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Incidental Gallbladder Cancer: Incidence, predictors, management and outcome in a Swedish population
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Cholecystectomy is a common surgical procedure and incidental gallbladder cancer is a rare and unexpected finding at a cholecystectomy performed upon benign indications. Whether to perform routine or selective histopathology of the gallbladder specimen is still a subject for discussion. The prognosis of gallbladder cancer is largely affected by tumour stage and treatment.

Aims: The overall aim was to study whether routine histological examination of the gallbladder specimen is of clinical and health economic value; determine if there are any predictive factors of incidental gallbladder cancer at benign cholecystectomy and compare the management and outcome of incidental gallbladder cancer patients in Sweden.

Methods: All studies were based on registry data from GallRiks (The Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography) between 2007 and 2016, with some modifications between studies. Complemental cross-linkage was made to national registries, and medical records were reviewed. Papers I, II and III were population-based observational studies with prospectively and retrospectively collected data. Paper IV was a health economic evaluation based on the results from papers I and III.

Results and conclusions: Hospitals submitting >75 per cent of gallbladder specimens diagnosed a higher proportion of incidental gallbladder cancer than did hospitals submitting ≤25 per cent of samples (paper I). Incidental gallbladder cancer was more prevalent in older patients, women and patients with acute or previous cholecystitis, as well as ongoing jaundice. The risk model based on predictive preoperative factors was further improved by adding a macroscopic assessment of the gallbladder (paper II). Predictive factors for gallbladder cancer appeared to have an impact on which specimens were submitted in hospitals with a selective approach of histopathology (paper I). For pT2 and pT3 patients, re-resection improved diseasespecific survival, although these groups differed in terms of age and comorbidity (paper III). Residual disease was an independent factor for impaired survival. A change to routine histopathology of gallbladder specimens in Sweden would lead to increased costs with little improved health outcomes. Instead, a more standardized approach to selective histology would be needed (paper IV).

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1695
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-159835ISBN: 9789176850152 (print)OAI: oai:DiVA.org:liu-159835DiVA, id: diva2:1345214
Public defence
2019-09-27, Hasselqvistsalen, Hus 511, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-08-23Bibliographically approved
List of papers
1. Are Incidental Gallbladder Cancers Missed with a Selective Approach of Gallbladder Histology at Cholecystectomy?
Open this publication in new window or tab >>Are Incidental Gallbladder Cancers Missed with a Selective Approach of Gallbladder Histology at Cholecystectomy?
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2018 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 4, p. 1092-1099Article in journal (Refereed) Published
Abstract [en]

Incidental gallbladder cancer (IGBC) is an unexpected finding when a cholecystectomy is performed upon a benign indication, and the use of routine or selective histological analysis of gallbladder specimen is still debated. The aim of this study was to investigate whether the proportion of submitted gallbladder specimens for pathological investigation influences the proportion of IGBC found, and what possible factors preoperatively or perioperatively could influence the selection process. All cholecystectomies between January 2007 and September 2014 registered in the Swedish Registry of Gallstone Surgery and ERCP (GallRiks) were included. Proportion of histological analysis was divided into four subgroups (0-25%, amp;gt; 25-50%, amp;gt; 50-75%, amp;gt; 75-100%). A total of 81,349 cholecystectomies were registered, and 36,010 (44.3%) gallbladder specimens were sent for histological analysis. A total of 213 cases of IGBC were discovered, which constituted 0.26% of all cholecystectomies performed and 0.59% of the number of gallbladder specimens sent for histological analysis. Hospitals submitting amp;gt; 75-100% of the gallbladder specimens had significantly more IGBC/1000 cholecystectomies performed (p = 0.003). Hospitals with the most selective approach had a significantly higher proportion of IGBC/1000 gallbladders that were sent for histological analysis (p amp;lt; 0.001). Factors such as higher age (p amp;lt; 0.001), female gender (p = 0.048) and macroscopic cholecystitis (p amp;lt; 0.001) were more common in gallbladder specimens from hospitals that had a selective approach to histological analysis. A routine approach to histological analysis in cholecystectomies with a benign indication for surgery can uncover a higher proportion of IGBC cases. When a selective approach is used, risk factors should be taken into account.

Place, publisher, year, edition, pages
SPRINGER, 2018
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-147095 (URN)10.1007/s00268-017-4215-0 (DOI)000427050900023 ()28900706 (PubMedID)
Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2019-08-23
2. Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease: Results from a population-based gallstone surgery registry
Open this publication in new window or tab >>Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease: Results from a population-based gallstone surgery registry
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2017 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 162, no 2, p. 256-263Article in journal (Refereed) Published
Abstract [en]

Background. Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental gallbladder cancer. Methods. Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. Results. A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 11 years for index cases and 54 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P amp;lt; .001), female sex (odds ratio = 3.58; P amp;lt; .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31 % of the cases. Conclusion. Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-139810 (URN)10.1016/j.surg.2017.02.009 (DOI)000406087900006 ()28400123 (PubMedID)
Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2019-08-23
3. Management of incidental gallbladder cancer in a national cohort
Open this publication in new window or tab >>Management of incidental gallbladder cancer in a national cohort
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2019 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 9, p. 1216-1227Article in journal (Refereed) Published
Abstract [en]

Background Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. Methods Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. Results In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36 center dot 9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12 center dot 4 versus 44 center dot 1 months for pT2, and 9 center dot 7 versus 23 center dot 0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32 center dot 2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0 center dot 030). Conclusion Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-159068 (URN)10.1002/bjs.11205 (DOI)000474059700001 ()31259388 (PubMedID)
Available from: 2019-07-22 Created: 2019-07-22 Last updated: 2019-08-23

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5678910118 of 16
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