used insulin. No statistically significant results were observed for insulin and ICC/GBC. Consistent results were also found in the original cohort.

Conclusions

The relationship between insulin therapy and BTC is type-specific. Further studies are warranted to provide evidence on the identification of ECC risk groups among type 2 diabetic patients.

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Most cited references 26

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Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies

Peter C Austin, Elizabeth A. Stuart (2015)

The propensity score is defined as a subject's probability of treatment selection, conditional on observed baseline covariates. Weighting subjects by the inverse probability of treatment received creates a synthetic sample in which treatment assignment is independent of measured baseline covariates. Inverse probability of treatment weighting (IPTW) using the propensity score allows one to obtain unbiased estimates of average treatment effects. However, these estimates are only valid if there are no residual systematic differences in observed baseline characteristics between treated and control subjects in the sample weighted by the estimated inverse probability of treatment. We report on a systematic literature review, in which we found that the use of IPTW has increased rapidly in recent years, but that in the most recent year, a majority of studies did not formally examine whether weighting balanced measured covariates between treatment groups. We then proceed to describe a suite of quantitative and qualitative methods that allow one to assess whether measured baseline covariates are balanced between treatment groups in the weighted sample. The quantitative methods use the weighted standardized difference to compare means, prevalences, higher‐order moments, and interactions. The qualitative methods employ graphical methods to compare the distribution of continuous baseline covariates between treated and control subjects in the weighted sample. Finally, we illustrate the application of these methods in an empirical case study. We propose a formal set of balance diagnostics that contribute towards an evolving concept of ‘best practice’ when using IPTW to estimate causal treatment effects using observational data. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

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Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Jesus Banales, Jose Marin, Angela Lamarca … (2020)

Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.

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Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

Jesus M. Banales, Vincenzo Cardinale, Guido Carpino … (2016)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 11 February 2022

Publication date Collection: 01 March 2022

Volume: 11

Issue: 3

Electronic Location Identifier: e210546

Affiliations

[1 ]Department of Endocrine and Metabolic Diseases , Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

[2 ]Shanghai National Clinical Research Center for Metabolic Diseases , Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

[3 ]Shanghai Hospital Link Center , Shanghai Hospital Development Center, Shanghai, China

[4 ]Computer Net Center , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

[5 ]Wonders Information Co. Ltd , Shanghai, China

Author notes

Correspondence should be addressed to B Cui or G Ning: bcui@ 123456sibs.ac.cn or gning@ 123456sibs.ac.cn

*(X Qi, P He and H Yao contributed equally to this work)

Author information

Xiaohui Qi http://orcid.org/0000-0001-6440-0554

Bin Cui http://orcid.org/0000-0002-7293-5740

Article

Publisher ID: EC-21-0546

DOI: 10.1530/EC-21-0546

PMC ID: 8942312

PubMed ID: 35148280

SO-VID: 1bc66f52-935d-4657-8dd1-565be78af731

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Insulin therapy and biliary tract cancer: insights from real-world data

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Bioscientifica Open Endocrinology

Most cited references 26

Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

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