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Kim HJ, Ryoo SB, Choi JS, Lim HK, Kim MJ, Park JW, Jeong SY, Park KJ. Ulcerative colitis-associated colorectal neoplasm is increasing as a surgical indication in the biologics era: a retrospective observational study of 20 years of experience in a single tertiary center. Ann Surg Treat Res 2025; 108:150-157. [PMID: 40083981 PMCID: PMC11896760 DOI: 10.4174/astr.2025.108.3.150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 03/16/2025] Open
Abstract
Purpose We aimed to identify changes in surgical indications in patients with ulcerative colitis (UC) in the biologics era in a single tertiary center. Methods In this retrospective observational study, 108 patients with UC who underwent abdominal surgery for UC at Seoul National University Hospital from 2000 to 2021 were included. We compared the total number of patients undergoing UC before and after the introduction of biologic therapy. Results Of the 108 patients with UC (male, 59 and female, 49; mean age, 46.8 years), 30 (27.8%) underwent surgery for neoplasms and 78 (72.2%) for medical intractability without neoplasms. The duration between diagnosis and surgery varied significantly (126.00 months vs. 60.50 months, P = 0.001). A significant difference was also noted in the surgical indications according to time (P = 0.02). Between 2000 and 2010, 12 patients (19.4%) underwent surgery for UC with neoplasms and 50 (80.6%) for UC without neoplasms, while between 2011 and 2021, 18 (39.1%) and 28 patients (60.9%) underwent surgery for UC with and without neoplasms, respectively. Conclusion Since 2011, when biological agents were covered by insurance in South Korea, there has been a relative increase in the incidence of surgical indications for neoplasia cases. Focusing on closely monitoring individuals with long-term UC for neoplasms is necessary.
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Affiliation(s)
- Hyo Jun Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Jin Sun Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Han-Ki Lim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Min Jung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Ji Won Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Kyu Joo Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Murmu N, Ghosh P, Namani A, Patra T. Glyoxylate supplementation ameliorates colitis associated colon cancer progression. J Cell Physiol 2024; 239:e31394. [PMID: 39238268 DOI: 10.1002/jcp.31394] [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: 04/05/2024] [Revised: 06/22/2024] [Accepted: 07/19/2024] [Indexed: 09/07/2024]
Abstract
Colon cancer is on the rise in younger adults. Despite multimodal treatment strategies, clinical outcomes in advanced stage colon cancer patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Overwhelming evidence supporting the small-molecule metabolites derived from breakdown of food or microbial sources confer an extensive array of host benefits, including chemo-preventive role in colon cancer. Our previous study indicated that the introduction of glyoxylate (Glx), an intermediate product of microbial or plant metabolism, exerts a cytotoxic effect in colon cancer cells. This study was designed to evaluate the effects of Glx on colon cancer with molecular insights. For this, we established an AOM/DSS-induced colitis associated colon cancer model in mice. Supplementation of Glx in vivo reduced colitis associated tumor growth and altered the metabolic characteristics of tumor tissue in mice without initiating any severe liver or renal toxicity. More specifically, intake of glyoxylate accumulated glycine in the colon tissue by elevation of alanine-glyoxylate transferase (AGXT) activity. Glycine accumulation increased intracellular Ca2+ concentration via glycine receptor activation and dysregulation of Ca2+ homeostasis lead to induction of apoptosis that resulted in arresting tumor growth. Interestingly, elevation of AGXT activity or Glx related specific metabolic pathway provides better survival in colon cancer patients. Collectively, our exclusive findings support the exploration of Glx either as a preventive molecule or its inclusion in the treatment regimens for colon cancer.
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Affiliation(s)
- Nabendu Murmu
- Department of Signal Transduction & Biogenic Amine, Chittaranjan National Cancer Institute, Kolkata, India
| | - Paramita Ghosh
- Department of Signal Transduction & Biogenic Amine, Chittaranjan National Cancer Institute, Kolkata, India
- Department of Biotechnology, Brainware University, Kolkata, India
| | - Akhileshwar Namani
- Department of Molecular Research, Sri Shankara Cancer Hospital and Research Centre, Bangalore, India
| | - Tapas Patra
- Department of Molecular Research, Sri Shankara Cancer Hospital and Research Centre, Bangalore, India
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Kobayashi K, Toritani K, Kimura H, Kawashima J, Goto K, Suwa Y, Ozawa M, Ishibe A, Watanabe J, Endo I. Differences in Prognosis and Recurrence Patterns Between Ulcerative Colitis-Associated Colorectal Cancer and Sporadic Colorectal Cancer: A Matched-Pair Analysis. Ann Surg Oncol 2024; 31:7807-7819. [PMID: 39244515 DOI: 10.1245/s10434-024-16158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 08/24/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC. PATIENTS AND METHODS This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage. RESULTS A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system. CONCLUSIONS Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference.
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Affiliation(s)
- Kei Kobayashi
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kenichiro Toritani
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Hideaki Kimura
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan.
| | - Jun Kawashima
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Koki Goto
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Yusuke Suwa
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Mayumi Ozawa
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Asushi Ishibe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Jun Watanabe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Palenca I, Basili Franzin S, Zilli A, Seguella L, Troiani A, Pepi F, Vincenzi M, Giugliano G, Catapano V, Di Filippo I, Sarnelli G, Esposito G. N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice. Phytother Res 2024; 38:5350-5362. [PMID: 39235753 DOI: 10.1002/ptr.8303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/15/2024] [Accepted: 07/18/2024] [Indexed: 09/06/2024]
Abstract
Chronic intestinal inflammation and neo-angiogenesis are interconnected in colorectal carcinoma (CRC) pathogenesis. Molecules reducing inflammation and angiogenesis hold promise for CRC prevention and treatment. N-Palmitoyl-d-glucosamine (PGA), a natural glycolipid analog with anti-inflammatory properties, has shown efficacy against acute colitis. Micronized PGA (mPGA) formulations exhibit superior anti-inflammatory activity. This study investigates the in vivo anti-angiogenic and protective effects of mPGA in a mouse model of colitis-associated CRC induced by azoxymethane/dextran sodium sulfate (AOM/DSS). CRC was induced in C57BL/6J mice using intraperitoneal azoxymethane followed by three cycles of 2.5% dextran sodium sulfate (DSS) in drinking water. Mice were treated with mPGA (30-150 mg/kg) with or without the PPARα inhibitor MK886 (10 mg/kg). At Day 70 post-azoxymethane injection, mice underwent anesthetized endoscopic colon evaluation. Post-mortem analysis of tumorigenesis and angiogenesis was performed using histological, immunohistochemical, and immunoblotting techniques. mPGA improved disease progression and survival rates in a dose- and PPARα-dependent manner in AOM/DSS-exposed mice. It reduced polyp formation, decreased pro-angiogenic CD31, pro-proliferative Ki67, and pro-inflammatory TLR4 expression levels, and inhibited VEGF and MMP-9 secretion by disrupting the pAkt/mTOR/HIF1α pathway. mPGA increased colon PEA levels, restoring anti-tumoral PPARα and wtp53 protein expression. Given its lack of toxicity, mPGA shows potential as a nutritional intervention to counteract inflammation-related angiogenesis in CRC.
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Affiliation(s)
- Irene Palenca
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
| | - Silvia Basili Franzin
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
| | - Aurora Zilli
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
| | - Luisa Seguella
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
| | - Anna Troiani
- Department of Chemistry and Drug Technologies, Sapienza University of Rome, Rome, Italy
| | - Federico Pepi
- Department of Chemistry and Drug Technologies, Sapienza University of Rome, Rome, Italy
| | - Martina Vincenzi
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
| | - Giuseppe Giugliano
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Viviana Catapano
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Italia Di Filippo
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Giuseppe Esposito
- Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
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Yamamoto N, Yamashita K, Takehara Y, Morimoto S, Tanino F, Kamigaichi Y, Tanaka H, Arihiro K, Shimamoto F, Oka S. Characteristics and Prognosis of Sporadic Neoplasias Detected in Patients with Ulcerative Colitis. Digestion 2024; 105:213-223. [PMID: 38417416 DOI: 10.1159/000537756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 02/08/2024] [Indexed: 03/01/2024]
Abstract
INTRODUCTION Patients with ulcerative colitis (UC) develop not only UC-associated neoplasias but also sporadic neoplasias (SNs). However, few studies have described the characteristics of SNs in patients with UC. Therefore, this study aimed to evaluate the clinical features and prognosis of SNs in patients with UC. METHODS A total of 141 SNs in 59 patients with UC, detected by surveillance colonoscopy at Hiroshima University Hospital between January 1999 and December 2021, were included. SNs were diagnosed based on their location, endoscopic features, and histopathologic findings along with immunohistochemical staining for Ki67 and p53. RESULTS Of the SNs, 91.5% were diagnosed as adenoma and 8.5% were diagnosed as carcinoma (Tis carcinoma, 3.5%; T1 carcinoma, 5.0%). 61.0% of the SNs were located in the right colon, 31.2% were located in the left colon, and 7.8% were located in the rectum. When classified based on the site of the lesion, 70.9% of SNs occurred outside and 29.1% within the affected area. Of all SNs included, 95.7% were endoscopically resected and 4.3% were surgically resected. Among the 59 patients included, synchronous SNs occurred in 23.7% and metachronous multiple SNs occurred in 40.7% during surveillance. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without synchronous multiple SNs (46.4%). CONCLUSION Patients with UC with synchronous multiple SNs are at a higher risk of developing metachronous multiple SNs and may require a closer follow-up by total colonoscopy than patients without synchronous SNs.
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Affiliation(s)
- Noriko Yamamoto
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Ken Yamashita
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Yudai Takehara
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Shin Morimoto
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Fumiaki Tanino
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Yuki Kamigaichi
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hidenori Tanaka
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan
| | - Fumio Shimamoto
- Faculty of Health Sciences, Hiroshima Cosmopolitan University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
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Lynn PB, Cronin C, Rangarajan S, Widmar M. Rectal Cancer and Radiation in Colitis. Clin Colon Rectal Surg 2024; 37:30-36. [PMID: 38188064 PMCID: PMC10769583 DOI: 10.1055/s-0043-1762561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer. When IBD patients develop a rectal cancer, this should be treated with the same oncological principles and guidelines as the general population. Rectal cancer treatment includes surgery, chemotherapy, and radiation therapy (RT). Many IBD patients will require a total proctocolectomy with an ileal-pouch anal anastomosis (IPAA) and others, restoration of intestinal continuity may not be feasible or advisable. The literature is scarce regarding outcomes of IPAA after RT. In the present review, we will summarize the evidence regarding RT toxicity in IBD patients and review surgical strategies and outcomes of IPAA after RT.
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Affiliation(s)
- Patricio B. Lynn
- Division of Colorectal Surgery, Department of General Surgery, New York Presbyterian – Weill-Cornell, New York, New York
| | - Catherine Cronin
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sriram Rangarajan
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maria Widmar
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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7
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Hammoudi N, Lehmann-Che J, Lambert J, Amoyel M, Maggiori L, Salfati D, Tran Minh ML, Baudry C, Asesio N, Poirot B, Lourenco N, Corte H, Allez M, Aparicio T, Gornet JM. Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center. Dig Liver Dis 2023; 55:1280-1287. [PMID: 36872200 DOI: 10.1016/j.dld.2023.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 02/10/2023] [Accepted: 02/16/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.
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Affiliation(s)
- N Hammoudi
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France; Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - J Lehmann-Che
- Department of molecular oncology, Hôpital Saint-Louis, Université Paris Cité, Paris, France
| | - J Lambert
- Department of biostatistics, Hôpital Saint-Louis, APHP, Paris University, Paris, France. Hôpital Saint-Louis, Paris - France
| | - M Amoyel
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - L Maggiori
- Department of digestive surgery, Hôpital Saint-Louis, APHP, Université Paris Cité, Paris, France
| | - D Salfati
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - M L Tran Minh
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - C Baudry
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - N Asesio
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - B Poirot
- Department of molecular oncology, Hôpital Saint-Louis, Université Paris Cité, Paris, France
| | - N Lourenco
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - H Corte
- Department of digestive surgery, Hôpital Saint-Louis, APHP, Université Paris Cité, Paris, France
| | - M Allez
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France; Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - T Aparicio
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France; Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France
| | - J M Gornet
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis / Lariboisière, Paris, France.
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Lepore Signorile M, Grossi V, Fasano C, Simone C. Colorectal Cancer Chemoprevention: A Dream Coming True? Int J Mol Sci 2023; 24:7597. [PMID: 37108756 PMCID: PMC10140862 DOI: 10.3390/ijms24087597] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.
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Affiliation(s)
- Martina Lepore Signorile
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Valentina Grossi
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Candida Fasano
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Cristiano Simone
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
- Medical Genetics, Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
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9
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Tatar C, Lightner AL, Jia X, Liska D, Kalady M, Steele SR, Gorgun E. Long-term outcomes of sporadic rectal cancer versus ulcerative colitis-associated rectal cancer: a matched case-control study. ANZ J Surg 2022; 92:3232-3236. [PMID: 36054252 DOI: 10.1111/ans.17992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/07/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Although patients with ulcerative colitis (UC) are at increased risk of rectal cancer compared to the general population, it remains unclear whether their oncologic outcomes are different than sporadic rectal cancer (S-RC).We aimed to compare survival and oncologic outcomes in S-RC versus UC-associated rectal cancer (UC-RC). METHODS We performed a retrospective case-control study of patients who underwent surgical resection for rectal cancer between 2005 and 2015. Data collected included patient demographics, intraoperative variables, postoperative outcomes, and oncological outcomes. RESULTS A total of 138 patients were included; 92 patients with S-RC and 46 with UC-RC. Both groups were comparable in terms of demographics, oncologic characteristics, oncologic treatment strategies, perioperative complications and operative factors except for preoperative radiotherapy. At a median follow-up time of 3.7 years the 3-and 5-year OS rates; the 1-and 3-year DFS rates were comparable between the groups. CONCLUSION Ulcerative colitis-associated rectal cancer patients have similar survival and oncologic outcomes as sporadic rectal cancer patients.
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Affiliation(s)
- Cihad Tatar
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amy L Lightner
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Xue Jia
- Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - David Liska
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Matthew Kalady
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Scott R Steele
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Emre Gorgun
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
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10
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Surgery for ulcerative colitis complicated with colorectal cancer: when ileal pouch-anal anastomosis is the right choice. Updates Surg 2022; 74:637-647. [PMID: 35217982 PMCID: PMC8995269 DOI: 10.1007/s13304-022-01250-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/27/2022] [Indexed: 11/29/2022]
Abstract
Patients with ulcerative colitis (UC) are at risk of developing a colorectal cancer. The aim of this study was to examine our experience in the treatment of ulcerative Colitis Cancer (CC), the role of the ileal pouch–anal anastomosis (IPAA), and the clinical outcome of the operated patients. Data from 417 patients operated on for ulcerative colitis were reviewed. Fifty-two (12%) were found to have carcinoma of the colon (n = 43) or the rectum (n = 9). The indication to surgery, the histopathological type, the cancer stage, the type of surgery, the oncologic outcome, and the functional result of IPAA were examined. The majority of the patients had a mucinous or signet-ring carcinoma. An advanced stage (III or IV) was present in 28% of the patients. Early (stage I or II) CC was found in all except one patient submitted to surgery for high-grade dysplasia, low-grade dysplasia, or refractory colitis. Thirty-nine (75%) of the 52 patients underwent IPAA, 10 patients were treated with a total abdominal proctocolectomy with terminal ileostomy. IPAA was possible in 6/9 rectal CC. Cumulative survival rate 5 and 10 years after surgery was 61% and 53%, respectively. The survival rate was significantly lower for mucinous or signet-ring carcinomas than for other adenocarcinoma. No significant differences of the functional results and quality of life were observed between IPAA patients aged less than or more than 65 years. Failure of the pouch occurred in 5 of 39 (12.8%) patients for cancer of the pouch (2 pts) or for tumoral recurrence at the pelvic or peritoneal level. Early surgery must be considered every time dysplasia is discovered in patients affected by UC. The advanced tumoral stage and the mucous or signet-ring hystotype influence negatively the response to therapy and the survival after surgery. IPAA can be proposed in the majority of the patients with a functional result similar to that of UC patients not affected by CC. Failures of IPAA for peritoneal recurrence or metachronous cancer of the pouch can be observed when CC is advanced, moucinous, localized in the distal rectum, or is associated with primary sclerosing cholangitis.
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11
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Vitali F, Wein A, Rath T, Eckstein M, Neufert C, Siebler J, Atreya R, Hartmann A, Hohenberger W, Weber K, Neurath MF, Grützmann R, Merkel S. The outcome of patients with inflammatory bowel disease-associated colorectal cancer is not worse than that of patients with sporadic colorectal cancer-a matched-pair analysis of survival. Int J Colorectal Dis 2022; 37:381-391. [PMID: 34865179 PMCID: PMC8803672 DOI: 10.1007/s00384-021-04072-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/22/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Patients with inflammatory bowel disease (IBD) have an increased risk for colorectal cancer (CRC). In IBD patients, cancer is often diagnosed in advanced stages and conflicting data on survival compared to sporadic CRC have been reported. The aim of this study was to directly compare clinical characteristics and prognosis of patients with IBD-CRC and sporadic CRC. METHODS The clinical and pathological data of 63 patients with IBD-CRC and 3710 patients with sporadic CRC treated at the University Hospital of Erlangen between 1995 and 2015 were compared. Forty-seven M0 patients with IBD were matched with sporadic CRC patients after curative resection (R0) according to tumor localization, stage, sex, and year of treatment. Overall and disease-free survival were compared. RESULTS Sixty-three patients presented IBD-CRC. Fifty were affected with ulcerative colitis (UC) and 13 with Crohn's disease (CD). CRC was diagnosed within 1.45 years since last endoscopic surveillance. Twelve patients (19%) had a diagnosis of primary sclerosing cholangitis. In matched analysis, IBD patients were diagnosed with CRC at younger age compared to sporadic CRC and were more likely to have right-sided CRC (40% versus 23.3%) and rare histological subtypes (19% versus 9.2%). No differences in 5-year overall (78.7 versus 80.9 months) and 5-year disease-free survival (74.5 versus 70.2 months) were noted. CONCLUSION IBD-CRC patients were younger and more frequently had right-sided carcinomas compared to sporadic CRC. CRC in IBD patients did not show survival difference compared to matched-pair sporadic CRC patients without distant metastases after curative resection. Surveillance might be important for early detection of CRC in IBD patients.
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Affiliation(s)
- Francesco Vitali
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany.
| | - Axel Wein
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Timo Rath
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Clemens Neufert
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Jürgen Siebler
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Raja Atreya
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Werner Hohenberger
- Department of General and Abdominal Surgery, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Klaus Weber
- Department of General and Abdominal Surgery, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Markus Friedrich Neurath
- Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Robert Grützmann
- Department of General and Abdominal Surgery, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Susanne Merkel
- Department of General and Abdominal Surgery, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany
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12
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Kanters A, Liska D. The Impact of Ulcerative Colitis on Colorectal Cancer Prognosis: The Jury is Still Out. Ann Surg Oncol 2022; 29:2761-2762. [PMID: 35015182 DOI: 10.1245/s10434-021-11307-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 12/25/2021] [Indexed: 01/10/2023]
Affiliation(s)
- Arielle Kanters
- Department of Colorectal Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, USA, Cleveland
| | - David Liska
- Department of Colorectal Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, USA, Cleveland.
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13
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Lee SA, Liu F, Yun DY, Riordan SM, Tay ACY, Liu L, Lee CS, Zhang L. Campylobacter concisus upregulates PD-L1 mRNA expression in IFN-γ sensitized intestinal epithelial cells and induces cell death in esophageal epithelial cells. J Oral Microbiol 2021; 13:1978732. [PMID: 34552702 PMCID: PMC8451702 DOI: 10.1080/20002297.2021.1978732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/20/2021] [Accepted: 09/06/2021] [Indexed: 12/23/2022] Open
Abstract
Introduction: Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) and Barrett's esophagus (BE). Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that is used by tumor cells for immune evasion and has increased expression in patients with IBD and BE. We examined whether C. concisus upregulates PD-L1 expression in intestinal and esophageal epithelial cells. Methods: Human intestinal epithelial HT-29 cells and esophageal epithelial FLO-1 cells with and without interferon (IFN)-γ sensitization were incubated with C. concisus strains. The level of PD-L1 mRNA was quantified using quantitative real-time PCR. Cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis of HT-29 and FLO-1 cells were measured using caspase 3/7 assay. Results: We found that intestinal epithelial cells with IFN-γ sensitization incubated with C. concisus significantly upregulated PD-L1 expression and significantly increased the production of interleukin (IL)-8. Whereas, PD-L1 expression was significantly inhibited in IFN-γ sensitized FLO-1 cells incubated with C. concisus strains. Furthermore, FLO-1 cells with and without IFN-γ sensitization incubated with C. concisus strains both had significantly higher levels of cell death. Conclusion: C. concisushas the potential to cause damage to both intestinal and esophageal epithelial cells, however, with different pathogenic effects.
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Affiliation(s)
- Seul A Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Doo Young Yun
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit,Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Cheok Soon Lee
- School of Medicine, Western Sydney University, Sydney, Australia
- South Western Sydney Clinical School, University of New South Wales, Sydney, Australia
- Central Clinical School, University of Sydney, Sydney, Australia
- Department of Anatomical Pathology, Liverpool Hospital, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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14
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Lin VA, Lohse R, Madsen MT, Fransgaard T, Remzi FH, Gögenur I. Long-Term Outcomes After Colorectal Surgery in Patients with Ulcerative Colitis-Associated Colorectal Cancer Versus Sporadic Colorectal Cancer. Ann Surg Oncol 2021; 29:2505-2512. [PMID: 34482452 DOI: 10.1245/s10434-021-10759-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 07/24/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Ulcerative colitis is associated with a higher risk for developing colorectal cancer. It is unknown whether this translates into a worse prognosis when malignancy occurs. The goal of this study was to compare long-term outcomes between patients with ulcerative colitis-associated colorectal cancer and sporadic colorectal cancer. METHODS All patients who underwent surgery with curative intent for colorectal cancer in Denmark between January 2004 and June 2016 were included in the study. Patients diagnosed with ulcerative colitis were identified and matched 1:5 with patients with sporadic colorectal cancer using propensity score matching. The primary outcome was disease-free survival, with recurrence-free survival and all-cause mortality as secondary outcomes. In order to relate the results of the study to the existing literature, a systematic review with meta-analysis was conducted. RESULTS A total of 1332 patients, 222 with ulcerative colitis and 1110 with sporadic colorectal cancer were included in the study. Disease-free survival was similar between the two groups with a hazards ratio (HR) 1.06 [95% confidence interval (CI) 0.85-1.32], as was recurrence-free survival HR 1.14 (95% CI 0.86-1.53) and all-cause mortality HR 1.15 (95% CI 0.89-1.48). The results of the systematic review identified seven other relevant studies. Meta-analysis showed a HR 1.67 (95% CI 0.61-4.56) for recurrence-free survival and HR 1.21 (95% CI 0.93-1.56) for all-cause mortality. CONCLUSIONS There were no significant differences in long-term outcomes between ulcerative colitis-associated and sporadic colorectal cancer. However, the current results are limited by possible residual confounding and the meta-analysis by heterogeneity in confounding adjustment.
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Affiliation(s)
- Viviane A Lin
- Department of Surgery, Center for Surgical Science, Zealand University Hospital, Køge, Denmark. .,Department of Surgery, Nordsjællands Hospital Hillerød, Hillerød, Denmark.
| | - Robin Lohse
- Department of Anesthesiology, Herlev Hospital, Herlev, Denmark
| | - Michael T Madsen
- Department of Surgery, Center for Surgical Science, Zealand University Hospital, Køge, Denmark
| | - Tina Fransgaard
- Department of Surgery, Center for Surgical Science, Zealand University Hospital, Køge, Denmark
| | - Feza H Remzi
- Department of Surgery, Langone Medical Center, New York University, New York, NY, USA
| | - Ismail Gögenur
- Department of Surgery, Center for Surgical Science, Zealand University Hospital, Køge, Denmark
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15
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Azizmohammad Looha M, Zarean E, Masaebi F, Pourhoseingholi MA, Zali MR. Assessment of prognostic factors in long-term survival of male and female patients with colorectal cancer using non-mixture cure model based on the Weibull distribution. Surg Oncol 2021; 38:101562. [PMID: 33862578 DOI: 10.1016/j.suronc.2021.101562] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 01/19/2021] [Accepted: 03/29/2021] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Colorectal cancer (CRC) is known as one of the malignant form of cells growing in the inner lining of colon and rectum which could seriously affect the cure rate of patients. We aimed to evaluate the effect of prognostic factors on cure fraction of CRC patients. METHODS A total of 1043 CRC patients were included to the study from December 2001 to January 2007 at the Research Center of Gastroenterology and Liver Disease in Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients' information was extracted from their medical records, then they were followed to identify their death status via phone-call. Weibull non-mixture cure model was used to evaluate the effect of the risk factors on cure fraction of CRC patients. RESULTS The five-years survival rate was 0.66 (males: 0.64 and female: 0.69). The median survival time for non-cured CRC patients were 3.45 years (males: 3.46; females = 3.45 years). In the single Weibull model, BMI≥30 (OR = 4.61, p-value = 0.033), poorly differentiated tumor grade (OR = 0.36, p-value = 0.036), tumor size≥25 mm (OR = 0.22, p-value = 0.046), and N1-stage (OR = 0.42, p-value = 0.005) had significant effect on females' cure fraction. Also, cure fraction of male CRC patients significantly affected by BMI (levels:25.0-29.9-OR = 12.13-p-value<0.001; ≥30-OR = 7.00-p-value = 0.017), T1-stage (OR = 0.52, p-value = 0.021), M1-stage (OR = 0.45, p-value = 0.007), IV-staging (OR = 0.36, p-value = 0.041) and IBD (OR = 0.26, p-value = 0.017). In multiple Weibull model, females were associated with tumor size≥25 mm (OR = 0.20, p-value = 0.044) and N1-stage (OR = 0.45, p-value = 0.013) and males were affected by M1-stage (OR = 0.41, p-value = 0.011) and IBD (OR = 0.20, p-value = 0.022).The cure fraction of males and females CRC patients was 64% and 69%, respectively. CONCLUSIONS The prognostic factors for cure fraction of patients with CRC may be different among males and females. Further multicenter studies are required to assess the effect of common prognostic factors between males and females.
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Affiliation(s)
- Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elaheh Zarean
- Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Fatemeh Masaebi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohamad Amin Pourhoseingholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohamad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Epidemiology of Colorectal Cancer in Inflammatory Bowel Disease - the Evolving Landscape. Curr Gastroenterol Rep 2021; 23:16. [PMID: 34338892 DOI: 10.1007/s11894-021-00816-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW To update changes in the epidemiology of colorectal cancer in patients with ulcerative colitis and Crohn's disease over the past decades. RECENT FINDINGS Since the mid twentieth century, studies have found that the incidence of colorectal cancer in patients with IBD has been greater than that of the general population, especially for patients with a family history of colorectal cancer, a diagnosis of primary sclerosing cholangitis, and/or pancolitis. While Crohn's disease and ulcerative colitis are still associated with a risk of colorectal cancer, current treatment approaches and surveillance measures have markedly reduced the risk according to population-based cohort studies such that the risk is now more comparable to that of the general population. It is predicted that by 2025, more than two million patients will be living with inflammatory bowel disease in the United States. As advanced treatment options become available to achieve histologic remissions and as surveillance techniques to detect neoplasia improve, guidelines for surveillance will continue to evolve.
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17
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Mark-Christensen A, Erichsen R, Veres K, Laurberg S, Sørensen HT. Rectal Cancer Risk and Survival After Total Colectomy for IBD: A Population-Based Study. Dis Colon Rectum 2021; 64:583-591. [PMID: 33496488 DOI: 10.1097/dcr.0000000000001810] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND:
Patients undergoing total colectomy for IBD may develop cancer in the rectal remnant, but the association is poorly understood.
OBJECTIVES:
This study aimed to examine the risk and prognosis of rectal cancer after total colectomy for IBD.
DESIGN:
This is a nationwide population-based study.
SETTING:
Treatment of the patients took place in Denmark from 1977 to 2013.
PATIENTS:
Patients with IBD undergoing total colectomy were included.
MAIN OUTCOME MEASURES:
We examined the incidence of rectal cancer among patients with IBD and total colectomy and compared cancer stage to that of other patients with rectal cancer in Denmark. We used Kaplan-Meier methodology to estimate survival and Cox regression to estimate adjusted mortality rate ratios following a rectal cancer diagnosis, comparing patients with and without IBD and a rectal remnant.
RESULTS:
We identified 4703 patients with IBD (1026 Crohn’s disease; 3677 ulcerative colitis) who underwent total colectomy with a rectal remnant. During 29,725 years of follow-up, 30 rectal cancers were observed, compared with 8 rectal cancers expected (standardized incidence ratio = 3.6 (95% CI, 2.4–5.1)). Cancer stage distributions were similar. Risk of rectal cancer 35 years after total colectomy was 1.9% (95% CI, 1.1%–2.9%). Five years after rectal cancer diagnosis, survival was 28% (95% CI, 12%–47%) and 38% (95% CI, 37%–38%) for patients with and without IBD and a rectal remnant. The adjusted mortality rate ratio 1 to 5 years after a rectal cancer diagnosis was 2.5 (95% CI, 1.6–3.9). Median time from last recorded nondiagnostic proctoscopy to rectal cancer diagnosis for patients with IBD and total colectomy was 1.1 years.
LIMITATIONS:
This study was limited by the few outcomes and the use of administrative and not clinical data.
CONCLUSION:
Long-term risk of rectal cancer following total colectomy for IBD was low. Survival following a diagnosis of rectal cancer was poorer for patients with IBD and total colectomy than for patients who had rectal cancer without IBD and total colectomy. Endoscopic surveillance, as it appeared to be practiced in this cohort, may be inadequate. See Video Abstract at http://links.lww.com/DCR/B497.
RIESGO DE CÁNCER DE RECTO Y SUPERVIVENCIA DESPUÉS DE UNA COLECTOMÍA TOTAL POR ENFERMEDAD INFLAMATORIA INTESTINAL: UN ESTUDIO POBLACIONAL
ANTECEDENTES:
Los pacientes sometidos a colectomía total por enfermedad inflamatoria intestinal (EII) pueden desarrollar cáncer en el remanente rectal, pero la asociación es poco conocida.
OBJETIVOS:
Examinar el riesgo y el pronóstico del cáncer de recto después de una colectomía total para la EII.
DISEÑO:
Estudio poblacional a nivel nacional.
ENTORNO CLINICO:
Dinamarca 1977-2013.
PACIENTES:
Pacientes con EII sometidos a colectomía total.
PRINCIPALES MEDIDAS DE VALORACION:
Examinamos la incidencia de cáncer de recto entre pacientes con EII y colectomía total y comparamos el estadio del cáncer con el de otros pacientes con cáncer de recto en Dinamarca. Utilizamos la metodología de Kaplan-Meier para estimar la supervivencia y la regresión de Cox para estimar las tasas de mortalidad ajustadas (aMRR) después de un diagnóstico de cáncer de recto, comparando pacientes con y sin EII y un remanente rectal.
RESULTADOS:
Identificamos 4.703 pacientes con EII (1.026 enfermedad de Crohn; 3.677 colitis ulcerosa) que se sometieron a colectomía total con remanente rectal. Durante 29,725 años de seguimiento, se observaron 30 cánceres de recto, en comparación con los 8 esperados [razón de incidencia estandarizada (SIR) = 3.6, (intervalo de confianza (IC) del 95%: 2.4-5.1)]. Las distribuciones de las etapas del cáncer fueron similares. El riesgo de cáncer de recto 35 años después de la colectomía total fue del 1,9% (IC del 95%: 1,1% -2,9%). Cinco años después del diagnóstico de cáncer de recto, la supervivencia fue del 28% (IC del 95%: 12% -47%) y del 38% (IC del 95%: 37% -38%) para los pacientes con y sin EII y un remanente rectal, respectivamente. La aMRR 1-5 años después de un diagnóstico de cáncer de recto fue de 2,5 (IC del 95%: 1,6-3,9). La mediana de tiempo desde la última proctoscopia no diagnóstica registrada hasta el diagnóstico de cáncer de recto en pacientes con EII y colectomía total fue de 1,1 años.
LIMITACIONES:
Pocos resultados, uso de datos administrativos y no clínicos.
CONCLUSIÓN:
El riesgo a largo plazo de cáncer de recto después de una colectomía total para la EII fue bajo. La supervivencia después de un diagnóstico de cáncer de recto fue más pobre para los pacientes con EII y colectomía total que para los pacientes con cáncer de recto sin EII y colectomía total. La vigilancia endoscópica, como parecía practicarse en esta cohorte, puede ser inadecuada. Consulte Video Resumen en http://links.lww.com/DCR/B497. (Traducción—Dr. Adrian Ortega)
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Affiliation(s)
- Anders Mark-Christensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Surgery, Section of Coloproctology, Aarhus University Hospital, Aarhus N, Denmark
| | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Surgery, Randers Regional Hospital, Randers, Denmark
| | - Katalin Veres
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
| | - Søren Laurberg
- Department of Surgery, Section of Coloproctology, Aarhus University Hospital, Aarhus N, Denmark
| | - Henrik Toft Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
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Altadill A, Eiro N, González LO, Andicoechea A, Fernández-Francos S, Rodrigo L, García-Muñiz JL, Vizoso FJ. Relationship between Metalloprotease-7 and -14 and Tissue Inhibitor of Metalloprotease 1 Expression by Mucosal Stromal Cells and Colorectal Cancer Development in Inflammatory Bowel Disease. Biomedicines 2021; 9:biomedicines9050495. [PMID: 33946534 PMCID: PMC8147221 DOI: 10.3390/biomedicines9050495] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/12/2021] [Accepted: 04/27/2021] [Indexed: 11/26/2022] Open
Abstract
Colorectal carcinoma (CRC) associated with inflammatory bowel disease (IBD) is an example of an inflammation-related cancer. Matrix metalloproteases (MMP) are known to be associated with both processes. The aim of the study was to compare the expression of MMP-7, MMP-14 and tissue inhibitor of metalloproteases-1 (TIMP-1) in sporadic CRC- and IBD-associated CRC, and to compare the expression in inflamed and non-inflamed colonic tissue samples from IBD patients without or with associated CRC. An immunohistochemical study of MMP-7, -14 and TIMP-1 was performed on sporadic CRC (n = 86), IBD-associated CRC (n = 23) and colorectal mucosa of non-tumor samples from IBD patients without (n = 47) and with (n = 23) associated CRC. These factors were more frequently expressed by cancer-associated fibroblasts (CAF) from IBD-associated CRC than by CAF from CRC not associated with IBD. Regarding the inflamed tissue of IBD patients, Crohn’s disease (CD) patients with CRC development showed a higher expression of MMP-14 by fibroblasts and by mononuclear inflammatory cells (MICs) than CD patients without CRC development. In non-inflamed tissue samples, MMP-7 associated with fibroblasts and MICs, and TIMP-1 associated with MICs, were more frequently expressed in CD patients with CRC development than in CD patients without CRC development. Our data suggest that these factor expressions by stromal cells may be biological markers of CRC development risk in IBD patients.
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Affiliation(s)
- Antonio Altadill
- Department of Internal Medicine, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain;
| | - Noemi Eiro
- Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain; (N.E.); (S.F.-F.); (J.L.G.-M.)
| | - Luis O. González
- Department of Anatomical Pathology, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain;
| | - Alejandro Andicoechea
- Department of Surgery, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain;
| | - Silvia Fernández-Francos
- Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain; (N.E.); (S.F.-F.); (J.L.G.-M.)
| | - Luis Rodrigo
- Department of Gastroenterology, Central University Hospital of Asturias, Av. Roma, s/n, 33011 Oviedo, Spain;
| | - José Luis García-Muñiz
- Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain; (N.E.); (S.F.-F.); (J.L.G.-M.)
| | - Francisco J. Vizoso
- Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain; (N.E.); (S.F.-F.); (J.L.G.-M.)
- Department of Surgery, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain;
- Correspondence: ; Tel.: +34-985320050
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Bocchetti M, Ferraro MG, Ricciardiello F, Ottaiano A, Luce A, Cossu AM, Scrima M, Leung WY, Abate M, Stiuso P, Caraglia M, Zappavigna S, Yau TO. The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer. Int J Mol Sci 2021; 22:3967. [PMID: 33921348 PMCID: PMC8068787 DOI: 10.3390/ijms22083967] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/01/2021] [Accepted: 04/08/2021] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18-25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes' expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.
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Affiliation(s)
- Marco Bocchetti
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
- Biogem Scarl, Molecular Oncology and Precision Medicine Laboratory, via Camporeale, 83031 Ariano Irpino, Italy;
| | - Maria Grazia Ferraro
- Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, via D. Montesano 49, 80131 Naples, Italy;
| | | | - Alessandro Ottaiano
- SSD-Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy;
| | - Amalia Luce
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
- School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
| | - Alessia Maria Cossu
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
- Biogem Scarl, Molecular Oncology and Precision Medicine Laboratory, via Camporeale, 83031 Ariano Irpino, Italy;
| | - Marianna Scrima
- Biogem Scarl, Molecular Oncology and Precision Medicine Laboratory, via Camporeale, 83031 Ariano Irpino, Italy;
| | - Wing-Yan Leung
- Division of Haematology, Department of Medicine, The University of Hong Kong, Hong Kong, China;
| | - Marianna Abate
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
| | - Paola Stiuso
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
- Biogem Scarl, Molecular Oncology and Precision Medicine Laboratory, via Camporeale, 83031 Ariano Irpino, Italy;
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.B.); (A.L.); (A.M.C.); (M.A.); (P.S.); (M.C.)
| | - Tung On Yau
- John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
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20
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Arhi C, Askari A, Nachiappan S, Bottle A, Arebi N, Athanasiou T, Ziprin P, Aylin P, Faiz O. Stage at Diagnosis and Survival of Colorectal Cancer With or Without Underlying Inflammatory Bowel Disease: A Population-based Study. J Crohns Colitis 2021; 15:375-382. [PMID: 32991688 DOI: 10.1093/ecco-jcc/jjaa196] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Inflammatory bowel disease [IBD] is a risk factor for colorectal cancer [CRC]. The aim of this study is to determine whether stage at diagnosis and survival differ between sporadic, ulcerative colitis [UC]- and Crohn's disease [CD]-related CRC. METHODS The English National Cancer Registry [NCIN], Hospital Episode Statistics [HES] and Office for National Statistics [ONS] datasets between 2000 and 2010 were linked, providing data on comorbidities, stage and date of death. A logistic regression model determined whether IBD was associated with an early [I/II] or late [III/IV] cancer. Cox regression analysis was used to examine survival differences between sporadic, UC- and CD-related cancers. RESULTS A total of 234 009 patients with CRC were included, of whom 985 [0.4%] and 1922 [0.8%] had CD and UC, respectively. UC, but not CD, was associated with an earlier stage compared with sporadic cancers (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.79 to 0.98, p = 0.02). CD had a significantly worse survival compared with sporadic patients for stage II [HR = 1.71, CI 1.26 to 2.31 p <0.005] and III [1.53, CI 1.20 to 1.96, p <0.005] cancer. UC patients were associated with worse survival compared with the sporadic group for both stage III [1.38, CI 1.17 to 1.63, p <0.0005] and IV [1.13, CI 1.01 to 1.28, p = 0.04] cancer. After excluding sporadic patients, UC was associated with improved survival compared with CD [0.62, CI 0.43 to 0.90, p = 0.01] for stage II cancer. CONCLUSIONS Patients with IBD are diagnosed at an earlier stage but tend to have a worse survival compared with sporadic cases of CRC, in particular for nodal disease [stage III].Specifically, patients with CD-related CRC appear to fare worst in terms of survival compared with both the sporadic and UC groups.
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Affiliation(s)
- Chanpreet Arhi
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Alan Askari
- St Mark's Hospital & Academic Institute, London, UK
| | | | - Alex Bottle
- School of Public Health, Imperial College London, Charing Cross Hospital, London, UK
| | - Naila Arebi
- St Mark's Hospital & Academic Institute, London, UK
| | | | - Paul Ziprin
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Paul Aylin
- School of Public Health, Imperial College London, Charing Cross Hospital, London, UK
| | - Omar Faiz
- St Mark's Hospital & Academic Institute, London, UK
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21
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Lee SA, Wang Y, Liu F, Riordan SM, Liu L, Zhang L. Escherichia coli K12 Upregulates Programmed Cell Death Ligand 1 (PD-L1) Expression in Gamma Interferon-Sensitized Intestinal Epithelial Cells via the NF-κB Pathway. Infect Immun 2020; 89:e00618-20. [PMID: 33046511 PMCID: PMC7927934 DOI: 10.1128/iai.00618-20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 10/06/2020] [Indexed: 01/09/2023] Open
Abstract
Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein which is used by tumor cells for immune evasion. PD-L1 is upregulated in inflamed intestinal tissues. The intestinal tract is colonized by millions of bacteria, most of which are commensal bacterial species. We hypothesized that under inflammatory conditions, some commensal bacterial species contribute to increased PD-L1 expression in intestinal epithelium and examined this hypothesis. Human intestinal epithelial HT-29 cells with and without interferon (IFN)-γ sensitization were incubated with six strains of four enteric bacterial species. The mRNA and protein levels of PD-L1 in HT-29 cells were examined using quantitative real-time PCR and flow cytometry, respectively. The levels of interleukin (IL)-1β, IL-18, IL-6, IL-8, and tumor necrosis factor (TNF)-α secreted by HT-29 cells were measured using enzyme-linked immunosorbent assay. Apoptosis of HT-29 cells was measured using a caspase 3/7 assay. We found that Escherichia coli K12 significantly upregulated both PD-L1 mRNA and protein in IFN-γ-sensitized HT-29 cells. E. coli K12 induced the production of IL-8 in HT-29 cells, however, IL-8 did not affect HT-29 PD-L1 expression. Inhibition of the nuclear factor-kappa B pathway significantly reduced E. coli K12-induced PD-L1 expression in HT-29 cells. The other two E. coli strains and two enteric bacterial species did not significantly affect PD-L1 expression in HT-29 cells. Enterococcus faecalis significantly inhibited PD-L1 expression due to induction of cell death. Data from this study suggest that some gut bacterial species have the potential to affect immune function under inflammatory conditions via upregulating epithelial PD-L1 expression.
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Affiliation(s)
- Seul A Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Yiming Wang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
- Infection & Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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22
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Abstract
BACKGROUND Patients with IBD are at increased risk for developing colorectal cancer. However, overall survival and disease-free survival for rectal cancer alone in patients with IBD has not been reported. OBJECTIVE This study aimed to determine overall survival and disease-free survival for patients with rectal cancer in IBD versus non-IBD cohorts. DESIGN This is a retrospective cohort study. SETTING This study was conducted at an IBD referral center. PATIENTS All consecutive adult patients with IBD diagnosed with rectal cancer and at least 1 year of postsurgery follow-up were included and matched in a 1:2 fashion (age, sex, preoperative stage) with patients with rectal cancer who did not have IBD. MAIN OUTCOMES MEASURES Five-year overall survival and disease-free survival, 30-day postoperative complication, readmission, reoperation, and mortality rates were measured. METHODS Survival rates were calculated using Kaplan-Meier estimates. The association of risk factors and long-term outcomes was assessed using Cox proportion hazard models. RESULTS A total of 107 study patients with IBD who had rectal cancer were matched to 215 control patients; preoperative stages were as follows: 31% with stage I, 19% with stage II, 40% with stage III, and 10% with stage IV. Differences were observed (IBD vs non-IBD) in neoadjuvant chemotherapy (33.6% vs 52.6%, p = 0.001) and preoperative radiotherapy (35.5% vs 53.5%, p = 0.003). Postoperative complication rates were similar. On surgical pathology, patients with IBD had more lymphovascular invasion (12.9% vs 5.6%, p = 0.04) and positive circumferential resection margins (5.4% vs 0.9%, p = 0.03). On multivariable analysis, the diagnosis of IBD did not significantly impact long-term mortality (HR, 0.91; 95% CI, 0.53-1.57; p = 0.73) or disease-free survival (HR, 1.36; 95% CI, 0.84-2.21; p = 0.22). LIMITATIONS This study was limited by its retrospective design and the use of single-center data. CONCLUSIONS Patients have rectal cancer with IBD and without IBD have similar long-term and disease-free survival, despite lower rates of neoadjuvant treatment and higher margin positivity in patients with IBD. See Video Abstract at http://links.lww.com/DCR/B271. ¿LA ENFERMEDAD INFLAMATORIA INTESTINAL ACARREA PEORES RESULTADOS EN PACIENTES CON CÁNCER RECTAL? UN ANÁLISIS DE CASOS-COINCIDENTES: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de desarrollar cáncer colorrectal. Sin embargo, no se ha informado la supervivencia general y la supervivencia libre de enfermedad para el cáncer rectal solo en pacientes con EII.Determinar la supervivencia general y la supervivencia libre de enfermedad para pacientes con cáncer rectal en cohortes con EII versus sin EII.Estudio de cohorte retrospectivo.Centro de referencia para enfermedad inflamatoria intestinal.todos los pacientes adultos con EII diagnosticados con cáncer rectal, consecutives, y al menos un año de seguimiento postoperatorio se incluyeron y se emparejaron de manera 1: 2 (edad, sexo, etapa preoperatoria) con pacientes con cáncer rectal sin EII.Se midieron la supervivencia general a cinco años y la supervivencia libre de enfermedad, complicaciones postoperatorias a los 30 días, reingreso, reoperación y tasas de mortalidad.Las tasas de supervivencia se calcularon utilizando estimaciones de Kaplan-Meier. La asociación de factores de riesgo y resultados a largo plazo se evaluó mediante modelos de riesgo de proporción de Cox.Un total de 107 pacientes con EII y cáncer rectal se compararon con 215 pacientes de control; las etapas preoperatorias fueron las siguientes: 31% de Etapa I, 19% de Etapa II, 40% de Etapa III y 10% de Etapa IV. Se observaron diferencias (EII versus no EII) en quimioterapia neoadyuvante (33.6% frente a 52.6%, p = 0.001) y radioterapia preoperatoria (35.5% frente a 53.5%, p = 0.003). Las tasas de complicaciones postoperatorias fueron similares. En la patología quirúrgica, los pacientes con EII tuvieron más invasión linfovascular (12.9% frente a 5.6%, p = 0.04) y márgenes de resección circunferencial positivos (5.4% frente a 0.9%, p = 0.03). En el análisis multivariable, el diagnóstico de EII no tuvo un impacto significativo en la mortalidad a largo plazo (HR 0.91; IC del 95%: 0.53-1.57, p = 0.73) o la supervivencia libre de enfermedad (HR 1.36; IC del 95%: 0.84-2.21, p = 0.22)Diseño retrospectivo, centro único de datos.Los pacientes con EII y sin EII con cáncer rectal tienen una supervivencia similar a largo plazo y libre de enfermedad, a pesar de las tasas más bajas de tratamiento sneoadyuvante y un mayor margen positivo en pacientes con EII. Consulte Video Resumen en http://links.lww.com/DCR/B271.
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23
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Askari A, Guillén LS, Millan M, Nachiappan S, Bottle A, Athanasiou T, Faiz O. Colorectal tumour characteristics and oncological outcome in patients with inflammatory bowel disease. SURGICAL PRACTICE 2020. [DOI: 10.1111/1744-1633.12421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Alan Askari
- Surgical Epidemiology, Trials and Outcome Centre (SETOC)St Mark′s Hospital Harrow UK
| | | | - Monica Millan
- Department of SurgeryBellvitge University Hospital Barcelona Spain
| | | | - Alex Bottle
- Faculty of MedicineSchool of Public Health, Dr Foster Unit, Imperial College London London UK
| | - Thanos Athanasiou
- Faculty of Medicine, Department of Surgery & CancerSt Mary′s Hospital London UK
| | - Omar Faiz
- Surgical Epidemiology, Trials and Outcome Centre (SETOC)St Mark′s Hospital Harrow UK
- Faculty of Medicine, Department of Surgery & CancerSt Mary′s Hospital London UK
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24
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Taylor CC, Millien VO, Hou JK, Massarweh NN. Association Between Inflammatory Bowel Disease and Colorectal Cancer Stage of Disease and Survival. J Surg Res 2019; 247:77-85. [PMID: 31767275 DOI: 10.1016/j.jss.2019.10.040] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 08/16/2019] [Accepted: 10/25/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). However, there are few data comparing outcomes between IBD and non-IBD-associated CRC. METHODS Retrospective cohort study of patients with CRC identified from the Veteran Affairs (VA) Central Cancer Registry from 1998 to 2012 linked to national VA administrative claims to identify patients with IBD using a previously validated algorithm. The association between IBD status and stage of disease and overall risk of death were evaluated using multivariable logistic and Cox regression, respectively. RESULTS Among 34,570 CRC patients, 217 had IBD. IBD patients were significantly younger for both colon and rectal cancer. IBD patients who developed rectal cancer were significantly more likely to present with locally advanced or metastatic disease (P = 0.007), but there was no difference in stage among patients with colon cancer. This difference persisted after multivariable adjustment (overall-odds ratio [OR] 1.40, 95% confidence interval [1.03-1.90]; colon-OR 1.22 [0.84-1.78]; rectum-OR 2.04 [1.22-3.40]). Total colectomy was more commonly performed among IBD patients. Overall, IBD was associated with a 52% increased risk of death (hazard ratio 1.52 [1.21-1.91]). CONCLUSIONS Although IBD is associated with more advanced stage at diagnosis for rectal cancer, it is associated with a worse survival primarily in patients with colon cancer. Further work is needed to better understand the reason for these observed differences between IBD and non-IBD patients and to better delineate the impact of endoscopic surveillance on CRC care and outcomes in IBD patients.
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Affiliation(s)
- Christopher C Taylor
- Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, Texas
| | - Valentine O Millien
- Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas
| | - Jason K Hou
- Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas
| | - Nader N Massarweh
- Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas.
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25
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Li J, Zhou WX, Liu S, Zheng WY, Wang YN, Li JN, Ferraz JG, Qian JM, Gui XY. Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada. Chin Med J (Engl) 2019; 132:2664-2669. [PMID: 31725457 PMCID: PMC6940096 DOI: 10.1097/cm9.0000000000000525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to explore the clinical-pathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada. METHODS Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics. RESULTS Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ± 12.8 years vs. 61.6 ± 14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002). CONCLUSIONS As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.
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Affiliation(s)
- Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei-Xun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Shuang Liu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei-Yang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ya-Nan Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jing-Nan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jose Gp Ferraz
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Jia-Ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xian-Yong Gui
- Department of Pathology and Laboratory Medicine, University of Calgary Cummings School of Medicine, and Calgary Laboratory Services, Calgary, Canada
- Department of Pathology, University of Washington School of Medicine, Seattle, USA
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Koh SJ, Kim JW, Kim BG, Lee KL, Kim DW, Kim JS. Matricellular protein periostin promotes colitis-associated colon tumorigenesis in mice. Carcinogenesis 2019; 40:102-111. [PMID: 30204842 DOI: 10.1093/carcin/bgy120] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 08/27/2018] [Accepted: 09/07/2018] [Indexed: 12/28/2022] Open
Abstract
Periostin is expressed in inflamed colonic mucosa and colon cancer tissue; however, its role in the development of colitis-associated colon cancer (CAC) remains unclear. Wild-type and periostin-deficient (Postn-/-) mice were given a single intraperitoneal injection of azoxymethane at 12.5 mg/kg on day 0. Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by untreated, free water consumption for 16 days. This cycle was repeated three times. In vitro assays were performed using COLO205 and HCT116 cells. Small interfering RNA was used to inhibit Postn gene translation. Periostin expression was determined using colon samples from patients with CAC. Postn-/- mice exhibited lower tumor burden compared with wild-type mice. Exposure to azoxymethane/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with that in wild-type mice. In addition, immunoreactivity for IκB kinase, β-catenin and COX2 was markedly reduced in Postn-/- mice. Expression of interleukin (IL)-1β and tumor necrosis factor α (TNF-α) significantly decreased, whereas that of IL-10 and transforming growth factor β (TGF-β) increased in peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene resulted in reduced cell viability, which was associated with caspase-3 activation, and this was reversed by treatment with recombinant periostin. Knockdown of Postn downregulated bcl-2, cIAP1, cFLIP-L, VEGF, Axin 2 and cyclin D1, and upregulated bak expression. Periostin expression was significantly increased in patients with CAC. Periostin aggravates CAC development, which suggests that periostin is a potential therapeutic target for the prevention of CAC in patients with inflammatory bowel disease.
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Affiliation(s)
- Seong-Joon Koh
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Woo Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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27
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Xu L, Zhang Y, Xue X, Liu J, Li ZS, Yang GY, Song Y, Pan Y, Ma Y, Hu S, Wen A, Jia Y, Rodriguez LM, Tull MB, Benante K, Khan SA, Cao Y, Jovanovic B, Richmond E, Umar A, Bergan R, Wu K. A Phase I Trial of Berberine in Chinese with Ulcerative Colitis. Cancer Prev Res (Phila) 2019; 13:117-126. [PMID: 31619442 DOI: 10.1158/1940-6207.capr-19-0258] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/10/2019] [Accepted: 10/07/2019] [Indexed: 11/16/2022]
Abstract
The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
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Affiliation(s)
- Li Xu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yujie Zhang
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xianmin Xue
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jie Liu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zeng-Shan Li
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University, Chicago, Illinois
| | - Ying Song
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yan Pan
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yueyun Ma
- Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Sijun Hu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Aidong Wen
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yanyan Jia
- Department of Pharmacology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Luz Maria Rodriguez
- Division of Cancer Prevention, NCI, Bethesda, Maryland.,Walter Reed Military Medical Center, Department of Surgery, Bethesda, Maryland
| | - Mary Beth Tull
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois
| | - Kelly Benante
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois
| | - Seema A Khan
- Department of Surgery and Northwestern University, Chicago, Illinois
| | - Ying Cao
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Borko Jovanovic
- Department of Preventive Medicine, Northwestern University, Chicago, Illinois
| | | | - Asad Umar
- Division of Cancer Prevention, NCI, Bethesda, Maryland
| | - Raymond Bergan
- Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
| | - Kaichun Wu
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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Bui TM, Sumagin R. Progressing from Recurring Tissue Injury to Genomic Instability: A New Mechanism of Neutrophil Pathogenesis. DNA Cell Biol 2019; 38:747-753. [PMID: 31188020 PMCID: PMC7643757 DOI: 10.1089/dna.2019.4842] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 05/14/2019] [Indexed: 12/11/2022] Open
Abstract
Aberrant neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. While the genotoxic function of PMNs and its implications in carcinogenesis have been primarily associated with oxidative stress, recent work by Butin-Israeli and colleagues has defined a novel mechanism where PMN-derived microparticles through the delivery and activity of specific miRNAs promoted formation of double-strand breaks (DSBs), and in parallel, suppressed DSB repair through the downregulation of lamin B1 and Rad51. Respective downregulation of these two proteins compromised the nuclear envelope and high-fidelity repair by homologous recombination, increasing DSB accumulation and aneuploidy. This discovery defined a novel mode of action where PMN-mediated suppression of DSB repair leading to genomic instability in the injured mucosa may facilitate progression toward colorectal cancer.
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Affiliation(s)
- Triet M. Bui
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Ronen Sumagin
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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29
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Hnatyszyn A, Hryhorowicz S, Kaczmarek-Ryś M, Lis E, Słomski R, Scott RJ, Pławski A. Colorectal carcinoma in the course of inflammatory bowel diseases. Hered Cancer Clin Pract 2019; 17:18. [PMID: 31338130 PMCID: PMC6626407 DOI: 10.1186/s13053-019-0118-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 07/01/2019] [Indexed: 02/08/2023] Open
Abstract
Background Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are the most prevalent diseases of the digestive system, and their association is unequivocal. A long-standing inflammatory process is one of the causes of sporadic as well as inherited cancers as it impacts on malignant transformation in a wide variety of neoplastic diseases, including colorectal cancer. Methods An extensive publication search was performed in Medline and PubMed database. The keywords: colorectal carcinoma, inflammation, Crohn disease, ulcerative colitis and inflammatory bowel disease were used. Results The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll like receptor (TLR) signaling pathways are clearly involved in the inflammatory process and are therefore implicated in the transformation of normal colonic mucosa to premalignant and malignant disease. Focal sites of inflammation could significantly increase the risk of initiation and development of cancer. Altered inflammatory activity is likely to be a result of either a disturbance of intestinal bacterial flora or an inadequate cellular response to it. Additionally, increasing the level of inflammation-related factors may also interfere with the control of cellular proliferation. Conclusions This review shows an overview of the genetic and environmental factors that appear to influence both the occurrence of IBD and CRC with particular reference to NOD2 and TLRs as well as pro- and anti-inflammatory cytokines associated with tumor initiation and progression (encompassing both tumor invasion and metastases), as they constitute potential targets for therapeutic intervention.
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Affiliation(s)
- Andrzej Hnatyszyn
- Health Care Center, Independent Public Hospital, Chałubińskiego 7, 67-100 Nowa Sól, Poland
| | - Szymon Hryhorowicz
- 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland
| | - Marta Kaczmarek-Ryś
- 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland
| | - Emilia Lis
- 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland
| | - Ryszard Słomski
- 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland.,3Department of Biochemistry and Biotechnology, University of Life Sciences, Dojazd 11, 60-632 Poznań, Poland
| | - Rodney J Scott
- Division of Molecular Medicine, NSW Health Pathology (Newcastle) New South Wales, Newcastle, NSW 2308 Australia.,5School of Biomedical Sciences, University of Newcastle, Newcastle, NSW 2308 Australia
| | - Andrzej Pławski
- 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland.,6Department of General and Endocrine Surgery and Gastroenterological Oncology, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, Poland
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30
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Wu XR, Zheng XB, Huang Y, Cao Q, Zhang HJ, Miao YL, Zou KF, Chen M, Zhang FM, Mei Q, Gonzalo D, Allende D, Hu PJ, Shen B, Liu XL, Lan P. Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease: a multicenter study. Gastroenterol Rep (Oxf) 2019; 7:67-73. [PMID: 30792868 PMCID: PMC6375343 DOI: 10.1093/gastro/goy039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 07/14/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND This study sought to evaluate the risk factors for the development of colitis-associated neoplasia (CAN) in Chinese patients with inflammatory bowel disease (IBD). METHODS IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers. In addition to initial pathology evaluation, a CAN diagnosis was confirmed by two expert pathologists. Patients with CAN (n = 29) were compared with non-CAN controls (n = 87). Matching was performed for gender and IBD type with a ratio of three controls to one subject. RESULTS Of the 29 patients with CAN, 8 (27.6%) had colorectal cancer (CRC), 20 (69.0%) had a final diagnosis of low-grade dysplasia and 1 (3.4%) had high-grade dysplasia. Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN, with odds ratios of 1.09 [95% confidence interval (CI): 1.04-1.14, P < 0.001] and 1.14 (95% CI: 1.03-1.27, P = 0.013), respectively. Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis (P = 0.012) and had longer IBD durations (P = 0.019). CONCLUSIONS Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.
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Affiliation(s)
- Xian-Rui Wu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiao-Bin Zheng
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yan Huang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Hong-Jie Zhang
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Kai-Fang Zou
- Department of Gastroenterology, Wuhan Union Hospital, Wuhan, China
| | - Min Chen
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Fa-Ming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qiao Mei
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - David Gonzalo
- Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
| | - Daniela Allende
- Department of Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Pin-Jin Hu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bo Shen
- Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Xiu-Li Liu
- Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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Gu L, Ge Z, Wang Y, Shen M, Zhao P. Activating transcription factor 3 promotes intestinal epithelial cell apoptosis in Crohn’s disease. Pathol Res Pract 2018; 214:862-870. [DOI: 10.1016/j.prp.2018.04.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 04/06/2018] [Accepted: 04/17/2018] [Indexed: 12/15/2022]
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Mosher CA, Brown GR, Weideman RA, Crook TW, Cipher DJ, Spechler SJ, Feagins LA. Incidence of Colorectal Cancer and Extracolonic Cancers in Veteran Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:617-623. [PMID: 29390104 DOI: 10.1093/ibd/izx046] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Indexed: 01/19/2023]
Abstract
Background The risk for colorectal cancer (CRC) and certain extracolonic cancers is thought to be increased in inflammatory bowel disease (IBD), but few recent US studies have evaluated this issue. We aimed to estimate the incidence of CRC and extracolonic cancers in IBD patients. Methods In this case-control study, cases were all IBD patients treated in our Department of Veterans Affairs (VA) hospital who developed CRC or extracolonic cancers between 1996 and 2015. Controls were patients in the general VA population who developed these cancers during the same time. We compared cancer incidence rates (IRs) in cases and controls. Results There was no significant difference between cases and controls in the 20-year IR for CRC (148/100 000 in IBD patients, 97/100 000 in controls; relative risk [RR], 1.53; 95% confidence interval [CI], 0.86-2.69). In contrast, IBD cases had a significantly higher 20-year IR for all extracolonic cancers than controls (2839/100 000 in IBD patients, 1960/100 000 in controls; RR, 1.45; 95% CI, 1.27-1.65). Site-specific analyses revealed that IBD patients had significantly elevated risks for nonmelanoma skin cancers (RR, 2.38; 95% CI, 1.99-2.85), melanoma skin cancers (RR, 2.85; 95% CI, 1.63-4.88), renal tumors (RR, 2.90; 95% CI, 1.46-5.84), prostate cancer (RR, 1.70; 95% CI, 1.28-2.27), and pancreatic cancer (RR, 4.23; 95% CI, 1.35-13.29). Conclusions The incidence of CRC was not significantly higher in our veteran patients with IBD than in control patients in the general VA population. In contrast, our IBD patients had a significantly higher risk for extracolonic cancers than controls, including cancers of the skin, kidneys, prostate, and pancreas. 10.1093/ibd/izx046_video1Video 1.izx046_Mosher_Video5734484616001.
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Affiliation(s)
- Christina A Mosher
- Department of Medicine, VA North Texas Healthcare System, Dallas, Texas
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Geri R Brown
- Department of Medicine, VA North Texas Healthcare System, Dallas, Texas
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Rick A Weideman
- Department of Pharmacy, VA North Texas Healthcare System, Dallas, Texas
| | - Terri W Crook
- Department of Pathology, VA North Texas Healthcare System, Dallas, Texas
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Daisha J Cipher
- College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas
| | - Stuart J Spechler
- Department of Medicine, VA North Texas Healthcare System, Dallas, Texas
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Linda A Feagins
- Department of Medicine, VA North Texas Healthcare System, Dallas, Texas
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Cho JM, Yun SM, Choi YH, Heo J, Kim NJ, Kim SH, Kim EH. Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKβ/NF-κB signaling in mice. Oncotarget 2017; 9:866-880. [PMID: 29416662 PMCID: PMC5787519 DOI: 10.18632/oncotarget.23183] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 11/15/2017] [Indexed: 01/13/2023] Open
Abstract
Xanthohumol (XN), a prenylated chalcone isolated from the hop plant, has been reported to exhibit multiple biological functions including anti-inflammation. However, the pharmacological function of XN on colitis remains unknown. In this study, we investigated the anti-inflammatory effect of synthesized XN and molecular mechanism on dextran sulfate sodium (DSS)-induced experimental colitis. XN attenuated the colitis symptoms along with the prevention of colonic lesions after DSS challenge. XN inhibited the production of pro-inflammatory cytokines, oxidative stress and cyclooxygenase-2 expression in DSS-treated mice. Moreover, XN inhibited the phosphorylation of IκBα, the nuclear translocation of NF-κB subunits and the transcriptional activity of NF-κB in vivo and in vitro. In contrast to XN, isoXN showed much less effects on the kinase activity of IKKβ and IκBα phosphorylation induced by XN in this study, suggesting that an electrophilic carbon center present in XN is critical for the anti-inflammation in colitis, especially inhibition of IKKβ/NF-κB signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKKβ. Taken together, these findings demonstrate a new function of XN to inhibit IKKβ/NF-κB signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.
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Affiliation(s)
- Jae-Min Cho
- College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea
| | - Sun-Mi Yun
- College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea
| | - Young-Ho Choi
- College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea
| | - Jinyuk Heo
- College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
| | - Nam-Jung Kim
- College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
| | - Seok-Ho Kim
- College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea
| | - Eun-Hee Kim
- College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea
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The potential role of platelets in the consensus molecular subtypes of colorectal cancer. Cancer Metastasis Rev 2017; 36:273-288. [DOI: 10.1007/s10555-017-9678-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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35
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Reynolds IS, O'Toole A, Deasy J, McNamara DA, Burke JP. A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer. Int J Colorectal Dis 2017; 32:443-451. [PMID: 28078433 DOI: 10.1007/s00384-017-2754-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/06/2017] [Indexed: 02/04/2023]
Abstract
PURPOSE The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC. METHODS A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines. RESULTS Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320-8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425-2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735-0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782-1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929-1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776-1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890-1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414-2.949; p = 0.842). CONCLUSIONS In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.
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Affiliation(s)
- Ian S Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Aobhlinn O'Toole
- Department of Gastroenterology, Beaumont Hospital, Dublin 9, Ireland
| | - Joseph Deasy
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | | | - John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
- Royal College of Surgeons, Dublin 2, Ireland.
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36
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Han YD, Al Bandar MH, Dulskas A, Cho MS, Hur H, Min BS, Lee KY, Kim NK. Prognosis of ulcerative colitis colorectal cancer vs. sporadic colorectal cancer: propensity score matching analysis. BMC Surg 2017; 17:28. [PMID: 28327112 PMCID: PMC5359905 DOI: 10.1186/s12893-017-0224-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 03/15/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) harbours a high risk of UC-associated colorectal cancer (UCCC), which is important cause of morbidity and mortality in patients with inflammatory bowel disease. Overall Survival (OS) of patients with UCCC has not been addressed well in the literature. Thus, we compared oncologic outcome of UCCC and sporadic colorectal cancer (SCC) using propensity score matching analysis. METHODS Propensity score matching was performed for 36 patients, a 1:1 matching method stratified into 18 in UCCC and 18 patients in SCC. Matched variables were sex, age, body mass index, tumour stage, histology, preoperative carcinoembryonic antigen (CEA) level, and adjuvant treatment status. Patients with SCC or UCCC were retrospectively retrieved from our database from March 2000 to December 2015. All patients had undergone either oncological segmental resection or total proctocolectomy. RESULTS The majority of cancers were found in the sigmoid colon. Total proctocolectomy was performed only in the UCCC group; however, half of the UCCC group underwent a standard operation. Five cases of postoperative complication occurred within six months in the UCCC group compared to one case in the SCC group. There was no significant difference in recurrence rate (p = 0.361) or OS (p = 0.896) between the arms. CONCLUSION UCCC showed more postoperative complications than SCC, and equivalent oncology outcome, however the difference was not statistically significant. This study represents an experience of a single institution, thus further randomized studies are required to confirm our.
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Affiliation(s)
- Yoon Dae Han
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Mahdi Hussain Al Bandar
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Audrius Dulskas
- Department of Oncosurgery, National Cancer Institute, Vilnius, Lithuania
| | - Min Soo Cho
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Hyuk Hur
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Byung Soh Min
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Kang Young Lee
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
| | - Nam Kyu Kim
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul, 120-752 Korea
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Al Rabadi L, Bergan R. A Way Forward for Cancer Chemoprevention: Think Local. Cancer Prev Res (Phila) 2016; 10:14-35. [PMID: 27780807 DOI: 10.1158/1940-6207.capr-16-0194] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 10/04/2016] [Accepted: 10/19/2016] [Indexed: 11/16/2022]
Abstract
As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact. Cancer Prev Res; 10(1); 14-35. ©2016 AACR.
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Affiliation(s)
- Luai Al Rabadi
- Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
| | - Raymond Bergan
- Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
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Taleban S, Elquza E, Gower-Rousseau C, Peyrin-Biroulet L. Cancer and inflammatory bowel disease in the elderly. Dig Liver Dis 2016; 48:1105-11. [PMID: 27289334 DOI: 10.1016/j.dld.2016.05.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/02/2016] [Accepted: 05/03/2016] [Indexed: 12/11/2022]
Abstract
Cancer may be a complication of inflammatory bowel disease (IBD) or its treatments. In older Crohn's disease and ulcerative colitis patients, the risk of malignancy is of particular concern. IBD diagnosis at an advanced age is associated with earlier development of colitis-associated colorectal cancer. Thiopurine use in older IBD patients is tied to an increased risk of non-Hodgkin's lymphoma, nonmelanoma skin cancer, and urinary tract cancers. Additionally, older age is accompanied by multimorbidity, an increased risk of malnutrition, and decreased life expectancy, factors that complicate the management of cancer in the elderly. The optimal approach to the increased risk of malignancy in older age IBD is appropriate cancer screening and medical treatment. This may include age-specific colorectal cancer screening and limiting UV radiation exposure. With a growing number of older IBD patients, further studies are necessary to delineate the risk of cancer in this population.
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Affiliation(s)
- Sasha Taleban
- Division of Gastroenterology, University of Arizona College of Medicine, Tucson, AZ, United States; University of Arizona Center of Aging, Department of Medicine, Tucson, AZ, United States.
| | - Emad Elquza
- Hematology/Oncology, University of Arizona College of Medicine, Tucson, AZ, United States
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Health Economics, EPIMAD Registery, Regional House of Clinical Research, Regional University Hospital, Lille Cedex, France; Lille Inflammation Research International Center, LIRIC-UMR 995 Inserm, Lille University 2, Lille University Hospital, Lille University, France
| | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandœuvre-lès-Nancy, France
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Dugum M, Lin J, Lopez R, Estfan B, Manilich E, Stocchi L, Shen B, Liu X. Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study. Gastroenterol Rep (Oxf) 2016; 5:57-61. [PMID: 27279644 PMCID: PMC5444248 DOI: 10.1093/gastro/gow016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 04/14/2016] [Indexed: 01/12/2023] Open
Abstract
Background and Aim: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. Methods: Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. Results: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn’s disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35–1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54–1.4; P = 0.58) between IBD and non-IBD patients. Conclusion: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.
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Affiliation(s)
- Mohannad Dugum
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jingmei Lin
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Rocio Lopez
- Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Bassam Estfan
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Elena Manilich
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Luca Stocchi
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bo Shen
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Xiuli Liu
- Department of Anatomic Pathology, Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
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Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan. Anticancer Drugs 2016; 27:457-63. [DOI: 10.1097/cad.0000000000000338] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Ulcerative colitis and Crohn disease are chronic inflammatory diseases with typical onset in early adulthood. These diseases, therefore, can affect a woman throughout the many stages of her life, including menstruation, sexuality, pregnancy, and menopause. Unique health issues face women during these stages and can affect the course of their inflammatory bowel disease as well as treatment strategies and health maintenance. This article covers the non-pregnancy-related issues that are important in caring for women with inflammatory bowel disease. The topics of pregnancy and fertility are covered in a separate review.
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Affiliation(s)
- Linda A Feagins
- Division of Gastroenterology and Hepatology, VA North Texas Healthcare System, University of Texas Southwestern Medical Center, 4500 S. Lancaster Rd (111B1), Dallas, TX 75216, USA
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
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Klos CL, Safar B, Wise PE, Hunt SR, Mutch MG, Birnbaum EH, Fleshman JW, Dharmarajan S. Impaired outcome colitis-associated rectal cancer versus sporadic cancer. J Surg Res 2016; 204:123-9. [PMID: 27451878 DOI: 10.1016/j.jss.2016.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 02/14/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The surgical management of colitis-associated rectal cancer (CARC) is not well defined. This study determines outcomes after surgery for CARC compared with sporadic rectal cancer. MATERIALS AND METHODS This is a retrospective cohort study comparing 27 patients with CARC with 54 matched patients with sporadic cancer. Matching criteria included age, gender, neoadjuvant chemoradiation, and American Joint Committee on Cancer stage. Outcome measures were disease-free and overall survival, tumor characteristics, and postoperative morbidity. RESULTS Compared to those with sporadic rectal cancer, patients with CARC underwent proctocolectomy more frequently (21 [78%] versus 6 [22%] P < 0.001) and were more likely to have mucinous tumors (11 [40.7%] versus 12 [22.3%] P = 0.03). Overall 3-y survival was significantly reduced in CARC patients compared with patients with sporadic rectal cancer. Those with CARC undergoing segmental proctectomy only demonstrated reduced overall and disease-free survival compared to patients with sporadic rectal cancer and to colitis patients undergoing proctocolectomy (P = 0.002). CONCLUSIONS Patients with CARC undergoing proctectomy demonstrate reduced disease-free survival versus those undergoing proctocolectomy, and versus patients with sporadic rectal cancer undergoing proctectomy. These findings warrant further study and suggest that proctocolectomy should be considered the preferred surgical approach for CARC.
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Affiliation(s)
- Coen L Klos
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Bashar Safar
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Paul E Wise
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Steven R Hunt
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Matthew G Mutch
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Elisa H Birnbaum
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - James W Fleshman
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Sekhar Dharmarajan
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri.
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Ou B, Zhao J, Guan S, Lu A. Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis. Dig Dis Sci 2016; 61:881-9. [PMID: 26518415 DOI: 10.1007/s10620-015-3940-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 10/22/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis. AIMS The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD. METHODS An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated. RESULTS Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity. CONCLUSION This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.
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Affiliation(s)
- Baochi Ou
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jingkun Zhao
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Shaopei Guan
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Aiguo Lu
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
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Abstract
Inflammatory bowel disease is associated with an increased risk of gastrointestinal neoplasia. Ulcerative colitis increases the risk of colorectal cancer, and patients with this condition should undergo routine colonoscopic surveillance to detect neoplasia. Crohn's disease increases the risk of malignancy in inflamed segments of bowel, which may include small bowel, colon, rectum, and anus.
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Affiliation(s)
- Jamie Cannon
- Department of Surgery, University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL 35294-0016, USA.
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Leowardi C, Schneider ML, Hinz U, Harnoss JM, Tarantino I, Lasitschka F, Ulrich A, Büchler MW, Kadmon M. Prognosis of Ulcerative Colitis-Associated Colorectal Carcinoma Compared to Sporadic Colorectal Carcinoma: A Matched Pair Analysis. Ann Surg Oncol 2015; 23:870-6. [PMID: 26467453 DOI: 10.1245/s10434-015-4915-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) patients have an increased risk of developing colorectal carcinoma (CRC). In contrast to clinical and pathogenetic differences, little is known about how prognosis compares between these patients and those with sporadic CRC. The aim of this study was to compare their characteristics and prognosis and identify independent risk factors for patients with UC-associated CRC. METHODS A total of 126 patients who underwent surgery in our department (1984-2010) for UC-associated (n = 63) or sporadic (n = 63) CRC were included in this analysis. Patients were matched according to sex, tumor location, and disease stage. Clinical parameters and overall, recurrence-free, and disease-specific survival were compared. In subgroup analyses, clinical parameters of UC patients were correlated with survival. RESULTS Median follow-up was 129 months in the UC group and 99 months in the sporadic CRC group. UC patients were significantly younger and had more multifocal, high-grade, and mucinous carcinomas. Five-year overall survival rate for UC-associated and sporadic CRC was similar (65.7 vs. 63.2%, p = 0.98). Recurrence-free survival for International Union Against Cancer (UICC) stage II disease was superior in the sporadic CRC group (p = 0.039). In a subgroup analysis of UC patients, a shorter duration of UC (p = 0.045) and male sex (p = 0.005) were associated with a worse prognosis. CONCLUSIONS Despite multiple clinical and histopathologic differences between UC-associated and sporadic CRC patients, overall survival and disease-specific survival are similar. In a subgroup analysis of UC patients with CRC, female sex was associated with a significantly better prognosis. This finding implies that estrogens may play a protective role in UC-associated CRC carcinogenesis.
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Affiliation(s)
- Christine Leowardi
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany.
| | - Marie-Luise Schneider
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Jonathan M Harnoss
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Ignazio Tarantino
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Felix Lasitschka
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Alexis Ulrich
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Martina Kadmon
- Department of General, Visceral and Transplantation Surgery,, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany
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Volodko N, Salla M, Eksteen B, Fedorak RN, Huynh HQ, Baksh S. TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development. World J Gastroenterol 2015; 21:10358-10366. [PMID: 26420962 PMCID: PMC4579882 DOI: 10.3748/wjg.v21.i36.10358] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Revised: 04/28/2015] [Accepted: 07/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development.
METHODS: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood.
RESULTS: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients.
CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.
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Oueriagli Nabih S, Biyi A, Benameur Y, Ait Sahel O, Bouyaallaoui H, Doudouh A. Fixation intestinale de radiobiphosphonates dans un cas de maladie de Crohn. MÉDECINE NUCLÉAIRE 2015; 39:409-413. [DOI: 10.1016/j.mednuc.2015.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Cai H, Zhang G, Wang Z, Luo Z, Zhou X. Relationship between the use of statins and patient survival in colorectal cancer: a systematic review and meta-analysis. PLoS One 2015; 10:e0126944. [PMID: 26030771 PMCID: PMC4451009 DOI: 10.1371/journal.pone.0126944] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 04/09/2015] [Indexed: 12/30/2022] Open
Abstract
Background Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear. Methods We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel–Haenszel random-effect modeling. All statistical tests were two-sided. Results Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use. Conclusions Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.
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Affiliation(s)
- Heping Cai
- Department of Pharmacy, Anhui Provincial Children's Hospital, Hefei, Anhui Province, China
| | - Gongwu Zhang
- Department of Pharmacy, Anhui Provincial Children's Hospital, Hefei, Anhui Province, China
| | - Zhuo Wang
- Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China
- * E-mail: (ZW); (ZL); (XZ)
| | - Zhihong Luo
- Department of Pharmacy, Anhui Provincial Children's Hospital, Hefei, Anhui Province, China
- * E-mail: (ZW); (ZL); (XZ)
| | - Xiaochun Zhou
- Department of General Surgery, Lianyungang Oriental Hospital, Lianyun District, Lianyungang City, Jiangsu Province, China
- * E-mail: (ZW); (ZL); (XZ)
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Renfro LA, Grothey A, Kerr D, Haller DG, André T, Van Cutsem E, Saltz L, Labianca R, Loprinzi CL, Alberts SR, Schmoll H, Twelves C, Yothers G, Sargent DJ. Survival following early-stage colon cancer: an ACCENT-based comparison of patients versus a matched international general population†. Ann Oncol 2015; 26:950-958. [PMID: 25697217 DOI: 10.1093/annonc/mdv073] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 02/05/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Post-treatment survival experience of early colon cancer (CC) patients is well described in the literature, which states that cure is probable for some patients. However, comparisons of treated patients' survival versus that expected from a matched general population (MGP) are limited. PATIENTS AND METHODS A total of 32 745 patients from 25 randomized adjuvant trials conducted from 1977 to 2012 in 41 countries were pooled. Observed long-term survival of these patients was compared with expected survival matched on sex, age, country, and year, both overall and by stage (II and III), sex, treatment [surgery, 5-fluorouracil (5-FU), 5-FU + oxaliplatin], age (<70 and 70+), enrollment year (pre/post 2000), and recurrence (yes/no). Comparisons were made at randomization and repeated conditional on survival to 1, 2, 3, and 5 years. CC and MGP equivalence was tested, and observed Kaplan-Meier survival rates compared with expected MGP rates 3 years out from each landmark. Analyses were also repeated in patients without recurrence. RESULTS Within most cohorts, long-term survival of CC patients remained statistically worse than the MGP, though conditional survival generally improved over time. Among those surviving 5 years, stage II, oxaliplatin-treated, elderly, and recurrence-free patients achieved subsequent 3-year survival rates within 5% of the MGP, with recurrence-free patients achieving equivalence. CONCLUSIONS Conditional on survival to 5 years, long-term survival of most CC patients on clinical trials remains modestly poorer than an MGP, but achieves MGP levels in some subgroups. These findings emphasize the need for access to quality care and improved treatment and follow-up strategies.
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Affiliation(s)
- L A Renfro
- Division of Biomedical Statistics and Informatics.
| | - A Grothey
- Department of Oncology, Mayo Clinic, Rochester, USA
| | - D Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - D G Haller
- School of Medicine, University of Pennsylvania, Philadelphia, USA
| | - T André
- Hôpital Saint Antoine, Paris; Pierre and Marie Curie University, Paris, France
| | - E Van Cutsem
- Digestive Oncology Unit, University Hospital Gasthuisberg/Leuven, Leuven, Belgium
| | - L Saltz
- Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, USA
| | - R Labianca
- Oncology Unit, Ospedale Giovanni XXIII, Bergamo, Italy
| | - C L Loprinzi
- Department of Oncology, Mayo Clinic, Rochester, USA
| | - S R Alberts
- Department of Oncology, Mayo Clinic, Rochester, USA
| | - H Schmoll
- Department for Internal Medicine IV, University Clinic Halle, Halle, Germany
| | - C Twelves
- Leeds Institute of Cancer and Pathology, University of Leeds and St James's University Hospital, Leeds Cancer Research UK Centre, Leeds, UK
| | - G Yothers
- National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Pittsburgh, USA
| | - D J Sargent
- Division of Biomedical Statistics and Informatics
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Herszényi L, Barabás L, Miheller P, Tulassay Z. Colorectal cancer in patients with inflammatory bowel disease: the true impact of the risk. Dig Dis 2014; 33:52-57. [PMID: 25531497 DOI: 10.1159/000368447] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.
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Affiliation(s)
- László Herszényi
- Second Departments of Internal Medicine, Semmelweis University, Budapest, Hungary
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