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Devasahayam Arokia Balaya R, Sen P, Grant CW, Zenka R, Sappani M, Lakshmanan J, Athreya AP, Kandasamy RK, Pandey A, Byeon SK. An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum. J Gastroenterol 2025; 60:496-511. [PMID: 39666045 DOI: 10.1007/s00535-024-02197-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 12/01/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC. METHODS We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC. RESULTS We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites. CONCLUSIONS Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.
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Affiliation(s)
| | - Partho Sen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Caroline W Grant
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA
| | - Roman Zenka
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Marimuthu Sappani
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, 632002, India
| | - Jeyaseelan Lakshmanan
- College of Medicine, Mohammad Bin Rashid University of Medicine and Health Sciences, Dubai, 505055, UAE
| | - Arjun P Athreya
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA
- Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Richard K Kandasamy
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA
- Manipal Academy of Higher Education, Manipal, Karnataka, 5761904, India
| | - Akhilesh Pandey
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
- Manipal Academy of Higher Education, Manipal, Karnataka, 5761904, India.
- Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
| | - Seul Kee Byeon
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
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Wu P, Chen K, He J. Palliative management for malignant biliary obstruction and gastric outlet obstruction from pancreatic cancer. Ann Gastroenterol Surg 2025; 9:218-225. [PMID: 40046529 PMCID: PMC11877337 DOI: 10.1002/ags3.12902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/17/2024] [Accepted: 12/11/2024] [Indexed: 06/01/2025] Open
Abstract
Pancreatic cancer is among the leading causes of gastrointestinal cancer-related death, with a dismal prognosis. Over 80% of pancreatic cancer patients present with advanced disease, making curative resection unfeasible. These patients are often presented with malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO). In these cases, palliative management is aimed to alleviate symptoms, enhance quality of life, and facilitate subsequent chemotherapy. Currently, neoadjuvant chemotherapy is frequently used in both borderline resectable and resectable pancreatic cancer, necessitating effective biliary and gastrointestinal drainage in a growing number of patients. Traditionally, surgical bypass was the gold standard, performed via either a minimally invasive or open approach. However, notable progress has emerged in developing endoscopic techniques, such as endoscopic retrograde cholangiopancreatography (ERCP) stenting for MBO and endoscopic enteral stenting for GOO. While these procedures provide rapid symptom relief, they are associated with higher stent dysfunction rates and more frequent re-intervention needs. When ERCP fails, percutaneous transhepatic biliary drainage is a widely accepted alternative for MBO. Endoscopic ultrasound (EUS)-guided techniques, including EUS-guided biliary drainage and EUS-guided gastroenterostomy, have recently gained prominence. Emerging clinical data suggest that these methods may be superior, potentially becoming the preferred first-line palliative treatment for unresectable pancreatic cancer. This review will summarize the current evidence on managing MBO and GOO in patients with pancreatic cancer.
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Affiliation(s)
- Pengfei Wu
- Department of SurgeryJohns Hopkins University School of MedicineBaltimoreMarylandUSA
- Pancreas CenterThe First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Pancreas Institute of Nanjing Medical UniversityNanjingChina
| | - Kai Chen
- Department of SurgeryJohns Hopkins University School of MedicineBaltimoreMarylandUSA
- Department of Hepatobiliary and Pancreatic SurgeryPeking University First HospitalBeijingChina
| | - Jin He
- Department of SurgeryJohns Hopkins University School of MedicineBaltimoreMarylandUSA
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Aeschbacher P, Wenning AS, Katou S, Morgul H, Juratli M, Becker F, Büdeyri I, Gloor B, Pascher A, Struecker B, Andreou A. Impact of Routine and Selective Preoperative Endoscopic Retrograde Cholangiopancreatography with Stent Placement on Postoperative and Oncologic Outcomes Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma. Biomedicines 2025; 13:333. [PMID: 40002746 PMCID: PMC11853506 DOI: 10.3390/biomedicines13020333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/17/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Background: According to current guidelines, preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting (ERCP/stenting) is often necessary in patients with obstructive jaundice due to pancreatic ductal adenocarcinoma (PDAC), including severe jaundice (bilirubin > 250 umol/l), pruritus, cholangitis, cholestatic liver dysfunction, renal failure, severe malnutrition, or delayed surgery for tumors requiring neoadjuvant chemotherapy. We aimed to investigate the impact of preoperative ERCP/stenting on postoperative and long-term outcomes following pancreaticoduodenectomy (PD) for PDAC. Methods: Clinicopathological data of patients who underwent partial/total PD for PDAC between 2012 and 2019 in two hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We compared patients treated with preoperative ERCP/stenting with those directly undergoing surgery according to postoperative morbidity, postoperative mortality, overall survival (OS) and disease-free survival (DFS). Results: During the study period, 192 patients underwent partial/total PD for PDAC. ERCP/stenting was performed in 105 patients, and 87 patients underwent resection without prior intervention. Postoperative 90-day overall morbidity rate (71% vs. 56%, p = 0.029) and superficial surgical site infection (SSI) rate (39% vs. 17%, p < 0.001) were significantly worse following preoperative ERCP/stenting. Major postoperative morbidity rate (18% vs. 21%, p = 0.650), organ/space SSI rate (7% vs. 14%, p = 0.100), and 90-day postoperative mortality rate (4% vs. 2%, p = 0.549) did not significantly differ between the two groups. After excluding 44 patients for whom the indication for ERCP/stenting was not consistent with current guidelines, ERCP/stenting was associated with a higher superficial SSI rate (36% vs. 17%, p = 0.009) and shorter length of stay (12 vs. 16 days, p = 0.004). Median OS (ERCP/stenting: 18 months vs. no ERCP/stenting: 23 months, p = 0.490) and median DFS (ERCP/stenting: 14 months vs. no ERCP/stenting: 18 months, p = 0.645) were independent from the utilization of ERCP/stenting. Conclusions: Preoperative ERCP/stenting in patients with PDAC can be performed without increasing organ/space SSI, major perioperative morbidity, and mortality rates and without worsening oncologic outcomes. However, it is associated with higher superficial SSI rates. If ERCP/stenting is not performed routinely but according to current guidelines, it is also associated with a shorter length of hospital stay. Further refinement of the indications for preoperative ERCP/stenting may reduce superficial SSI rates.
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Affiliation(s)
- Pauline Aeschbacher
- Department of Visceral Surgery und Medicine, lnselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Anna Silvia Wenning
- Department of Visceral Surgery und Medicine, lnselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Shadi Katou
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Haluk Morgul
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Mazen Juratli
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Felix Becker
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Ibrahim Büdeyri
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Beat Gloor
- Department of Visceral Surgery und Medicine, lnselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Benjamin Struecker
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
| | - Andreas Andreou
- Department of General, Visceral and Transplant Surgery, University Hospital Munster, 48149 Münster, Germany
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Maatouk M, Kbir GH, Ben Dhaou A, Nouira M, Chamekh A, Daldoul S, Sayari S, Ben Moussa M. Pancreatic surgery after preoperative biliary drainage in periampullary cancers: does timing matter? A systematic review and meta-analysis. HPB (Oxford) 2025; 27:10-20. [PMID: 39500706 DOI: 10.1016/j.hpb.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 09/14/2024] [Accepted: 10/08/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND Preoperative biliary drainage (PBD) has been introduced to control the negative effects of obstructive jaundice in patients undergoing pancreaticoduodenectomy (PD). The optimal time interval between PBD and PD remains unclear. The purpose of our systematic review and meta-analysis was to evaluate the optimal period for PBD before PD. METHODS Studies were searched in PubMed, Science Direct, Google Scholar and Cochrane Library until 30 March 2024. Studies using PBD in patients with malignant obstructive jaundice that compared the short duration group (SDG) with prolonged duration group (PDG) were included in this study. The definitions of short and prolonged drainage were based on cut-off times reported in the included studies. RESULTS Twelve studies were included. Based on the available data, short and prolonged drainage periods were defined by comparing the outcomes of surgeries performed within specific cut-off times of 2 weeks, 3 weeks, and 4 weeks after PBD. No significant differences were observed between the SDG and PDG in mortality, major morbidity, pancreatic fistula, post pancreatectomy haemorrhage, septic complications, operative time, and hospital stay, regardless of the delay of surgery. CONCLUSION When PBD is needed, pancreatic resection could be performed at the earliest possible stage after achieving optimal perioperative care.
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Affiliation(s)
- Mohamed Maatouk
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia.
| | - Ghassen H Kbir
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Anis Ben Dhaou
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Mariem Nouira
- Service of Medical Epidemiology, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Atef Chamekh
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Sami Daldoul
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Sofien Sayari
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Mounir Ben Moussa
- A21 Surgery Department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia
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Zhang W, Chen J, Zhang W, Xu M. Advances in Endoscopic Ultrasound in Pancreatic Cancer Screening, Diagnosis, and Palliative Care. Biomedicines 2024; 13:76. [PMID: 39857661 PMCID: PMC11762820 DOI: 10.3390/biomedicines13010076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/27/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
Pancreatic cancer is a highly aggressive malignancy with a profoundly poor prognosis. Clinically, the condition most frequently manifests with symptoms including painless jaundice, abdominal discomfort, and back pain. Early diagnosis and the implementation of effective therapeutic strategies are critical for improving patient survival outcomes. However, merely 10-20% of patients are diagnosed at an early stage, with the majority presenting at advanced stages, often with metastasis. Consequently, early detection and intervention are crucial for enhancing prognosis. The widespread adoption of endoscopic ultrasonography (EUS) technology in recent years has significantly enhanced the diagnostic accuracy for pancreatic space-occupying lesions. EUS is increasingly recognized for its pivotal role in alleviating malignant biliary obstruction (MBO), gastric outlet obstruction (GOO), and refractory pain in advanced pancreatic cancer. This article aims to provide an overall review of the current applications of EUS in the diagnosis and treatment of pancreatic cancer, exploring its advantages and limitations in early screening, diagnosis, and palliative care. Furthermore, this review explores potential future directions in the field, aiming to provide valuable insights to inform and enhance the clinical management of pancreatic cancer.
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Affiliation(s)
- Wenyu Zhang
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
| | - Jingzheng Chen
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
| | - Wei Zhang
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
- Department of Gastroenterology, Digestive Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
| | - Min Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
- Department of Gastroenterology, Digestive Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China
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Ledenko M, Toskich B, Mehner C, Ceylan H, Patel T. Therapeutic biliary stents: applications and opportunities. Expert Rev Med Devices 2024; 21:399-409. [PMID: 38716580 DOI: 10.1080/17434440.2024.2341960] [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: 01/05/2024] [Accepted: 04/08/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION Biliary stents are used to optimize ductal patency and enable bile flow in the management of obstruction or injury related to biliary tract tumors, strictures, stones, or leaks. Although direct therapeutic applications of biliary stents are less well developed, stents can be used to deliver drugs, radioisotopes, and photodynamic therapy. AREAS COVERED This report provides an in-depth overview of the clinical indications, and therapeutic utility of biliary stents. Unique considerations for the design of biliary stents are described. The properties and functionalities of materials used for stents such as metal alloys, plastic polymers, or biodegradable materials are described, and opportunities for design of future stents are outlined. Current and potential applications of stents for therapeutic applications for biliary tract diseases are described. EXPERT OPINION Therapeutic biliary stents could be used to minimize inflammation, prevent stricture formation, reduce infections, or provide localized anti-cancer therapy for biliary tract cancers. Stents could be transformed into therapeutic platforms using advanced materials, 3D printing, nanotechnology, and artificial intelligence. Whilst clinical study and validation will be required for adoption, future advances in stent design and materials are expected to expand the use of therapeutic biliary stents for the treatment of biliary tract disorders.
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Affiliation(s)
- Matthew Ledenko
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Beau Toskich
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Christine Mehner
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
| | - Hakan Ceylan
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
| | - Tushar Patel
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
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Eaglehouse YL, Darmon S, Gage MM, Shriver CD, Zhu K. Characteristics Associated With Survival in Surgically Nonresected Pancreatic Adenocarcinoma in the Military Health System. Am J Clin Oncol 2024; 47:64-70. [PMID: 37851358 PMCID: PMC10805355 DOI: 10.1097/coc.0000000000001057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
OBJECTIVES Pancreatic cancer is often diagnosed at advanced stages with high-case fatality. Many tumors are not surgically resectable. We aimed to identify features associated with survival in patients with surgically nonresected pancreatic cancer in the Military Health System. METHODS We used the Military Cancer Epidemiology database to identify the Department of Defense beneficiaries aged 18 and older diagnosed with a primary pancreatic adenocarcinoma between January 1998 and December 2014 who did not receive oncologic surgery as treatment. We used Cox Proportional Hazard regression with stepwise procedures to select the sociodemographic and clinical characteristics related to 2-year overall survival, expressed as adjusted hazard ratios (aHR) and 95% CIs. RESULTS Among 1148 patients with surgically nonresected pancreatic cancer, sex, race-ethnicity, marital status, and socioeconomic indicators were not selected in association with survival. A higher comorbidity count (aHR 1.30, 95% CI: 1.06-1.59 for 5 vs. 0), jaundice at diagnosis (aHR 1.57, 95% CI: 1.33-1.85 vs. no), tumor grade G3 or G4 (aHR 1.32, 95% CI: 1.05-1.67 vs. G1/G2), tumor location in pancreas tail (aHR 1.49, 95% CI: 1.22-1.83 vs. head) or body (aHR 1.30, 95% CI: 1.04-1.62 vs. head), and metastases were associated with survival. Patients receiving chemotherapy (aHR 0.66, 95% CI: 0.57-0.76) had better survival compared with no treatment. CONCLUSIONS In a comprehensive health system, sociodemographic characteristics were not related to survival in surgically nonresected pancreatic cancer. This implicates access to care in reducing survival disparities in advanced pancreatic cancer and emphasizes the importance of treating patients based on clinical features.
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Affiliation(s)
- Yvonne L. Eaglehouse
- Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc
| | - Sarah Darmon
- Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc
| | - Michele M. Gage
- Departments of Surgery
- Division of Surgical Oncology, Walter Reed National Military Medical Center, Bethesda, MD
| | - Craig D. Shriver
- Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Departments of Surgery
| | - Kangmin Zhu
- Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc
- Preventive Medicine & Biostatistics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences
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Chen Z, Lin Y. A commentary on 'Minimally invasive versus open total pancreatectomy: a systematic review and meta-analysis'. Int J Surg 2024; 110:600-601. [PMID: 37738018 PMCID: PMC10793832 DOI: 10.1097/js9.0000000000000770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 09/09/2023] [Indexed: 09/23/2023]
Affiliation(s)
| | - Yonghua Lin
- Hepatological Surgery Department, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
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Hjaltelin JX, Novitski SI, Jørgensen IF, Siggaard T, Vulpius SA, Westergaard D, Johansen JS, Chen IM, Juhl Jensen L, Brunak S. Pancreatic cancer symptom trajectories from Danish registry data and free text in electronic health records. eLife 2023; 12:e84919. [PMID: 37988407 PMCID: PMC10662947 DOI: 10.7554/elife.84919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 10/19/2023] [Indexed: 11/23/2023] Open
Abstract
Pancreatic cancer is one of the deadliest cancer types with poor treatment options. Better detection of early symptoms and relevant disease correlations could improve pancreatic cancer prognosis. In this retrospective study, we used symptom and disease codes (ICD-10) from the Danish National Patient Registry (NPR) encompassing 6.9 million patients from 1994 to 2018,, of whom 23,592 were diagnosed with pancreatic cancer. The Danish cancer registry included 18,523 of these patients. To complement and compare the registry diagnosis codes with deeper clinical data, we used a text mining approach to extract symptoms from free text clinical notes in electronic health records (3078 pancreatic cancer patients and 30,780 controls). We used both data sources to generate and compare symptom disease trajectories to uncover temporal patterns of symptoms prior to pancreatic cancer diagnosis for the same patients. We show that the text mining of the clinical notes was able to complement the registry-based symptoms by capturing more symptoms prior to pancreatic cancer diagnosis. For example, 'Blood pressure reading without diagnosis', 'Abnormalities of heartbeat', and 'Intestinal obstruction' were not found for the registry-based analysis. Chaining symptoms together in trajectories identified two groups of patients with lower median survival (<90 days) following the trajectories 'Cough→Jaundice→Intestinal obstruction' and 'Pain→Jaundice→Abnormal results of function studies'. These results provide a comprehensive comparison of the two types of pancreatic cancer symptom trajectories, which in combination can leverage the full potential of the health data and ultimately provide a fuller picture for detection of early risk factors for pancreatic cancer.
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Affiliation(s)
- Jessica Xin Hjaltelin
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Sif Ingibergsdóttir Novitski
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Isabella Friis Jørgensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Troels Siggaard
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Siri Amalie Vulpius
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - David Westergaard
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | | | - Inna M Chen
- Department of Oncology, Copenhagen University Hospital - Herlev and GentofteHerlevDenmark
| | - Lars Juhl Jensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Søren Brunak
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
- Copenhagen University Hospital, Rigshospitalet, BlegdamsvejCopenhagenDenmark
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10
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Mazur R, Trna J. Principles of Palliative and Supportive Care in Pancreatic Cancer: A Review. Biomedicines 2023; 11:2690. [PMID: 37893064 PMCID: PMC10603964 DOI: 10.3390/biomedicines11102690] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/24/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms often appear that make diagnosis difficult, e.g., weight loss, loss of appetite, nausea and vomiting, and general weakness. Only 10-20% of patients are diagnosed at an early stage. A cure is practically only possible with a radical surgical operation. In the case of locally advanced findings, neoadjuvant therapy is administered. Among the therapeutic options offered are chemotherapy, radiotherapy (including stereotactic radiotherapy-SBRT), targeted treatment, or immunotherapy. In the case of metastatic disease, of which more than half are present at diagnosis, the goal is to relieve the patient of problems. Metastatic PDAC can cause problems arising from the localization of distant metastases, but it also locally affects the organs it infiltrates. In our review article, we focus on the largest group of patients, those with locally advanced disease and metastatic disease-symptoms related to the infiltration or destruction of the pancreatic parenchyma and the growth of the tumor into the surrounding. Therefore, we deal with biliary or duodenal obstruction, gastric outlet syndrome, bleeding and thromboembolic diseases, pain, depression, and fatigue, as well as pancreatic exocrine insufficiency and malnutrition. Metastatic spread is most often to the liver, peritoneum, or lungs. The presented overview aims to offer current therapeutic options across disciplines. In accordance with modern oncology, a multidisciplinary approach with a procedure tailored to the specific patient remains the gold standard.
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Affiliation(s)
| | - Jan Trna
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic;
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11
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Qin X, Ran T, Chen Y, Zhang Y, Wang D, Zhou C, Zou D. Artificial Intelligence in Endoscopic Ultrasonography-Guided Fine-Needle Aspiration/Biopsy (EUS-FNA/B) for Solid Pancreatic Lesions: Opportunities and Challenges. Diagnostics (Basel) 2023; 13:3054. [PMID: 37835797 PMCID: PMC10572518 DOI: 10.3390/diagnostics13193054] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/06/2023] [Accepted: 09/06/2023] [Indexed: 10/15/2023] Open
Abstract
Solid pancreatic lesions (SPLs) encompass a variety of benign and malignant diseases and accurate diagnosis is crucial for guiding appropriate treatment decisions. Endoscopic ultrasonography-guided fine-needle aspiration/biopsy (EUS-FNA/B) serves as a front-line diagnostic tool for pancreatic mass lesions and is widely used in clinical practice. Artificial intelligence (AI) is a mathematical technique that automates the learning and recognition of data patterns. Its strong self-learning ability and unbiased nature have led to its gradual adoption in the medical field. In this paper, we describe the fundamentals of AI and provide a summary of reports on AI in EUS-FNA/B to help endoscopists understand and realize its potential in improving pathological diagnosis and guiding targeted EUS-FNA/B. However, AI models have limitations and shortages that need to be addressed before clinical use. Furthermore, as most AI studies are retrospective, large-scale prospective clinical trials are necessary to evaluate their clinical usefulness accurately. Although AI in EUS-FNA/B is still in its infancy, the constant input of clinical data and the advancements in computer technology are expected to make computer-aided diagnosis and treatment more feasible.
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Affiliation(s)
| | | | | | | | | | - Chunhua Zhou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China; (X.Q.); (T.R.); (Y.C.); (Y.Z.); (D.W.)
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China; (X.Q.); (T.R.); (Y.C.); (Y.Z.); (D.W.)
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12
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Fu Z, Song J, Pi Y, Sun X, Liu M, Xiao Z, Chen J. A Risk Prediction Model for Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis After Stent Insertion for Malignant Biliary Obstruction: Development and Validation. Dig Dis Sci 2023; 68:1574-1584. [PMID: 35989385 DOI: 10.1007/s10620-022-07649-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 07/25/2022] [Indexed: 12/09/2022]
Abstract
OBJECTIVES Pancreatitis is the most common complication of post-endoscopic retrograde cholangiopancreatography (ERCP). There are currently no prediction models, particularly for post-ERCP pancreatitis (PEP) after biliary stent placement due to malignant biliary obstruction (MBO). To that end, we aim to develop and validate a predictive model for PEP. METHODS We retrospectively analyzed the data of patients who underwent ERCP for biliary stent placement due to MBO at the Second Affiliated Hospital of Harbin Medical University from January 1, 2014 to August 31, 2021. The eligible patients were randomly allocated to the development and validation cohorts. A prediction model was built using the development cohort, and the model's effect was validated using a validation cohort. RESULTS A total of 1524 patients were enrolled, including 1016 in the development cohort and 508 in the validation cohort, with an overall PEP rate of 7.1%. The model's predictors included acute pancreatitis history, the absence of pancreatic duct dilation, nonpancreatic cancer, difficult cannulation, and pancreatic injection. The area under the curve (AUC) in the development cohort was 0.810, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 1.53%, 9.12%, and 36.36%, respectively. Meanwhile, the AUC of the validation cohort was 0.781, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 4.17%, 8.75%, and 41.67%, respectively. CONCLUSIONS This study was the first to build and validate a risk prediction model, especially for PEP after biliary stent placement due to MBO. Moreover, this model might assist clinicians in identifying high-risk patients and help implement preventive measures in a more timely manner.
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Affiliation(s)
- Zhifeng Fu
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Jitao Song
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Yilin Pi
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Xianxin Sun
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Maoning Liu
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Zunlong Xiao
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China
| | - Jing Chen
- Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China.
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13
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Svatoň R, Procházka V, Hanslianová M, Kala Z. Influence of bacteriobilia on postoperative complications in patients with periampullary tumors. Asian J Surg 2023; 46:1193-1198. [PMID: 36057492 DOI: 10.1016/j.asjsur.2022.08.072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/21/2021] [Accepted: 08/17/2022] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND Periampullary tumours (PAT) may cause obstruction of distal choledochus. The bile stasis is a risk factor for microbial colonisation of bile (bacteriobilia), cholangitis, hepatic insufficiency and coagulopathy. PAT obstruction can be managed surgically or non-operatively - by inserting a biliary drain or stent (BDS). Although BDS allows for adequate bile drainage, liver function restitution and coagulopathy, increased bacteriobilia has been reported and this is associated with an increased incidence of postoperative complications. METHODS A monocentric, prospective, comparative study including 100 patients operated with PAT. The effects of bacteriobilia and the presence of a drain in the biliary tract on the development of postoperative complications were evaluated. RESULTS Positive microbial findings in bile were found in 67% of patients. It was 98% in the biliary drain group vs. 36% in non-drained patients (p = 0.0001). In 68% 2 or more different bacterial strains were simultaneously present (p = 0.0001). Patients with a positive microbial finding in bile had more frequent incidence of infectious complications 40.2% (27) vs. 9.1% (3); p = 0.0011. The most frequent infectious complication was wound infection 29.8% (20) vs. 3.03% (1); p = 0.0014. Similarly, a higher incidence of postoperative infectious complications occurred in patients with BDS - 36% (18) vs. 24% (12); p = 0.2752. CONCLUSION The presence of a drain or stent in the biliary tract significantly increases the microbial colonisation of bile. It is associated with a significant increase in infectious complications, especially infections in the wound.
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Affiliation(s)
- Roman Svatoň
- Department of Surgery, University Hospital Brno Faculty of Medicine, Masaryk University, Brno, Czech Republic.
| | - Vladimír Procházka
- Department of Surgery, University Hospital Brno Faculty of Medicine, Masaryk University, Brno, Czech Republic.
| | - Markéta Hanslianová
- Department of Microbiology, University Hospital Brno Faculty of Medicine, Masaryk University, Brno, Czech Republic.
| | - Zdeněk Kala
- Department of Surgery, University Hospital Brno Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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14
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Mejia A, Shah J, Vivian E, Beard R, Acharya P, Gutierrez JCB. Outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing robotic (RPD) or open pancreaticoduodenectomies (OPD): a propensity score-weighted survival analysis. J Robot Surg 2022; 17:1085-1096. [PMID: 36581740 DOI: 10.1007/s11701-022-01510-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/04/2022] [Indexed: 12/31/2022]
Abstract
The purpose of this study was to compare the survival, recurrence, and complication rates in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent robotic pancreaticoduodenectomy (RPD) or open pancreaticoduodenectomy (OPD) and who received adjuvant therapy. The study was a single-center retrospective analysis of consecutive PDAC patients who underwent RPD/OPD. Patient characteristics, tumor findings, neoadjuvant therapy, adjuvant therapies, overall survival (OS) and recurrence-free survival (RFS) were compared between the OPD and RPD cohorts. Cox proportional hazard regression with and without propensity score matching was used to establish the association between predictors and outcomes. One hundred PDAC patients underwent OPD (n = 36) or RPD (n = 64) from 2013 to 2019. Cox proportional hazard models showed that baseline bilirubin (HR 1.6, p = 0.0006) and operative characteristics such as the number of positive lymph nodes (HR 1.1, p = 0.002), lymph node ratio (HR 1.6, p = 0.001), tumor grade (HR 1.7, p = 0.02), and TNM classification (HR 2.3, p = 0.01) were associated with OS. The independent predictors post-intervention associated with mortality were adjuvant therapy (HR 0.4, p = 0.0003), ISGPS complications (HR 2.8, p = 0.02), and 90-day readmission (HR 2, p = 0.004). After adjustment for these predictors, adjuvant therapy, baseline bilirubin, lymph node ratio, and tumor grade remained the main predictors of mortality. Baseline bilirubin, adjuvant therapy, lymph node ratio, and tumor grade were the main determinants of mortality after OPD or RPD. There was no significant difference in OS and RFS after RPD or OPD in PC patients who received adjuvant therapy.
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Affiliation(s)
- Alejandro Mejia
- The Liver Institute, Methodist Dallas Medical Center, 1411 Beckley Avenue, Suite 268, Dallas, TX, 75203, USA.
| | - Jimmy Shah
- Methodist Digestive Institute, Methodist Dallas Medical Center, Dallas, TX, 75203, USA
| | - Elaina Vivian
- Methodist Digestive Institute, Methodist Dallas Medical Center, Dallas, TX, 75203, USA
| | - Robyn Beard
- Methodist Digestive Institute, Methodist Dallas Medical Center, Dallas, TX, 75203, USA
| | - Priyanka Acharya
- Clinical Research Institute, Methodist Health System, Dallas, TX, 75203, USA
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15
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van Gils L, Verbeek R, Wellerdieck N, Bollen T, van Leeuwen M, Schwartz M, Vleggaar F, Molenaar IQQ, van Santvoort H, van Hooft J, Verdonk R, Weusten B. Preoperative biliary drainage in severely jaundiced patients with pancreatic head cancer: A retrospective cohort study. HPB (Oxford) 2022; 24:1888-1897. [PMID: 35803831 DOI: 10.1016/j.hpb.2022.05.1345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 05/22/2022] [Accepted: 05/30/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Guidelines recommend against preoperative biliary drainage (PBD) in patients with pancreatic head cancer if bilirubin levels are <250 μmol/l. However, patients with higher bilirubin levels undergo PBD, despite the lack of supporting evidence. This study aims to evaluate outcomes in patients with a bilirubin level ≥250 and < 250. METHODS Patients were identified from databases of 3 centers. Outcomes were compared in patients with a bilirubin level ≥250 versus <250 both at the time of diagnosis and directly prior to surgery. RESULTS 244 patients were included. PBD was performed in 64% (123/191) with bilirubin <250 at diagnosis and 91% (48/53) with bilirubin ≥250. PBD technical success (83% vs. 81%, p = 0.80) and PBD related complications (33% vs. 29%, p = 0.60) did not differ between these groups. Analyzing bilirubin levels ≥250 versus <250 directly prior to surgery, no differences in severe postoperative complications and mortality were found. CONCLUSIONS In patients with a pancreatic head cancer, PBD technical success and complications, and severe postoperative complications did not differ between patients with a bilirubin level ≥250 and < 250. Our study does not support a different approach regarding PBD in patients with severe jaundice.
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Affiliation(s)
- Luuk van Gils
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Romy Verbeek
- Department of Gastroenterology and Hepatology, Groene Hart Hospital, Gouda, the Netherlands
| | - Nienke Wellerdieck
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Thomas Bollen
- Department of Radiology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Maarten van Leeuwen
- Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Matthijs Schwartz
- Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, the Netherlands
| | - Frank Vleggaar
- Department of Radiology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - I Q Quintus Molenaar
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Hjalmar van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Janine van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Robert Verdonk
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Bas Weusten
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
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16
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Biesel EA, Chikhladze S, Ruess DA, Hopt UT, Fichtner-Feigl S, Wittel UA. Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy: An Analysis of Single-Center Standards. Pancreas 2022; 51:1140-1145. [PMID: 37078937 DOI: 10.1097/mpa.0000000000002166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2023]
Abstract
OBJECTIVES Perioperative morbidity after pancreatoduodenectomies is still high. One potentially responsible factor is the insertion of bile duct stents before surgery. In our single-center study, we evaluated the influence of preoperative bile duct stenting combined with perioperative antibiotic therapy versus primary surgery in carcinoma patients. METHODS Clinical data of 973 patients undergoing pancreatoduodenectomy at the University Hospital Freiburg from 2002 to 2018 were explored retrospectively. Postoperative pancreatic fistula, delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) were graded by current international definitions. Patients with pancreatic ductal adenocarcinoma or periampullary carcinoma were included. RESULTS We included 634 patients of whom 372 (58.7%) were treated with preoperative bile duct stenting. No difference concerning postoperative pancreatic fistula was observed (P = 0.479). We found more wound infections (stent 18.4%, no stent 11.1%, P = 0.008) but a significantly lower rate of PPH and DGE in stented patients (PPH 7.5% vs 11.9%, P = 0.044; DGE 16.5% vs 22.5%, P = 0.039). Surprisingly, intra-abdominal abscesses were reduced in stented patients (9.4% vs 15.0%, P = 0.022), just as insufficiencies of the biliodigestive anastomosis (P = 0.021). CONCLUSIONS Perioperative antibiotic therapy seems to reduce the risk for severe intra-abdominal infectious complications in stent-bearing patients.
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Affiliation(s)
- Esther A Biesel
- From the Department of General and Visceral Surgery, University of Freiburg Medical Center, Freiburg, Germany
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17
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Balzano V, Laurent E, Florence AM, Lecuyer AI, Lefebvre C, Heitzmann P, Hammel P, Lecomte T, Grammatico-Guillon L. Time interval from last visit to imaging diagnosis influences outcome in pancreatic adenocarcinoma: A regional population-based study on linked medico-administrative and clinical data. Ther Adv Med Oncol 2022; 14:17588359221113264. [PMID: 36090802 PMCID: PMC9449516 DOI: 10.1177/17588359221113264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/24/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Excessive waiting time intervals for the diagnosis and treatment of patients with pancreatic cancer can influence their prognosis but they remain unclear. The objective was to describe time intervals from the medical visit to diagnostic imaging and to treatment and their prognostic impact in pancreatic cancer in one French region. Methods: This retrospective observational multicentre study included all patients with pancreatic cancer seen for the first time in 2017 in multidisciplinary team meetings (MTMs), where clinical data were collected. A probabilistic matching with the medico-administrative data from the French national healthcare database (Système National des Données de Santé) was performed to define the care pathway from clinical presentation to the beginning of treatment. Median key time intervals were estimated for both resected and unresected tumours. Factors associated with 1-year survival were studied using Cox model. Results: A total of 324 patients (88% of total patients with MTM presentation) were matched and included: male 54%, mean age 72 years ±9.2, Eastern Cooperative Oncology Group (ECOG) PS > 1 19.5%, metastatic disease at diagnosis 47.4%, tumour resection 16%. At 1 year, 57% had died (65% in the unresected group and 17% in the resected group). The median time interval from the medical visit to diagnostic imaging was 15 days [Q1–Q3: 8–44]. After imaging, median time intervals to definite diagnosis and to first treatment were 11 and 20 days, respectively. Significant prognostic factors associated with the risk of death at 1 year were ECOG PS > 1 (hazard ratio (HR) 2.1 [1.4–3.0]), metastasis (HR 2.7 [1.9–3.9]), no tumour resection (HR 2.7 [1.3–5.6]) and time interval between the medical visit and diagnostic imaging ⩾25 days (HR 1.7 [1.2–2.3]). Conclusion: Delay in access to diagnostic imaging impacted survival in patients with pancreatic cancer, regardless of whether tumour resection had been performed.
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Affiliation(s)
- Vittoria Balzano
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France.,Gastroenterology and Digestive Oncology Department, Teaching Hospital of Tours, Tours, France
| | - Emeline Laurent
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Research Unit EA7505 "Education, Ethics and Health", University of Tours, Tours, France
| | - Aline-Marie Florence
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Department of Public Healht, Faculty of Medicine,University of Tours, France
| | - Anne-Isabelle Lecuyer
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Research Unit EA7505 "Education, Ethics and Health", University of Tours, Tours, France
| | - Carole Lefebvre
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France
| | - Patrick Heitzmann
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France
| | - Pascal Hammel
- Digestive and Medical Oncology Department, Paul Brousse University Hospital, Villejuif, France.,Paris-Saclay University, Villejuif, France
| | - Thierry Lecomte
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France.,University of Tours, Faculty of Medicine, Tours, France.,Gastroenterology and Digestive Oncology Department, Teaching Hospital of Tours, Tours, France
| | - Leslie Grammatico-Guillon
- Department of Public Healht, Faculty of Medicine, University of Tours, France.,Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, 2 Boulevard Tonnellé, 37044 Tours cedex 9, France
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18
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Anger F, Lock JF, Klein I, Hartlapp I, Wiegering A, Germer CT, Kunzmann V, Löb S. Does Concurrent Cholestasis Alter the Prognostic Value of Preoperatively Elevated CA19-9 Serum Levels in Patients with Pancreatic Head Adenocarcinoma? Ann Surg Oncol 2022; 29:8523-8533. [PMID: 36094690 PMCID: PMC9640457 DOI: 10.1245/s10434-022-12460-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 08/06/2022] [Indexed: 11/28/2022]
Abstract
Background Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified. Methods Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values. Results Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 %) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 % of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment. Conclusions In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-12460-w.
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Affiliation(s)
- Friedrich Anger
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.
| | - Johan Friso Lock
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Ingo Klein
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Ingo Hartlapp
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Volker Kunzmann
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Stefan Löb
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
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19
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A Propensity-Matched Analysis of the Postoperative Venous Thromboembolism Rate After Pancreatoduodenectomy Based on Operative Approach. J Gastrointest Surg 2022; 26:623-634. [PMID: 34757511 DOI: 10.1007/s11605-021-05191-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/23/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The use of minimally invasive approaches for pancreatoduodenectomy has increased in recent years, but the risk of postoperative VTE is undefined. We aimed to compare venous thromboembolism (VTE) rates after open and minimally invasive pancreatoduodenectomy using an administrative dataset. METHODS Patients who underwent pancreatoduodenectomy within the National Surgical Quality Improvement Program targeted pancreatectomy database (2016-2018) were identified. VTE was compared between patients who underwent open or minimally invasive pancreatoduodenectomy directly and after propensity score matching 1:1 for demographics, comorbidities, and peri-/intra-operative factors. RESULTS A total of 12,227 patients underwent pancreatoduodenectomy during the study period (open: n = 11,217; minimally invasive: n = 1010). Before matching, the VTE rate was higher among patients who underwent minimally invasive pancreatoduodenectomy (5.2% vs. 3.8%, p = 0.033), and minimally invasive resection was independently associated with VTE (OR = 1.46, 95%CI = 1.09-2.06). After matching, there were 916 patients per group without differences in demographics or comorbidities. Patients who underwent minimally invasive pancreatoduodenectomy had longer median operative times (422 vs. 348 min). The VTE rate remained higher following minimally invasive pancreatoduodenectomy after matching (5.1% vs. 2.9%, p = 0.018), mainly driven by a higher DVT rate (3.9% vs. 1.7%, p = 0.005). CONCLUSIONS Minimally invasive pancreatoduodenectomy is associated with a higher postoperative VTE rate compared to open pancreatoduodenectomy.
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20
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Hasegawa S, Endo I, Kubota K. Plastic or self-expandable metal stent: Which is the most suitable for patients with pancreatic head cancer in the upcoming era of neoadjuvant chemotherapy? A review. Dig Endosc 2022; 34:297-306. [PMID: 34388286 DOI: 10.1111/den.14107] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 08/11/2021] [Indexed: 01/15/2023]
Abstract
Obstructive jaundice is a major symptom of pancreatic head cancer, and although its amelioration is required before scheduling chemotherapy, the decision to perform biliary drainage for resectable pancreatic cancer has remained controversial. In recent years, the effectiveness of neoadjuvant therapy for pancreatic cancer has been reported. Preoperative biliary drainage has become increasingly necessary, making the choice of stent an important one; thus, the longer the waiting period extends through neoadjuvant chemotherapy, the more durable stents - such as self-expandable metallic stents, rather than plastic stents - would be desired as an option. Still, there is insufficient evidence regarding surgical outcomes and long-term prognosis, and further confirmatory studies are needed. Through this review, we aim to provide an update on the characteristics of biliary stents and preoperative biliary drainage for potentially resectable pancreatic cancer.
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Affiliation(s)
- Sho Hasegawa
- Division of, Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Kanagawa, Japan
| | - Itaru Endo
- Division of, Gastroenterological Surgery, Yokohama City University School of Medicine Graduate School of Medicine, Kanagawa, Japan
| | - Kensuke Kubota
- Division of, Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Kanagawa, Japan
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21
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Baig Z, Abu-Omar N, Khan R, Verdiales C, Frehlick R, Shaw J, Wu FX, Luo Y. Prognosticating Outcome in Pancreatic Head Cancer With the use of a Machine Learning Algorithm. Technol Cancer Res Treat 2021; 20:15330338211050767. [PMID: 34738844 PMCID: PMC8573477 DOI: 10.1177/15330338211050767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background: The purpose of this project is to identify prognostic features in resectable pancreatic head adenocarcinoma and use these features to develop a machine learning algorithm that prognosticates survival for patients pursuing pancreaticoduodenectomy. Methods: A retrospective cohort study of 93 patients who underwent a pancreaticoduodenectomy was performed. The patients were analyzed in 2 groups: Group 1 (n = 38) comprised of patients who survived < 2 years, and Group 2 (n = 55) comprised of patients who survived > 2 years. After comparing the two groups, 9 categorical features and 2 continuous features (11 total) were selected to be statistically significant (p < .05) in predicting outcome after surgery. These 11 features were used to train a machine learning algorithm that prognosticates survival. Results: The algorithm obtained 75% accuracy, 41.9% sensitivity, and 97.5% specificity in predicting whether survival is less than 2 years after surgery. Conclusion: A supervised machine learning algorithm that prognosticates survival can be a useful tool to personalize treatment plans for patients with pancreatic cancer.
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Affiliation(s)
- Zarrukh Baig
- 7235University of Saskatchewan, Saskatoon, Canada
| | | | - Rayyan Khan
- 7235University of Saskatchewan, Saskatoon, Canada
| | - Carlos Verdiales
- 12371College of Medicine, 7235University of Saskatchewan, Saskatoon, Canada
| | - Ryan Frehlick
- 12371College of Medicine, 7235University of Saskatchewan, Saskatoon, Canada
| | - John Shaw
- 7235University of Saskatchewan, Saskatoon, Canada
| | | | - Yigang Luo
- 7235University of Saskatchewan, Saskatoon, Canada
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22
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Zhou W, Han X, Fang Y, Han S, Cai Y, Kuang T, Lou W, Wang D. Clinical Analysis of Acinar Cell Carcinoma of the Pancreas: A Single-Center Experience of 45 Consecutive Cases. Cancer Control 2021; 27:1073274820969447. [PMID: 33121259 PMCID: PMC7791459 DOI: 10.1177/1073274820969447] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Backgrounds: Acinar cell carcinoma of the pancreas is a rare malignancy, and its features
remain unclear. We aimed to analyze the clinical characteristics, treatment
and prognosis of acinar cell carcinoma with our institutional case
series. Methods: Patients diagnosed with acinar cell carcinoma in our hospital between 2005
and 2019 were reviewed. Investigations on clinicopathological features,
treatment details and long-term survival were performed. Results: A total of 45 pathologically confirmed acinar cell carcinomas were
identified. The median age at diagnosis was 58 years with a male-to-female
ratio of 3.1:1. There were 24 (53.3%) localized, 5 (11.1%) locally advanced
and 16 (35.6%) metastatic cases, with a pancreatic head-to-body/tail ratio
of 1:1.4 for all the primary lesions. In the localized group, there were 10
pancreatoduodenectomy, 12 distal pancreatectomy, 1 total pancreatectomy, and
1 distal pancreatectomy combined with proximal gastrectomy. Among the
locally advanced and metastatic cases, 13 patients received chemotherapy, 1
received concurrent radiochemotherapy, 1 underwent synchronous resection of
primary tumor and liver metastasis, 1 underwent palliative operation, 1
underwent exploratory laparotomy, and 4 required no treatment. The median
overall survival of this series was 18.9 months with a 5-year survival rate
of 19.6%. Moreover, the resected acinar cell carcinoma patients were
associated with prolonged survival compared with the unresected cases (36.6
vs. 8.5 months, P < 0.001). Conclusions: Surgical resection could improve the long-term survival of acinar cell
carcinoma patients, which might also improve the prognosis of selected
metastatic cases. Large-scale studies are needed to further clarify the
biological behavior and clinical features, and to seek the optimal
treatments.
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Affiliation(s)
- Wentao Zhou
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xu Han
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Fang
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyang Han
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yumeng Cai
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tiantao Kuang
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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23
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Wang HB, Peng F, Wang M, Qin RY, Zhu F. Impact of Percutaneous Transhepatic Biliary Drainage on Clinical Outcomes of Patients with Malignant Obstructive Jaundice Undergoing Laparoscopic Pancreaticoduodenectomy. Curr Med Sci 2021; 41:375-380. [PMID: 33877556 DOI: 10.1007/s11596-021-2357-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 06/19/2020] [Indexed: 11/30/2022]
Abstract
Preoperative biliary drainage may increase the morbidity and mortality of pancreaticoduodenectomy. Studies on percutaneous transhepatic biliary drainage (PTBD) before laparoscopic pancreaticoduodenectomy (LPD), however, are scarce. The aim of this study was to examine the impact of PTBD on clinical outcomes of patients with malignant obstructive jaundice undergoing LPD. Clinical data of 172 patients who had malignant obstructive jaundice and underwent LPD from 2014 to 2017 in our hospital were retrospectively analyzed. Demographics, catheter-related complications, postoperative complications, and oncological outcomes were collected and analyzed. Propensity score matching was performed to minimize selection bias associated with the comparison of data between patients who underwent PTBD and then LPD (PTBD group), and those given LPD alone (LPD group). The results showed that, in the PTBD group relative to the LPD group, the operating time was significantly shortened (250.28±69.95 vs. 278.58±86.51 min, P=0.0196), the intraoperative blood loss was markedly reduced (271.96±403.47 vs. 429.72±482.47 mL, P=0.022), and overall rates of complications (16.33% vs. 36.49%, P=0.0025) including postoperative haemorrhage (2.04% vs. 12.16%, P=0.0072) and delayed gastric emptying (4.08% vs. 13.51%, P=0.0251) were greatly decreased. The propensity score-matched analysis, with 48 patients enrolled in each group, revealed no statistically significant differences in operating duration (262.71±68.64 vs. 280.25±83.52 min, P=0.264), intraoperative blood loss (290.21±407.71 vs. 373.75±422.33 mL, P=0.327) and delayed gastric emptying (4.17% vs. 12.50%, P=0.1396). PTBD group had lower incidences in overall complications (22.92% vs. 39.58%, P=0.0481) and postoperative haemorrhage (2.08% vs. 12.50%, P=0.0497) than LPD group. In conclusion, patients with malignant obstructive jaundice may benefit from PTBD procedure before LPD in terms of perioperative outcomes.
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Affiliation(s)
- He-Bin Wang
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Feng Peng
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ren-Yi Qin
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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24
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Jang DK, Kim J, Yoon SB, Yoon WJ, Kim JW, Lee TH, Jang JY, Paik CN, Lee JK. Palliative endoscopic retrograde biliary drainage for malignant biliary obstruction in Korea: A nationwide assessment. Saudi J Gastroenterol 2021; 27:173-177. [PMID: 33723093 PMCID: PMC8265398 DOI: 10.4103/sjg.sjg_589_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data. METHODS Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients. RESULTS A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different. CONCLUSION This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.
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Affiliation(s)
- Dong Kee Jang
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea
| | - Jungmee Kim
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Won Jae Yoon
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Jung-Wook Kim
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Tae Hee Lee
- Institute for Digestive Research, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Chang Nyol Paik
- Department of Internal Medicine, Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jun Kyu Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea,Address for correspondence: Dr. Jun Kyu Lee, Department of Internal Medicine, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang, 10326, Republic of Korea. E-mail:
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25
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Mosquera C, Mitsakos AT, Guyton RL, Fitzgerald TL, Zervos EE. When Is It Safe to Proceed With Pancreaticoduodenectomy Without Biliary Decompression? Am Surg 2020; 87:825-832. [PMID: 33228390 DOI: 10.1177/0003134820971618] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND An absolute bilirubin level where preoperative biliary decompression (PBD) is indicated before pancreaticoduodenectomy has been elusive. Our goal was to identify a total bilirubin level whereby biliary decompression provides clear benefit, despite associated expenses and potential complications. MATERIALS AND METHODS We reviewed a prospectively collected database of patients undergoing pancreaticoduodenectomy at the Vidant Medical Center between 2007 and 2016. Patients were arbitrarily subdivided into 3 groups based on presenting bilirubin level (≤10 mg/dL, 10.1-14.9 mg/dL, and ≥15 mg/dL) to determine the presence of overall complications, severe complications (Clavien-Dindo classification ≥3), prolonged length of stay (>1 SD), readmissions, or mortality. RESULTS Common bile duct stenting independently predicted a higher incidence of complications in patients presenting with bilirubin ≤10 mg/dL (P = .03) vs. those patients going directly to surgery. No differences were observed for patients with bilirubin between 10.1 mg/dL and 14.9 mg/dL. Biliary decompression in patients with bilirubin ≥15 mg/dL independently predicted fewer overall (73.8% vs. 100%, P = .0082) and less severe complications (14.3% vs. 44.5%, P = .03) and lower readmission rates (15.8% vs. 55.6%, P = .03) vs. those going directly to surgery. Patients not undergoing biliary decompression underwent pancreaticoduodenectomy sooner than those decompressed (4.7 days vs. 17.2 days, P = .01). DISCUSSION All patients presenting with bilirubin ≥15 mg/dL should undergo PBD, while those with bilirubin ≤10 mg/dL should forego stent placement to avoid stent-related complications. The decision to stent between 10.1 and 14.9 mg/dL should be made on a case-by-case basis keeping in mind timeliness to definitive cancer treatment.
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Affiliation(s)
- Catalina Mosquera
- Department of Surgery, Division of Surgical Oncology, Brody School of Medicine, 3627East Carolina University, Greenville, NC, USA
| | - Anastasios T Mitsakos
- Department of Surgery, Division of Surgical Oncology, Brody School of Medicine, 3627East Carolina University, Greenville, NC, USA
| | - Rodney L Guyton
- Department of Surgery, Division of Surgical Oncology, Brody School of Medicine, 3627East Carolina University, Greenville, NC, USA
| | - Timothy L Fitzgerald
- Department of Surgery, Division of Surgical Oncology, Brody School of Medicine, 3627East Carolina University, Greenville, NC, USA
| | - Emmanuel E Zervos
- Department of Surgery, Division of Surgical Oncology, Brody School of Medicine, 3627East Carolina University, Greenville, NC, USA
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26
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Shen Z, Zhang J, Chen H, Wang W, Xu W, Lu X, Zhou Y, Zhao S, Xu Z, Deng X, Wang J, Weng Y, Shen B. Does Pre-operative Biliary Drainage Influence Long-Term Survival in Patients With Obstructive Jaundice With Resectable Pancreatic Head Cancer? Front Oncol 2020; 10:575316. [PMID: 33042848 PMCID: PMC7525216 DOI: 10.3389/fonc.2020.575316] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 08/18/2020] [Indexed: 12/16/2022] Open
Abstract
Objectives: Whether pre-operative biliary drainage (PBD) affects long-term survival of patients with obstructive jaundice with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy is still controversial. Most of the previous research did not include the important total serum bilirubin (TB) level before intervention as well as before surgery. The aim of this study is to evaluate the impact of PBD on long-term survival after considering the TB level. Methods: Data were collected retrospectively from patients with obstructive jaundice who underwent resection of pancreatic head cancer in a high-volume center. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal cut-off levels for TB and age based on the minimal probability (P)-value and the largest χ2-value. Multivariate Cox regression analyses were performed after univariate analysis to assess independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Results: Of 426 patients with obstructive jaundice who underwent pancreaticoduodenectomy for resectable pancreatic head cancer during a 7 year period, 242 (56.8%) received PBD and 184 (43.2%) underwent surgery directly. The OS of patients who received PBD was significantly worse than that of patients who did not receive PBD by univariate analysis (median of 16.6 vs. 22.2 months, P = 0.048). After including liver function parameters in the multivariate Cox regression, we found that the use of PBD was not associated with OS or DFS, while TB before intervention >150 μmol/L was an independent adverse prognostic factor for both OS [hazard ratio (HR), 1.42; 95% CI, 1.05–1.91] and DFS (HR, 1.38; 95% CI, 1.08–1.77). Conclusions: In patients with obstructive jaundice with resectable pancreatic head cancer, undergoing PBD before pancreaticoduodenectomy did not impair or benefit survival rates compared with surgery alone. However, TB before intervention >150 μmol/L predicted an unfavorable prognosis, irrespective of the PBD procedure.
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Affiliation(s)
- Ziyun Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Jun Zhang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Haoda Chen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Weishen Wang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Wei Xu
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Xiongxiong Lu
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Yiran Zhou
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Shiwei Zhao
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Zhiwei Xu
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Xiaxing Deng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Jiancheng Wang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Yuanchi Weng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.,Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
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27
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Thomaidis T, Kallimanis G, May G, Zhou P, Sivanathan V, Mosko J, Triantafillidis JK, Teshima C, Moehler M. Advances in the endoscopic management of malignant biliary obstruction. Ann Gastroenterol 2020; 33:338-347. [PMID: 32624653 PMCID: PMC7315700 DOI: 10.20524/aog.2020.0497] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022] Open
Abstract
Biliary obstruction is common in pancreatobiliary malignancies and has a negative impact on the patient's quality of life, postoperative complications, and survival rates. Particularly in the last decade, there has been enormous progress regarding the diagnostic and therapeutic options in patients with malignant biliary obstruction. Endoscopy has given a new insight in this direction and novel techniques have been developed for the better characterization and treatment of malignant strictures. We herein summarize the available data on the different endoscopic techniques, and clarify their role in the diagnosis and treatment of malignant biliary obstructive disease. Finally, we propose an algorithm that can facilitate management decisions in these patients.
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Affiliation(s)
- Thomas Thomaidis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - George Kallimanis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
| | - Gary May
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Pinghong Zhou
- Interventional endoscopy, Zhongshan Hospital, Fudan University, Shanghai, China (Pinghong Zhou)
| | - Visvakanth Sivanathan
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - Jeff Mosko
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | | | - Christopher Teshima
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Markus Moehler
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
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28
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Bosch X, Moreno P, Guerra-García M, Guasch N, López-Soto A. What is the relevance of an ambulatory quick diagnosis unit or inpatient admission for the diagnosis of pancreatic cancer? A retrospective study of 1004 patients. Medicine (Baltimore) 2020; 99:e19009. [PMID: 32176029 PMCID: PMC7440208 DOI: 10.1097/md.0000000000019009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Quick diagnosis units (QDU) have become an alternative hospital-based ambulatory medicine strategy to inpatient hospitalization for potentially serious illnesses in Spain. Whether diagnosis of pancreatic cancer is better accomplished by an ambulatory or inpatient approach is unknown. The main objective of this retrospective study was to examine and compare the diagnostic effectiveness of a QDU or inpatient setting in patients with pancreatic cancer.Patients with a diagnosis of pancreatic adenocarcinoma who had been referred to a university, tertiary hospital-based QDU or hospitalized between 2005 and 2018 were eligible. Presenting symptoms and signs, risk and prognostic factors, and time to diagnosis were compared. The costs incurred during the diagnostic assessment were analyzed with a microcosting method.A total of 1004 patients (508 QDU patients and 496 inpatients) were eligible. Admitted patients were more likely than QDU patients to have weight loss, asthenia, anorexia, abdominal pain, jaundice, and palpable hepatomegaly. Time to diagnosis of inpatients was similar to that of QDU patients (4.1 [0.8 vs 4.3 [0.6] days; P = .163). Inpatients were more likely than QDU patients to have a tumor on the head of the pancreas, a tumor size >2 cm, a more advanced nodal stage, and a poorer histological differentiation. No differences were observed in the proportion of metastatic and locally advanced disease and surgical resections. Microcosting revealed a cost of &OV0556;347.76 (48.69) per QDU patient and &OV0556;634.36 (80.56) per inpatient (P < .001).Diagnosis of pancreatic cancer is similarly achieved by an inpatient or QDU clinical approach, but the latter seems to be cost-effective. Because the high costs of hospitalization, an ambulatory diagnostic assessment may be preferable in these patients.
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Affiliation(s)
- Xavier Bosch
- Quick Diagnosis Unit, Adult Day Care Center, Hospital Clínic, University of Barcelona
| | - Pedro Moreno
- Department of Internal Medicine, Hospital Clínic, University of Barcelona
| | - Mar Guerra-García
- Adult Day Care Center, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Neus Guasch
- Adult Day Care Center, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Alfons López-Soto
- Department of Internal Medicine, Hospital Clínic, University of Barcelona
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29
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Kulezneva YV, Melekhina OV, Efanov MG, Alikhanov RB, Musatov AB, Ogneva AY, Tsvirkun VV. Disputable issues of biliary drainage procedures in malignant obstructive jaundice. ANNALY KHIRURGICHESKOY GEPATOLOGII = ANNALS OF HPB SURGERY 2019; 24:111-122. [DOI: 10.16931/1995-5464.20194111-122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Affiliation(s)
- Yu. V. Kulezneva
- Loginov Moscow Clinical Scientific Center of Moscow Department of Health
| | - O. V. Melekhina
- Loginov Moscow Clinical Scientific Center of Moscow Department of Health
| | - M. G. Efanov
- Loginov Moscow Clinical Scientific Center of Moscow Department of Health
| | - R. B. Alikhanov
- Loginov Moscow Clinical Scientific Center of Moscow Department of Health
| | - A. B. Musatov
- Loginov Moscow Clinical Scientific Center of Moscow Department of Health
| | - A. Yu. Ogneva
- Yevdokimov Moscow State University of Medicine and Dentistry of Ministry of Health of Russia
| | - V. V. Tsvirkun
- Loginov Moscow Clinical Scientific Center
of Moscow Department of Health
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30
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Chen B, Trudeau MT, Maggino L, Ecker BL, Keele LJ, DeMatteo RP, Drebin JA, Fraker DL, Lee MK, Roses RE, Vollmer CM. Defining the Safety Profile for Performing Pancreatoduodenectomy in the Setting of Hyperbilirubinemia. Ann Surg Oncol 2019; 27:1595-1605. [PMID: 31691110 DOI: 10.1245/s10434-019-08044-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Hyperbilirubinemia is commonly observed in patients requiring pancreatoduodenectomy (PD). Thus far, literature regarding the danger of operating in the setting of hyperbilirubinemia is equivocal. What remains undefined is at what specific level of bilirubin there is an adverse safety profile for undergoing PD. The aim of this study is to identify the optimal safety profile of patients with hyperbilirubinemia undergoing PD. PATIENTS AND METHODS The present work analyzed 803 PDs from 2004 to 2018. A generalized additive model was used to determine cutoff values of total serum bilirubin (TB) that were associated with increases in adverse outcomes, including 90-day mortality. Subgroup comparisons and biliary stent-specific analyses were performed for patients with TB below and above the cutoff. RESULTS TB of 13 mg/dL was associated with an increase in 90-day mortality (P = 0.043) and was the dominant risk factor on multivariate logistic regression [odds ratio (OR) 8.193, P = 0.001]. Increased TB levels were also associated with reoperations, number of complications per patient, and length of stay. Patients with TB greater than or equal to 13 mg/dL (TB ≥ 13) who received successful biliary decompression through stenting had less combined death and serious morbidity (P = 0.048). CONCLUSIONS Preoperative TB ≥ 13 mg/dL was associated with increased 90-day mortality after PD. Reducing a TB ≥ 13 is generally recommended before proceeding to surgery.
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Affiliation(s)
- Bofeng Chen
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Maxwell T Trudeau
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Laura Maggino
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.,Department of Surgery, University of Verona, The Pancreas Institute, Verona, Italy
| | - Brett L Ecker
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Luke J Keele
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Ronald P DeMatteo
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Jeffrey A Drebin
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Douglas L Fraker
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Major K Lee
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Robert E Roses
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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31
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Peng X, Jiao X, Zhao P, Zhu R, Sun Y, Zhou L. Influence of non-jaundice stage at diagnosis on clinicopathological features and long-term survival of patients with periampullary carcinomas. Medicine (Baltimore) 2019; 98:e17673. [PMID: 31702620 PMCID: PMC6855658 DOI: 10.1097/md.0000000000017673] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 09/24/2019] [Accepted: 09/29/2019] [Indexed: 12/11/2022] Open
Abstract
The effect of non-jaundice stage at diagnosis on clinicopathological features and prognosis of patients with periampullary carcinomas (PACs) remains uncertain.The 504 patients who were pathologically diagnosed with PACs between 2012 and 2017 were retrospective analyzed. Kaplan-Meier method was used to estimate survival and log-rank tests were used for comparisons between groups.Patients were divided into the non-jaundice group and the jaundice group according to serum total bilirubin (3 mg/dL) at diagnosis. By comparison with the jaundice group, more patients of the non-jaundice group manifested abdominal pain with longer duration. The degree of deterioration of complete blood count, liver function and CA19-9 in the non-jaundice group was significantly lower (P < .001). The non-jaundice group had larger tumor size (P = .001), more duodenal carcinoma and pancreatic carcinoma (P < .001), lower resection rate (P = .001) and less pancreatic and perineural invasion (P = .017, P = .002). The I stage was significantly more common in the non-jaundice group (P < .001). The cumulative 5-year survival of the non-jaundice group was significantly higher (P = .032). Multivariate analysis for all patients demonstrated that CEA level, cell differentiation, chemotherapy, and recurrence were independent prognostic factors.Patients with PACs in a non-jaundice stage at diagnosis showed more favorable clinicopathological features and long-term survival than such patients with jaundice.
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Affiliation(s)
- Xiaoqian Peng
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
| | - Xiaoxiao Jiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
| | - Ping Zhao
- Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
| | - Rongtao Zhu
- Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuling Sun
- Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou
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Kusakabe J, Anderson B, Liu J, Williams GA, Chapman WC, Doyle MMB, Khan AS, Sanford DE, Hammill CW, Strasberg SM, Hawkins WG, Fields RC. Long-Term Endocrine and Exocrine Insufficiency After Pancreatectomy. J Gastrointest Surg 2019; 23:1604-1613. [PMID: 30671791 PMCID: PMC6646099 DOI: 10.1007/s11605-018-04084-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE To identify peri-operative risk factors and time to onset of pancreatic endocrine/exocrine insufficiency. METHODS We retrospectively analyzed a single institutional series of patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between 2000 and 2015. Endocrine/exocrine insufficiencies were defined as need for new pharmacologic intervention. Cox proportional modeling was used to identify peri-operative variables to determine their impact on post-operative pancreatic insufficiency. RESULTS A total of 1717 patient records were analyzed (75.47% PD, 24.53% DP) at median follow-up 17.88 months. Average age was 62.62 years, 51.78% were male, and surgery was for malignancy in 74.35% of patients. Post-operative endocrine insufficiency was present in 20.15% (n = 346). Male gender (p = 0.015), increased body mass index (BMI) (p < 0.001), tobacco use (p = 0.011), family history of diabetes (DM) (p < 0.001), personal history of DM (p ≤ 0.001), and DP (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 20.80 ± 33.60 (IQR: 0.49-28.37) months. Post-operative exocrine insufficiency was present in 36.23% (n = 622). Race (p = 0.014), lower BMI (p < 0.001), family history of DM (p = 0.007), steatorrhea (p < 0.001), elevated pre-operative bilirubin (p = 0.019), and PD (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 14.20 ± 26.90 (IQR: 0.89-12.69) months. CONCLUSIONS In this large series of pancreatectomy patients, 20.15% and 36.23% of patients developed post-operative endocrine and exocrine insufficiency at a mean time to onset of 20.80 and 14.20 months, respectively. Patients should be educated regarding post-resection insufficiencies and providers should have heightened awareness long-term.
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Affiliation(s)
- Jiro Kusakabe
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Blaire Anderson
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Jingxia Liu
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Gregory A Williams
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - William C Chapman
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Majella MB Doyle
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Adeel S Khan
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Dominic E Sanford
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Chet W Hammill
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Steven M Strasberg
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - William G Hawkins
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Ryan C Fields
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
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33
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Aadam AA, Liu K. Endoscopic palliation of biliary obstruction. J Surg Oncol 2019; 120:57-64. [PMID: 31055849 DOI: 10.1002/jso.25483] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 04/07/2019] [Indexed: 02/06/2023]
Abstract
Advanced pancreaticobiliary malignancy tends to be uncurable at presentation and causes significant morbidity for patients. Palliation for malignant biliary obstruction should be minimally invasive, cost-effective, and aim to improve quality of life of patients. Strategies of endoscopic palliation of malignant biliary obstruction can differ based on sites and degree of biliary obstruction with complex decisions of optimal stent type and placement that involve conscientious planning by a multidisciplinary team.
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Affiliation(s)
- A Aziz Aadam
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Kevin Liu
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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34
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Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable? J Gastrointest Surg 2017; 21:1245-1253. [PMID: 28497252 PMCID: PMC5907798 DOI: 10.1007/s11605-017-3440-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/27/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. METHODS Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. RESULTS Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). CONCLUSION Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.
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35
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Bai Z, Shi Y, Wang J, Qiu L, Teng G, Zhang F, Yang X. Multi-modality imaging-monitored creation of rat orthotopic pancreatic head cancer with obstructive jaundice. Oncotarget 2017; 8:54277-54284. [PMID: 28903340 PMCID: PMC5589579 DOI: 10.18632/oncotarget.17347] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 04/07/2017] [Indexed: 02/07/2023] Open
Abstract
Purpose To investigate the feasibility of using multi-modality imaging to monitor the creation of rat models with orthotopic pancreatic head cancer with obstructive jaundice. Results 27 of 52 rats (51.92%) developed pancreatic head cancer. The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]. Both ultrasound imaging and MRI clearly characterized the orthotopic tumors. Laboratory biochemistry test for those rats with obstructive jaundice showed elevated levels of bilirubin, aspartate transaminase (AST), alkaline phosphatase (ALT) and gamma-glutamyl transpeptidase (λ-GGT), compared with those rats without jaundice (P < 0.05). Correlative pathology confirmed that all tumors were ductal adenocarcinomas, and located in pancreatic head regions. Materials and Methods Rat pancreatic adenocarcinoma cells (DSL-6A/C1) were first transfected with lentivirus/mCherry-luciferase genes, and then subcutaneously implanted into flanks of donor immunocompetent Lewis rats, to create pancreatic tumor tissues. The tumor tissues from donor rats with either bioluminescence signal or without the signal were then transplanted into the pancreatic heads of 52 recipient Lewis rats. Bioluminescence optical and ultrasound imaging, as well as magnetic resonance imaging (MRI), were performed to follow up the tumor formation and growth in these tumor-transplanted rats. Physical examination and biochemistry test were used to discern the rats with obstructive jaundice. The rats were euthanized for subsequent histologic correlation and confirmation. Conclusions We successfully created a new rat model with orthotopic pancreatic head cancer, which can be accurately monitored and visualized by different imaging modalities.
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Affiliation(s)
- Zhibin Bai
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.,Department of Radiology, Zhongda Hospital, Southeastern University, Nanjing, China
| | - Yaoping Shi
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
| | - Jianfeng Wang
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
| | - Longhua Qiu
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
| | - Gaojun Teng
- Department of Radiology, Zhongda Hospital, Southeastern University, Nanjing, China
| | - Feng Zhang
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
| | - Xiaoming Yang
- Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.,Department of Radiology, Sir Run Run Show Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Yamada D, Eguchi H, Asaoka T, Tomihara H, Noda T, Wada H, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Mori M, Doki Y. The basal nutritional state of PDAC patients is the dominant factor for completing adjuvant chemotherapy. Surg Today 2017; 47:1361-1371. [PMID: 28421348 DOI: 10.1007/s00595-017-1522-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 03/13/2017] [Indexed: 12/19/2022]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and several clinical trials have shown that adjuvant chemotherapy after curative resection can improve the prognosis of these patients. However, the adjuvant chemotherapy completion rate is less than satisfactory. If this rate could be increased then the overall prognosis of PDAC might be improved; however, reports addressing this problem are insufficient. To elucidate the factors, we retrospectively investigated PDAC patients. METHODS Various factors of 121 PDAC patients undergoing R0 resection, including preoperatively treated patients, were investigated. Univariate and multivariate analyses were performed to investigate the factors that were associated with the completion of adjuvant chemotherapy. RESULTS The analysis identified age and the prognostic nutritional index (PNI) as significant independent factors. A receiver operating characteristic curve analysis of age yielded a cutoff value of 67 years (sensitivity, 64%; specificity, 78%). Univariate and multivariate analyses of the 61 patients who were over 67 years of age revealed that the PNI (odds ratio, 0.85; P = 0.048) and Evans grade (odds ratio, 0.041; P = 0.0010) were significant factors for the completion of chemotherapy. CONCLUSIONS The results of our investigation suggest that nutrition should be controlled in older PDAC patients to facilitate the completion of adjuvant chemotherapy.
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Affiliation(s)
- Daisaku Yamada
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan.
| | - Tadafumi Asaoka
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Hideo Tomihara
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Koichi Kawamoto
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Yutaka Takeda
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan.,Department of Surgery, Kansai Rosai Hospital, Inabasou 3-1-69, Amagasaki, Hyogo, 660-8511, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan.,Department of Surgery, Osaka Police Hospital, Tennoji-ku Kitayamacho 10-31, Osaka, Osaka, 543-0035, Japan
| | - Masaki Mori
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Dr.surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 (E2), Suita, 565-0871, Osaka, Japan
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Dolejs S, Zarzaur BL, Zyromski NJ, Pitt HA, Riall TS, Hall BL, Behrman SW. Does Hyperbilirubinemia Contribute to Adverse Patient Outcomes Following Pancreatoduodenectomy? J Gastrointest Surg 2017; 21:647-656. [PMID: 28205125 DOI: 10.1007/s11605-017-3381-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 01/27/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND Jaundice due to biliary obstruction leads to multiple physiologic derangements and a decline in performance status that may result in unfavorable intra- and postoperative outcomes following a Whipple procedure. While preoperative biliary decompression may improve synthetic function, this strategy has been reported to increase the incidence of infectious complications following surgery. We hypothesized that hyperbilirubinemia at the time of pancreatoduodenectomy (PD) would be a risk factor for increased morbidity and mortality postoperatively. METHODS The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pancreatectomy Demonstration Project and the 2014 Procedure Targeted Pancreatectomy databases were queried for patients with a bilirubin level obtained within 7 days of PD. Results were compared among patients with bilirubin level percentiles <80th (0-2.9 mg/dL), 80-90th (3-7.3 mg/dL), and >90th (>7.3 mg/dL). Data were further evaluated between those with a bilirubin ≥10 mg/dL and those with a normal level and by utilizing bilirubin as a continuous variable. Outcomes included 30-day mortality and overall and serious morbidity as previously defined by ACS-NSQIP. Categorical variables were compared using chi-squared, Fisher's exact, Kruskal-Wallis, or Wilcoxon rank sum tests with a p = 0.05 considered significant. RESULTS The combined databases yielded 2556 patients who had PD and a preoperative bilirubin level for analysis. When comparing patients with bilirubin levels at the 80th (n = 2055), 80-90th (n = 273), and >90th percentiles (n = 228), no difference was observed among groups with respect to overall and serious morbidity or mortality. Similarly, no difference in postoperative outcomes was observed between the 147 patients who had a bilirubin ≥10 mg/dL and those with normal levels or when bilirubin increased when levels were analyzed as a continuous variable. CONCLUSION Modest degrees of hyperbilirubinemia were not shown to affect morbidity and mortality following pancreatoduodenectomy. The indication and need for preoperative biliary decompression should be reserved, and utilized selectively, only for those with symptomatic, elevated bilirubin levels.
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Affiliation(s)
- Scott Dolejs
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Ben L Zarzaur
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Nicholas J Zyromski
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Henry A Pitt
- Department of Surgery, Lewis Katz School of Medicine at Temple University School of Medicine, Philadelphia, PA, USA
| | - Taylor S Riall
- Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Bruce L Hall
- Department of Surgery, Washington University School of Medicine, Olin Business School, and Center for Health Policy, St. Louis, MO, USA.,Department of Surgery, American College of Surgeons, Chicago, IL, USA.,Department of Surgery, BJC Healthcare, St. Louis, MO, USA
| | - Stephen W Behrman
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Avenue #203, Memphis, TN, 38163, USA.
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Xia BT, Habib DA, Dhar VK, Levinsky NC, Kim Y, Hanseman DJ, Sutton JM, Wilson GC, Smith M, Choe KA, Sussman JJ, Ahmad SA, Abbott DE. Early Recurrence and Omission of Adjuvant Therapy after Pancreaticoduodenectomy Argue against a Surgery-First Approach. Ann Surg Oncol 2016; 23:4156-4164. [PMID: 27459987 DOI: 10.1245/s10434-016-5457-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Sequencing therapy for patients with periampullary malignancy is controversial. Clinical trial data report high rates of adjuvant therapy completion, though contemporary, real-world rates remain incomplete. We sought to identify patients who failed to receive adjuvant therapy and those at risk for early recurrence (ER) who might benefit most from neoadjuvant therapy (NT). METHODS We retrospectively reviewed medical records of 201 patients who underwent pancreaticoduodenectomy for periampullary malignancies between 1999 and 2015; patients receiving NT were excluded. Univariate and multivariate analyses were performed to identify predictors of failure to receive adjuvant therapy and ER (within 6 months) as the primary end points. RESULTS The median age at the time of surgery was 65.5 years (interquartile range 57-74 years). The majority of tumors were pancreatic ductal adenocarcinoma (76.6 %), and 71.6 % of patients received adjuvant therapy after resection. Univariate predictors of failure to undergo adjuvant therapy were advanced age, age-adjusted Charlson comorbidity index, operative transfusion, reoperation, length of stay, and 30- to 90-day readmissions (all p < 0.05). Advanced age, specifically among patients >70 years, persisted as a significant preoperative predictor on multivariate analysis (p < 0.01). Patients who failed to receive adjuvant therapy and/or developed ER had significantly worse overall survival rates compared to all other patients (27.8 vs. 9.7 months; p < 0.01). CONCLUSIONS Approximately one-third of surgery-first patients undergoing pancreaticoduodenectomy at our institution did not receive adjuvant therapy and/or demonstrated ER. This substantial subset of patients may particularly benefit from NT, ensuring completion of multimodal therapy and/or avoiding futile surgical intervention.
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Affiliation(s)
- Brent T Xia
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - David A Habib
- College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Vikrom K Dhar
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Nick C Levinsky
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Young Kim
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Dennis J Hanseman
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Jeffrey M Sutton
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Gregory C Wilson
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Milton Smith
- Department of Medicine, Division of Gastroenterology, University of Cincinnati, Cincinnati, OH, USA
| | - Kyuran Ann Choe
- Department of Radiology, University of Cincinnati, Cincinnati, OH, USA
| | - Jeffrey J Sussman
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Syed A Ahmad
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Daniel E Abbott
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, WI, USA.
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Boulay BR, Birg A. Malignant biliary obstruction: From palliation to treatment. World J Gastrointest Oncol 2016; 8:498-508. [PMID: 27326319 PMCID: PMC4909451 DOI: 10.4251/wjgo.v8.i6.498] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 11/04/2015] [Accepted: 04/22/2016] [Indexed: 02/05/2023] Open
Abstract
Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction.
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Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography. Clin Sci (Lond) 2016; 130:1535-44. [PMID: 27252406 PMCID: PMC4947925 DOI: 10.1042/cs20160326] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Accepted: 06/01/2016] [Indexed: 02/07/2023]
Abstract
This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1β: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1β: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1β: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 μm, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage.
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Baekelandt BMG, Hjermstad MJ, Nordby T, Fagerland MW, Kure EH, Heiberg T, Buanes T, Labori KJ. Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma. HPB (Oxford) 2016; 18:247-254. [PMID: 27017164 PMCID: PMC4814590 DOI: 10.1016/j.hpb.2015.09.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 09/18/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND The purpose of this prospective study was to evaluate whether pre-surgery health-related quality of life (HRQoL) and subjectively rated symptom scores are prognostic factors for survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS Patients undergoing pancreatic resection for PDAC completed the Edmonton Symptom Assessment System (ESAS) and the EORTC QLQ-C30 and QLQ-PAN26 questionnaires preoperatively. Patient, tumor and treatment characteristics, recurrence and survival were registered. RESULTS Sixty-six consecutive patients underwent R0/R1 resection for PDAC. Baseline ESAS and EORTC questionnaire compliance was 44/66 (67%) with no statistically significant differences between compliers (n = 44) and non-compliers (n = 22) when comparing clinicopathological parameters and survival. Univariable analyses showed that three symptoms (nausea, dry mouth, cognitive function) and two clinicopathological factors (CA 19-9 > 400 U/ml, lymph node ratio > 0.1) were significantly associated with shorter survival (p < 0.05). In multivariable analysis, cognitive function was the only independent predictor for survival: hazard ratio = 0.35 (95%CI 0.13-0.93) for high vs low cognitive function. Median survival times for patients with high and low cognitive function were 21 and 10 months, respectively (p < 0.001). CONCLUSION Presurgery cognitive function is a significant independent predictor of survival in patients with resectable PDAC. Thus, presurgery patient reported outcomes may provide as strong prognostic information as clinicopathological factors.
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Affiliation(s)
- Bart M G Baekelandt
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Marianne J Hjermstad
- Regional Centre for Excellence in Palliative Care, Department of Oncology, Oslo University Hospital, Norway; European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Tom Nordby
- Department of Gastroenterological Surgery, Østfold Hospital Trust, Norway
| | - Morten W Fagerland
- Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Norway
| | - Elin H Kure
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Turid Heiberg
- Østfold University College, Faculty of Health and Social Studies, Halden, Norway
| | - Trond Buanes
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway
| | - Knut J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway.
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Vogel A, Kullmann F, Kunzmann V, Al-Batran SE, Oettle H, Plentz R, Siveke J, Springfeld C, Riess H. Patients with Advanced Pancreatic Cancer and Hyperbilirubinaemia: Review and German Expert Opinion on Treatment with nab-Paclitaxel plus Gemcitabine. Oncol Res Treat 2015; 38:596-603. [PMID: 26599274 DOI: 10.1159/000441310] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 09/28/2015] [Indexed: 11/19/2022]
Abstract
In patients with advanced unresectable pancreatic cancer, the prognosis is generally poor. Within recent years, new treatment options such as the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) or the combination of nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine have shown a clinically relevant survival benefit over the standard gemcitabine in patients with good performance status. Unfortunately, patients with hyperbilirubinaemia, who constitute a substantial proportion of the pancreatic cancer patients, have been excluded from most clinical studies. Consequently, our knowledge on the appropriate medical treatment of this patient group is limited. In a meeting of German medical oncology experts, the available clinical evidence and own clinical experience regarding the management of patients with advanced pancreatic cancer and hyperbilirubinaemia was discussed. The present publication summarises the discussion outcomes with regard to appropriate management of these patients, including consensus-based recommendations for nab-paclitaxel/gemcitabine treatment, according to the best available evidence. In summary, knowledge of the underlying aetiology of hyperbilirubinaemia and the metabolisation routes of the cytotoxic drugs is crucial before initiating chemotherapy. As effective treatment options should also be made available to patients with comorbid conditions, including hyperbilirubinaemia, the experts provide advice for an initial dose reduction of chemotherapy with nab-paclitaxel/gemcitabine based on the total bilirubin level in patients with biliary obstruction or extensive liver metastasis.
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Affiliation(s)
- Arndt Vogel
- Klinik fx00FC;r Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Germany
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Abstract
Preoperative biliary drainage (PBD) has been thought to be preferable regardless of the site of biliary strictures, e.g., distal or proximal strictures because PBD by endoscopy or interventional radiology decreases postoperative mortality and morbidity rates. However, recently, several studies have revealed that PBD strategy showed an increased mortality rate or a high frequency of surgical site infection. Herein, we reviewed reports in the literature regarding the current status of PBD and investigated the effects of PBD on patients with distal and proximal biliary obstructions due to potentially resectable pancreatobiliary cancers. Our summary demonstrated that there is as yet no optimal PBD method regardless of the distal and proximal biliary strictures because of the small sample size and the lack of better control groups in previous studies. Thus, prospective randomized studies with a large sample size are needed to establish the optimal mode of PBD and to evaluate the potential benefits of PBD in patients with both distal and proximal biliary obstructions.
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Sauvanet A, Boher JM, Paye F, Bachellier P, Sa Cuhna A, Le Treut YP, Adham M, Mabrut JY, Chiche L, Delpero JR. Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma. J Am Coll Surg 2015. [PMID: 26206638 DOI: 10.1016/j.jamcollsurg.2015.03.058] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND The influence of jaundice on outcomes after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to determine, in a large multicentric series, the influence of severe jaundice (serum bilirubin level ≥250 μmol/L and 300 μmol/L) on early severe morbidity and survival after PD. STUDY DESIGN From 2004 to 2009, twelve hundred patients (median age 66 years, 57% male) with resectable PDAC underwent PD. Patients who received preoperative biliary drainage for neoadjuvant treatment or cholangitis were excluded. Pre- and intraoperative data were collected by a standardized form. Serum bilirubin level and creatinine clearance were analyzed as categorical variables. Predictive factors of severe complications and poor survival (Kaplan-Meier method) were identified by univariate and multivariate analysis. RESULTS Median follow-up was 21 months (95% CI, 19-23). Operative mortality was 3.9% (n = 47), with no predictive factors in multivariate analysis. Severe complications (Dindo-Clavien grade III to IV) occurred in 22% (n = 268), with male sex (p = 0.025), America Society of Anesthesiologists score 3 to 4 (p = 0.022), serum bilirubin level ≥300 μmol/L (p = 0.034), and creatinine clearance <60 mL/min/1.73 m(2) (p = 0.013) identified as predictive factors in multivariate analysis. Overall 3-year survival rate was 41% (95% CI, 37-45%). In multivariate analysis, serum bilirubin level ≥300 μmol/L (p = 0.048), low-volume center (p < 0.001), venous resection (p = 0.014), N1 status (p < 0.01), R1 status (p < 0.001), and absence of adjuvant treatment (p < 0.001) negatively impacted survival. There was a negative relationship between survival at 12 months or later and higher rates of bilirubin. Presence of a biliary stent did not influence early or long-term results. CONCLUSIONS In this multicentric study, serum bilirubin level ≥300 μmol/L increased severe morbidity and decreased long-term survival after PD for PDAC. These findings suggest that biliary stenting is appropriately indicated before PD in patients with PDAC and severe jaundice.
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Affiliation(s)
- Alain Sauvanet
- Department of Hepato-Biliary and Pancreatic Surgery, Hôpital Beaujon, Clichy, France.
| | - Jean-Marie Boher
- Department of Biostatistics and Methodology, Institut Paoli Calmettes, Marseille, France; Unité Mixte de Recherche Institut de Recherche pour le Développement, Aix-Marseille University, Marseille, France
| | - François Paye
- Department of Digestive Surgery, Hôpital Saint Antoine, Paris, France
| | | | - Antonio Sa Cuhna
- Centre Hépato-Biliaire, AP-HP, Hôpital Paul Brousse, Villejuif, France
| | | | - Mustapha Adham
- Department of Surgery, Hôpital Edouard-Herriot, Lyon, France
| | | | - Laurence Chiche
- Department of Surgery, Maison du Haut-Levêque, Pessac, France
| | - Jean-Robert Delpero
- Department of Surgical Oncology, Institut Paoli Calmettes, Marseille, France
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Tavano F, Fontana A, Pellegrini F, Burbaci FP, Rappa F, Cappello F, Copetti M, Maiello E, Lombardi L, Graziano P, Vinciguerra M, di Mola FF, di Sebastiano P, Andriulli A, Pazienza V. Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to predict clinical outcomes in pancreatic ductal adenocarcinoma patients. J Transl Med 2014; 12:248. [PMID: 25199538 PMCID: PMC4172900 DOI: 10.1186/s12967-014-0248-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Accepted: 08/29/2014] [Indexed: 01/17/2023] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. Methods mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used. Results RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. Conclusion: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.
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Bilici A. Prognostic factors related with survival in patients with pancreatic adenocarcinoma. World J Gastroenterol 2014; 20:10802-10812. [PMID: 25152583 PMCID: PMC4138460 DOI: 10.3748/wjg.v20.i31.10802] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 01/27/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
The prognosis in patients with pancreatic cancer is poor and this cancer is the fourth leading cause of cancer-related death worldwide. Although surgical resection is the only curative treatment of choice for pancreatic cancer, the majority of patients are diagnosed at an advanced stage, thus only 10%-15% of them are suitable for curative resection and the overall survival is less than 5%. Chemotherapy for metastatic disease is to palliate symptoms of patients and to improve survival. Therefore, prognostic factors are important and a correct definition of poor prognostic factors may help to guide more aggressive adjuvant or aggressive treatment protocols in patients with pancreatic cancer. This article reviews the prognostic factors affecting survival of patients with pancreatic cancer in the light of recent advances in the literature.
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Zhou L, Li J, Zhao YP, Cui QC, Zhou WX, Guo JC, You L, Wu WM, Zhang TP. The prognostic value of Cyclin B1 in pancreatic cancer. Med Oncol 2014; 31:107. [DOI: 10.1007/s12032-014-0107-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Accepted: 06/25/2014] [Indexed: 02/08/2023]
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Feld FM, Lennerz JK. Jaundice in resected pancreatic cancer patients. HPB (Oxford) 2014; 16:195. [PMID: 24423079 PMCID: PMC3921017 DOI: 10.1111/hpb.12158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
| | - Jochen K Lennerz
- Jochen K. Lennerz, Institute of Pathology, University of Ulm, Ulm, Germany. E-mail:
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