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Kuehn F, Mullins CS, Krohn M, Harnack C, Ramer R, Krämer OH, Klar E, Huehns M, Linnebacher M. Establishment and characterization of HROC69 - a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft. Sci Rep 2016; 6:24671. [PMID: 27087592 PMCID: PMC4834534 DOI: 10.1038/srep24671] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/23/2016] [Indexed: 02/07/2023] Open
Abstract
Colitis-associated colorectal cancer (CAC) seems to be a rather unique entity and differs in its genetic alterations, tumour formation capacities, and clinical features from sporadic colorectal carcinoma. Most descriptions about tumour biology of CAC refer to ulcerative colitis; data about Crohn´s colitis related carcinomas are scarce. The majority of patients with Crohn´s disease are under immunosuppression which generates a different environment for tumour growth. We first describe the clinical case of a fast growing CAC in a long-term immunosuppressed patient with Crohn´s disease and successful establishment and characterization of carcinoma cell lines along with their corresponding patient-derived xenograft. Subsequently, these tumor models were molecularly and functionally analysed. Beside numerous chromosomal alterations, mutations in TP53, APC, PTEN and SMAD3 were identified. The cell lines express numerous cancer testis antigens, surface molecules involved in immune evasion but low levels of HLA class I molecules. They show strong invasive but in comparison weak migratory activity. The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient. They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.
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Affiliation(s)
- Florian Kuehn
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Christina S Mullins
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Mathias Krohn
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Christine Harnack
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Robert Ramer
- University Medicine Rostock, Institute of Toxicology and Pharmacology, Rostock, Germany
| | - Oliver H Krämer
- University Medical Center Mainz, Department of Toxicology, Mainz, Germany
| | - Ernst Klar
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Maja Huehns
- University Medicine Rostock, Institute of Pathology, Rostock, Germany
| | - Michael Linnebacher
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
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2
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Ben Musa R, Usha L, Hibbeln J, Mutlu EA. TNF inhibitors to treat ulcerative colitis in a metastatic breast cancer patient: A case report and literature review. World J Gastroenterol 2014; 20:5912-5917. [PMID: 24914353 PMCID: PMC4024802 DOI: 10.3748/wjg.v20.i19.5912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 12/02/2013] [Accepted: 01/05/2014] [Indexed: 02/07/2023] Open
Abstract
Adalimumab (ADA) is a tumor necrosis factor (TNF) inhibitor, used for the treatment of inflammatory bowel disease. Previous studies have reported an increased risk of cancer following exposure to TNF inhibitors, but little has been reported for patients with cancer receiving TNF-inhibitor treatment. We present a female patient with metastatic breast cancer and ulcerative colitis (UC) who was treated with ADA. A 54-year-old African American female with a past history of left-sided breast cancer (BC) diagnosed at age 30 was initially treated with left-breast lumpectomy, axillary dissection, followed by chemotherapy and radiation therapy. Years after initial diagnosis, she developed recurrent, bilateral BC and had bilateral mastectomy. Subsequent restaging computed tomography (CT) scan demonstrated distant metastases to the bone and lymph nodes. Three years into her treatment of metastatic breast cancer, she was diagnosed with UC by colonoscopy. Her UC was not controlled for 5 mo with 5-aminosalicylates. Subcutaneous ADA was started and resulted in dramatic improvement of UC. Four months after starting ADA, along with ongoing chemotherapy, restaging CT scan showed resolution of the previously seen metastatic lymph nodes. Bone scan and follow-up positron emission tomography/CT scans performed every 6 mo indicated the stability of healed metastatic bone lesions for the past 3 years on ADA. While TNF-α inhibitors could theoretically promote further metastases in patients with prior cancer, this is the first report of a patient with metastatic breast cancer in whom the cancer has remained stable for 3 years after ADA initiation for UC.
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3
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Betteridge JD, Veerappan GR. Pulmonary carcinoid tumor in a patient on adalimumab for Crohn's disease. Inflamm Bowel Dis 2013; 19:E29-30. [PMID: 22447376 DOI: 10.1002/ibd.22913] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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4
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Quartey B. Primary Hepatic Neuroendocrine Tumor: What Do We Know Now? World J Oncol 2011; 2:209-216. [PMID: 29147250 PMCID: PMC5649681 DOI: 10.4021/wjon341w] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2011] [Indexed: 12/17/2022] Open
Abstract
Primary hepatic neuroendocrine tumors (PHNETs) are rear neoplasm. Diagnosis is an evolution, and requires a systematic clinical exclusion with histological confirmation. Treatment is surgical with excellent prognosis, and a long-term follow-up is required due to high tumor recurring rate. Knowledge from this species of tumor remains limited due to paucity of cases. This article elaborates the key features, diagnosis algorithm, current management, other treatment options and extensive review of literature on this rear tumor.
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Affiliation(s)
- Benjamin Quartey
- National Capital Consortium, National Naval Medical Center, Department of Surgery, 8901 Wisconsin Ave, Bethesda, MD 20889, USA
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Basic-Jukic N, Furic-Cunko V, Coric M, Bubic-Filipi LJ, Kastelan Z, Pasini J, Kes P. Appendiceal carcinoid and mucinous cystadenoma in renal transplant recipients: case reports. Transplant Proc 2010; 42:1704-7. [PMID: 20620505 DOI: 10.1016/j.transproceed.2009.11.045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2009] [Accepted: 11/24/2009] [Indexed: 01/06/2023]
Abstract
There is an increased incidence of tumors among renal transplant patients, which are associated with immunosuppression. Carcinoids are rare neuroendocrine tumors that arise from the enterochromaffin cells. Although appendiceal carcinoid tumors are the commonest malignant neoplasms affecting the appendix, and mucinous cystadenoma is the commonest benign appendiceal neoplasm, they have not been reported in immunosuppressed patients. We present two renal transplant recipients who developed combined appendiceal carcinoid and mucinous cystadenoma.
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Affiliation(s)
- N Basic-Jukic
- Department of Dialysis, University Hospital Centre Zagreb, Zagreb, Croatia.
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Cavoli GL, Rondello G, Zagarrigo C, Tortorici C, Rotolo U. A patient with an asymptomatic carcinoid tumour. Clin Kidney J 2010. [DOI: 10.1093/ndtplus/sfp195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Nemes B, Toronyi É, Rajczy K, Szakos A, Somlai B, Doros A, Chmel R, Derner F, Kóbori L. De novo malignant melanoma occurred in renal allograft: DNA typing to determine the origin of the tumour. Interv Med Appl Sci 2010. [DOI: 10.1556/imas.2.2010.1.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Abstract
Malignant diseases are considered as great challenges in clinical transplantation. It is well known that the incidence of malignancy is higher in the transplanted population if compared with the normal population. It is important to distinguish between neoplastic diseases originating from pre-existing lesions in the transplanted organs and de novo graft tumours. Post-transplant malignancy of donor origin is a rare complication of organ transplantation, most likely transmitted as micrometastases within the parenchyma of the donor organ or from circulating tumour cells contained within the organ. Malignant melanoma, although its incidence is rather low, is one of the most common donor-derived tumour inadvertently transplanted, comprising 28% of donor transmitted tumours. Malignant melanoma in the graft without dermatological localisation is extremely rare. We report a case of de novo melanoma occurring in the allograft, where transmission from the donor was excluded by DNA (desoxyribonucleic acid) investigation. We did not find any data in the literature where a malignant melanoma occurred after transplantation in the transplanted kidney without any skin lesions and the donor origin was excluded. We draw attention to the importance of the DNA typing in case of tumours occurring in immunosuppressed patients.
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Affiliation(s)
- Balázs Nemes
- 1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
- 5 Transplantation and Surgical Department, Semmelweis University, Baross u. 23–25, H-1082, Budapest, Hungary
| | - É. Toronyi
- 1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
| | - K. Rajczy
- 4 National Institute of Hematology and Immunology Budapest, Budapest, Hungary
| | - A. Szakos
- 2 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - B. Somlai
- 3 Dermatological Department, Semmelweis University Budapest, Budapest, Hungary
| | - A. Doros
- 1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
| | - R. Chmel
- 1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
| | | | - L. Kóbori
- 1 Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
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Balta Z, Sauerbruch T, Hirner A, Büttner R, Fischer HP. [Primary neuroendocrine carcinoma of the liver. From carcinoid tumor to small-cell hepatic carcinoma: case reports and review of the literature]. DER PATHOLOGE 2009; 29:53-60. [PMID: 18210116 DOI: 10.1007/s00292-007-0957-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Primary hepatic neuroendocrine tumors are rare neoplasms. While primary hepatic carcinoid tumors (PHCT) are well-differentiated tumors, primary hepatic small-cell carcinomas (PHSCC) represent the poorly differentiated end of the spectrum of neuroendocrine carcinomas. The first patient, suffering from PHCT, has had a follow-up for 32 years and is still alive. Within this time, the tumor relapsed 4 times with unchanged histology and immunohistochemistry features. The second patient suffered from small-cell carcinoma of the liver. There were no risk factors for a hepatocellular carcinoma. An extensive preoperative and postoperative diagnostic investigation could rule out an extrahepatic primary site. Immunohistochemically the tumor was negative for Hepar-1, AFP, TTF1 and CDX2 but reacted positively with CD56 and sporadically with the keratins 8, 18 and 20. A neuroendocrine PHSCC was diagnosed. After neoadjuvant cytostatic treatment the carcinoma was completely extirpated and 18 months after treatment the patient is healthy.PHCT and PHSCC have to be clearly separated from hepatocellular and cholangiocellular carcinomas. Exclusion of an extrahepatic primary site requires an accurate and synoptic analysis of clinical, radiologic and pathologic findings. Surgical resection is the treatment of choice.
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Affiliation(s)
- Z Balta
- Institut für Pathologie, Universitätsklinik Bonn.
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Jin K, Hwang E, Han S, Park S, Kim H, Kwon K, Kim H, Cho W, Kwak J, Ahn K. Rectal Carcinoid Tumor in a Renal Transplant Patient. Transplant Proc 2008; 40:2433-4. [DOI: 10.1016/j.transproceed.2008.07.066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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10
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Rannikko A, Krogerus L, Nyberg M, Salmela K, Ruutu M. Rapid progression of small cell carcinoma in a renal transplant recipient. Int J Urol 2006; 13:817-9. [PMID: 16834670 DOI: 10.1111/j.1442-2042.2006.01412.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Immunosuppression is thought to be responsible for the increased incidence of tumor development after organ transplantation. Natural history of these tumors may be more aggressive than would be expected for a similar tumor in a patient without transplant. We describe the fulminant course of small cell carcinoma, likely of prostatic origin, in a kidney transplant patient. Small cell carcinoma (SCC) and especially SCC of the prostate is an aggressive and rare type of tumor. Due to its rarity, only case reports have been published. To our knowledge, this is the first case of SCC, likely of prostatic origin, in an organ transplant recipient (OTR). The case illustrates the aggressiveness of the disease as reflected by its fulminant progression, which may have been further accentuated by the immunosuppression.
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Affiliation(s)
- Antti Rannikko
- Department of Urology, Helsinki University Central Hospital, Helsinki, Finland.
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Shih WJ, Samayoa L, Shih GL, Milan P. Primary hepatic carcinoid tumor presenting as a large multicystic lesion of the liver and on Tc-99m RBC abdominal imaging showing photopenic areas. Clin Nucl Med 2005; 30:530-1. [PMID: 15965342 DOI: 10.1097/01.rlu.0000167507.77894.a7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Wei-Jen Shih
- Nuclear Medicine Service, VA Medical Center, Lexington, KY 40502-2236, USA.
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Nishimori H, Tsuji K, Miyamoto N, Sakurai Y, Mitsui S, Kang JH, Yoshida M, Nomura M, Fuminori I, Ishiwatari H, Matsunaga T, Osanai M, Katanuma A, Takahashi K, Anbo Y, Masuda T, Kashimura N, Shinohara T, Maguchi H. Recurrence of primary hepatic carcinoid tumor in the remnant liver 13 yr after resection. ACTA ACUST UNITED AC 2005; 35:147-51. [PMID: 15879630 DOI: 10.1385/ijgc:35:2:147] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
We report here a case of primary hepatic carcinoid tumor (PHCT) recurring in the remnant liver 13 yr and 10 mo after first resection. A 70-yr-old man developed four hypervascular tumors in the liver in December 2003. He had undergone curative left-lobe hepatectomy for PHCT in February 1990. Histopathological examination of the tumor biopsy specimen showed that the tumor was composed of uniform round-to-oval cells with solid arrangement and the tumor cells stained positive for chromogranin A, synaptophysin, and neuron-specific enolase. We diagnosed this case as an intrahepatic metastasis of PHCT with a long latency period, based on the fact that no primary site of carcinoid tumor could be found despite intensive examination and the immunohistochemical findings of the resected tumors were essentially same as those of PHCT in 1990. Although PHCT is reported to have a more favorable prognosis than other hepatic cancer or metastatic carcinoid tumor in the liver, long-term observation is recommended.
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Affiliation(s)
- Hiroyuki Nishimori
- Center for Gastroenterology, Teine Keijinkai Hospital, 1-12-1-40 Maeda, Teine-ku, Sapporo, 006-8555, Japan.
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Fenwick SW, Wyatt JI, Toogood GJ, Lodge JPA. Hepatic resection and transplantation for primary carcinoid tumors of the liver. Ann Surg 2004; 239:210-9. [PMID: 14745329 PMCID: PMC1356214 DOI: 10.1097/01.sla.0000109155.89514.42] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To discuss the diagnosis and management of primary carcinoid tumors of the liver in light of our experience and a literature review. SUMMARY BACKGROUND DATA Carcinoid tumors of the liver are rare and pose a diagnostic and management dilemma. This series is the largest reported and the only one to include liver transplantation as a treatment option. METHODS Between March 1994 and May 2002, we treated 8 patients (4 male, 4 female) with primary hepatic carcinoid tumors. Carcinoid syndrome complicated only 1 of the cases. Treatment was by liver resection in 6 patients and orthotopic liver transplantation in 2. RESULTS The diagnosis was confirmed histologically with light microscopy and immunohistochemistry in the absence of an alternative primary site. Six patients remain alive and disease free after follow-up of more than 3 years: 39, 43, 45, 50, 50, and 95 months. Two patients are recently postoperative. CONCLUSIONS Active exclusion of an extrahepatic primary site is essential for the diagnosis of primary carcinoid of the liver. The mainstay of treatment should be liver resection, although liver transplantation may be considered in patients with widespread hepatic involvement. A radical surgical approach is warranted as this disease carries a better prognosis than for other primary hepatic tumors and for secondary hepatic carcinoids.
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Affiliation(s)
- Stephen W Fenwick
- Hepatobiliary and Transplant Unit, St James's University Hospital, Leeds, UK
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Abstract
BACKGROUND Carcinoid tumours of the liver are predominantly metastases from the gastrointestinal tract. Primary hepatic carcinoids are extremely rare. DISCUSSION In contrast to metastases, primary hepatic carcinoids are usually solitary and resectable. It is important that these tumours are differentiated from metastases. Complete surgical resection should be contemplated and is generally curative.
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Affiliation(s)
- M Nikfarjam
- Department of Surgery, University of Melbourne, Austin HospitalMelbourne VictoriaAustralia
| | - V Muralidharan
- Department of Surgery, University of Melbourne, Austin HospitalMelbourne VictoriaAustralia
| | - C Christophi
- Department of Surgery, University of Melbourne, Austin HospitalMelbourne VictoriaAustralia
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