|
1
|
Fonseca GM, Braghiroli MIFM, Pirola Kruger JA, Coelho FF, Herman P. Is There a Role for Locoregional Therapies for Non-colorectal Gastrointestinal Malignancies? Hematol Oncol Clin North Am 2025; 39:125-141. [PMID: 39510669 DOI: 10.1016/j.hoc.2024.08.004] [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] [Indexed: 11/15/2024]
Abstract
The liver is the most common site of metastases from solid gastrointestinal tract tumors. Over the past few decades, the role of locoregional therapies, resection and thermal ablation, for neuroendocrine and colorectal liver metastases has been widely studied. However, for liver metastases originating from other gastrointestinal organs, the role of locoregional treatment remains unclear. This review summarizes and discusses the available evidence regarding benefits, risks, and indications for locoregional therapies for non-colorectal and non-neuroendocrine gastrointestinal liver metastases, highlighting the importance of multidisciplinary approach and patient selection.
Collapse
Affiliation(s)
- Gilton Marques Fonseca
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Maria Ignez Freitas Melro Braghiroli
- Instituto do Cancer do Estado de Sao Paulo (ICESP), University of Sao Paulo, and Rede D'Or Sao Paulo, Av. Dr. Arnaldo, 251 - São Paulo, SP, Brazil. CEP: 01246-000, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil.
| |
Collapse
|
|
2
|
Wang LT, Yang J, Wu J, Lu WJ. Combined Therapy of Chemotherapy and Radiofrequency Ablation for Pancreatic Cancer Patients With Metachronous Hepatic Metastatic Lesions After Radical Pancreatic Resection. Cancer Control 2024; 31:10732748241274559. [PMID: 39150275 PMCID: PMC11329956 DOI: 10.1177/10732748241274559] [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: 03/28/2024] [Revised: 07/09/2024] [Accepted: 07/22/2024] [Indexed: 08/17/2024] Open
Abstract
PURPOSE Hepatic metastasis frequently occurs in patients who have undergone radical pancreatic resection for pancreatic cancer. Besides chemotherapy, various local treatment approaches targeting hepatic lesions have been explored. However, research on radiofrequency ablation (RFA) as a localized therapy for hepatic metastasis is limited. Therefore, we conducted this retrospective study to provide clinical evidence. METHODS This is a single-center, retrospective, cohort study. After radical pancreaticoduodenectomy, 32 patients developed metachronous hepatic metastasis with fewer than 3 lesions, the largest of which was less than 3 cm in diameter. These patients underwent combined treatment with chemotherapy and RFA. After 8 weeks of chemotherapy, patients received RFA for hepatic lesions. Additional chemotherapy was administered, and the patients' tumor status and survival were monitored. The primary endpoint of this study was overall survival (OS). Factors affecting OS were analyzed using the Cox risk model. RESULTS Among the 32 patients, the mean OS was 28.4 months. Univariate and multivariate Cox regression analysis revealed that the time (in months) of liver metastasis (HR = 0.04, 95% CI: 0.01 to 0.19; P < 0.001), the number of liver metastases (HR = 7.08, 95% CI: 1.85 to 27.08, P = 0.004), and PD (progressive disease) response to the second round of chemotherapy (HR = 29.50, 95% CI: 1.46 to 597.27; P = 0.027) were independent predictors of poorer survival. CONCLUSION Combined therapy with RFA and chemotherapy is safe in patients with hepatic metastasis after radical pancreaticoduodenectomy. Early recurrence (≤12 months), three liver metastatic lesions, and a poor response to the second round of chemotherapy were associated with poor survival.
Collapse
Affiliation(s)
- L. T. Wang
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - J. Yang
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - J. Wu
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - W. J. Lu
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
3
|
Kong Q, Teng F, Li H, Chen Z. Radical resection benefits patients suffering pancreatic ductal adenocarcinoma with liver oligometastases. Ann Surg Treat Res 2024; 106:51-60. [PMID: 38205094 PMCID: PMC10774701 DOI: 10.4174/astr.2024.106.1.51] [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] [Received: 08/11/2023] [Revised: 10/16/2023] [Accepted: 11/15/2023] [Indexed: 01/12/2024] Open
Abstract
Purpose Whether patients suffering liver oligometastases from pancreatic ductal adenocarcinoma (LOPDA) should undergo surgical treatment remains controversial. Methods PubMed and Embase databases were systematically reviewed until 2023 June. Survival data were collected from the Kaplan-Meier curves. Safety and survival were evaluated using primary outcomes such as 1-year, 3-year, and 5-year survival rates, and 30-day mortality and morbidity. A subgroup meta-analysis was conducted to compare survival rates post-synchronous resection and resection post-neoadjuvant chemotherapy in LOPDA. Results Our analysis of 15 studies involving 1,818 patients (surgical group, 648 and nonsurgical group, 1,170) indicates that radical hepatectomy for LOPDA notably improved 1-year (odds ratio [OR], 3.24; 95% confidence interval [CI], 2.45-4.28; P < 0.001), 3-year (OR, 5.74; 95% CI, 3.36-8.90; P < 0.001), and 5-year (OR, 4.89; 95% CI, 2.56-9.35; P < 0.001) overall survival (OS) rates. A separate analysis of 6 studies with 750 patients demonstrated the safety of LOPDA surgery, with no increase in postoperative complications (P = 0.26 for overall morbidity and P = 0.99 for mortality) compared to the patients with no metastatic disease from the pancreatic ductal adenocarcinoma (NMPDA) group. The NMPDA group showed superior 1-year and 3-year OS rates, but not 5-year OS rates compared to the LOPDA group. Conclusion Surgical treatment apparently offers a survival advantage to LOPDA by comparing with nonsurgical groups in 1-, 3-, and 5-year OS rates. Radical resection for LOPDA is a safe treatment without more postoperative complications than NMPDA.
Collapse
Affiliation(s)
- Qingyan Kong
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fei Teng
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hang Li
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zheyu Chen
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
4
|
Walter D, Schnitzbauer AA, Schulze F, Trojan J. The Diagnosis and Treatment of Ampullary Carcinoma. DEUTSCHES ARZTEBLATT INTERNATIONAL 2023; 120:729-735. [PMID: 37656482 DOI: 10.3238/arztebl.m2023.0195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care. METHODS A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition. RESULTS Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct. CONCLUSION The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.
Collapse
Affiliation(s)
- Dirk Walter
- Department of Internal Medicine, J.W. Goethe University Hospital, Frankfurt/Main; Department of General, Visceral, Transplant- and Thoracic Surgery, J.W. Goethe University Hospital, Frankfurt/Main; Dr. Senckenberg Institute for Pathology, University Hospital Frankfurt, Goethe University Frankfurt am Main
| | | | | | | |
Collapse
|
|
5
|
Lu W, Wang L, Lou J, Tang K. Sequential therapy for pancreatic cancer patients with synchronous oligo-hepatic metastatic lesions. TUMORI JOURNAL 2023; 109:307-313. [PMID: 35815545 DOI: 10.1177/03008916221110265] [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] [Indexed: 11/15/2022]
Abstract
BACKGROUND Treatments for patients suffering from pancreatic cancer with oligo-hepatic metastasis have always been a cause of certain controversy. Herein, we reported 15 pancreatic cancer patients with oligo-hepatic metastasis who accepted sequential therapy of chemotherapy, radiofrequency ablation (RFA), and radical resection of the primary tumor. METHODS A total of 87 pancreatic cancer patients with synchronous oligo-metastatic hepatic lesions who received treatments in the 2nd Affiliated Hospital of Zhejiang University between January 2017 and July 2020 were enrolled. The chemotherapy regimens included modified folfirinox (54/87) and gemcitabine plus nab-paclitaxel (33/87). Test of blood tumor markers and contrast-enhanced computed tomography (CT) or magnetic resonance (MR) scan was performed at diagnosis and after eight weeks of chemotherapy. RESULTS Thirty-five patients received just chemotherapy because of poor reaction to the first round of chemotherapy(Overall survival (OS), 6.47±1.80 months); 15 patients reassessed as stable disease (SD)/partial response (PR) continued chemotherapy (OS, 10.35±3.15); nine patients reassessed as progressive disease (PD) after RFA and continued chemotherapy (OS, 10.90±2.60). The primary tumors in 13 patients were unresectable after chemotherapy and RFA (OS, 12.92±2.47), while 15 patients completed the sequential therapy of chemotherapy, radio-frequency ablation, and radical resection (OS, 16.76±6.55). CONCLUSIONS Sequential chemotherapy and RFA is a good treatment strategy to select the best candidates for surgical treatment among patients with pancreatic cancer with oligo-hepatic metastasis.
Collapse
Affiliation(s)
- Wenjie Lu
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lantian Wang
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianyao Lou
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kezhong Tang
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
6
|
Kniepeiss D, Talakić E, Portugaller RH, Fuchsjäger M, Schemmer P. Non-colorectal liver metastases: A review of interventional and surgical treatment modalities. Front Surg 2022; 9:945755. [PMID: 36406370 PMCID: PMC9666734 DOI: 10.3389/fsurg.2022.945755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 10/13/2022] [Indexed: 12/31/2023] Open
Abstract
Liver metastases (LM) occur in up to 90% either simultaneously with the diagnosis of the primary tumor or at a later time-point. While resection of colorectal LM and resection or transplantation of neuroendocrine LM is part of a standard therapy with a 5-year patient survival of up to 80%, resection of non-colorectal and non-neuroendocrine LM is still discussed controversially. The reason for it is the significantly lower survival benefit of all different tumor entities depending on the biological aggressiveness of the tumor. Randomized controlled trials are lacking. However, reviews of case series with ≥100 liver resections are available. They show a 5-year patient survival of up to 42% compared to only <5% in patients without treatment. Risk factors for poor survival include the type of primary tumor, a short interval between resection of the primary tumor and liver resection, extrahepatic manifestation of the tumor, number and size of the LM, and extent of liver resection. Overall, it has recently been shown that a good patient selection, the technical advances in surgical therapy and the use of a risk score to predict the prognosis lead to a significantly better outcome so that it is no longer justified not to offer liver resection to patients with non-colorectal, non- endocrine LM. Since modern therapy of LM is multimodal, the optimal therapeutic approach is decided individually by a multidisciplinary team consisting of visceral surgeons, oncologists, interventional radiologists and radiologists as part of a tumor board.
Collapse
Affiliation(s)
- Daniela Kniepeiss
- General, Visceral and Transplant Surgery, Medical University of Graz, Graz, Austria
- University Transplant Center Graz, Medical University of Graz, Graz, Austria
| | - Emina Talakić
- University Transplant Center Graz, Medical University of Graz, Graz, Austria
- Department of Radiology, Division of General Radiology, Medical University of Graz, Graz, Austria
| | - Rupert Horst Portugaller
- University Transplant Center Graz, Medical University of Graz, Graz, Austria
- Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria
| | - Michael Fuchsjäger
- University Transplant Center Graz, Medical University of Graz, Graz, Austria
- Department of Radiology, Division of General Radiology, Medical University of Graz, Graz, Austria
| | - Peter Schemmer
- General, Visceral and Transplant Surgery, Medical University of Graz, Graz, Austria
- University Transplant Center Graz, Medical University of Graz, Graz, Austria
| |
Collapse
|
|
7
|
Sutton TL, Grossberg A, Ey F, O’Reilly EM, Sheppard BC. Multimodality therapy in metastatic pancreas cancer with a BRCA mutation and durable long-term outcome: biology, intervention, or both? Cancer Biol Ther 2021; 22:532-536. [PMID: 34696697 PMCID: PMC8726708 DOI: 10.1080/15384047.2021.1991739] [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: 06/15/2021] [Revised: 09/09/2021] [Accepted: 10/06/2021] [Indexed: 10/20/2022] Open
Abstract
Metastatic pancreatic adenocarcinoma (PDAC) is a rapidly lethal disease, with less than half of patients surviving 12 months, and 5-year survival approximately 3%. These outcomes are in large part due to a lack of effective medical and surgical therapies for metastatic PDAC. Herein, we present the case of a patient with oligometastatic liver recurrence of BRCA2-mutated PDAC following a curative-intent resection. Through a combination of systemic chemotherapy, metastasectomy, radiotherapy, and subsequent targeted therapy with olaparib, the patient is asymptomatic four years following metastatic diagnosis with stable low-volume disease. This patient's excellent outcome is attributable to the multi-disciplinary care received, all aspects of which were informed by new evidence surrounding metastasectomy for metastatic PDAC, the unique biology and medical treatment of BRCA-mutated PDAC, and the role of radiotherapy in controlling locoregional recurrence. We provide a review of this evidence, while highlighting the importance of evaluating disease biology through somatic and germline genetic testing as well as monitoring response to systemic chemotherapy.
Collapse
Affiliation(s)
- Thomas L. Sutton
- Department of Surgery, Oregon Heath & Science University (OHSU), Portland, Oregon, USA
| | - Aaron Grossberg
- Department of Radiation Medicine, OHSU, Portland, Oregon, USA
| | - Frederick Ey
- Department of Hematology/Oncology, OHSU, Portland, Oregon, USA
| | - Eileen M. O’Reilly
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Brett C. Sheppard
- Department of Surgery, Oregon Heath & Science University (OHSU), Portland, Oregon, USA
| |
Collapse
|
|
8
|
Gebauer F, Damanakis AI, Popp F, Quaas A, Kütting F, Lutz K, Held S, Deuß B, Göser T, Waldschmidt D, Bruns C. Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC). BMC Cancer 2021; 21:1239. [PMID: 34794396 PMCID: PMC8600696 DOI: 10.1186/s12885-021-08966-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/04/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. METHODS In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. DISCUSSION This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. TRIAL REGISTRATION NUMBERS EudraCT 2019-002734-37 ; NCT04617457 .
Collapse
Affiliation(s)
- Florian Gebauer
- Department of General, Visceral, Tumor and Transplantation Surgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.
| | - Alexander Ioannis Damanakis
- Department of General, Visceral, Tumor and Transplantation Surgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Felix Popp
- Department of General, Visceral, Tumor and Transplantation Surgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Alexander Quaas
- Institute of Pathology, University of Cologne, Cologne, Germany
| | - Fabian Kütting
- Department of Gastroenterology, University of Cologne, Cologne, Germany
| | | | | | | | - Tobias Göser
- Department of Gastroenterology, University of Cologne, Cologne, Germany
| | - Dirk Waldschmidt
- Department of Gastroenterology, University of Cologne, Cologne, Germany
| | - Christiane Bruns
- Department of General, Visceral, Tumor and Transplantation Surgery, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| |
Collapse
|
|
9
|
Kniepeiss D, Talakić E, Schemmer P. Interventionelle und chirurgische Therapie non-kolorektaler Lebermetastasen. TUMORDIAGNOSTIK & THERAPIE 2021; 42:585-597. [DOI: 10.1055/a-1557-7043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
ZusammenfassungIn der Vergangenheit wurden Resektionen oder Transplantationen wegen non-kolorektaler Lebermetastasen durch die Abwägung von geringem Überlebensvorteil und Komplikationsrate eher zurückhaltend indiziert. Mittlerweile zählt die Leberchirurgie jedoch zu den komplikationsarmen Standardverfahren in der Tumortherapie, die unter Einbettung in multimodale Therapiekonzepte zu einer deutlichen Steigerung des Patientenüberlebens führen.
Collapse
Affiliation(s)
- Daniela Kniepeiss
- Klinische Abteilung für Transplantationschirurgie an der Universitätsklinik für Chirurgie; Universitätsklinikum Graz, Österreich
| | - Emina Talakić
- Klinische Abteilung für Allgemeine Radiologie, Universitätsklinik für Radiologie, Medizinische Universität Graz, Österreich
| | - Peter Schemmer
- Fachbereich für Allgemein-, Viszeral- und Transplantationschirurgie Graz an der Universitätsklinik für Chirurgie; Medizinische Universität Graz, Österreich
| |
Collapse
|
|
10
|
Wellner UF, Bolm L, Vladimirov M, Keck T. [Preoperative diagnostics in periampullary adenocarcinomas]. Chirurg 2021; 92:771-775. [PMID: 34264368 DOI: 10.1007/s00104-021-01452-3] [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] [Accepted: 06/01/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Approximately 30-40% of pancreatoduodenectomies for adenocarcinomas result in nonpancreatic periampullary adenocarcinoma as the final diagnosis. Depending on the origin, a distinction is made between four different carcinomas with histomorphological subtypes. OBJECTIVE Carcinoma location and subtype are of prognostic and therapeutic relevance; however, the preoperative differentiation is often incorrect despite modern diagnostics. MATERIAL AND METHODS Overview of the current literature on the classification and preoperative diagnostics of periampullary adenocarcinomas. RESULTS A precise knowledge of the papillary anatomy is necessary for the correct classification of diagnostic findings. Current studies demonstrate diagnostically valuable information from the anamnesis, imaging and endoscopy. CONCLUSION In ca. 70-80% of cases a correct diagnosis of the type of periampullary adenocarcinoma is possible on the basis of interdisciplinary diagnostics. This potentially enables a correspondingly individualized treatment planning in the preoperative phase.
Collapse
Affiliation(s)
- Ulrich Friedrich Wellner
- Klinik für Chirurgie, Campus Lübeck, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Deutschland
| | - Louisa Bolm
- Klinik für Chirurgie, Campus Lübeck, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Deutschland
| | - Miljana Vladimirov
- Klinik für Allgemein‑, Viszeral- und Thoraxchirurgie, Paracelsus Medizinische Privatuniversität Nürnberg, Nürnberg, Deutschland
| | - Tobias Keck
- Klinik für Chirurgie, Campus Lübeck, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Deutschland.
| |
Collapse
|
|
11
|
Zhou W, Wang D, Lou W. Current Role of Surgery in Pancreatic Cancer With Synchronous Liver Metastasis. Cancer Control 2021; 27:1073274820976593. [PMID: 33238715 PMCID: PMC7791445 DOI: 10.1177/1073274820976593] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer with synchronous liver metastasis has an extremely poor
prognosis, and surgery is not recommended for such patients by the current
guidelines. However, an increasing body of studies have shown that concurrent
resection of pancreatic cancer and liver metastasis is not only technically
feasible but also beneficial to the survival in the selected patients. In this
review, we aim to summarize the short- and long-term outcomes following
synchronous liver metastasectomy for pancreatic cancer patients, and discuss the
potential criteria in selecting appropriate surgical candidates, which might be
helpful in clinical decision-making.
Collapse
Affiliation(s)
- Wentao Zhou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
Yamamoto M, Yoshida M, Furuse J, Sano K, Ohtsuka M, Yamashita S, Beppu T, Iwashita Y, Wada K, Nakajima TE, Sakamoto K, Hayano K, Mori Y, Asai K, Matsuyama R, Hirashita T, Hibi T, Sakai N, Tabata T, Kawakami H, Takeda H, Mizukami T, Ozaka M, Ueno M, Naito Y, Okano N, Ueno T, Hijioka S, Shikata S, Ukai T, Strasberg S, Sarr MG, Jagannath P, Hwang TL, Han HS, Yoon YS, Wang HJ, Luo SC, Adam R, Gimenez M, Scatton O, Oh DY, Takada T. Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:1-25. [PMID: 33200538 DOI: 10.1002/jhbp.868] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/30/2020] [Accepted: 11/08/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.
Collapse
Affiliation(s)
- Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare, School of Medicine, Ichikawa, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shingo Yamashita
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Yukio Iwashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Keita Wada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Takako Eguchi Nakajima
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
- Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, Kyoto, Japan
| | - Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Koichi Hayano
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasuhisa Mori
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Asai
- Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokoama, Japan
| | - Teijiro Hirashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nozomu Sakai
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tsutomu Tabata
- Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Hiroyuki Takeda
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Takuro Mizukami
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Masato Ozaka
- Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makoto Ueno
- Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yoichi Naito
- Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Naohiro Okano
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan
| | - Takayuki Ueno
- Breast Surgical Oncology, Cancer Institute Hospital, Tokyo, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | - Tomohiko Ukai
- Division of Public Health, Osaka Institute of Public Health, Higashinari, Japan
| | - Steven Strasberg
- Section of HPB Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | | | | | - Tsann-Long Hwang
- Division of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Ho-Seong Han
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo-Seok Yoon
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | | | - Shao-Ciao Luo
- Taichung Veterans General Hospital, Taichung, Taiwan
| | - René Adam
- AP HP Paul Brousse Hospital, University Paris Sud, Villejuif, France
| | - Mariano Gimenez
- Docencia Asistencia Investigación en Cirugía Invasiva Mínima Foundation, General and Minimally Invasive Surgery, University of Buenos Aires, Viamonte, Argentina
- Institute of Image-Guided Surgery, Strasbourg, France
| | - Olivier Scatton
- Department of Hepatobiliary Surgery and Liver Transplantation, APHP Pitié-Salpêtrière Hospital, Sorbonne Université, CRSA, Paris, France
| | - Do-Youn Oh
- Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Tadahiro Takada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
14
|
Fonseca GM, Braghiroli MIFM, Pirola Kruger JA, Coelho FF, Herman P. Is There a Role for Locoregional Therapies for Non-colorectal Gastrointestinal Malignancies? Surg Oncol Clin N Am 2020; 30:125-142. [PMID: 33220801 DOI: 10.1016/j.soc.2020.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The liver is the most common site of metastases from solid gastrointestinal tract tumors. Over the past few decades, the role of locoregional therapies, resection and thermal ablation, for neuroendocrine and colorectal liver metastases has been widely studied. However, for liver metastases originating from other gastrointestinal organs, the role of locoregional treatment remains unclear. This review summarizes and discusses the available evidence regarding benefits, risks, and indications for locoregional therapies for non-colorectal and non-neuroendocrine gastrointestinal liver metastases, highlighting the importance of multidisciplinary approach and patient selection.
Collapse
Affiliation(s)
- Gilton Marques Fonseca
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Maria Ignez Freitas Melro Braghiroli
- Instituto do Cancer do Estado de Sao Paulo (ICESP), University of Sao Paulo, and Rede D'Or Sao Paulo, Av. Dr. Arnaldo, 251 - São Paulo, SP, Brazil. CEP: 01246-000, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil.
| |
Collapse
|
|
15
|
Criteria for liver resection for metastasis from bile duct cancer. Surg Today 2020; 51:727-732. [PMID: 33034741 DOI: 10.1007/s00595-020-02159-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/20/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND The surgical indications for liver metastasis from bile duct cancer remain contentious, because surgery is generally thought unlikely to improve survival. However, recent reports show that long-term survival has been achieved with liver resection of metastasis from recurrent bile duct cancer in selected patients. METHODS Liver resection for liver metastasis from bile duct cancer was proposed only when the following criteria were met: liver-only metastasis, a solitary tumor, and no increase in the number of lesions during 3 months of observation. This study aimed to validate our criteria and to analyze which factors impact on survival. RESULT Between 2003 and 2017, 164 patients underwent pathologically curative resection for bile duct cancer. Recurrence developed in 98 of these patients, as liver-only metastasis in 25. Eleven of these 25 patients underwent liver resection (liver resection group), and 14 did not (non-liver resection group). The median overall survival was longer in the liver resection group than in all the patients (44 months vs. 17.8 months, respectively p = 0.040). The median overall survival was better in the liver resection group than in the non-liver resection group (44 months vs. 19.9 months, p = 0.012). The disease-free interval was also significantly longer in the liver resection group than in the non-liver resection group [22 months (range; 4-34 months) vs. 3 months (2-11), p < 0.001]. CONCLUSION Potentially, metachronous solitary liver metastasis from bile duct cancer is an indication for liver resection when the patient has had a long disease-free interval. Observation for 3 months from first detection of metastasis may optimize the selection for this surgery.
Collapse
|
|
16
|
Treatment of hepatic pancreatic ductal adenocarcinoma metastases with high-dose-rate image-guided interstitial brachytherapy: a single center experience. J Contemp Brachytherapy 2019; 11:329-336. [PMID: 31523233 PMCID: PMC6737574 DOI: 10.5114/jcb.2019.87269] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 07/23/2019] [Indexed: 01/05/2023] Open
Abstract
Purpose To evaluate the efficacy and safety of image-guided (computed tomography/magnetic resonance imaging – CT/MRI) high-dose-rate (HDR) interstitial brachytherapy (iBT) as a salvage maneuver for the treatment of hepatic metastases originating from hepatic pancreatic ductal adenocarcinoma (PDAC). PDAC metastases present a major and unresolved problem, and any surgical approach or local therapeutic intervention remains extremely controversial. Material and methods A cumulative number of 45 hepatic PDAC metastases in 16 patients were treated and retrospectively analyzed. Synchronous metastatic spread was observed in five patients, metachronous in eleven. 14 patients had resection of the pancreatic primary prior to iBT: eight Whipple/PPPD and six distal pancreatectomy procedures. The hepatic metastases were progressing under chemotherapy, thus iBT was applied as a salvage maneuver with the intention of local tumor control and prolonged survival. iBT is applied interstitially, with temporarily introduced 192Ir source in a single fraction HDR irradiation regime to eradicate vital tumor cells. Response to treatment was assessed clinically with CT/MRI every three months. Results Local tumor control was achieved in 87% of all treated metastases. The median diameter of the irradiated lesions was 2.2 cm (range, 1-11.2 cm), the median irradiation dose was 21 Gy (range, 5-29.1 Gy). Median progression-free survival (PFS) after iBT was 3.4 months (range, 1.5-19.6 months), the median overall survival (OS) after iBT was 8.9 months (range, 3.1-29.3 months). Three major complications (CTCAE grade 3) occurred following iBT: three cases of liver abscess, which were successfully resolved with drainage and antibiotics. Conclusions Overall, iBT is a safe procedure, which enables excellent rates of local tumor control and presents a viable anti-neoplastic treatment option as a salvage therapy for metastatic PDAC patients.
Collapse
|
|
17
|
[Oligometastasis in pancreatic cancer : Current state of knowledge and spectrum of local therapy]. Chirurg 2019; 89:510-515. [PMID: 29557488 DOI: 10.1007/s00104-018-0626-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several case series reported results of surgical resection in patients with pancreatic ductal adenocarcinoma in a metastasized stage. AIM A summarized overview of the current state of knowledge and a summary of the results of currently available studies. MATERIAL AND METHODS A systematic search was carried out in MEDLINE and PubMed with respect to metastasized pancreatic cancer and surgical resection. RESULTS The evidence level for surgical resection in the metastasized stage is weak and so far no prospective trials are available. The largest single-arm trial included 85 patients with hepatic metastasis. In cases of hepatic oligometastasis an overall survival of 11-14 months was observed. In the presence of pulmonary metastasis, overall survival seems to be prolonged compared to intra-abdominal metastasis, although the evidence level is relatively weak. CONCLUSION According to the available results, a general recommendation for surgical resection in a metastasized stage cannot be given; however, the results show a possible benefit for some well-selected patient subgroups. Prospective trials must validate these data and investigate the use of combined surgical and systemic treatments in the case of resectable metastatic pancreatic cancer.
Collapse
|
|
18
|
Surgical and local therapeutic concepts of oligometastatic pancreatic cancer in the era of effective chemotherapy. Eur Surg 2019. [DOI: 10.1007/s10353-019-0589-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
19
|
Bowitz Lothe IM, Kleive D, Pomianowska E, Cvancarova M, Kure E, Dueland S, Gladhaug IP, Labori KJ. Clinical relevance of pancreatobiliary and intestinal subtypes of ampullary and duodenal adenocarcinoma: Pattern of recurrence, chemotherapy, and survival after pancreatoduodenectomy. Pancreatology 2019; 19:316-324. [PMID: 30713128 DOI: 10.1016/j.pan.2019.01.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 11/07/2018] [Accepted: 01/24/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The clinical relevance of the classification of ampullary adenocarcinoma (AC) into pancreatobiliary (PB) or intestinal (Int) subtypes has not been resolved. METHODS Clinicopathological factors, survival, and localization and treatment of recurrence were investigated for patients with AC and duodenal adenocarcinoma (DC) treated by pancreatoduodenectomy from 2000 to 2015. RESULTS A total of 109 AC (45 PB, 64 Int) and 71 DC (all Int) were identified. Median overall survival (OS) for ACPB vs DC vs ACInt was 43.6 vs 51 vs 75 months, respectively. ACPB had significantly shorter OS than ACInt (p = 0.036). However, for AC stage (HR = 2.39; 95 %CI 1.23-4.64, p = 0.010) was the only factor associated with mortality risk in multivariate analysis. Localization of recurrence (n = 88) was predominantly distant (ACPB 81.5%; ACInt 92%; DC 91.7%, p = 0.371). Post-recurrence survival (PRS) for ACPB, ACInt and DC did not differ (6.9 vs 9.2 vs 7.5 months, p = 0.755). Best supportive care or palliative chemotherapy were offered for recurrent disease to 44.5%/48.1% for ACPB, 40%/56% for ACInt, and 41.7%/52.8% for DC (p = 0.947). The choice of chemotherapy regimen varied considerably. Five patients underwent surgical resection or ablation with curative intent. All deaths among ACPB were caused by recurrent disease, whereas 29.4% of ACInt and 23.1% of DC deaths was non-cancer related or caused by other specific cancer. CONCLUSION ACPB, ACInt and DC have similar recurrence patterns and PRS. The difference in survival between ACPB and ACInt was not statistically significant when stratified by stage. The optimal chemotherapy in patients with recurrent AC remains undefined.
Collapse
Affiliation(s)
- Inger Marie Bowitz Lothe
- Department of Pathology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Dyre Kleive
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway
| | - Ewa Pomianowska
- Department of Surgery, Baerum Hospital, Vestre Viken Hospital Trust, Norway
| | - Milada Cvancarova
- Faculty of Health Sciences, Department of Nursing and Health Promotion, Oslo Metropolitan University, Oslo, Norway
| | - Elin Kure
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital, Norway
| | - Ivar P Gladhaug
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway
| | - Knut Jørgen Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway.
| |
Collapse
|
|
20
|
Lee RC, Kanhere H, Trochsler M, Broadbridge V, Maddern G, Price TJ. Pancreatic, periampullary and biliary cancer with liver metastases: Should we consider resection in selected cases? World J Gastrointest Oncol 2018; 10:211-220. [PMID: 30147847 PMCID: PMC6107475 DOI: 10.4251/wjgo.v10.i8.211] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 05/14/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To analyse the safety and efficacy of curative intent surgery in biliary and pancreatic cancer.
METHODS An extensive literature review was performed using MEDLINE, Google Scholar and EMBASE to identify articles regarding hepato-pancreatoduodenectomy or resection of liver metastasis in patients with pancreatic, biliary tract, periampullary and gallbladder cancers.
RESULTS A total of 19 studies were identified and reviewed. Major hepatectomy was undertaken in 391 patients. The median overall survival for pancreatic cancer ranged from 5-36 mo and for biliary tract/gallbladder cancer, it was 8-38 mo. The 30 d mortality rate was only 1%-9%. Overall Survival was significantly better for patients, who had good response to neoadjuvant chemotherapy, underwent metachronous liver resection and who had intestinal type tumours.
CONCLUSION Resection of liver metastases in pancreatic and biliary cancers may provide survival benefit without compromising safety and quality of life in a very select group of patients. These data may be utilised to formulate selection criteria that may allow future investigation of resection in the era of more effective systemic therapy.
Collapse
Affiliation(s)
- Rachael Chang Lee
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Harsh Kanhere
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Markus Trochsler
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Vy Broadbridge
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Guy Maddern
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Timothy J Price
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| |
Collapse
|
|
21
|
Meijer LL, Alberga AJ, de Bakker JK, van der Vliet HJ, Le Large TYS, van Grieken NCT, de Vries R, Daams F, Zonderhuis BM, Kazemier G. Outcomes and Treatment Options for Duodenal Adenocarcinoma: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2018; 25:2681-2692. [PMID: 29946997 PMCID: PMC6097725 DOI: 10.1245/s10434-018-6567-6] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Indexed: 12/18/2022]
Abstract
Background Duodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims to summarize the current literature on patient outcome after surgical, (neo)adjuvant, and palliative treatment in patients with DA. Methods A systematic search was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary outcome was overall survival (OS), specified for treatment strategy or disease stage. Random-effects models were used for the calculation of pooled odds ratios per treatment modality. Included papers were also screened for prognostic factors. Results A total of 26 observational studies, comprising 6438 patients with DA, were included. Of these, resection with curative intent was performed in 71% (range 53–100%) of patients, and 29% received palliative treatment (range 0–61%). The pooled 5-year OS rate was 46% after curative resection, compared with 1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02–0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed adequate assessment of lymph node involvement and resulted in similar OS. Lymph node involvement correlated with worse OS (pooled 5-year survival rate 21% for nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11–0.27, p < 0.0001). In the current literature, no survival benefit for adjuvant therapy after curative resection was found. Conclusion Resection with curative intent, either pancreaticoduodenectomy or segmental resection, and lack of nodal metastases, favors survival for DA. Further studies exploring multimodality (neo)adjuvant therapy are warranted to investigate their benefit. Electronic supplementary material The online version of this article (10.1245/s10434-018-6567-6) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Laura L Meijer
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Anna J Alberga
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Jacob K de Bakker
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Tessa Y S Le Large
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Ralph de Vries
- Medical Library, VU University Amsterdam, Amsterdam, The Netherlands
| | - Freek Daams
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Barbara M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
| |
Collapse
|
|
22
|
Yu X, Gu J, Fu D, Jin C. Dose surgical resection of hepatic metastases bring benefits to pancreatic ductal adenocarcinoma? A systematic review and meta-analysis. Int J Surg 2017; 48:149-154. [PMID: 29081375 DOI: 10.1016/j.ijsu.2017.10.066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/07/2017] [Accepted: 10/21/2017] [Indexed: 01/11/2023]
Abstract
OBJECTIVE The objectives of this systematic review and meta-analysis were to examine morbidity, mortality, and long-term survival after surgical resection of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC) patients. BACKGROUND Patients with hepatic metastases from pancreatic ductal adenocarcinoma are facing a dilemma of whether to make hepatic resection. METHODS A systematic literature research was undertaken through computerized databases as well as manually research from unpublished data. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and non-surgical treatments based on the evaluation of morbidity, 30-day mortality, and 1-, 3-, or 5-year survival. RESULTS 11 cohort studies with 1147 patients were identified in the pool. Compared with the non-surgical approach, hepatic resection can be performed in a safe and feasible manner for all pancreatic cancer patients with liver metastases (p = 0.13 for overall morbidity; p = 0.63 for mortality). For surgical group, the median 1-year, 3-year, and 5-year survival were 40.9%, 13.3%, 2.9%, respectively, with a median survival of 9.9 months. Surgical resection of hepatic metastases was associated with a significantly improved overall 1-year and 3-year survival (p < 0.001). CONCLUSIONS Hepatic resection is a safe procedure; furthermore, it is worth doing such an extended surgery for PDAC patients due to additional survival benefit in the medium-term (less than 3 years). However, further randomized, controlled trials are urgently needed.
Collapse
Affiliation(s)
- Xinzhe Yu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Jichun Gu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Deliang Fu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Chen Jin
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China.
| |
Collapse
|
|
23
|
Frigerio I, Regi P, Giardino A, Scopelliti F, Girelli R, Bassi C, Gobbo S, Martini PT, Capelli P, D'Onofrio M, Malleo G, Maggino L, Viviani E, Butturini G. Downstaging in Stage IV Pancreatic Cancer: A New Population Eligible for Surgery? Ann Surg Oncol 2017; 24:2397-2403. [PMID: 28516291 DOI: 10.1245/s10434-017-5885-4] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Recent papers consider surgery as an option for synchronous liver oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)]. In this study, we present our series of resected mPDACs after neoadjuvant chemotherapy (nCT). PATIENTS AND METHODS All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS Overall, 24 of 535 patients (4.5%) observed with mPDAC were included. These patients received gemcitabine alone (5/24), gemcitabine + nanoparticle albumin-bound (nab)-paclitaxel (3/24), and FOLFIRINOX (16/24). Primary tumor size decreased from 31 to 19 mm (p < 0.001), and serum CA19-9 decreased from 596 to 18 U/mL (p < 0.001). In 14/24 patients, the tumor was located in the head. Median interval nCT surgery was 2 months, there were no mortalities, and the postoperative course was uneventful in 34% of cases. Grade B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4, and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was achieved in 88% of cases, with 17% complete pathological response. Positive nodes were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was 56 and 27 months, respectively. CONCLUSIONS Patients with mPDAC who were fully responsive to nCT may be cautiously considered for surgery, with potential benefit in survival compared with palliative chemotherapy alone. This is supported by results of our retrospective study, which is the largest ever reported.
Collapse
Affiliation(s)
| | - Paolo Regi
- HPB Surgical Unit, Pederzoli Hospital, Verona, Italy
| | | | | | | | - Claudio Bassi
- General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Gobbo
- Department of Pathology, Pederzoli Hospital, Verona, Italy
| | | | - Paola Capelli
- Department of Pathology, Pederzoli Hospital, Verona, Italy
| | - Mirko D'Onofrio
- Department of Radiology, G.B. Rossi Hospital, University of Verona, Verona, Italy
| | - Giuseppe Malleo
- General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Laura Maggino
- General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Elena Viviani
- General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | | |
Collapse
|
|
24
|
Zhou Y, Li D, Wu L, Si X. The histopathologic type predicts survival of patients with ampullary carcinoma after resection: A meta-analysis. Pancreatology 2017; 17:273-278. [PMID: 28131524 DOI: 10.1016/j.pan.2017.01.007] [Citation(s) in RCA: 12] [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: 11/16/2016] [Revised: 12/27/2016] [Accepted: 01/19/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The results of studies on the prognostic value of histopathologic differentiation of the intestinal and pancreatobiliary types of ampullary carcinoma after resection are conflicting. A meta-analysis was undertaken to investigate this issue. METHODS A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3. RESULTS Twenty three retrospective studies involving a total of 2234 patients were identified for inclusion, of whom 1021 (45.7%) had intestinal type tumors and 899 (40.2%) had pancreaticobiliary type tumors. Patients with the pancreaticobiliary type had high rates of poor tumor differentiation (P < 0.001), lymph node metastasis (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and positive resection margins (P = 0.004), as compared with those with the intestinal type. The pancreaticobiliary type predicted a worse overall survival (hazard ratio [HR] 1.84, 95% CI 1.49-2.27; P < 0.001) and disease-free survival (HR 1.93, 95% CI 1.23-3.01; P = 0.004). CONCLUSION The histopathologic type has major impact on survival in patients with ampullary carcinoma after resection, and the pancreaticobiliary type reflects a more aggressive tumor biology and is associated with worse survival.
Collapse
Affiliation(s)
- Yanming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China.
| | - Dianqi Li
- Department of the First Surgery, Chinese PLA 413 Hospital, Zhoushan, China
| | - Lupeng Wu
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Xiaoying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| |
Collapse
|
|
25
|
Takemura N, Saiura A. Role of surgical resection for non-colorectal non-neuroendocrine liver metastases. World J Hepatol 2017; 9:242-251. [PMID: 28261381 PMCID: PMC5316844 DOI: 10.4254/wjh.v9.i5.242] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 10/29/2016] [Accepted: 12/07/2016] [Indexed: 02/06/2023] Open
Abstract
It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases (NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.
Collapse
Affiliation(s)
- Nobuyuki Takemura
- Nobuyuki Takemura, Department of Gastroenterological Surgery, JR Tokyo General Hospital, Tokyo 151-8528, Japan
| | - Akio Saiura
- Nobuyuki Takemura, Department of Gastroenterological Surgery, JR Tokyo General Hospital, Tokyo 151-8528, Japan
| |
Collapse
|
|
26
|
Buanes TA. Updated therapeutic outcome for patients with periampullary and pancreatic cancer related to recent translational research. World J Gastroenterol 2016; 22:10502-10511. [PMID: 28082802 PMCID: PMC5192261 DOI: 10.3748/wjg.v22.i48.10502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/14/2016] [Accepted: 11/23/2016] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy with improved effect in patients with metastatic pancreatic cancer has recently been established, launching a new era for patients with this very aggressive disease. FOLFIRINOX and gemcitabine plus nab-paclitaxel are different regimens, both capable of stabilizing the disease, thus increasing the number of patients who can reach second line and even third line of treatment. Concurrently, new windows of opportunity open for nutritional support and other therapeutic interventions, improving quality of life. Also pancreatic surgery has changed significantly during the latest years. Extended operations, including vascular/multivisceral resections are frequently performed in specialized centers, pushing borders of resectability. Potentially curative treatment including neoadjuvant and adjuvant chemotherapy is offered new patient groups. Translational research is the basis for the essential understanding of the ongoing development. Even thou biomarkers for clinical management of patients with periampullary tumors have almost been lacking, biomarker driven trials are now in progress. New insight is constantly made available for clinicians; one recent example is selection of patients for gemcitabine treatment based on the expression level of the human equilibrium nucleoside transporter 1. An example of new diagnostic tools is identification of early pancreatic cancer patients by a three-biomarker panel in urine: The proteins lymphatic vessel endothelial hyaluronan receptor 1, regenerating gene 1 alpha and translation elongation factor 1 alpha. Requirement of treatment guideline revisions is intensifying, as combined chemotherapy regimens result in unexpected advantages. The European Study Group for Pancreatic Cancer 4 trial outcome is an illustration: Addition of capecitabine in the adjuvant setting improved overall survival more than expected from the effect in advanced disease. Rapid implementation of new treatment options is mandatory when progress finally extends to patients with this serious disease.
Collapse
|
|
27
|
Shi HJ, Jin C, Fu DL. Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability. World J Gastroenterol 2016; 22:10024-10037. [PMID: 28018110 PMCID: PMC5143749 DOI: 10.3748/wjg.v22.i45.10024] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 09/09/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma (PDAC) and assess unresectability of synchronous liver metastasis. METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group. RESULTS CA125 > 38 U/mL (OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus (OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL (OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years (OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with post-operatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels (7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone (7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula (P = 0.072) or other complications (P = 0.230) and no greater impacts on length of hospital stay (P = 0.602) or post-operative diabetic control (P = 0.479). CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.
Collapse
|
|
28
|
Benzing C, Hau HM, Atanasov G, Broschewitz J, Krenzien F, Bartels M, Wiltberger G. Outcome and complications of combined liver and pancreas resections: a retrospective analysis. Acta Chir Belg 2016; 116:340-345. [PMID: 27471834 DOI: 10.1080/00015458.2016.1186962] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Combined resections of the liver and pancreas are related to high complication and mortality rates. The present study assessed the outcome of these procedures and identified specific risk factors for morbidity and mortality. METHODS Between January 2001 and April 2012, 28 combined liver/pancreas resections were performed at our institution. All patients were retrospectively analysed using a database with regards to baseline characteristics, surgical procedures, complications and survival. RESULTS Among the pancreatic resections, there were 12 (42.9%) Kausch-Whipple (KW), 9 (32.1%) pylorus-preserving pancreaticoduodenectomy (PPPD), 6 (21.4%) distal pancreatectomies (DP) and 1 (3.6%) total pancreaticoduodenectomy (TPD). In 12 (48.9%) cases, major complications (grade IIIb-V) were observed. Overall survival was 35 months (SD = 40.5) and the 3-year survival rate was 35.7% (1-year survival rate: 50%). DISCUSSION Combined resections of the liver and pancreas are associated with high complication rates, especially if major liver resections are performed. Therefore, it is mandatory to do a thorough evaluation of potential patients.
Collapse
Affiliation(s)
- Christian Benzing
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Hans-Michael Hau
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Georgi Atanasov
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Johannes Broschewitz
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Felix Krenzien
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Michael Bartels
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Georg Wiltberger
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| |
Collapse
|
|
29
|
Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? Eur J Surg Oncol 2016; 42:1533-9. [PMID: 27423449 DOI: 10.1016/j.ejso.2016.06.398] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/05/2016] [Accepted: 06/21/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS Retrospective analysis. EXCLUSION CRITERIA patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.
Collapse
|
|
30
|
Schiergens TS, Lüning J, Renz BW, Thomas M, Pratschke S, Feng H, Lee SML, Engel J, Rentsch M, Guba M, Werner J, Thasler WE. Liver Resection for Non-colorectal Non-neuroendocrine Metastases: Where Do We Stand Today Compared to Colorectal Cancer? J Gastrointest Surg 2016; 20:1163-72. [PMID: 26921025 DOI: 10.1007/s11605-016-3115-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 02/16/2016] [Indexed: 01/31/2023]
Abstract
The continuing controversy about surgery for non-colorectal non-neuroendocrine liver metastases (NCRNNE) necessitates identifying risk factors of worsened outcomes to improve patient selection and survival. Prospectively collected data of 167 patients undergoing hepatectomy for NCRNNE were analyzed, and a comparison to a matched population of colorectal liver metastases (CLM) was performed. Overall survival (OS) (35 vs. 54 months; P = 0.008) and recurrence-free survival (RFS) (15 vs. 29 months; P = 0.004) of NCRNNE patients were significantly shorter compared to those with CLM. The best survival was found in the genitourinary (GU; OS, 45 months; RFS, 21 months) NCRNNE subgroup, whereas survival for gastrointestinal (GI) metastases was low (OS, 8 months; RFS, 7 months). Patients with renal cell carcinoma (RCC) showed excellent outcomes when compared to CLM (OS, 50 vs. 51 months; P = 0.901). Extrahepatic disease (EHD) was identified as independent prognostic factor for reducing both RFS (P = 0.040) and OS (P = 0.046). The number of liver lesions (P = 0.024), residual tumor (P = 0.025), and major complications (P = 0.048) independently diminished OS. The degree of survival advantage by surgery is determined by the primary tumor site, EHD, the number of metastases, and residual tumor. Thus-even more than in CLM-these oncological selection criteria must prevail. GU metastases, especially RCC, represent a favorable subgroup.
Collapse
Affiliation(s)
- Tobias S Schiergens
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
| | - Juliane Lüning
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Bernhard W Renz
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Michael Thomas
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Sebastian Pratschke
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Hao Feng
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Serene M L Lee
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Jutta Engel
- Munich Cancer Registry (MCR) of the Munich Tumor Center (TZM), Institute for Medical Information Sciences, Biometry, and Epidemiology (IBE), University Hospital of Munich, Munich, Germany
| | - Markus Rentsch
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Markus Guba
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Jens Werner
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Wolfgang E Thasler
- Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| |
Collapse
|
|
31
|
Gandy RC, Bergamin PA, Haghighi KS. Hepatic resection of non-colorectal non-endocrine liver metastases. ANZ J Surg 2016; 87:810-814. [PMID: 27037839 DOI: 10.1111/ans.13470] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2015] [Indexed: 01/01/2023]
Abstract
BACKGROUND Hepatic resection is standard treatment for liver metastases from colorectal and neuroendocrine cancers as well as primary biliary and hepatic carcinomas. The role of hepatic resection in patients with non-colorectal non-endocrine liver metastases (NCNELM) is less defined. Overall survival in this group of patients is poor with few patients surviving beyond two years, even with modern chemotherapy. METHODS A prospective database of all liver resections performed by a single surgeon (KSH) from January 2007 to December 2014 was maintained. Patient demographics, surgical and pathological data were collected prospectively; survival data were updated retrospectively. Patients were grouped according to pathology and analysis was performed using SPSS (version 21). RESULTS A total of 48 patients underwent hepatic resection for NCNELM, of which 18 were major resections. Pathologies encountered included sarcoma in 8/48, both breast and ovarian in 6/48 each and renal cell carcinoma and melanoma, each representing 5/48. A result of 38/48 patients undertook chemotherapy prior to surgery. R0 margin was achieved in 96%. Seven patients suffered complications from surgery and one peri-operative mortality. Overall survival at 1, 3 and 5 years was 93%, 83% and 61%, respectively. Forty-four percent of patients developed disease recurrence, 29% at distant sites. CONCLUSION Hepatic resection can be achieved safely for NCNELM. Patient selection is key, along with a standardized surgical and anaesthetic technique. Patients should be rigorously investigated to exclude disseminated disease and multidisciplinary discussion must take place prior to surgery. Patients with NCNELM should not routinely be excluded from liver resection and selected patients may benefit from resection.
Collapse
Affiliation(s)
- Robert C Gandy
- The Prince of Wales Hospital, Sydney, New South Wales, Australia.,The University of New South Wales, Sydney, New South Wales, Australia
| | - Paul A Bergamin
- The Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Koroush S Haghighi
- The Prince of Wales Hospital, Sydney, New South Wales, Australia.,The University of New South Wales, Sydney, New South Wales, Australia.,St Vincent's Hospital, Sydney, New South Wales, Australia
| |
Collapse
|
|
32
|
Lai ZW, Bolm L, Fuellgraf H, Biniossek ML, Makowiec F, Hopt UT, Werner M, Keck T, Bausch D, Sorio C, Scarpa A, Schilling O, Bronsert P, Wellner UF. Characterization of various cell lines from different ampullary cancer subtypes and cancer associated fibroblast-mediated responses. BMC Cancer 2016; 16:195. [PMID: 26951071 PMCID: PMC4782372 DOI: 10.1186/s12885-016-2193-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 02/17/2016] [Indexed: 12/20/2022] Open
Abstract
Background Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. Methods We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). Results On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. Conclusion Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2193-5) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Zon Weng Lai
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany
| | - Louisa Bolm
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Hannah Fuellgraf
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany
| | - Martin L Biniossek
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany
| | - Frank Makowiec
- Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany
| | - Ulrich Theodor Hopt
- Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany.,Klinik für Chirurgie, Ratzeburger Allee 160, 23562, Lübeck, Germany
| | - Martin Werner
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany
| | - Tobias Keck
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Dirk Bausch
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Claudio Sorio
- Dipartimento di Patologia, Universita di Verona, Verona, Italy
| | - Aldo Scarpa
- Dipartimento di Patologia, Universita di Verona, Verona, Italy
| | - Oliver Schilling
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany. .,BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany. .,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.
| | - Peter Bronsert
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany
| | - Ulrich Friedrich Wellner
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany.,Klinik für Chirurgie, Ratzeburger Allee 160, 23562, Lübeck, Germany
| |
Collapse
|
|
33
|
Morphological heterogeneity in ductal adenocarcinoma of the pancreas - Does it matter? Pancreatology 2016; 16:295-301. [PMID: 26924665 DOI: 10.1016/j.pan.2016.02.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 02/07/2016] [Accepted: 02/08/2016] [Indexed: 02/08/2023]
Abstract
Morphological heterogeneity is a common finding in pancreatic ductal adenocarcinoma. Inter- and intra-tumour heterogeneity relates not only to the microscopic appearances of the tumour cell population, but pertains also to other essential aspects of the cancer, including the grade of differentiation, growth pattern and desmoplastic stroma. While the existence of considerable morphological variation is well known among pathologists, it is usually not fully appreciated by the wider community. Morphological heterogeneity in pancreatic cancer is only partially represented in the WHO classification, and current pathology guidelines do not recommend reporting on morphological variation other than the conventional variants of ductal adenocarcinoma. Although tumour heterogeneity is increasingly recognized as a major determinant of therapeutic response, morphological heterogeneity has been left unconsidered as a possible proxy for underlying aberrations - genomic or otherwise - that determine the effect of treatment. Various aspects of morphological heterogeneity in pancreatic ductal adenocarcinoma are illustrated in this article and discussed along with the possible implications for patient management and research.
Collapse
|
|
34
|
Wieners G, Schippers AC, Collettini F, Schnapauff D, Hamm B, Wust P, Riess H, Gebauer B. CT-guided high-dose-rate brachytherapy in the interdisciplinary treatment of patients with liver metastases of pancreatic cancer. Hepatobiliary Pancreat Dis Int 2015; 14:530-8. [PMID: 26459730 DOI: 10.1016/s1499-3872(15)60409-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND CT-guided high-dose-rate brachytherapy (CT-HDRBT) is an interventional radiologic technique for local ablation of primary and secondary malignomas applying a radiation source through a brachycatheter percutaneously into the targeted lesion. The aim of this study was to assess local tumor control, safety and efficacy of CT-HDRBT in the treatment of liver metastases of pancreatic cancer. METHODS Twenty consecutive patients with 49 unresectable liver metastases of pancreatic cancer were included in this retrospective trial and treated with CT-HDRBT, applied as a single fraction high-dose irradiation (15-20 Gy) using a 192Ir-source. Primary endpoint was local tumor control and secondary endpoints were complications, progression-free survival and overall survival. RESULTS The mean tumor diameter was 29 mm (range 10-73). The mean irradiation time was 20 minutes (range 7-42). The mean coverage of the clinical target volume was 98% (range 88%-100%). The mean D100 was 18.1 Gy and the median D100 was 19.78 Gy. Three major complications occurred with post-interventional abscesses, three of which were seen in 15 patients with biliodigestive anastomosis (20%) and overall 15%. The mean follow-up time was 13.7 months (range 1.4-55.0). The median progression-free survival was 4.9 months (range 1.4-42.9, mean 9.4). Local recurrence occurred in 5 (10%) of 49 metastases treated. The median overall survival after CT-HDRBT was 8.6 months (range 1.5-55.3). Eleven patients received chemotherapy after ablation with a median progression-free survival of 4.9 months (mean 12.9). Nine patients did not receive chemotherapy after intervention with a median progression-free survival of 3.2 months (mean 5.0). The rate of local tumor control was 91% in both groups after 12 months. CONCLUSION CT-HDRBT was safe and effective for the treatment of liver metastases of pancreatic cancer.
Collapse
Affiliation(s)
- Gero Wieners
- Department of Diagnostic and Interventional Radiology, Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
| | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Lu F, Poruk KE, Weiss MJ. Surgery for oligometastasis of pancreatic cancer. Chin J Cancer Res 2015; 27:358-67. [PMID: 26361405 DOI: 10.3978/j.issn.1000-9604.2015.05.02] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 04/08/2015] [Indexed: 12/17/2022] Open
Abstract
The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.
Collapse
Affiliation(s)
- Fengchun Lu
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Katherine E Poruk
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Matthew J Weiss
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| |
Collapse
|
|
36
|
Sandhu V, Bowitz Lothe IM, Labori KJ, Lingjærde OC, Buanes T, Dalsgaard AM, Skrede ML, Hamfjord J, Haaland T, Eide TJ, Børresen-Dale AL, Ikdahl T, Kure EH. Molecular signatures of mRNAs and miRNAs as prognostic biomarkers in pancreatobiliary and intestinal types of periampullary adenocarcinomas. Mol Oncol 2015; 9:758-771. [PMID: 25579086 PMCID: PMC5528780 DOI: 10.1016/j.molonc.2014.12.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 12/02/2014] [Accepted: 12/08/2014] [Indexed: 02/08/2023] Open
Abstract
Periampullary adenocarcinomas include four anatomical sites of origin (the pancreatic duct, bile duct, ampulla and duodenum) and most of them fall into two histological subgroups (pancreatobiliary and intestinal). Determining the exact origin of the tumor is sometimes difficult, due to overlapping histopathological characteristics. The prognosis depends on the histological subtype, as well as on the anatomical site of origin, the former being the more important. The molecular basis for these differences in prognosis is poorly understood. Whole-genome analyses were used to investigate the association between molecular tumor profiles, pathogenesis and prognosis. A total of 85 periampullary adenocarcinomas were characterized by mRNA and miRNA expressions profiling. Molecular profiles of the tumors from the different anatomical sites of origin as well as of the different histological subtypes were compared. Differentially expressed mRNAs and miRNAs between the two histopathological subtypes were linked to specific molecular pathways. Six miRNA families were downregulated and four were upregulated in the pancreatobiliary type as compared to the intestinal type (P < 0.05). miRNAs and mRNAs associated with improved overall and recurrence free survival for the two histopathological subtypes were identified. For the pancreatobiliary type the genes ATM, PTEN, RB1 and the miRNAs miR-592 and miR-497, and for the intestinal type the genes PDPK1, PIK3R2, G6PC and the miRNAs miR-127-3p, miR-377* were linked to enriched pathways and identified as prognostic markers. The molecular signatures identified may in the future guide the clinicians in the therapeutic decision making to an individualized treatment, if confirmed in other larger datasets.
Collapse
Affiliation(s)
- V Sandhu
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Environmental and Health Studies, Faculty of Arts and Sciences, Telemark University College, Telemark, Norway
| | - I M Bowitz Lothe
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - K J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - O C Lingjærde
- Department of Informatics, University of Oslo, Oslo, Norway
| | - T Buanes
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - A M Dalsgaard
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - M L Skrede
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - J Hamfjord
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - T Haaland
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - T J Eide
- Department of Pathology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - A-L Børresen-Dale
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - T Ikdahl
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - E H Kure
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Environmental and Health Studies, Faculty of Arts and Sciences, Telemark University College, Telemark, Norway.
| |
Collapse
|
|
37
|
Verbeke C, Löhr M, Karlsson JS, Del Chiaro M. Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. Cancer Treat Rev 2015; 41:17-26. [PMID: 25434282 DOI: 10.1016/j.ctrv.2014.11.002] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/07/2014] [Accepted: 11/08/2014] [Indexed: 12/22/2022]
Abstract
An increasing number of studies investigate the use of neoadjuvant treatment for ductal adenocarcinoma of the pancreas. While a strong rationale supports this approach, study results are difficult to interpret and compare due to marked variance in multiple aspects of study design and performance. Divergence in pathology examination and reporting as a cause for heterogeneity and incomparability of study results has not been brought into this discussion yet, despite the fact that several key outcome measures for neoadjuvant treatment are pathology-based. This article discusses areas of controversy and difficulty regarding the evaluation of the extent of residual tumour tissue, grading of tumour regression and assessment of the margins, and explains the important clinical implications of the present uncertainty and divergence in pathology practice.
Collapse
Affiliation(s)
- C Verbeke
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden; Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden.
| | - M Löhr
- Gastrocentrum, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden.
| | - J Severin Karlsson
- Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden.
| | - M Del Chiaro
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden.
| |
Collapse
|
|
38
|
Page AJ, Weiss MJ, Pawlik TM. Surgical management of noncolorectal cancer liver metastases. Cancer 2014; 120:3111-3121. [DOI: 10.1002/cncr.28743] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Andrew J. Page
- Department of Surgery; Johns Hopkins Hospital; Baltimore Maryland
| | - Matthew J. Weiss
- Department of Surgery; Johns Hopkins Hospital; Baltimore Maryland
| | | |
Collapse
|
|
39
|
Fitzgerald TL, Brinkley J, Banks S, Vohra N, Englert ZP, Zervos EE. The benefits of liver resection for non-colorectal, non-neuroendocrine liver metastases: a systematic review. Langenbecks Arch Surg 2014; 399:989-1000. [PMID: 25148767 DOI: 10.1007/s00423-014-1241-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 08/11/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE Defining the benefits of resection of isolated non-colorectal, non-neuroendocrine (NCRNNE) liver metastases is difficult. To better understand the survival benefit in this group of patients, we conducted a systematic review of the previous literature. METHODS Medline, Web of Knowledge, and manual searches were performed using search terms, such as "liver resection" and "primary tumor." Inclusion criteria were year>1990, >five patients, and median survival reported or derived. An expected median survival was calculated from weighted averages of median survivals, and differences were assessed using a permutation test. RESULTS A total of 7,857 references were identified. Overall 4,735 abstracts were reviewed; 120 manuscripts evaluated and of these, 73 met the study inclusion criteria. The final population consisted of 3,596 patients with renal (n=234), ovarian (n=119), testicular (n=153), adrenal (n=90), small bowel (n=28), gallbladder (n=21), duodenum (n=38), gastric (n=481), pancreatic (n=55), esophageal (n=23), head and neck (n=15), and lung (n=36) cancers, gastrointestinal stromal tumors (GISTs) (n=106), cholangiocarcinoma (n=13), sarcoma (n=189), and melanoma (n=643). The greatest expected median was 63 months for genitourinary (GU) primaries (n=549; range 5.4-142 months) followed by 44.4 months for breast cancer (n=1,013; range 8-74 months), 22.3 months for gastrointestinal cancer (n=549; range 5-58 months), and 23.7 months for other tumor types (n=1,082; range 10-72 months). Using a permutation test, we observed that survival was best for patients with GU primaries followed by that for breast cancer patients. Additionally, we also observed that survival was similar for those with cancer of the GI tract and other primary sites. CONCLUSIONS There appears to be a benefit to resection for patients with NCRNNE liver metastases. The degree of survival advantage is predicated by primary site.
Collapse
Affiliation(s)
- Timothy L Fitzgerald
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine, East Carolina University, 4S24 600 Moye Boulevard, Greenville, NC, 27834, USA,
| | | | | | | | | | | |
Collapse
|
|
40
|
Bronsert P, Kohler I, Werner M, Makowiec F, Kuesters S, Hoeppner J, Hopt UT, Keck T, Bausch D, Wellner UF. Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin. BMC Cancer 2013; 13:428. [PMID: 24053229 PMCID: PMC3849372 DOI: 10.1186/1471-2407-13-428] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 09/17/2013] [Indexed: 12/15/2022] Open
Abstract
Background Periampullary adenocarcinomas comprise pancreatic, distal bile duct, ampullary and duodenal adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. With steadily increasing numbers of pancreatoduodenectomies over the last decades, pathologists, surgeons and oncologists are more often confronted with the diagnosis of “other than pancreatic” periampullary cancers. The intestinal subtype of ampullary cancer has been shown to correlate with better prognosis. Methods Histological subtype and immunohistochemical staining pattern for CK7, CK20 and CDX2 were assessed for n = 198 cases of pancreatic ductal, distal bile duct, ampullary and duodenal adenocarcinoma with clinical follow-up. Routine pathological parameters were included in survival analysis performed with SPSS 20. Results In univariate analysis, intestinal subtype was associated with better survival in ampullary, pancreatic ductal and duodenal adenocarcinoma. The intestinal type of pancreatic ductal adenocarcinoma was not associated with intraductal papillary mucinous neoplasm and could not be reliably diagnosed by immunohistochemical staining pattern alone. Intestinal differentiation and lymph node ratio, but not tumor location were independent predictors of survival when all significant predictor variables from univariate analysis (grade, TNM stage, presence of precursor lesions, surgical margin status, perineural, vascular and lymphatic vessel invasion, CK7 and CDX2 staining pattern) were included in a Cox proportional hazards model. Conclusions Intestinal type differentiation and lymph node ratio but not tumor location are independent prognostic factors in pooled analysis of periampullary adenocarcinomas. We conclude that differentiation is more important than tumor location for prognostic stratification in periampullary adenocarcinomas.
Collapse
Affiliation(s)
- Peter Bronsert
- Clinic for General and Visceral Surgery, University of Freiburg, Hugstetter Str, 55, Freiburg 79106, Germany.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Edwards J, Scoggins C, McMasters K, Martin R. Combined pancreas and liver therapies: Resection and ablation in hepato-pancreatico-biliary malignancies. J Surg Oncol 2013; 107:709-12. [DOI: 10.1002/jso.23318] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2012] [Accepted: 12/17/2012] [Indexed: 01/22/2023]
|
|
42
|
Westgaard A, Pomianowska E, Clausen OPF, Gladhaug IP. Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary carcinoma differ from other periampullary malignancies? Ann Surg Oncol 2012; 20:430-9. [PMID: 22956064 DOI: 10.1245/s10434-012-2603-0] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ampullary carcinomas typically have either intestinal or pancreatobiliary type of differentiation, histopathologically resembling carcinomas of its adjacent tissues (duodenum, bile duct, or pancreas). We evaluated whether the histologic type itself is more important for long-term survival than the fact that the tumor originated in the ampulla. METHODS Microscopic slides from 207 consecutive pancreatoduodenectomies were reviewed (72 pancreatic, 46 biliary, 61 ampullary, and 28 duodenal adenocarcinomas; 76 intestinal type, 131 pancreatobiliary type). Tumor size, nodal involvement, margin involvement, degree of differentiation, vascular involvement, and perineural growth, as well as overall survival, were compared between different origins of the same histologic type. RESULTS Intestinal-type ampullary adenocarcinomas had similar frequency of poor histopathologic factors compared to duodenal adenocarcinomas, and pancreatobiliary-type ampullary adenocarcinomas had similar frequency of poor histopathologic factors compared to pancreatobiliary-type biliary and pancreatic adenocarcinomas. Adjusting for tumor size and nodal involvement, there was no difference in long-term survival between patients with intestinal-type ampullary, duodenal, or biliary and pancreatic tumors (p = 0.79), and there was no difference in long-term survival between patients with pancreatobiliary-type ampullary, biliary, or pancreatic tumors (p = 0.41). CONCLUSIONS Long-term survival for patients with ampullary carcinomas equals pancreatic, biliary, and duodenal carcinomas when the same histologic type is compared. It can be questioned whether ampullary carcinomas should be regarded as a separate entity in classification of solid tumors. Clinical trials on adjuvant treatments for periampullary carcinomas should stratify by pancreatobiliary type versus intestinal type of histologic differentiation.
Collapse
Affiliation(s)
- Arne Westgaard
- Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
| | | | | | | |
Collapse
|
|
43
|
Kamel SI, de Jong MC, Schulick RD, Diaz-Montes TP, Wolfgang CL, Hirose K, Edil BH, Choti MA, Anders RA, Pawlik TM. The role of liver-directed surgery in patients with hepatic metastasis from a gynecologic primary carcinoma. World J Surg 2011; 35:1345-54. [PMID: 21452068 DOI: 10.1007/s00268-011-1074-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The management of patients with liver metastasis from a gynecologic carcinoma remains controversial, as there is currently little data available. We sought to determine the safety and efficacy of liver-directed surgery for hepatic metastasis from gynecologic primaries. METHODS Between 1990 and 2010, 87 patients with biopsy-proven liver metastasis from a gynecologic carcinoma were identified from an institutional hepatobiliary database. Fifty-two (60%) patients who underwent hepatic surgery for their liver disease and 35 (40%) patients who underwent biopsy only were matched for age, primary tumor characteristics, and hepatic tumor burden. Clinicopathologic, operative, and outcome data were collected and analyzed. RESULTS Of the 87 patients, 30 (34%) presented with synchronous metastasis. The majority of patients had multiple hepatic tumors (63%), with a median size of the largest lesion being 2.5 cm. Of those patients who underwent liver surgery (n=52), most underwent a minor hepatic resection (n=44; 85%), while 29 (56%) patients underwent concurrent lymphadenectomy and 45 (87%) patients underwent simultaneous peritoneal debulking. Postoperative morbidity and mortality were 37% and 0%, respectively. Median survival from time of diagnosis was 53 months for patients who underwent liver-directed surgery compared with 21 months for patients who underwent biopsy alone (n=35) (p=0.01). Among those patients who underwent liver-directed surgery, 5-year survival following hepatic resection was 41%. CONCLUSIONS Hepatic surgery for liver metastasis from gynecologic cancer can be performed safely. Liver surgery may be associated with prolonged survival in a subset of patients with hepatic metastasis from gynecologic primaries and therefore should be considered in carefully selected patients.
Collapse
Affiliation(s)
- Sarah I Kamel
- Department of Surgery, Johns Hopkins University School of Medicine, Harvey 611, 600 N Wolfe Street, Baltimore, MD 21287, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
WESTGAARD ARNE, CLAUSEN OLEPETTERF, GLADHAUG IVARP. Survival estimates after pancreatoduodenectomy skewed by non-standardized histopathology reports. APMIS 2011; 119:689-700. [DOI: 10.1111/j.1600-0463.2011.02783.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
45
|
Hepatic resection for liver metastases from carcinomas of the distal bile duct and of the papilla of Vater. Langenbecks Arch Surg 2011; 396:607-13. [PMID: 21347688 DOI: 10.1007/s00423-011-0752-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Accepted: 02/11/2011] [Indexed: 12/19/2022]
Abstract
PURPOSE Hepatectomy for liver metastasis from carcinomas of the distal bile duct (BDC) and of the papilla of Vater (PVC) has not been studied in detail. The purpose of this study is to analyze risk factors of liver metastasis and to evaluate outcome of hepatectomy for liver metastasis. METHODS Risk factors of liver metastasis were analyzed in 122 patients who underwent pancreaticoduodenectomy for BDC or PVC. In addition, 13 patients who underwent hepatectomy were reviewed. RESULTS Liver metastasis after pancreaticoduodenectomy occurred in 33.8% of BDC and 26.3% of PVC patients. Multivariate analyses revealed that microvenous invasion was a significant risk factor common to BDC and PVC (p ≤ 0.05). However, 4 of the 13 resected cases survived more than 5 years (5-year survival rate, 44.9%). All four long-term survivors underwent margin-negative hepatectomy for a solitary metastasis and were given postoperative adjuvant chemotherapy. Margin-positive hepatectomy in four patients resulted in early re-recurrence of tumor. Limited hepatectomy (three cases) provided margin-positive surgery. CONCLUSIONS Hepatectomy for a solitary metastasis is the treatment of choice even after pancreaticoduodenectomy, but indication of hepatectomy for multiple metastases is still limited. The combination of surgery and adjuvant chemotherapy should be studied further to improve survival rates.
Collapse
|