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Li M, Lopez‐Aguiar AG, Poultsides G, Rocha F, Weber S, Fields R, Idrees K, Cho C, Maithel SK, Zhang X, Pawlik TM. Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors. J Surg Oncol 2025; 131:473-480. [PMID: 39387595 PMCID: PMC12044285 DOI: 10.1002/jso.27951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 09/16/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). METHODS Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. RESULTS A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). CONCLUSIONS Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.
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Affiliation(s)
- Mu‐Xing Li
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and EngineeringThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
- Department of General SurgeryPeking University Third HospitalBeijingChina
| | - Alexandra G. Lopez‐Aguiar
- Department of Surgery, Division of Surgical Oncology, Winship Cancer InstituteEmory UniversityAtlantaGeorgiaUSA
| | | | - Flavio Rocha
- Department of SurgeryVirginia Mason Medical CenterSeattleWashington
| | - Sharon Weber
- Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Ryan Fields
- Department of SurgeryWashington University School of MedicineSt. LouisWisconsin
| | - Kamran Idrees
- Department of Surgery, Division of Surgical OncologyVanderbilt UniversityNashvilleTennesseeUSA
| | - Cliff Cho
- Department of Surgery, Division of Hepatopancreatobiliary and Advanced Gastrointestinal SurgeryUniversity of MichiganAnn ArborMichiganUSA
| | - Shishir K. Maithel
- Department of Surgery, Division of Surgical Oncology, Winship Cancer InstituteEmory UniversityAtlantaGeorgiaUSA
| | - Xu‐Feng Zhang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and EngineeringThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
- Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
| | - Timothy M. Pawlik
- Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
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Keyl J, Keyl P, Montavon G, Hosch R, Brehmer A, Mochmann L, Jurmeister P, Dernbach G, Kim M, Koitka S, Bauer S, Bechrakis N, Forsting M, Führer-Sakel D, Glas M, Grünwald V, Hadaschik B, Haubold J, Herrmann K, Kasper S, Kimmig R, Lang S, Rassaf T, Roesch A, Schadendorf D, Siveke JT, Stuschke M, Sure U, Totzeck M, Welt A, Wiesweg M, Baba HA, Nensa F, Egger J, Müller KR, Schuler M, Klauschen F, Kleesiek J. Decoding pan-cancer treatment outcomes using multimodal real-world data and explainable artificial intelligence. NATURE CANCER 2025; 6:307-322. [PMID: 39885364 PMCID: PMC11864985 DOI: 10.1038/s43018-024-00891-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 12/06/2024] [Indexed: 02/01/2025]
Abstract
Despite advances in precision oncology, clinical decision-making still relies on limited variables and expert knowledge. To address this limitation, we combined multimodal real-world data and explainable artificial intelligence (xAI) to introduce AI-derived (AID) markers for clinical decision support. We used xAI to decode the outcome of 15,726 patients across 38 solid cancer entities based on 350 markers, including clinical records, image-derived body compositions, and mutational tumor profiles. xAI determined the prognostic contribution of each clinical marker at the patient level and identified 114 key markers that accounted for 90% of the neural network's decision process. Moreover, xAI enabled us to uncover 1,373 prognostic interactions between markers. Our approach was validated in an independent cohort of 3,288 patients with lung cancer from a US nationwide electronic health record-derived database. These results show the potential of xAI to transform the assessment of clinical variables and enable personalized, data-driven cancer care.
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Affiliation(s)
- Julius Keyl
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
- Institute of Pathology, University Hospital Essen (AöR), Essen, Germany
| | - Philipp Keyl
- Institute of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany
- BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany
| | - Grégoire Montavon
- BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany
- Machine Learning Group, Technical University of Berlin, Berlin, Germany
- Department of Mathematics and Computer Science, Freie Universität Berlin, Berlin, Germany
| | - René Hosch
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
| | - Alexander Brehmer
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
| | - Liliana Mochmann
- Institute of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Philipp Jurmeister
- Institute of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Gabriel Dernbach
- Machine Learning Group, Technical University of Berlin, Berlin, Germany
| | - Moon Kim
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
| | - Sven Koitka
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (AöR), Essen, Germany
| | - Sebastian Bauer
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
| | - Nikolaos Bechrakis
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Ophthalmology, University Hospital Essen (AöR), Essen, Germany
| | - Michael Forsting
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
| | - Dagmar Führer-Sakel
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen (AöR), Essen, Germany
| | - Martin Glas
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Division of Clinical Neurooncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Essen, Germany
| | - Viktor Grünwald
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Urology, University Hospital Essen (AöR), Essen, Germany
| | - Boris Hadaschik
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Urology, University Hospital Essen (AöR), Essen, Germany
| | - Johannes Haubold
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Ken Herrmann
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Nuclear Medicine, University Hospital Essen (AöR), Essen, Germany
| | - Stefan Kasper
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
| | - Rainer Kimmig
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- Department of Gynecology and Obstetrics, University Hospital Essen (AöR), Essen, Germany
| | - Stephan Lang
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Department of Otorhinolaryngology, University Hospital Essen (AöR), Essen, Germany
| | - Tienush Rassaf
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center Essen, University Hospital Essen (AöR), Essen, Germany
| | - Alexander Roesch
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Dermatology, University Hospital Essen (AöR), Essen, Germany
| | - Dirk Schadendorf
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Dermatology, University Hospital Essen (AöR), Essen, Germany
- Research Alliance Ruhr, Research Center One Health, University of Duisburg-Essen, Essen, Germany
| | - Jens T Siveke
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen (AöR), University of Duisburg-Essen, Essen, Germany
- Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany
| | - Martin Stuschke
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Radiotherapy, University Hospital Essen (AöR), Essen, Germany
| | - Ulrich Sure
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
- Department of Neurosurgery and Spine Surgery, University Hospital Essen (AöR), Essen, Germany
| | - Matthias Totzeck
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center Essen, University Hospital Essen (AöR), Essen, Germany
| | - Anja Welt
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
| | - Marcel Wiesweg
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
| | - Hideo A Baba
- Institute of Pathology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Felix Nensa
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (AöR), Essen, Germany
- Medical Faculty, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany
| | - Jan Egger
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany
| | - Klaus-Robert Müller
- BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany.
- Machine Learning Group, Technical University of Berlin, Berlin, Germany.
- Department of Artificial Intelligence, Korea University, Seoul, South Korea.
- MPI for Informatics, Saarbrücken, Germany.
| | - Martin Schuler
- Department of Medical Oncology, University Hospital Essen (AöR), Essen, Germany.
- Medical Faculty, University of Duisburg-Essen, Essen, Germany.
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany.
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany.
| | - Frederick Klauschen
- Institute of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany.
- BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany.
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Berlin partner site, Berlin, Germany.
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Munich partner site, Munich, Germany.
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany.
| | - Jens Kleesiek
- Institute for Artificial Intelligence in Medicine, University Hospital Essen (AöR), Essen, Germany.
- Medical Faculty, University of Duisburg-Essen, Essen, Germany.
- West German Cancer Center, University Hospital Essen (AöR), Essen, Germany.
- German Cancer Consortium (DKTK), Partner site University Hospital Essen (AöR), Essen, Germany.
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Ling S, Sweeting M, Zaccardi F, Adlam D, Kadam UT. Glycosylated haemoglobin and prognosis in 10,536 people with cancer and pre-existing diabetes: a meta-analysis with dose-response analysis. BMC Cancer 2022; 22:1048. [PMID: 36203139 PMCID: PMC9535893 DOI: 10.1186/s12885-022-10144-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 09/29/2022] [Indexed: 11/10/2022] Open
Abstract
AIMS To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. METHODS In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA1c) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA1c or per 1-unit HbA1c increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. RESULTS Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA1c ≥ 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03-1.27]; p-value: 0.012), cancer-specific mortality (5; 1.68 [1.13-2.49]; p-value: 0.011) and cancer recurrence (8; 1.68 [1.18-2.38; p-value: 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA1c (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01-1.08]; p-value: 0.016) and cancer-specific mortality (4; 1.11 [1.04-1.20]; p-value: 0.003). All RRs were attenuated in trim-and-fill analyses. CONCLUSIONS Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control.
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Affiliation(s)
- Suping Ling
- Department of Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK.
- Present address: Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
| | - Michael Sweeting
- Department of Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK
| | - Francesco Zaccardi
- Leicester Real World Evidence Unit, Leicester Diabetes Centre, University of Leicester, Leicester, UK
- Leicester Diabetes Centre, University of Leicester, Leicester, UK
| | - David Adlam
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
| | - Umesh T Kadam
- Department of Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK
- Leicester Diabetes Centre, University of Leicester, Leicester, UK
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Suto H, Kamei K, Kato H, Misawa T, Unno M, Nitta H, Satoi S, Kawabata Y, Ohtsuka M, Rikiyama T, Sudo T, Matsumoto I, Hirao T, Okano K, Suzuki Y, Sata N, Isaji S, Sugiyama M, Takeyama Y. Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan. Surgery 2022; 172:962-967. [PMID: 35820975 DOI: 10.1016/j.surg.2022.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/27/2022] [Accepted: 04/25/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy. METHODS Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study. RESULTS Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period. CONCLUSION Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.
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Affiliation(s)
- Hironobu Suto
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
| | - Keiko Kamei
- Department of Surgery, Kindai University, Osaka, Japan
| | - Hiroyuki Kato
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Mie, Japan
| | - Takeyuki Misawa
- Department of Surgery, The Jikei University Kashiwa Hospital, Chiba, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University, Miyagi, Japan
| | - Hiroyuki Nitta
- Department of Surgery, Iwate Medical University, Iwate, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Yasunari Kawabata
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Shimane, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Takeshi Sudo
- Department of Surgery, Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
| | | | - Tomohiro Hirao
- Department of Public Health, Kagawa University, Kagawa, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - Yasuyuki Suzuki
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - Naohiro Sata
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Shuji Isaji
- Director of Mie University Hospital, Mie, Japan
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Pilotti E, Cassetti T, Mirante VG, Sereni G, Rossi PG, Sassatelli R. Exhaled breath condensate proteomic signatures potentially distinguish adenocarcinoma from benign cystic lesions of the pancreas. Curr Res Transl Med 2022; 70:103361. [PMID: 35963150 DOI: 10.1016/j.retram.2022.103361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/26/2022] [Accepted: 07/29/2022] [Indexed: 01/31/2023]
Affiliation(s)
| | - Tiziana Cassetti
- Department of Oncology and Advanced Technologies, Gastroenterology and Digestive Endoscopy Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Vincenzo G Mirante
- Department of Oncology and Advanced Technologies, Gastroenterology and Digestive Endoscopy Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
| | - Giuliana Sereni
- Department of Oncology and Advanced Technologies, Gastroenterology and Digestive Endoscopy Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Paolo Giorgi Rossi
- Epidemiology Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Romano Sassatelli
- Department of Oncology and Advanced Technologies, Gastroenterology and Digestive Endoscopy Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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6
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Wang X, Xu W, Hu X, Yang X, Zhang M. The Prognostic Role of Glycemia in Patients With Pancreatic Carcinoma: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:780909. [PMID: 35223469 PMCID: PMC8866248 DOI: 10.3389/fonc.2022.780909] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/03/2022] [Indexed: 12/14/2022] Open
Abstract
Background Fasting blood glucose and glycated hemoglobin (HbA1c) levels are associated with the risk of pancreatic cancer. Aim To examine the relationship between perioperative glucose and HbA1c levels and prognosis in patients with pancreatic cancer. Methods PubMed, Embase, and the Cochrane Library were queried for potentially eligible studies published up to May 2021. The exposures were perioperative fasting glucose and HbA1c levels. The primary outcome was survival. The secondary outcome was complications. All analyses were performed using the random-effects model. Results Ten studies (48,424 patients) were included. The pre-operative (HR=1.10, 95%CI: 0.89-1.35; I2 = 45.1%, Pheterogeneity=0.078) and postoperative (HR=1.19, 95%CI: 0.92-1.54; I2 = 67.9%, Pheterogeneity=0.001) blood glucose levels were not associated with the survival to pancreatic cancer. Similar results were observed for HbA1c (HR=1.09, 95%CI: 0.75-1.58; I2 = 64.2%, Pheterogeneity=0.039), fasting blood glucose (FBG)/HbA1c (HR=1.16, 95%CI: 0.67-1.68; I2 = 0.0%, Pheterogeneity=0.928), and FBG (HR=1.75, 95%CI: 0.81-3.75; I2 = 79.4%, Pheterogeneity=0.008). Pre-operative blood glucose levels were not associated with postoperative complications (OR=0.90, 95%CI: 0.52-1.56), but postoperative glucose levels were associated with postoperative complications (OR=3.06, 95%CI: 1.88-4.97; I2 = 0.0%, Pheterogeneity=0.619). Conclusion Blood glucose, FBG, and HbA1c levels are not associated with the survival of patients with pancreatic cancer. Postoperative blood glucose levels could predict postoperative complications.
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Affiliation(s)
- Xiaofang Wang
- Department of Clinical Oncology and Department of Hospice Care, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wanfeng Xu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoru Hu
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xianghong Yang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mingming Zhang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
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7
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Li Q, Feng Z, Miao R, Liu X, Liu C, Liu Z. Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution. World J Surg Oncol 2022; 20:11. [PMID: 34996486 PMCID: PMC8742338 DOI: 10.1186/s12957-021-02478-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 12/07/2021] [Indexed: 12/15/2022] Open
Abstract
Background The overall survival of patients with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer. Methods The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected. Results Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup. Conclusions Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.
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Affiliation(s)
- Qi Li
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Zijian Feng
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Ruyi Miao
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Xun Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Chenxi Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Zhen Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China.
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Roy A, Sahoo J, Kamalanathan S, Naik D, Mohan P, Kalayarasan R. Diabetes and pancreatic cancer: Exploring the two-way traffic. World J Gastroenterol 2021; 27:4939-4962. [PMID: 34497428 PMCID: PMC8384733 DOI: 10.3748/wjg.v27.i30.4939] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 06/16/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is often associated with a poor prognosis. Long-standing diabetes mellitus is considered as an important risk factor for its development. This risk can be modified by the use of certain antidiabetic medications. On the other hand, new-onset diabetes can signal towards an underlying PC in the elderly population. Recently, several attempts have been made to develop an effective clinical tool for PC screening using a combination of history of new-onset diabetes and several other clinical and biochemical markers. On the contrary, diabetes affects the survival after treatment for PC. We describe this intimate and complex two-way relationship of diabetes and PC in this review by exploring the underlying pathogenesis.
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Affiliation(s)
- Ayan Roy
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Pazhanivel Mohan
- Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Raja Kalayarasan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
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Alpertunga I, Sadiq R, Pandya D, Lo T, Dulgher M, Evans S, Bennett B, Rennert N, Frank RC. Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer. Front Oncol 2021; 11:571855. [PMID: 33718132 PMCID: PMC7947820 DOI: 10.3389/fonc.2021.571855] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 01/20/2021] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Impaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting. PATIENTS AND METHODS Seventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables. RESULTS One thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS. CONCLUSION Lower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.
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Affiliation(s)
- Ipek Alpertunga
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Rabail Sadiq
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Deep Pandya
- Rudy L. Ruggles Biomedical Research Institute, Nuvance Health, Danbury, CT, United States
| | - Tammy Lo
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Maxim Dulgher
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Sarah Evans
- Department of Medicine, Danbury Hospital, Nuvance Health, Danbury, CT, United States
| | - Bridget Bennett
- Department of Nutrition, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Nancy Rennert
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
| | - Richard C. Frank
- Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States
- Rudy L. Ruggles Biomedical Research Institute, Nuvance Health, Danbury, CT, United States
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Shi YQ, Zhou XC, Du P, Yin MY, Xu L, Chen WJ, Xu CF. Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e21687. [PMID: 32925714 PMCID: PMC7489714 DOI: 10.1097/md.0000000000021687] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/14/2020] [Accepted: 07/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Increased risk and cancer-related mortality is observed in pancreatic cancer (PC) patients with diabetes mellitus (DM). Whether using metformin as glucose-lowering therapy can result in survival benefit in this group of patients is still unclear. METHODS A meta-analysis of 21 studies that including 38,772 patients was performed to investigate the association between metformin and overall survival in patients with PC and concurrent DM. RESULTS A significant survival benefit was observed in metformin treatment group compared with non-metformin group (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.74-0.91). These associations were observed in both subgroups of Asian countries (HR = 0.69, 95% CI: 0.60-0.79) and Western countries (HR = 0.86, 95% CI: 0.76-0.95), the former was more obvious. Survival benefit was gained for patients at early stage (HR = 0.75, 95% CI: 0.64-0.85) and mixed stage (HR = 0.81, 95% CI: 0.70-0.91), but not for patients at advanced stage (HR = 0.99, 95% CI: 0.74-1.24). Similarly, survival benefit was also observed in patients receiving surgery (HR = 0.82, 95% CI: 0.69-0.94) and comprehensive treatment (HR = 0.85, 95% CI: 0.77-0.93), but not in chemotherapy group (HR = 0.99, 95% CI: 0.67-1.30). No obvious benefit was suggested when pooled by time-varying COX model (HR = 0.94, 95% CI: 0.86-1.03). CONCLUSIONS These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings.
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Affiliation(s)
- Yu-Qi Shi
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University
| | | | - Peng Du
- Department of Invasive Technology, The First Affiliated Hospital of Soochow University
| | | | | | | | - Chun-Fang Xu
- The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
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11
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Ran Z, Chen W, Shang J, Li X. The prognostic implication of pre-treatment hemoglobin levels in esophageal cancer patients: A systematic review and meta-analysis. Meta Gene 2020. [DOI: 10.1016/j.mgene.2020.100734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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12
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Determining the Impact of a Cancer Diagnosis on Diabetes Management: A Systematic Literature Review. Am J Clin Oncol 2020; 42:870-883. [PMID: 31592804 DOI: 10.1097/coc.0000000000000612] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Cancer patients with comorbid diabetes have a 50% increased risk of all-cause mortality compared with cancer patients without diabetes. Less attention to diabetes management (glucose control, medication adherence, and diabetes self-management behaviors) during active cancer treatment is hypothesized as an explanation for worse outcomes among diabetic cancer patients. The objective of this systematic review is to determine and quantify how a cancer diagnosis impacts diabetes management. METHODS Quantitative and qualitative studies evaluating diabetes management among patients were identified by searching 4 databases: MEDLINE, EMBASE, The Cochrane Library, and Web of Science. Two independent reviewers extracted data and summarized results from eligible studies. Study quality was formally assessed. RESULTS Thirty-six studies met all inclusion criteria. We observed heterogeneity across studies in terms of study design, sample size, cancer site, type of diabetes management evaluated, and quality. Numerous articles discussed that overall, glucose control, medication adherence, and diabetes self-management behaviors declined following a cancer diagnosis. However, findings were inconsistent across studies. CONCLUSIONS Although the effects of a cancer diagnosis on diabetes management are mixed, when results across studies were synthesized together, diabetes management appeared to generally decline after a cancer diagnosis. Declines in diabetes management seem to be primarily due to shifts in the priority of care from diabetes management to cancer. A next critical step in this line of work is to identify patient and provider level predictors of better or worse diabetes management to design and test interventions aimed at improving effective diabetes management for cancer patients.
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Peila R, Rohan TE. Diabetes, Glycated Hemoglobin, and Risk of Cancer in the UK Biobank Study. Cancer Epidemiol Biomarkers Prev 2020; 29:1107-1119. [PMID: 32179703 DOI: 10.1158/1055-9965.epi-19-1623] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/24/2020] [Accepted: 03/06/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Evidence suggest that diabetes and glycated hemoglobin (HbA1c) levels are associated with cancer risk. However, previous studies have been limited variably by failure to adjust for cancer-specific risk factors (e.g., body mass index), inattention to diabetes duration and use of antidiabetic medications, and failure to stratify by obesity. METHODS We examined the association between diabetes, HbA1c, and cancer risk in the UK Biobank, using data from 476,517 participants (54% women), followed for an average period of 7.1 years. Diabetes was defined on the basis of baseline self-reported diagnosis of diabetes and/or use of diabetes medication, while HbA1c measured at baseline was categorized as low (<31 mmol/mol), normal (31-<39 mmol/mol), increased risk (39-<48 mmol/mol), and high risk for diabetes (≥48 mmol/mol). Multivariable Cox proportional hazards models were used to estimate the association of diabetes and cancer at different anatomical sites, with adjustment for cancer-specific risk factors. RESULTS Diabetes was associated with increased risk of cancers of the stomach, liver, bladder, endometrium, and lung among smokers, and with decreased risk of prostate cancer. Compared with the normal HbA1c category, the increased risk category was positively associated with risk of cancers of the colon, liver, bladder, and lung among smokers, and the high-risk category was associated with increased risk of cancers of the esophagus, liver, pancreas, and bladder, and with decreased risk of prostate cancer. CONCLUSIONS These results suggest that both diabetes and/or elevated HbA1c are associated with risk of cancer at several anatomic sites. IMPACT The associations of diabetes and HbA1c levels with cancer suggest their importance in cancer prevention.
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Affiliation(s)
- Rita Peila
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
| | - Thomas E Rohan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
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14
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Iarrobino NA, Gill BS, Klement RJ, Bernard M, Champ CE. The Impact of Serum Glucose in the Treatment of Locoregionally Advanced Pancreatic Cancer. Am J Clin Oncol 2019; 42:692-697. [PMID: 31335348 PMCID: PMC6710125 DOI: 10.1097/coc.0000000000000580] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Studies have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. This work aims to evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer. MATERIALS AND METHODS This retrospective study consisted of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated from 2004 to 2014. Kaplan-Meier survival analysis method was used to estimate time to event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios (HRs) and identify independent prognostic factors. A 6-month conditional landmark analysis excluding patients with <6 months follow-up or survival was conducted. RESULTS Median follow-up and survival was 18.1 and 18.4 months, respectively. On univariate analysis, maximum pretreatment glucose value was associated with reduced overall survival (HR 1.005, P=0.023) and locoregional control (HR 1.001, P=0.001). A pretreatment glucose value ≥200 mg/dL was associated with increased mortality in multivariable analysis (adjusted HR 1.01, P=0.015). After conditional analysis, glucose ≥200 mg/dL before local treatment was associated with reduced overall survival (adjusted HR 1.562; 95% confidence interval [CI], 1.16-2.11; P=0.003). CONCLUSIONS Elevated blood glucose before treatment of locoregionally advanced pancreatic cancer was associated with poorer outcomes. These findings should be incorporated in future clinical trial design.
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Affiliation(s)
| | - Beant S. Gill
- Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Rainer J. Klement
- Department of Radiation Oncology, Leopoldina Hospital, Schweinfurt, Germany
| | - Mark Bernard
- Department of Radiation Medicine, University of Kentucky, Lexington, KY
| | - Colin E. Champ
- Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
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15
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Wei M, Liu Y, Bi Y, Zhang ZJ. Metformin and pancreatic cancer survival: Real effect or immortal time bias? Int J Cancer 2019; 145:1822-1828. [PMID: 30848544 DOI: 10.1002/ijc.32254] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 02/25/2019] [Accepted: 03/05/2019] [Indexed: 12/20/2022]
Abstract
High heterogeneity has been reported among cohort studies investigating the association between metformin and pancreatic cancer survival. Immortal time bias may be one importance source of heterogeneity, as it is widely present in previous cohort studies and may severely impair the validity. Our study aimed to examine whether metformin therapy improves pancreatic cancer survival, and to assess the impact of immortal time bias on the effect estimation of metformin in cohort studies. PubMed, EMbase and SciVerse Scopus were searched. Pooled relative risks (RRs) were derived using a random-effects model. Pooled RR from the six studies without immortal time bias showed no association between metformin and mortality in pancreatic cancer patients (RR 0.93, 95% CI 0.82, 1.05; p = 0.22 and I2 = 75%). In contrast, pooled RR from the nine studies with immortal time bias showed a reduction of 24% in mortality associated with metformin (RR 0.76, 95% CI 0.69, 0.84; p < 0.001 and I2 = 1%). From a meta-regression model, existence of immortal time bias was associated with a reduction of 18% in the effect estimate of metformin on pancreatic cancer survival (ratio of RR 0.82, 95% CI 0.70, 0.96; p = 0.02). In conclusions, cumulative evidence from cohort studies does not support a beneficial effect of metformin on pancreatic cancer survival. The association between metformin and pancreatic cancer survival has been greatly exaggerated in previous cohort studies due to the wide existence of immortal time bias. More rigorous designs and statistical methods are needed to account for immortal time bias.
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Affiliation(s)
- Min Wei
- Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, China.,Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan, China
| | - Yu Liu
- Department of Statistics and Management, School of Management, Wuhan Institute of Technology, Wuhan, China
| | - Yongyi Bi
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan, China
| | - Zhi-Jiang Zhang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan, China
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16
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Barua R, Templeton A, Seruga B, Ocana A, Amir E, Ethier JL. Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis. Clin Oncol (R Coll Radiol) 2018; 30:215-224. [DOI: 10.1016/j.clon.2018.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 12/01/2017] [Accepted: 12/22/2017] [Indexed: 02/07/2023]
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Goehringer C, Sutter C, Kloor M, Gebert J, Slater EP, Keller M, Treiber I, Ganschow P, Kadmon M, Moog U. Double germline mutations in APC and BRCA2 in an individual with a pancreatic tumor. Fam Cancer 2017; 16:303-309. [PMID: 27838800 DOI: 10.1007/s10689-016-9952-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
We report on three brothers affected by pancreatic tumors, all due to different causes, including mutations associated with two different cancer predisposition syndromes in the same individual. In the index patient a germline mutation both in the APC and BRCA2 gene was identified while one affected brother showed the BRCA2 mutation only and another brother is supposed to have developed pancreatic cancer due to multiple non-genetic risk factors. We outline the impact of a double germline mutation in two tumor predisposition genes in one individual and proven heterogeneity of multiple cases of pancreatic tumors in one family. With the growing implementation of next generation sequence based panel testing for multiple genes involved in tumor predisposition syndromes, relevant variants in two (or more) genes will be found more frequently. This family illustrates the importance of family studies, especially when using gene panel tests.
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Affiliation(s)
- Caroline Goehringer
- Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
| | - Christian Sutter
- Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany
| | - Matthias Kloor
- Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany
| | - Johannes Gebert
- Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany
| | - Emily P Slater
- Department of Surgery, Philipps-University Marburg, Baldingerstraße, 35043, Marburg, Germany
| | - Monika Keller
- Department of Psychosomatic and General Clinical Medicine, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Irmgard Treiber
- Department of General Surgery, Heidelberg University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Petra Ganschow
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Martina Kadmon
- Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Str. 9-11, 26129, Oldenburg, Germany
| | - Ute Moog
- Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany
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Huang Y, Zheng H, Chen P, Yang J, Lin S, Liu T, Chen S, Lu S, Chen J, Chen W, Peng N. An Elevated HbA1c Level Is Associated With Short-Term Adverse Outcomes in Patients With Gastrointestinal Cancer and Type 2 Diabetes Mellitus. J Clin Med Res 2017; 9:303-309. [PMID: 28270890 PMCID: PMC5330773 DOI: 10.14740/jocmr2607w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2016] [Indexed: 02/07/2023] Open
Abstract
Background Although an elevated hemoglobin A1c (HbAc1) level is an independent predictor of worse survival in patients with both digestive cancer and diabetes mellitus, its relationship to short-term prognosis in these patients has not been addressed. This study assessed this relationship in gastrointestinal cancer (GIC) patients with type 2 diabetes mellitus (T2DM). Methods A retrospective review of patients with GIC with or without T2DM from 2004 to 2014 was performed. Patients with T2DM were grouped according to HbA1c level, either normal (mean < 7.0%) or elevated (mean ≥ 7.0%). Age- and sex-matched GIC patients without T2DM served as controls. Results One hundred and eighteen patients aged 33 - 81 years with T2DM met the study eligibility criteria; 51 were in the normal HbA1c group, and 67 were in the elevated HbA1c group. The 91 patients in the non-T2DM group were randomly selected and matched to the T2DM group in terms of admittance date, age, and sex. There was a trend toward a higher 180-day mortality rate in the T2DM group compared with the non-T2DM group (15.3% vs. 7.7%, P = 0.095) and in the elevated HbA1c group compared with the normal HbA1c group (19.4% vs. 9.8%, P = 0.151); however, the differences were not significant. The duration of the hospital stay was longer in patients with T2DM than in those without T2DM (13.2 vs. 8.9 days, P < 0.05) and in patients with elevated versus normal HbA1c levels (14.5 vs. 11.4 days, P < 0.05). Diabetic GIC patients with elevated HbA1c levels had significantly more total postoperative complications than those with normal HbA1c levels (25.4% vs. 9.8%, P < 0.05). In multivariate regression analyses, short-term adverse outcomes were strongly associated with elevated HbA1c levels (odds ratio (OR): 5.276; 95% confidence level (CI): 1.73 - 16.095; P < 0.05) and no strict antidiabetic treatment (OR: 7.65; 95% CI: 2.49 - 23.54; P < 0.001). Conclusion An elevated level of HbA1c significantly correlated with and was an independent predictor of short-term adverse outcomes in GIC patients with T2DM.
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Affiliation(s)
- Yingchun Huang
- Department of General Surgery, Jinling Hospital, Nanjing, Jiangsu Province, China; These authors contributed equally to this work
| | - Huazhen Zheng
- Department of Clinical Laboratory, The First People's Hospital of Foshan, Guangdong Province, China; These authors contributed equally to this work
| | - Peicong Chen
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China; These authors contributed equally to this work
| | - Jin Yang
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Shaomin Lin
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Tingting Liu
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Shanwei Chen
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Siqiang Lu
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Junlian Chen
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Wenpu Chen
- First Clinical Medical College, Guangdong Medical University, Zhanjiang, Guangdong Province, China; Department of Endocrinology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China
| | - Nanhai Peng
- Department of General Surgery, Jinling Hospital, Nanjing, Jiangsu Province, China
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Shi HJ, Jin C, Fu DL. Impact of postoperative glycemic control and nutritional status on clinical outcomes after total pancreatectomy. World J Gastroenterol 2017; 23:265-274. [PMID: 28127200 PMCID: PMC5236506 DOI: 10.3748/wjg.v23.i2.265] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 11/26/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the impact of glycemic control and nutritional status after total pancreatectomy (TP) on complications, tumor recurrence and overall survival. METHODS Retrospective records of 52 patients with pancreatic tumors who underwent TP were collected from 2007 to 2015. A series of clinical parameters collected before and after surgery, and during the follow-up were evaluated. The associations of glycemic control and nutritional status with complications, tumor recurrence and long-term survival were determined. Risk factors for postoperative glycemic control and nutritional status were identified. RESULTS High early postoperative fasting blood glucose (FBG) levels (OR = 4.074, 95%CI: 1.188-13.965, P = 0.025) and low early postoperative prealbumin levels (OR = 3.816, 95%CI: 1.110-13.122, P = 0.034) were significantly associated with complications after TP. Postoperative HbA1c levels over 7% (HR = 2.655, 95%CI: 1.299-5.425, P = 0.007) were identified as one of the independent risk factors for tumor recurrence. Patients with postoperative HbA1c levels over 7% had much poorer overall survival than those with HbA1c levels less than 7% (9.3 mo vs 27.6 mo, HR = 3.212, 95%CI: 1.147-8.999, P = 0.026). Patients with long-term diabetes mellitus (HR = 15.019, 95%CI: 1.278-176.211, P = 0.031) and alcohol history (B = 1.985, SE = 0.860, P = 0.025) tended to have poor glycemic control and lower body mass index levels after TP, respectively. CONCLUSION At least 3 mo are required after TP to adapt to diabetes and recover nutritional status. Glycemic control appears to have more influence over nutritional status on long-term outcomes after TP. Improvement in glycemic control and nutritional status after TP is important to prevent early complications and tumor recurrence, and improve survival.
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He L, Zhang S, Liu X, Jiang Y, Wang X, Yang Z. HbA1c-Based Score Model for Predicting Death Risk in Patients with Hepatocellular Carcinoma and Type 2 Diabetes Mellitus. J Diabetes Res 2017; 2017:3819502. [PMID: 28154829 PMCID: PMC5244025 DOI: 10.1155/2017/3819502] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 11/28/2016] [Accepted: 12/12/2016] [Indexed: 12/21/2022] Open
Abstract
Aim. To establish a new score model to predict risk of death in patients with hepatocellular carcinoma and type 2 diabetes mellitus. Methods. This was a retrospective study of 147 patients with hepatocellular carcinoma and type 2 diabetes mellitus who came to Beijing Ditan Hospital between October 2008 and June 2013. Univariate and multivariate logistic regression analysis was performed to obtain the independent factors associated with death risk. A new score model was devised according to these factors. Results. A prediction score model composed of HbA1c, NLR, age, and CTP class was devised, which ranged from 0 to 7. AUROC of the score was 0.853 (P < 0.001, 95% CI: 0.791-0.915). Scores 0-2, 3-4, and 5-7 identified patients as low-, medium-, and high-risk categories. The cumulative survival rate was 93.6%, 83.0%, and 74.5% in the low-risk group in 1, 2, and 3 years, while it was 64.0%, 46.0%, and 26.0% in the medium-risk group, whereas it was 24.0%, 12.0%, and 6.0% in the high-risk group, respectively. The cumulative survival rate was significantly higher in the low-risk group than that in the medium-risk group and high-risk group (P < 0.001). Conclusion. The HbA1c-based score model can be used to predict death risk in patients with hepatocellular carcinoma and type 2 diabetes mellitus.
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Affiliation(s)
- Lingling He
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
| | - Shuan Zhang
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
| | - Xiaoli Liu
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
| | - Yuyong Jiang
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
| | - Xianbo Wang
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
| | - Zhiyun Yang
- Department of Traditional Chinese Medicine, Beijing Ditan Hospital and Collaborative Innovation Center of Infectious Diseases, Capital Medical University, Chaoyang, Beijing 100015, China
- *Zhiyun Yang:
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Balzano G, Dugnani E, Gandolfi A, Scavini M, Pasquale V, Aleotti F, Liberati D, Di Terlizzi G, Petrella G, Reni M, Doglioni C, Bosi E, Falconi M, Piemonti L. Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study. PLoS One 2016; 11:e0166008. [PMID: 27814399 PMCID: PMC5096703 DOI: 10.1371/journal.pone.0166008] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 10/21/2016] [Indexed: 12/14/2022] Open
Abstract
AIM To investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS Prospective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery). RESULTS Of 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06-1.99]). CONCLUSION Preoperative recent onset DM has an impact on survival after the resection of PDAC.
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Affiliation(s)
- Gianpaolo Balzano
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center; IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Erica Dugnani
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alessandra Gandolfi
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Marina Scavini
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Valentina Pasquale
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Aleotti
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center; IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniela Liberati
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gaetano Di Terlizzi
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giovanna Petrella
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Michele Reni
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Doglioni
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Emanuele Bosi
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center; IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Lorenzo Piemonti
- San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy
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Hope C, Robertshaw A, Cheung KL, Idris I, English E. Relationship between HbA1c and cancer in people with or without diabetes: a systematic review. Diabet Med 2016; 33:1013-25. [PMID: 26577885 DOI: 10.1111/dme.13031] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2015] [Indexed: 12/25/2022]
Abstract
AIM To identify the relationship between HbA1c and cancers in people with or without diabetes. BACKGROUND Cancer is a major public health problem, accounting for 8.2 million deaths worldwide in 2012. HbA1c level has been associated with the risk of developing certain cancers, although the existing evidence is conflicting. METHODS EMBASE, MEDLINE, CINAHL and the Cochrane Library were searched. Eligible articles included randomized controlled trials, cohort studies, case-control studies, systematic reviews and meta-analyses. Participants of either sex, with or without Type 1 or 2 diabetes, were included. The studies were assessed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria by two independent assessors. No meta-analysis was performed because of the heterogeneity of results. RESULTS A total of 19 studies from 1006 met the inclusion criteria, of which 14 were cohort studies and five were nested case-control studies. Eight studies investigated outcomes for all cancer sites. Four of these studies reported that higher HbA1c levels were associated with higher incidence and/or mortality risk for all cancers. One study observed a U-shaped relationship between HbA1c and cancer incidence and mortality. Increasing HbA1c levels were associated with increasing risk of developing colorectal, pancreatic, respiratory and female genital tract cancers. No increased risk was observed for breast cancer, gastrointestinal or urological malignancies. CONCLUSION HbA1c appears to be associated with cancer incidence and/or cancer mortality, but further studies are needed to fully understand the complex relationship between HbA1c and cancer.
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Affiliation(s)
- C Hope
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - A Robertshaw
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - K L Cheung
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - I Idris
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - E English
- School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK
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Song S, Wang B, Zhang X, Hao L, Hu X, Li Z, Sun S. Long-Term Diabetes Mellitus Is Associated with an Increased Risk of Pancreatic Cancer: A Meta-Analysis. PLoS One 2015. [PMID: 26222906 PMCID: PMC4519136 DOI: 10.1371/journal.pone.0134321] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose Previous studies have shown a bidirectional relationship between diabetes and pancreatic cancer (PC). In particular, new-onset diabetes might be induced by PC, and people with long-term diabetes might be at increased risk for the development of PC. The purpose of our study was to examine whether long-term diabetes represented an independent risk factor for PC development. Methodology A literature search was performed by searching electronic databases for studies published before July 1, 2014, and relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. Data pertaining to diabetes were recorded at both individual and study levels, with RRs calculated separately to analyze the relationship between the duration of diabetes and the development of PC. Results Forty-four studies were included in this meta-analysis, including 18 studies with a case-control design, 5 with a nested case-control design and 21 with a cohort design. The overall summary estimate for the relationship between the population with a duration of diabetes ≥2 years and PC was 1.64 (1.52-1.78). The pooled RR (95% CI) of PC for the population with a duration of diabetes ≥5 years was 1.58 (1.42-1.75). For the population with a duration of diabetes ≥10 years, the RR (95% CI) of PC was 1.50 (1.28-1.75). Conclusions Our study suggests that long-term diabetes mellitus is associated with an increased risk of PC. However, the level of risk is negatively correlated with increasing diabetes mellitus duration.
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Affiliation(s)
- Shanshan Song
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Baosheng Wang
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xin Zhang
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Liliang Hao
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xianliang Hu
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongxiang Li
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shaolong Sun
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- * E-mail:
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