Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer.


Journal

The British journal of surgery
ISSN: 1365-2168
Titre abrégé: Br J Surg
Pays: England
ID NLM: 0372553

Informations de publication

Date de publication:
22 06 2021
Historique:
received: 19 04 2020
revised: 03 06 2020
accepted: 23 07 2020
entrez: 22 6 2021
pubmed: 23 6 2021
medline: 5 10 2021
Statut: ppublish

Résumé

An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

Sections du résumé

BACKGROUND
An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect.
METHODS
This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis.
RESULTS
Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001).
CONCLUSION
K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

Identifiants

pubmed: 34157083
pii: 6307788
doi: 10.1002/bjs.12003
doi:

Substances chimiques

Anti-Bacterial Agents 0
Quinolones 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

709-716

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

M Weniger (M)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

T Hank (T)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

M Qadan (M)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

D Ciprani (D)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

T Michelakos (T)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

H Niess (H)

Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

C Heiliger (C)

Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

M Ilmer (M)

Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

J G D'Haese (JG)

Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

C R Ferrone (CR)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

A L Warshaw (AL)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

K D Lillemoe (KD)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

J Werner (J)

Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.

A Liss (A)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

C Fernández-Del Castillo (C)

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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